Markers Of Insulin Sensitivity Research Articles

Effect of Time-Restricted Eating on Circulating Levels of IGF1 and Its Binding Proteins in Obesity: An Exploratory Analysis of a Randomized Controlled Trial.

This study aimed to investigate the effects of TRE on plasma IGF1, IGFBP1, IGFBP2, and IGFBP3, and whether these effects were mediated by weight loss or body composition changes. Insulin sensitivity, glucose control, adipokines, and inflammatory markers were also examined. An exploratory analysis of an 8-week randomized controlled trial implementing a daily TRE intervention was carried out. This study was conducted at the University of Illinois at Chicago in 2019. Participants with obesity were randomized to 4 or 6 h TRE (n = 35) or a control (n = 14) group. Plasma biomarkers were measured by ELISA at baseline and week 8. In a sub-analysis, participants were stratified into higher- (>3.5%) and lower- (≤3.5%) weight-loss groups. Participants fasted daily from 7 p.m. to 3 p.m. in the 4 h TRE group (20 h) and from 7 p.m. to 1 p.m. in the 6 h TRE group (18 h), followed by ad libitum eating for the remainder of the day. Controls received no dietary recommendations. IGF1, IGFBPs, hsCRP, and adipokines were the main outcome measures of this analysis. Repeated measures ANOVA and mediation analysis were conducted. Body weight significantly decreased with TRE (-3.6 ± 0.3%), contrasting with controls (+0.2 ± 0.5%, p < 0.001). Significant effects of TRE over time were observed on plasma IGFBP2, insulin, HOMA-IR, and 8-isoprostane levels, without affecting other biomarkers. In the sub-analysis, IGFBP2 increased while leptin and 8-isoprostane decreased significantly only in the "higher weight loss" subgroup. Changes in insulin and HOMA-IR were related to TRE adherence. Eight-week daily 4 to 6 h TRE did not affect IGF1, IGFBP1, or IGFBP3 levels but improved insulin, HOMA-IR, and 8-isoprostane. IGFBP2 increased and leptin decreased when weight loss exceeded 3.5% of baseline.

Low serum glycine strengthens the association between branched-chain amino acids and impaired insulin sensitivity assessed before and after weight loss in a population with pre-diabetes: The PREVIEW_NZ cohort

AimAccumulation of circulating branched-chain amino acids (BCAA) is a hallmark feature of impaired insulin sensitivity. As intracellular BCAA catabolism is dependent on glycine availability, we hypothesised that the concurrent measurement of circulating glycine and BCAA may yield a stronger association with markers of insulin sensitivity than either BCAA or glycine alone. This study therefore examined the correlative relationships of BCAA, BCAA and glycine together, plus glycine alone on insulin sensitivity-related markers before and after an 8-week low energy diet (LED) intervention. MethodsThis is a secondary analysis of the PREVIEW (PREVention of diabetes through lifestyle Intervention in Europe and Worldwide) Study sub-cohort. Eligible participants with pre-diabetes at baseline who achieved ≥8% body weight loss following an LED intervention were included, of which 167 paired (Week 0 and Week 8) blood samples were available for amino acid analysis. Glycemic and other data were retrieved from the PREVIEW consortium database. Repeated measures linear mixed models were used to test the association between amino acids and insulin sensitivity-related markers (HOMA2-IR, glucose, insulin, and C-peptide). ResultsElevated BCAA was associated with impaired insulin sensitivity (p < 0.05), with strength of association (ηp2) almost doubled when glycine was added to the model. However, glycine in isolation was not associated with insulin sensitivity-related markers. The magnitude (β-estimates) of positive association between BCAA and HOMA2-IR, and inverse association between glycine and HOMA2-IR, increased when body weight was higher (Body weight*BCAA, Body weight*glycine, p < 0.05, both). ConclusionLow serum glycine strengthened the association between BCAA and impaired insulin sensitivity. Given that glycine is necessary to facilitate intracellular BCAA catabolism, measurement of glycine is necessary to complement BCAA analysis to comprehensively understand the contribution of amino acid metabolism in insulin sensitivity. Clinical Trial RegistrationThis study was registered with ClinicalTrials.gov (NCT01777893).

The Effect of Selenium, Zinc, and their Combined Supplementation on Cardiometabolic Biomarkers-comparing their Effects in the Energy Restriction and High-fat Diet Methods in Obese Rats.

