Sex-Specific Cardiometabolic Phenotypes of Metabolic Syndrome Identified by Latent Class Analysis in Indian Adults

BackgroundPrior studies have shown insulin resistance is associated with reduced cardiac autonomic function measured at rest, but few studies have determined whether insulin resistance is associated with reduced cardiac autonomic function measured during daily activities.MethodsWe examined older adults without diabetes with 48-h ambulatory electrocardiography (n = 759) in an ancillary study of the Atherosclerosis Risk in Communities Study. Insulin resistance, the exposure, was defined by quartiles for three indexes: 1) the homeostatic model assessment of insulin resistance (HOMA-IR), 2) the triglyceride and glucose index (TyG), and 3) the triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C). Low heart rate variability, the outcome, was defined by <25th percentile for four measures: 1) standard deviation of normal-to-normal R-R intervals (SDNN), a measure of total variability; 2) root mean square of successive differences in normal-to-normal R-R intervals (RMSSD), a measure of vagal activity; 3) low frequency spectral component (LF), a measure of sympathetic and vagal activity; and 4) high frequency spectral component (HF), a measure of vagal activity. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals weighted for sampling/non-response, adjusted for age at ancillary visit, sex, and race/study-site. Insulin resistance quartiles 4, 3, and 2 were compared to quartile 1; high indexes refer to quartile 4 versus quartile 1.ResultsThe average age was 78 years, 66% (n = 497) were women, and 58% (n = 438) were African American. Estimates of association were not robust at all levels of HOMA-IR, TyG, and TG/HDL-C, but suggest that high indexes were associated consistently with indicators of vagal activity. High HOMA-IR, high TyG, and high TG/HDL-C were consistently associated with low RMSSD (OR: 1.68 (1.00, 2.81), OR: 2.03 (1.21, 3.39), and OR: 1.73 (1.01, 2.91), respectively). High HOMA-IR, high TyG, and high TG/HDL-C were consistently associated with low HF (OR: 1.90 (1.14, 3.18), OR: 1.98 (1.21, 3.25), and OR: 1.76 (1.07, 2.90), respectively).ConclusionsIn older adults without diabetes, insulin resistance was associated with reduced cardiac autonomic function – specifically and consistently for indicators of vagal activity – measured during daily activities. Primary prevention of insulin resistance may reduce the related risk of cardiac autonomic dysfunction.

To measure retinol binding protein 4 (RBP4) levels in serum and bile and to analyze their relationship with insulin resistance, dyslipidemia or cholesterol saturation index (CSI). A total of 60 patients with gallstone were divided into a diabetes group (n=30) and a control group (n=30). The concentrations of RBP4 in serum and bile were detected by enzyme-linked immunosorbent assay (ELISA). Enzyme colorimetric method was used to measure the concentration of biliary cholesterol, bile acid and phospholipid. Biliary CSI was calculated by Carey table. Partial correlation and multiple linear regression analysis were used to evaluate the correlation between the RBP4 levels in serum or bile and the above indexes. The RBP4 concentrations in serum and bile in the diabetes group were significantly elevated compared with those in the control group (both P<0.01). There was no significant difference in the serum total bile acid (TBA), serum triglyceride (TG), serum high-density lipoprotein (HDL), bile TBA, bile total cholesterol (TC) , bile phospholipids and bile CSI between the 2 groups (all P>0.05); but the serum TC, low density lipoprotein (LDL), fasting blood glucose (FBG), fasting insulin (FINS), and homeostasis model assessment for insulin resistance (HOMA-IR) in the diabetes group were significantly increased compared to those in the control group (all P<0.05). The partial correlation analysis, which was adjusted by age, showed that the bile RBP4 was positively correlated with body mass index (BMI), waist circumference (WC), FINS, FBG, TC, LDL and HOMA-IR (r=0.283, 0.405, 0.685, 0.667, 0.553, 0.424 and 0.735, respectively), and the serum RBP4 was also positively correlated with the WC, FINS, FBG, TC, LDL and HOMA-IR (r=0.317, 0.734, 0.609, 0.528, 0.386 and 0.751, respectively). Stepwise multivariate linear regression analysis suggested that the HOMA-IR, BMI and WC were independently correlated with the level of bile RBP4 (multiple regression equation: Ybile RBP4=2.372XHOMA-IR+0.420XBMI+0.178XWC-26.813), and the serum RBP4 level was correlated with the HOMA-IR and WC independently (multiple regression equation: Yserum RBP4=2.832XHOMA-IR +0.235XWC-20.128). Multiple regression equations showed that HOMA-IR was the strongest correlation factor with RBP4. RBP4 concentrations in serum and bile in the diabetes group are significantly higher than those in the control group. HOMA-IR, BMI and WC are independently correlated with the level of bile RBP4. HOMA-IR and WC are independently correlated with the serum RBP4 level. HOMA-IR is the strongest correlation factor with RBP4. RBP4 might play an important role in the course of gallstone formation in Type 2 diabetes mellitus.

