Obesity, unfavourable lifestyle and genetic risk of type 2 diabetes: a case-cohort study
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/m 2) 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.
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Some factors are also related to obesity comorbidities such as fatty liver diseases and type 2 diabetes.
“Some are also related to obesity comorbidities such as fatty liver diseases [6] and type 2 diabetes [7,8].”
From Identification of factors associated with sarcopenic obesity development: Literature review and expert panel voting (2024) · cites this paper as [8]
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References 29 · Cited by 231
- Authors
- Schnurr, T. M., Jakupović, H., Carrasquilla, G. D., Ängquist, L., Grarup, N., Sørensen, T. I. A., Tjønneland, A., Overvad, K., Pedersen, O., Hansen, T., & Kilpeläinen, T. O.
- Affiliations
- University of Copenhagen (DK)
- Aarhus University (DK)
- Corresponding author
- Jakupović, Hermina
- ORCID
- Venue
- Diabetologia
- Published
- 2020-04-15
- Volume
- 63
- Issue
- 7
- Pages
- 1324-1332
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W3016191918
- Cited by
- 231
- References
- 29
- Citations by year
- 2026: 16 · 2025: 38 · 2024: 36 · 2023: 56 · 2022: 35 · 2021: 38 · 2020: 11
- FWCI
- 20.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- VBN Forskningsportal (Aalborg Universitet) (submittedVersion)
- Funders
- Det Frie Forskningsråd (DFF – 1333-00124, DFF – 1331-00730B)
- Danish Diabetes Academy (NNF17SA0031406)
- Novo Nordisk Foundation (NNF18CC0034900, Sapere Aude program grant NNF17OC0)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Nutrition, Genetics, and Disease
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- type 2 diabetes, obesity, genetic susceptibility, polygenic risk score, gene-environment interaction, lifestyle score, smoking, alcohol consumption, physical activity, diet, body weight, diabetes prevention
- MeSH terms
- Alcohol Drinking, Body Weight, Diabetes Mellitus, Type 2, Humans, Life Style, Obesity, Risk Factors, Smoking, Cohort Studies, Exercise, Genetic Predisposition to Disease
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