Hypoglycemia Assessed by Continuous Glucose Monitoring Is Associated with Preclinical Atherosclerosis in Individuals with Impaired Glucose Tolerance

Hypoglycemia is associated with increased risk of cardiovascular adverse clinical outcomes. There is evidence that impaired glucose tolerance (IGT) is associated with cardiovascular morbidity and mortality. Whether IGT individuals have asymptomatic hypoglycemia under real-life conditions that are related to early atherosclerosis is unknown. To this aim, we measured episodes of hypoglycemia during continuous interstitial glucose monitoring (CGM) and evaluated their relationship with early manifestation of vascular atherosclerosis in glucose tolerant and intolerant individuals. An oral glucose tolerance test (OGTT) was performed in 79 non-diabetic subjects. Each individual underwent continuous glucose monitoring for 72 h. Cardiovascular risk factors and ultrasound measurement of carotid intima-media thickness (IMT) were evaluated. IGT individuals had a worse cardiovascular risk profile, including higher IMT, and spent significantly more time in hypoglycemia than glucose-tolerant individuals. IMT was significantly correlated with systolic (r = 0.22; P = 0.05) and diastolic blood pressure (r = 0.28; P = 0.01), total (r = 0.26; P = 0.02) and LDL cholesterol (r = 0.27; P = 0.01), 2-h glucose (r = 0.39; P<0.0001), insulin sensitivity (r = −0.26; P = 0.03), and minutes spent in hypoglycemia (r = 0.45; P<0.0001). In univariate analyses adjusted for gender, minutes spent in hypoglycemia were significantly correlated with age (r = 0.26; P = 0.01), waist circumference (r = 0.33; P = 0.003), 2-h glucose (r = 0.58; P<0.0001), and 2-h insulin (r = 0.27; P = 0.02). In a stepwise multivariate regression analysis, the variables significantly associated with IMT were minutes spent in hypoglycemia (r2 = 0.252; P<0.0001), and ISI index (r2 = 0.089; P = 0.004), accounting for 34.1% of the variation. Episodes of hypoglycemia may be considered as a new potential cardiovascular risk factor for IGT individuals

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 &gt; 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.Methods: Cross-sectional data of the CATAMERI study (n = 2335) were analyzed. Participants underwent anthropometric measurements, liver enzyme determinations, cardiometabolic profiling, and a 75-gram oral glucose tolerance test, including fasting, 1-h and 2-h PG determinations and measurement of FIB-4 score to assess degree of hepatic fibrosis. Multivariable logistic regression analysis was performed to evaluate risk of advanced hepatic fibrosis with worsening glycemic status.Results: We stratified the study group into 6 categories based on glycemic status: normal glucose tolerance (NGT) 1h-PG Low, NGT 1h-PG High, iIFG 1h-PG Low, iIFG 1h-PG High, IGT, and newly detected T2D. Anthropometric and cardiometabolic profiles worsened gradually with glycemic status. Moreover, compared to NGT-1h-PG Low group, worsening glycemic status was significantly associated with the severity of fibrosis, independent of other significant clinical risk factors.Conclusions: 1-PG is a valuable tool for stratifying subjects with NGT or IFG at heightened risk of hepatic fibrosis requiring further evaluation with elastography

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. Formal tests for glucose tolerance status x sex interaction were statistically significant for waist circumference (P=0.008), HOMA-IR (P=0.03), total cholesterol (P=0.003), LDL (P=0.001), HDL (P=0.006), triglycerides (P&lt;0.0001), and hsCRP (P&lt;0.05). In a logistic regression analysis, prediabetic and diabetic women exhibited a higher OR for NAFLD than their male counterparts with test for glucose tolerance status x sex interaction being statistically significant. Conclusions: Prediabetic and diabetic women have higher OR of having NAFLD than men. Deterioration of glucose homeostasis in women is associated with a greater worsening in metabolic risk factors than men, which may explain the stronger impact of prediabetes and T2DM on NAFLD in women

