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Secondary diabetes mellitus (DM) is a common complication of acromegaly, encountered in up to 55% of cases. Vice versa, the prevalence of acromegaly is markedly higher in cohorts of patients with type 2 DM (T2DM). The presence of secondary DM depends primarily on acromegaly status and is associated with increased cardiovascular morbidity, malignancy rate and overall mortality. The principal pathophysiologic mechanism is increased insulin resistance due to excessive lipolysis and altered fat distribution, reflected at the presence of intermuscular fat and attenuated, dysfunctional adipose tissue. Insulin resistance is ascribed to the direct, diabetogenic effects of growth hormone (GH), which prevail over the insulin-sensitizing effects of insulin-like growth factor 1 (IGF-1), probably due to higher glucometabolic potency of GH, IGF-1 resistance, or both. Inversely, GH and IGF-1 act synergistically in increasing insulin secretion. Hyperinsulinemia in portal vein leads to enhanced responsiveness of liver GH receptors and IGF-1 production, pointing towards a mutually amplifying loop between GH-IGF-1 axis and insulin. Secondary DM occurs upon beta cell exhaustion, principally due to gluco-lipo-toxicity. Somatostatin analogues inhibit insulin secretion; especially pasireotide (PASI) impairs glycaemic profile in up to 75% of cases, establishing a separate pathophysiologic entity, PASI-induced DM. In contrast, pegvisomant and dopamine agonizts improve insulin sensitivity. In turn, metformin, pioglitazone and sodium-glucose transporters 2 inhibitors might be disease-modifying by counteracting hyperinsulinemia or acting pleiotropically. Large, prospective cohort studies are needed to validate the above notions and define optimal DM management in acromegaly., (© 2023. The Author(s).)

The exact mechanisms mediating the metabolic effects of Orthodox fasting remain unclear. Plasma adiponectin, biochemical and anthropometrical data were evaluated in 55 Orthodox fasters (OF) and 42 time-restricted eating controls (all women, mean age 47.8 years) at three time points: baseline, end of the dietary intervention (7 weeks) and 5 weeks after participants returned to their typical dietary habits (12 weeks from baseline). In the OF group, there was an increase in adiponectin values at 12 weeks compared with baseline (9815.99 vs 8983.52 mg/ml, p  = 0.02) and a reduction in body fat mass between baseline and 12 weeks (35.44 vs 32.17%, p  = 0.004) and between 7 and 12 weeks (35.33 vs 32.17%, p  = 0.003). In the same group, an inverse correlation between adiponectin and waist circumference values was observed over the entire study period. Our results provide novel evidence that Orthodox fasting has favourable metabolic effects related to improved adiponectin concentrations.

Efforts to unravel the pathophysiological mechanisms of type 2 diabetes (T2D) have been traditionally trapped into a metabolic perspective. However, T2D is a phenotypically and pathophysiologically heterogenous disorder, and the need for a tailored approach in its management is becoming increasingly evident. There is emerging evidence that irregular immune responses contribute to the development of hyperglycemia in T2D and, inversely, that insulin resistance is a component of the pathogenesis of autoimmune diabetes. Nevertheless, it has not yet been fully elucidated to what extent the presence of conventional autoimmune markers, such as autoantibodies, in subjects with T2D might affect the natural history of the disease and particularly each response to various treatments. The challenge for future research in the field is the discovery of novel genetic, molecular, or phenotypical indicators that would enable the characterization of specific subpopulations of people with T2D who would benefit most from the addition of immunomodulatory therapies to standard glucose-lowering treatment. This narrative review aims to discuss the plausible mechanisms through which the immune system might be implicated in the development of metabolic disturbances in T2D and obesity and explore a potential role of immunotherapy in the future management of the disorder and its complications., (© 2021 World Obesity Federation.)

The provocative idea that type 2 diabetes (T2D) may be a surgically treated disorder is based on accumulating evidence suggesting impressive remission rates of obesity and diabetes following bariatric surgery interventions. According to the "anti-incretin" theory, ingestion of food in the gastrointestinal (GI) tract, apart from activating the well-described incretin effect, also results in the parallel stimulation of a series of negative feedback mechanisms (anti-incretin effect). The primary goal of these regulations is to counteract the effects of incretins and other postprandial glucose-lowering adaptive mechanisms. Disruption of the equilibrium between incretins and anti-incretins could be an additional pathway leading to the development of insulin resistance and hyperglycemia. This theory provides an alternative theoretical framework to explain the mechanisms behind the optimal effects of metabolic surgery on T2D and underlines the importance of the GI tract in the homeostatic regulation of energy balance in humans. The anti-incretin concept is currently based on a limited amount of evidence and certainly requires further validation by additional studies. The aim of the present review is to discuss and critically evaluate recent evidence on the anti-incretin theory, providing an insight into current state and future perspectives., (© 2019 World Obesity Federation.)

