Higher Genetic Risk for Type 2 Diabetes Linked to Increased Mortality Risk

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The genetic basis for mortality risk likely consists of factors related to type 2 diabetes, ethnicity, and body weight.
The genetic basis for mortality risk likely consists of factors related to type 2 diabetes, ethnicity, and body weight.

Risk for mortality may be increased among people with a higher genetic risk for type 2 diabetes, particularly obese non-Hispanic white individuals, according to research recently published in Diabetes Care.

Type 2 diabetes has been previously associated with increased mortality among ethnically diverse populations. However, it has not been determined whether there is a genetic association between type 2 diabetes and mortality risk.

Researchers investigated whether genetic variants associated with type 2 diabetes could predict all-cause mortality. They measured mortality risk using a genetic risk score, which was calculated from a weighted sum of risk alleles from 38 nucleotide polymorphisms related to type 2 diabetes. They tested the association of type 2 diabetes and mortality in 6501 participants, using logistic regression models to adjust for age, sex, and BMI.

The analysis was repeated within ethnicities, including 2528 non-Hispanic white individuals, 1979 non-Hispanic black individuals, and 1994 Mexican American individuals. The analysis was also repeated within BMI categories (less than 25, 25 to 30, and greater than 30; P<.05).

After 17 years, 1556 deaths were observed and the genetic risk scores were associated with increased mortality risk (odd ratio [OR]=1.04 per type 2 diabetes-associated risk allele; 95% CI, 1.00-1.07; P=.05).

“In the midst of a [type 2 diabetes] and obesity coepidemic 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],” the authors wrote.

The genetic risk scores were also positively associated with mortality risk in non-Hispanic white individuals and non-Hispanic black individuals, but not among Mexican American individuals (OR=0.95; 95% CI, 0.90-1.01; P=.07). The researchers note that the negative trend among Mexican American individuals was likely due to those with a BMI  less than 25 (OR=0.91; 95% CI, 0.82-1.00; P=.06).

In non-Hispanic white individuals, the association was strongest among participants with a BMI of at least 30 (OR=1.07; 95% CI, 1.02-1.12; P=.01).

The results suggest that the genetic basis for mortality risk likely consists of complex interactions of factors related to type 2 diabetes, ethnicity, and body weight.

“Lifestyle intervention studies targeting weight loss could consider the influence of genetic variation on clinical response and clinical outcomes,” the authors noted. “Future genetic-environment interaction studies may clarify the mechanisms underlying the heterogeneous effects of [type 2 diabetes]-related genetic variants on mortality by ethnicity and BMI, and inform lifestyle intervention strategies directed at those with stronger genetic susceptibility to [type 2 diabetes]-related mortality.”

Reference

  1. Leong A, Porneala B, Dupuis J, Florez JC, Meigs JB. Type 2 Diabetes Genetic Predisposition, Obesity, and All-Cause Mortality Risk in the United States: A Multiethnic Analysis. Diabetes Care. 2016;39. doi:10.2337/dc15-2080.
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