Brothers of women with polycystic ovary syndrome are characterised by impaired glucose tolerance, reduced insulin sensitivity and related metabolic defects

Abstract

Aims/hypothesis Since it has been shown that polycystic ovary syndrome (PCOS) is highly inherited and characterised by insulin resistance, we hypothesised that male siblings of PCOS women would also be insulin resistant. Thus, our aim was to assess insulin sensitivity and metabolic parameters in brothers of women with PCOS and male control individuals. Methods Seventeen brothers of PCOS women and 28 male control volunteers were assessed with 75 g OGTTs and euglycaemic-hyperinsulinaemic clamps. PCOS index women were identified using criteria developed at the 1990 National Institutes of Health conference. Results Brothers and control individuals were similar in terms of BMI, waist circumference, percentage body fat and BP. However, brothers had increased triacylglycerol (p=0.02), plasminogen activator inhibitor-1 (PAI-1; p=0.02), factor VIII (p=0.02), 2 h glucose (p<0.001), AUC glucose (p<0.001) and AUC insulin (p<0.001). Insulin sensitivity was reduced by 38% in brothers (p<0.001), and this was primarily due to a 65% decrease in insulin-stimulated non-oxidative carbohydrate metabolism (p<0.001). These differences remained significant after adjustment for age and BMI, except for triacylglycerol, PAI-1 and fasting glucose. The main findings also persisted after excluding individuals with impaired glucose tolerance or diabetic siblings. Significant interactions with BMI status were found for sex hormone-binding globulin, androstenedione, PAI-1 and AUC insulin , which were significantly altered only in obese brothers (vs control individuals). Conclusions/interpretation Brothers of PCOS women are characterised by decreased insulin sensitivity and glucose tolerance, as well as hypercoagulability, independently of obesity. Therefore, brothers of PCOS women may have inherited the insulin resistance and metabolic syndrome typical of PCOS.

Hyperinsulinemia is closely related to low urinary clearance of d-chiro-inositol in men with a wide range of insulin sensitivity

“…We have also found that brothers of women with PCOS, who were similar to control men for anthropometric measures, displayed decreased insulin sensitivity (measured by insulin-glucose clamp), increased insulin levels, decreased glucose tolerance, increased triglyceride levels, and increased levels of plasminogen activator inhibitor-1 (PAI-1) and factor VIII [15]. Except for triglycerides and PAI-1, all these differences remained significant after adjustments for age and body mass index (BMI).…”

Ovarian cytoarchitectual changes following fennel ingestion in senile diabetic albino rat

“…These results were confirmed by the electron microscopic finding of presence of numerous lipid droplets. The most popular theories that have been put forward to explain the pathogenesis of PCOS in hyperinsulinemia is "selective insulin resistance" theory by Baillargeon and Carpentier [37] . They contributed insulin resistance, consequent hyperinsulinemia and glucose intolerance to hyperandrogenism which is the cardinal feature of PCOS.…”

Polycystic Ovary Syndrome in the Pediatric Population

“…[83][84][85][86][87] However, despite a large number of genetic studies, no one single gene has been associated with the development of all the syndrome's phenotypes. [88][89][90] Although a comprehensive review of the genetics of PCOS is beyond the scope of this review, to date, the most promising candidate gene associated with PCOS maps to a locus on chromosome 19p13.2 within an intron of the fibrillin-3 gene, which interestingly is located near the insulin receptor gene.…”