1 Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China
2 Medical Insurance Office, Liuzhou General Hospital, Liuzhou, Guangxi, People’s Republic of China
3 Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China
Previous studies have uncovered a progestin-only contraceptive association with an increased risk of diabetes, but limited studies have explored the relationship of endogenous progesterone and pregnenolone levels with diabetes status. A case–control study was conducted in Henan Rural Cohort (register number: ChiCTR-OOC-15006699) to evaluate the dose–response independent and interactive relationship of progesterone and pregnenolone levels with prediabetes and type 2 diabetes mellitus (T2DM) in Chinese rural population.
A case-control study.
A total of 798 T2DM patients, 779 prediabetes patients, and 782 individuals with normal fasting plasma glucose were included in this study. Serum progesterone and pregnenolone were detected by liquid chromatography-tandem mass spectrometry. Logistic regression and restricted cubic splines were used to assess the independent effects of progesterone and pregnenolone on prediabetes and T2DM. Interactive plots were employed to examine the interaction effects of progesterone and pregnenolone.
Progesterone in the fourth versus first quartile was positively associated with prediabetes (odds ratio (OR) (95% CI): 2.66 (1.99–3.55)) and T2DM (OR (95% CI): 6.41 (4.57–8.98)), whereas pregnenolone in the fourth versus first quartile was inversely related to prediabetes (OR (95% CI): 0.23 (0.16–0.33)) and T2DM (OR (95% CI): 0.44 (0.31–0.62)). Additionally, the nonlinear dose–response associations between progesterone and pregnenolone with prediabetes and T2DM were found. Interactive effects of progesterone and pregnenolone on prediabetes and T2DM were observed, and these significant associations remained in gender-stratified analysis.
Prediabetes and T2DM were positively linked to serum concentration of progesterone and negatively related to pregnenolone in a dose–response manner in Chinese rural population.
Supplementary Table 1. Coefficients of variation for laboratory measurement.
Supplementary Table 2. The calibration range, correlation coefficient, LOD, LOQ, intra- and inter-day coefficients of variation.
Supplementary Table 3. The parameters of monitored multiple-reaction-monitoring mode for serum progestogens detection.
Supplementary Table 4. Associations of progesterone and pregnenolone with glucose homeostasis markers.
Supplementary Table 5. Relationships of progesterone and pregnenolone with prediabetes and T2DM independent of glucose homeostasis markers.