Adiposity is a major determinant of plasma levels of the novel vasodilator hydrogen sulphide

Hydrogen sulphide is a recently identified endogenous endothelium-dependent vasodilator. Animal models of diabetes have shown that low plasma H(2)S levels are associated with marked endothelial dysfunction and insulin resistance. However, human studies on H(2)S and vascular function in health and disease are lacking. Plasma was obtained from male patients with type 2 diabetes (n = 11), overweight (n = 16) and lean (n = 11) volunteers. H(2)S levels were determined by zinc trap spectrophotometry. Anthropometric measurements (BMI/waist:hip ratio), lipid profile, systemic blood pressure, biochemical indices of diabetes (fasting glucose, insulin sensitivity, Hb(1Ac)) and microvascular function (minimum vascular resistance) were determined. Median plasma H(2)S levels (25th, 75th percentiles) in age-matched lean, overweight and type 2 diabetes individuals were 38.9 (29.7, 45.1) A mu mol/l, 22.0 (18.6, 26.7) A mu mol/l and 10.5 (4.8, 22.0) A mu mol/l, respectively. Median plasma H(2)S levels were significantly lower in patients with type 2 diabetes compared with lean (p = 0.001, Mann-Whitney) and overweight participants (p = 0.008). Median plasma H(2)S levels in overweight participants were significantly lower than in lean controls (p = 0.003). Waist circumference was an independent predictor of plasma H(2)S (R (2) = 0.423, standardised beta: -0.650, p < 0.001). This relationship was independent of diabetes, which only contributed a further 5% to the model (R (2) = 0.477). Waist circumference or other measures of adiposity (waist:hip ratio/BMI) remained independent predictors of plasma H(2)S after adjustment for systolic blood pressure, microvascular function, insulin sensitivity, glycaemic control and lipid profile. Plasma H(2)S levels are reduced in overweight participants and patients with type 2 diabetes. Increasing adiposity is a major determinant of plasma H(2)S levels.