Roles of insulin resistance and beta cell dysfunction in macrosomia among Chinese women with gestational diabetes mellitus

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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Association Between a Melatonin Receptor 1B Genetic Polymorphism and Its Protein Expression in Gestational Diabetes Mellitus

Reproductive Sciences ◽

10.1177/1933719118765983 ◽

2018 ◽

Vol 26 (10) ◽

pp. 1382-1388 ◽

Cited By ~ 3

Author(s):

Chao Li ◽

Yubin Zhou ◽

Binglong Qiao ◽

Lin Xu ◽

Yan Li ◽

...

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Genetic Polymorphism ◽

Gestational Diabetes ◽

Protein Expression ◽

Gestational Diabetes Mellitus ◽

Chinese Women ◽

Han Chinese ◽

Melatonin Receptor ◽

Melatonin Receptor 1B

Aims: This study was conducted to investigate the relationship between a genetic polymorphism and the expression of melatonin receptor 1B (MTNR1B) in the placenta of Han Chinese women with gestational diabetes mellitus (GDM). Methods: In this study, 215 patients with GDM and 243 healthy controls were genotyped using direct sequencing for the MTNR1B single-nucleotide polymorphism rs10830963. The expression of MTNR1B in placenta was detected by immunohistochemistry and Western blotting. The association of rs10830963 with the expression of MTNR1B, plasma glucose, and insulin levels as well as blood lipid levels was investigated. Results: The genotype and allele frequencies of rs10830963 were significantly different between women with GDM and controls ( P < .05). Fasting blood glucose, fasting insulin, and homeostasis model assessment for insulin resistance in women with GDM with the GG and GC genotypes were significantly higher than those with the CC genotype ( P < .05). The expression level of MTNR1B in placenta was significantly higher in the GDM group than in the control group ( P < .05). The expression of MTNR1B was significantly higher in all participants with the GG and GC genotypes (1.31 [0.74]) than in pregnant women with the CC genotype (0.92 [0.52], P < .05). Conclusions: The genetic polymorphism rs10830963 in MTNR1B and its protein expression levels in placenta are associated with an increased risk of developing GDM. Furthermore, rs10830963 may tag a molecular mechanism leading to insulin resistance in Han Chinese women with GDM.

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Role of beta-cell dysfunction, ectopic fat accumulation and insulin resistance in the pathogenesis of type 2 diabetes mellitus

Diabetes Research and Clinical Practice ◽

10.1016/s0168-8227(11)70015-8 ◽

2011 ◽

Vol 93 ◽

pp. S60-S65 ◽

Cited By ~ 58

Author(s):

Amalia Gastaldelli

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Beta Cell ◽

Beta Cell Dysfunction ◽

Ectopic Fat ◽

Cell Dysfunction

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Glucose homeostasis, beta cell function, and insulin resistance in relation to vitamin D status after gestational diabetes mellitus

Acta Obstetricia Et Gynecologica Scandinavica ◽

10.1111/aogs.13124 ◽

2017 ◽

Vol 96 (7) ◽

pp. 821-827 ◽

Cited By ~ 4

Author(s):

Nael Shaat ◽

Claes Ignell ◽

Anastasia Katsarou ◽

Kerstin Berntorp

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Vitamin D ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Beta Cell ◽

Glucose Homeostasis ◽

Beta Cell Function ◽

Cell Function ◽

Vitamin D Status

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Abstract MP70: Pre-pregnancy Beta Cell Compensation for Insulin Resistance Associated With Subsequent Gestational Diabetes Mellitus: The CARDIA Study

Circulation ◽

10.1161/circ.137.suppl_1.mp70 ◽

2018 ◽

Vol 137 (suppl_1) ◽

Author(s):

Erica P Gunderson ◽

Amy Krefman ◽

Cora E Lewis ◽

Janet Catov ◽

Norrina B Allen

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Family History ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Beta Cell ◽

Pancreatic Beta Cell ◽

Family History Of Diabetes ◽

History Of ◽

Beta Cell Compensation

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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