Statins Are Associated With Increased Insulin Resistance and Secretion.

Objective: Statin treatment reduces the risk of atherosclerotic cardiovascular disease but is associated with a modest increased risk of type 2 diabetes, especially in those with insulin resistance or prediabetes. Our objective was to determine the physiological mechanism for the increased type 2 diabetes risk.

Approach And Results: We conducted an open-label clinical trial of atorvastatin 40 mg daily in adults without known atherosclerotic cardiovascular disease or type 2 diabetes at baseline.

FAM13A affects body fat distribution and adipocyte function.

Genetic variation in the FAM13A (Family with Sequence Similarity 13 Member A) locus has been associated with several glycemic and metabolic traits in genome-wide association studies (GWAS). Here, we demonstrate that in humans, FAM13A alleles are associated with increased FAM13A expression in subcutaneous adipose tissue (SAT) and an insulin resistance-related phenotype (e.g.

Cardiorespiratory Fitness, Body Mass Index, and Markers of Insulin Resistance in Apparently Healthy Women and Men.

Background: Insulin resistance may be present in healthy adults and is associated with poor health outcomes. Obesity is a risk factor for insulin resistance, but most obese adults do not have insulin resistance. Fitness may be protective, but the association between fitness, weight, and insulin resistance has not been studied in a large population of healthy adults.

Impact of race/ethnicity on insulin resistance and hypertriglyceridaemia.

Objective: Insulin sensitivity affects plasma triglyceride concentration and both differ by race/ethnicity. The purpose of this study was to provide a comprehensive assessment of the variation in insulin sensitivity and its relationship to hypertriglyceridaemia between five race/ethnic groups.

Research Design And Methods: In this cross-sectional study, clinical data for 1025 healthy non-Hispanic White, Hispanic White, East Asian, South Asian and African American individuals were analysed.

Relationship among obesity, insulin resistance, and hyperinsulinemia in the polycystic ovary syndrome.

Purpose: To evaluate the relationship between obesity and insulin resistance among women with polycystic ovary syndrome (PCOS) using a gold standard test.

Methods: A retrospective database analysis of 75 women with PCOS and 118 normal controls who underwent a modification of the insulin suppression test. The relationships between body mass index (BMI) and steady-state plasma glucose (SSPG) levels were investigated.

Plasma glucose concentration 60 min post oral glucose load and risk of type 2 diabetes and cardiovascular disease: Pathophysiological implications.

Aim: The aim of this study was to gain insight into the pathophysiological significance of elevated plasma glucose concentrations (mmol/L) 60 min post oral glucose load in apparently healthy individuals.

Methods: Comparison of resistance to insulin action and associated cardio-metabolic risk factors in 490 apparently healthy persons, subdivided into those with a plasma glucose concentration 60 min following a 75-g oral glucose challenge of <8.6 versus ⩾8.

Relationship between surrogate estimates and direct measurement of insulin resistance in women with polycystic ovary syndrome.

Purpose: To evaluate the relationship between surrogate estimates of insulin resistance and a direct measurement of insulin-mediated glucose uptake women with and without PCOS.

Methods: Retrospective cohort study of 75 PCOS and 118 controls. Fasting plasma glucose and insulin concentrations, insulin resistance as determined by the insulin suppression test, calculation of multiple surrogate estimates of insulin resistance, total and free testosterone concentrations, and correlations between the direct measure and surrogate estimates of insulin resistance were evaluated.

Can the Plasma Concentration Ratio of Triglyceride/High-Density Lipoprotein Cholesterol Identify Individuals at High Risk of Cardiovascular Disease During 40-Year Follow-Up?

Background: The plasma concentration ratio of triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) is a simple way to estimate insulin resistance. We aimed to evaluate the TG/HDL-C ratio as a simple clinical way to identify apparently healthy individuals with insulin resistance and enhanced risk of future cardiovascular disease (CVD).

