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Consuming a "modern" Western diet and overnutrition may increase insulin secretion. Additionally, nutrition-mediated hyperinsulinemia is a major driver of ectopic fat deposition. The global prevalence of metabolic syndrome is high and growing. Within this context, people with congenital lipodystrophy often experience a severe form of metabolic syndrome. Evidence is increasingly supporting that subtle partial lipodystrophy plays an important role in the development of metabolic syndrome in the general population. In individuals in the general population with subtle partial lipodystrophy, as well as in those with congenital lipodystrophy, the subcutaneous adipose tissues are unable to accommodate surplus energy intake. In both conditions, (excess) fat is directed toward the liver, pancreas, and muscles, where it is deposited as ectopic fat, as this fat can no longer be stored in the "safe" subcutaneous fat depots. Ectopic fat depositions cause insulin resistance in the liver and muscles, as well as β-cell dysfunction in the pancreas. Support of a direct pathological role of ectopic fat deposition in this condition is further provided by the rapid normalization of hepatic insulin sensitivity and improvement in pancreatic β-cell function after marked reductions in ectopic fat depositions. Thus, ectopic fat deposition in the liver, pancreas, and muscles may play a causal role in the pathogenesis of metabolic syndrome even in the general population. As such, the prevention of ectopic fat deposition may reduce the risk of metabolic syndrome and mitigate its effects. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes (T2DM) and obesity are characterized by altered insulin metabolism and action. Reduced hepatic insulin clearance is increasingly recognized as a key contributor to hyperinsulinemia and insulin resistance. CEACAM1 promotes hepatic insulin clearance, and its loss in hepatocytes is associated with reduced insulin clearance in mice and men. This study examines whether CEACAM1 circulating levels reflect compromised insulin metabolism and resistance in the PREVADIAB2 cohort. Methods: A total of 1019 individuals from the PREVADIAB2 cohort were evaluated for diabetes by 75 g‐OGTT and classified according to WHO 2019 criteria. CEACAM1 circulating levels were measured by ELISA, and insulin metabolism parameters were calculated. Hierarchical clustering of insulin metabolic indices and CEACAM1 levels was performed. Statistical significance was assessed using Kruskal–Wallis and Wilcoxon–Mann–Whitney tests. Results: BMI, insulin resistance (HOMA‐IR), and hepatic steatosis progressively increased with disease severity. Insulin secretion rose and its clearance declined in parallel to circulating CEACAM1 levels in prediabetes and T2DM, indicating compensatory hyperinsulinemia. Hierarchical metabolic clustering identified four clusters with distinct patterns and further showed that insulin clearance positively correlated with circulating CEACAM1, especially in individuals with normoglycemia, lower obesity and hepatic steatosis. This suggests that circulating CEACAM1 can reflect the status of hepatic insulin clearance. Conclusions: This study demonstrates a progressive increase in insulin resistance and hyperinsulinemia in parallel to elevated BMI and hepatic steatosis prevalence, accompanied by declining circulating CEACAM1 levels. Cluster analysis further linked reduced insulin clearance to lower circulating CEACAM1 levels, suggesting its potential usefulness as a biomarker for metabolic disease progression. [ABSTRACT FROM AUTHOR]

Eosinophils contribute to metabolic homeostasis and airway hyperresponsiveness, but their specific role in obesity-related airway hyperresponsiveness remains unclear. To address this, we used transgenic mice that overexpress interleukin-5 (IL-5) in peripheral T cells (+IL-5T) and wild-type controls. On a normal diet, +IL-5T and wild-type mice have similar body weight, body fat, and airway nerve-mediated reflex bronchoconstriction in response to inhaled serotonin. Feeding wild-type mice a 61.6% high-fat diet resulted in significantly increased body weight, body fat, fasting glucose, fasting insulin, and reflex bronchoconstriction induced by serotonin, which was blocked by vagotomy. In contrast, +IL-5T mice on a high-fat diet gained less body weight and fat than wild-type mice on the same diet and did not exhibit potentiation in fasting glucose, fasting insulin, or reflex bronchoconstriction induced by serotonin. Compared with wild-type mice, +IL-5T mice on normal diet had significantly more adipose tissue eosinophils, and this was further increased by high-fat diet. High-fat diet did not increase adipose tissue eosinophils in wild-type mice. Our findings suggest that adipose tissue eosinophils may play a role in regulating body fat, thereby reducing insulin, which is a mediator of obesity-related airway hyperresponsiveness. Thus, our data indicate adipose tissue eosinophils may be an important avenue for research in obesity-related asthma. NEW & NOTEWORTHY: This study investigates how eosinophils influence systemic metabolism and airway function in obesity. Known for their immune functions, eosinophils also mitigate obesity-related hyperinsulinemia, reducing airway hyperresponsiveness in obese mice models. The findings suggest potential therapeutic strategies targeting the intricate interplay among neurons, eosinophils, and the endocrine system to alleviate asthma in obesity. This research provides novel insights into the critical neuro-immune-endocrine interactions essential for managing obesity-related asthma. [ABSTRACT FROM AUTHOR]

In our research, we present a data mining model for the early diagnosis of hyperinsulinemia, potentially reducing the risk of diabetes, heart disease, and other chronic conditions. The dataset, gathered from 2019 to 2022 by Serbia's Healthcare Center through an observational cross-sectional study, includes 1008 adolescents. Medical datasets are often highly imbalanced and may contain irrelevant features that hinder predictive performance. To address these challenges in the medical data analysis, we propose a model employing Functional Principal Component Analysis (FPCA), which also accounts for outliers that could otherwise lead to the inclusion of irrelevant features. Unlike standard Principal Component Analysis (PCA), which is sensitive to the initial positions of cluster centers influencing the final outcome, our model integrates FPCA with K-Means clustering to improve the preprocessing stage. Additionally, we have incorporated the post-hoc explanatory method SHAP (SHapley Additive exPlanations) alongside algorithms such as Random Forest, XGBoost, and LightGBM to provide deeper insights into our model, identifying the most contributory features for the development of hyperinsulinemia. Experimental results showed that combining FPCA with K-Means clustering enhances the accuracy of the XGBoost classifier, with this model achieving an accuracy score of 0.99. [ABSTRACT FROM AUTHOR]

Hyperinsulinemic hypoglycemias resulting from variants in the insulin receptor (INSR) gene are rare but clinically important disorders. We present a male patient in his 30s, experiencing recurrent postprandial hypoglycemic events. Endocrine evaluation revealed an elevated insulin-to-C-peptide ratio. A hypoglycemia gene panel, using next-generation sequencing, identified a heterozygous nonsense variant in the INSR gene (NM_000208.4) c.3079C > T, p.(Arg1027*). Initial treatment with diazoxide reduced hypoglycemic symptoms and led to weight loss and decreased hemoglobin A1c due to reduced compensatory carbohydrate intake. However, limiting side effects on diazoxide prompted a treatment switch to lanreotide with maintained absence of hypoglycemic events. This case highlights the importance of considering variants in the INSR gene as a differential diagnosis in hyperinsulinemic hypoglycemia cases, even in adults. [ABSTRACT FROM AUTHOR]

