Obese Individuals Nearly 6 Times More Likely to Develop T2D, Study Finds

Obesity increases the risk of developing type 2 diabetes (T2D) regardless of genetic predisposition to the disease, according to a study published in Diabetologia. These findings emphasize that having a normal body weight is crucial to prevent T2D.

Researchers examined obesity, lifestyle factors, and genetic risk of T2D in 4729 participants of the Danish Diet, Cancer and Health cohort, a study established in 1993 comprising of 57,053 Danish citizens. The 4729 individuals all developed T2D during a median follow-up time of 14.7 years. In addition, a randomly selected sub-cohort sample of 5402 controls was also included in the study, of whom 575 developed incident T2D.

To quantify genetic predisposition, researchers used a genetic risk score (GRS) comprising of 193 known T2D associated loci and stratified participants into low (quintile 1), intermediate, and high (quintile 5) genetic risk groups. Lifestyle quality was measured by the presence of smoking and alcohol consumption, along with examination of physical activity and diet. Body mass index (BMI) was used to determine obesity.

Researchers found “compared with people of normal weight, those with obesity were almost 6 times more likely to develop T2D, while people who were overweight had a 2.4 times increased risk,” according to a statement.

Hazard ratios (HRs) for development of incident T2D were determined for the following characteristics:

• High genetic risk: HR of 2.00; 95% CI 1.76, 2.27
• Intermediate genetic risk: HR of 1.49; 95% CI 1.34, 1.66
• Unfavorable lifestyle: HR of 1.18; 95% CI 1.06, 1.30
• Intermediate lifestyle: HR of 1.10; 95% CI 1.00, 1.20
• Overweight: HR of 2.37; 95% CI 2.15, 2.62
• Obese: HR of 5.81; 95% CI 5.16, 6.55

In addition, researchers found “individuals who ranked high for all 3 risk factors, with obesity, high GRS, and unfavorable lifestyle, had a 14.5 times increased risk of developing T2D, compared with individuals who had a normal body weight, low GRS, and favorable lifestyle (95% CI 8.09, 26.13)."

No significant interactions were found between GRS and continuous BMI (P = .35) or lifestyle score (P = .72) on development of T2D. Data also showed a greater than 8-fold increase in risk of T2D in obese individuals who, despite being overweight, led a favorable lifestyle.

“We found that the effect of obesity on T2D risk is dominant over other risk factors, highlighting the importance of weight management in T2D prevention,” researchers concluded.

Reference:

Schnurr TM, Jakupović H, Carrasquilla GD, et al. Obesity, unfavorable lifestyle and genetic risk of type 2 diabetes: a case-cohort study [published online April 15, 2020]. Diabetologia. doi: 10.1007/s00125-020-05140-5.