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Genetic predisposition to type 2 diabetes linked to mortality risk
Individuals who carry more type 2 diabetes risk-increasing alleles appear to have a higher mortality risk, indicating that a higher genetic predisposition for type 2 diabetes may increase mortality risk.
Aaron Leong, MD, research fellow in medicine at Massachusetts General Hospital in Boston, and colleagues evaluated data from 6,501 individuals (2,528 whites; 1,979 blacks; 1,994 Mexican Americans) enrolled in the Third National Health and Nutrition Examination Survey to determine whether type 2 diabetes-related genetic variants predict all-cause mortality.
Aaron Leong
Researchers successfully genotyped 38 type 2 diabetes-related single nucleotide polymorphisms (SNPs) or proxies with ORs of at least 1.05 for type 2 diabetes. The researchers modeled type 2 diabetes risk using a genetic risk score (GRS) consisting of the SNPs and age-, sex- and BMI-adjusted logistic regression models to evaluate the relationship between GRS and mortality. The analysis was repeated within ethnicities and within BMI categories.
The researchers found that over the course of 17 years, 19.1% of participants died with cardiovascular disease identified as the leading cause of death (39.2%) followed by cancer (21.2%). Those with BMI at least 30 kg/m2 had a higher rate of death (15.7 deaths per 1,000 person-years) compared with those with BMI less than 25 kg/m2 (8.1 deaths per 1,000 person-years).
An association was found between baseline type 2 diabetes status and increased risk for mortality over follow-up (OR = 1.69; 95% CI, 1.21-2.36). Mortality risk was linked with GRS (P = .05 per type 2 diabetes-associated risk allele). These effect estimates remained constant in whites and blacks, but not Mexican Americans; adjusting for baseline type 2 diabetes did not significantly influence the effect estimates. After adjusting for family history, educational attainment, insurance coverage, Healthcare Eating Index, physical activity, smoking, alcohol consumption, total cholesterol, HDL cholesterol, hypertension and waist circumference, the negative trend in Mexican Americans persisted.
In the analysis stratified by BMI, a slightly higher mortality risk per allele was seen in whites with obesity (OR = 1.07; 95% CI, 1.02-1.12) compared with normal-weight whites. A negative trend was found between GRS per allele and mortality risk in normal-weight Mexican Americans (OR = 0.91; 95% CI, 0.82-1).
“The underlying genetic basis of mortality likely involves complex interactions with nongenetic factors related to ethnicity, [type 2 diabetes] or body weight,” the researchers wrote. “In the midst of a [type 2 diabetes] and obesity co-epidemic from an increasingly obesogenic environment, maintaining a normal body weight may be especially important for lowering mortality risk in individuals with a high genetic predisposition to [type 2 diabetes].” – by Jennifer Byrne
Disclosure: The researchers report no relevant financial disclosures.