Background Hypothesis/Objectives Animals Methods Results Conclusion and Clinical Importance Phenylbutazone is prescribed for laminitis‐associated pain and decreases glucose and insulin responses to an oral glucose test (OGT) in horses with insulin dysregulation (ID).Investigate the effect of phenylbutazone administration on the enteroinsular axis in horses.Sixteen horses, including 7 with ID.Randomized cross‐over study design, with horses assigned to treatment with phenylbutazone (4.4 mg/kg IV q24h) or placebo (5 mL 0.9% saline). On Day 9 of treatment, an OGT was conducted, followed by a 10‐day washout period, administration of the alternative treatment, and repetition of the OGT. Glucose‐dependent insulinotropic polypeptide (GIP), and active glucagon‐like peptide 1 and 2 (aGLP‐1 and GLP‐2) concentrations were determined by ELISA. The effects of ID status and treatment on peptide concentrations were assessed using t tests and analyses of variance.Horses with ID had significantly higher maximum GIP concentrations (Cmax) than controls (median, 279.1; interquartile range [IQR], 117.5‐319.4 pg/mL vs median, 90.12; IQR, 74.62‐116.5 pg/mL; P = .01), but no significant effect of ID was detected on aGLP‐1 and GLP‐2 concentrations. In horses with ID, phenylbutazone treatment significantly decreased GIP Cmax compared with placebo (168.1 ± 59.26 pg/mL vs 242.8 ± 121.8 pg/mL; P = .04), but no significant effect of phenylbutazone was detected on aGLP‐1 and GLP‐2 concentrations.Glucose‐dependent insulinotropic polypeptide, aGLP‐1 and GLP‐2 do not mediate the decrease in glucose and insulin concentrations observed after phenylbutazone administration. Only GIP was repeatedly associated with ID status, calling into question the role of the enteroinsular axis in ID. [ABSTRACT FROM AUTHOR]

Kidney stones or Nephrolithiasis are the most common health condition associated with the urinary system. Dietary factors stand as important factors in the occurrence and development of kidney stones. This study aimed to examine the potential link between dietary insulin index (DII) and dietary insulin load (DIL) with prevalence of kidney stones. This cross-sectional study was conducted among adults aged 30 to 75 years in the Shahedieh district of Yazd, Iran, over the period of 2015–2016. DII and DIL were calculated using a validated semi-quantitative food-frequency questionnaire and mathematical formula. Diagnosis of kidney stones is made on the basis of information obtained from self-reported questionnaire (Yes/ No). To explore the association between DII and DIL with the odds of kidney stones, logistic regression was employed in crude and adjusted models. A total of 4,829 participants were included in this study. Individuals in the last quartile of DIL had 214% higher odds of kidney stones in the crude model (OR: 2.14, 95% CI: 1.62–2.83; P-trend < 0.001); this association was remained significant after adjustments for confounding variables (OR: 1.44, 95% CI: 1.04–1.97; P-trend: 0.019). There was a direct significant relationship between DII and odds of kidney stones among third and forth quartiles of DII (OR: 1.52, 95% CI: 1.16–1.98, P-trend = 0.002); but this association disappeared for adjusted models. Higher DII and DIL were associated with an increased odd of renal stones. Large longitudinal study is required to clarify these associations. [ABSTRACT FROM AUTHOR]

Background & Aims: Pregnancy is a diabetogenic state characterized by hyperinsulinemia and insulin resistance. The primary goal of identifying gestational diabetes mellitus (GDM) is to detect women at risk for adverse perinatal outcomes. Proper diagnosis of this condition and its complications is essential for the benefit of both maternal and child health. The uric acid/HDL-C ratio (UHR), which combines two metabolic parameters—serum uric acid and HDL-C— is a powerful predictor of metabolic deterioration. The present study aims to understand the role of metabolic derangement in the development of GDM in pregnant women and to compare these findings with those of healthy controls. The objectives of the study are to compare the serum UHR in the GDM and control populations and to correlate UHR in each group with glycemic status markers and BMI. Materials & Methods: Based on inclusion and exclusion criteria, a total of 30 cases and 30 age-matched controls were selected for the study. The age range was 18 to 35 years. All serum parameters were analyzed using a Beckman Coulter AU-480 fully automated analyser. UHR was calculated from serum uric acid and HDL-C values using the formula: UHR = UA/HDL-C. Results: The results show that patients with GDM had higher uric acid levels and UHR and lower HDL-C levels than healthy controls, suggesting significant metabolic derangement in this group. Conclusion: Routine use of UHR as an early screening tool can help identify metabolic abnormalities in GDM. This will also aid in early pharmacological intervention, thereby preventing future complications for both the mother and foetus.

Abstract Kidney stones or Nephrolithiasis are the most common health condition associated with the urinary system. Dietary factors stand as important factors in the occurrence and development of kidney stones. This study aimed to examine the potential link between dietary insulin index (DII) and dietary insulin load (DIL) with prevalence of kidney stones. This cross-sectional study was conducted among adults aged 30 to 75 years in the Shahedieh district of Yazd, Iran, over the period of 2015–2016. DII and DIL were calculated using a validated semi-quantitative food-frequency questionnaire and mathematical formula. Diagnosis of kidney stones is made on the basis of information obtained from self-reported questionnaire (Yes/ No). To explore the association between DII and DIL with the odds of kidney stones, logistic regression was employed in crude and adjusted models. A total of 4,829 participants were included in this study. Individuals in the last quartile of DIL had 214% higher odds of kidney stones in the crude model (OR: 2.14, 95% CI: 1.62–2.83; P-trend

Abstract Background The possible role of the insulinemic potential of diet in the etiology of type 2 diabetes (T2D) has recently received significant attention in observational studies. This meta-analysis aimed to synthesize available evidence and quantify the potential association between the empirical dietary index for hyperinsulinemia (EDIH) score and T2D risk. Methods Various electronic databases, including Scopus, PubMed, and Web of Science, were comprehensively searched up to January 2024 using related keywords to identify relevant studies. The hazard ratios (HR) or odds ratios were extracted from eligible cohort studies, and a random-effects model with an inverse variance weighting method was used to calculate the pooled effect size, which was expressed as HR. Results The analysis included six cohort studies (four publications), with sample sizes ranging from 3,732 to 90,786 individuals aged 20 to 79 years. During follow-up periods of 5 to over 20 years, 31,284 T2D incidents were identified. The pooled results showed that a higher EDIH score was associated with an increased risk of T2D incidence (HR: 1.47; 95%CI 1.21–1.77; I2 = 91.3%). Significant publication bias was observed in the present meta-analysis (P = 0.020). Geographical region and follow-up period can be as sources of heterogeneity (Pheterogeneity

