Abstract
ABSTRACTBackgroundWhether genetic susceptibility to type 2 diabetes is modified by a healthy lifestyle among Chinese remains unknown.ObjectivesThe aim of the study was to determine whether genetic risk and adherence to a healthy lifestyle contribute independently to the risk of developing type 2 diabetes.MethodsWe defined a lifestyle score using BMI, alcohol intake, smoking, physical activities, and diets in 461,030 participants from the China Kadoorie Biobank and 38,434 participants from the Singapore Chinese Health Study. A genetic risk score was constructed based on type 2 diabetes loci among 100,175 and 16,172 participants in each cohort, respectively. A Cox proportional-hazards model was used to estimate the interaction between genetic and lifestyle factors on the risk of type 2 diabetes.ResultsIn 2 independent Asian cohorts, we consistently found a healthy lifestyle (the bottom quintile of lifestyle score) was associated with a substantially lower risk of type 2 diabetes than an unhealthy lifestyle (the top quintile of lifestyle score) regardless of genetic risk. In those at a high genetic risk, the risk of type 2 diabetes was 57% lower among participants with a healthy lifestyle than among those with an unhealthy lifestyle in the pooled cohorts. Among participants at high genetic risk, the standardized 10-y incidence of type 2 diabetes was 7.11% in those with an unhealthy lifestyle vs. 2.45% in those with a healthy lifestyle.ConclusionsIn 2 independent cohorts involving 558,302 Chinese participants, we did not observe an interaction between genetics and lifestyle with type 2 diabetes risk, but our findings provide replicable evidence to show lifestyle factors and genetic factors were independently associated with the risk of type 2 diabetes. Within any genetic risk category, a healthy lifestyle was associated with a significantly lower risk of type 2 diabetes among the Chinese population.
Highlights
Over the past several decades, the diabetes burden has increased rapidly around the world [1]
Our study showed that a higher lifestyle score was significantly associated with a higher risk of type 2 diabetes with a dose–response relation within each cohort (Supplemental Figures 4, 5)
We observed that participants in the bottom quintile of the lifestyle score, as compared with participants in the top quintile of the lifestyle score, were at significantly lower risk of type 2 diabetes, with adjusted HRs of 0.30 in the China Kadoorie Biobank (CKB), 0.41 in the Singapore Chinese Health Study (SCHS), and 0.30 in the pooled cohorts (Table 2)
Summary
Over the past several decades, the diabetes burden has increased rapidly around the world [1]. The number of diabetes cases continues to increase in China, which has the largest diabetic population in the world [2,3,4] It is well-known that type 2 diabetes is caused by both genetic and lifestyle factors [5, 6]. It has been documented that genetic risk score (GRS), calculated based on the identified risk alleles, is predictive of incident type 2 diabetes and provides a continuous and quantitative measure of genetic susceptibility [8]. Results: In 2 independent Asian cohorts, we consistently found a healthy lifestyle (the bottom quintile of lifestyle score) was associated with a substantially lower risk of type 2 diabetes than an unhealthy lifestyle (the top quintile of lifestyle score) regardless of genetic risk.
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