Babies born with a low birthweight were more likely to develop type 2 diabetes in adulthood, and the relationship between the two might be causal, according to recent findings.
For every one point increase in genetic risk score for low birthweight, there was an associated 6% higher risk of type 2 diabetes (95% CI 3%-9%), according to lead author Lu Qi, MD, PhD, of the Tulane University School of Public Health and Tropical Medicine in New Orleans, and colleagues. They published their findings on Thursday in Diabetologia.
The authors also reported that for every one standard deviation of lower birthweight, the Mendelian randomization odds ratio was 2.94 (95% CI 1.70-5.16; P<0.001), providing support for the hypothesis that there is a causal relationship between a lower birthweight and an increased risk for developing type 2 diabetes.
"The relation between prenatal growth retardation, which may be caused by malnutrition or other stresses, and later life diabetes risk is probably causal," Qi said in an email to MedPage Today acknowledging what he felt were the most important findings of the study. He went on to explain that healthcare professionals could implement more diet and lifestyle interventions aimed at improving prenatal growth. Such interventions would hopefully play a role in lowering the risk for diabetes later on.
Data for the study were gathered from both the Nurses' Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS). The number of participants totaled 3,627, all of whom had type 2 diabetes on the basis of standard criteria. In a meta-analysis of individuals from both studies, the genetic risk score was determined using five single nucleotide polymorphisms (SNPs), all of which were genetic variations related to low birthweight.
The genetic risk scores ranged from 1 to 10, and were calculated based on the five SNPs, which a previous genome-wide association study (GWAS) found were associated with birthweight.
There were multiple steps in assessing the causality between being genetically defined as having a low birthweight and developing type 2 diabetes. First, the association between the overall genetic risk score and individual SNPs and type 2 diabetes was analyzed. Second, a Mendelian randomization analysis was performed.
In analyzing the association between genetic risk score and individual SNPs with type 2 diabetes, the researchers assigned median values of birthweight categories and used a linear model to observe the hypothesized relationships. Based on these results, they then performed the Mendelian randomization analysis and determined that low birthweight could potentially be a cause for an elevated risk for type 2 diabetes.
Type 2 diabetes was determined based on self-reports, and covariates such as smoking cigarettes, drinking alcohol, and doing physical activity were all assessed.
While previous studies have suggested a link between intrauterine malnutrition and type 2 diabetes, this study is unique in that it suggests a link that is specifically causal. Due to covariates including socioeconomic and lifestyle factors, it can be difficult to prove that causality does indeed exist.
The authors noted that the association found between increases in genetic risk score and risk of type 2 diabetes was shown to be stronger among female participants (OR 1.09; 95% CI 1.05-1.13) than among male participants (OR 1.02; 95% CI 0.97-1.07). They also proposed that maybe it is not the low birthweight itself that causes type 2 diabetes, but "the exposures influencing intrauterine growth" that cause development of the disease.
Qi and colleagues noted limitations of the study, including that the participants were all white, so the findings may not be generalizable. They also addressed some of the drawbacks of their Mendelian randomization analysis. For instance, they used the five individual SNPs as opposed to an overall genetic risk score as an instrumental variable in the statistical assessment. Another limitation they referenced was the relatively small sample size that they used in performing the Mendelian randomization act.
"Future studies with larger sample sizes are warranted to confirm the findings," concluded the authors.
The authors received support from the National Institutes of Health; the National Heart, Lung, and Blood Institute; the National Institute of Diabetes and Digestive and Kidney Diseases. Grants were provided by the United States-Israel Binational Science Foundation; and the American Heart Association.
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