Insulin resistance and endothelial dysfunction in the brothers of Indian subcontinent Asian women with polycystic ovaries

BACKGROUND: Ultrasonographic appearances of polycystic ovaries (PCO) are found in 50% of South London Indian subcontinent Asians, a population at high risk of coronary disease and type 2 diabetes (DM). PCO is a familial condition but the genetics remain to be clarified. At present, the only characteristic documented in male family members is premature male pattern balding before the age of 30 years. Our aim was to quantify insulin resistance and endothelial cell function in the brothers of Indian subcontinent Asian women with PCO and/or a family history of type 2 DM. METHODS: Indian subcontinent Asian women (n = 40, age 16-40 years) with a brother available for study were recruited from the local population. They were stratified into four groups according to the ultrasound appearances of PCO and/or a family history of type 2 DM. Control subjects had no PCO and no family history of DM. Insulin sensitivity (KITT) was measured using a short insulin tolerance test and endothelial function using brachial artery ultrasound to measure flow-mediated dilatation (FMD). FINDINGS: Groups were well matched for age, body mass index (BMI) and waist-hip circumference ratios. Asian women with PCO demonstrated insulin resistance independent of BMI or family history of diabetes. Women with PCO and a family history of DM have reduced FMD, though PCO alone was not a marker. The brothers of women with PCO also have insulin resistance, comparable to that associated with a family history of type 2 DM. This was associated with elevations of blood pressure, abnormalities in serum lipid concentrations and impaired endothelial cell function. Endothelial cell function was particularly impaired in those subjects with both a sister with PCO and a family history of DM. INTERPRETATION: In an ethnic minority population at higher risk of coronary heart disease, brothers of women with PCO have evidence of insulin resistance and endothelial cell dysfunction in early adult life. Further study is required to establish whether these findings are associated with an increased incidence of cardiovascular events in this population.