Sex-differences in insulin sensitivity and insulin secretion in subjects with impaired fasting glucose and impaired glucose tolerance.

Aims: To assess sex-related differences in whole-body insulin sensitivity and insulin secretion in a group of Caucasian subjects with varying degrees of glucose tolerance.

Methods: Sex-related differences in insulin sensitivity using the hyperinsulinemic-euglycemic clamp technique and insulin secretion using validated indexes obtained during an oral glucose tolerance test were examined among 570 non-diabetic offspring individuals having only one parent with type 2 diabetes. Participants were classified as having with NGT, isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT) and combined IFG/IGT.

Sex-specific differences in prevalence of nonalcoholic fatty liver disease in subjects with prediabetes and type 2 diabetes.

Aims: To characterize the prevalence of NAFLD among subjects with NGT, prediabetes and type 2 diabetes (T2DM) by sex in adults with one or more cardio-metabolic risk factors, and to assess whether cardio-metabolic factors explained sex-related differences in NAFLD prevalence.

Methods: The study sample encompasses 742 individuals with NGT, 553 with prediabetes, and 431 with T2DM.

Results: Women with prediabetes and T2DM exhibited greater relative differences in waist circumference, HOMA-IR, hsCRP, and lipid profile than prediabetic and diabetic men when compared with their NGT counterparts.

One-hour post-load glucose is associated with severity of hepatic fibrosis risk.

Aim: Individuals with high 1-hour post-load glucose (1-h PG > 155 mg/dl; 8.6 mmol/l) during an oral glucose tolerance test are at increased risk of type 2 diabetes (T2D) and cardiovascular complications, hepatic steatosis, and mortality. However,the clinical relevance of 1-h PG for the severity of hepatic fibrosis risk remains undefined.

HDL cholesterol is an independent predictor of β-cell function decline and incident type 2 diabetes: A longitudinal study.

Background: Experimental evidence indicates that high-density lipoprotein (HDL) may stimulate glucose uptake and improve β-cell function. The aim of this study was to evaluate whether lower levels of HDL may affect the risk to develop type 2 diabetes.

Methods: Incident rate of type 2 diabetes and changes in insulin sensitivity and β-cell function over 5.

Relationships of surrogate indexes of insulin resistance with insulin sensitivity assessed by euglycemic hyperinsulinemic clamp and subclinical vascular damage.

Introduction: Insulin resistance plays a crucial role in the pathogenesis of type 2 diabetes and cardiovascular disease. The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, visceral adiposity index (VAI), lipid accumulation product (LAP) and triglycerides × fasting glucose (TyG) index are surrogate measures of insulin sensitivity based on anthropometric and/or biochemical parameters routinely collected in clinical practice. Herein, we compared the relationships of these four surrogate indexes with insulin sensitivity assessed by the gold standard euglycemic hyperinsulinemic clamp technique, and subclinical vascular damage.

The polymorphism rs35767 at IGF1 locus is associated with serum urate levels.

Previous studies suggested that the IGF-1/IGF-1 receptor signaling pathway may contribute to regulate uric acid levels. To confirm this hypothesis, we assessed the effects of the IGF-1-raising genetic variant rs35767 on urate levels in serum and urine, and we investigated IGF-1 ability to modulate the expression of transporters involved in reabsorption and secretion of uric acid in the kidney. The study population included 2794 adult Whites.

One-Hour Postload Hyperglycemia: Implications for Prediction and Prevention of Type 2 Diabetes.

Context: Recently, a value of 1-hour postload glucose concentration (1-h-PG) ≥155 mg/dL (8.6 mmol/L) in individuals with normal glucose tolerance (NGT) has been found to be associated with an increased risk for future type 2 diabetes mellitus (T2DM). In this review, we analyze the implication of 1-h-PG determination in prediction of T2DM and cardiovascular disease.

Elevated hemoglobin glycation index identify non-diabetic individuals at increased risk of kidney dysfunction.

Hemoglobin glycation index (HGI), calculated as the difference between the observed value of HbA1 and the predicted HbA1c based on plasma glucose concentration, is a measure of the individual tendency toward non-enzymatic hemoglobin glycation which has been found to be positively associated with nephropathy in subjects with diabetes. In this cross-sectional study we aimed to evaluate whether higher HGI levels are associated with impaired kidney function also among nondiabetic individuals. The study group comprised 1505 White nondiabetic individuals stratified in quartiles according to HGI levels.

Association between hemoglobin glycation index and hepatic steatosis in non-diabetic individuals.

Aims: Hemoglobin glycation index (HGI), which is the difference between the observed value of HbA1 and the predicted HbA1c based on plasma glucose levels, represents a measure of the degree of non-enzymatic glycation of hemoglobin and it has been found to be positively associated with diabetic complications. Herein we investigated whether HGI is associated with hepatic steatosis and related biomarkers in subjects without diabetes.

Methods: 1120 White individuals without diabetes were stratified in quartiles according to HGI levels.

Elevated 1-h post-challenge plasma glucose levels in subjects with normal glucose tolerance or impaired glucose tolerance are associated with whole blood viscosity.

Aim: It has been suggested that glucose levels ≥155 mg/dl at 1-h during an oral glucose tolerance test (OGTT) may predict development of type 2 diabetes and cardiovascular events among adults with normal glucose tolerance (NGT 1 h-high). Studies showed a link between increased blood viscosity and type 2 diabetes. However, whether blood viscosity is associated with dysglycemic conditions such as NGT 1 h-high, impaired glucose tolerance (IGT) or impaired fasting glucose (IFG) is unsettled.

Association between hemoglobin glycation index with insulin resistance and carotid atherosclerosis in non-diabetic individuals.

