Aims Microvascular dysfunction occurs in Type 2 diabetes and in subjects with fasting hyperglycaemia. It is unclear whether this dysfunction relates to dysglycaemia. This study investigated in normogylcaemic individuals whether a genetic predisposition to diabetes, or indices of insulin resistance including endothelial markers, were associated with impaired microvascular function.Methods Maximum microvascular hyperaemia to local heating of the skin was measured using laser Doppler¯owmetry in 21 normoglycaemic subjects with no family history of diabetes (Group 1) and 21 normoglycaemic age, sex and body mass index-matched offspring of two parents with Type 2 diabetes (Group 2).Results Although Group 2 had normal fasting plasma glucose and glucose tolerance tests, the 120-min glucose values were signi®cantly higher at 6.4 (5.3±6.6) mmol/l (median (25th ± 75th centile)) than the control group at 4.9 (4.6±5.9) mmol/l (P = 0.005) and the insulinogenic index was lower at 97.1 (60.9±130.8) vs. 124.0 (97.2±177.7) (P = 0.027). Skin maximum microvascular hyperaemia (Group 1: 1.56 (1.39±1.80) vs. Group 2: 1.53 (1.30±1.98) V, P = 0.99) and minimum microvascular resistance which normalizes the hyperaemia data for blood pressure (Group 1: 52.0 (43.2±67.4) vs. Group 2: 56.0 (43.7±69.6) mmHg/V, P = 0.70) did not differ in the two groups. Signi®cant positive associations occurred between minimum microvascular resistance and indices of the insulin resistance syndrome; plasminogen activator inhibitor type 1 (R s = 0.46, P = 0.003), t-PA (R s = 0.36, P = 0.03), total cholesterol (R s = 0.35, P = 0.02), and triglyceride concentration (R s = 0.35, P = 0.02), and an inverse association with insulin sensitivity (R s = ±0.33, P = 0.03).Conclusions In normoglycaemic adults cutaneous microvascular vasodilatory capacity is associated with features of insulin resistance syndrome, particularly with plasminogen activator inhibitor type 1. A strong family history of Type 2 diabetes alone does not result in impairment in the maximum hyperaemic response.

The results suggest that the duration of diabetes is a determinant of impaired microvascular hyperaemia in MODY3 patients. The pattern of vasodilatory impairment is similar to that observed in Type 1 diabetes mellitus and differs from that seen in Type 2 diabetes. This provides support for the concept that beta cell dysfunction and insulin resistance may have differing effects on microvascular behaviour.