Impaired maximum microvascular hyperaemia in patients with MODY 3 (hepatocyte nuclear factor-1 alpha gene mutations)

Aims Functional abnormalities of blood flow and capillary pressure may be i nvolved in the pathogenesis of diabetic microangiopathy. Important differen ces in microvascular behaviour are observed between Type 1 and Type 2 diabe tes mellitus, raising the possibility that the pathogenesis of microangiopa thy may differ between these. MODY3 patients have hyperglycaemia as a resul t of genetic defect of beta-cell function rather than increased insulin res istance and are susceptible to microvascular complications and offer an opp ortunity to examine microvascular behaviour in this setting. Methods The maximum microvascular hyperaemic response to local heating of t he skin was studied in 12 MODY3 patients and age and sex-matched control su bjects using laser Doppler fluximetry. Results Maximum hyperaemia was reduced in MODY3 patients (median 1.17 (rang e 0.88-1.92) V vs. 1.70 (1.07-2.19)V normal control subjects; P = 0.03) and thus was negatively associated with duration of diabetes (r(s)=-0.79; P=0. 002). Conclusions The results suggest that the duration of diabetes is a determin ant of impaired microvascular hyperaemia in MODY3 patients. The pattern of vasodilatory impairment is similar to that observed in Type 1 diabetes mell itus and differs from that seen in Type 2 diabetes. This provides support f or the concept that beta cell dysfunction and insulin resistance may have d iffering effects on microvascular behaviour.