(1) Background: Among the chronic complications of type 2 diabetes mellitus, cancer became the leading cause of death in several countries. Our objective was the determination of whether prevalent type 2 diabetes mellitus is associated with a higher incidence of cancer. (2) Methods: This study is a nationwide analysis performed in Hungary. Study population was divided into a group with type 2 diabetes mellitus and into a non-diabetic group. The primary outcome was the risk related to overall cancer incidence. A key secondary outcome was the overall incidence of cancer in distinct study years. Further outcomes were the annual percent changes. (3) Results: The odds ratio related to the overall incidence of cancer was 2.50 (95% confidence interval: 2.46-2.55, P<0.0001) in patients with diabetes as related to controls. The odds ratio was higher in males than in females. The highest risk was found in the 18-39-year-old subgroup. The annual cancer incidence rate declined in controls, but not in patients with diabetes. Several types of cancer showed a decreasing tendency in non-diabetic controls.; (4) Conclusions: type 2 diabetes is associated with a higher risk of cancer. High risk in young patients with type 2 diabetes suggests that these young individuals should be considered as a risk group.

(1) Background: Patients with type 2 diabetes mellitus (T2DM) are at higher risk of cancer but how these two diseases associate is still debated. The goal was the assessment of the overall incidence of cancer among patients with newly diagnosed T2DM in Hungary. Summarizing, incident T2DM is associated with a significantly higher overall risk of incident cancer, with a reverse correlation of age. Newly registered T2DM patients were suggested to be screened for cancer within 6 months. (2) Methods: A nationwide, retrospective, longitudinal study was performed using a Hungarian database. The incident T2DM and diabetes free Hungarian population were included in the study. The primary endpoints were the overall and site-specific incidence and annual percentage change of the incidence of cancer in both populations. (3) Results: The overall incidence of cancer in patients amounted to 29.4/1000 and 6.6/1000 with or without T2DM, respectively, and the OR (95%CI) of cancer of the T2DM group was 4.32 (4.14-4.53), p<0.0001. The risk of having cancer was age-dependent, having the highest odd in the age group 18-39. The incidence of cancer was declining in the non-diabetic but was unchanged in T2DM population. The average lag time of diagnosing a cancer after the detection of T2DM was 3.86 months.; (4) Conclusions: Iincident T2DM is associated with a significantly higher overall risk of incident cancer, with a reverse correlation of age. Newly registered T2DM patients were suggested to be screened for cancer within 6 months.

Type two diabetes mellitus (T2DM) represents a chronic condition with increasing prevalence worldwide among the older population. T2DM condition increases the risk of micro and macro-vascular complications as well as the risk of geriatric syndromes as falls, fractures and cognitive impairment. The management of T2DM in the older population represents a challenge for the cli-nician, and a Comprehensive Geriatric Assessment should always be prioritized, in order to tailor the glycate haemoglobin target according to functional and cognitive status comorbidities, life ex-pectancy and type of therapy. According to the most recent guidelines, older adults with T2DM should be cathegorized in three groups: healthy patients with good functional status, patients with complications and reduced functionality and patients at the end of life; for each group the target for the glycemic control is different, also according to the type of treatment drug. The therapeutic ap-proach should always begin with lifestyle changes; after that, several lines of therapies are available, with different mechanism of action and potential effect other than glucose level reduction. Partic-ular interest is growing around sodium-glucose cotransporter-2 inhibitors, due to their effect on the cardiovascular system. In this review we evaluate the therapeutic options available for the treat-ment of older diabetic patients, to ensure a correct treatment approach

Type 2 diabetes mellitus (T2DM), a multifactorial and complicated metabolic disorder, is a growing public health problems. Numerous studies indicated that bioactive compounds from herbal medicine have beneficial effects on T2DM prevention and treatment, owing to their numerous biological properties. Curcumin, the major curcuminoid of turmeric, is one of the most studied bioactive components of herbal supplements, which has a variety of biological activities. Clinical trials and preclinical research have recently produced compelling data to demonstrate the crucial functions of curcumin against T2DM via several routes. Accordingly, this review systematically summarizes the antidiabetic activity of curcumin, along with various mechanisms. Results showed that effectiveness of curcumin on T2DM is due to it being anti-inflammatory, anti-oxidant, anti-hyperglycemic, anti-apoptotic, anti-hyperlipidemia and other activities. In light of these results, curcumin may be a promising prevention/treatment choice for T2DM.

Background and Objectives: Cardiovascular disease is one of the leading causes of morbidity and mortality among the diabetic population. Given the high prevalence of diabetes mellitus (DM) in Saudi Arabia and the high prevalence of heart failure in the diabetic population, this study assesses the echocardiographic changes in Saudi patients with type 2 DM (T2DM) compared with healthy controls. Materials and Methods: In this retrospective case control study, 80 patients with diabetes (45 males, age: 58.78±10.2 years) were compared with 80 controls (45 males, age: 58.6±10 years) who underwent an echocardiographic study in the King Saud University Medical City, Riyadh, Saudi Arabia. Results: There were no significant differences between patients with diabetes and controls in terms of aortic root diameter, left atrium diameter, posterior wall, interventricular wall thickness, left ventricular diameters and ejection fraction. However, diastolic dysfunction was statistically significantly higher in the diabetic group compared with the control group (P <0.05). Conclusions: This is the first case control study in Saudi Arabia that assesses echocardiographic parameters in T2DM patients. DM is an independent risk factor for diastolic dysfunction regardless of its association with hypertension and dyslipidemia.

Type 2 diabetes mellitus (T2DM) is a common metabolic disease characterised by insulin resistance and elevated blood glucose levels, affecting millions of people worldwide. T2DM patients with dyslipidaemia have an increased risk of cardiovascular disease (CVD). A complex interplay of risk factors such as hyperglycaemia, dyslipidaemia, hypertension, obesity, inflammation and oxidative stress favour the development of atherosclerosis, a central mechanism in the pathogenesis of cardiovascular disease. Dyslipidaemia, a hallmark of T2DM, is characterised by elevated triglycerides, decreased high-density lipoprotein (HDL) cholesterol and the presence of small, dense low-density lipoprotein (LDL) particles, all of which promote atherosclerosis. In this article, we have attempted to present various treatment strategies that include pharmacological interventions such as statins, ezetimibe, PCSK9 inhibitors, fibrates and omega-3 fatty acids. We have also tried to highlight the pivotal role of lifestyle modifications, including physical activity and dietary changes, in improving lipid profiles and overall cardiovascular health in T2DM patients. We have also tried to present the latest clinical guidelines for the management of dyslipidaemia in T2DM patients. In conclusion, the treatment of dyslipidaemia in T2DM patients is of great importance as it lowers lipid particle levels, slows the progression of atherosclerosis and ultimately reduces susceptibility to cardiovascular disease.

Rapid urbanization, increasing population and increased industrialization to cater to demands of the growing population has imposed upon us a huge environmental cost. The significantly deteriorated air quality across the globe is associated with a direct and indirect impact on public health. While associated disorders such as chronic obstructive pulmonary diseases, heart failures are well documented, less is known about the biological basis of the process. We hypothesize that the worsening air quality may likely impact common systemic inflammatory processes, thus driving communicable and non-communicable diseases alike.Receptor mediated entry of particulate matter (PM2.5) results in activation of signaling cascades which culminate in production of inflammatory chemokine and cytokine responses, traversing through the blood mediating impacting not only on other organs but also dysbiosis of microflora. For the purpose of the review we choose tuberculosis (TB) as a model for communicable infectious disease and type 2 diabetes mellitus (T2DM) as a marker for non-communicable disorder. The increasing prevalence of these co-morbidities and the burdening of public health systems justifies this example. However the hypothesis may be applicable to other inflammation driven disorders also.

Background and Objectives: In this current state, Type 2 Diabetes Mellitus (T2DM) is more prevalent in the population, and metformin is used as a first-line medication for treating it. There was up surge in the utilization of alternative therapies in the management of diabetes. Especially in diabetes, Herbal medicines are considered safe and reliable by majority of the population. Aim: The purpose of this research is aimed to estimate the safety and efficacy of Polyherbal Metabolite Compounds (PHMC) capsules in adults with T2DM. Materials and Methods: In this study, 60 T2DM patients aged 18-60 years were randomly assigned to Groups A (30) receiving Metformin 500 mg twice a day after food and Group B (30) receiving PHMC capsule 500 mg twice a day after food in a prospective, randomized and open-label clinical study. The in-silico simulation study was performed to selected plants major compounds on target protein Insulin-like Growth Factor-1 (1K3A). Result: The PHMC is found to be safe and effective in the management of T2DM. The FBS, PPBS and HbA1c were significantly lowered (p

Diabetic kidney disease (DKD) is a major cause of morbidity and mortality of type 2 diabetes mellitus (T2DM). Aim of this study was to investigate whether albumin structural alterations correlate with DKD severity and evaluate whether native and reduced albumin concentrations could complement the diagnosis of DKD. To this aim, one hundred and seventeen T2DM patients without (n=42) and with (n=75) DKD (DKD I-III upon KDIGO classification) were evaluated; total albumin concentration (tHA) was quantified by bromocresol green assay, while structural alterations were profiled assessed by liquid chromatography-high resolution mass spectrometry (LC-HRMS). The concentrations of albumin in native (eHA, effective albumin) and reduced (rHA) forms were then assessed. HRMS analyses showed a reduced relative amount of native albumin in DKD patients along with an increased abundance of altered forms, especially those bearing oxidative modifications. Accordingly, both eHA and rHA values varied along the stages of progressive renal failure, and alterations dose-dependently correlated with renal dysfunction. ROC curves analysis showed a significantly higher sensitivity and specificity of eHA and rHA with respect to tHA for the diagnosis of DKD. Importantly, at multivariable logistic regression analysis, eHA was identified as independent predictor of DKD.

Background: Diabetes mellitus (DM) and osteoporosis are two of the most widespread metabolic disease in the world. The aim of this study is to investigate the prevalence of DM among patients affected by osteoporosis and fragility fractures, and to search differences in clinical features. Methods: 713 patients belonging to CTO Bone Unit because of osteoporosis and fragility fractures were divided into two groups, according to the diagnosis of DM. The clinical and bone characteristics of patients were compared. Results: Prevalence of DM was 10.8%. When compared to patients without DM, the median age at the time of first fracture was similar (72 years ± 14 IQR vs 71 years ± 12 IQR); prevalence of combination of vertebral and hip fractures was higher (p=0.039), as well as prevalence of males, although not significantly (p=0.051). Bone mineral density (BMD) at all sites was higher in DM group; Trabecular Bone Score (TBS), instead, was significantly lower (p<0.001). Conclusions: Patients with fragility fractures and DM more frequently show combination of major fractures with higher BMD levels. In these patients, TBS could be a better indicator of bone health than BMD and therefore should be used as a diagnostic tool in clinical practice.

Abstract: (1) Background: The relationship between non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2DM) is bidirectional: NAFLD increases the risk of T2DM, and T2DM promotes the progression of the disease to non-alcoholic steatohepatitis (NASH). (2) Material and methods: We performed a retrospective, open study that included 59 patients with NAFLD and T2DM who were distributed into two groups: 44 (74.57%) patients were diagnosed with HS and 15 (25.42%) patients were diagnosed with NASH. (3) Results: Among the non-specific inflammatory biomarkers statistically significant (p=0.003 respectively p=0.03) higher mean values were recorded in patients with NASH and T2DM in the case of ferritin and the neutrophil percentage-to-albumin ratio (NPAR). (4) Conclusions: Consequently, it is essential to identify alternative "surrogate" markers for the inflammatory process, particularly in individuals with diabetes, as it is a key characteristic of NASH. This need arises from the desire to avoid the risks associated with liver biopsy procedures and to prevent the unpredictable and unfavorable progression of NAFLD in patients with T2DM.

Type-2 diabetes mellitus is recognized as a serious public health concern with a considerable impact on human life, long-term health expenditures, and substantial health losses. In this context, the use of dietary polyphenols to prevent and manage Type 2 diabetes mellitus is widely documented. These dietary compounds exert their beneficial effects by several actions, including the protection of pancreatic islet β-cell, the antioxidant capacities of these molecules, their effects on insulin secretion and actions, the regulation of intestinal microbiota, and their contribution to ameliorating diabetic complications, particularly those of vascular origin. In the present review, we intend to highlight these multifaceted actions and the molecular mechanisms by which these plant-derived secondary metabolites exert their beneficial effects on type-2 diabetes patients.

Background: The systemic inflammatory index (SII) is a new inflammatory marker that has been the subject of various studies in diseases with chronic inflammation. Diabetic nephropathy is also a disease that goes with chronic inflammation. We aimed to evaluate the relationship be-tween SII and diabetic nephropathy. Methods: Patients with diabetes who applied to our outpatient clinic are included in the study. Diabetic patients are divided into two groups: those with diabetic nephropathy and those with-out. In addition, healthy individuals who applied to our clinic for general check-ups during these dates are included as control group. The SII values and other characteristics of the three study groups are compared. Results: The median SII value for those with DKI was 584 (178-4819); for those without DKI, it was 282 (64-618); and for the control group, it was 236 (77.5-617) (p<0.001). SII was significantly and positively correlated with BMI, weight, blood glucose, HbA1c, CRP and creatinine, and neg-atively correlated with glomerular filtration rate (GFR) value. The SII value higher than 336 has 75% sensitivity and 70% specificity in detecting DKI. Conclusion: The SII value could predict diabetic kidney injury in diabetics and it could be used as an adjunctive diagnostic tool.

Type-2 diabetes mellitus (T2DM) have been strongly associated with single nucleotide polymorphisms (SNPs) in the TCF7L2 gene. This study investigated the association between rs12255372, rs7903146 and T2DM in a Ghanaian population. A case-control study design was used for this study. A total of 106 T2DM patients and 110 control participants were selected. Basic data collected included body mass index, blood pressure and socio-demographics. Fasting blood samples were collected and used for serum lipid analysis, HbA1c, plasma glucose estimation and DNA extraction. Common and allele-specific primers were designed for genotyping using the Modified Tetra-Primer Amplification assay. Associations were evaluated using logistic regression models. The rs7903146 risk variant was significantly associated with 2.16 vs 4.06 increased odds for T2DM in patients <60 years vs ≥60 years. Both rs7903146 and rs12255372 are significantly associated with increased odds of T2DM in women, overweight/obese; T2DM negative family history (T2DM-NFH) and low-HDL-C. In a multivariate model, rs7903146 but not rs12255372 was significantly associated with 2.18, 5.01 and 2.25 increased odds of T2DM, under the codominant, recessive and additive model, respectively (p<0.05). The association between rs7903146 and rs12255372 with T2DM is more highly associated in a subgroup- women and those with T2DM-NFH, yet have cardiometabolic risk.