The fat distribution in the body determines the risk of cardiometabolic problems such as heart disease and diabetes. Some dietary supplements, such as selenium and zinc, possess lipolytic and anti-angiogenic functions, which may be a useful strategy in reducing the risk of cardiometabolic complications. This study evaluated the effect of zinc (Zn), selenium (Se), and their combined supplementation on cardiometabolic risk factors in male Wistar rats in two nutritional models, including caloric restriction (CR) and high-fat diet (HFD). The 48 male Wistar rats were divided into three diet groups (HFD and CR and normal diet (ND)). The HFD group was subdivided into four groups (N=8 rats in each group) that received (HFD+Se), (HFD+Zn), (HFD+Zn+Se), and HFD alone as the control group, respectively. After 8 weeks of intervention, biochemical tests were performed on serum levels, including measurement of lipid profile (triglyceride, Cholesterol, LDL and HDL) and glycemic indices (fasting blood sugar, insulin and insulin sensitivity markers). The results showed that supplementation significantly improved the lipid profile (P <0.001). A comparison of glucose homeostasis indices in the study groups also showed a significant difference. The serum level of glucose was higher in the HFD group than in the intervention groups (P <0.001). Also, the rate of improvement of lipid profile and glycemic indexes in the group receiving the combination of two supplements showed a better trend than those receiving zinc and selenium alone. However, the values were statistically significant only for glucose homeostasis indices (P <0.001). Although obesity is a multifactorial condition, controlling other risk factors, zinc and selenium and their combined supplementation can lead to promising solutions for the treatment of obesity-induced glucose and lipid homeostasis disorders.

Irisin levels in type 2 diabetes mellitus with and without non-alcoholic fatty liver disease: a case-control study

Background: Fatty liver disease, particularly non-alcoholic fatty liver disease (NAFLD), affects around 25% of adults globally and up to 40% in developed countries. Often coexisting with type 2 diabetes mellitus (T2DM), NAFLD is linked to insulin resistance and metabolic syndrome. Irisin, a myokine induced by exercise, shows promise in enhancing insulin sensitivity, reducing hepatic steatosis, and improving metabolic health. Despite its potential, further research is needed to fully understand irisin's mechanisms and clinical implications in NAFLD and T2DM. Objectives: This study investigates the irisin levels in T2DM patients with and without NAFLD and compares them with healthy controls. Methods: A case-control study has been conducted involving 90 T2DM patients and 90 healthy controls, aged 30-55 years, recruited from SCB Medical College, Cuttack, between September 2021 and August 2022. Participants were screened for NAFLD using the Hepatosis Steatosis Index (HSI) and divided into four groups: T2DM with NAFLD, T2DM without NAFLD, controls with NAFLD, and controls without NAFLD. Serum irisin levels were measured using ELISA. Anthropometric data, physical activity, and various biochemical parameters were assessed and analyzed. Results: The irisin levels were significantly lower in T2DM patients compared to healthy controls (p = 0.001). Among T2DM patients, those with NAFLD had lower irisin levels than those without NAFLD, though not statistically significant (p = 0.299). Significant correlations were observed between irisin levels and insulin sensitivity markers such as HOMA-IR and QUICKI across different groups. Conclusion: Lower irisin levels in T2DM patients, particularly those with NAFLD, highlight its potential role in the pathogenesis of metabolic disorders. Further research is needed to elucidate irisin's therapeutic implications in T2DM and NAFLD.

Associations of plasma phospholipid cis-vaccenic acid with insulin resistance markers in non-diabetic men with hyperlipidemia

BackgroundThe role of fatty acids (FA) in the pathogenesis of insulin resistance and hyperlipidemia is a subject of intensive research. Several recent works have suggested cis-vaccenic acid (cVA) in plasma lipid compartments, especially in plasma phospholipids (PL) or erythrocyte membranes, could be associated with markers of insulin sensitivity and cardiovascular health. Nevertheless, not all the results of research work testify to these beneficial effects of cVA. Therefore, we decided to investigate the relations of proportion of cVA in plasma PL to markers of insulin resistance in hyperlipidemic men.SubjectsIn 231 men (median age 50) with newly diagnosed hyperlipidemia, we analyzed basic clinical parameters together with FA composition of plasma PL and stratified them according to the content of cVA into upper quartile (Q4) and lower quartile (Q1) groups. We examined also small control group of 50 healthy men.ResultsThe individuals in Q4 differed from Q1 by lower plasma insulin (p < 0.05), HOMA-IR values (p < 0.01), and apolipoprotein B concentrations (p < 0.001), but by the higher total level of nonesterified FA (p < 0.01). Both groups had similar age, anthropometrical, and other lipid parameters. In plasma PL, the Q4 group had lower content of the sum of n-6 polyunsaturated FA, due to decrease of γ-linolenic and dihomo-γ-linolenic acids, whereas the content of monounsaturated FA (mainly oleic and palmitoleic) was in Q4 higher.ConclusionsOur results support hypothesis that plasma PL cVA could be associated with insulin sensitivity in men with hyperlipidemia.