ABSTRACT Background Type 2 diabetes (T2D) is a complex metabolic disorder characterized by insulin resistance, hyperglycemia, and hyperinsulinemia. A significant portion of individuals with T2D are unaware of their condition until it has reached advanced stages. T2D is also associated with an increased risk and worse prognosis of cardiovascular disease, cognitive decline, and cancer. Understanding the mechanisms underlying the emergence of insulin resistance is critical for improving early detection and therapeutic interventions. Methods An updated framework is proposed to describe the emergence of insulin resistance that precedes the development of T2D. The model focuses on the impact of diminishing capacity to store excess glucose, which can occur due to a multitude of factors, including age‐related muscle loss. The model is used to simulate responses to oral glucose tolerance tests (OGTTs) to capture the transition from a normal to a diabetic phenotype, as defined by the Kraft criteria. Additionally, the model is used to explore how the metabolic environment influences tumor progression, drawing on experimental data regarding the impact of transient diabetic phenotypes and hyperinsulinemia on cancer therapy efficacy. Results The model successfully demonstrates that reduced glucose storage capacity can qualitatively reproduce the progression from normal to diabetic phenotypes observed in OGTT responses. Furthermore, it shows that tumor progression or regression is highly dependent on the host's metabolic environment, particularly hyperinsulinemia. This aligns with experimental results that connect drug‐induced hyperinsulinemia to a loss of therapeutic efficacy against tumors, whereas the reversal of the diabetic phenotype could restore drug sensitivity and treatment response. Conclusions This study highlights the critical role of hyperinsulinemia, even in normoglycemic individuals, in both the progression of T2D and the modulation of cancer therapy outcomes. Addressing hyperinsulinemia emerges as a promising strategy to enhance cancer treatment efficacy and improve overall health outcomes in patients with or at risk for T2D.

Background: The possible role of the insulinemic potential of diet in the etiology of type 2 diabetes (T2D) has recently received significant attention in observational studies. This meta-analysis aimed to synthesize available evidence and quantify the potential association between the empirical dietary index for hyperinsulinemia (EDIH) score and T2D risk. Methods: Various electronic databases, including Scopus, PubMed, and Web of Science, were comprehensively searched up to January 2024 using related keywords to identify relevant studies. The hazard ratios (HR) or odds ratios were extracted from eligible cohort studies, and a random-effects model with an inverse variance weighting method was used to calculate the pooled effect size, which was expressed as HR. Results: The analysis included six cohort studies (four publications), with sample sizes ranging from 3,732 to 90,786 individuals aged 20 to 79 years. During follow-up periods of 5 to over 20 years, 31,284 T2D incidents were identified. The pooled results showed that a higher EDIH score was associated with an increased risk of T2D incidence (HR: 1.47; 95%CI 1.21–1.77; I2 = 91.3%). Significant publication bias was observed in the present meta-analysis (P = 0.020). Geographical region and follow-up period can be as sources of heterogeneity (Pheterogeneity <0.001). Conclusion: Our meta-analysis of observational studies suggested that a diet with a higher EDIH score may be associated with an increased risk of incidence of T2D. [ABSTRACT FROM AUTHOR]

Background: The rising global number of Diabetes mellitus (DM) cases indicated the significance of early detection of insulin resistance trying to decrease the economic and healthcare burden caused by DM. Objectives: This study aimed to evaluate the efficacy of using Homeostasis Model Assessment-Estimated Insulin Resistance (HOMA-IR) and to define a suitable HOMA-IR cut-off value. The difficulty of performing a euglycaemic-hyperinsulinaemic clamp in extensive studies has stimulated the importance of using and developing surrogate insulin sensitivity indices. Design: Retrospective cohort study. Setting: Involved 397 participants referred from outpatient clinics at Dr. Sulaiman Alhabib Hospital between January 2011 and December 2021 for a Glucose Tolerance/Insulin Response test. Methods: Data was obtained from the electronic medical system in Dr. Sulaiman Alhabib hospital. Insulin response interpretation was based on the Kraft pattern, classifying insulin patterns into five types. HOMA-IR was calculated using the formula HOMA-IR = (FPI*FPG)/22.5. Statistical analyses were performed using MedCalc Statistical Software version 20. Receiver Operating Characteristic curves were plotted to assess the diagnostic performance of HOMA-IR in distinguishing between cases and non-cases of insulin resistance. The area under the curve and 95% confidence intervals were calculated. The Youden index was used to select the optimum cut-off points. Results: Youden index was used for selecting the optimum cut off points. For the combined dataset, a cut-off value of >1.93 showed a sensitivity of 66.91% and specificity of 71.31%. The logistic regression was used to assess various predictors of the development of diabetes mellitus. impaired glucose tolerance, impaired fasting glucose, or gestational diabetes. Insulin resistance based on HOMA-IR was a significant predictor. Conclusion: Insulin resistance is a hallmark of type 2 diabetes. Establishing and using a sensitive and specific population-based cut-off for HOMAIR is highly recommended for early detection of insulin resistance. The study faced some challenges such as limited participants and incomplete follow-up. [ABSTRACT FROM AUTHOR]

Objective Fasting hyperglycemia and hypertriglyceridemia are characteristic of insulin resistance (IR) and rodent work has suggested this may be due to selective hepatic IR, defined by increased hepatic gluconeogenesis and de novo lipogenesis (DNL), but this has not been shown in humans. Design Cross-sectional study in men and women across a range of adiposity. Methods Medication-free participants (n = 177) were classified as normoinsulinemic (NI) or hyperinsulinemic (HI) and as having low (LF) or high (HF) liver fat content measured by magnetic resonance spectroscopy. Fractional gluconeogenesis (frGNG) and hepatic DNL were measured using stable isotope tracer methodology following an overnight fast. Results Although HI and HF groups had higher fasting plasma glucose and triglyceride concentrations when compared to NI and LF groups respectively, there was no difference in frGNG. However, HF participants tended to have lower frGNG than LF participants. HI participants had higher DNL compared to NI participants but there was no difference observed between liver fat groups. Conclusions Taken together, we found no metabolic signature of selective hepatic IR in fasting humans. DNL may contribute to hypertriglyceridemia in individuals with HI but not those with HF. Glycogenolysis and systemic glucose clearance may have a larger contribution to fasting hyperglycemia than gluconeogenesis, especially in those with HF, and these pathways should be considered for therapeutic targeting. [ABSTRACT FROM AUTHOR]