BackgroundVisceral obesity is positively related to insulin resistance. The nature of the relationship between waist circumference and insulin resistance has not been known in Japanese populations. This study examined the relationship between waist circumference and insulin resistance and evaluated the optimal cutoff point for waist circumference in relation to insulin resistance in middle-aged Japanese men.MethodsStudy subjects included 4800 Japanese men aged 39 to 60 years. Insulin resistance was evaluated by the homeostasis model assessment of insulin resistance (HOMA-IR). The relationship of waist circumference with HOMA-IR was assessed by use of adjusted means of HOMA-IR and odds ratios of elevated HOMA-IR defined as the highest quintile (≥2.00). Receiver operating characteristics (ROC) curve analysis using Youden index and the area under curve (AUC) was employed to determine optimal cutoffs of waist circumference in relation to HOMA-IR.ResultsAdjusted geometric means of HOMA-IR and prevalence odds of elevated HOMA-IR were progressively higher with increasing levels of waist circumference. In the ROC curve analysis, the highest value of Youden index was obtained for a cutoff point of 85 cm in waist circumference across different values of HOMA-IR. Multiple logistic regression analysis also indicated that the AUC was consistently the largest for a waist circumference of 85 cm.ConclusionWaist circumference is linearly related to insulin resistance, and 85 cm in waist circumference is an optimal cutoff in predicting insulin resistance in middle-aged Japanese men.

Prevalence of Elevated Alanine Aminotransferase Among US Adolescents and Associated Factors: NHANES 1999–2004

No study has previously investigated insulin resistance in collegiate baseball players. The purposes of this study were to examine: 1) the insulin resistance; and 2) the usefulness of the adiponectin/leptin (A/L) ratio compared with the homeostasis model assessment of insulin resistance (HOMA-IR) for assessing insulin resistance in collegiate baseball players. Twenty collegiate baseball players with abdominal obesity (AO group) defined by a waist circumference (WC) ≥85 cm, 65 lean baseball players with a WC<85 cm (L group), and 20 controls who were sedentary for at least 1 year (C group) were compared. The Body Mass Index, WC, systolic and diastolic blood pressures, fasting plasma glucose, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, apolipoprotein B, insulin, leptin, adiponectin, and high-sensitivity C-reactive protein (hs-CRP) were measured. The AO group had a significantly higher insulin level, HOMA-IR, and leptin level, and lower A/L ratio than the L and C groups. The AO group had a significantly higher prevalence of insulin resistance (50%) than the L (14%) group. The A/L ratio was significantly negatively correlated with body weight, Body Mass Index, WC, triglycerides, triglycerides/HDL-C ratio, apolipoprotein B, hs-CRP, insulin, HOMA-IR, and leptin, and positively correlated with HDL-C, whereas HOMA-IR was significantly positively correlated with body weight, Body Mass Index, WC, systolic and diastolic blood pressures, fasting plasma glucose, and insulin, and negatively correlated with adiponectin and the A/L ratio. In the forward stepwise multiple regression analysis, WC, triglycerides, and hs-CRP were the significant determinants for the A/L ratio, whereas diastolic blood pressure and WC were the significant determinants for HOMA-IR. This model explained 53.7% of the variance in the A/L ratio and 13.6% of the variance in HOMA-IR. The present study suggested that the baseball players with abdominal obesity had a significantly higher prevalence of insulin resistance than the lean baseball group. The A/L ratio may be more useful than HOMA-IR to accurately assess insulin resistance in male collegiate baseball players.

