PREDIABETES PHENOTYPE DOES NOT EXACERBATE MICROVASCULAR INSULIN SENSITIVITY IN METABOLIC SYNDROME

Abstract

Metabolic syndrome (MetS) and elevated glucose each promote microvascular dysfunction. Whether in combination these two conditions create increased dysfunction is not clear. Here, we tested whether glucose status worsens microvascular insulin sensitivity in MetS. Thirty-two sedentary, obese adults (54.2±1.2yrs; 35.9±1.3kg/m2; VO2max: 19.9±1.3ml/kg/min) with MetS (≥3 ATP III criteria) were classified as normal glucose tolerant (NGT, n=8; 6F), impaired fasting glucose (IFG; n=10; 7F) or IFG+IGT (n=14; 11F) according to ADA criteria using a 75g OGTT. Capillary perfusion (microvascular blood volume, MBV), filling rate (microvascular flow velocity, MFV) and blood flow (MBF=MBV*MFV) were assessed as the change before and after a 2hr euglycemic-hyperinsulinemic clamp (90mg/dl, 40mU/m2/min) using contrast enhanced ultrasound. Glucose infusion rate (GIR) was used to determine metabolic insulin sensitivity while carbohydrate oxidation (CHOox) was measured before and after the clamp to understand nutrient utilization. T-tests, repeated measures ANOVAs and correlations were used when appropriate. Significance was accepted as P≤0.05. There were no differences in age, BMI, VO2max or GIR (NGT: 2.26±0.48 vs. IFG: 2.66±0.46 vs. IFG+IGT: 1.91±0.37mg/kg/min, P=0.44) among groups. Insulin did not stimulate capillary perfusion (NGT: 0.16±0.19 vs. IFG: -0.02±0.14 vs. IFG+IGT: 0.08±0.12AI, P=0.40), filling rate (NGT: 0.006±0.005 vs. IFG: 0.003±0.004 vs. IFG+IGT: 0.004±0.004sec-1, P=0.11) or blood flow (NGT: 0.02±0.02 vs. IFG: 0.01±0.01 vs. IFG+IGT: 0.01±0.01AI/sec, P=0.21). CHOox was likewise unresponsive to insulin (P=0.34). Although age, BMI, fasting and 2hr glucose concentrations did not relate to insulin effects on microvascular function, fasting triglycerides was related to insulin-stimulated MBF (r=-0.39, P=0.03). Prediabetes phenotype does not worsen microvascular insulin sensitivity in adults with MetS. Future work is warranted to examine the effects of different therapies (lifestyle, medication) on microvascular function. Funding was supported by the National Institutes of Health RO1-HL130296.