Search Results (196)

Adult-onset diabetes increases one’s risk of neurodegenerative disease including Alzheimer’s disease (AD); however, the risk associated with youth-onset diabetes (Y-DM) remains underexplored. We quantified plasma biomarkers of neurodegeneration and AD in participants with Y-DM from the SEARCH cohort at adolescence and young adulthood (Type 1, n = 25; Type 2, n = 25; 59% female; adolescence, age = 15 y/o [2.6]; adulthood, age = 27.4 y/o [2.2]), comparing them with controls (adolescence, n = 25, age = 14.8 y/o [2.7]; adulthood, n = 21, age = 24.9 y/o [2.8]). Plasma biomarkers, including glial fibrillary acidic protein (GFAP), neurofilament light chain protein (NfL), phosphorylated tau-181 (pTau181), and amyloid beta (Aβ40, Aβ42), were measured via Simoa. A subset of participants (n = 7; age = 27.5 y/o [5.7]) and six controls (age = 25.1 y/o [4.5]) underwent PET scans to quantify brain amyloid and tau densities in AD sensitive brain regions. Y-DM adolescents exhibited lower plasma levels of Aβ40, Aβ42, and GFAP, and higher pTau181 compared to controls (p < 0.05), a pattern persisting into adulthood (p < 0.001). All biomarkers showed significant increases from adolescence to adulthood in Y-DM (p < 0.01), though no significant differences in brain amyloid or tau were noted between Y-DM and controls in adulthood. Preliminary evidence suggests that preclinical AD neuropathology is present in young people with Y-DM, indicating a potential increased risk of neurodegenerative diseases. Full article

(1) Background: Subclinical hypothyroidism (SHT) is a condition that has been a subject of controversy in the literature due to its association with psychological and psychiatric symptoms as well as autonomic imbalances. To gain a better understanding of the effects of SHT on patients, a research study has been undertaken to investigate the presence of psychological symptoms and autonomic imbalances in a group of individuals diagnosed with SHT. (2) Methods: In this case–control study, 50 patients diagnosed with SHT who accessed the Department of Endocrinology of the University of Pisa were consecutively recruited. Psychological symptoms were measured through the Crown–Crisp Experiential Index (CCEI), whereas autonomic imbalance was described using the Psychophysiological Stress Profile (PSP), with simultaneous recording of the following psychophysiological parameters: Surface Electromyogram (sEMG), Skin Conductance Level (SCL), heart rate (HR), and peripheral temperature (PT). The patients’ values were compared to those of 50 healthy control subjects. (3) Results: The comparison between groups highlighted significant differences in the CCEI and PSP. In particular, patients reported higher rates of psychological symptoms (anxiety, depression, somatic complaints, and hysteria behavior). Significantly higher levels of autonomic arousal were also recorded. More specifically, the sEMG, SCL, HR, and PT values were different between the two groups. (4) Conclusions: The study has confirmed the presence of autonomic hyperarousal in patients diagnosed with subclinical hypothyroidism. This is likely due to the body’s attempt to compensate for a general lack of energy by accelerating the autonomic activity. The findings also underline the significance of a comprehensive assessment approach that takes into account various dimensions such as psychological and psychophysical well-being. Such an approach helps in evaluating the impact of subclinical diseases on overall health and well-being. Full article

Most patients with non-alcoholic steatohepatitis (NASH) have insulin resistance, and there is a near-universal association between NASH and insulin resistance. Insulin resistance induces lipid accumulation in the liver, leading to the development of metabolic syndrome. However, most NASH rodent models fail to develop metabolic syndrome. LEW.1WR1 rats that are 23 weeks old showed increased body mass, epididymal fat, and liver mass, suggesting obesity-driven metabolic dysfunction. We have characterized steatosis, inflammation, Mallory–Denk body formation with hematoxylin and eosin (H&E), and fibrosis with Trichome blue staining. The presence of hepatic fibrosis with other features of NASH described above is one of the major strengths of this model since most of the currently available NASH models do not develop microvesicular steatosis or fibrosis. Together with the other important features of NASH described above, we confirm that male LEW.1WR1 rats develop NASH and insulin resistance with a standard diet. Full article

