Diabetes mellitus and insulin resistance in mothers, fathers, sisters, and brothers of women with polycystic ovary syndrome: a systematic review and meta-analysis

Fertil Steril. 2018 Aug;110(3):523-533.e14. doi: 10.1016/j.fertnstert.2018.04.024. Epub 2018 Jun 28.


Objective(s): To analyze whether first-degree relatives (FDR) of patients with polysystic ovary syndrome (PCOS) have an increased risk of insulin resistance and glucose intolerance.

Design: Systematic review and meta-analysis.

Setting: None.

Patient(s): Parents and siblings of women with and without PCOS.

Intervention(s): Search of PubMed database from 1960 to September 2017 with cross-checking of references of relevant articles in English.

Main outcome measure(s): Prevalence of type 2 diabetes mellitus (T2DM) and impaired glucose tolerance, and levels of fasting insulin, 2-hour insulin levels, and homeostatic model assessment insulin resistance (HOMA IR).

Result(s): Our search retrieved 4,796 articles of which 19 were included. The prevalence of T2DM was significantly increased in mothers and fathers of PCOS probands (rate ratio [RR] 2.43; 95% confidence interval [CI], 1.58-3.75, and RR 2.27; 95% CI, 1.25-4.12). Moreover, the fasting insulin (in mothers, fathers, and sisters) and HOMA IR (in mothers, fathers, and sisters) levels were statistically significantly higher in parents and siblings of PCOS patients. The sisters (RR 1.34; 95% CI, 0.59-3.03) and brothers (RR 1.51; 95% CI, 0.63-3.62) had a higher prevalence of T2DM than the control subjects, but the difference was not statistically significant.

Conclusion(s): Our meta-analysis provides quantitative evidence demonstrating clustering of T2DM and insulin resistance in the parents and siblings of PCOS probands.

Systematic review registration number: PROSPERO 2016 CRD42016048551.

Keywords: Diabetes mellitus; first-degree relatives; insulin resistance; meta-analysis; polycystic ovary syndrome; systematic review.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Systematic Review

MeSH terms

  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / genetics*
  • Fathers*
  • Female
  • Humans
  • Insulin Resistance / genetics*
  • Male
  • Mothers*
  • Polycystic Ovary Syndrome / diagnosis
  • Polycystic Ovary Syndrome / genetics*
  • Siblings*