Genetic variation in MTNR1B is associated with gestational diabetes mellitus and contributes only to the absolute level of beta cell compensation in Mexican Americans

Hypothesis: Gestational diabetes mellitus (GDM) is a disorder of glucose metabolism during pregnancy characterized by pancreatic beta cell dysfunction and greater insulin resistance, but it is unclear whether dysfunction exists before pregnancy. The disposition index (DI) is a physiologic measure of beta cell compensation for insulin resistance strongly predictive of future diabetes. This prospective study evaluates whether a clinical approximation of DI before pregnancy is associated with risk of GDM. Methods: This analysis included 696 women (45% black, 55% white) enrolled in the CARDIA Study, a U.S. multi-center prospective cohort of young adults aged 18-30 at baseline (1985-86) who gave birth at least once during 30 years of follow up, reported GDM status and had fasting glucose and insulin measured before one or more post-baseline births. DI was defined as HOMA-B divided by HOMA-IR using standard formulas. Multinomial logistic regression models estimated odds ratios (OR) and 95%CI for GDM among pre-pregnancy DI tertiles (low, moderate, high) and fully adjusted for time to birth, race, age, parity, BMI, lifestyle behaviors and family history of diabetes, and also stratified by pre-pregnancy BMI. Results: 9% of women reported GDM (64/696) for 794 births. 55% of GDM and 30% of non-GDM were categorized as low DI. Low pre-pregnancy DI compared to moderate DI was associated with higher fully adjusted odds of GDM (OR=2.71, 95%CI:1.37-5.35) in the entire sample. In models stratified by pre-pregnancy BMI, low DI was associated with 4-fold higher odds of GDM among Overweight/Obese (OR=4.22, 95%CI: 1.35-13.91) and somewhat attenuated higher odds of GDM among Normal BMI (OR=1.94, 95%CI: 0.78–4.86); Table 1. Only family history of diabetes was strongly associated with GDM independent of DI. Conclusions: Inadequate beta cell compensation is present before pregnancy and discriminates greatest risk of GDM among high BMI, and may identify higher risk among women of normal BMI.

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Is there a genetic variation association in the IL-10 and TNF α promoter gene with gestational diabetes mellitus?

Hereditas ◽

10.1111/j.1601-5223.2009.02134.x ◽

2010 ◽

Vol 147 (2) ◽

pp. 94-102 ◽

Cited By ~ 19

Author(s):

Shabnam Montazeri ◽

Sivalingam Nalliah ◽

Ammu Kutty Radhakrishnan

Keyword(s):

Diabetes Mellitus ◽

Genetic Variation ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Tnf Α ◽

Promoter Gene

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Genetic variants associated with beta-cell function and insulin sensitivity potentially influence bile acid metabolites and gestational diabetes mellitus in a Chinese population

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2021-002287 ◽

2021 ◽

Vol 9 (1) ◽

pp. e002287

Author(s):

Qiulun Zhou ◽

Ying Wang ◽

Yuqin Gu ◽

Jing Li ◽

Hui Wang ◽

...

Keyword(s):

Diabetes Mellitus ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Beta Cell ◽

Genetic Variants ◽

Cell Function ◽

Chinese Women ◽

Risk Scores ◽

Nucleotide Polymorphisms ◽

Mediation Analyses

IntroductionTo investigate associations between genetic variants related to beta-cell (BC) dysfunction or insulin resistance (IR) in type 2 diabetes (T2D) and bile acids (BAs), as well as the risk of gestational diabetes mellitus (GDM).Research design and methodsWe organized a case-control study of 230 women with GDM and 217 without GDM nested in a large prospective cohort of 22 302 Chinese women in Tianjin, China. Two weighted genetic risk scores (GRSs), namely BC-GRS and IR-GRS, were established by combining 39 and 23 single nucleotide polymorphisms known to be associated with BC dysfunction and IR, respectively. Regression and mediation analyses were performed to evaluate the relationship of GRSs with BAs and GDM.ResultsWe found that the BC-GRS was inversely associated with taurodeoxycholic acid (TDCA) after adjustment for confounders (Beta (SE)=−0.177 (0.048); p=2.66×10−4). The BC-GRS was also associated with the risk of GDM (OR (95% CI): 1.40 (1.10 to 1.77); p=0.005), but not mediated by TDCA. Compared with individuals in the low tertile of BC-GRS, the OR for GDM was 2.25 (95% CI 1.26 to 4.01) in the high tertile. An interaction effect of IR-GRS with taurochenodeoxycholic acid (TCDCA) on the risk of GDM was evidenced (p=0.005). Women with high IR-GRS and low concentration of TCDCA had a markedly higher OR of 14.39 (95% CI 1.59 to 130.16; p=0.018), compared with those with low IR-GRS and high TCDCA.ConclusionsGenetic variants related to BC dysfunction and IR in T2D potentially influence BAs at early pregnancy and the development of GDM. The identification of both modifiable and non-modifiable risk factors may facilitate the identification of high-risk individuals to prevent GDM.

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