Introduction: Insulin resistance is a common condition affecting thousands of people worldwide. This paper aims to examine the mechanisms underlying insulin resistance among people suffering from obesity. Methods and Design: This study entailed identifying articles related to insulin resistance and obesity. The publications were obtained using different electronic databases, including PubMed, EBSCO, and LILACS. The search terms included “insulin”, “resistance”, “obesity”, and “mechanisms”. Boolean operators were used to combine terms and phrases. Results: Insulin resistance is a physiological condition characterized by the impaired action of insulin in the body. The association between obesity and insulin resistance is linked to inflammatory, neural, and endocrine pathways that affect the sensitivity of organs to the level of insulin in the body. Discussion: Molecular studies have helped discover some of the fundamental mechanisms leading to the development of insulin resistance. Further investigations are needed to enhance our understanding of the connections among the inflammatory, neural, and cellular processes underlying the association between insulin resistance and obesity. Conclusion: This study revealed that a complex correlation exists between insulin resistance and obesity. This relationship involves a wide range of inflammatory, neural, and endocrine processes. Full article

Mangifera indica (Anacardiaceae family) is renowned for its diverse pharmacological properties, encompassing antidiabetic, antioxidant, and anti-inflammatory effects. The present study delves into the insulin-releasing and glucose-lowering potential of the ethanolic extract of Mangifera indica (EEMI) leaves in streptozotocin-induced type 2 diabetic (STZ-T2D) rats, concurrently investigating its phytoconstituents. EEMI’s effects on insulin secretion were measured using BRIN BD11 β-cells and isolated mouse islets. Its enzymatic inhibitory properties on carbohydrate digestion, and absorption, and free radicals were investigated using in vitro methods. In vivo parameters including the lipid profile and liver glycogen content were assessed in STZ-T2D rats. EEMI exhibited a dose-dependent increase in insulin secretion from clonal pancreatic BRIN BD11 β-cells and isolated mouse islets. EEMI inhibited starch digestion, glucose diffusion over time, and DPPH activity in vitro. In acute in vivo studies, EEMI improved food intake and oral glucose tolerance. Moreover, following 28 days of treatment with EEMI, a remarkable amelioration in body weight, fasting blood glucose, plasma insulin, liver glycogen content, total cholesterol, triglyceride, LDL, VLDL, and HDL levels was observed. Further phytochemical analysis with EEMI identified the presence of alkaloids, tannins, saponins, steroids, and flavonoids. The synergistic effects of EEMI, potentially attributable to naturally occurring phytoconstituents, hold promise for the development of enriched antidiabetic therapies, offering a promising avenue for the management of type 2 diabetes. Full article

Purpose: Lipid lowering treatments (LLTs) can reduce the risk of atherosclerotic cardiovascular disease (ASCVD). Despite the availability of potent LLTs, our clinical observations suggest an inadequate use of such agents. To evaluate this treatment deficit, we designed the present study. Methods: We reviewed the charts of all patients with a history of ASCVD (coronary artery disease—CAD; carotid stenosis—CS; or peripheral artery disease—PAD) diagnosed prior to their first visit to one of our clinics. We recorded their gender, age, ASCVD risk factors (diabetes, hypertension, tobacco use, body mass index), lipid values during that visit and the LLT used. We estimated the rates of the attainment of guideline-specific lipid goals by year, and assessed factors influencing the likelihood of treatment success. Results: Overall, n = 1003 subjects were recruited: CAD n = 703 (70.1%), PAD n = 168 (16.8%), CS n = 325 (32.4%); age 64.7 ± 11.2 years; n = 376 (37.5%) females; n = 642 (64.0%) had diabetes; n = 740 (73.8%) had hypertension; n = 299 (29.8%) were former and n = 367 (36.6%) were current smokers. An appropriate LLT was used in 361 (36.0%) subjects, n = 159 (15.9%) were on no treatment, n = 483 (48.2%) were receiving inadequate therapy, n = 434 (43.3%) were on a high-intensity LLT and n = 361 (36.0%) had achieved the year-specific LDL goals. Success rates ranged from 5.7% to 81.5%, with the lowest being 2020–2023 (5.7–14.5%), p < 0.001. The use of a combination of LLTs and PCSK9 inhibitors led to higher rates of LDL-C goals achievement (p < 0.001). Discussion: Recent secondary ASCVD risk prevention guidelines’ goals are rarely achieved in daily clinical practice, producing a major treatment deficit in this population. Newer systematic interventions are needed to curb this public health issue. Full article