The purpose of current study was to investigate the expression characteristic of circular RNAs (circRNAs) in peripheral blood of type 2 diabetes mellitus (T2DM) patients and their potentials as diagnostic biomarkers for pre-diabetes and T2DM. In present study, the circRNAs in the peripheral blood from 6 healthy individuals and 6 T2DM patients were collected for microarray analysis. The results indicated that there were 489 differentially expressed circRNAs, of which 78 were upregulated and 411 were downregulated in the T2DM group. Then we selected 5 circRNAs as the candidate biomarkers under a stricter screening criteria and further verified them in another cohort (control group, n=20; pre-diabetes group, n =20; T2DM group; n=20). 3 of the 5 circRNAs presented upregulated expression in the experimental groups, including 2 circRNAs of the T2DM group that had higher expression than the pre-diabetes group. Hsa_circ_0054633 was identified to have the largest area value under the carve (AUC). In another independent cohort (control group, n=60; pre-diabetes group, n=63; T2DM group, n=64), the diagnostic capacity of hsa_circ_0054633 was tested. The results showed that the AUC for the diagnosis of pre-diabetes was 0.751(95% confidence interval=[0. 666-0.835], P＜0.001) while it was 0.793 ([0.716-0.871], P＜0.001) for the diagnosis of T2DM. After including the risk factors of T2DM, the AUC increased to 0.841 ([0.773-0.910], P <0.001) and 0.834 ([0.762-0.905], P <0.001), respectively. Hsa_circ_0054633 presented a certain diagnostic capability for pre-diabetes and T2DM.

Diabetes mellitus – type 2 (DM2) is a hypercoaguable state with enhanced platelets (PLTs) activation and increased clotting factor production. Simultaneously, the fibrinolytic cell system is inhibited due to formation of clots with high resistance to fibrinolysis. The stages of PLTs "activation" have been well-characterized microscopically, morphometrically and nanomechanically (by light microscope, transmisiion electron microscope - TEM, scanning electron microscope - SEM and atomic force microscope - AFM). Thrombocytes in "acivated" (pro-coagulant) state play central role in two main biological processes: hemostasis and repair of vascular vessels. Pro-coagulant PLTs participate in generation of thrombin and in development of fibrin fibers in the clot matrix. Enhanced PLTs reactivity in dibetic- (diabetes mellitus - DM2) patients is considered as a "pro-thrombotic" state. In the retrospective- and prospective- studies on the topic, the higher are the PLTs' hematometrical indices: PLTs (count), MPV (mean platelet volume), PDW (platelet distribution width), PCR (plateletcrit), as well as PLTs/Ly ratio. The PLТs parameters/indices are usefull biomarkers in early diagnosis and prognosis of DM2. The precise studies of PLTs' state of activation during DM2 might be useful for creation of new diabetes (DM2) treatment strategies and effective medicines. Using the amount of blood glucose, attached to hemoglobin (HbA1c values) as markers of glycemic control in diabetic patients, researchers have observed association between MPV and medications as Insulin, Metformin, sulphonyl ureas. Computational modellng of PLTs' activation in DM2 is also a controlling factor for thrombocyte distribution and margination in bood vessels, associated with micro- and macrovascular disease in DM2. PLTs-derived miRNAs are novel molecular biomarkers for diagnosis and prognosis of DM2, insulin resistance and diabetes complications. We have proposed (2010) oleic acid (OA) as a substance suppressing "PLT hyperactivation" and inhibiting “thrombocyte aggregation”. Antiplatelet agents, natural plant products including, could be effective in the prevention and the secondary treatment of micro- and macrovascular complications in the type 2 Diabetes mellitus. Our proposal on following up of a combination of hematological-, hemorheological- and hemostatic parameters (indices) as a new way in diagnosis, treatment, predicting and management of DM2 and its related vascular complications, probably could be more explored in future studies.

Diabetes mellitus (DM) is a metabolic disease characterized by chronic hyperglycemia associated with impaired carbohydrate, lipid and protein metabolism, with concomitant absence of insulin secretion or reduced sensitivity to its metabolic effects. Patients with diabetes mellitus have 30% more risk of developing heart failure and cardiovascular disease with respect to healthy people. Heart and cardiovascular problems are the first cause of death worldwide and the main complications which lead to high healthcare costs. Such complications can be delayed or avoided by taking prescribed medications in conjunction with a healthy lifestyle (i.e. diet and physical activity). The American College of Sports Medicine and the American Diabetes Association recommend that diabetic people reduce total sedentary time by incorporating physical activity in their weekly routine. This narrative literature review has the aim to summarize and present the main guidelines, pre-exercise cardiovascular screening recommendations, and considerations for patients with diabetes and comorbidities who are planning to participate in regular exercise regimens.

Glucagon-like peptide-1 (GLP-1) is an incretin hormone that acts on the pancreas to increase insulin and decrease glucagon secretion. Albuminuria is the pivotal marker for diabetic nephropathy, which is the leading microvascular complication of diabetes mellitus. Most of the previous studies mainly focused on the clinical trials of the therapeutic renal protective effect after administration of GLP-1 receptor agonists (GLP-1 RAs), not prior to administration. Therefore, this study aimed to investigate the association between fasting plasma GLP-1 levels and albuminuria before GLP-1 RA administration. A cross-sectional study was designed to evaluate the association between fasting plasma GLP-1 levels and albuminuria in patients with type 2 diabetes mellitus (T2DM). A total of 68 T2DM participants were analyzed from the data at Wonkwang University Hospital in Iksan, Korea. Logistic regression analysis was performed to evaluate the odds ratio (OR) and 95% confidence interval (CI) of the incidence of albuminuria between the GLP-1 low group (Group L) and the high group (Group H). The OR (95% CI) for the incidence of albuminuria comparing the Group L with the Group H of fasting plasma GLP-1 levels was 3.410 (1.160-10.023), p = 0.026 after adjustment for age, gender, fasting plasma glucose, HbA1c, C-peptide, the use of ACE inhibitors or ARBs, SGLT-2 inhibitors, and DPP-4 inhibitors. As a continuous variable, the OR (95% CI) for the incidence of albuminuria associated with the reduction of each 1 pmol/L in fasting plasma GLP-1 levels was 1.673 (1.173-1.870), p = 0.018, after full adjustment. This study showed the negative association between fasting plasma GLP-1 levels and the incidence of albuminuria in Korean patients with T2DM, before GLP-1 RA administration. This result suggests that endogenous GLP-1 may play a role in attenuating albuminuria.

In this study, we aimed to reveal the proinflammatory effects of serum 25-hydroxyvitamin D3 (Vit D) deficiency and insufficiency in new-onset type 2 diabetes mellitus (T2DM) and prediabe-tes. We recruited 84 prediabetes patients, 94 new-onset T2DM patients and 113 healthy partici-pants. Levels of C-reactive protein (CRP), fibrinogen, ferritin, interleukin-1β (IL-1β), interleu-kin-6 (IL-6), interleukin-8 (IL-8), tumour necrosis factor-α (TNF-α), nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) were measured in the serum of the par-ticipants. The ANOVA Bonferonni and Kruskal Wallis Dunn tests were used for the comparison of the inflammation markers and vitamin D levels between the groups. Upon covariance analy-sis with age, gender and BMI; Vit D levels of T2DM group were found to be significantly lower (p<0.003). Proinflammatory markers and CRP were found to be significantly higher in predia-betic and diabetic subjects. In the prediabetes group, IL-1β, IL-6, IL-8, TNF-α and MAPK were significantly higher in those with Vit D insufficiency and deficiency groups. In T2DM group, IL-1β, IL-6, IL-8, TNF-α, NF-κB, MAPK and CRP were significantly higher in those with Vit D insufficiency and deficiency. Our study emphasizes the proinflammatory effects of Vit D on the initiation of inflammation in both prediabetes and diabetes mellitus.

Diabetes mellitus (DM) has been defined as a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. This study includes (84) subjects, their age ranged from (40 to 54) years. (20) subjects were healthy chosen as control group and (64) patients with type 2 diabetes mellitus were divided into three groups according to their type of anti diabetic therapy: (23) newly diagnosed group without therapy (Group1), (20) with metformin therapy (Group2) and (21) with metformin plus glibenclamide therapies (Group3). In the study lipid profile level were quantitatively determine by enzymatic methods, in addition to that fasting plasma glucose (FPG), Glycated hemoglobin (HbA1c%) and body mass index (BMI) were identified in the patients. There is significant increase in the level of lipid profile in patients group. Metformin alone produce a non-significant favorable effect on all lipids profile parameters while metformin plus glibenclamide showed a significant reduction in TC and LDL-C.

Background and Objective: Type 2 diabetes mellitus (DM2) and breast cancer (BC) are diseases of high prevalence worldwide. Both alter lung function separately. So suffering both tables would increase this decrease in lung function. The objetive was to determine the effects of DM2 and BC on ventilation volumes and pressures in adult women. Material and Methods: Forty-two women patients were recruited, of whom 40 were accepted under the exclusion criteria. They were divided into four groups: control group (CG), DM2, BC and DM2+BC. Body plethysmography was used to measure forced vital capacity, lung volumes, airway resistance and muscle pressures. Finally the normality of the data was determined using Student's t test or the Mann-Whitney U test; the threshold of significance was p<0.05. Results: No significant differences were observed in the anthropometric variables between the control group and the other groups. The ventilation flows showed no significant differences, while the lung volumes presented significant differences in the inspiratory capacity (IC) variables (p<0,002). Maximum inspiratory and expiratory pressures (MIP-MEP) also presented significant diminution (p<0,001; p<0,041, respectively). Conclusions: From the results obtained we can conclude that the combination of type 2 diabetes mellitus with breast cancer caused a diminution in ventilation volumes and pressures, specifically in IC, MIP and MEP.

The aim of this study was to evaluate the relationship between serum levels of advanced glycation end products (AGEs) and abdominal aortic calcification (AAC) in patients with type 2 diabetes mellitus (DM2). This was a prospective cross-sectional study conducted from January 2017 to June 2018. One-hundred and four consecutive patients with DM2 were given lateral lumbar X-rays in order to quantify aortic abdominal calcification AAC. Circulating levels of AGEs and classical cardiovascular risk factors were determined. Clinical history was also registered. Patients with higher AGEs values had higher grades of aortic calcification and higher number of diabetic related complications. Multivariate logistic regression analysis showed that being older, male and having high levels of AGEs and triglycerides were the independent risk factors associated to moderate-severe AAC when compared to no-mild AAC. Our results suggest that AGEs plays a role in the pathogenesis of aortic calcifications. In addition, the measurement of AGEs levels may be useful for assessing the severity of AAC in the setting of diabetic complications.

Alexithymia as the inability to describe one's own feelings, is being increasingly researched. According to contemporary psychodynamic theories, negative emotions cannot be adequately named and externalized, but remain trapped in the body. Recent research shows the connection of alexithymia with numerous somatic diseases. Diabetes mellitus type 2 and obesity represent a great challenge in treatment, and the psychological profiles in these diseases are being studied more and more often. Therefore, alexithymia enters the focus of some research as one that could play a significant role namely in these diseases as the factor that makes a difference. The aim of this paper is a review of the literature with the purpose of understanding the current knowledge about the interconnection between alexithymia, obesity and type 2 diabetes mellitus.

Type 2 diabetes (T2D) has a complex pathophysiology which makes modeling the disease difficult. We aimed to develop a novel model for simulating T2D in vitro, including hyperglycemia, hyperlipidemia, and variably elevated insulin levels targeting muscle cells. We investigated insulin resistance (IR), cellular respiration, mitochondrial morphometry and the associated function in different T2D -mimicking conditions in rodent skeletal (C2C12) and cardiac (H9C2) myotubes. Physiological controls included 5mM glucose with 20mM mannitol as osmotic controls. To mimic hyperglycemia, cells were exposed to 25mM glucose. Further treatments included insulin, palmitate, or both. After short-term (24h) or long-term (96h) exposure, we performed radioactive glucose uptake and mitochondrial function assays. Mitochondrial size and relative frequencies were assessed by morphometric analyses using electron micrographs. C2C12 and H9C2 cells treated short- or long-term with insulin and/or palmitate and HG showed IR. C2C12 myotubes exposed to T2D -mimicking conditions showed significantly decreased ATP-linked respiration and spare respiratory capacity, and less cytoplasmic area occupied by mitochondria, implying mitochondrial dysfunction. In contrast, H9C2 myotubes showed elevated ATP-linked and maximal respiration and increased cytoplasmic area occupied by mitochondria, indicating better adaptation to stress and compensatory lipid oxidation in a T2D environment. Both cell lines displayed elevated fractions of swollen/vacuolated mitochondria after T2D -mimicking treatments.Our stable and reproducible in vitro model of T2D rapidly induced IR, changes in ATP-linked respiration, shifts in energetic phenotypes, and mitochondrial morphology, which are comparable to the muscles of patients suffering from T2D. Thus, our model should allow studying disease mechanisms, potential new targets, and screen candidate therapeutic compounds.

Diabetes mellitus (DM) poses a significant challenge to global health, with its prevalence projected to rise dramatically by 2045. This narrative review explores the bidirectional relationship between periodontitis (PD) and type 1 diabetes mellitus (T1DM), focusing on cellular and molecular mechanisms derived by the interplay between oral microbiota and the host immune response. A comprehensive search of literature published between 2008 and 2023 was conducted to elucidate the association between these two diseases. Preclinical and clinical evidence suggests a bidirectional relationship, with individuals with T1DM exhibiting heightened susceptibility to periodontitis, and vice versa. The review includes recent findings from human clinical studies, revealing variations in oral microbiota composition in T1DM patients, including increases in certain pathogenic species such as Porphyromonas gingivalis, Prevotella intermedia, and Aggregatibacter actinomycetemcomitans, along with shifts in microbial diversity and abundance. Molecular mechanisms underlying this association involve oxidative stress and dysregulated host immune responses, mediated by inflammatory cytokines such as IL-6, IL-8, and MMPs. Furthermore, disruptions in bone turnover markers, such as RANKL and OPG, contribute to periodontal complications in T1DM patients. While preventive measures to manage periodontal complications in T1DM patients may improve overall health outcomes, further research is needed to understand the intricate interactions between oral microbiota, host response, periodontal disease, and systemic health in this population.

Background: The aim was to diagnose Candida in the oral cavity of subjects with type 2 diabetes mellitus (T2DM) using a genotyping technique and to compare the results with those from con-ventional diagnosis by Papanicolau (Pap) staining. Methods: Palatal mucosa smears were per-formed in 18 dental care patients diagnosed with T2DM and grade I, II, and III prosthetic stomatitis who met the inclusion criteria; 18 healthy control subjects were also included in the study. He-moglobin A1c (HbA1c) levels were determined from total blood. Using exfoliative cytology, the Pap staining technique was used to diagnose candidiasis. Exfoliative cytology was also used for molecular diagnosis; DNA was obtained for Candida genotyping and RNA was used for gene ex-pression studies. Results: Clinical patterns indicated that all subjects were positive for Candida; however, Pap analysis revealed only three positive subjects, whereas end-point polymerase chain reaction (PCR) analysis revealed fifteen subjects with some type of Candida. The most common Candida species found were Candida guilliermondii (38.8%), Candida krusei (33.3%), Candida tropicalis, and Candida lusitaniae (22.2%). Interestingly, the coexpression of different species of Candida was found in various patients. In all patients, HbA1c levels were increased. Gene expression analysis showed a significant decrease (p ≤ 0.05) in TLR2 expression in positive subjects, whereas TLR4 expression did not differ significantly among patients. Conclusions: The end-point PCR technique showed better sensitivity for diagnosis of Candida when compared with diagnosis by Pap staining. T2DM subjects showed an increased presence of C. guilliermondii that was correlated with decreased TLR2 expression

Background: Dynapenia and non-alcoholic fatty liver disease (NAFLD) are common, especially in the middle and advanced-age diabetic male population. We aimed to examine the clinical features, NAFLD severity, and parameters associated with the presence of dynapenia in type 2 diabetes mellitus (T2DM) cases. Material and Methods: One hundred thirty-five male patients diagnosed with T2DM between 45 and 65 years of age were included. Patients were staged by ultrasonography according to NAFLD status. Results: There were significant differences in muscle strength, upper arm circumference, calf circumference, and up-and-go test scores between the NAFLD groups (p<0.001 for all). The frequency of dynapenia was lower, and arm and calf circumferences were higher in patients without NAFLD. The muscle strength, upper arm circumference, calf circumference, and up-and-go test scores were significantly lower in the dynapenic group compared to the non-dynapenic group (p<0.005 for all). The prevalence of dynapenia increased along with the increase in NAFLD stages (p<0.001). Conclusions: We detected a significant association between NAFLD and dynapenia in middle-aged men with T2DM. As muscle strength decreases, the amount of fat in the liver increases, and as the fat in the liver increases, muscle strength decreases.

