Obesity increases type 2 diabetes risk six-fold, regardless of genetics

Organisation: Position: Deadline Date: Location:

Obesity increases the risk of developing type 2 diabetes by at least 6 times, regardless of genetic predisposition to the disease, concludes research. The study is by Dr Theresia Schnurr and Hermina Jakupovi, Novo Nordisk Foundation Centre for Basic Metabolic Research, faculty of health and medical sciences, University of Copenhagen, Denmark, and colleagues.

Using data from a case-cohort study nested within the Diet Cancer and Health cohort in Denmark, the authors examined the joint association of obesity, genetic predisposition, and unfavourable lifestyle with incident type 2 diabetes (T2D). The study sample included 4,729 individuals who developed type 2 diabetes during a median 14.7 years of follow-up, and a randomly selected cohort sample of 5,402 individuals (the control group).

The mean age of all participants was 56.1 years (range 50-65) and 49.6% were women. Overall, 21.8% of all participants were classified as obese, 43.0% as overweight and 35.2% as having normal weight; and 40.0% of the participants had a favourable lifestyle, 34.6% had an intermediate lifestyle and 25.4% had an unfavourable lifestyle.

Genetic predisposition was quantified using a genetic risk score (GRS) comprising 193 known type 2 diabetes-associated genetic variants and divided into 5 risk groups of 20% each (quintiles), from lowest (quintile 1) to highest (quintile 5) genetic risk. Lifestyle was assessed by a lifestyle score composed of smoking, alcohol consumption, physical activity and diet. Statistical modelling was used to calculate the individual and combined associations of the GRS, obesity and lifestyle score with developing T2D.

Compared with people of normal weight, those with obesity were almost six times more likely to develop T2D, while people who were overweight had a 2.4 times increased risk. For genetic risk, those with the highest GRS were twice as likely to develop T2D as those with the lowest, while those with the unhealthiest lifestyle were 18% more likely to develop T2D than those with the healthiest.

Individuals who ranked high for all three risk factors, with obesity, high GRS and unfavourable lifestyle, had a 14.5 times increased risk of developing T2D, compared with individuals who had a normal body weight, low GRS and favourable lifestyle. Notably, even among individuals with a low GRS and favourable lifestyle, obesity was associated with 8.4 times increased risk of T2D compared with normal weight individuals in the same genetic and lifestyle risk group.

The authors conclude: “The results suggest that type 2 diabetes prevention by weight management and healthy lifestyle is critical across all genetic risk groups. Furthermore, we found that the effect of obesity on type 2 diabetes risk is dominant over other risk factors, highlighting the importance of weight management in type 2 diabetes prevention.”

Abstract
Aims/hypothesis: We aimed to investigate whether the impact of obesity and unfavourable lifestyle on type 2 diabetes risk is accentuated by genetic predisposition.

Methods: We examined the joint association of genetic predisposition, obesity and unfavourable lifestyle with incident type 2 diabetes using a case-cohort study nested within the Diet, Cancer and Health cohort in Denmark. The study sample included 4729 individuals who developed type 2 diabetes during a median 14.7 years of follow-up, and a randomly selected cohort sample of 5402 individuals. Genetic predisposition was quantified using a genetic risk score (GRS) comprising 193 known type 2 diabetes-associated loci (excluding known BMI loci) and stratified into low (quintile 1), intermediate and high (quintile 5) genetic risk groups. Lifestyle was assessed by a lifestyle score composed of smoking, alcohol consumption, physical activity and diet. We used Prentice-weighted Cox proportional-hazards models to test the associations of the GRS, obesity and lifestyle score with incident type 2 diabetes, as well as the interactions of the GRS with obesity and unfavourable lifestyle in relation to incident type 2 diabetes.
Results: Obesity (BMI ≥ 30 kg/m2) and unfavourable lifestyle were associated with higher risk for incident type 2 diabetes regardless of genetic predisposition (p > 0.05 for GRS–obesity and GRS–lifestyle interaction). The effect of obesity on type 2 diabetes risk (HR 5.81 [95% CI 5.16, 6.55]) was high, whereas the effects of high genetic risk (HR 2.00 [95% CI 1.76, 2.27]) and unfavourable lifestyle (HR 1.18 [95% CI 1.06, 1.30]) were relatively modest. Even among individuals with low GRS and favourable lifestyle, obesity was associated with a >8-fold risk of type 2 diabetes compared with normal-weight individuals in the same GRS and lifestyle stratum.
Conclusions/interpretation: Having normal body weight is crucial in the prevention of type 2 diabetes, regardless of genetic predisposition.

Authors
Theresia M Schnurr, Hermina Jakupović, Germán D Carrasquilla, Lars Ängquist, Niels Grarup, Thorkild IA Sørensen, Anne Tjønneland, Kim Overvad, Oluf Pedersen, Torben Hansen, Tuomas O Kilpeläinen

Diabetologia material

Diabetologia abstract

Receive Medical Brief's free weekly e-newsletter



Related Posts

Thank you for subscribing to MedicalBrief


MedicalBrief is Africa’s premier medical news and research weekly newsletter. MedicalBrief is published every Thursday and delivered free of charge by email to over 33 000 health professionals.

Please consider completing the form below. The information you supply is optional and will only be used to compile a demographic profile of our subscribers. Your personal details will never be shared with a third party.


Thank you for taking the time to complete the form.