GHRH regulates the secretion of GH from the anterior pituitary gland, previously associated with cancer progression and inflammation. An emerging body of evidence suggests that GHRHAnt support endothelial barrier function, but the mechanisms mediating these events are not completely understood. In the present study, it is demonstrated that the GHRHAnt JV-1-36 counteracts barrier dysfunction due to LPS or LTA treatment in HUVECs, utilizing the Dextran–FITC assay. Moreover, it is shown in BPAECs that these bacterial toxins increase ROS generation, and that this effect is counteracted by JV-1-36, which reinstates the redox balance. The possible involvement of NEK2 in the beneficial activities of GHRHAnt in IFN-γ- and LPS-triggered hyperpermeability was also assessed, since that kinase is involved in inflammatory responses. NEK2 was increased in the inflamed cells, and JV-1-36 counteracted those endothelial events. Our data support the beneficial effects of GHRHAnt in toxin-induced endothelial injury. Full article

The evolution of breast cancers results from the emergence of epithelial cell subpopulations containing variant Estrogen Receptor α which is able to bypass conventional treatments aimed at antagonizing the activity of this tumor-promoting receptor. The present investigation concerns a few estradiol derivates bearing substituents in position 11β that might not only contribute to the development of drugs to alleviate this unfortunate issue but that may be also helpful in identifying molecular aspects of resistance to this receptor in order to elaborate other therapeutic approaches. In this regard, AP-1 assisted and ERE-directed ERα transcriptions are demonstrated to be key factors in this area: AP-1 transcriptions are shown to antagonize ERE transcriptions, thereby limiting their tumor-promoting activity. This property results from a conformal change in the receptor, which is induced essentially by estrogenic ligands which, inserted into a cavity of ERα’s ligand-binding pocket, govern this regulatory mechanism. Flexible 11β side-chains favor this insertion, in contrast to their rigid counterparts, which counteract it; these properties give rise to strong estrogenic, SERM or SERD profiles. Suspected extracellular regulatory mechanisms resulting from these ligand-induced transcriptions are elaborated on in the present work in the context of breast cancer development. Full article

Binge eating disorder (BED) is the most common eating disorder categorized in the DSM-V, but it is often not diagnosed in patients with obesity because it can be difficult to detect in these patients who often have altered eating patterns. In this narrative review, we have highlighted the most recent findings in the screening, diagnosis, and treatment of patients with BED and obesity. The results of our search showed that many BED patients are not obese, and most people with obesity do not have binge behavior. In the diagnostic assessment of these patients, it is important to evaluate not only the clinical and nutritional status and the presence of medical comorbidities, but also the psychological signs and symptoms related to psychiatric comorbidities to define the appropriate diagnosis and the consequent level of treatment. Well-tolerated drugs with action on both body weight and binges can be useful as a second-line complement to cognitive behavioral therapy (CBT). Specific guidelines are needed to obtain consensus on appropriate recommendations in patients with obesity and BED approaching bariatric surgery, taking into account not only weight reduction and clinical data, but also eating behaviors. Identification of BED is important for targeting individuals at high risk of obesity, adverse metabolic patterns, and cardiovascular disease. The challenge is to also achieve lasting weight loss in patients with BED and concomitant obesity. Full article