Osteoporosis is a common metabolic bone disease in patients with diabetes, which can develop simultane-ously with Type 2 diabetes (T2D) in postmenopausal women. Bisphosphonate (BP) is administered to pa-tients with both the conditions and may cause medication-related osteonecrosis of the jaws (MRONJ). It affects the differentiation and function of osteoclasts as well as thickness of cortical bone through bone mineralization. Therefore, this study aimed to investigate the effects of T2D on osteoclast differentiation and activity as well as cortical bone formation in postmenopausal patients with MRONJ. Tissue samples were collected from 10 patients diagnosed with T2D and Stage III MRONJ in the experimental group and from 10 patients without T2D in the control group. Histological examination was conducted, and expres-sion of dendritic cell-specific transmembrane protein (DC-STAMP) and tartrate resistant acid phosphatase (TRAP) was assessed. Cortical bone formation was analyzed using CBCT images. The number of TRAP-positive osteoclasts and DC-STAMP-positive mononuclear cells were significantly less in the experi-mental group (p < 0.05). Furthermore, the thickness and ratio of cortical bone were significantly greater in the experimental group (p < 0.05). In conclusion, T2D decreased the differentiation and function of osteo-clasts, and increased cortical bone formation in postmenopausal patients with MRONJ.

Despite the effectiveness of insulin injections in managing hyperglycemia in Type 1 Diabetes, they fall short in addressing autoimmunity and regenerating damaged islets. This review aims to explore the potential of various treatment modalities for T1DM, including mesenchymal stem cells (MSCs), MSC-derived exosomes, gene therapy, islet allotransplantation, and pancreatic islet cell transplantation. Results: MSCs demonstrate efficacy in T1DM treatment through immunomodulation and tissue regeneration, although further research is warranted to optimize their therapeutic potential. Gene therapy presents a promising approach despite challenges such as donor shortage and immune rejection. Pancreatic islet cell transplantation emerges as a viable option, albeit with associated risks including graft rejection and the need for immunosuppression. Teplizumab, an FDA-approved humanized monoclonal antibody, revolutionizes the treatment landscape of Type 1 Diabetes by significantly delaying its onset, offering a paradigm shift since the discovery of insulin Conclusion: Ongoing studies and technological advancements in T1DM management offer a promising outlook for improved treatments and possibly even eradication on a global scale. MSCs, MSC-derived exosomes, gene therapy, and pancreatic islet transplantation hold considerable potential.

The late diagnosis of Type 2 Diabetes Mellitus can occur due to lack of access to the primary health care system and the non-manifestation of symptoms. Faced with this problem, this work presents the creation of a mobile application, called DiabetesCheck, for predicting the risk of Type 2 Diabetes Mellitus. A mathematical model is used, which classifies the risk of Type 2 Diabetes Mellitus for a group of patients with intervention and for a comparative group, using Fuzzy Classification and Decision Trees. The proposed application allows the health professional to monitor patients through the history stored in a database, allowing a representation of the evolution of patients and indication of medications. Therefore, this proposal aims to carry out the diagnosis in the initial phase of the disease and help in the prescription of more effective treatments and in the proposition of public policy strategies in epidemiology and screening.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by elevated blood glucose levels. Despite the availability of pharmacological treatments, dietary plans, and exercise regimens, T2DM remains a significant global cause of mortality. Consequently, there is a growing interest in exploring lifestyle interventions, such as Intermittent Fasting (IF). This study aims to identify underlying patterns and principles for effectively improving T2DM risk parameters through IF. By analyzing data from multiple randomized clinical trials investigating various IF interventions in humans, a machine learning algorithm was employed to develop a personalized recommendation system. This system advises pre-diabetic and diabetic individuals on the most suitable IF interventions to improve T2DM risk parameters. With a success rate of 95%, this recommendation system offers highly tailored guidance, optimizing intermittent fasting's benefits for diverse population subgroups. The results of this study allow us to conclude that weight is the crucial feature for females, while age is the determining factor for males to reduce glucose levels in blood. By revealing patterns in diabetes risk parameters among individuals, this study not only provides practical guidance but also sheds light on the underlying mechanisms of T2DM, contributing to a deeper understanding of this complex metabolic disorder.

Type 2 diabetes mellitus (T2DM) is a polygenic metabolic disease described by hyperglycemia, which is caused by insulin resistance or reduced insulin secretion. Interaction between various genetic variants and environmental factors triggers T2DM. The main aim of this study was to find the risk associated with genetic variant (rs5210) of KCNJ11gene in the development of T2D in Indian Population. A total number of 300 cases of T2D and 100 control samples were studied to find the polymorphism in KCNJ11 through PCR-RFLP. The genotype and allele frequencies in T2DM cases were significantly different from the control population. We found a significant association of KCNJ11 (rs5210) gene polymorphism with T2DM in North Indian patients indicating the role of this variant in developing risk for T2DM.

Abstract—Low-frequency Fahræus–Lindqvist-driven (not blood pressure-driven) oscillations in the small vessels are crucial because oscillations in small vessels support nutrient supply. Understanding of this is critical in type 2 diabetes mellitus (T2DM) to develop therapeutic measures to prevent Alzheimer's Disease Related Dementias: vascular factors contribute to cerebrovascular disease as well as mild cognitive impairment and dementia, which are predicted to affect 152 million people by 2050 (Alzheimer's Disease International London, UK, 2019). In this clinical study, we performed functional near-infrared spectroscopy (fNIRS) of the forehead to investigate the effect of the Mini-Cog with three-item recall test on the prefrontal cortex (PFC) activation and the relative oscillatory power in the 0.01–0.02-Hz (Fahræus–Lindqvist effect) and 0.021–0.052 Hz (smooth muscle autonomic innervation) frequency bands in elderly (60 years and older) T2DM and age-matched controls. We found a significant (p<0.01) difference in the PFC activation between elderly subjects with T2DM and age-matched elderly controls. Moreover, power spectral density (PSD) analysis revealed a significantly lower relative power in 0.021–0.052 Hz (smooth muscle autonomic innervation) frequency band in elderly subjects with T2DM during the Mini-Cog three-item recall test. Furthermore, a drop in the oscillatory power in the 0.01–0.02-Hz frequency band during Mini-Cog three-item recall test was found more pronounced in the elderly subjects with T2DM. Therefore, our study highlighted portable brain imaging to capture cerebrovascular reactivity to cognitive load that may provide a biomarker of cerebrovascular dysfunction in T2DM.Clinical Relevance— Our study establishes forehead portable brain imaging for monitoring cerebrovascular function in T2DM under cognitive load.

Type 2 diabetes mellitus (T2DM) and late-onset Alzheimer’s disease-dementia (LOAD) are increasing in global prevalence and current predictions indicate they will only increase over the coming decades. These increases may be a result of the concurrent increases of obesity and aging. T2DM is associated with cognitive impairments associated with metabolic factors and increases the cellular vulnerability to develop the age-related increased risk of LOAD. This review addresses possible mechanisms due to obesity, aging, multiple intersections between T2DM and LOAD and mechanisms for the continuum of progression. Multiple ultrastructural images in female diabetic db/db models are utilized to demonstrate marked cellular remodeling changes of mural and glia cells and provide for the discussion of functional changes in T2DM. Throughout this review multiple endeavors to demonstrate how T2DM increases the vulnerability of the brain’s neurovascular unit (NVU), neuroglia and neurons are presented. Five major intersecting links are considered: i. aging (chronic age-related diseases); ii. metabolic (hyperglycemia - advanced glycation end-products and its receptor (AGE/RAGE) interactions and hyperinsulinemia – insulin resistance (a linking linchpin); iii. oxidative stress (reactive oxygen-nitrogen species); iv. inflammation (peripheral macrophage and central brain microglia); v. vascular (macrovascular accelerated atherosclerosis - vascular stiffening and microvascular NVU/neuroglial remodeling) with resulting impaired cerebral blood flow.

Diabetes is a risk factor for mild cognitive impairment (MCI) and dementia. However, how the clinical characteristics of type 2 diabetic patients with MCI are linked to sarcopenia and/or its criterion remain to be elucidated. Japanese patients with type 2 diabetes mellitus were categorized into the MCI group for MoCA-J (the Japanese version of the Montreal cognitive assessment) score <26, and into the non-MCI group for MoCA-J ≥26. Sarcopenia was defined by a low skeletal mass index along with low muscle strength (handgrip strength) or low physical performance (walking speed <1.0 m/s). Univariate and multivariate-adjusted odds ratio models were used to determine the independent contributors for MoCA-J <26. Among 438 participants, 221 (50.5%) and 217 (49.5%) comprised the non-MCI and MCI groups, respectively. In the MCI group, age (61 ± 12 vs. 71 ± 10 years, p < 0.01) and duration of diabetes (14 ± 9 vs. 17 ± 9 years, p < 0.01) were higher than those in the non-MCI group. Patients in the MCI group exhibited lower hand grip strength, walking speed, and skeletal mass index, but higher prevalence of sarcopenia. Only walking speed (rather than muscle loss or muscle weakness) was found to be an independent determinant of MCI after adjusting for multiple factors, such as age, gender, BMI, duration of diabetes, hypertension, dyslipidemia, smoking, drinking, eGFR, HbA1c, and history of coronary heart diseases and stroke. In subgroup analysis, a group consisting of male patients aged ≥65 years, with BMI <25, showed a significant OR for walking speed. This is the first study to show that slow walking speed is a sole determinant for the presence of MCI in patients with type 2 diabetes. It was suggested that walking speed is an important factor in the prediction and prevention of MCI development in patients with diabetes mellitus.

Cardiovascular diseases (CVDs) and type 2 diabetes mellitus (T2DM) are two of the four major chronic non-communicable diseases (NCDs), representing the leading cause of death worldwide. Several studies demonstrate that endothelial dysfunction (ED) plays a central role in the pathogenesis of these chronic diseases. Although it is well known that systemic chronic inflammation and oxidative stress are primarily involved in the development of ED, recent studies have shown that perivascular adipose tissue (PVAT) is implicated in its pathogenesis, also contributing to the progression of atherosclerosis and to insulin resistance (IR). In this review we describe the relationship between PVAT and ED, and we also analyse the role of PVAT in the pathogenesis of CVDs and T2DM, further assessing its potential therapeutic target with the aim of restoring normal ED and reducing global cardiovascular risk.

Polymorphism in cytochrome P450 (CYP) 2C9 enzyme is known to cause significant inter-individual differences in drug response and occurrence of adverse drug reactions. Different alleles of the CYP2C9 gene have been identified but the notable alleles responsible for reduced enzyme activity are CYP2C9*2 and CYP2C9*3. No pharmacogenetic data is available on CYP2C9*2 and CYP2C9*3 alleles in Pakistani population. In Pakistan pharmacogenetics which examines the relationship between genetic factors and drug response, are in the early stages of development. We for the first time investigated the association between the CYP2C9 variant alleles CYP2C9*2 and CYP2C9*3 and the incidence of hypoglycemia in diabetic patients who were receiving the sulfonylurea medications. A total of n=400 individuals of Pashtun ethnicity were recruited from ten different districts of Khyber Pakhtunkhwa, Pakistan to participate in the study. The study participants were divided into two distinct groups: the case group (n=200) and the control group (n=200). The case group consisted of individuals with Type 2 Diabetes Mellitus (T2DM) who were receiving sulfonylurea medications and experience hypoglycaemia with it whereas the control group included individuals with T2DM who were receiving sulfonylurea medication but did not experience sulfonylurea-induced hypoglycaemia (SIH). Blood samples were obtained from study participants following informed consent. DNA was isolated from whole blood samples using Wiz-Prep DNA extraction kit. Following DNA isolation, CYP2C9 alleles were genotyped using MassARRAY sequencing platform at centre of genomics Rehman Medical Institute (RMI). The frequency of CYP2C9*2 (low activity allele) was more frequent in the diabetic patients with sulphonylurea-induced hypoglycaemia (SIH) compared to the control group (17.5% vs. 6.0%, p=0.021). The frequency of its corresponding genotype CYP2C9*1/*2 was higher in cases compared to control group (10% vs. 6% with P=0.036), same was true for genotype CYP2C9*2/*2 (7% vs. 3.5 % with P=0.028). Logistic regression analysis evident potential association of CYP2C9*2 allele and its genotypes with SIH. When adjusted for confounding factors such age, weight, sex, daily dose of sulphonylurea and triglyceride level the association between the CYP2C9*2 allele and hypoglycemia remains consistent. Confounding factors played no role in SIH because both groups (cases and controls) were closely matched in term of age, weight, sex, mean daily dose of sulphonylurea and trigyleride levels. Our study suggests that genetic information about a patient's CYP2C9 gene/enzyme can potentially assist physicians in prescribing the most suitable and safest drug based on their genetic make-up.

Diabetes mellitus is one of the most common endocrinopathies, estimated to affect about 5.4% of the world's population around 2025. It is thought that nearly a third of diabetic patients have some type of skin condition. Frequently, the cutaneous effects of this heterogeneous syndrome are ac-curately detected late in the progressive form of the disease. The main objective of the present study was to identify the main cellular characteristics of the cutaneous microenvironment in exper- imentally induced diabetes mellitus. Skin fragments were harvested from adult white Wistar rats of both sexes, with the weight of 200 g, 12 weeks after streptozotocin diabetes was induced. In parallel with histopathological diagnosis by using hematoxylin and eosine staining, samples were processed by transmission electron microscopy technique and examined with a Philips CM100 microscope. In the apparently macroscopically unchanged tegument, photon microscopy revealed both progres ive thinning of the epidermis in the early stages of diabetes and a significant process of fibrosis and collagen hyalinization in the dermis. In addition, in the early stages, the electron microscopic study provided ultrastructural details characteristic of a senescent phenotype with reduced cell proliferation. The morphological changes in the skin may be the first signs of disruption of carbohydrate metabolism and in the case of established diabetes may reflect its progression and the efficacy of therapy.