The 5:2 Diet Affects Markers of Insulin Secretion and Sensitivity in Subjects with and without Type 2 Diabetes-A Non-Randomized Controlled Trial.

This non-randomized controlled trial aimed to compare the effect of the 5:2 diet on insulin levels as a primary outcome and markers of insulin secretion (connecting peptide (C-peptide) and insulin-like growth factor binding protein-1 (IGFBP-1)) and sensitivity (Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)), as well as body composition as secondary outcomes in overweight/obese individuals with and without type 2 diabetes (T2D). Ninety-seven participants (62% women), 35 with T2D and 62 BMI- and waist-matched controls without T2D, followed the 5:2 diet (two days per week of fasting) for six months with a 12-month follow-up. At six months, there was no loss to follow-up in the T2D group, whereas four controls discontinued this study. Overall, 82% attended the 12-month follow-up. After the intervention, insulin levels decreased in the control group and glucose decreased in the T2D group, while C-peptide, HOMA-IR, waist circumference, BMI, trunk, and total fat% decreased in both groups. Furthermore, low IGFBP-1, indicating hyperinsulinemia, improved in the T2D group. The changes in fasting glucose and waist measurement were significantly more improved in the T2D group than in the controls. Persistent positive effects were observed at the 12-month follow-up. The 5:2 diet for six months was feasible and efficient to reduce markers of insulin secretion and resistance and therefore holds promise as management of overweight/obesity in subjects with and without T2D.

Comparative analysis of the effects of high-intensity interval training and traditional aerobic training on improving physical fitness and biochemical indicators in patients with non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD), linked to sedentary lifestyles and metabolic dysfunction, is highly prevalent. Exercise is an established intervention, but the relative efficacy of different exercise modalities remains unclear. The aim of this study was to compare the effects of moderate-intensity continuous aerobic training and High-Intensity Interval Training (HIIT) on physical fitness, biochemical parameters, and liver function in NAFLD patients. Sixty NAFLD patients (32 males, 28 females; age: 49.7±8.7 years; BMI: 31.1±3.3 kg/m2) were randomized into HIIT, aerobic training, and control cohorts. The HIIT cohort performed 4-minute high-intensity intervals at 85-95% of peak heart rate, interspersed with 3-minute active recovery at 60-70% of peak heart rate for 30-40 minutes per session. The aerobic training cohort performed continuous exercise at 60-70% of peak heart rate for 45-60 minutes per session. Both intervention cohorts underwent 12 weeks of supervised training, thrice weekly. Before and after the intervention, assessments included cardiorespiratory fitness, muscular strength, flexibility, lipid profile, liver enzymes, inflammatory markers, insulin sensitivity, and oxidative stress markers. Compared to controls, both exercise cohorts showed significant improvements in cardiorespiratory fitness, muscular strength, and flexibility. However, HIIT elicited superior enhancements in cardiorespiratory fitness and muscular strength. Biochemically, both exercise cohorts exhibited reductions in triglycerides, low-density lipoprotein (LDL) cholesterol, liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST]), inflammatory markers (C-reactive protein [CRP], interleukin-6 [IL-6]), insulin resistance (homeostatic model assessment of insulin resistance [HOMA-IR]), and oxidative stress markers (malondialdehyde [MDA], protein carbonyl). Notably, HIIT yielded more substantial improvements in these parameters. HIIT and traditional aerobic training are effective in improving physical fitness and ameliorating biochemical indicators in NAFLD patients. Notably, HIIT appears to be more advantageous in enhancing cardiorespiratory fitness, muscular strength, and metabolic, inflammatory, and oxidative stress profiles, suggesting its potential as a time-efficient and effective exercise modality for managing NAFLD.