Despite all the progress made by science in the prevention and treatment of cardiovascular diseases and cancers, these are still the main reasons for hospitalizations and death in the Western world. Among the possible causes of this situation, disorders related to hyperinsulinemia and insulin resistance (Hyperin/IR) are still little-known topics. An analysis of the literature shows that this condition is a multiple risk factor for type 2 diabetes, cardiovascular diseases, cellular senescence and cancer, and neurodegenerative diseases. Hyperin/IR is progressively increasing worldwide, and its prevalence has now exceeded 50% of the general population and in overweight children. Asymptomatic or poorly symptomatic, it can last for many years before manifesting itself as diabetes, cardiovascular disease, neoplasm, cognitive deficit, or dementia, therefore leading to enormous social and healthcare costs. For these reasons, a screening plan for this pathology should be implemented for the purpose of identifying people with Hyperin/IR and promptly starting them on preventive treatment. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder affecting people worldwide. It is characterized by several key features, including hyperinsulinemia, hyperglycemia, hyperlipidemia, and dysbiosis. Epidemiologic studies have shown that T2DM is closely associated with the development and progression of cancer. T2DM-related hyperinsulinemia, hyperglycemia, and hyperlipidemia contribute to cancer progression through complex signaling pathways. These factors increase drug resistance, apoptosis resistance, and the migration, invasion, and proliferation of cancer cells. Here, we will focus on the role of hyperinsulinemia, hyperglycemia, and hyperlipidemia associated with T2DM in cancer development. Additionally, we will elucidate the potential molecular mechanisms underlying their effects on cancer progression. We aim to identify potential therapeutic targets for T2DM-related malignancies and explore relevant directions for future investigation. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a prevalent metabolic disorder among women of reproductive age, characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. The pathogenesis of PCOS involves a complex interplay of genetic and environmental factors, including insulin resistance (IR) and resultant hyperinsulinemia. Insulin receptors, primarily in skeletal muscle, liver, and adipose tissue, activate downstream signaling pathways like PI3K-AKT and MAPK-ERK upon binding. These pathways regulate glucose uptake, storage, and lipid metabolism. Genome-wide association studies (GWASs) have identified several candidate genes related to steroidogenesis and insulin signaling. Environmental factors such as endocrine-disrupting chemicals and lifestyle choices also exacerbate PCOS traits. Other than lifestyle modification and surgical intervention, management strategies for PCOS can be achieved by using pharmacological treatments like antiandrogens, metformin, thiazolidinediones, aromatase inhibitor, and ovulation drugs to improve insulin sensitivity and ovulatory function, as well as combined oral contraceptives with or without cyproterone to resume menstrual regularity. Despite the complex pathophysiology and significant economic burden of PCOS, a comprehensive understanding of its molecular and cellular mechanisms is crucial for developing effective public health policies and treatment strategies. Nevertheless, many unknown aspects of PCOS, including detailed mechanisms of actions, along with the safety and effectiveness for the treatment, warrant further investigation. [ABSTRACT FROM AUTHOR]

Introduction: Using a non-human primate (NHP) model of maternal Westernstyle diet (mWSD) feeding during pregnancy and lactation, we previously reported altered offspring beta:alpha cell ratio in vivo and insulin hypersecretion ex vivo. Mitochondria are known to maintain beta-cell function by producing ATP for insulin secretion. In response to nutrient stress, the mitochondrial network within beta cells undergoes morphological changes to maintain respiration and metabolic adaptability. Given that mitochondrial dynamics have also been associated with cellular fate transitions, we assessed whether mWSD exposure was associated with changes in markers of beta-cell maturity and/or mitochondrial morphology that might explain the offspring islet phenotype. Methods: We evaluated the expression of beta-cell identity/maturity markers (NKX6.1, MAFB, UCN3) via florescence microscopy in islets of Japanese macaque pre-adolescent (1 year old) and peri-adolescent (3-year-old) offspring born to dams fed either a control diet or WSD during pregnancy and lactation and weaned onto WSD. Mitochondrial morphology in NHP offspring beta cells was analyzed in 2D by transmission electron microscopy and in 3D using super resolution microscopy to deconvolve the beta-cell mitochondrial network. Results: There was no difference in the percent of beta cells expressing key maturity markers in NHP offspring from WSD-fed dams at 1 or 3 years of age; however, beta cells of WSD-exposed 3 year old offspring showed increased levels of NKX6.1 per beta cell at 3 years of age. Regardless of maternal diet, the beta-cell mitochondrial network was found to be primarily short and fragmented at both ages in NHP; overall mitochondrial volume increased with age. In utero and lactational exposure to maternal WSD consumption may increase mitochondrial fragmentation. Discussion: Despite mWSD consumption having clear developmental effects on offspring beta:alpha cell ratio and insulin secretory response to glucose, this does not appear to be mediated by changes to beta-cell maturity or the beta-cell mitochondrial network. In general, the more fragmented mitochondrial network in NHP beta cells suggests greater ability for metabolic flexibility. [ABSTRACT FROM AUTHOR]

ObjectiveTo explore any correlation between serum urate (SU) level or insulin resistance (IR) and metabolic dysfunction associated steatotic liver disease (MASLD) in patients with metabolic syndrome (MS).MethodsData from all MASLD patients, diagnosed by liver biopsy, were enrolled and divided into MASLD alone group and MASLD with MS group. They were subdivided into hyperuricemia group and normal SU group to find correlation between SU/IR and MASLD in patients with MS and independent risk factors for MASLD.ResultsData from 539 MASLD patients were analyzed. Body mass index (BMI) (p = 0.000), waist circumference (WC) (p = 0.004), and low-density lipoprotein (LDL) (p = 0.000) were dramatically higher in MASLD with MS group than those with MASLD alone; MASLD with MS patients had significantly more family history of diabetes (p = 0.000) and hypertension (p = 0.000) than patients with MASLD alone. Height (p = 0.000), weight (p = 0.000), BMI (p = 0.000) and WC (p = 0.001), and LDL (p = 0.007) were dramatically higher in hyperuricemia patients than those with normal SU. SU was inversely associated with age (p = 0.000) and high-density lipoprotein (HDL) (p = 0.003), and positively correlated with weight (p = 0.000), BMI (p = 0.000) and WC (p = 0.000), TG (p = 0.000), and LDL (p = 0.000). Logistic Regression analysis showed that age (p = 0.031), TG (p = 0.002), LDL (p = 0.010), HbA1c (p = 0.026), and family history of hypertension (p = 0.000) may be independent risk factors for MASLD in patient with MS.ConclusionInsulin resistance (IR) in MASLD patients with MS, but not higher SU levels, has closer correlation with the occurrence of MASLD in patients with family history of hypertension and diabetes having higher BMI, LDL, HbA1c.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women, characterized by irregular menstrual cycles, elevated levels of male hormones (hyperandrogenism), and characteristic ovarian appearance on ultrasound. A cornerstone in the development of PCOS is insulin resistance, a condition in which the body’s cells do not respond normally to insulin, the hormone that regulates blood sugar levels. In response, the pancreas produces more insulin, leading to hyperinsulinemia. This hormonal imbalance stimulates the production of male hormones by the ovaries and adrenal glands, contributing to the development of hyperandrogenism and ovulatory dysfunction. Hyperandrogenism in PCOS manifests with symptoms such as acne, hirsutism (excess hair growth), androgenic alopecia (hair loss), and menstrual disturbances. Ovulatory dysfunction, partly caused by insulin resistance, is a major cause of infertility in women with PCOS. [ABSTRACT FROM AUTHOR]

Disentangling which of insulin hypersecretion and insulin resistance is upstream in obesity-related type 2 diabetes (T2D) is challenging. Here, we consider the dynamics of insulin secretion and action in the fetuses of mothers with diabetes. We argue that fetal insulin hypersecretion occurs first, with insulin resistance being an adaptive protective response. [ABSTRACT FROM AUTHOR]