Embryonic genetic mechanisms are present in the brain and ready to be placed into action upon cellular injury termed the response to injury wound healing (RTIWH) mechanism. When injured, regional brain endothelial cells initially undergo activation and dysfunction with initiation of hemostasis, inflammation (peripheral leukocytes and innate microglia and perivascular macrophage cells), proliferation (astrogliosis), remodeling, repair, and resolution phases if the injurious stimuli are removed. In conditions wherein the injurious stimuli are chronic as occurs in obesity, metabolic syndrome, and type 2 diabetes mellitus this process does not undergo resolution and there is persistent RTIWH with remodeling. Indeed, the brain is unique, in that it utilizes its neuroglia: the microglia cell along with peripheral inflammatory cells and its astroglia instead of peripheral scar-forming fibrocytes/fibroblasts. The brain undergoes astrogliosis to form a gliosis scar instead of a fibrosis scar to protect the surrounding neuropil from regional parenchymal injury. One of the unique and evolving remodeling changes in the brain is the development of enlarged perivascular spaces (EPVS), which is the focus of this brief review. EPVS are important since they serve as a biomarker for cerebral small vessel disease and also represent an impairment of the effluxing glymphatic system that is important for the clearance of metabolic waste from the interstitial fluid to the cerebrospinal fluid and disposal. Therefore, it is important to better understand how the RTIWH mechanism is involved in the development of EPVS that are closely associated with and important to the development of premature and age-related cerebrovascular and neurodegenerative diseases with impaired cognition.

Background: Evidence supports a causal relationship between circadian disturbance and impaired glucose homeostasis. Method: To determine the effect of a nursing educational intervention on improving healthy sleep, a parallel, open-label clinical trial in subjects with Impaired Fasting Glucose (IFG) or Type 2 Diabetes Mellitus (T2DM) and 18 and older was performed. Study variables were sex, age, fasting glucose, glycated hemoglobin A1c (HbA1c), Pittsburgh Sleep Quality Index (PSQI), sleep duration and efficiency, BMI, antidiabetic treatment and diet and physical exercise. An individual informative educational intervention was carried out following a bidirectional feedback method. It was intended to develop skills to improve sleep through 9 simple tips. An analysis of covariance was performed on all the mean centered outcome variables controlling for the respective baseline scores. Results: After the intervention, in the experimental group, PSQI dropped, the duration and quality of sleep increased. Further, a decrease in fasting glucose and in HbA1c levels was observed. Conclusion: The proposed intervention has proven to be effective to improve sleep quality, time, and efficiency and in only 3 months, to achieve a decrease in fasting glucose and HbA1c levels. These findings support the importance of sleep and circadian rhythms education focused on improving in T2DM or IFG.

Type 2 diabetes mellitus may be complicated with chronic complications including diabetic neuropathy (DN). Timely diagnosis is crucial in treatment and maybe reversal of this complication. C reactive protein to albumin ratio (CAR) is considered as a marker of inflammation in various diseases that characterized with acute or chronic inflammation. Since diabetic neuropathy and type 2 diabetes mellitus are also associated with chronic, low grade inflammation, we aimed to study CAR levels of type 2 diabetic subjects with diabetic neuropathy and to compare to those in patients without diabetic neuropathy. Type 2 diabetic patients presented to our institutional outpatient clinics were divided into two according to the presence of DN. Subjects with DN were listed as DN group and others were as non-DN group. Characteristics and laboratory data, including CAR, in DN and non-DN groups were compared. Median CAR of the DN and non-DN groups were 2,19 (0,2-49)% and 0,56 (0,02-5,8)%, respectively (p&lt;0.001). CAR was significantly and positively correlated with age (r=0.15, p&lt;0.001), weight (r=0.19, p=0.01), BMI (r=0.11, p=0.03), waist circumference (r=0.10, p=0.046), fasting plasma glucose (r=0.14, p=0.004), serum creatinine (r=0.25, p&lt;0.001), triglyceride (r=0.17, p&lt;0.001), and LDL-cholesterol (r=0.13, p=0.001) levels. Moreover, CAR was inversely correlated with eGFR levels (r=-0.16, p&lt;0.001). The sensitivity and specificity of CAR (when higher than 1,02%) in predicting diabetic neuropathy were 78% and 73%, respectively (AUC: 0.84, p&lt;0.001, 95% CI: 0,82-0,87). Moreover, high CAR level was an independent risk factor of diabetic neuropathy (p&lt;0.001, OR: 1.34, 95% CI: 0.48-1.62). In conclusion, elevated CAR levels could be considered as a marker of diabetic neuropathy.

This observational pilot study aimed to investigate continuous glucose monitoring (CGM) metrics in older Japanese patients with type 2 diabetes mellitus (T2DM) using a continuous glucose monitoring system (FreeStyle Libre Pro) for CGM during the first tirzepatide administration and compared the glycemic control measures before and after the treatment. The four patients re-ported a mean age of 79.5 years (standard deviation [SD]: 5.8), mean body mass index of 24.63 kg/m2 (SD: 4.7), and mean glycated hemoglobin level of 9.1% (SD: 2.1). After tirzepatide treatment, the mean of time in range, time above range, and time below range changed from 53.2% to 78.9% (p = 0.041), 45.8% to 19.7% (p = 0.038), and 1.0% to 1.5% (p = 0.206), respectively. Improved hy-perglycemia reduced the oral glucose medication in two cases and decreased the frequency of insulin injections in two cases. All cases demonstrated the CGM index improvement during short-term observation despite some differences. Future studies need to investigate the long-term impact on functional prognosis, safety, and tolerability, especially in nonobese older Asian pa-tients, to elucidate the potential benefits of tirzepatide. However, tirzepatide-associated robust glycemic improvement may simplify and reduce diabetes treatment-associated complication in older patients with T2DM.

Excessive intracellular glucose in insulin independent tissues including nerve, nephron, lens and retina invites mishandling of metabolism of glucose resulting in a background of increased oxidative stress, advanced glycation end products (AGE) formation, lipid peroxidation and failure of antioxidant defense systems in type 2 diabetes mellitus (T2DM). All these detrimental biochemical anomalies ultimately attack biological membranes and especially capillary beds of retina and glomerulus of kidney, resulting in break-down of inner blood-retinal i.e. initiation of diabetic retinopathy (DR). If these disarrays are corrected to a large extent, development of DR can be avoided or delayed. In this prospective clinical trial, 185 patients with T2DM who received B-vitamins, vitamin-C, and E along with anti-diabetic medication for five years, demonstrated a slower rate of the development of DR and reduced abnormal biochemical mediators like reactive oxygen species (ROS), malondialdehyde (MDA), AGE, and vascular endothelial growth factor (VEGF) compared to 175 T2DM individuals who were treated with only anti-hyperglycemic drugs.

Type 2 diabetes mellitus (T2DM) is an endocrine illness associate with various changes in the immune system and adaptor protein levels. Cytokine dependent hematopoietic cell linker (CLNK) is an adapter protein that regulates immune receptor signaling and acts as a regulator of the receptor signaling of T-cells and natural killer T-cell. The role of CLNK in T2DM is not studied previously. In the present study, serum CLNK level was measured and correlated with some sociodemographic and insulin resistance (IR) parameters. This is achieved by performing measurement of CLNK and insulin parameters (glucose, insulin, and HbA1c in addition to the calculation of the functions of IR (HOMA2IR), insulin sensitivity (HOMA%S), and beta-cell function (HOMA%B)) in 60 T2DM patients and 30 controls. The results indicated a significant increase (p=0.025) in serum CLNK in patients group in comparison with the controls. Multivariate generalized linear model (GLM) analysis revealed no significant effect of age, BMI, and sex on the CLNK level. The results of tests for between-subjects showed that the CLNK affects diagnosis significantly (F=7.445, p=0.008, partial η² =0.081) and its effect is approximately the same as the effect of insulin (F=8.107, p=0.006, partial η² =0.087). The correlation study showed a highly significant positive correlation between CLNK and the duration of disease (rho=0.420, p<0.001). It can be concluded that the increase CLNK in T2DM revealing the role of the adaptor proteins level in the nature of disease. Elevation of CLNK level may be used as a predictor for diabetes complications, which needs more investigations.

Type II diabetes (T2D) is a multifaceted metabolic disease influenced by various factors (genetic, epigenetic, environmental, and other). An alarming surge in T2D prevalence is estimated, reaching 700 million cases by 2045 worldwide. This review explores the complex interactions of multiple risk factors throughout life and offers a new perspective on T2D. Genetic and epigenetic influences are described in detail. Prenatal factors, such as exposure to undernutrition and maternal overfeeding, induce lasting epigenetic changes, affecting T2D susceptibility. Furthermore, birthweight is a crude proxy for perinatal programming, with low and high birthweights associated with increased T2D risk. Often overlooked, the early postnatal period also significantly contributes to perinatal programming. Neonatal over-nutrition and feeding choices exert lasting effects on DNA methylation and metabolic outcomes later in life. Stress during this period further exacerbates T2D susceptibility. In continuation, childhood behaviors which are influenced by prior periods contribute substantially to T2D risk. Adverse childhood experiences amplify the risk of many diseases, including T2D. Sleep hygiene throughout life plays a role in metabolic health, influencing insulin resistance and appetite regulation. In adulthood, obesity remains a prominent predictor of T2D, with chronic stress contributing to weight gain and unhealthy lifestyle. This review proposes a novel perspective, considering T2D pathophysiology as a nonlinear process governed by numerous factors and their interactions throughout life. The inherent unpredictability suggests a need for personalized interventions tailored to specific risk profiles, emphasizing the importance of understanding gene-environment interactions and embracing a holistic view of T2D pathogenesis.

Lung cancer (LC) is the second most common cancer and the leading cause of cancer deaths in the U.S. Insulin therapy, a key treatment for managing Type 2 Diabetes Mellitus (T2DM), may increase LC risk. The impact of non-insulin antidiabetic drugs, particularly GLP-1 receptor agonists (GLP-1RAs), on LC risk is not well understood. This study evaluated LC risk in T2DM patients comparing seven non-insulin antidiabetic agents to insulin. Using the TriNetX Analytics platform, we analyzed de-identified electronic health records of 1,040,341 T2DM patients treated between 2005-2019, excluding those with prior antidiabetic use or LC diagnoses. We calculated hazard ratios and confidence intervals for LC risk and used propensity score matching to control for confounding factors. All non-insulin antidiabetic drugs, except alpha-glucosidase inhibitors, significantly reduced LC risk compared to insulin, with GLP-1RAs showing the greatest reduction (HR: 0.49, 95% CI: 0.41, 0.59). GLP-1RAs were consistently associated with lowered LC risk across all histological types, races, genders, and smoking statuses. These findings suggest that non-insulin antidiabetic drugs, particularly GLP-1RAs, may be preferable for managing T2DM while reducing LC risk.

Introduction: The presence of multiple comorbidities increases the risk of all-cause mortality, but the effects of the comorbidity sequence before the baseline date on mortality remained unexplored. This study investigated the relationship between coronary heart disease (CHD), atrial fibrillation (AF) and heart failure (HF) sequence on all-cause mortality risk in type 2 diabetes mellitus. Methods: This study included patients with type 2 diabetes mellitus prescribed antidiabetic/cardiovascular medications in public hospitals of Hong Kong between January 1st, 2009 and December 31st, 2009 with follow-up until death or December 31st, 2019. Cox regression was used to identify comorbidity sequences predicting all-cause mortality in patients with different medication subgroups. Results: A total of 249291 patients (age: 66.0±12.4 years, 47.4% male) were included. At baseline, 7564, 10900 and 25589 patients had AF, HF and CHD, respectively. Over follow-up (3524±1218 days), 85870 patients died (mortality rate: 35.7 per 1000 person-years). Sulphonylurea users with CHD developed later, but insulin users with CHD developing earlier, in the disease course had lower mortality risks. Amongst insulin users with two of the three comorbidities, CHD with preceding AF (hazard ratio [HR]: 3.06, 95% CI: [2.60-3.61], p<0.001) or HF (HR: 3.84 [3.47- 4.24], p<0.001) had a higher mortality. In users of lipid-lowering agents with all three comorbidities, those with preceding AF had higher risk of mortality (AF-CHD-HF: HR: 3.22, [2.24-4.61], p<0.001; AF-HF-CHD: HR: 3.71, [2.66-5.16], p<0.001). Conclusion: The sequence of comorbidity development affects the risk of all-cause mortality to varying degrees in diabetic patients on different antidiabetic/cardiovascular medications.

To assess the community health workers’ (CHWs) knowledge, attitude, and practices (KAP) in type-2 diabetes (T2D) and hypertension (HTN) management. We thus also sought to assess the potential health system barriers for incorporating CHWs in T2D and HTN management. Mixed-method study comprised (1) a survey among 153 active CHWs to assess their KAP of T2D and HTN, and (2) semi-structured interviews with key informants to understand challenges of the health system and proposed solutions in incorporating CHWs in T2D and HTN management. The majority of CHWs correctly answered general knowledge questions on NCDs, risk factors, and prevention; however, only one-quarter correctly answered questions on smoking, family history, or tobacco use as risk factors. Most respondents appeared to have positive attitudes and have been practicing some activities related to T2D and HTN. Both financial and non-financial resource constraints were cited as challenges of the health system; therefore, re-structuring the role definition of CHWs and task of responsibilities, and assessment the need and workload have been proposed as ways forwards to effectively incorporate CHWs in T2D and HTN care. CHWs in Cambodia have shown their potential in T2D and HTN management; however, a well-designed strategy including technical training, clearly defined roles and responsibilities, and strong supporting structure are important to maximize their potential in the health system.

C-reactive protein to lymphocyte ratio (CLR) has been shown to be associated with diseases characterized by chronic, low-grade inflammation. Since type 2 diabetes (T2DM) is also associated with inflammation, we aimed to study the association between CLR and T2DM. Patients with T2DM who presented to internal medicine outpatient clinics of our institution were divided into 2 groups according to their glycosylated hemoglobin (HbA1c) levels as well-controlled (HbA1c&lt;7%) and poorly controlled (HbA1c≥7%) T2DM groups. Subjects assigned as healthy in routine check-up were included as control group. CLR values of the well and poorly controlled diabetics and control cases were compared. CLR of T2DM group (3.51 (0.03-21.78)) was significantly higher than that of the controls (0.65 (0.02-2.92)) (p&lt;0.001). CLR was found to have a sensitivity of 63.2% and a specificity of 97.3% in predicting T2DM. The CLR value of patients with poor diabetic control was 4.76 (0.06-21.78), while the CLR value of patients with well controlled disease was 2.53 (0.03-12.07) (p&lt;0.001). The sensitivity and specificity of the CLR in demonstrating poor diabetic control was 41.2% and the 86.1%, respectively. In conclusion, elevated CLR in T2DM patients and even more increased levels in poorly controlled diabetics suggest that CLR could be a useful additional diagnostic tool in treatment follow-up of the T2DM population.

Abstract: Viremia in coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is often only discussed in passing and there are very few references detailing its structural mechanisms. In addition to viremia in the classic closed cardiovascular system, the lymphatic system is discussed in relation to a possible “lympho-viremia”. The cells that comprise each of these separate but interacting systems will be examined and include endothelial cells, erythrocytes, leukocytes (monocytes/monocyte-derived macrophages and resident tissue macrophages) (lymphocytes) (neutrophils) and thrombocytes -platelets. The SARS-CoV-2 virus has been identified in multiple extrapulmonary target organs at autopsy in those with severe COVID-19 requiring intensive care. Vulnerable COVID-19 patients may suffer from multiple storms including viral/virion storm, redox storm, cytokine storm and thrombo-embolic storm. Therefore, it is important that the possible mechanisms of viremia be explored in greater detail and how these mechanisms might affect intravascular blood components, extracellular tissue interstitium and organ structural remodeling and function. While the co-morbidity of T2DM does not increase the risk of acquiring COVID-19, it is commonly accepted that T2DM increases the risk for COVID-19 admissions to hospitals, assisted ventilation, morbidity and mortality. Importantly, the co-existence of T2DM and COVID-19 may have synergistic detrimental outcomes.