Background: Tirzepatide (TZP) is a once-weekly glucagon-like peptide 1 (GLP-1) and glucose-dependent-insulinotropic-polypeptide (GIP) receptor co-agonist approved for T2D. TZP provides promising evidence in improving glucose control and weight loss in T2D and obesity across preclinical and human studies, including data from the SURPASS program. Aims: The goal of this paper was to review the evidence on TZP in terms of glucose control, body weight, and the progression of chronic diabetes-related complications and comorbidities. Results: The mean change in HbA1c ranged from −1.6% to −2.06% over placebo, from −0.29% to −0.92% over each GLP-1RAs, and from −0.7% to −1.09% over basal insulins. In SURPASS-6, TZP was more effective than insulin lispro U100 added to basal insulin in reducing HbA_1c levels at the study end (−2.1% vs. −1.1%, respectively). Compared to placebo, TZP induces a significant weight loss: 7.5 (5 mg/week); 11 (10 mg/week); and 12 kg (15 mg/week). Compared to GLP-1RAs, TZP reduces body weight from −1.68 kg to −7.16 kg depending on the dose (5 to 15 mg, respectively). Compared to basal insulin alone rigorously titrated, TZP added onto basal-insulin results in the best strategy for the composite endpoint of improvement of glucose control and weight loss. In SURPASS-6, TZP compared to insulin lispro U100 in add-on to insulin glargine U100 reduced body weight by 9 kg in mean (versus weight gain in basal-bolus users: +3.2 kg). TZP has pleiotropic effects potentially dampening the individual cardiovascular risk, including a reduction in systolic arterial pressure by 4 to 6 mmHg and total cholesterol by 4–6% compared to baseline. A post hoc analysis of SURPASS-4 revealed that TZP, compared to glargine U100, delayed the rate of glomerular filtration decline (−1.4 mL/min vs. −3.6 mL/min, respectively), reduced the rate of urinary albumin excretion (−6.8% vs. +36.9%, respectively), and was associated with a lower occurrence of the composite renal endpoint (HR 0.58 [0.43; 0.80]). Conclusions: Consistent evidence indicates that TZP dramatically changes the clinical course of T2D in different clinical scenarios. The efficacy and safety of TZP on chronic diabetes-related comorbidities and complications seem promising, but ongoing trials will clarify the real benefits. Full article

Adenomyosis (ADM) is a multifaceted uterine pathology characterized by the ectopic infiltration of endometrial tissue into the myometrium, affecting approximately 20% of women in the reproductive age group seeking gynecological care. This condition manifests as a range of debilitating symptoms, including dysmenorrhea, menorrhagia, impaired fertility, and heightened susceptibility to miscarriage and obstetric complications. Substantial research has been dedicated to exploring its underlying molecular mechanisms and developing non-invasive precision medical therapies. ADM is primarily characterized by a dysregulation in sex steroid hormone homeostasis, particularly estrogen and progesterone. However, emerging evidence suggests that additional endocrine mediators and disruptors may play contributory roles in the etiology of ADM. Genetic and epigenetic alterations of endocrine signaling pathways have been implicated as prevailing mechanisms underlying the development and progression of the disease. The present review aims to provide an updated and comprehensive overview of the current understanding of the pathophysiology of ADM, with a particular emphasis on the dysregulated hormonal milieu and the potential involvement of endocrine disruptors. By elucidating these intricate molecular mechanisms, this review seeks to pave the way for novel research directions in the development of targeted therapeutic strategies for ADM management. Full article

Background: Combined oral contraceptives (COCs) work mostly by preventing the pre-ovulatory gonadotropin surge, but the action of COCs on spontaneous episodic and GnRH (gonadotropin-releasing hormone)-induced LH (luteinizing hormone) release has been poorly evaluated. Oral contraceptives are known to act on the spontaneous hypothalamic–pituitary functions reducing both GnRH and gonadotropin release and blocking ovulation. Aim: To evaluate spontaneous and GnRH-induced LH release during both phases of the menstrual cycle or under the use of the contraceptive pill. Methods: A group of 12 women, subdivided into two groups, volunteered for the study. Group A (n = 6, controls) received no treatments, while Group B (n = 6) received a 21 + 7 combination of ethinyl-estradiol (EE) 30 µg + drospirenone (DRSP) 3 mg. Both groups were evaluated twice: Group A during follicular and luteal phases, Group B during pill assumption and during the suspension interval, performing a pulsatility test, GnRH stimulation test, and hormonal parameters evaluation. Spontaneous and GnRH-induced secretory pulses were evaluated, as well as the instantaneous secretory rate (ISR). Results: COC treatment lowered LH and FSH (follicle stimulating hormone) levels significantly if compared to the follicular phase of spontaneous cycles. During the suspension interval, hormone levels rapidly rose and became comparable to those of the follicular phase of the control group. The LH pulse frequency under COC administration during the suspension interval was similar to that observed during the follicular phase (2.6 ± 0.3 pulses/180 min and 2.3 ± 0.2 pulses/180 min, respectively). The GnRH-induced LH peaks were greater in amplitude and duration than those observed after ISR computation in both groups. The GnRH-induced LH release during the luteal phase of the control subjects was higher than in the follicular phase (51.2 ± 12.3 mIU/mL and 14.9 ± 1.8 mIU/mL, respectively). Conversely, subjects under COC showed a GnRH-induced LH response similar during COC and during the suspension interval. Conclusions: Our data support that the EE + DRSP preparation acts on both spontaneous pulsatile release and GnRH-induced LH release during the withdrawal period of the treatment, and that after 5–7 days from the treatment suspension, steroidal secretion from the ovary is resumed, such as that of androgens. This suggests that in hyperandrogenic patients, a suspension interval as short as 4 days might be clinically better. Full article