Hemoglobin glycation index (HGI), defined as the difference between the observed HbA1c value and the value of HbA1c predicted from plasma glucose levels, represents a measure of the degree of non-enzymatic glycation of hemoglobin and it has been found to be positively associated with micro- and macro-vascular complications in subjects with type 2 diabetes. To investigate the pathophysiological abnormalities responsible for the increased cardiovascular risk of patients with higher HGI, we evaluated the association of HGI with cardio-metabolic characteristics in nondiabetic offspring of type 2 diabetic individuals. Insulin sensitivity, measured by a hyperinsulinemic-euglycemic clamp, cardio-metabolic risk factors including lipid profile, uric acid and inflammatory factors, and ultrasound measurement of carotid intima-media thickness (IMT) were assessed in 387 nondiabetic individuals.

A polymorphism at IGF1 locus is associated with anemia.

In vitro and in vivo studies suggest that IGF-1 has a role in erythropoiesis. There is evidence that the rs35767 C/T polymorphism near IGF1 is associated with plasma IGF-1 levels. We investigated the effect of this polymorphism on hemoglobin (Hb) concentration and anemia.

Uric Acid Is Associated With Inflammatory Biomarkers and Induces Inflammation Via Activating the NF-κB Signaling Pathway in HepG2 Cells.

Objective: Serum uric acid (UA) has been associated with increased risk of cardiovascular and metabolic diseases. However, the causal mechanisms linking elevated UA levels to cardio-metabolic diseases are still unsettled. One potential explanation for how UA might contribute to cardio-metabolic disease might be its ability to induce systemic inflammation.

One-Hour Postload Hyperglycemia Is a Stronger Predictor of Type 2 Diabetes Than Impaired Fasting Glucose.

Context: Subjects with normal glucose tolerance (NGT) but 1-h postload glucose ≥ 155 mg/dL (NGT-1h-high) exhibit an intermediate cardiometabolic risk profile between individuals with NGT and impaired glucose tolerance (IGT).

Objective: This study aimed to evaluate whether NGT-1h-high subjects have different cardiometabolic characteristics and an increased risk of type 2 diabetes compared with individuals with isolated impaired fasting glucose (IFG).

Setting, Design, And Patients: A cross-sectional analysis was performed on 595 nondiabetic subjects who underwent an oral glucose tolerance test and an euglycemic hyperinsulinemic clamp in an ambulatory care setting.

A polymorphism at IGF1 locus is associated with carotid intima media thickness and endothelium-dependent vasodilatation.

Objective: Whether IGF-1 has a protective or a detrimental role in vascular homeostasis remains unsettled. There is evidence that the C/T polymorphism rs35767 near the promoter region of the IGF1 gene located in chromosome 12 is associated with plasma IGF-1 levels. We investigated the effects of this polymorphism on circulating IGF-1 levels, carotid intima media thickness (cIMT) and endothelial-dependent vasodilation.

A fasting insulin-raising allele at IGF1 locus is associated with circulating levels of IGF-1 and insulin sensitivity.

Background: A meta-analysis of genome-wide data reported the discovery of the rs35767 polymorphism near IGF1 with genome-wide significant association with fasting insulin levels. However, it is unclear whether the effects of this polymorphism on fasting insulin are mediated by a reduced insulin sensitivity or impaired insulin clearance. We investigated the effects of the rs35767 polymorphism on circulating IGF-1 levels, insulin sensitivity, and insulin clearance.

Decreased insulin clearance in individuals with elevated 1-h post-load plasma glucose levels.

Reduced insulin clearance has been shown to predict the development of type 2 diabetes. Recently, it has been suggested that plasma glucose concentrations ≥ 8.6 mmol/l (155 mg/dl) at 1 h during an oral glucose tolerance test (OGTT) can identify individuals at high risk for type 2 diabetes among those who have normal glucose tolerance (NGT 1 h-high).

A functional variant of the dimethylarginine dimethylaminohydrolase-2 gene is associated with chronic kidney disease.

Objective: Studies reported a relationship between elevated asymmetric dimethylarginine (ADMA) concentrations and adverse renal outcomes. There is evidence that the rs9267551 variant in the DDAH2 gene has a functional impact with the C allele having a higher transcriptional activity resulting in increased expression of DDAH2 in endothelial cells and lower plasma ADMA levels in C allele carriers.

Methods: To address whether this variant is associated with chronic kidney disease (CDK), 2852 White European were studied.

Differences in insulin clearance between metabolically healthy and unhealthy obese subjects.

Metabolically healthy obese (MHO) are relatively insulin sensitive and have a favorable cardio-metabolic risk profile compared with metabolically abnormal obese (MAO). To evaluate whether MAO individuals have a decreased insulin clearance compared with MHO individuals, 49 MHO, 147 MAO, and 172 non-obese individuals were analyzed in this cross-sectional study. Insulin clearance and insulin sensitivity were assessed through euglycemic hyperinsulinemic clamp.

Insulin clearance is associated with carotid artery intima-media thickness.

Objective: The aim of this study was to investigate whether insulin clearance is independently associated with carotid artery intima-media thickness (IMT), a well-recognized index of vascular damage.

Methods: 361 Non-diabetic Caucasian subjects were subjected to euglycemic hyperinsulinemic clamp to assess insulin sensitivity, and insulin clearance. IMT of the common carotid was measured by ultrasonography.

Association of insulin resistance indexes to carotid intima-media thickness.

Objectives: Accumulating evidence suggests an association between insulin resistance (IR) and cardiovascular diseases The aim of this study was to examine the relationship between indexes of IR and common carotid intima-media thickness (IMT), an indicator of vascular damage.

Methods: In 847 non-diabetic Caucasians a 75 g oral glucose tolerance test was performed and surrogate indexes of IR were computed according to published formulas. IMT was measured by ultrasound method.