Low Birth Weight Associated With Increased Type 2 Diabetes Risk

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The findings validate the inverse association between birth weight and type 2 diabetes.
The findings validate the inverse association between birth weight and type 2 diabetes.

A genetically lowered birth weight may be associated with an increased susceptibility to type 2 diabetes, according to recent data published in Diabetologia. The findings support a potential causal relationship between birth weight and risk for type 2 diabetes.

Lu Qi, MD, PhD, from the department of epidemiology at the Tulane University School of Public Health and Tropical Medicine, and colleagues sought to determine whether the genetic predisposition to low birth weight was associated with type 2 diabetes.

Researchers included 3627 individuals with type 2 diabetes and 12,974 control participants from the Nurses' Health Study and the Health Professionals Follow-Up Study. They calculated the genetic risk score (GRS) based on 5 single nucleotide polymorphisms (SNPs) related to low birth weight.

Using the GRS, they assessed the evidence for causality by examining the association of the score and the individual SNPs with type 2 diabetes. The researchers also performed a Mendelian randomization analysis to estimate the potentially casual effect size of low birth weight on type 2 diabetes.

“We found an association between the overall genetic susceptibility to low birth weight, which was estimated by a GRS, and an increased risk of type 2 diabetes,” the authors noted. “We further applied the Mendelian randomization approach to provide supportive evidence for the causality, and the findings were confirmed using the summary statistics from the latest GWAS [genome-wide association studies].”

The researchers found that each 1-point increment in the GRS was associated with a 6% higher risk of type 2 diabetes (95% CI, 3-9). Of the SNPs that were tested, CCNLI rs900400 (odds ratio [OR], 1.09; 95% CI, 1.03-1.16) and 5q11.2 rs4432842 (OR, 1.09; 95% CI, 1.02-1.16) showed dose-response associations with risk of type 2 diabetes.

The overall Mendelian randomization analysis yielded an OR of 2.94 (95% CI, 1.70-5.16; P<.001) for type 2 diabetes per 1 standard deviation lower genetically determined birth weight. The researchers noted that the Mendelian randomization analysis was relatively small, and that future studies should be conducted with larger sample sizes to confirm the findings.

“In conclusion, we demonstrated that genetically lowered birth weight was associated with an increased risk of type 2 diabetes,” the authors wrote. “Our findings validate the epidemiological observation of an inverse association between birth weight and type 2 diabetes, and provide new evidence of a role for intrauterine exposures in the pathogenesis of type 2 diabetes.”

Disclosures: The researchers report no conflicts of interest.


  1. Wang T, Huang T, Li Y, et al. Low birthweight and risk of type 2 diabetes: a Mendelian randomization study. Diabetologia. 2016. doi:10.1007/s00125-016-4019-z.
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