Chapter 6 – Metabolic and Vascular Insulin Sensitivity in Obesity and Hypertension

Impaired insulin-induced glucose disposal and capillary recruitment (i.e. metabolic and microvascular insulin resistance, respectively) are characteristics of coexisting conditions obesity and hypertension. Whereas hypertension is considered a metabolic insulin resistant state in itself, it is presently unclear to what extent microvascular insulin resistance is independent of adiposity in hypertensive individuals. We addressed this question in a four-corner model, using four distinct phenotypic groups of individuals: non-obese normotensive (NN), non-obese hypertensive (NH), obese normotensive (ON), and obese hypertensive (OH). In a crosssectional study 21 individuals with hypertension (12 lean and 9 obese) and 23 ageand BMI-matched normotensive controls (11 lean and 12 obese) were included. We examined capillary density in skin by capillary videomicroscopy at baseline and during a 120-min euglycemic-hyperinsulinemic clamp. Blood pressure was assessed using 24-h ambulatory blood pressure monitoring. Compared to NN individuals, metabolic insulin sensitivity decreased gradually from NH, ON to OH individuals (8.2 ± 2.4, 6.4 ± 2.2, 3.9 ± 1.8, and 2.8 ± 1.9 mg·kg-1·min-1, p for trend <0.001). Obesity showed a more profound decrease in metabolic insulin resistance (non-obese vs. obese 7.27±2.38 vs. 3.42±1.82 mg·kg-1·min-1 , p<0.001) than the presence of hypertension (normotensive vs. hypertensive 5.98±2.93 vs. 4.84±2.67 mg·kg-1·min-1, p=0.23). Compared to NN individuals, insulin-augmented capillary recruitment decreased gradually from NH, ON to OH individuals (13.1 ± 15.9, 4.4 ± 10.9, 2.8 ± 4.7, and -6.5 ± 12.0 percent-points, respectively, p for trend <0.0001). Both obese and hypertensive individuals displayed a significantly lower insulin-augmented capillary recruitment when compared with their respective controls (non-obese 8.6±13.6 %-points vs. obese -1.2±9.3 %-points, p<0.01 and normotensive 7.7±12.1 %-points vs. hypertensive -0.26±12.1 %-points, p<0.05). Obesity and hypertension have compounding detrimental effects on metabolic and microvascular insulin sensitivity. Obesity seems to be of greater impact than hypertension on metabolic insulin-sensitivity, whereas both have a similar impact on microvascular insulin sensitivity.