This study unveils verapamil's compelling cytoprotective and proliferative effects on pancreatic β-cells amidst diabetic stressors, spotlighting its unforeseen role in augmenting cholecystokinin (CCK) expression. Through rigorous investigations employing MIN6 β-cells and zebrafish models under type 1 and type 2 diabetic conditions, we demonstrate verapamil's capacity to significantly boost β-cell proliferation, enhance glucose-stimulated insulin secretion, and fortify cellular resil-ience. A pivotal revelation of our research is verapamil's induction of CCK, a peptide hormone known for its role in nutrient digestion and insulin secretion, which signifies a novel pathway through which verapamil exerts its therapeutic effects. Furthermore, our mechanistic insights reveal that verapamil orchestrates a broad spectrum of gene and protein expressions pivotal for β-cell survival and adaptation to immune-metabolic challenges. In vivo validation in a zebrafish larvae model confirms verapamil's efficacy in fostering β-cell recovery post-metronidazole inflic-tion. Collectively, our findings advocate for verapamil's reevaluation as a multifaceted agent in diabetes therapy, highlighting its novel function in CCK upregulation alongside enhancing β-cell proliferation, glucose sensing, and oxidative respiration. This research enriches the therapeutic landscape, proposing verapamil not only as a cytoprotector but also as a promoter of β-cell re-generation, thereby offering fresh avenues for diabetes management strategies aimed at pre-serving and augmenting β-cell functionality.

Abstract: The recently described perivascular unit (PVU) resides immediately adjacent to the true capillary neurovascular unit (NVU) in the postcapillary venule and contains the normal-benign perivascular spaces (PVS) and pathological enlarged perivascular spaces (EPVS). The PVS are important, in that, they also have recently been identified to be the construct and the conduit responsible for the delivery of metabolic waste from the interstitial fluid to the ventricular cerebrospinal fluid for disposal into the systemic circulation and has been termed the glymphatic system. Importantly, the outermost boundary of the PVS is lined by protoplasmic perivascular astrocyte endfeet (pvACef) that communicate with regional neurons. As compared to the well-recognized and described neurovascular unit (NVU) and NVU coupling, the PVU is less well understood and remains an emerging concept. The primary focus of this narrative review is to compare the similarities and differences between these two units and discuss each of their structural and functional relationships and how they relate not only to brain homeostasis but also how they may relate to the development of multiple clinical neurological disease states and specifically how they may relate to obesity, metabolic syndrome, and type 2 diabetes mellitus. Additionally, the concept and importance of a perisynaptic astrocyte coupling to the neuronal synapses with pre- and postsynaptic neurons will also be considered as a perisynaptic unit to provide for the creation of the information transfer in the brain via synaptic transmission and brain homeostasis. Multiple electron microscopic images and illustrations will be utilized in order to help explain these complex units.

Abstract: Astrocytes (ACs) are the most abundant human cell in the brain and importantly, are the master connecting and communicating cells that provide structural and functional support of brain cells at all levels of organization. Further, they are recognized to be the guardians and housekeepers of the brain. Protoplasmic perivascular astrocyte endfeet and their basal lamina form the delimiting outermost barrier (glia limitans) of the perivascular spaces in postcapillary venules and are important for the clearance of metabolic waste and comprise the glymphatic system, which is critically dependent on the proper waste removal by the pvACef polarized aquaporin 4 water channels. Also, the protoplasmic perisynaptic astrocyte endfeet (psACef) are important in cradling the neuronal synapses that serve to maintain homeostasis and serve a functional and supportive role for synaptic transmission. Enlarged perivascular spaces (EPVS) are emerging as important aberrant findings on magnetic resonance imaging (MRI) and associate with white matter hyperintensities, lacunes, aging, accepted to be biomarkers for cerebral small vessel disease, increased in obesity, metabolic syndrome, and type 2 diabetes. Knowledge is exponentially expanding regarding EPVS along with the glymphatic system, since EPVS are closely associated with impaired glymphatic function and waste removal from the brain to the cerebrospinal fluid and systemic circulation. This review intends to focus on how the pvACef play a crucial role in the development of EPVS.

Type 2 diabetes mellitus(T2DM) is an increasingly prevalent and serious health problem. Its onset is typically associated with metabolic disorders and disturbances in the gut microbiota. Previous studies have reported the anti-T2DM effects of Pueraria thomsonii Radix as a functional food. However, the mechanism of action is still unknown. In this study, the effects of Pueraria thomsonii Radix water extract(PTR) on db/db mice were evaluated by pharmacology, metabolomics, and 16S rRNA gene sequencing. The results showed that PTR could improve the body weight of mice, reduce fasting blood glucose(FBG), urinary glucose(UGLU), homeostasis model assessment insulin resistance(HOMA-IR), urinary albumin/creatinine ratio(UACR), and reduce pancreatic tissue damage. Metabolomics showed that the Model group produced 109 differential metabolites, of which 74 could be regulated by PTR. 16S rRNA sequencing was done in fecal samples and results showed that PTR could reduce the Firmicutes/Bacteroidetes ratio(F/B) associated with obesity and regulate 3 beneficial bacteria and 1 harmful bacteria. In conclusion, the results showed that PTR could ameliorate T2DM symptoms, metabolic disorder, and gut microbiota imbalance of db/db mice, and it was superior to metformin in some aspects. We suggested for the first time that γ-aminobutyric(GABA) may be involved in the regulation of the microbiota-gut-brain axis(MGB) and thus affect the metabolic disorders associated with T2DM. This study will provide a scientific basis for the development of functional food with PTR.

Background: Even though a number of studies have verified the positive effect of physical activity (PA) on self-related health (SRH) no previous research has examined this association among pediatric patients with Type 1 diabetes mellitus (T1DM). Objective: The purpose of this study was to investigate the association between regular physical activity (PA) and self-rated health (SRH) in pediatric patients with Type 1 diabetes mellitus (T1DM) who lacked diabetes care. Methods: We conducted a retrospective study among pediatric patients with T1DM who lacked diabetes care and were enrolled in a diabetes education program between January 2011 to January 2015 at the endocrinology clinic of Seoul National University Children’s Hospital in South Korea. The eligible participants for this study were 37 pediatric patients with T1DM aged 9 to 17 years. PA was divided into regular PA and muscle strength exercise to analyze the relationship with SRH using binomial logistic regression analysis. Results: The results showed SRH of pediatric patients with T1DM who did not engage in regular PA was significantly lower than those who did (OR in regular PA = .199 [95% CI: .040, .995]; OR in regular muscle strength exercise = .097 [95% CI: .023, .825]). Conclusions: In conclusion, regular PA and muscle strength exercise in pediatric patients with T1DM who lacked diabetes care were effective in improving their SRH. A systematic plan is required to enhance regular PA for pediatric patients with T1DM.

Gestational Diabetes Mellitus (GDM) is related with adverse outcomes for both the mother and the offspring. Immune and senescence play a crucial role in GDM progression. This study aims to explore the diagnostic significance of immune-related senescence (IRS) genes in GDM. We used weighted gene co-expression network analysis (WGCNA) and single sample gene set enrichment analysis (ssGSEA) to compute the immune score and aging score in control and GDM samples. Machine learning identified core IRS genes. Then we performed unsupervised cluster analysis in GDM patients to explore immune infiltration. Finally, we validated the core genes in clinical samples. We used the intersection of MEblack module from WGCNA and differentially expressed genes (DEGs) to obtain the potential genes. Next, a univariate logistic regression model including 23 potential genes were constructed, and these genes were filtered by least absolute shrinkage and selection operator (LASSO) algorithm. There were 5 potential genes (COX17, RRAS2, RRAGC, CECR1, and TACC2), which defined as biomarkers, remained eventually, and the efficacy of these biomarkers was evaluated by nomogram. Finally, the results from both qRT-PCR and western blot analyses demonstrated CECR1 was down-regulated, while TACC2 was up-regulated in GDM placental tissue. Our study identified CECR1 and TACC2 as diagnostic biomarkers for GDM associating with immune and senescence, providing a new perspective on GDM progression.

This review aimed at synthesizing the mechanisms and outcomes of metabolic surgery on hormones, adipokines, metabolomics, and at the molecular level. We reviewed the endocrine, microRNA, and metabolomics changes in human and animal models following metabolic surgery for the treatment of obesity and diabetes. PubMed, Science Direct, Scopus, and Google Scholar databases were searched up to February 2022. The most relevant studies in the area over the past 17 years have been considered for this review. In most cases, metabolic procedures especially those that include intestinal bypass components, showed remission of type 2 diabetes. This involves a variety of weight-independent mechanisms to improve glucose homeostasis, improving insulin sensitivity, and secretion. The miRNAs’ dysregulated expressions have essential roles in metabolic processes. Metabolic surgery is a potentially sustainable treatment that can modify a patient’s physiology and glucose regulation mechanism. The feasibility and role of miRNA are important for potential targeted genetic pathways in future obesity with type 2 diabetes management.

Introduction: Type 2 Diabetes mellitus (T2DM) is a common disease burdened with significant morbidity and mortality. Despite the substantial number of new available drug treatments, adherence to therapy and adverse drug reactions (ADRs) are the major constrain in the management of this disease. We evaluated the use, the adherence and the dsaftey of antidiabetic drugs in patients with T2DM. Methods: we performed an observational, retrospective, multicenter study on medical records of outpatients referred to general practitioners. Drug adherence was measured in agreement to the European Society for Patient Adherence, Compliance and Persistence Medication Adherence Reporting Guideline. ADRs were evaluated using the Naranjo probability scale. Collected data were analyzed using the Statistical Package for the Social Sciences. Results: During the study we evaluated 12,170 medical records of 7 general practitioners. The most prescribed drug was metformin alone (28.4%) or with other oral antidiabetics (19.6%) and then insulin (n: 354; men 190, women 164). Enrolled patients were stratified as high (35%), medium (41%) and low (24%) adherence. Logistic regression showed an association between T2DM less than or equal to 5 years and low adherence (P = 0.023). During the study we recorded 26 ADRs that was correlated with sex (women) and insulin treatment. Conclusion: this real-life study shows that patients with T2DM have high adherence probably related dto a low number of ADRs

Abstract: Pericyte(s) (Pcs) and resident perivascular macrophages (rPVMΦs) are positioned perfectly in the neurovascular unit (NVU) and perivascular spaces to facilitate metainflammation that results in brain endothelial cell activation and dysfunction and neuroinflammation. Their positions within the NVU allow intimate contact with one another as follows: Brain endothelial cells (BECs) and the Pcs via their shared basement membrane and physical contact peg-socket junctions with N cadherins and gap junctions Cx43; Pcs and rPVMΦs intimate contacts. Additionally, rPVMΦs have intimate contact with the astrocyte endfeet (ACef) that form the outermost membrane of perivascular spaces. Importantly, ACef have intimate contact with BECs that have intimate physical contact with neuronal axons and dendrites to complete NVU coupling. The multiplicity of intimate contacts of NVU cells allow for continuous crosstalk communications to provide brain homeostasis. While each of the cells of the NVU play important roles in the development of enlarged perivascular spaces (EPVS), this review focuses on the Pcs and rPVMΦs and discusses each of the intimate contacts and their functional significance in detail with numerous illustrations and transition electron microscopic images to demonstrate their role in the development of EPVS. EPVS are known to be biomarkers for cerebral small vessel disease and impaired glymphatic system waste clearance. Additionally, EPVS associate with mixed dementias of vascular dementia, vascular contributions to cognitive impairment and dementia, and Alzheimer’s disease that results in high economic and psychosocial cost to the global community.

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted from the gut upon nutrient stimulation and regulate postprandial metabolism. These hormones are known as classical incretin hormones and are responsible for a major part of postprandial insulin release. The incretin effect is severely reduced in patients with type 2 diabetes, but it was discovered that administration of GLP-1 agonists was capable of normalizing glucose control in these patients. Over the last decades, much research has been focused on the development of incretin-based therapies for type 2 diabetes. These therapies include incretin receptor agonists and inhibitors of the incretin-degrading enzyme dipeptidyl peptidase-4. Especially the development of diverse GLP-1 receptor agonists has shown immense success, whereas studies of GIP monotherapy in patients with type 2 diabetes have consistently been disappointing. Interestingly, both GIP-GLP-1 co-agonists and GIP receptor antagonists administered in combination with GLP-1R agonists appear to be efficient with respect to both weight loss and control of diabetes, although the molecular mechanisms behind these effects remain unknown. This review describes our current knowledge of the two incretin hormones and the development of incretin-based therapies for treatment of type 2 diabetes.

Type 2 diabetes (T2D) is a chronic systemic disease with a complex etiology, characterized by insulin resistance and mitochondrial dysfunction in various cell tissues. To explore this relationship, we conducted a secondary analysis of complete mtDNA sequences from 1,261 T2D patients and 1,105 control individuals. Our findings revealed significant associations between certain single nucleotide polymorphisms (SNPs) and T2D. Notably, the variants m.1438A>G (controls: 32 [27.6%], T2D: 84 [72.4%]; OR: 2.46; 95%CI: 1.64-3.78; p<0.001), m.14766C>T (controls: 498 [36.9%], T2D: 853 [63.1%]; OR: 2.57, 95%CI: 2.18-3.04, p<0.001), and m.16519T>C (controls: 363 [43.4%], T2D: 474 [56.6%]; OR: 1.24, 95%CI: 1.05-1.47, p=0.012) were significantly associated with diabetes probability. The variant m.16189T>C Previously reported in multiple studies in different populations, it was not found to be associated with T2D in our analysis (controls: 148 [13.39] T2D: 171 [13.56%]; OR: 1.03; 95%CI: 0.815-1.31,; p=0.83). These results provide evidence suggesting a link between some mtDNA polymorphisms and T2D, probably related to association rules and topological patterns and three-dimensional confirmation associated to regions where the changes are, rather than to point mutations in the sequence.

Diabetes mellitus is a heterogeneous disease of complex etiology and pathogenesis. Hyperglycemia leads to many serious complications, but also directly initiates the process of β cell apoptosis. A potential strategy for the preservation of pancreatic β cells in diabetes may be to inhibit the implementation of pro-apoptotic pathways or to enhance the action of pancreatic protective factors. The HIPPO signaling pathway is proposed and selected as a target to manipulate the activity of its core proteins in therapy - basic research. MST1 and LATS2 as major upstream signaling kinases of the Hippo pathway are considered as target candidates for pharmacologically induced tissue regeneration and inhibition of apoptosis. Manipulating the activity of components of the HiPPO pathway offers a wide range of possibilities, and thus is a potential tool in the treatment of diabetes and the regeneration of β cells. Therefore, it is important to fully understand the processes involved in apoptosis in diabetic states and to fully characterize the role of this pathway in diabetes. Therapy consisting in slowing down or stopping the mechanisms of apoptosis may be an important direction of diabetes treatment shortly.

