MedWire News: Carriers of the obesity-associated allele of 12 single nucleotide polymorphisms previously linked to variation in body mass index (BMI) are at increased risk for Type 2 diabetes, suggest study findings.
The researchers note that the association became nonsignificant after adjustment for BMI, suggesting that any increase in diabetes risk is "completely mediated by its obesity predisposing effect."
Ruth Loos (Institute of Metabolic Science, Cambridge, UK) and colleagues genotyped 20,428 participants of the European Prospective Investigation of Cancer (EPIC) Norfolk cohort, aged 39-79 years at baseline, for 12 SNPs previously associated with variation in BMI. A combined obesity predisposition score was created by adding up all BMI-increasing alleles present.
The cohort had a mean follow-up period of 12.9 years, during which time 729 individuals reported the onset of Type 2 diabetes.
Of the 12 SNPs genotyped, eight were associated with an increased Type 2 diabetes risk ranging from 2-15% per risk allele carried.
Regarding the obesity predisposition score, each additional BMI-increasing allele carried by the patient was linked to a significant 4% increase in risk for Type 2 diabetes. However, when the researchers adjusted for BMI, the association disappeared, suggesting that elevated BMI is responsible for any increase in diabetes risk.
"Our results suggest that the overall genetic susceptibility to obesity, estimated by the genetic predisposition score, increases susceptibility to Type 2 diabetes," write the authors.
However, they concede that as the genetic predisposition score has been shown to explain less than 1% of the overall variation in BMI in the general population, its influence on Type 2 diabetes risk is likely to be limited.
Loos et al conclude in the journal Diabetologia: "Larger studies will be required to convincingly establish associations between individual SNPs and Type 2 diabetes, and to identify subtle differences between these associations that might enhance our insight into the biological pathways they implicate."
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