Insulin resistance (IR) and metabolic disorders are non-pulmonary adverse effects induced by fine particulate matter (PM2.5) exposure. The worldwide pandemic of high fructose sweeteners and fat rich modern diets, also contribute to IR development. We investigated some of the underlying effects of IR, altered biochemical insulin action and Insulin/AKT pathway biomarkers. Male Sprague Dawley rats were subchronically exposed to filtered air, PM2.5, a fructose rich diet (FRD), or PM2.5 + FRD. Exposure to PM2.5 or FRD alone did not induce metabolic changes. However, PM2.5 + FRD induced leptin release, systemic hyperinsulinemia, and Insulin/AKT dysregulation in insulin-sensitive tissues preceded by altered AT1R levels. Histological damage and increased HOMA-IR were also observed from PM2.5 + FRD co-exposure. Our results indicate that the concomitant exposure to a ubiquitous environmental pollutant, such as PM2.5, and a metabolic disease risk factor, a FRD, can contribute to the metabolic disorder pandemic occurring in highly polluted locations.

We previously demonstrated that antisense oligonucleotide-mediated knockdown of Mboat7, the gene encoding membrane bound O-acyltransferase 7, in the liver and adipose tissue of mice promoted high fat diet-induced hepatic steatosis, hyperinsulinemia, and systemic insulin resistance. Thereafter, other groups showed that hepatocyte-specific genetic deletion of Mboat7 promoted striking fatty liver and NAFLD progression in mice but does not alter insulin sensitivity, suggesting the potential for cell autonomous roles. Here, we show that MBOAT7 function in adipocytes contributes to diet-induced metabolic disturbances including hyperinsulinemia and systemic insulin resistance. We generated Mboat7 floxed mice and created hepatocyte- and adipocyte-specific Mboat7 knockout mice using Cre-recombinase mice under the control of the albumin and adiponectin promoter, respectively. Here, we show that MBOAT7 function in adipocytes contributes to diet-induced metabolic disturbances including hyperinsulinemia and systemic insulin resistance. The expression of Mboat7 in white adipose tissue closely correlates with diet-induced obesity across a panel of ∼100 inbred strains of mice fed a high fat/high sucrose diet. Moreover, we found that adipocyte-specific genetic deletion of Mboat7 is sufficient to promote hyperinsulinemia, systemic insulin resistance, and mild fatty liver. Unlike in the liver, where Mboat7 plays a relatively minor role in maintaining arachidonic acid-containing PI pools, Mboat7 is the major source of arachidonic acid-containing PI pools in adipose tissue. Our data demonstrate that MBOAT7 is a critical regulator of adipose tissue PI homeostasis, and adipocyte MBOAT7-driven PI biosynthesis is closely linked to hyperinsulinemia and insulin resistance in mice.

Polycystic ovary syndrome (PCOS) is a leading cause of infertility, with an estimated worldwide prevalence between 5% and 15%. We conducted a case–control study with 121 PCOS patients and 155 controls to assess the association between coffee intake and the presence of having a diagnosis of PCOS in women in Murcia, Spain. The PCOS diagnosis was determined following Rotterdam criteria (the presence of two of the following three conditions: hyperandrogenism, oligo-anovulation, and/or polycystic ovarian morphology). Coffee consumption was assessed using a validated food frequency questionnaire. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multiple logistic regression. Coffee consumption was categorized into never, less than one cup per day, one cup per day, and two or more cups per day. We found a significant inverse linear trend: the higher the coffee consumption, the lower the probability of having PCOS in multivariable analysis (p-trend = 0.034). Women who presented with PCOS were less likely to drink one cup of coffee compared to those who had never drunk coffee (OR = 0.313, 95% CI: 0.141–0.69). The consumption of at least one cup of coffee per day may be associated with a decrease in PCOS symptoms. [ABSTRACT FROM AUTHOR]

Polycystic ovarian syndrome is a perplexed condition addressing endocrinal, cardiometabolic and gynaecological issues. It affects women of adolescent age and is drastically increasing in the Indo-Asian ethnicity over the recent years. According to Rotterdam criteria, PCOS is characterized by clinical or biochemical excess androgen and polycystic ovarian morphology; however, it has been established in the recent years that PCOS exacerbates to further serious metabolic conditions on the long term. This is a narrative literature review and not systematic review and is based on PubMed searches with relevant keywords "Polycystic ovarian syndrome AND acarbose OR metformin OR myoinositol; PCOS AND metabolic syndrome OR cardiovascular disease OR menstrual irregularity OR infertility OR chronic anovulation OR clinical hyperandrogenism" used in the title and are limited to articles published in English language with no time limits. A prominent aspect of PCOS is hyperandrogenaemia and hyperinsulinemia. About 50-70% of afflicted women have compensatory hyperinsulinemia and close to one tierce suffer from anovulation and infertility. Insulin resistance leads to metabolic complications and works with luteinizing hormone in increasing the ovarian androgen production. This excess androgen leads to clinical manifestations, irregular menstrual cycles and infertility. There isn't an entire cure, only the symptomatic clinical factors are considered rather than focusing on the underlying long-term complications. Therefore, the article focuses on a potent alpha glucosidase inhibitor, acarbose which suppresses the post meal glucose and insulin by delaying the absorption of complex carbs. It exhibits cardio-metabolic and hormonal benefits and is well tolerable in the south asian population. This review highlights the safety, effectiveness of acarbose in ameliorating the long-term complications of PCOS. [ABSTRACT FROM AUTHOR]

Unfortunately, cardiovascular diseases and cancers are still the leading causes of death in developed and developing countries despite the considerable progress made in the prevention and treatment of diseases. Maybe we missed something? Insulin resistance (IR) with associated hyperinsulinemia (Hypein) is a silent pandemic whose prevalence is continually growing in developed and developing countries, now exceeding 51% of the general population. IR/Hypein, despite the vast scientific literature supporting its adverse action on the development of type 2 diabetes, cardiovascular alterations, tumors, neurological disorders, and cellular senescence, is not yet considered an independent risk factor and, therefore, is not screened in the general population and adequately treated. There are now numerous substances, drugs, and natural substances that, in association with the correction of a wrong lifestyle, can help to reduce IR/Hypein. We are convinced that the time has come to implement a prevention plan against this critical risk factor. Therefore, this manuscript aims to highlight IR/Hypein as an independent risk factor for type 2 diabetes, cardiovascular diseases, cancers, cellular senescence, and neuropsychiatric disorders, supporting our conviction with the available scientific literature on the topic. [ABSTRACT FROM AUTHOR]

