Glucose Intolerance, Insulin Resistance and Cardiovascular Risk Factors in First Degree Relatives of Women With Polycystic Ovary Syndrome

Abstract

Findings on familial aggregation of polycystic ovary syndrome (PCOS) are consistent with a genetic component. Studies have shown greater insulin resistance (IR), higher serum androgen levels, more frequent glucose tolerance disorder, and more type II diabetes in first-degree relatives of patients with PCOS. The present study examined these variables in addition to cardiovascular risk factors in 120 family members of 55 patients with PCOS. There were 40 mothers, 38 fathers, 25 sisters, and 17 brothers. The control group included 75 healthy subjects with no family history of PCOS or diabetes. The study and control groups were matched for age and body weight. Insulin resistance was estimated by homeostatic model assessment (HOMA IR), log HOMA, insulin sensitivity index, the quantitative insulin sensitivity check index (QUICKI), and the area under the curve for insulin (AUCI) during an oral glucose tolerance test. Glucose intolerance of any degree was documented in 40% of mothers and 52% of fathers of patients with PCOS. Six cases of glucose tolerance disorder were found in control mothers and fathers (15%). First-degree relatives of patients with PCOS, compared with control subjects, had significantly higher serum levels of fasting insulin, HOMA-IR, log HOMA, and AUCI. Control subjects had significantly increased QUCKI, ISI levels. In addition, serum levels of adiponectin were significantly higher than in all subgroups of relatives of PCOS subjects. Fathers and mothers of patients with PCOS, but not brothers or sisters, had higher serum homocysteine and resistin levels. Blood lipid levels, including total cholesterol and low-density lipoprotein (LDL)-cholesterol, were significantly higher in fathers of patients with PCOS than in the control group. The opposite was the case for serum levels of high-density lipoprotein (HDL)-cholesterol and apoprotein A. Levels of total cholesterol, LDL-cholesterol, apoprotein B, and triglycerides were higher in mothers of patients with PCOS than in control subjects, but levels of HDL-cholesterol and apoprotein A were similar. Levels of most blood lipids were similar in patients' sisters than in control subjects, but brothers of patients had higher blood lipid levels than control subjects (exceptions were HDL-cholesterol and apoprotein A). Both groups of parents of patients with PCOS had higher blood pressure, but this was not true for the brothers and sisters. These findings indicate that first-degree relatives of patients with PCOS, like the patients themselves, are at increased risk of developing cardiovascular disease (CVD). These family members should be monitored for both CVD and diabetes, and preventive measures should be taken when appropriate.