Obesity and risk of gestational diabetes mellitus: A two-sample Mendelian randomization study

Xinli Song; Cheng Wang; Tingting Wang; Senmao Zhang; Jiabi Qin

doi:10.1016/j.diabres.2023.110561

Obesity and risk of gestational diabetes mellitus: A two-sample Mendelian randomization study

Diabetes Res Clin Pract. 2023 Mar:197:110561. doi: 10.1016/j.diabres.2023.110561. Epub 2023 Feb 3.

Authors

Xinli Song¹, Cheng Wang², Tingting Wang¹, Senmao Zhang¹, Jiabi Qin³

Affiliations

¹ Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, China.
² Department of Thoracic Surgery, The Second Xiangya Hospital of Central South University, Changsha, China.
³ Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, China; National Health Committee Key Laboratory of Birth Defect for Research and Prevention, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, China; Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China; Hunan Provincial Key Laboratory of clinical epidemiology, Changsha, Hunan, China. Electronic address: qinjiabi123@163.com.

PMID: 36738839
DOI: 10.1016/j.diabres.2023.110561

Abstract

Aims: To estimate genetically predicted causal associations of general and central obesity with GDM, and to determine the mediating role of circulating lipids.

Methods: Summary-level data was obtained from the largest available genome-wide association studies of five obesity traits, five lipid traits and GDM. Two-sample univariate Mendelian randomization (MR), multivariate MR, and MR-based mediation analysis was applied to determine the total effect, direct effect and the mediating effect, respectively.

Results: Univariate MR showed that the odds of GDM increased per 1-SD increase in body mass index (BMI) (OR = 1.64, P = 5.05 × 10^-17), waist-to-hip ratio (WHR) (OR = 1.57, P = 2.27 × 10^-14) and WHR adjusted for BMI (OR = 1.42, P = 6.11 × 10^-15). The heterogeneous associations of waist circumference (OR = 1.64, P = 5.57 × 10^-14) and hip circumference (OR = 1.20, P = 0.002) on GDM further reflected that body fat distribution could influence GDM risk. Mediation analysis suggested that triglycerides, high-density lipoprotein-cholesterol and apolipoprotein A-I each mediated between 5% and 10% of the association between obesity and GDM.

Conclusion: Our findings supported a deleterious causal effect of obesity on GDM risk, where lipid metabolism acted as potential drivers of the relationships between both general and central obesity and GDM.

Keywords: Gestational diabetes mellitus; High-density lipoprotein cholesterol; Low-density lipoprotein cholesterol; Obesity; Triglycerides.

MeSH terms

Body Mass Index
Diabetes, Gestational* / genetics
Female
Genome-Wide Association Study
Humans
Mendelian Randomization Analysis
Obesity / genetics
Obesity, Abdominal
Polymorphism, Single Nucleotide
Pregnancy
Risk Factors