Neonatal Respiratory Distress Syndrome (NRDS) in infants of diabetic mothers (IDMs) is significantly influenced by maternal hyperglycemia and hyperinsulinemia, which impair surfactant production necessary for lung function. It is known that NRDS occurs in preterm infants, but research is limited on whether this occurs in near-term to full-term IDMS, which is what we discuss further in this paper. Studies indicate that maternal diabetes, both type 1 and type 2, increases the risk of NRDS, with hyperinsulinemia in the fetus inhibiting surfactant synthesis and contributing to respiratory complications. Furthermore, while insulin therapy manages maternal glucose levels, it can also be a risk factor for NRDS. Effective prenatal care, proper glycemic control, and further research into maternal HbA1C levels and insulin's role in surfactant production are essential for reducing NRDS incidence. Improved diagnostic criteria for gestational diabetes and enhanced management strategies can potentially prevent NRDS, benefiting neonatal outcomes globally. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

There is increasing evidence of metabolic perturbations in multiple sclerosis (MS) patients, and insulin is an important parameter that has controversial effects on neurological disease. Therefore, this systematic review and meta-analysis study aimed to explore the association between insulin resistance (IR) and MS as well as insulin levels and MS. Three electronic databases, including Medline, Scopus, and the Web of Science, were examined up to 26 May 2023 for observational studies. Two independent reviewers assessed the studies according to a pre-specified protocol. Random-effects model using a Restricted-maximum Likelihood (REML) estimator was used to meta-analyze the association between IR [assessed by Homeostatic Model Assessment (HOMA-IR)], insulin and MS. Eighteen datasets from 2012 to 2022 were included in this meta-analysis. The standardized mean difference (SMD) for comparison IR and insulin between MS and healthy control group as outcomes 1 and 2 were 0.78 and 0.72 respectively. Furthermore, for outcome 1, we observed a greater effect size in studies that recruited different types of MS (Mix) (SMD: 1.09) than in those that included only relapsing-remitting MS (RRMS) (SMD: 0.59). The meta-analysis revealed a significant association between IR, insulin and MS, with stronger associations in studies that recruited mixed patients. However, high heterogeneity has been observed in the present study. Therefore, more studies are needed to confirm the association between these parameters and MS. [ABSTRACT FROM AUTHOR]

Previous studies have shown that dietary cholest-4-en-3-one (4-cholestenone, 4-STN) exerts anti-obesity and lipid-lowering effects in mice. However, its underlying mechanisms are not fully understood. In the present study, we evaluated whether 4-STN supplementation would protect obese diabetic db/db mice from obesity-related metabolic disorders. After four weeks of feeding of a 0.25% 4-STN-containing diet, dietary 4-STN was found to have significantly alleviated hyperlipidemia, hepatic cholesterol accumulation, and hyperinsulinemia; however, the effect was not sufficient to improve hepatic triglyceride accumulation or obesity. Further analysis demonstrated that dietary 4-STN significantly increased the content of free fatty acids and neutral steroids in the feces of db/db mice, indicating that the alleviation of hyperlipidemia by 4-STN was due to an increase in lipid excretion. In addition, dietary 4-STN significantly reduced the levels of desmosterol, a cholesterol precursor, in the plasma but not in the liver, suggesting that normalization of cholesterol metabolism by 4-STN is partly attributable to the suppression of cholesterol synthesis in extrahepatic tissues. In addition, dietary 4-STN increased the plasma and hepatic levels of 4-STN metabolites cholestanol (5α-cholestan-3β-ol) and coprostanol (5β-cholestan-3β-ol). Our results show that dietary 4-STN alleviates obesity-related metabolic disorders, such as hyperlipidemia, hepatic cholesterol accumulation, and hyperinsulinemia, in db/db mice. [ABSTRACT FROM AUTHOR]

The worldwide incidence of prediabetes/type 2 has continued to rise the last 40 years. In the same period, the mean daily energy intake has increased, and the quality of food has significantly changed. The chronic exposure of pancreatic β-cells to calorie excess (excessive energy intake) and food additives may increase pancreatic insulin secretion, decrease insulin pulses and/or reduce hepatic insulin clearance, thereby causing chronic hyperinsulinemia and peripheral insulin resistance. Chronic calorie excess and hyperinsulinemia may promote lipogenesis, inhibit lipolysis and increase lipid storage in adipocytes. In addition, calorie excess and hyperinsulinemia can induce insulin resistance and contribute to progressive and excessive ectopic fat accumulation in the liver and pancreas by the conversion of excess calories into fat. The personal fat threshold hypothesis proposes that in susceptible individuals, excessive ectopic fat accumulation may eventually lead to hepatic insulin receptor resistance, the loss of pancreatic insulin secretion, hyperglycemia and the development of frank type 2 diabetes. Thus, type 2 diabetes seems (partly) to be caused by hyperinsulinemia-induced excess ectopic fat accumulation in the liver and pancreas. Increasing evidence further shows that interventions (hypocaloric diet and/or bariatric surgery), which remove ectopic fat in the liver and pancreas by introducing a negative energy balance, can normalize insulin secretion and glucose tolerance and induce the sustained biochemical remission of type 2 diabetes. This pathophysiological insight may have major implications and may cause a paradigm shift in the management of type 2 diabetes: avoiding/reducing ectopic fat accumulation in the liver and pancreas may both be essential to prevent and cure type 2 diabetes. [ABSTRACT FROM AUTHOR]

Metabolic-associated fatty liver disease (MAFLD) has been identified as risk factor of incident type 2 diabetes (T2D), but the underlying postprandial mechanisms remain unclear. We compared the glucose metabolism, insulin resistance, insulin secretion, and insulin clearance post-oral glucose tolerance test (OGTT) between individuals with and without MAFLD. We included 50 individuals with a body mass index (BMI) between 25 and 40 kg/m2 and ≥1 metabolic alteration: increased fasting triglycerides or insulin, plasma glucose 5.5–6.9 mmol/L, or glycated hemoglobin 5.7–5.9%. Participants were grouped according to MAFLD status, defined as hepatic fat fraction (HFF) ≥5% on MRI. We used oral minimal model on a frequently sampled 3 h 75 g-OGTT to estimate insulin sensitivity, insulin secretion, and pancreatic β-cell function. Fifty percent of participants had MAFLD. Median age (IQR) [57 (45–65) vs. 57 (44–63) yr] and sex (60% vs. 56% female) were comparable between groups. Post-OGTT glucose concentrations did not differ between groups, whereas post-OGTT insulin concentrations were higher in the MAFLD group (P < 0.03). Individuals with MAFLD exhibited lower insulin clearance, insulin sensitivity, and first-phase pancreatic β-cell function. In all individuals, increased insulin incremental area under the curve and decreased insulin clearance were associated with HFF after adjusting for age, sex, and BMI (P < 0.02). Among individuals with metabolic alterations, the presence of MAFLD was characterized mainly by post-OGTT hyperinsulinemia and reduced insulin clearance while exhibiting lower first phase β-cell function and insulin sensitivity. This suggests that MAFLD is linked with impaired insulin metabolism that may precede T2D. NEW & NOTEWORTHY: Using an oral glucose tolerance test, we found hyperinsulinemia, lower insulin sensitivity, lower insulin clearance, and lower first-phase pancreatic β-cell function in individuals with MAFLD. This may explain part of the increased risk of incident type 2 diabetes in this population. These data also highlight implications of hyperinsulinemia and impaired insulin clearance in the progression of MAFLD to type 2 diabetes. [ABSTRACT FROM AUTHOR]