Objectives To compare serum leptin levels in women with polycystic ovary syndrome (PCOS) and healthy subjects, and to evaluate the relationship between leptin concentration and insulin resistance.Methods Forty-five women with PCOS and 20 controls were included in the study. Serum levels of leptin, testosterone, immune-reactive insulin (IRI), sex hormone-binding globulin, dehydroepiandrosterone sulfate, cortisol, LH and FSH were measured. Free androgen index (FAI) and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. Body mass index (BMI) and waist-to-hip ratio (WHR) were assessed.Results Serum leptin levels in PCOS patients were higher than in the control group independently of BMI, WHR and waist circumference. In PCOS patients there was a strong positive correlation between leptin and IRI (r = 0.592, p < 0.01) on the one hand, and leptin and HOMA-IR, on the other (r = 0.637, p < 0.01). In PCOS patients with more pronounced insulin resistance (IR) the correlation between leptin levels and HOMA-IR is independent of BMI, WHR and waist circumference. We did not find any correlation between leptin and other hormonal indices in PCOS patients.Conclusions Our study confirms the existence of a significant positive correlation between serum leptin levels and clinical and hormonal indices of IR. The hyperleptinaemia is probably due to leptin resistance and may be characteristic of the syndrome. The lack of correlation with other hormonal parameters is probably due to the heterogeneity of the PCOS group.

BACKGROUND: Adipose tissue expansion in obesity leads to abnormal adipocyte function, chronic low grade inflammation, primary reticulum stress, and mitochondrial stress. This induces mitochondrial unfolded protein response (UPRmt) that selectively upregulates mitochondrial chaperone protein. Heat shock Protein 60 (HSP60) is the primary chaperone in mitochondrial matrix. Inflammatory stress promotes HSP60 released from adipocytes and induces insulin resistance. In this study we attempted to investigate the correlation between exHSP60 and HOMA-IR in men with different ranges of waist circumference (WC).METHODS: This study was an observational cross sectional study carried out on 141 non diabetic men, aged 30-55 years old, who were divided into three groups based on WC; WC ≤90 cm, 90 cm &lt; WC ≤ 100 cm and WC &gt; 100 cm. Fasting plasma glucose, triglyceride, HDL-C, hsCRP, HSP60 serum and anti-HSP60 antibody, serum IL-1β serum, insulin, were examined. For statistical analysis, Kolmogorov-Smirnov and Spearman’s correlation analysis were conducted.RESULTS: There were a significant correlation between exHSP60 and HOMA-IR (r=0.281; p=0.041) in WC ≤ 90 cm group; and a negative significant correlation between exHSP60 and HOMA-IR (r=-0.508; p=0.007) in WC &gt; 100 cm group.CONCLUSION: This study showed that there was a dynamic correlation between exHSP60 and HOMA-IR in WC ≤ 90 cm group compared with WC &gt; 100 cm group. We also found inverse correlation patterns between exHSP60 and HOMA-IR, and between anti-HSP60 antibody and HOMA-IR in non diabetic subjects.KEYWORDS: obesity, insulin resistance, mitochondrial stress, exHSP60, hsCRP, HOMA-IR