N-terminal pro-B-type natriuretic peptide levels vary by ethnicity and are associated with insulin sensitivity after gestational diabetes mellitus

BackgroundIndividuals of South Asian origin have a greater risk of cardiovascular disease after gestational diabetes mellitus (GDM) than European individuals. B-type natriuretic peptide (BNP) and the amino-terminal fragment of its prohormone (NT-proBNP) are commonly used for heart failure screening and diagnosis, but biologically BNP exerts several beneficial cardiovascular effects primarily by counteracting the renin-angiotensin-aldosterone-system. We asked whether ethnic differences in circulating NT-proBNP levels could be explained by the differences in cardiometabolic and inflammatory risk markers?MethodsWe examined 162 South Asian and 107 Nordic women in Norway 1–3 years after GDM with a clinical examination, fasting blood samples and an oral glucose tolerance test. We measured the levels of NT-proBNP, high-sensitivity cardiac troponin T, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), leptin, adiponectin and markers of insulin sensitivity, such as the Matsuda insulin sensitivity index (ISI). Finally, we tried to identify which independent covariate best mediated the ethnic differences in NT-proBNP.ResultsThe mean (SD) age was 35.3 (4.5) years, BMI 29.1 (6.0) kg/m2, waist-height ratio 0.60 (0.08) and 164 women (61%) had prediabetes/diabetes. Notably, South Asian women had lower levels of NT-proBNP than Nordic women in both the normoglycemic and prediabetes/diabetes groups (median (IQR) 26 (15–38) vs. 42 (22–66) ng/L, p < 0.001). Higher NT-proBNP levels were associated with greater insulin sensitivity in both South Asian and Nordic women (p = 0.005 and p < 0.001). South Asian women had higher levels of hsCRP (median (IQR) 2.2 (1.1–4.4) vs. 1.2 (0.3–4.2) mg/L), IL-6 (2.3 (1.5–3.2) vs. 1.5 (1.5–2.5) pg/mL), leptin (1647 (1176–2480) vs. 1223 (876–2313) pmol/L), and lower adiponectin levels (7.2 (5.3–9.3) vs. 10.0 (7.2–13.5) mg/L) and Matsuda ISI (2.4 (1.7–3.7) vs. 4.2 (2.9–6.1), pall<0.01) than Nordic women. Even after adjusting for these differences, higher NT-proBNP levels remained associated with insulin sensitivity (22% higher NT-proBNP per SD Matsuda ISI, p = 0.015). Insulin sensitivity and adiponectin mediated 53% and 41% of the ethnic difference in NT-proBNP.ConclusionsNT-proBNP levels are lower in South Asian than in Nordic women after GDM. Lower NT-proBNP levels correlate with impaired insulin sensitivity. Lower NT-proBNP levels in South Asian women could, therefore, be attributed to impaired insulin sensitivity rather than total body fat.

Effects of Plant-Based Diets on Markers of Insulin Sensitivity: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

The aim of this systematic review and meta-analysis was to examine the effects of plant-based diets on markers of insulin sensitivity in people with overweight/obesity, prediabetes, or type 2 diabetes (T2D). A systematic literature search in MEDLINE, Embase, CINAHL, and CENTRAL was conducted, and randomised controlled trials (RCTs) investigating the effect of plant-based diets (vegan, ovo-vegetarian, lacto-vegetarian, and lacto-ovo-vegetarian) for ≥14 d on markers of insulin sensitivity in adults (≥18 years) with BMI ≥ 25 kg/m2, prediabetes, or T2D were eligible. We identified eight RCTs, including 716 participants. In comparison with control diets, plant-based diets improved Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (-0.97, 95% confidence interval (CI) (-1.67, -0.27), p = 0.007) and fasting insulin (-4.13 µU/mL, 95% CI (-7.22, -1.04), p = 0.009) in people with overweight/obesity. In people with prediabetes, one study compared vegan and vegetarian diets and found no difference in HOMA-IR, or fasting insulin. One study of people with T2D reported no difference in immunoreactive insulin and metabolic glucose clearance compared with a conventional diabetes diet. In conclusion, adhering to plant-based diets for ≥14 d improved HOMA-IR and fasting insulin in people with overweight/obesity. Long-term RCTs are needed to determine whether plant-based diets can result in prolonged improvements in insulin sensitivity in people at risk of or with T2D.

