Abstract
BackgroundThis study aims to investigate the independent and combined effects of progesterone and suppressor of cytokine signaling (SOCS)-3 DNA methylation on type 2 diabetes mellitus (T2DM) among men and postmenopausal women in rural China.MethodsA case–control study with 914 participants (329 T2DM, 585 controls) was conducted. Serum progesterone was detected with liquid chromatography-tandem mass spectrometry. DNA methylation of SOCS3 was determined by MethylTarget™. Linear regression was applied to evaluate the associations of progesterone and SOCS3 methylation with marks of glucose metabolism. Logistic regression was employed to investigate the independent and combined effects of progesterone and SOCS3 methylation with T2DM in men and postmenopausal women.ResultsAfter multiple adjustment, progesterone was positively associated with T2DM in both men (odds ratio (OR) (95% confidence interval (CI)): 2.77 (1.79, 4.29)) and postmenopausal women (OR (95% CI): 1.85 (1.26, 2.72)). Methylation level of Chr17:76,356,190 or Chr17:76,356,199 (SOCS3) was negatively associated with T2DM in both men (OR (95% CI): 0.58 (0.39, 0.86) or 0.27 (0.14, 0.51)) and postmenopausal women (OR (95% CI): 0.43 (0.29, 0.65) or 0.53 (0.28, 0.99)). Subjects with high progesterone and low Chr17:76,356,190 or Chr17:76,356,199 methylation were more susceptible to have a higher prevalence of T2DM (men: OR (95% CI): 5.20 (2.49, 10.85) or 5.62 (2.74, 11.54); postmenopausal women: OR (95% CI): 3.66 (1.85, 7.26) or 3.27 (1.66, 6.45)).ConclusionsThe independent and combined effects of progesterone and SOCS3 methylation on T2DM were found among men and postmenopausal women, suggesting that ensuring low levels of progesterone and high methylation of SOCS3 could reduce the prevalence of T2DM.Trial registration The Chinese Clinical Trial registration: The Henan Rural Cohort Study, ChiCTR-OOC-15006699. Registered 06 July 2015, http://www.chictr.org.cn/showproj.aspx?proj=11375
Highlights
This study aims to investigate the independent and combined effects of progesterone and suppressor of cytokine signaling (SOCS)-3 DNA methylation on type 2 diabetes mellitus (T2DM) among men and postmenopausal women in rural China
Postmenopausal women, suggesting that individuals who exposed to high levels of progesterone and low level of Chr17:76356190 or Chr17:76356199 methylation had a greater risk of prevalence of T2DM than those who exposed to low levels of serum progesterone and high level of Chr17:76356190 or Chr17:76356199 methylation (men: Odds ratio (OR): 5.20 (2.49, 10.85) or 5.62 (2.74, 11.54); postmenopausal women: OR: 3.66 (1.85, 7.26) or 3.27 (1.66, 6.45))
In the present study, we investigated the independent and combined effects of progesterone and SOCS3 methylation on T2DM among men and postmenopausal women in Henan rural areas, and discovered that progesterone was associated with an increased risk of T2DM; methylation of Chr17:76356190 or Chr17:76356199 was associated with a decreased risk of T2DM
Summary
This study aims to investigate the independent and combined effects of progesterone and suppressor of cytokine signaling (SOCS)-3 DNA methylation on type 2 diabetes mellitus (T2DM) among men and postmenopausal women in rural China. A growing number of researches have reported that steroid hormones may influence the incidence of diabetes [3]. A recent cross-sectional study drawn from the KORA F4/FF4 cohort study which were followed up for approximately 6.4 years, reported an inverse association of progesterone with fasting insulin, and a positive association of progesterone with quantitative insulin sensitivity check index (QUICKI) among men. Our previous study found that high levels of progesterone were correlated with a higher chance of presenting T2DM among men and postmenopausal women [11]. A cross-sectional study reported a decrease in progesterone levels among T2DM patients compared with those in control group [12]. Previous evidence from pregnant population is much limited [13, 14], so it is essential to explore the correlations among general population
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