Time in range (TIR) derived from continuous glucose monitoring and the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) are independent predictors of maternal and neonatal outcomes in gestational diabetes mellitus (GDM). However, their combined effect on neonatal outcomes remains unclear. This study aimed to investigate the joint influence of TIR and HOMA-IR on neonatal outcomes in GDM patients. In this retrospective cohort study, 166 women with GDM were categorized into 4 groups based on TIR levels (cutoff: 90%) and HOMA-IR (cutoff: cohort median): Group A (high-TIR/low-IR), Group B (high-TIR/high-IR), Group C (low-TIR/low-IR), and Group D (low-TIR/high-IR). HOMA-IR was calculated at “24 to 28 weeks’ gestation” gestation using fasting plasma glucose and insulin levels obtained during the oral glucose tolerance test. Neonatal complications, including hypoglycemia, macrosomia, and hyperbilirubinemia, were compared across groups. Compared with Group A (high-TIR/low-IR), Group D (low-TIR/high-IR) demonstrated the highest risk for adverse neonatal outcomes, with significantly higher incidence of neonatal hypoglycemia (OR: 4.52, 95% CI: 1.89–10.78) and macrosomia (OR: 3.45, 95% CI: 1.45–8.19), along with higher mean neonatal bilirubin levels (10.97 ± 1.72 mg/dL vs 8.99 ± 2.09 mg/dL, P < .001). Poor glycemic control (low TIR) combined with significant insulin resistance (high HOMA-IR) identifies a subgroup of GDM patients at the highest risk for adverse neonatal outcomes. The joint assessment of TIR and HOMA-IR may facilitate precise risk stratification and personalized management in clinical practice.

MP03-04 IMPACT OF INSULIN RESISTANCE AND PHYSICAL ACTIVITY ON KIDNEY STONE FORMATION IN THE JAPANESE POPULATION

Leptin has been shown to be linked to adiposity and insulin resistance in middle-aged participants. However, the association between leptin and metabolic syndrome independently of body fat and body fat distribution has not been evaluated in healthy elderly people. We studied the independent relation between leptin and the components of the metabolic syndrome in 107 women aged 67-78 years with body mass index (BMI) ranging from 18.19 to 36.16 kg/m2. In all participants, we evaluated BMI, waist and hip circumferences, body composition by dual energy X-ray absorptiometry, fasting, and 2-hour glucose, lipids, insulin, homeostasis model assessment of insulin resistance (HOMA), systolic (SBP), diastolic blood pressure (DBP), and leptin. Significant correlation was found between leptin, BMI, waist circumference, fat mass, DBP, SBP, cholesterol, triglycerides, insulin, and HOMA. After adjusting for age and waist circumference, as well for age and fat mass, leptin was significantly related to insulin levels, HOMA, and cholesterol. In a stepwise multiple regression analysis using insulin levels or HOMA as dependent variables and age, waist circumference, fat mass, leptin, SBP, DBP, cholesterol, and triglycerides as independent variables, leptin entered the regression first, waist circumference second, and age third. Our study shows that leptin is significantly related to indices of adiposity in elderly women, and leptin is significantly associated with insulin levels, HOMA, and cholesterol independent of age, body fat, and fat distribution. Leptin, waist circumference, and age together explained 31% and 33% of insulin levels and HOMA variance, respectively, in healthy elderly women.

THU0084 The relationship between serum leptin: Adiponectin ratio, insulin resistance, and carotid atherosclerosis in patients with rheumatoid arthritis

