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Higher Serum Bilirubin Levels in Response to Higher Carbohydrate Intake During Early Pregnancy and Lower Gestational Diabetes Mellitus Occurrence in Overweight and Obese Gravidae.

ABSTRACT: Background and Aim: Serum bilirubin levels are recently shown to be a novel protector of gestational diabetes mellitus (GDM), yet whether they could be affected by carbohydrate quality is unclear. We aimed to examine the associations between dietary carbohydrate parameters and serum bilirubin levels during early pregnancy, with further exploration on a potential mediating role of serum bilirubin levels on carbohydrate parameters-GDM pathways. Methods: 260 healthy but overweight or obese gravidae (BMI ≥24 kg/m²) derived from a historical cohort in two hospitals in China were included. The associations between carbohydrate parameters (total carbohydrate intake, glycemic index GI, fiber intake, glycemic load GL) and serum bilirubin levels (total bilirubin, TB and direct bilirubin, DB) and GDM were evaluated by multivariable regression analysis. Generalized structural equation modeling was then applied to perform adjusted mediation analysis. Results: Increased serum bilirubin levels (mmol/L) and decreased GDM occurrence were observed following dietary carbohydrate intake (%E) and GL (g/1,000 kcal) in highest tertile compared to the lowest tertile [carbohydrate: TB: β = 0.926 (95%CI: 0.069, 1.782), DB: β = 0.554 (95%CI: 0.192, 0.916);GL:TB: β = 1.170 (95%CI: 0.339, 2.001); DB: β = 0.369 (95%CI: 0.016, 0.700); carbohydrate: adjusted OR = 0.43 (95%CI:0.19-0.99); GL: adjusted OR = 0.36 (95%CI:0.16, 0.84)]. The mediating effect of carbohydrate intake and GL on GDM through bilirubin levels was evaluated as modest (carbohydrate: 6.2% for TB, 1.3% for DB; GL: 8.7% for TB, 2.3% for DB). No association was observed regarding GI and fiber. Conclusions: Mildly elevated serum bilirubin levels appeared to be in response to higher energies consumed from carbohydrate during early pregnancy in healthy overweight or obese gravidae. However, the mediating effect of bilirubin levels on carbohydrate-GDM pathways is not evident. Larger investigation is further needed for solid evidence.

SUBMITTER: He W

PROVIDER: S-EPMC8435579 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Obesity is highly associated with elevated serum triglycerides, hepatic steatosis and type 2 diabetes (T2D). The I148M (rs738409) genetic variant of patatin-like phospholipase domain-containing 3 gene (PNPLA3) is known to modulate hepatic triglyceride accumulation, leading to steatosis. No association between PNPLA3 I148M genotype and T2D in Europeans has been reported. Aim of this study is to examine the relationship between PNPLA3 I148M genotypes and serum triglycerides, insulin resistance and T2D susceptibility by testing a gene-environment interaction model with severe obesity.PNPLA3 I148M was genotyped in a large obese cohort, the SOS study (n = 3,473) and in the Go-DARTS (n = 15,448), a T2D case-control study. Metabolic parameters were examined across the PNPLA3 I148M genotypes in participants of the SOS study at baseline and at 2- and 10-year follow up after bariatric surgery or conventional therapy. The associations with metabolic parameters were validated in the Go-DARTS study. Serum triglycerides were found to be lower in the PNPLA3 148M carriers from the SOS study at baseline and from the Go-DARTS T2D cohort. An increased risk for T2D conferred by the 148M allele was found in the SOS study (O.R. 1.09, 95% C.I. 1.01-1.39, P = 0.040) and in severely obese individuals in the Go-DARTS study (O.R. 1.37, 95% C.I. 1.13-1.66, P = 0.001). The 148M allele was no longer associated with insulin resistance or T2D after bariatric surgery in the SOS study and no association with the 148M allele was observed in the less obese (BMI<35) individuals in the Go-DARTS study (P for interaction ?= 0.002). This provides evidence for the obesity interaction with I48M allele and T2D risk in a large-scale cross-sectional and a prospective interventional study.Severely obese individuals carrying the PNPLA3 148M allele have lower serum triglyceride levels, are more insulin resistant and more susceptible to T2D. This study supports the hypothesis that obesity-driven hepatic lipid accumulation may contribute to T2D susceptibility.

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Higher Serum Bilirubin Levels in Response to Higher Carbohydrate Intake During Early Pregnancy and Lower Gestational Diabetes Mellitus Occurrence in Overweight and Obese Gravidae.

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