The single point insulin sensitivity estimator (SPISE) is associated with bone health in Arab adults

BackgroundThe Single Point Insulin Sensitivity Estimator (SPISE) index is a surrogate marker for insulin sensitivity. Given the emerging role of bone as an active endocrine organ, its associations with non-invasive measures of extra-skeletal functions such as insulin sensitivity warrant investigation.AimsThis study aimed to explore the relationship between the SPISE index and Bone Mineral Density (BMD) in an adult population.MethodsData from a total of 1270 Arab adults (84% females, mean age 56.7 ± 8.1 years) from the Osteoporosis Registry Database of the Chair for Biomarkers of Chronic Diseases in King Saud University, Riyadh, Saudi Arabia was used in this study. T-scores and SPISE were calculated. Regression models were used to determine associations between SPISE and bone health indices.ResultsThe low BMD group (N = 853; T-score <-1.0) had significantly higher SPISE values than those with normal BMD (N = 417; T-score − 1.0 and above) (4.6 ± 1.3 vs. 4.3 ± 1.2, p < 0.001). Multivariate linear regression, adjusted for covariates, confirmed a significant inverse association between SPISE and BMD for all participants (β=-0.22, p < 0.001), as well as both groups [normal BMD (β = -0.10, p = 0.02) and low BMD groups (β = -0.15, p < 0.001)]. SPISE, family history of T2DM, and history of fractures collectively account for 17% of the variances perceived in T-score for all participants (p < 0.001).ConclusionsA significant inverse association between the SPISE index and BMD was observed in adults, suggesting a link between BMD and extra-skeletal health. Underlying mechanisms need to be investigated prospectively using BMD as secondary outcomes in lifestyle modification programs.

Tirzepatide Improved Markers of Islet Cell Function (Fasting Glucagon and HOMA2-B) and Insulin Sensitivity (Fasting Insulin and HOMA2-IR) Compared to Semaglutide in People with Type 2 Diabetes

Tirzepatide Improved Markers of Islet Cell Function (Fasting Glucagon and HOMA2-B) and Insulin Sensitivity (Fasting Insulin and HOMA2-IR) Compared to Semaglutide in People with Type 2 Diabetes

Higher Expression of miR-15b-5p with Inclusion of Fresh, Lean Beef as Part of a Healthy Dietary Pattern Is Inversely Associated with Markers of Cardiometabolic Disease Risk

BackgroundConsiderable controversy exists surrounding the consumption of red meat and its impacts on cardiometabolic health and if it may further impact risk factors at the molecular level. ObjectiveThe purpose of this study was to examine the acute effects of dietary patterns, varying in red meat quantity, on the expression of circulating microRNAs (miRNAs), which are emerging biomarkers of metabolic dysfunction and chronic disease severity. MethodsSecondary analyses were performed on plasma samples collected within a randomized, crossover design study in 16 women with overweight (mean ± standard deviation, age = 33 ± 9.89 y; body mass index = 27.9 ± 1.66 kg/m2). Participants were provided with eucaloric, isonitrogenous diets (15% of daily intake as protein) containing either 2 servings of fresh, lean beef/day (BEEF) or 0 servings of fresh, lean beef/day (PLANT) for 7 d/pattern. Fasting blood samples were collected at the end of each dietary pattern for the assessment of 12 circulating metabolic miRNA expression levels (determined a priori by quantitative reverse transcriptase-polymerase chain reaction), plasma glucose, insulin, interleukin-6, tumor necrosis factor-α, C-reactive protein (CRP), adiponectin, glucagon-like peptide-1, and branched-chain amino acids. ResultsOf the 12 miRNAs, miR-15b-5p expression was higher following BEEF versus PLANT (P = 0.024). Increased miR-15b-5p expression correlated with decreased fasting CRP (r = −0.494; P = 0.086) and insulin concentrations (r = −0.670; P = 0.017). miR-15b-5p was inversely correlated with insulin resistance (r = −0.642; P = 0.024) and β cell function (r = −0.646; P = 0.023) and positively correlated with markers of insulin sensitivity (r = 0.520; P = 0.083). However, the correlations were only observed following BEEF, not PLANT. ConclusionsThese data indicate that the short-term intake of fresh, lean beef as part of a healthy dietary pattern impacts potential biomarkers of cardiometabolic health that are associated with cardiometabolic risk factors in women with overweight.This study was registered at clinicaltrials.gov as NCT02614729.

Bariatric Surgery and Its Metabolic Echo Effect on Serum Uric Acid Levels.