Abstract: The brain endothelial cell (BEC) glycocalyx (ecGCx) is a BEC surface coating consisting of a complex interwoven polysaccharide (sweet husk) mesh-like network of membrane-bound proteoglycans, glycoproteins, and glycosaminoglycans (GAGs) covering the apical luminal layer of the brain endothelial cells. The ecGCx may considered as the 1st barrier of a tripartite blood-brain barrier (BBB) consisting of 1) ecGCx; 2) BECs; (3) extravascular compartment of pericytes, extracellular matrix, and perivascular astrocytes, Perturbations of this barrier allow for increased permeability in the postcapillary venule that will be permissive to both fluids, solutes, and proinflammatory peripherally-derived leukocytes into the perivascular spaces (PVS) to result in enlargement as well as increased neuroinflammation. The ecGCx is known to have multiple functions, which include its physical and charge barrier, mechanical transduction, regulation of vascular permeability, modulation of inflammatory response, and anticoagulation functions. This review discusses each of the listed functions in detail and utilizes multiple transmission electron micrographs and illustrations to allow for a better understanding of the ecGCx structural and functional roles as it relates to enlarged perivascular spaces (EPVS). This is the 5th review of a series quintet that discuss the importance of EPVS from the perspective of the cells of brain barriers. Attenuation and/or loss of the ecGCx results in brain barrier disruption with increased permeability to proinflammatory leukocytes, fluids and solutes, which accumulate in the postcapillary venule perivascular spaces. This accumulation results in obstruction and results in EPVS with impaired waste removal of the recently recognized glymphatic system. Importantly, EPVS are progressively being regarded as a marker of cerebrovascular and neurodegenerative pathology.

Type 2 diabetes mellitus (T2DM) is frequently accompanied by affective disorders with a prevalence of comorbid depression of around 25%. Nevertheless, the biomarkers of affective symptoms including depression and anxiety due to T2DM are not well established.Aims: This study was conducted to delineate the serum biomarkers predicting affective symptoms due to T2DM above and beyond the effects of insulin resistance and atherogenicity. Methods: The present study delineated the effects of serum levels of copper, zinc, β-arrestin-1, FBXW7, lactosylceramide (LacCer), serotonin, albumin, calcium, magnesium, IR and atherogenicity on severity of depression and anxiety in 58 men with T2DM and 30 healthy male controls. Severity of affective symptoms was assessed using the Hamilton Depression and Anxiety rating scales.Results: We found that 61.7% of the variance in affective symptoms was explained by the multivariate regression on copper, β-arrestin-1, calcium, and insulin resistance coupled with atherogenicity, while 44.4% of the variance in the latter was explained by copper, β-arrestin-1, LacCer (all positively) and calcium and FBXW7 (both negatively). Copper and LacCer (positive) and calcium and BXW7 (inverse) had significant specific indirect effects on affective symptoms which were mediated by insulin resistance and atherogenicity. Copper, β-arrestin-1, and calcium were associated with affective symptoms above and beyond the effects of insulin resistance and atherogenicity.Discussion: T2DM and affective symptoms share common pathways namely increased atherogenicity, insulin resistance, copper, and β-arrestin-1, and lowered calcium, whereas copper, β-arrestin-1, calcium, LacCer, and FBXW7 may modulate depression and anxiety symptoms by affecting T2DM.

Type 2 Diabetes (T2D) is a growing global health problem that requires new and effective prevention and management strategies. Recent research has highlighted the role of epigenetic changes in the development and progression of T2D, and the potential of functional foods as complementary therapy for the disease. This review aims to provide an overview of the current state of knowledge on the preventive epigenetic mechanisms of functional foods in T2D. We provide background information on T2D and its current treatment approaches, an explanation of the concept of epigenetics, and an overview of the different functional foods with demonstrated preventive epigenetic effects in T2D. We also discuss the epigenetic mechanisms by which these functional foods prevent or manage T2D and the studies that have investigated their preventive epigenetic effects. In addition, we revisit works on the beneficial influence of functional foods against the programming and complications of parentally-triggered offspring diabetes. We also postulate, albeit based on the scarce data, that epigenetic inheritance mechanistically mediates the impacts of functional nutrition against the metabolic risk of diabetes in the offspring. Finally, our review highlights the importance of considering the preventive epigenetic mechanisms of functional foods as a potential avenue for the development of new prevention and management strategies for T2D.

ObjectivesAbrus precatorius (AP) is a medicinal plant seldomly studied for its beneficial effects and as such significant gap exists in understanding the basis by which AP leaf bioactives (APLBs) elicit beneficial effects against diabetes mellitus (DM) type-1. MethodsWe estimated DM type-1 related parameters - total protein (TP), direct bilirubin (DB), urea, creatinine, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and serum glucose (SG) after treatment with methanol extracts of AP leaves (APMLE) for 21 days followed by histopathological analysis of kidney and liver sections. APLBs were collected from GCMS fractions, database and literature searches and common targets were cross-intersected with annotated DM type-1 genes from experimental GSE14503 microarray dataset and genecard database. Overlapping differentially expressed genes were collected, their protein-protein interaction network was constructed and analyzed using various bioinformatics tools: Enrichr, SRplot, GSEA, Cytoscape, PyRx, and Discovery Studio to provide insight into the potential molecular basis of APLBs in DM-type-1.Results 15 compounds were identified from GCMS analysis of APMLE. Antidiabetic potential of APMLE was observed with significant (p <0.05) normalization of SG, TP, DB, ALT, AST, ALP, urea & creatinine while hepatorenal photomicrographs indicated moderate safety of use. Erucic acid, oleic acid, phytol and stigmasterol interact with 25 type-1 DM biomarkers revealed to be enriched in lipid and prostaglandin metabolic processes, neuroactive ligand receptor interaction, PPAR signaling pathway, diabetic cardiomyopathy, and cAMP signaling pathway. Furthermore, PPARalpha (peroxisome proliferator-activated alpha) and SCD (stearoyl-coenzyme A desaturase) were revealed as core biotargets interacting with APLBs via hydrogen bond, hydrophobic interaction and van der Waals forces from docking study. ConclusionThis study demonstrated the potency of APLBs in vivo against type-1 DM. The potential basis of action has been studied from computational perspective. Future interests may provide additional experimental data into mechanisms by which APLBs elicit this remarkable ability.

New onset diabetes mellitus after transplantation (NODAT) is a common complication following solid organ transplantation, with varying incidence rates due to discrepancies in defining NODAT and follow-up duration, alongside modifiable and non-modifiable risk factors. NODAT adversely affects patient survival and graft longevity, warranting early detection, especially in countries experiencing a rise in kidney transplant cases, emphasizing the need for understanding diagnostic criteria, risk factors, pathogenic mechanisms, and post-transplant outcomes.

A good management of diabetes requires at the same time self-regulation behaviour and a balanced involvement of family components. This study’s aims were: understanding fear of injections and perceptions of family conflicts in preadolescents and adolescents with type 1 diabetes mellitus and their mothers, comparing their perceptions, and identifying the risk factors impacting patients’ quality of life. Participants were one hundred and two patients (Mean age = 14.63, SD = 2.43; age range = 10-19 years; Females = 52) and their mothers (Mean age = 46.94, SD = 6.2, age range = 27-63 years), who filled in self and proxy-report questionnaires. Twenty % of patients and 14.7% of their mothers reported clinical score for fear of self-injection and blood testing. Mothers reported higher fear of injecting and family conflicts compared with the patients. Age, fear of injecting and family conflicts impacted significantly on patients’ quality of life perceptions. Clinical consideration and recommendations are given basing on the empirical results.

We aimed to study the knowledge of diabetes among high-risk individuals for diabetes in the Indian state of Kerala. The baseline data collected from 1007 participants of the Kerala Diabetes Prevention Program were analyzed. Diabetes knowledge was assessed using a scale adapted from a large nationwide study conducted in India. The composite score of the scale ranges from 0 to 8. The mean age of participants was 46.0 (SD: 7.5) years, and 47.2% were female. The mean diabetes knowledge score was 6.9 (SD: 2.1), with 59.5% having the maximum possible score of 8. Of 1007 participants, 968 (96.1%) had heard the term diabetes, and of them, 84.7% know what diabetes is, 87.2% think more and more people are getting diabetes nowadays, 79.6% know that diabetes can cause complications in organs, and 75.9% know that diabetes can be prevented. While the level of diabetes knowledge was high among our participants, a quarter of them (24.1%) were not aware that diabetes can be prevented. Thus, there is a need for health promotion programs to increase the knowledge of diabetes prevention among high-risk individuals in Kerala.

The study aimed to estimate the prevalence and association between sarcopenia and blood biochemical parameters, nutritional intake, anthropometric measurements, physical performance, and physical activity in patients with Type 2 Diabetes Mellitus (T2DM). According to the diagnosis criteria of the Asian Working Group for Sarcopenia (AWGS) in 2019, 110 patients with T2DM (aged: 50–80 years) were divided into three groups: Non-sarcopenia (n = 38), Possible Sarcopenia (n = 31, 28.2%), and Sarcopenia (n = 41, 37.3%). Blood samples were collected and nutritional intake was evaluated by a registered dietitian. A food frequency questionnaire and Godin leisure-time exercise questionnaire were used to assess their daily vitamin D intake and physical activity. There were significant differences in age, serum vitamin D3 levels, nutritional intake, anthropometric measurements, and physical performance between the three groups. In elderly patients with T2DM, there was a significant association between sarcopenia with BMI, body fat percentage (BF%), and dietary energy and protein intake. Low serum vitamin D3 is a significant risk factor for possible sarcopenia.

Glycated hemoglobin (HbA1c) is used to assess glycemic control in Type 1 diabetes (DM1) patients. Apolipoproteins play an essential role in DM1 pathophysiology and may be associated with complications, as well as HbA1c. This cross-sectional observational study consisting of 81 children and adolescents of both sexes diagnosed with DM1 investigated the relationship between body fat distribution and lean mass with HbA1C and apolipoprotein values analyzing biochemical and body composition measurements. Shapiro-Wilk test with Lilliefors correction, non-parametric Mann-Whitney test, and others were used with a significance level of 5%. The sample had a diagnosis time of 4.32 years and high blood glucose levels (mean 178.19 mg/dL) and HbA1c (mean 8.57%). Subjects also had a moderate level of adiposity, as indicated by arm and thigh fat areas. The study also found significant differences in the distribution of patients concerning levels of apolipoproteins A and B, with a smaller proportion of patients having undesirable levels. Finally, the study found a significant difference in the distribution of patients with estimated cardiovascular risk based on the ApoB/ApoA-1 ratio. Conclusively, visceral fat in children and adolescents with DM1 may increase the risk of DM1 long-term complications owing to its association with elevated HbA1C and apolipoprotein values.

Stress is an inherent sensation of being unable to handle demands and occurrences. If not properly managed, stress can develop into a chronic condition, leading to the onset of additional chronic health issues like cardiovascular illnesses and diabetes. Various stress meters have been suggested in the past, along with diverse approaches for its estimate. However, in the case of more serious health issues such as hypertension and diabetes, the results can be significantly improved. This study presents the design and implementation of a distributed wearable sensor computing platform with multiple channels. The platform aims to estimate stress levels in diabetes patients by utilizing a fuzzy logic algorithm that is based on the assessment of several physiological indicators. Additionally, a mobile application was created to monitor users' stress levels and integrate data on their blood pressure and blood glucose levels. Validation experiments were performed on patients with chronic diabetes, and the initial findings are presented in the study.

A growing body of research has identified fetal risk factors associated with adult diseases that form the basis for the Developmental Origins of Health and Disease (DOHaD) hypothesis. This theory proposes a critical developmental period during which the fetus is highly susceptible to specific environmental influences that significantly impact health from short to long term. Maternal stress and T2DM during pregnancy are among these influences, likely leading to fetal overexposure to glucocorticoids and suggesting a shared pathway between maternal dysregulated HPA axis and fetal environmental insults. Studies demonstrate that prenatal glucocorticoid exposure alters fetal HPA axis function, affecting brain function, tissue glucocorticoid availability, and fetal growth in utero. These programmed changes, such as altered HPA axis function and reduced fetal growth, contribute to metabolic disorders persisting into adulthood. T2DM is preceded by a prediabetic state, often asymptomatic, which shares similar pathophysiological complications with T2DM, including HPA axis dysregulation observed in animals. Therefore, investigating prediabetes during pregnancy alongside maternal HPA axis function and its effects on fetal outcomes is crucial, as these areas remain understudied. This review aims to synthesize existing literature on pre-existing T2DM during pregnancy, its links to fetal programming via HPA axis changes, and possible links to pregestational prediabetes.

In 2019, due to the global pandemic of the new coronavirus (SARS-CoV-2), lockdown was imposed in Greece. Children with Type 1 Diabetes (T1D) during that period had to maintain a good level of glycemic control despite the subversive changes in their lives. The aim of this study was to assess the impact of lockdown on glycemic control and lifestyle changes of children with type 1 diabetes. The present cross-sectional study included 59 children with T1D who measured their glucose levels through glucose monitoring systems (Continuous Glucose Monitoring, CGM) and Flash Glucose Monitoring (FGM)). Their glycemic profile and demographic data were recorded in three different periods (before, during and after the lockdown). The changes in their daily routine were farther investigated through a short questionnaire which assesses changes in lifestyle-related behavior during COVID 19 pandemic. A significant improvement was noted in the glycemic control of children with T1D during the restrictive measures. Boys scored higher on scale of lifestyle behavior changes during the pandemic (-0.1 vs. -0.3, p=0.015). The results of this study highlight the need for continuous education and insistence on children's adherence with the treatment plan and the beneficial effects of using the new technology for easier monitoring.

The increased consumption of high fat-containing foods has been linked to the prevalence of obesity and abnormal metabolic syndromes. Rhizopus oligosporus, a fungus in the family Mucoraceae, is widely used as a starter for homemade tempeh. Although R. oligosporus can prevent the growth of other microorganisms, it grows well with lactic acid bacteria (LAB). Lactobacillus plantarum can produce β-glucosidase, which catalyzes the hydrolysis of glucoside isoflavones into aglycones (with greater bioavailability). Therefore, the development of a soybean-based functional food by the co-inoculation of R. oligosporus and L. plantarum is a promising approach to increase the bioactivity of tempeh. In this study, the ameliorative effect of L. plantarum in soy tempeh on abnormal carbohydrate metabolism in high-fat diet (HFD)-induced hyperglycemic rats was evaluated. The co-incubation of L. plantarum with R. oligosporus during soy tempeh fermentation reduced the homeostatic model assessment of insulin resistance, HbA1c, serum glucose, total cholesterol, triglyceride, free fatty acid, insulin, and low-density lipoprotein contents and significantly increased the high-density lipoprotein content in HFD rats. It also increased the LAB counts as well as the bile acid, cholesterol, triglyceride, and short-chain fatty acid contents in the feces of HFD rats. Our results suggested that the modulation of serum glucose and lipid levels by LAB occurs via alterations in the internal microbiota, leading to the inhibition of cholesterol synthesis and promotion of lipolysis. Tempeh, produced with both L. plantarum and R. oligosporus, may be a beneficial dietary supplement for individuals with abnormal carbohydrate metabolism.

