Background

Metabolic syndrome (MetS) plus type 2 diabetes increases cardiovascular disease risk about 3-fold compared with having MetS alone. The exact mechanism explaining this is unclear, but low vasculature, compared with metabolic, insulin sensitivity may play a role. However, it is unknown if prediabetes (PD) exacerbates the effect of MetS on vascular and/or metabolic insulin sensitivity.

Methods

Thirty obese adults (54.4±1.3 yrs; 35.6±1.4 kg/m2) were screened for MetS using ATP III criteria and categorized as MetS (n=16, 2M) or MetS+PD (fasting glucose >100 mg/dl; n=14, 4M). Subjects underwent a 2-hr euglycemic-hyperinsulinemic clamp (40 mU·m2·min−1) to determine vascular and metabolic (i.e. glucose infusion rate) insulin sensitivity. Endothelial function was assessed by brachial artery flow mediated dilation (FMD) and systemic aortic waveform was measured via augmentation index (AIx). Waist circumference, blood pressure, fasting lipids, glucose, MetS severity (z-score) and cardiovascular fitness (VO2peak) were also evaluated.

Results

Although age, BMI and VO2peak were similar, MetS+PD had lower metabolic insulin sensitivity (1.85±0.39 vs 3.03±0.33 mg/kg/min, P=0.01) and increased fasting glucose (112.4±1.9 vs 95.5±1.8 mg/dl, P<0.01), waist circumference (119.5±3.3 vs 111.0±2.1 cm, P=0.04) and MetS severity (3.18±0.56 vs 0.72±0.43, P<0.01) compared to MetS. Interestingly, MetS+PD and MetS had similar fasting FMD (5.81±0.65 vs 5.80±0.49%, P=0.99) and AIx (25.7±3.0 vs 26.2±1.6%, P=0.89). Insulin stimulation tended to increase FMD (P=0.07) and decrease AIx (P=0.09) in both groups, respectively

Conclusions

While MetS+PD results in a less favorable metabolic profile than MetS, this is not necessarily reflective of the vasculature, as both groups had comparable insulin-stimulated improvements in endothelial function and systemic aortic waveform. Thus, having MetS+PD appears to increase metabolic but not vascular risk above MetS alone.