Bariatric surgery (BS) has been a significant means of reducing weight in obese individuals. The metabolic changes after bariatric surgery are crucial as they extend its advantages beyond weight loss. As its name implies, "metabolic surgery" also addresses obesity-related metabolic concerns. Bariatric surgery has always been associated with lessened serum uric acid (SUA) levels. In this review, we examined current studies to understand how surgical therapies impact serum uric acid levels. Strongly minded on the extent and timing of changes in the level of serum uric acid after bariatric surgeries. We conducted a comprehensive search for relevant current studies in PubMed, Google Scholar, JAMA, and the Cochrane Library until February 1, 2024. We aimed to analyze the metabolic advantages of bariatric surgery, focusing on its function in treating hyperuricemia and lowering the risk of associated disorders. Our review elaborates on factors contributing to decreased serum uric acid levels after bariatric surgery, such as alterations in renal function, insulin sensitivity, and inflammatory markers.

Comparative impact of Roux-en-Y gastric bypass, sleeve gastrectomy or diet alone on beta-cell function in insulin-treated type 2 diabetes patients.

Although bariatric surgery is an effective treatment for type 2 diabetes by inducing weight loss and augmenting gut hormone secretion, the immediate effect on beta-cell function itself remains to be elucidated in type 2 diabetes. Therefore, a prospective, randomized trial was performed in 30 patients with insulin-treated type 2 diabetes and a body mass index ≥ 35kg/m2. Patients were randomly assigned (1:1:1) to Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) in combination with protein-sparing modified fast (PSMF), or to PSMF alone. Eu- and hyperglycemic clamps were performed before and 3weeks after surgery and/or PSMF initiation. The primary outcome was the evolution of insulin sensitivity and beta-cell function after surgery, calculated using the composite measures of glucose disposal rate, insulin secretion rate, and disposition index (DI). Results revealed that markers of insulin sensitivity increased similarly in all arms (p = 0.43). A higher marker for maximal beta-cell function was observed when comparing SG to PSMF (p = 0.007). The DI showed a clear positive evolution after RYGB and SG, but not after PSMF alone. Altogether, these findings indicate that bariatric surgery results in an immediate beta-cell function recovery in insulin-treated type 2 diabetes.

Triglyceride-glucose index predicts type 2 diabetes mellitus more effectively than oral glucose tolerance test-derived insulin sensitivity and secretion markers

AimsWe explored the role of the triglyceride-glucose (TyG) index as an early and superior predictor of type 2 diabetes mellitus (T2DM) in individuals with normal glucose tolerance (NGT) using a community-based Korean cohort over 18 years. MethodsWe retrospectively examined 6,072 adults with NGT from the Korean Genome and Epidemiology Study. Cox proportional hazard regression models were employed to evaluate the risk of incidence of T2DM and receiver operating characteristic analysis was used to calculate the area under the curve (AUC). ResultsAt baseline, the TyG index correlated with the homeostasis model assessment of insulin resistance (HOMA-IR) and the composite insulin sensitivity index (ISI) (β: 0.045, p < 0.001; β: −0.105, p < 0.001, respectively). Over the 18-year follow-up period, 999 individuals developed T2DM. An increase in the TyG quartile independently predicted the incidence of T2DM [hazard ratio, 2.36 (1.9–2.93) for Q4]. The AUC value of the TyG index was 0.642, the highest value among HOMA-IR and OGTT-derived insulin sensitivity and secretion markers. ConclusionsThe TyG index is associated with HOMA-IR and composite ISI even with NGT. The TyG index demonstrated independent predictability for T2DM incidence in individuals with NGT, better than OGTT-derived insulin sensitivity and secretion markers.

Glucose tolerance and insulin resistance/sensitivity associate with retinal layer characteristics: the LIFE-Adult-Study