Gestational diabetes mellitus (GDM) pathophysiology comprises clinical and genetic factors. In fact, GDM has been associated with several single nucleotide polymorphisms (SNPs). This study aimed to build a prediction model of GDM combining clinical and genetic risk factors. A total of 1588 pregnant women from the San Carlos Cohort participated in the present study, 1069 (67.3%) Caucasian (CAU) and 519 (32.7%) Latin American (LAT), 255 (16.1%) with GDM. The incidence of GDM was similar in both groups (16.1% CAU and 16.0% LAT). Genotyping was performed by IPLEX Mass ARRAY PCR selecting 110 SNPs based on literature references. The SNPs showing the strongest likelihood of GDM development were the rs10830963, rs7651090 and rs1371614 in CAU and rs1387153 and the rs9368222 in LAT. Clinical variables including age, pre-pregnancy body mass index and fasting plasma glucose (FPG) at 12 gestational weeks predicted the risk of GDM (AUC 0.648, 95%CI 0.601-0.695 in CAU; AUC 0.688, 95%CI 0.628-9.748 in LAT) and adding the SNPs modestly improved prediction (AUC 0.722, 95%CI 0.680-0.764 in CAU; AUC 0.769, 95%CI 0.711-0.826 in LAT). In conclusion, adding genetic variants enhanced the prediction model of GDM risk in CAU and LAT pregnant women. An RCT is underway to demonstrate its usefulness

Aim: To perform a descriptive analysis of eating patterns and biophysical conditions of previously diagnosed and currently under treatment individuals from a semi-urban Mayan community of Yucatan, and to contrast them with T2DM therapeutic guidelines. Methods: The present study is derived from a randomized clinical trial conducted at Komchen, Yucatan. Participants’ diagnosed with T2DM were included. A 24-hour dietary recall, anthropometric parameters (weight, visceral fat, height, and waist circumference), biochemical (HbA1c) and clinical (blood pressure) variables were evaluated and compared via hypothesis test with T2DM treatment cut-off points (based on World Health Organization criteria). Results: Anthropometric characteristics differ significantly from the ideal criteria. Obesity prevalence within women with T2DM was 92.9%. Only 21% of the participants were under T2DM control (≤7%). Energy and carbohydrates consumption, significantly exceed therapeutic guidelines, whereas protein, fat, and fiber intake were lower than the recommendations. Conclusions: Komchen’s diet, concomitantly with food characteristics, could be related to glycemic decontrol. There is a disproportion in macronutrients consumption in favor of carbohydrates, probably associated with socioeconomic limitations, food availability, and price. Developing nutritional assistance programs which contemplate cultural and economic factors in this Mayan population must be taken into consideration.

Background: Type 2 diabetes mellitus (T2DM) is associated with increased atherogenicity and inflammatory responses, which may be related to increased levels of high mobility group box 1 (HMGB1) and Dickkopf-related protein 1 (DKK1). Objective: The role of HMGB1 and DKK1 in T2DM is examined in association with lipid and insulin profiles. Methods: Serum HMGB1 and DKK1 were measured in T2DM with and without hypertension and compared with controls. Results: HMGB1 and DKK1 are significantly higher in T2DM irrespective of hypertension. T2DM was also accompanied by increased atherogenicity indices. HMGB1 and DKK1 are significantly correlated with HbA1c, glucose, indices of insulin resistance, β-cell function, and glucose toxicity, and different atherogenic indices. A large part of the variance in the β-cell index (30.5%) and glucose toxicity (34.8%) was explained by the combined effects of HMGB1 and DKK1 and hypertension. We found that 18.3% of the variance of the atherogenic index of plasma was explained by HMGB1 and DKK1 levels and that 31.2% was explained by glucose toxicity, HMGB1 and body weight. Conclusion: The higher serum HMGB1 and DKK1 levels in T2DM patients and the associations with atherogenicity indicate that low grade inflammation and disorders in the Wnt pathways are associated with T2DM and that both HMGB1 and DKK1 may contribute to increased atherogenicity in T2DM. Moreover, both biomarkers may cause more deficits in β-cell function and increase glucose toxicity leading to the development of more inflammation and diabetic complications. HMGB1 and the Wnt pathways are new drug targets in the treatment of T2DM.

Type 2 Diabetes Mellitus and Alzheimer's disease are two diseases with a high incidence today that share similar pathophysiological mechanisms suggesting a potential causal relationship between them. In fact, Alzheimer-associated Mellitus Diabetes is also known as Type 3 Diabetes Mellitus and constitutes a diabetes intricately linked to Alzheimer's disease. Central to this association is insulin resistance, a key factor leading to decreased insulin sensitivity, hyperglycemia, and impaired glucose uptake. Because of this, the brain is altered resulting in energy deficits and neuronal damage associated with neurodegenerative disorder characteristic of Alzheimer's disease. Both diseases exhibit common biochemical and physiological characteristics such as inflammation, mitochondrial dysfunction, oxidative stress, and the formation of advanced glycation end products. Understanding the complex pathophysiology of Type 3 Mellitus Diabetes and identifying common features shared with Diabetes and Alzheimer's disease are essential steps towards potential therapeutic interventions targeting the insulin resistance pathway. The authors of this review on the relationships between type 2 diabetes and Alzheimer's disease have developed two works. In the first (Relationships between Type 2 Diabetes Mellitus and Alzheimer's Disease. I. Common pathogenic mechanisms), authors explore the shared (physiological, genetics and molecular) pathological changes occurring in Type 2 Mellitus Diabetes and Alzheimer's disease as well as pathways such as AMPK, PPARγ, cAMP, and PI3K/Akt as potential targets for managing Type 3 Diabetes Mellitus. By exploring these intricate mechanisms, the goal is to uncover their interdependencies and facilitate the discovery of innovative pharmacological and nutritional (epigenetics) strategies. In the second paper (Relationships between Type 2 Diabetes Mellitus and Alzheimer's Disease. II Potential therapies) we describe possible nutritional intervention, particularly dietary patterns and phytochemicals that can enhance the effects of pharmaceutical drugs designed against pathological mechanisms involved in the complex dual disease Type 2 Diabetes Mellitus and Alzheimer's disease (or in Type 3 Diabetes Mellitus as other authors consider).

The pandemic of coronavirus disease (COVID-19), a disease caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), is causing substantial morbidity and mortality. Older age and presence of diabetes mellitus, hypertension and obesity significantly increases the risk for hospitalization and death in COVID-19 patients. In this Perspective, informed by the studies on SARS-CoV-2, Middle East respiratory syndrome (MERS-CoV), and the current literature on SARS-CoV-2, we discuss potential mechanisms by which diabetes modulates the host-viral interactions and host-immune responses. We hope to highlight gaps in knowledge that require further studies pertinent to COVID-19 in patients with diabetes mellitus, hypertension and obesity.

Type 1 Diabetes mellitus (T1DM) occurs when insulin is not produced in the Pancreas due to the autoimmune destruction of the beta cells. The patients may be diagnosed after 80-90% of the beta cells are destroyed. Insulin remains the essential medicine in T1DM management, under continuous monitoring of glucose levels. T1DM management consists of a complex and precise set of self-care measures for the entire life; during this continuous process, the patients could become overwhelmed, angry, anxious, frustrated, and/or discouraged. Therefore, to be widely used and provide general benefits, new technologies for DM management must provide clinical advantages without compromising safety. The compliance of T1DM patients is also essential, thus improving their quality of life (QoL). Moreover, the accessibility of the new system for patients through healthcare coverage is critical; they must be able to buy the new devices and accessories and pay for their maintenance. In this context, our work aims to describe the most recent technologies regarding continuous glucose monitors (CGMs) and continuous subcutaneous insulin infusion (CSII) systems, correlated with psychosocial impact and capacity to improve T1DM patients' life quality.

Background: Maternal diabetes mellitus (MDM) is associated with increased risks for adverse neonatal outcomes. However, the impact of MDM on neonatal outcomes in Bisha, a city in Saudi Arabia, is not well-documented. This study aims to investigate the impact of MDM on neonatal outcomes in the Maternity and Children’s Hospital (MCH), Bisha, Saudi Arabia. Methods: A retrospective cohort study was conducted on 181 pregnant women with diabetes and their neonates diagnosed at Maternity and Children’s Hospital (MCH), Bisha, Saudi Arabia, between October 5, 2020, and November 5, 2022. The primary outcome was a composite of adverse neonatal outcomes, including stillbirth, neonatal death, macrosomia, preterm birth, respiratory distress syndrome, hypoglycemia, and congenital anomalies. Logistic regression analyses were used to adjust for potential confounders. Results: The total sample size was 181. The average age of patients was 34 years (SD=6.45). The majority of the patients were diagnosed with GDM, 147 (81.2%), and pre-GDM, 34 (18.8%). Neonates born to mothers with MDM had a higher risk of adverse neonatal outcomes compared to those born to mothers without MDM (adjusted odds ratio [aOR] = 1.46, 95% confidence interval [CI]: 1.25-1.70). The risks of macrosomia (aOR = 1.74, 95% CI: 1.38-2.19), LBW (aOR = 1.32, 95% CI: 1.06-1.66), and RDS (aOR = 1.57, 95% CI: 1.28-1.93) were significantly higher among neonates born to mothers with MDM. Types of DM were statistically significant with some neonatal outcomes: hypoglycemia (p-value = 0.017), macrosomia (p-value = 0.050), and neonatal death (p-value = 0.017). Conclusion: MDM is associated with an increased risk of adverse neonatal outcomes in Bisha. Early identification and management of MDM may improve neonatal outcomes and reduce the burden of neonatal morbidity and mortality in this population.

Achieving glycemic control and sustaining functional pancreatic β-cell activity remains an unmet medical need in the treatment of type 2 diabetes mellitus (T2DM). Glucokinase activators (GKAs) constitute a class of anti-diabetic drugs designed to regulate blood sugar levels and enhance β-cell function in patients with diabetes. A significant progression in GKA development is underway to address the limitations of earlier generations. Dorzagliatin, a dual-acting GKA, targets both the liver and pancreas and has successfully completed two Phase III trials, demonstrating favorable results in diabetes treatment. The hepato-selective GKA—TTP399— emerges as a strong contender, displaying clinically noteworthy outcomes with minimal adverse effects. This paper seeks to review the current literature, delve into the mechanisms of action of these new-generation GKAs, and assess their efficacy and safety in treating T2DM based on published pre-clinical studies and clinical trials.

Metabolic surgery can promote integrated physiologic improvement to ameliorate metabolic illness, particularly type 2 diabetes. Nevertheless, the therapeutic scope has been limited by unexpectedly inconsistent surgical outcomes. Therefore, the purpose of this study is to overcome the obstacles by determining the core mechanism of conflicting results. The surgical anatomy, clinical course, and outcomes of various metabolic surgeries, including modified types of duodenal-jejunal bypass procedures, were compared to comprehend specific surgical patterns from distinctive perspectives. Patients in exclusively nonobese groups are subjected to avoid compounding by weight fluctuations. During intestinal anastomosis, the epithelial identity of the succeeding intestine is replaced by that of the proximal epithelium through altered crosstalk between the epithelium and opposing mesenchymal cells. The rapid turnover rate and compensatory proliferation of the succeeding intestine accelerate the propagation of the replaced epithelium. Propagation of replaced epithelium could provoke inconsistent outcomes of metabolic surgery. The major determinants of the conflicting results of metabolic surgery are inadequate duodenal exclusion and inappropriate length of the biliopancreatic limbs. The replaced enteroendocrine cells during regeneration provoke inconsistent outcomes of metabolic surgery. The critical factors are the type and density of enteroendocrine cells distributed at the terminal end of the preceding proximal intestine.

Type 2 diabetes has been linked to the expression of Human Leukocyte Antigens, principally to the major Histocompatibility Complex Class II and only scarce reports to Major Histocompatibility Complex class I in specific populations. The objective of the present work was to explore the presence of polymorphisms in the MHC class I related to Type 2 diabetes in the Mexican population using the GWAS SIGMA database. This database contains information of 3,848 Mexican individuals with type 2 diabetes and 4,366 control individuals from the same population without clinical or hereditary history of the disease. The searching criteria considered a P value < 0.005 and odds ratio, OR > 1.0. Ten novel statistically significant nucleotide variants were identified: four polymorphisms associated with HLA-A (A*03:01:01:01), and six with HLA-C (C*01:02:01:01). These alleles have a high prevalence in Latin American populations and could potentially be associated with autoimmunity mechanisms related with the development of Type 2 diabetes complications.

Type 2 Diabetes Mellitus (T2DM) is associated with a high risk of atherosclerotic cardiovascular (CV) disease. Contributing pathophysiologic factors include endothelial dysfunction caused by excessive production of reactive oxygen species (ROS), increased activity of nuclear factor kB (NFkB), altered macrophage polarization, and reduced synthesis of endothelial progenitor cells (EPC). Consequently, there can be a potentially rapid progression of the atherosclerotic disease with a higher propensity to unstable plaque, leading to increased cardiovascular mortality. Management is aimed at prevention, early diagnosis, and treatment of hyperglycemia and vascular complications. Innovative therapeutic approaches for T2DM seek to customize the antidiabetic treatment to each patient in order to optimize glucose-lowering effects, minimize hypoglycemia and adverse effects, and prevent cardiovascular events. The newer drugs (Glucagon Like Peptide-1 Receptor Agonists, GLP-1 RAs; Sodium GLucose coTransporter-2 inhibitors, SGLT2is; DiPeptidyl Peptidase-4 inhibitors, DPP4is) impact body weight, lipid parameters, and blood pressure, as well as endothelial function, inflammatory markers, markers of oxidative stress, and subclinical atherosclerosis. The present review summarizes the results of trials that evaluated the cardiovascular safety of these drugs and found them to be safe from the CV standpoint.

Aims/Hypothesis): Type 1 diabetes is an immune-mediated disease with destruction of the pancreatic β-cells, a process that is conditioned by multiple genes and other factors. HLA counts as the major susceptibility gene. Significant variations in HLA genetic susceptibility to type 1 diabetes between Caucasians, African and Asian and other ethnic groups may have led to the variation in incidence of type 1 diabetes globally. Type 1 diabetes is characterized upon HLA identification. In this chapter we discuss global variations in genetic susceptibility of HLA with regard to type 1 diabetes globally with a particular attention to Arab population. Methods): Haplotype configuration of HLA class I A, B, C and Class II –DR/DQ/DP were studied in Caucasians, African and Asian and in Arab population to see if that is responsible for the exponential rise in the rate of type 1 diabetes. Results): Although Arabs have one of the highest global incidence and prevalence rates of type 1 diabetes, unfortunately, there is a dearth amount of information regarding HLA genetic susceptibility to type 1 diabetes in the Arab world. HLA haplotype configurations contribute to its risk value. However, out of an insufficient present study there are examples of misjudgment of HLA risk according to HLA alleles rather than haplotypes. Conclusion): To date HLA outlooks for the characterization of type 1 diabetes. There is an ethnicity difference in HLA characteristics which is responsible for variation in type 1 diabetes. Although Arab population have contributed heavily in the rise of burden of type 1 diabetes, however, there is significantly a dearth amount of studies on HLA in Arab population. Obviously, any future prediction, prevention or cure of the disease will be based on the HLA genetics. There is a dire need for a systematic screening of HLA for Arab population with type 1 diabetes, identification of Arab HLA-risk values and identify those who are prone to get the disease.