Systemic inflammation has been recognized as the cause and consequence of metabolic dysregulation in diabetes mellitus (DM). Presepsin has recently emerged as a promising biomarker for the detection of bacterial infections and sepsis. There is evidence that gut dysbiosis results in the increased circulating concentrations of Gram-negative bacteria lipopolysaccharide, the linkage of presepsin, which in turn promotes insulin resistance and correlates with the risk of diabetic complications. Thus, we hypothesized that presepsin could reflect the magnitude of systemic inflammation and metabolic decompensation in patients with DM even in the absence of infection. In this cross-sectional pilot study, we included 75 infection-free individuals with well-controlled (n = 19) and uncontrolled (n = 23) type 2 diabetes (T2D), well-controlled (n = 10) and uncontrolled (n = 10) type 1 diabetes (T1D), and normoglycemic controls (n = 13). Presepsin levels were compared between the groups and potential associations with demographic, clinical, and laboratory parameters were explored. We observed that the duration of DM was associated with presepsin values (p = 0.008). When the participants were classified into the type of DM groups, the presepsin levels were found to be lower in the patients with T2D compared to those with T1D (p = 0.008). However, significance in that case was driven by the difference between the well-controlled groups. After adjusting for the effects of DM duration, presepsin was significantly lower in the well-controlled T2D group compared to the well-controlled T1D group [1.34 (2.02) vs. 2.22 (4.20) ng/mL, p = 0.01]. Furthermore, we adjusted our findings for various confounders, including age, body mass index, and waist circumference, and found that the difference in the presepsin values between the adequately controlled groups remained significant (p = 0.048). In conclusion, our findings suggest that presepsin could potentially serve as a surrogate marker of inflammation and metabolic control in people with DM. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction-associated steatotic liver disease (MASLD) and polycystic ovary syndrome (PCOS) are prevalent conditions that have been correlated with infertility through overlapped pathophysiological mechanisms. MASLD is associated with metabolic syndrome and is considered among the major causes of chronic liver disease, while PCOS, which is characterized by ovulatory dysfunction and hyperandrogenism, is one of the leading causes of female infertility. The pathophysiological links between PCOS and MASLD have not yet been fully elucidated, with insulin resistance, hyperandrogenemia, obesity, and dyslipidemia being among the key pathways that contribute to liver lipid accumulation, inflammation, and fibrosis, aggravating liver dysfunction. On the other hand, MASLD exacerbates insulin resistance and metabolic dysregulation in women with PCOS, creating a vicious cycle of disease progression. Understanding the intricate relationship between MASLD and PCOS is crucial to improving clinical management, while collaborative efforts between different medical specialties are essential to optimize fertility and liver health outcomes in individuals with MASLD and PCOS. In this review, we summarize the complex interplay between MASLD and PCOS, highlighting the importance of increasing clinical attention to the prevention, diagnosis, and treatment of both entities. [ABSTRACT FROM AUTHOR]

Thyroid disorders (TD) and diabetes mellitus (DM) are the two endocrinopathies with the highest prevalence in the general population that frequently coexist. Thyroid dysfunction is more common in people with type 2 diabetes mellitus (T2DM) compared to normoglycemic individuals. Untreated TD can impair glycemic control, increasing the risk of diabetes complications. Hyperinsulinemia can affect the morphology of the thyroid gland by promoting the proliferation of thyroid tissue and increasing the size of thyroid nodules. Metformin can confer benefits in both endocrinopathies, while other antidiabetics, such as sulfonylureas, can negatively affect thyroid function. Animal and human observational data suggest an increased risk of medullary thyroid carcinoma after treatment with glucagon-like peptide-1 receptor agonists. However, randomized trials have so far been reassuring. Furthermore, some observational studies suggest an association between thyroid cancer and T2DM, especially in women. This narrative review aims to shed light on the epidemiological, pathophysiological, and clinical aspects of the interplay between TD and T2DM. Taking into account the important clinical implications of the coexistence of T2DM and TD, proper screening and management strategies are needed for both endocrinopathies to ensure optimal patient care. [ABSTRACT FROM AUTHOR]