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. In addition, a longitudinal analysis was performed on 392 individuals, who were reexamined after a followup of 5.2 ± 0.9 y. Main Outcome Measures: Insulin sensitivity, beta-cell function, and risk of developing diabetes were measured. Results: Subjects with NGT-1h-high have a significant reduction of peripheral insulin sensitivity and beta-cell function, assessed by the disposition index, compared with either 1-h postload glucose &lt; 155 mg/dL (NGT-1h-low) or IFG individuals, but not compared with IGT. Among the 392 subjects studied in the longitudinal analysis the incidence rate of type 2 diabetes over the follow-up period was 2.9, 16.7, 12.5, and 31.4% for subjects with NGT-1h-low, NGT-1h-high, IFG, and IGT, respectively. In a Cox proportional hazard regression analysis the risk of developing diabetes for NGT-1h-high subjects was 4.02 (95% confidence interval [CI] 1.06–15.26); an even higher risk (6.67; 95% CI, 2.09–21.24) was observed in subjects with IGT, but not in the isolated IFG group (1.91; 95% CI, 0.44–8.29). Conclusions: NGT-1h-high subjects exhibit a higher risk of developing diabetes than those with IFG or NGT-1h-low, likely due to decreased insulin sensitivity and beta-cell function

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. Results: Isolated IFG, isolated IGT, and combined IFG/IGT women exhibited greater relative differences in BMI, waist circumference, and insulin-stimulated glucose disposal than their male counterparts. Formal tests for glucose tolerance status&nbsp;×&nbsp;sex interaction were statistically significant for BMI (P&nbsp;=&nbsp;0.05) waist circumference (P&nbsp;=&nbsp;0.04), and insulin-stimulated glucose disposal (P&nbsp;=&nbsp;0.01) suggesting a sex-specific association. By contrast, tests for glucose tolerance status&nbsp;×&nbsp;sex interaction regarding both insulinogenic and disposition indexes were not significant. Conclusions: This study suggests that deterioration of glucose homeostasis in women is associated with a greater fat accumulation and worsening in insulin sensitivity as compared with men

Increased abundance of insulin/IGF-I hybrid receptors in adipose tissue front NIDDM patients

Insulin/IGF-I hybrid receptors composed of an insulin receptor (IR) alpha beta-hemireceptor and a type 1 IGF receptor (IGF-IR) alpha beta-hemireceptor are formed in tissues expressing both molecules. To date there is a limited information about the proportion of hybrids in tissues of normal or diabetic subjects. In this study, we determined the abundance of hybrids in fat from control and NIDDM subjects by using a microwell-based immunoassay. Microwells coated with MA-20 anti-IR or alpha-IGF-IR-PA anti-IGF-IR antibody were incubated with tissue extracts. Immunoadsorbed receptors were incubated with I-125-insulin or I-125-IGF-I in the presence or absence of unlabeled ligands, and hybrids were quantitated as the fraction of I-125-IGF-I binding immunoadsorbed with MA-20. Abundance of hybrids was increased in NIDDM patients as compared with controls (B/T = 1.29 +/- 0.18 and 0.52 +/- 0.06%; P < 0.008, respectively), and it was inversely correlated with both IR number (r = -0.65; P < 0.002), and in vivo insulin sensitivity measured by insulin tolerance test (r = -0.75; P < 0.005), whereas it was positively correlated with insulinemia (r = 0.63: P < 0.003). Insulin binding affinity was lower in NIDDM subjects than in controls (ED50 = 1.87 +/- 0.32 and 0.54 +/- 0.20 nmol/l; P < 0.009, respectively), and was correlated with the percentage of hybrids. Maximal IGF-I binding was significantly greater in NIDDM patients than controls and was positively correlated with the percentage of hybrids whereas IGF-I binding affinity did not differ between the two groups. Results show that expression of hybrids is increased in fat of NIDDM patients compared to control subjects and is correlated with in vivo insulin sensitivity thus raising the possibility that alterations in expression of hybrids which bind IGF-I with higher affinity than insulin may contribute, at least in part, to insulin resistance. (C) 1997 Elsevier Science Ireland Ltd

Univariate correlations between IMT and anthropometric and biochemical variables.

<p>Partial correlation coefficients adjusted for age and gender were computed between variables. <i>P</i> values refer to results after analyses with adjustment for age, and gender.</p><p>*<i>P</i> values refer to results after analysis with adjustment for gender. BMI = Body Mass Index, SBP = systolic blood pressure; DBP = diastolic blood pressure.</p

Twenty-four-hour glucose profiles of 10 representative individuals with IGT.

<p>Dashed line indicates the 70 mg/dl glucose threshold.</p