Ghrelin and its growth hormone secretagogue receptor (GHSR) have been found in the placenta, both in endothelial and trophoblast cells. Ghrelin has been shown to decrease blood pressure in several systems and improve endothelial function by stimulating VEGF production. Because locally increased Ghrelin was detected in the preeclamptic fetoplacental unit, we hypothesized its involvement in the fibrinolysis and vascular tone typically observed in preeclamptic patients. This study aimed to evaluate the synthesis of plasminogen activators (PAs), PA inhibitor-1 (PAI-1), and urokinase-type PA (uPA) receptor (uPAR) in human umbilical vein endothelial cells (HUVECs) since the components of the PA/plasmin system are vital players in the extracellular matrix remodeling process necessary for angiogenesis. HUVECs were treated for 24 h with increasing concentrations of Ghrelin (10⁻¹¹–10⁻⁷ M) or IL-1β (0.1 ng/mL). PAs, PAI-1, and uPAR mRNAs were determined by real-time PCR and PA activity was determined by casein underlay. We demonstrated an increase in uPA, tissue-type PA (tPA), and uPAR mRNA; a reduction in PAI-1 mRNA in HUVECs treated with Ghrelin; and an increase in total uPA activity. In conclusion, our results suggest a potential compensatory physiological mechanism for Ghrelin in response to the maternal endothelial dysfunction observed in the preeclamptic fetoplacental unit. Full article

Medical (healthcare) deserts and food deserts, either separate or combined, exist in rural areas, globally. The physicians and other healthcare professionals who serve rural and other underserved populations, to some extent, also experience life in these areas. Dietary guidelines, from expert societies, for people with diabetes, have been helpful in guiding healthcare professionals through nutritional interventions. However, these guidelines are not designed for rural areas where healthcare resources are scarce, and access to the built environment for a healthy lifestyle and affordable healthy foods are not available. Therefore, the guidelines were reviewed, with rural physicians and healthcare professionals who work in underserved areas in mind, to assess their appropriateness. Based on the guidelines and other literature, potential solutions to guideline gaps are proposed to aid in providing nutritional therapy for the underserved. The overall goals are to improve the nutritional component of healthcare for underserved people with diabetes, and to begin the conversation around creating specific guidelines for rural physicians and other healthcare professionals, where patients are at a higher risk for diabetes. Full article

Thyroid cancer is more aggressive in elderly patients due to biological causes related to age, histotype, and the advanced stage at diagnosis. In the elderly, both the diagnosis and treatment of thyroid cancer impact quality of life. This review aimed to collect and discuss the different therapeutic approaches in elderly patients affected by thyroid cancer. Our analysis examined the therapeutic surgical approach according to age and how this affects the prognosis of patients with thyroid cancer, along with how iodine 131 therapy is tolerated and how effective it is. Furthermore, we investigated whether levothyroxine suppressive therapy is always necessary and safe in elderly patients with thyroid cancer and the safety and efficacy of systemic therapy in the elderly. We also intended to identify peculiar features of thyroid cancer in elderly subjects and to evaluate how the disease and its treatment affect their quality of life. Full article