Data on the efficacy of vitamin D in improving the glycemic status of elderly people with prediabetes are scarce. This open-label, randomized-controlled trial investigated the effect of vitamin D supplementation on glycemic markers of Greek people with prediabetes aged 60 years or above, over 12 months. Participants were randomized to a weekly vitamin D3 dose of 25,000 IU (n = 45) or nothing (n = 45), on top of lifestyle measures. Anthropometric and glycemic markers were assessed at baseline, 3, 6, and 12 months Supplemented participants demonstrated a significant increase in 25(OH)D concentrations at 3, 6, and 12 months compared to baseline. In the intervention group, fasting glucose was decreased at 6 months compared to baseline (96.12 ± 5.51 vs 103.40 ± 12.05 mg/dl, p < 0.01) and glycated hemoglobin was significantly lower at 6 and 12 months compared to baseline [5.82 ± 0.21% vs 5.87 ± 0.21%, p = 0.004 and 5.80 ± 0.23% vs 5.87 ± 0.21%, p < 0.001, respectively]. Vitamin D could be complementary to lifestyle change strategy for the management of prediabetes in the elderly. ISRCTN51643592. [ABSTRACT FROM AUTHOR]

For seven weeks, 37 overweight adults followed a hypocaloric diet based on Orthodox Fasting (OF). A hypocaloric, time restricted eating (TRE) plan (eating between 08:00 to 16:00 h, water fasting from 16:00 to 08:00 h) was followed by 23 Body Mass Index (BMI)-matched participants. Anthropometric, glycaemic and inflammation markers and serum lipids were assessed before and after the diets. Both OF and TRE groups demonstrated reductions in BMI (28.54 ± 5.45 vs 27.20 ± 5.10 kg/m2, p < 0.001 and 26.40 ± 4.11 vs 25.81 ± 3.78 kg/m2p = 0.001, respectively). Following the intervention, the OF group presented lower concentrations of total and low-density lipoprotein-cholesterol, compared with the pre-fasting values (178.40 ± 34.14 vs 197.17 ± 34.30 mg/dl, p < 0.001 and 105.89 ± 28.08 vs 122.37 ± 29.70 mg/dl, p < 0.001, respectively). Neither group manifested significant differences in glycaemic and inflammatory parameters. Our findings suggest that OF has superior lipid lowering effects than the TRE pattern. [ABSTRACT FROM AUTHOR]

Background: The combined effect of vitamin D and parathyroid hormone on glucose homeostasis has not been adequately investigated. The aim of this study was to examine the role of parathyroid hormone/vitamin D axis on glucose homeostasis in elderly persons with prediabetes. Methods: Patients with prediabetes (n = 144) and healthy age-matched controls (n = 81) were included in this cross-sectional study. Study parameters included anthropometric characteristics, morning fasting glucose (fasting plasma glucose), insulin (fasting plasma insulin), parathyroid hormone, 25-hydroxyvitamin D, homeostasis model assessment of insulin resistance and homeostasis model assessment of β-cell function. Both groups were stratified into subgroups according to vitamin D status and tertiles of parathyroid hormone. Results: Both groups were comparable in terms of body mass index, 25-hydroxyvitamin D and parathyroid hormone status. In the prediabetes group, fasting plasma glucose differed significantly across parathyroid hormone tertiles, increasing from the first to the third tertile (p = 0.011). There were higher fasting plasma glucose values in participants with vitamin D deficiency/parathyroid hormone third tertile compared to all other groups (p = 0.031, 0.027 and 0.039, respectively). Conclusion: Parathyroid hormone status is associated with impaired glucose homeostasis; hypovitaminosis D combined with high parathyroid hormone concentrations are associated with glycaemic dysregulation in elderly patients with prediabetes. [ABSTRACT FROM AUTHOR]

Background: Insulin resistance is considered to play an important role in the pathogenesis of polycystic ovary syndrome (PCOS) and in the progression to type 2 diabetes. Recent reports concentrate on a possible relationship between incretin secretion and beta-cell function in PCOS. The aim of the present study is to investigate the incretin effect in obese and lean women with PCOS. Methods: Twenty women with PCOS and ten age-matched healthy women were recruited in the study. The oral glucose tolerance test (OGTT) and isoglycemic test were carried out on each participant after an overnight fast at 2-weeks interval. Plasma levels of insulin, glucose, C-peptide, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) were assayed. Results: Obese women with PCOS demonstrated lower GIP concentrations (area under the curve [AUC]) in response to OGTT compared to the control group. The incretin effect was found significantly augmented in the obese women with PCOS compared to controls. This finding remained robust in the subgroup analysis including only body mass index (BMI)-matched healthy women. Conclusions: Increased insulinotropic effect could counteract the blunted GIP response to OGTT in obese women with PCOS. It is suggested that the pathology of PCOS may also include impaired activity of the enteroinsular axis. [ABSTRACT FROM AUTHOR]