Aims/hypothesisAs the prevalence of insulin resistance and glucose intolerance is increasing throughout the world, diabetes-induced eye diseases are a global health burden. We aim to identify distinct optical bands which are closely related to insulin and glucose metabolism, using non-invasive, high-resolution spectral domain optical coherence tomography (SD-OCT) in a large, population-based dataset.MethodsThe LIFE-Adult-Study randomly selected 10,000 participants from the population registry of Leipzig, Germany. Cross-sectional, standardised phenotyping included the assessment of various metabolic risk markers and ocular imaging, such as SD-OCT-derived thicknesses of ten optical bands of the retina. Global and Early Treatment Diabetic Retinopathy Study (ETDRS) subfield-specific optical retinal layer thicknesses were investigated in 7384 healthy eyes of 7384 participants from the LIFE-Adult-Study stratified by normal glucose tolerance, prediabetes (impaired fasting glucose and/or impaired glucose tolerance and/or HbA1c 5.7–6.4% [39–47 mmol/mol]) and diabetes. The association of optical retinal band characteristics with different indices of glucose tolerance (e.g. fasting glucose, area under the glucose curve), insulin resistance (e.g. HOMA2-IR, triglyceride glucose index), or insulin sensitivity (e.g. estimated glucose disposal rate [eGDR], Stumvoll metabolic clearance rate) was determined using multivariable linear regression analyses for the individual markers adjusted for age, sex and refraction. Various sensitivity analyses were performed to validate the observed findings.ResultsIn the study cohort, nine out of ten optical bands of the retina showed significant sex- and glucose tolerance-dependent differences in band thicknesses. Multivariable linear regression analyses revealed a significant, independent, and inverse association between markers of glucose intolerance and insulin resistance (e.g. HOMA2-IR) with the thickness of the optical bands representing the anatomical retinal outer nuclear layer (ONL, standardised β=−0.096; p<0.001 for HOMA2-IR) and myoid zone (MZ; β=−0.096; p<0.001 for HOMA2-IR) of the photoreceptors. Conversely, markers of insulin sensitivity (e.g. eGDR) positively and independently associated with ONL (β=0.090; p<0.001 for eGDR) and MZ (β=0.133; p<0.001 for eGDR) band thicknesses. These global associations were confirmed in ETDRS subfield-specific analyses. Sensitivity analyses further validated our findings when physical activity, neuroanatomical cell/tissue types and ETDRS subfield categories were investigated after stratifying the cohort by glucose homeostasis.Conclusions/interpretationAn impaired glucose homeostasis associates with a thinning of the optical bands of retinal ONL and photoreceptor MZ. Changes in ONL and MZ thicknesses might predict early metabolic retinal alterations in diabetes.Graphical

IL-6 signaling drives self-renewal and alternative activation of adipose tissue macrophages.

Obesity is associated with chronic low-grade inflammation of adipose tissue (AT) and an increase of AT macrophages (ATMs) that is linked to the onset of type 2 diabetes. We have recently shown that neutralization of interleukin (IL)-6 in obese AT organ cultures inhibits proliferation of ATMs, which occurs preferentially in alternatively activated macrophage phenotype. In this study, we investigated AT biology and the metabolic phenotype of mice with myeloid cell-specific IL-6Rα deficiency (Il6ra Δmyel) after normal chow and 20 weeks of high-fat diet focusing on AT inflammation, ATM polarization and proliferation. Using organotypical AT culture and bone marrow derived macrophages (BMDMs) of IL-4Rα knockout mice (Il4ra -/-) we studied IL-6 signaling. Obese Il6ra Δmyel mice exhibited no differences in insulin sensitivity or histological markers of AT inflammation. Notably, we found a reduction of ATMs expressing the mannose receptor 1 (CD206), as well as a decrease of the proliferation marker Ki67 in ATMs of Il6ra Δmyel mice. Importantly, organotypical AT culture and BMDM data of Il4ra -/- mice revealed that IL-6 mediates a shift towards the M2 phenotype independent from the IL-6/IL-4Rα axis. Our results demonstrate IL-4Rα-independent anti-inflammatory effects of IL-6 on macrophages and the ability of IL-6 to maintain proliferation rates in obese AT.

Fasting and meal-related zonulin serum levels in a large cohort of obese children and adolescents.

Zonulin recently emerged as a valuable biological marker to assess the integrity of the intestinal mucosal barrier. Nevertheless, data about zonulin in pediatric age are extremely scarce. Aim of this study was to investigate the relationship between serum zonulin levels, both fasting and postprandial, with body mass index (BMI) and biochemical markers of insulin resistance (IR), insulin sensitivity, b-cell function and cardio-metabolic risk in obese non-diabetic youths. One hundred and four children and adolescents with obesity (BMI ≥ 2.0 SDS) were enrolled (mean age 11.43 ± 2.66). All the patients underwent clinical and biochemical assessment, including oral glucose tolerance test (OGTT) and liver ultrasonography. Zonulin serum levels were measured at fasting state, at 60-minute and 120-minute OGTT timepoint. Impaired fasting glycaemia and impaired glucose tolerance were documented in 27.9% and 11.5% of patients, respectively. IR was documented in 69.2% of cases. Liver steatosis was diagnosed in 39.4%. Zonulin serum levels significantly increased from baseline to 60-minute and 120-minute OGTT timepoint (p positive correlation between BMI SDS and serum zonulin levels at 120-minute OGTT timepoint (p highlighted a positive association of zonulin fasting levels with IR and glutamicoxalacetic transaminase levels (GOT, p zonulin levels were demonstrated for age, sex, pubertal status, glucose, lipid profile and the other obesity-related parameters. Our results show, for the first time in a pediatric cohort, the meal-related pattern of secretion of serum zonulin, which tends to significantly increase during and at 2-hours postprandial assessment. Even if the underlying mechanisms associating intestinal permeability and obesity have not been fully elucidated yet, our data confirm a close relationship between zonulin concentration and obesity in pediatric population. IR seems to significantly influence zonulin serum levels, thus a central role of IR in this pathway is conceivable.