Methods: One thousand seven hundred twenty men, aged 50 years, free from diabetes and CVD when evaluated at baseline in 1970-1974 were followed for 40 years regarding incident CVD (myocardial infarction and/or ischemic stroke, n = 576).

Short-Term Repeatability of Insulin Resistance Indexes in Older Adults: The Atherosclerosis Risk in Communities Study.

Context: The homeostatic model assessment of insulin resistance (HOMA-IR) and triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) ratio (TG/HDL-C) are insulin resistance indexes routinely used in clinical and population-based studies; however, their short-term repeatability is not well characterized.

Objective: To quantify the short-term repeatability of insulin resistance indexes and their analytes, consisting of fasting glucose and insulin for HOMA-IR and TG and HDL-C for TG/HDL-C.

Design: Prospective cohort study.

First Trimester Plasma Glucose Values in Women without Diabetes are Associated with Risk for Congenital Heart Disease in Offspring.

In a retrospective study of 19 171 mother-child dyads, elevated random plasma glucose values during early pregnancy were directly correlated with increased risk for congenital heart disease in offspring. Plasma glucose levels proximal to the period of cardiac development may represent a modifiable risk factor for congenital heart disease in expectant mothers without diabetes.

Relationship between several surrogate estimates of insulin resistance and a direct measure of insulin-mediated glucose disposal: Comparison of fasting versus post-glucose load measurements.

Aims: The study aim was to determine the correlation of several surrogate estimates of insulin resistance with a direct measure of insulin action and the ability of these estimates to identify insulin resistant persons.

Methods: Retrospective analysis of 454 apparently healthy individuals studied in a clinical research center. The correlations between 11 surrogate estimates of insulin resistance, using either fasting or post-oral glucose challenge values, and a direct measure of insulin-mediated glucose uptake (SSPG concentration during the Insulin Suppression Test) were determined as well as the ability of the surrogate estimates to identify insulin resistant individuals.

Adapting to insulin resistance in obesity: role of insulin secretion and clearance.

Aims/hypothesis: The aim of this study was to quantify the relative contributions of increased insulin secretion rate (ISR) and decreased insulin clearance rate (ICR) in the compensatory hyperinsulinaemia characteristic of insulin-resistant individuals without diabetes.

Methods: Obese (BMI ≥30 kg/m) individuals without diabetes (n = 91) were identified from a registry of volunteers. Volunteers underwent the following measurements: oral glucose tolerance; insulin resistance (steady-state plasma glucose [SSPG] concentration during the insulin suppression test [IST]); ISR (using the graded glucose infusion test [GGIT]); and ICR (using the IST and GGIT).

Relationship between simple markers of insulin resistance and coronary artery calcification.

Background: Insulin resistance in apparently healthy persons is associated with a cluster of metabolic abnormalities that promote coronary atherosclerosis. Identifying these individuals before manifest disease would provide useful clinical information.

Objective: We hypothesized that combining 2 simple markers of insulin resistance, prediabetes (PreDM) and triglyceride (TG) concentration ≥150 mg/dL, would identify apparently healthy persons with adverse cardiometabolic risk profiles and increased coronary artery calcium (CAC) compared with those with neither or only 1 abnormality.

Relationship among age, insulin resistance, and blood pressure.

The effect of age to modify the relationship between insulin resistance and hypertension is unclear. In this retrospective, cross-sectional study, median age was used to create two age groups (<52 vs. ≥52 years), and comparisons were made of metabolic characteristics, including steady-state plasma glucose (SSPG) concentrations measured during the insulin suppression test to quantify insulin resistance.

Comparison of two surrogate estimates of insulin resistance to predict cardiovascular disease in apparently healthy individuals.

Background And Aims: Insulin resistance is associated with a cluster of abnormalities that increase cardiovascular disease (CVD). Several indices have been proposed to identify individuals who are insulin resistant, and thereby at increased CVD risk. The aim of this study was to compare the abilities of 3 indices to accomplish that goal: 1) plasma triglyceride × glucose index (TG × G); 2) plasma triglyceride/high-density lipoprotein cholesterol ratio (TG/HDL-C); and 3) Metabolic Syndrome (MetS).