Diabetes self-management education helps to improve health outcomes, quality of life and to reduce expenses for diabetic patients. This systematic review aimed to examine the effectiveness of diabetes self-management education used for newly diagnosed patients with type 2 diabetes (T2DM). A review of studies that have researched the use and the impact of health education in newly diabetic patients with T2DM was implemented. A literature search was conducted using the electronic database of Pub MED, Walters Kluwer, Cochrane Library, Elsevier, JSTORE between January 2017 – November 2022. The data on participants and intervention characteristics were extracted by two reviewers independently. We found 789 studies and after selection of PRISMA flow chart we selected 19 studies, including 2512 newly diagnosed adult T2DM. Biomedical results presented the pooled effect of HbA1c -0.64%, FBG -0.32. The evaluation of emotional and social results and behavioral effects has been evaluated respectively in 10 and 9 studies. The education and support of recently diabetic patients help to improve biomedical, psychosocial, and behavioral results. This intervention must be ongoing to maintain healthy behaviors

Dementia, characterized by cognitive decline beyond age-related expectations, poses a formidable global health challenge. With an estimated 55 million individuals affected worldwide and 10 million new cases annually, dementia profoundly impacts memory, comprehension, language, and behavior. Then, the global diabetes population increased from 108 million in 1980 to 422 million in 2014, with a more rapid rise in prevalence observed in low- and middle-income countries compared to high-income countries. Individuals with diabetes have an increased risk of cognitive problems, including a higher likelihood of developing dementia, Alzheimer's disease, and vascular dementia, especially in older age. Managing diabetes through diet, physical activity, medication, and consistent screening and treatment for complications can prevent or delay its consequences.Globally ranking as the seventh leading cause of death, dementia's societal implications are substantial. The chapter delves into Mild Cognitive Impairment (MCI), a precursor to dementia, emphasizing its global epidemiological trends. Neuroimaging, particularly Functional Near-Infrared Spectroscopy (fNIRS), emerges as a non-invasive diagnostic tool, surpassing traditional imaging methods' portability. The chapter investigates the effects of non-invasive electrical stimulation on neurovascular tissues, shedding light on its impact including potential to address metaboreflex related reduced exercise tolerance. Furthermore, the chapter presents a clinical trial (ClinicalTrials.gov NCT04626453 and NCT04812288) examining the effects of a 2-month exercise program on cognitive function and muscular oxidative capacity in older adults with type 2 diabetes. The study's design, individualized exercise regimens to address muscle mechanoreflex and metaboreflex responses, and their physiological changes during exercise are discussed, offering insights into the interplay between exercise tolerance, cognition, and vascular health. The findings contribute to tailored and effective interventions for cognitive well-being. Here, our exploration extends to the application of transcranial electrical stimulation (tES) in optimizing exercise performance, with a focus on its various forms, including transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS). A physiological modeling approach based on the neurovascular unit (NVU) is employed, revealing potential avenues for also treating vascular dementia (often noted to have a strong association with type 2 diabetes) through tACS, guided by human-in-the-loop approaches. Here, modal analysis for control is applied to assess the NVU model's characteristic dynamics under tACS, providing a comprehensive understanding of neurovascular coupling modes.In summary, this chapter synthesizes diverse facets in type 2 diabetes comorbidity and cognitive decline, ranging from global impact and diagnostic criteria to innovative interventions like exercise and transcranial electrical stimulation. The multidisciplinary approach integrates epidemiology, clinical trials, and physiological modeling, contributing valuable insights into the holistic management of cognitive health and neurovascular function.

One of the major challenges in the post-genomic era is elucidating the genetic basis of human diseases. In recent years, studies have shown that polygenic risk scores (PRS), based on aggregated information from millions of variants across the human genome, can estimate individual risk for common diseases. In practice, the current medical practice still predominantly relies on physiological and clinical indicators to assess personal disease risk. For example, caregivers mark individuals with high body mass index (BMI) as having an increased risk to develop type 2 diabetes (T2D). An important question is whether combining PRS with clinical metrics can increase the power of disease prediction in particular from early life. In this work we examined this question, focusing on T2D. We show that an integrated approach combining adult BMI and PRS achieves considerably better prediction than each of the measures on unrelated Caucasians in the UK Biobank (UKB, n=290,584). Likewise, integrating PRS with self-reports on birth weight (n=172,239) and comparative body size at age ten (n=287,203) also substantially enhance prediction as compared to each of its components. While the integration of PRS with BMI achieved better results as compared to the other measurements, the latter are early-life measurements that can be integrated already at childhood, to allow preemptive intervention for those at high risk to develop T2D. Our integrated approach can be easily generalized to other diseases, with the relevant early-life measurements.

Background: The dietary factors and nutrients contributing to the prevention of microalbuminuria in type 2 diabetic nephropathy is unclear, so we investigated dietary factors affecting urinary albumin excretion in patients with type 2 diabetes. Methods: 42 patients with type 2 diabetes were participated, the subjects were divided to a normal albuminuria group (urinary albumin / creatinine ratio of less than 30 mg / g Cr) and a microalbuminuria group of 30 mg / g to 299 mg / g Cr. We performed casual blood sampling and conducted a food frequency questionnaire survey. Results: There were no significant differences in age, BMI and other physiological and biochemical data, the average daily intake of energy and many of nutrients, while β-cryptoxanthin was significantly lower in the microalbuminuria group than in the normal group (506.4 ± 793.9 μg/day vs. 715.3 ± 500.3 μg/day, p <0.05). The intake of 17 food groups per day showed that the intakes of fruits were significantly lower in the microalbuminuria group than in the normal group (76.9 ± 134.1 g vs. 111.9 ± 84.5 g, p <0.05). Conclusion: These results suggest that fruits and foods rich in β-cryptoxanthin would make it possible to prevent diabetic nephropathy progression.

Background: Cardiovascular (CV) morbidity and mortality are many times higher in chronic kidney disease (CKD), as well as IgA nephropathy (IgAN), than in the general population. The occurrence of metabolic syndrome (MetS) and metabolic risk factors are independent risk factors for CV disease and renal progression. The study aimed to determine the prognostic role of metabolic profiles in a homogenous group of CKD patients. Methods: One hundred and forty-five IgA nephropathy patients (92 male, 53 female, age 54.7 ± 13 years) with CKD stage 1-4 were investigated and followed for a median of 190 months. The composite (CV and renal) endpoints included all-cause mortality and any CV event such as stroke, myocardial infarction, revascularization (CV), end-stage renal disease, and renal replacement therapy (renal). Results: Patients with MetS had significantly more endpoint events (16/27 patients vs. 15/98 patients, p = 0.001) compared to the nonMetS group. Of the secondary endpoints (CV or renal separately), the rate of the renal and CV endpoints was significantly higher in the MetS group (p = 0.001 and p = 0.029). The primary endpoint independent predictors of survival were dyslipidemia, eGFR, hemoglobin, urine albuminuria, and diabetes mellitus, as determined by Cox regression analysis. Independent predictors of secondary renal endpoint were dyslipidemia, hemoglobin, urine albumin, and eGFR. Predictors of secondary cardiovascular endpoints were gender, BMI, and diabetes. Kaplan-Meier curves showed significant differences in MetS and non-MetS when examined at the combined endpoints (CV and renal) or at each endpoint separately. The primary endpoint rate increased significantly with the increased number of MetS components (MetS comp. 0 vs. MetS comp. 2+, primary endpoints, p = 0.012). Conclusion: Our results showed that the metabolic profile has a prognostic role not only for renal endpoints but also for CV endpoints in IgAN. BMI, hyperuricemia, hypertension, and diabetes have a predictive value for the prognosis of IgA nephropathy.

Type 1 diabetes imposes a complex and challenging routine on patients and caregivers. Therefore, considering individual experiences and personal facilitators to promote assertive interventions is crucial. However, no studies have addressed these perspectives in the Brazilian adult population. We aimed to identify psycho-behavioral characteristics perceived as facilitators for coping with the condition. We used a biographical method to conduct semi-structured, face-to-face, in-depth interviews for each participant. Transcripts were analyzed using inductive thematic analysis. Participants (n = 22) were aged 18–57 years (mean: 30.2, standard deviation (SD): 8.7), and the duration since diagnosis was approximately 20.6 years (SD: 4.6). Twelve (54.4%) were women, 13 (59.1%) used insulin pumps, 14 (63.6%) had at least a college degree, and 13 (59.1%) had HbA1C (glycated hemoglobin) levels above 58 mmol/mol (7.5%). Five major themes emerged: 1) peer learning, 2) ownership, 3) welcoming experiences, 4) equity, and 5) reframe the path (P.O.W.E.R.). All themes appeared in the lived experiences shared by participants with HbA1C levels below 58 mmol/mol (7.5%). Improved glycemic control can be achieved, and the challenges encountered in diabetes care within similar socioeconomic contexts can be addressed, by an interdisciplinary care team that takes P.O.W.E.R into consideration when providing person-centered care strategies.

Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM) are comorbidities that result from the sharing of common genes. The molecular background of comorbidities can provide clues for the development of treatment and management strategies. Here, the common genes involved in the development of the two diseases and in memory and cognitive function are reviewed. Network clustering based on protein-protein interaction networks identified tightly connected gene clusters that have an impact on memory and cognition among the comorbidity genes of AD and T2DM. Genes with functional implications were intensively reviewed, and relevant evidence was summarized. Gene information will be useful in the discovery of biomarkers and the identification of therapeutic targets for AD.

Mothers of children with a specific clinical condition such as type 1 diabetes mellitus (T1DM) may experience higher levels of stress predisposing them to a poorer perception of quality of life and alterations in nutritional status. The aim of this research was to evaluate the relationship between nutritional status and quality of life perception of mothers caring for children with Type 1 Diabetes Mellitus. This research was conducted from July to September 2022, with mothers of children aged 5 to 10 years with diabetes. Data were collected through an online questionnaire including soci-oeconomic information, anthropometric data, clinical data of the children, and the WHO-QOL-abbreviated quality of life questionnaire. For statistical analysis, Statistical Package for Social Science 24 was used. Fifty-five mothers of children with diabetes were evaluated. Over 33% of the mothers were overweight and reported a regular perception of quality of life. Higher BMI was associated with poorer perception of quality of life in the psychological and self-assessment domains, and longer diagnosis time was associated with better perception of quality of life in the physical, psychological, and environmental domains. Therefore, it is understood that actions aimed at improving the quality of life of these mothers are necessary.

Diabetes mellitus is acknowledged as a significant contributor to severe complications. The present work has explorated the potential role amentoflavone as an aldose reductase inhibitor through Docking Simulations. From these results this compound has shown excellent results with this enzyme with a high binding energy of -11 kcal/mol. If amentoflavone,a natural biflavonoid, proves effective in inhibiting aldose reductase, it could hold therapeutic promise for managing diabetic complications. However, it's crucial to emphasize that while computational studies offer valuable insights, experimental validation is essential to confirm the actual inhibitory effects and to establish the safety and efficacy of amentoflavone for this purpose. Further research and clinical studies are warranted to fully understand and harness the potential therapeutic benefits of amentoflavone in the context of diabetes.

Type 2 Diabetes Mellitus is being increasingly associated with dysfunction of cognition. Dementia, including vascular dementia and Alzheimer’s disease, is being recognized as comorbidities of this metabolic disorder. The progressive hallmarks of this cognitive dysfunction include mild impairment of cognition and cognitive decline. Dementia and mild impairment of cognition appear in older patients primarily. Studies on risk factors, neuropathology, and brain imaging have provided important suggestions for mechanisms that lie behind the development of dementia. It is a significant challenge to understand the disease processes related to diabetes which affect the brain and lead to dementia development. The connection between Diabetes Mellitus and dysfunction of cognition has been observed in many human and animal studies that have noted mechanisms related to Diabetes Mellitus are possibly responsible for aggravating cognitive dysfunction. This article attempts to narrate the possible association between type 2 diabetes and Dementia, reviewing studies that have noted this association in vascular dementia and Alzheimer’s disease and helping to explain the potential mechanisms behind the disease process. The Google search for ‘Diabetes Mellitus and Dementia’ was carried out. Also, the search was done using ‘Diabetes Mellitus,’ ‘Vascular Dementia,’ ‘Alzheimer’s Disease.’ The literature search was done from Google Scholar, Pubmed, Embase, ScienceDirect, and MEDLINE. Keeping in mind the increasing rate of Diabetes Mellitus, it is important to establish the type 2 diabetes effect on the brain and diseases of neurodegeneration. This narrative review aims to build awareness regarding different types of dementia and their relationship with diabetes.

In order for the body to function properly, it needs not only food, but also nutrients and non-nutritive bioactive compounds that have an immunomodulating effect. This applies not only to healthy people, but especially to people with accompanying chronic diseases, including type 2 diabetes. Unfortunately, the current food industry and the use of highly processed food promote nutritional deficiencies. Many studies confirm their occurrence in patients with type 2 diabetes. The article presents the influence of selected nutrients on the functioning of the immune system, which ensures homeostasis of the body, with particular emphasis on type 2 diabetes. The role of macroelements, microelements, vitamins and selected substances, such as omega-3 acids, coenzyme Q10 and alpha-lipoic acid. The minimum scope of tests that should be performed in patients to directly or indirectly determine the degree of malnutrition in this group of patients is presented.

Background: The therapeutic benefits of fermented foods in the treatment and prevention of Type 2 diabetes mellitus have been reported. Aim: Inhibitory effect of fermented rice beverages on α-amylase, α-glucosidase and pancreatic lipase was evaluated. Method: Two fermented rice beverages-fermented rice alone (FKR) and fermented rice plus roasted peanuts (FKRG) were produced using spontaneous fermentation. Capacity of the beverages to inhibit al-pha-glucosidase, alpha-amylase and pancreatic lipase in vitro was evaluated and compared with standards (positive controls). Results: FKR exerted inhibition of α-glucosidase between 9.23-21.11% and FKRG 1.11-17.36% at the various concentrations respectively, with both samples showing the most significant inhibition (about 20%) at 125 μg/mL. FKRG exhibited greater alpha-amylase inhibition activity than FKR, but for both samples, the most significant (P < 0.05) inhibition occurred at 500 μg/mL. With pancreatic lipase, no significant inhibition was observed for both FKR and FKRG at the tested concentrations compared to Orlistat used as control; how-ever, at 31.25 μg /mL FKRG showed an inhibitory effect of approximately 15%, which was not evident at higher concentrations. Conclusion: Low to moderate inhibition of α-amylase, α-glucosidase and pancreatic lipase by both FKR and FKRG, showed that the fermented rice beverages have potential to modulate hyperglycemia in type 2 diabetes in vitro. This is an indi-cation that fermented rice beverage could prevent postprandial hyperglycemia in vivo.

Nutrition is one of the most influential environmental factor in both taxonomical shifts in gut microbiota as well as development of Type 2 Diabetes Mellitus (T2DM). Emerging evidence has shown that the effects of nutrition on both these parameters is not mutually exclusive and that changes in gut microbiota and related metabolites such as short chain fatty acids (SCFA) and branched chain amino acids (BCAA) may influence systemic inflammation and signaling pathways that contribute to pathophysiological processes associated with T2DM. With this background, our review highlights the effects of macronutrients, carbohydrates, proteins and lipids, as well as micronutrients, vitamins, and minerals, on T2DM, specifically through their alterations in gut microbiota and the metabolites they produce. Additionally, we describe the influences of common food groups, which incorporate varying combinations of these macronutrients and micronutrients, on both microbiota and metabolic parameters in the context of diabetes mellitus. Overall, nutrition is one of the first line modifiable therapies in the management of T2DM and better understanding of the mechanisms by which gut microbiota influence its pathophysiology provides opportunities for optimizing dietary interventions.