Hypoglycaemic syndromes are rare in apparently healthy individuals and their diagnosis can be a difficult challenge for clinicians as there are no shared guidelines that suggest how to approach patients with a suspect hypoglycaemic disorder. Since hypoglycaemia symptoms are common and nonspecific, it's necessary to document the Whipple Triad (signs and/or symptoms compatible with hypoglycaemia; relief of symptoms following glucose administration; low plasma glucose levels) before starting any procedure. Once the triad is documented, a meticulous anamnesis and laboratory tests (blood glucose, insulin, proinsulin, C-peptide, β-hydroxybutyrate and anti-insulin antibodies) should be performed. Results can guide the physician towards further specific tests, concerning the suspected disease. In this review, we consider all current causes of hypoglycaemia, including rare diseases such as nesidioblastosis and Hirata's syndrome, describe appropriate tests for diagnosis and suggest strategies to differentiate hypoglycaemia aetiology. [ABSTRACT FROM AUTHOR]

Objectives. Pre-impaired glucose tolerance (pre-IGT) is a prediabetes stage characterized by normoglycemia and compensatory hyperinsulinemia due to insulin resistance. Hyperinsulinemia increases cardiovascular disease (CVD) risk, especially, endothelial dysfunction (ED). However, there is paucity of studies on ED with hyperinsulinemia alone, particularly in individuals with pre-IGT. This study aimed to determine the presence of ED using brachial artery flow-mediated dilatation (FMD) among adult participants with pre-IGT and its correlation with insulin levels and other related clinical parameters. Methodology. This is a cross-sectional analytical study. We screened adult patients with risk factors for developing diabetes (first-degree relative with type 2 diabetes mellitus, obesity, history of gestational diabetes and polycystic ovary syndrome). Brachial artery FMD was performed among participants with pre-IGT and findings were correlated with CVD risk factors using Pearson’s correlation and linear regression. Results. Of the 23 pre-IGT patients, 5 (21.74%) had decreased FMD values with significant associations with serum insulin and HbA1c. It was further observed that for every 1-unit increase in second-hour serum insulin and in HbA1c, there was a decrease in FMD values by 0.38% and 0.50%, respectively. Serum insulin was elevated, while other biochemical parameters were normal. Moreover, participants with low FMD were older, with higher BMI and had higher HBA1c, total cholesterol and low-density lipoprotein (LDL) cholesterol. Conclusion. As early as the pre-IGT stage, endothelial dysfunction using the FMD test is already present, with red flags on other CVD risk factors already developing. etes stage characterized by normoglycemia and compensatory hyperinsulinemia due to insulin resistance. Hyperinsulinemia increases cardiovascular disease (CVD) risk, especially, endothelial dysfunction (ED). However, there is paucity of studies on ED with hyperinsulinemia alone, particularly in individuals with pre-IGT. This study aimed to determine the presence of ED using brachial artery flow-mediated dilatation (FMD) among adult participants with pre-IGT and its correlation with insulin levels and other related clinical parameters. Methods: This is a cross-sectional analytical study. We screened adult patients with risk factors for developing diabetes (First-degree relative with type 2 diabetes mellitus, obesity, history of gestational diabetes, and polycystic ovary syndrome). Brachial artery FMD was performed among participants with pre-IGT, and findings were correlated with CVD risk factors using Pearson’s correlation and linear regression. Results: Of the 23 pre-IGT patients, five (21.74%) had decreased FMD values with significant associations with serum insulin and HbA1c, wherein every 1-unit increase in second-hour serum insulin and in HbA1c decrease FMD values by 0.38% and 0.50%, respectively. Serum insulin was elevated, while other biochemical parameters were normal. Moreover, participants with low FMD were older, more obese, and have higher HBA1c, total cholesterol, and LDL. Conclusion: As early as the pre-IGT stage, endothelial dysfunction using FMD test is already present, with red flags on other CVD risk factors already developing.

Metabolic disturbances associated with obesity increase the risk and advancement of various tumor forms, including postmenopausal lung cancer, in humans. Betaxanthin, a type of yellow-orange pigment found in certain plants, particularly in some flowers, fruits, and vegetables, can be utilized to inhibit the growth of tumors and lessen the metabolic dysfunctions brought on by obesity. However, the functional role of betaxanthin (BET) in suppressing lung cancer progression and its potential mechanisms are still not fully understood. In this study, we examined the regulation of BET in obese mice with postmenopausal lung cancer receiving a high-fat diet (HFD). Initially, we found that BET could significantly mitigate the metabolic dysfunction that a high-fat diet causes in mice. Improved histological changes in the mammary fat pad, lower hepatic lipid deposition, and improved glucose tolerance and insulin resistance demonstrated this. Following that, BET treatment inhibited the formation of lung neoplasms in in-situ cancer animal models that were stimulated by HFD. Furthermore, in a postmenopausal mouse model fed HFD, BET significantly reduced the growth of pre-existing lung tumors, as well as attenuating metabolic abnormalities. Notably, in vitro research revealed that BET co-culture significantly reduced the proliferation and migration of mouse lung cancer cells, whereas insulin exposure increased these processes. Research on animals verified that lung cancer progressed due to hyperinsulinemia; however, BET treatment might inhibit this condition in postmenopausal mice on a high-fat diet. BET could up-regulate sirtuin 3 (SIRT3) expression levels in tumor, liver, and mammary fat pad tissues in postmenopausal mice with HFD-induced obesity, according to a bioinformatic and molecular biology study. Crucially, eradicating SIRT3 expression completely eliminated BET’s inhibitory effects on insulin-stimulated cancer cell proliferation and migration. This suggests that increasing SIRT3 expression may be required for BET to perform its anti-tumor function against lung cancer in conditions of hyperinsulinemia. Our findings showed that by modifying SIRT3 signaling, BET consumption is probably effective in the prevention and treatment of obesity-related lung cancer.

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.