Objective: To determine the effect of treatment with vitamin D(3) analogue in the parameters of glucose metabolism in obese women with polycystic ovary syndrome (PCOS).Design: Observational study.Setting: Obese women with PCOS in an academic research environment.Patient(s): Fifteen obese women (mean age 28 +/- 1.3 years, mean body mass index 32.55 +/- 0.43) with documented chronic anovulation and hyperandrogenism were recruited into the study.Intervention(s): Alphacalcidol (1-alpha-hydroxyvitamin D(3)) was administered orally 1 microg/day for 3 months. All subjects underwent a frequently sampled IV glucose tolerance test after a 10- to 12-hour overnight fast during a spontaneous bleeding episode before and after treatment with alphacalcidol.Main Outcome Measure(s): Peripheral insulin resistance and insulin effectiveness were estimated with minimal model.Result(s): The first phase of insulin secretion was significantly increased after treatment with alphacalcidol. A favorable statistically significant change also was observed in the lipid profile.Conclusion(s): Treatment with the vitamin D(3) analogue (alphacalcidol) could be of value in the management of PCOS. [ABSTRACT FROM AUTHOR]

Exposure to high altitude activates several complex and adaptive mechanisms aiming to protect human homeostasis from extreme environmental conditions, such as hypoxia and low temperatures. Short-term exposure is followed by transient hyperglycemia, mainly triggered by the activation of the sympathetic system, whereas long-term exposure results in lower plasma glucose concentrations, mediated by improved insulin sensitivity and augmented peripheral glucose disposal. An inverse relationship between altitude, diabetes, and obesity has been well documented. This is the result of genetic and physiological adaptations principally to hypoxia that favorably affect glucose metabolism; however, the contribution of financial, dietary, and other life-style parameters may also be important. According to existing evidence, people with diabetes are capable of undertaking demanding physical challenges even at extreme altitudes. Still, a number of issues should be taken into account, including the increased physical activity leading to changes in insulin demands and resistance, the performance of measurement systems under extreme weather conditions and the potential deterioration of metabolic control during climbing expeditions. The aim of this review is to present available evidence in the field in a comprehensive way, beginning from the physiology of glucose homeostasis adaptation mechanisms to high altitudes and ending to what real life experience has taught us. [ABSTRACT FROM AUTHOR]

Aims: This pilot study aimed to evaluate differences in glycemic parameters between patients with prediabetes and normocalcemic primary hyperparathyroidism (NPHPT) and controls with prediabetes and normal parathyroid hormone (PTH) and calcium concentrations.Methods: 20 patients with NPHPT and prediabetes and 42 age-, gender-, and body mass index-matched controls with prediabetes were included. Glycemic parameters [fasting glucose (fGlu), glycosylated hemoglobin (HbA1c), fasting insulin (fIns)] were evaluated. Homeostasis Model Assessment was used for estimating insulin secretion (HOMA-B) and resistance (HOMA-IR). Participants underwent a 75-g oral glucose tolerance test.Results: HbA1c (5.9 ± 0.0 vs 5.9 ± 0.0%, p = 0.44), HOMA-IR (3.7 ± 1.2 vs 2.9 ± 0.2, p = 0.48), HOMA-B (117.8 ± 31.8 vs 146.9 ± 22.0%, p = 0.14), fIns (14.0 ± 4.3 vs 12.2 ± 1.1 μIU/ml, p = 0.53) and 2-hour post-load glucose concentrations (157.2 ± 2.2 vs 152.2 ± 2.0 mg/dl, p = 0.07), were nondifferent in the two groups. Higher fGlu levels were evident in the NPHPT, compared to the control group (105.6 ± 2.8 vs 98.2 ± 1.8 mg/dl, p = 0.01). fGlu demonstrated a positive correlation with PTH concentrations (rho = 0.374, p = 0.005).Conclusions: Individuals with NPHPT and prediabetes present an unfavorable glycemic profile compared to age-matched people with prediabetes, suggesting a direct adverse effect of elevated PTH on glucose homeostasis. [ABSTRACT FROM AUTHOR]