Background: Diabetes mellitus (DM) is a group of endocrine diseases, resulting from insufficient or improper use of insulin. It is characterized by prolonged high blood sugar levels. The exponential increase in DM poses serious public health concerns. Again, obesity is a complex condition with substantial accumulation of excess total body fat (visceral and subcutaneous) that could impact health. Visceral fat previously thought to be inert, has been found to be an endocrine organ, that produces adipokines such as leptin and adiponectin, which regulate several body functions including metabolism, inflammation, appetite, cardiovascular function and immunity. Visceral adiposity index (VAI), a sex specific mathematical model which indicates fat distribution and function, is a better indicator for obesity, as opposed to body mass index (BMI), which cannot differentiate between subcutaneous and visceral fat, making it a valuable tool for assessing metabolic dysfunction in diabetes. Aim: This study evaluated visceral adiposity index (VAI) and leptin levels in type 2 diabetic subjects in Port Harcourt, Nigeria, highlighting the effect of disease duration and sex differences. Materials and Methods: A cross-sectional study design was adopted for the study. A total of 225 participants were involved in the study. This was made up of 125 type 2 diabetic (test) subjects and 100 non-diabetic (control) subjects. Subjects observed an overnight fast prior to sample collection. Fasting blood sugar (FBS) was determined using the glucose oxidase method. Glycated haemoglobin (HbA1c) was determined using the electrochemical piezoelectric sensor method. Fasting insulin and leptin were determined using the enzyme–linked immunosorbent assay (ELISA) method. Insulin resistance was determined using the homeostatic model assessment for insulin resistance (HOMA-IR) method. Triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) were determined by the enzymatic method. Body mass index (BMI) was determined with the formula: BMI = weight (kg) / height² (m²). Waist to hip ratio (WHR) was determined with the formula: WHR= Waist circumference (WC) (cm) / Hip Circumference (HC) (cm). Visceral adiposity index (VAI) was determined with the formula: VAI = [WC/39.68 + (1.88 × BMI)] × (TG/1.03) × (1.31/HDL) for men, and [WC/36.58 + (1.89 × BMI)] × (TG/0.81) × (1.52/HDL) for women. Data generated was analysed using GraphPad Prism version 8.0.2. Independent student’s t-test, analysis of variance (ANOVA) and Tukey Post-test were done where necessary. Pearson’s correlation was also used to correlate parameters. Results were considered significant at a 95% confidence interval (P ≤ 0.05). Results: HbA1c, FBS, insulin and HOMA-IR were significantly higher (P&lt;0.05) in the diabetics, compared to the controls. Leptin levels, VAI, BMI and WHR of the diabetics were significantly higher (P&lt;0.05), compared to the controls. Leptin levels were significantly higher (P&lt;0.05) in the female diabetics, compared to the male diabetics. There were no significant differences (P&gt;0.05) in HOMA-IR and WHR between the male and female diabetics. VAI and BMI were significantly higher (P&lt;0.05) in the female diabetics, compared to their male counterparts. There were no significant differences (P&gt;0.05) in leptin levels, HOMA-IR, VAI, HbA1c and BMI in subjects with diabetes for 1 – 5 years, 6 – 10 years and those with diabetes for 11 years and above. Leptin was positively correlated with insulin (r=0.363), insulin resistance (r=0.540) and VAI (r=0.210). There was a significant (P&lt;0.05) and positive correlation between leptin and WHR (r=0.229), and leptin and BMI (r=0.238). VAI (r=0.698) and WHR (r=0.638) were significantly (P&lt;0.05) and positively correlated with insulin resistance (HOMA-IR). Conclusion: Type 2 diabetes is associated with visceral fat accumulation, hyperleptinaemia, and leptin resistance. Sex differences contributed significantly to elevated VAI, BMI and leptin levels in the female diabetics, compared to the male diabetics. Disease duration had no effect on the parameters, as leptin, VAI, BMI, HOMA-IR and HbA1c remained elevated throughout the duration of diabetes. VAI and leptin estimation should be incorporated into routine clinical assessments as reliable biomarkers for insulin resistance and metabolic dysfunction.

The objective of the study was to determine whether race plays a role in the relationship between waist circumference and insulin resistance in an African American and white sample of subjects with schizophrenia. A cross-sectional comparison was conducted to determine the relationship between waist circumference and insulin resistance in 55 subjects treated with antipsychotic medication. Each subject underwent an anthropometric assessment of waist and hip circumference, height, weight and body mass index. Laboratory assays were performed to assess insulin resistance by the homeostasis model assessment for insulin resistance (HOMA-IR). Data for fifty-five subjects are reported: white/Caucasian (n=38) and African American (n=17). Mean waist circumference was higher in whites (98 cm±11 cm) compared with African Americans (94 cm±11 cm) but not statistically significant (p=0.181). There was no correlation between waist circumference and insulin resistance calculated by HOMA-IR in the African American subject s...

Leisure time and occupational physical activity in relation to obesity and insulin resistance: a population-based study from the Skaraborg Project in Sweden

Effects of oral fat and glucose tolerance test on serum lipid profile, apolipoprotein, and CRP concentration, and insulin resistance in patients with polycystic ovary syndrome