Abstract Background Women with type 1 diabetes depend on insulin injections throughout their life. However, the recommendation for strict metabolic control of diabetes requires the administration of supra-physiological doses of insulin, which might result in insulin-mediated stimulation of androgen synthesis. Hyperandrogenism in women with type 1 diabetes may be associated with polycystic ovary syndrome (PCOS). This study was performed to investigate PCOS and its associated clinical symptoms and biochemical alterations in women with type 1 diabetes in the Palestinian Territories. This retrospective cohort study consists of 50 women with type 1 diabetes and 50 apparently healthy non-diabetic controls. Questionnaire interviews were conducted. The diagnosis of PCOS was based on chronic anovulation and biochemical evidence of hyperandrogenism. Serum total testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and insulin were measured by ELISA. Results The mean waist-to-hip ratio and age at menarche were significantly higher in diabetic women than in non-diabetic controls (81.9 ± 7.9 and 13.9 ± 1.6 years vs. 78.8 ± 5.7 and 13.2 ± 1.2 years, and P = 0.045, P = 0.020, respectively). Oligomenorrhea, acanthosis nigricans, seborrhea, and hirsutism were more frequent in diabetics. The levels of total testosterone and insulin were significantly higher in diabetics (0.58 ± 0.11 ng/ml and 15.8 ± 12.4 mlU/ml vs. 0.44 ± 0.11 ng/ml and 10.8 ± 4.5 mlU/ml, P

Abstract Background Phenylbutazone is often prescribed to manage pain caused by hyperinsulinemia‐associated laminitis, but in diabetic people nonsteroidal anti‐inflammatory drugs increase insulin secretion and pancreatic activity. Hypothesis/Objectives Investigate the effect of phenylbutazone administration on insulin secretion in horses. It was hypothesized that phenylbutazone will increase insulin secretion in horses with insulin dysregulation (ID). Animals Sixteen light breed horses, including 7 with ID. Methods Randomized cross‐over study design. Horses underwent an oral glucose test (OGT) after 9 days of treatment with phenylbutazone (4.4 mg/kg IV q24h) or placebo (5 mL 0.9% saline). After a 10‐day washout period, horses received the alternative treatment, and a second OGT was performed. Insulin and glucose responses were compared between groups (ID or controls) and treatments using paired t test and analyses of variance with P

Polycystic ovary syndrome (PCOS) is a common endocrinopathy occurring in reproductive-age women. Hyperandrogenism, polycystic ovaries, chronic anovulation, and metabolic aberrations are the common features in PCOS. Hormonal changes are causing pathological symptoms in women with PCOS. The various hormone alterations in PCOS have been demonstrated. Hormones, such as insulin, growth hormones (GH), ghrelin, LEAP-2, gonadotropinreleasing hormone (GnRH), insulin, the luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio, androgens, and estrogens, are all abnormal in PCOS women. These hormones are related to metabolic disorders, such as diabetes and insulin resistance, overweight and obesity, infertility, and disturbed menstrual cycle in PCOS patients. The pathological changes of these hormones, such as increased insulin, reduced GH, increased ghrelin, and leptin resistance, result in an increased prevalence of diabetes and obesity in PCOS women. A reduced GH, increased LEAP-2 levels, high LH basal, increased LH/FSH ratio, high androgens, and low estrogen are demonstrated in PCOS and linked to infertility. This narrative review aims to clarify the changes of hormone profiles, such as insulin, GH, LH, FSH, androgens, estrogen, progesterone, ghrelin, LEAP-2, asprosin, and subfatin, in PCOS, which may reveal novel targets for better diagnosis and treatment of PCOS. [ABSTRACT FROM AUTHOR]

Heart failure (HF) has become a subject of continuous interest since it was declared a new pandemic in 1997 because of the exponential increase in hospitalizations for HF in the latest years. HF is the final state to which all heart diseases of different etiologies lead if not adequately treated. It is highly prevalent worldwide, with a progressive increase with age, reaching a prevalence of 10% in subjects over the age of 65 years. During the last two decades, it was possible to see that the prevalence of heart failure with preserved ejection fraction (HFpEF) was increasing while that of heart failure with reduced ejection fraction (HFrEF) was decreasing. HFpEF is typically characterized by concentric remodeling of the left ventricle (LV) with impaired diastolic function and increased filling pressures. Over the years, also the prevalence of insulin resistance (IR)/hyperinsulinemia (Hyperins) in the general adult population has progressively increased, primarily due to lifestyle changes, particularly in developed and developing countries, with a range that globally ranges between 15.5% and 46.5%. Notably, over 50% of patients with HF also have IR/Hyperins, and the percentage is even higher in those with HFpEF. In the scientific literature, it has been well highlighted that the increased circulating levels of insulin, associated with conditions of insulin resistance, are responsible for progressive cardiovascular alterations over the years that could stimulate the development and/or the worsening of HFpEF. The aim of this manuscript was to review the scientific literature that supports a pathophysiologic connection between IR/Hyperins and HFpEF to stimulate the scientific community toward the identification of hyperinsulinemia associated with insulin resistance as an independent cardiovascular risk factor in the development and worsening of HF, believing that its adequate screening in the general population and an appropriate treatment could reduce the prevalence of HFpEF and improve its progression. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of b-cell dysfunction on IVF outcomes in women with PCOS. Methods: This retrospective cohort study includes 1,212 women with PCOS undergoing their first IVF cycle between September 2010 and December 2019. Beta-cell dysfunction was measured by homeostasis model assessment of b-cell function (HOMA-b) index. Results: In quartiles of HOMA-b, the incidence of miscarriage dramatically increased from 10.2% (Q1) to 31.1% (Q4) (P for trend <0.001). Likewise, the incidence of miscarriage in quartiles of HOMA-b also showed a similar trend (P for trend <0.001). After adjusting for confounding factors, logistic regression analyses showed that high HOMA-IR values were independently associated with a high risk of miscarriage, with the odds ratios (OR) and 95% confidence intervals for quartiles 2-4 versus quartile 1 were 1.30 (0.69-2.46), 1.82 (0.97-3.43), and 3.57 (1.86-6.85), respectively (P for trend <0.001). When analyzed jointly, women in the highest HOMA-IR and highest HOMA-b group exhibited the highest risk for miscarriage compared with all other groups. Furthermore, higher HOMA-IR values were associated with higher risks of miscarriage among PCOS women regardless of HOMA-b values. Conclusions: b-cell dysfunction is independently associated with increased miscarriage rate and decreased live birth rate in women with PCOS. It also plays a synergistic role with IR in terms of the reproductive outcomes, while the influence of IR overweighs that of b-cell dysfunction. [ABSTRACT FROM AUTHOR]

To evaluate the effects of high dairy (HD) (≥4 servings/day), compared to adequate dairy (AD) (2–3 servings/day as per Canada's Food Guide for Healthy Eating (2007)), on blood pressure (BP) and measures of arterial stiffness in hyperinsulinemic subjects. In this cross-over clinical trial, hyperinsulinemic adults were randomized to AD and HD for 6 weeks. Anthropometric, glycemic, and lipid parameters were analyzed and dietary intake was evaluated; BP, carotid-femoral pulse wave velocity, augmentation index, and measures of arterial stiffness were assessed. Twenty-seven participants completed the study. Dairy intake was 2.2 ± 1.2 servings/day during AD. In addition, lower total and low-density lipoprotein (LDL) cholesterol were observed without significant change in BP or arterial stiffness between before and after AD. During HD, the subjects consumed 5.8 ± 1.9 servings/day of dairy products, providing a higher intake of protein, saturated fat, calcium, phosphorus, sodium, and potassium compared to the baseline diet. After the HD, subjects had higher body fat, fasting insulin, homeostatic model assessment for insulin resistance (HOMA-IR) index, and triglycerides without altering BP or arterial stiffness compared to before HD. Overall, adequate or high intake of total dairy did not modify BP or arterial stiffness in hyperinsulinemic adults after 6 weeks. [ABSTRACT FROM AUTHOR]