Childhood obesity linked to higher risk for most type 2 diabetes subtypes in adulthood
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Key takeaways:
- Genetic variations linked to childhood obesity are associated with a higher likelihood for four common type 2 diabetes subtypes.
- The findings emphasize the importance of reducing the burden of childhood obesity.
People with a genetic risk factor for childhood obesity have increased likelihood of developing most subtypes of type 2 diabetes as adults, according to findings from a Mendelian randomization published in Diabetologia.
“The prevalence of childhood overweight and obesity is increasing worldwide,” Yuxia Wei, MSc, a PhD student in the unit of epidemiology, Institute of Environmental Medicine at Karolinska Institutet in Stockholm, Sweden, told Healio. “The clinical implication of our findings is that it is important to prevent overweight and obesity in children since this may have such long-term detrimental effects on their health, affecting the risk of disease that develops at middle age and older. Furthermore, effective intervention that prevents obese children from becoming obese adults will result in major health gains.”
Wei and colleagues conducted a two-sample Mendelian randomization using data from genome-wide association studies (GWAS) of obesity and diabetes subtypes in adults. Data from a study of 453,169 people in Europe who self-reported body size at age 10 years in the UK Biobank were used for childhood body size. Data on adult BMI were collected from a GWAS of 359,983 adults in the UK Biobank. Data on novel diabetes subtypes were mostly obtained from a GWAS conducted in Sweden, with the study including 3,937 adults with severe insulin-deficient diabetes, 3,874 with severe insulin-resistant diabetes, 4,118 with mild obesity-related diabetes and 5,605 with mild-age related diabetes. Data from another study of adults with latent autoimmune diabetes in adults were collected from 8,581 people in Europe.
Researchers identified 275 single nucleotide polymorphisms (SNPs) associated with childhood body size that were included in the diabetes GWAS. An inverse-variance weighted Mendelian randomization was used as the main estimator for assessing associations between SNPs linked to childhood obesity and diabetes subtypes. Four other Mendelian randomization methods were also used for supplemental analysis.
Researchers observed that children who had a SNP for childhood obesity are more likely to develop latent autoimmune diabetes (OR = 1.62; 95% CI, 1.05-2.52), severe insulin-deficient diabetes (OR = 2.11; 95% CI, 1.18-3.8), severe insulin-resistant diabetes (OR = 2.76; 95% CI, 1.6-4.75) and mild obesity-related diabetes (OR = 7.3; 95% CI, 4.17-12.78) than those without a genetic risk factor. No increased risk was observed for mild age-related diabetes. The associations were consistent across multiple Mendelian randomization methods, and no major change was observed when a SNP was left out of the analysis.
“Childhood obesity is closely linked to insulin resistance and obesity in adults,” Wei said. “It is therefore not out of expectation that childhood obesity is associated with increased risks of mild obesity-related diabetes and severe insulin-resistant diabetes. But what surprises us is that childhood obesity also increases the risks of developing the diabetes subtypes dominated by severe autoimmunity and severe insulin deficiency.”
Childhood body size was genetically correlated with mild obesity-related diabetes (r = 0.282; P < . 001), but not other subtypes. Adult BMI was genetically correlated with all four diabetes subtypes, with the highest correlation with mild obesity-related diabetes (r = 0.761; P < . 001).
“It is now increasingly clear that diabetes in adults is a very heterogenous condition,” Wei said. “New research suggests that type 2 diabetes consists of several subtypes with different clinical and genetic characteristics. The risk of complications also seems to differ across such subtypes. Whether the influence is modifiable remains to be investigated. This study is a first attempt to shed light on this, and even though we find that childhood adiposity affects most of these subtypes, the strengths of these associations differ. Thus, it seems that intervening on childhood obesity will prevent a larger proportion of the obese and insulin resistant-related cases, and fewer diabetes cases that are characterized by insulin deficiency or autoimmunity. Further research into this area is clearly warranted.”
For more information:
Yuxia Wei, MSc, can be reached at yuxia.wei@ki.se.
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