Obesity, lifestyle influence type 2 diabetes risk regardless of genetic factors
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Adults with obesity and unfavorable lifestyle factors are more likely to develop type 2 diabetes during 15 years of follow-up than those without excess weight and favorable lifestyle factors, regardless of their genetic predisposition for the disease, according to findings published in Diabetologia.
“Obesity and unfavorable lifestyle are associated with increased risk of incident type 2 diabetes irrespective of genetic risk,” Hermina Jakupovi, MSc, a doctoral student at the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen, told Healio. “Weight management by healthy lifestyle should be recommended as a prevention strategy regardless of genetic predisposition to type 2 diabetes.”
In a case-cohort study nested within the Diet, Cancer and Health cohort in Denmark, Jakupovi and colleagues analyzed data from 4,729 adults recruited between 1993 and 1997 who developed type 2 diabetes during a median 14.7 years of follow-up (mean age, 57 years; 45.6% women), and a randomly selected cohort of 5,402 adults (mean age, 56 years; 49.6% women). All participants underwent genotyping; researchers quantified a genetic risk score comprising 193 known type 2 diabetes-associated loci (excluding known BMI loci) and stratified participants by genetic risk quintiles. Researchers assessed smoking status, alcohol consumption, physical activity and diet to compile a lifestyle score. Researchers used Cox proportional-hazard models to test associations of genetic risk score, obesity and lifestyle score with incident type 2 diabetes, as well as the interactions of the genetic risk score with obesity and unfavorable lifestyle in relation to incident type 2 diabetes.
Compared with adults with low genetic risk for type 2 diabetes, those with a high genetic risk score were twice as likely to develop type 2 diabetes during follow-up (HR = 2; 95% CI, 1.76-2.27). Adults with an unfavorable lifestyle score were 18% more likely to develop type 2 diabetes compared with those who had a favorable lifestyle score (HR = 1.18; 95% CI, 1.06-1.3). Compared with adults with a normal BMI, those with obesity had a 5.8-fold increased risk for developing type 2 diabetes during follow-up (HR = 5.81; 95% CI, 5.16-6.55).
Researchers found that participants who had obesity, a high genetic risk score and unfavorable lifestyle were more than 14 times more likely to develop type 2 diabetes during follow-up vs. those with normal weight, a low genetic risk score and favorable lifestyle.
“Notably, even among individuals with low genetic risk score and favorable lifestyle, obesity was strongly associated with higher type 2 diabetes risk with an HR of 8.44 (95% CI, 5.43-13.14) compared with normal-weight individuals in the same genetic risk score and lifestyle stratum,” the researchers wrote.
The researchers also noted that receiver operating characteristic analyses suggested that genetic risk score and lifestyle score offer “very little predictive utility” for predicting type 2 diabetes risk when added to BMI, age and sex.
“Similar longitudinal analyses need to be performed in populations of all genetic ancestries, not just Europeans, to gain more knowledge in this area,” Jakupovi said. “Analyses with bigger study populations, with data as detailed as in the cohort used here, would also be helpful.” – by Regina Schaffer
For more information:
Hermina Jakupovi, MSc, can be reached at the University of Copenhagen, Novo Nordisk Foundation Center for Basic Metabolic Research, Blegdamsvej 3B, Building 7 (Maersk tower), Copenhagen 2200, Denmark; email: hermina.jakupovic@sund.ku.dk.
Disclosures: The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent research center at the University of Copenhagen, partially funded by an unrestricted donation from the Novo Nordisk Foundation. One study author was supported by the Danish Council for Independent Research and the Novo Nordisk Foundation. Three of the study authors were supported by the Danish Diabetes Academy, which is funded by the Novo Nordisk Foundation.
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Schnurr TM, et al. Diabetologia. 2020;doi:10.1007/s00125-020-05140-5.
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