Effect of Pioglitazone on Cardiometabolic Risk in Patients With Obstructive Sleep Apnea.

Prevalence of insulin resistance is increased in patients with obstructive sleep apnea (OSA). Because insulin resistance is an independent predictor of cardiovascular disease (CVD), this study was initiated to see if pioglitazone administration would improve insulin sensitivity and thereby decrease risk of CVD in overweight/obese, nondiabetic, insulin-resistant patients with untreated OSA. Patients (n = 30) were administered pioglitazone (45 mg/day) for 8 weeks, and measurements were made before and after intervention of insulin action (insulin-mediated glucose uptake by the insulin suppression test), C-reactive protein, lipid/lipoprotein profile, and gene expression profile of periumbilical subcutaneous fat tissue.

Analysis of Transcriptional Variability in a Large Human iPSC Library Reveals Genetic and Non-genetic Determinants of Heterogeneity.

Variability in induced pluripotent stem cell (iPSC) lines remains a concern for disease modeling and regenerative medicine. We have used RNA-sequencing analysis and linear mixed models to examine the sources of gene expression variability in 317 human iPSC lines from 101 individuals. We found that ∼50% of genome-wide expression variability is explained by variation across individuals and identified a set of expression quantitative trait loci that contribute to this variation.

Dissecting the relationship between obesity and hyperinsulinemia: Role of insulin secretion and insulin clearance.

Objective: The aim of this study was to better delineate the complex interrelationship among insulin resistance (IR), secretion rate (ISR), and clearance rate (ICR) to increase plasma insulin concentrations in obesity.

Methods: Healthy volunteers (92 nondiabetic individuals) had an insulin suppression test to measure IR and graded-glucose infusion test to measure ISR and ICR. Obesity was defined as a body mass index (BMI) ≥30 kg/m , and IR was defined as steady-state plasma glucose (SSPG) ≥10 mmol/L during the insulin suppression test.

Metabolic Markers to Predict Incident Diabetes Mellitus in Statin-Treated Patients (from the Treating to New Targets and the Stroke Prevention by Aggressive Reduction in Cholesterol Levels Trials).

The goal of this analysis was to evaluate the ability of insulin resistance, identified by the presence of prediabetes mellitus (PreDM) combined with either an elevated triglyceride (TG >1.7 mmol/l) or body mass index (BMI ≥27.0 kg/m), to identify increased risk of statin-associated type 2 diabetes mellitus (T2DM).

Nat1 Deficiency Is Associated with Mitochondrial Dysfunction and Exercise Intolerance in Mice.

We recently identified human N-acetyltransferase 2 (NAT2) as an insulin resistance (IR) gene. Here, we examine the cellular mechanism linking NAT2 to IR and find that Nat1 (mouse ortholog of NAT2) is co-regulated with key mitochondrial genes. RNAi-mediated silencing of Nat1 led to mitochondrial dysfunction characterized by increased intracellular reactive oxygen species and mitochondrial fragmentation as well as decreased mitochondrial membrane potential, biogenesis, mass, cellular respiration, and ATP generation.

Use of the triglyceride/high-density lipoprotein cholesterol ratio to identify cardiometabolic risk: impact of obesity?

There is evidence that the plasma concentration ratio of triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) identifies insulin resistance and increased cardiometabolic risk and outcome in apparently healthy individuals. Since use of the TG/HDL-C ratio to accomplish this task in persons over a wide range of adiposity has not been studied, the ability of previously defined sex-specific TG/HDL-C cut-points to identify increased cardiometabolic risk was evaluated in apparently healthy normal weight, overweight, and obese individuals. Data were analyzed from a population-based study of apparently healthy men (n=416) and women (n=893), subdivided into categories by body mass index (BMI, kg/m): normal weight (BMI 20.