Tirzepatide Improved Markers of Islet Cell Function and Insulin Sensitivity in People With T2D (SURPASS-2).

In previous SURPASS studies tirzepatide reduced hemoglobin glycated A1c (HbA1c) and body weight and improved markers of insulin sensitivity and β-cell function to a greater extent than comparators. Explore changes in biomarkers of β-cell function and insulin sensitivity and in efficacy profiles in baseline biomarker quartile analyses with tirzepatide compared to semaglutide. Post hoc analysis of SURPASS-2 phase 3 trial (participants randomly assigned to receive weekly subcutaneous tirzepatide or semaglutide for 40 weeks). Post hoc analysis of 128 sites in 8 countries. A total of 1879 participants with type 2 diabetes. Once-weekly tirzepatide (5, 10, 15 mg) or semaglutide 1 mg. Change in homeostatic model assessment indices for pancreatic β-cell function (HOMA2-B) and for insulin resistance (HOMA2-IR), fasting glucagon, fasting C-peptide, and fasting insulin. At week 40, a greater increase in HOMA2-B was seen with tirzepatide (5, 10, 15 mg) doses (96.9-120.4%) than with semaglutide 1 mg (84.0%) (P < .05). There was a greater reduction in HOMA2-IR with all doses of tirzepatide (15.5%-24.0%) than with semaglutide 1 mg (5.1%) (P < .05). Tirzepatide 10 and 15 mg resulted in a significant reduction in both fasting C-peptide (5.2%-6.0%) and fasting glucagon (53.0%-55.3%) compared with an increase of C-peptide (3.3%) and a reduction of glucagon (47.7%) with semaglutide 1 mg (P < .05). HbA1c and body weight reductions were greater with all tirzepatide doses than semaglutide within each HOMA2-B and HOMA2-IR baseline quartile. In this post hoc analysis, improvements in HbA1c and weight loss were consistent and significantly higher with tirzepatide, regardless of baseline β-cell function and insulin resistance, compared with semaglutide.

A Detailed Analysis of the Carotenoids and their Derivatives, including their Multiple Health Advantages

Background: The majority of foods, vegetation, plankton, and photosynthetic bacteria all include carotenoids, which are pigments that naturally exist. Since humans are unable to produce carotenoids, they must be consumed through food or supplements. There are many roles for carotenoids in ensuring human health. They generally act as antioxidants, but different carotenoids may also have other functions. For instance, β-carotene functions as pro-vitamin A, while lutein and zeaxanthin make up the macular pigmentation in the eyes. Objective: The primary goal of this review article is to emphasise the numerous health advantages of the various carotenoids and their derivatives, including neuro, cardio, bone, immune, and cancer protection. Methods: The information for this review article was acquired by using Google Scholar and PubMed as search engines, as well as a number of publishers, including Springer Nature, Bentham Science, Taylor &amp; Francis, and Elsevier. Results: Carotenoids are biologically active antioxidants, and their anti-inflammatory and antioxidant properties may help to lessen cardiovascular events such as adiposity, insulin sensitivity, hyperlipidemia, and inflammatory markers. Evidence shows they enhance eyesight, cognitive ability, and cardiovascular health. They could also reduce the risk of a number of malignancies. Carotenoids' diverse properties and therapeutic capacity to prevent neurodegeneration in conditions including Alzheimer's, Parkinson's, stroke, and others are reviewed. Conclusion: Despite the data supporting the health advantages of carotenoids, extensive population-based supplement research on several carotenoids has yielded conflicting results. Further study, especially clinical studies, is required to demonstrate and validate the medical benefits of the various carotenoids.