Parenthood and the risk of diabetes in men and women: a 7 year prospective study of 0.5 million individuals

Background: In women, higher parity has been associated with increased risk of diabetes later in life. It is unclear, however, whether this association is mainly due to biological effects of childbearing, or to socioeconomic and lifestyle factors associated with childrearing. We assessed the association between number of children and diabetes risk separately in women and men. Methods: In 2004-08, the nationwide China Kadoorie Biobank recruited 0.5 million individuals aged 30-79 (mean 51) from 10 diverse regions across China. During 7 years of follow-up, 8,840 incident cases of diabetes were recorded among 463,347 participants without prior cardiovascular diseases or diabetes. Multivariable Cox regression yielded sex-specific hazard ratios (HRs) and 95% confidence intervals (CI) for incident diabetes by number of children. Results: Overall, ~98% of all participants had children. In women, there was a J-shaped association between number of children and risk of diabetes. Compared to women with one child, the adjusted HRs for diabetes were 1.39 (95% CI 1.11, 1.73) for childless women, and 1.12 (1.07, 1.18) for two, 1.23 (1.16, 1.31) for three, and 1.32 (1.21, 1.44) for ≥four children. In men, there was a similar association with risk of diabetes, with the corresponding HRs being 1.28 (1.02, 1.60), 1.19 (1.12, 1.26), 1.32 (1.21, 1.44), and 1.41 (1.24, 1.60), respectively. In both sexes, the findings were broadly similar in different population subgroups. Conclusion: The similarity between women and men in the association between number of children and risk of diabetes suggests that parenthood is most likely to affect diabetes risk through factors associated with childrearing rather than via biological effects of childbearing

The effect of androgen excess on maternal metabolism, placental function and fetal growth in obese dams

Pregnant women with polycystic ovary syndrome (PCOS) are often overweight or obese. To study the effects of maternal androgen excess in obese dams on metabolism, placental function and fetal growth, female C57Bl6J mice were fed a control (CD) or a high fat/high sucrose (HF/HS) diet for 4-10 weeks, and then mated. On gestational day (GD) 15.5-17.5, dams were injected with dihydrotestosterone (CD-DHT, HF/HS-DHT) or a vehicle (CD-Veh, HF/HS-Veh). HF/HS dams had higher fat content, both before mating and on GD18.5, with no difference in glucose homeostasis, whereas the insulin sensitivity was higher in DHT-exposed dams. Compared to the CD groups, the livers from HF/HS dams weighed more on GD18.5, the triglyceride content was higher, and there was a dysregulation of liver enzymes related to lipogenesis and higher mRNA expression of Fitm1. Fetuses from HF/HS-Veh dams had lower liver triglyceride content and mRNA expression of Srebf1c. Maternal DHT exposure, regardless of diet, decreased fetal liver Pparg mRNA expression and increased placental androgen receptor protein expression. Maternal diet-induced obesity, together with androgen excess, affects maternal and fetal liver function as demonstrated by increased triglyceride content and dysfunctional expression of enzymes and transcription factors involved in de novo lipogenesis and fat storage.Swedish Medical Research Council 2014-2775 Jane and Dan Ohlsson Foundation Wilhelm and Martina Lundgren's Science Fund Hjalmar Svensson Foundation Adlerbert Research Foundation Novo Nordisk Foundation NNF16OC0020744 Strategic Research Programme (SRP) in Diabetes at Karolinska Institutet Swedish federal government under LUA/ALF ALFGBG-429501 FONDECYT 11130250 National Commission for Scientific and Technological Research (CONICYT, Chile) Stockholm County Council Karolinska Institute