Genetic risk, adherence to a healthy lifestyle, and type 2 diabetes risk among 550,000 Chinese adults: results from 2 independent Asian cohorts

ABSTRACT Background Whether genetic susceptibility to type 2 diabetes is modified by a healthy lifestyle among Chinese remains unknown. Objectives The 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. Methods We 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. 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. 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. Conclusions In 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.

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SNP-Based Genetic Risk Score Modeling Suggests No Increased Genetic Susceptibility of the Roma Population to Type 2 Diabetes Mellitus

Genes ◽

10.3390/genes10110942 ◽

2019 ◽

Vol 10 (11) ◽

pp. 942 ◽

Cited By ~ 7

Author(s):

Nardos Abebe Werissa ◽

Peter Piko ◽

Szilvia Fiatal ◽

Zsigmond Kosa ◽

Janos Sandor ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

General Population ◽

Genetic Risk ◽

Genetic Risk Score ◽

Risk Scores ◽

Unhealthy Lifestyle ◽

Roma Population

Background: In a previous survey, an elevated fasting glucose level (FG) and/or known type 2 diabetes mellitus (T2DM) were significantly more frequent in the Roma population than in the Hungarian general population. We assessed whether the distribution of 16 single nucleotide polymorphisms (SNPs) with unequivocal effects on the development of T2DM contributes to this higher prevalence. Methods: Genetic risk scores, unweighted (GRS) and weighted (wGRS), were computed and compared between the study populations. Associations between GRSs and FG levels and T2DM status were investigated in separate and combined study populations. Results: The Hungarian general population carried a greater genetic risk for the development of T2DM (GRSGeneral = 15.38 ± 2.70 vs. GRSRoma = 14.80 ± 2.68, p < 0.001; wGRSGeneral = 1.41 ± 0.32 vs. wGRSRoma = 1.36 ± 0.31, p < 0.001). In the combined population models, GRSs and wGRSs showed significant associations with elevated FG (p < 0.001) and T2DM (p < 0.001) after adjusting for ethnicity, age, sex, body mass index (BMI), high-density Lipoprotein Cholesterol (HDL-C), and triglyceride (TG). In these models, the effect of ethnicity was relatively strong on both outcomes (FG levels: βethnicity = 0.918, p < 0.001; T2DM status: ORethnicity = 2.484, p < 0.001). Conclusions: The higher prevalence of elevated FG and/or T2DM among Roma does not seem to be directly linked to their increased genetic load but rather to their environmental/cultural attributes. Interventions targeting T2DM prevention among Roma should focus on harmful environmental exposures related to their unhealthy lifestyle.

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A genetic risk score that includes common type 2 diabetes risk variants is associated with gestational diabetes

Clinical Endocrinology ◽

10.1111/cen.13356 ◽

2017 ◽

Vol 87 (2) ◽

pp. 149-155 ◽

Cited By ~ 19

Author(s):

V. K. Kawai ◽

R. T. Levinson ◽

A. Adefurin ◽

D. Kurnik ◽

S. P. Collier ◽

...

Keyword(s):

Type 2 Diabetes ◽

Gestational Diabetes ◽

Risk Score ◽

Genetic Risk ◽

Genetic Risk Score ◽

Common Type ◽

Diabetes Risk ◽

Risk Variants

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Genetic Risk, a Healthy Lifestyle, and Type 2 Diabetes: the Dongfeng-Tongji Cohort Study

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgz325 ◽

2020 ◽

Vol 105 (4) ◽

pp. 1242-1250

Author(s):

Xu Han ◽

Yue Wei ◽

Hua Hu ◽

Jing Wang ◽

Zhaoyang Li ◽

...

Keyword(s):

Cohort Study ◽

Risk Score ◽

Genetic Risk ◽

Healthy Lifestyle ◽

Genetic Risk Score ◽

Lifestyle Factors ◽

Diabetes Risk ◽

Incident Diabetes ◽

Polygenic Risk Score ◽

Weighted Genetic Risk Score

Abstract Objective The objective of this study is to examine whether healthy lifestyle could reduce diabetes risk among individuals with different genetic profiles. Design A prospective cohort study with a median follow-up of 4.6 years from the Dongfeng-Tongji cohort was performed. Participants A total of 19 005 individuals without diabetes at baseline participated in the study. Main Variable Measure A healthy lifestyle was determined based on 6 factors: nonsmoker, nondrinker, healthy diet, body mass index of 18.5 to 23.9 kg/m2, waist circumference less than 85 cm for men and less than 80 cm for women, and higher level of physical activity. Associations of combined lifestyle factors and incident diabetes were estimated using Cox proportional hazard regression. A polygenic risk score of 88 single-nucleotide polymorphisms previously associated with diabetes was constructed to test for association with diabetes risk among 7344 individuals, using logistic regression. Results A total of 1555 incident diabetes were ascertained. Per SD increment of simple and weighted genetic risk score was associated with a 1.39- and 1.34-fold higher diabetes risk, respectively. Compared with poor lifestyle, intermediate and ideal lifestyle were reduced to a 23% and 46% risk of incident diabetes, respectively. Association of lifestyle with diabetes risk was independent of genetic risk. Even among individuals with high genetic risk, intermediate and ideal lifestyle were separately associated with a 29% and 49% lower risk of diabetes. Conclusion Genetic and combined lifestyle factors were independently associated with diabetes risk. A healthy lifestyle could lower diabetes risk across different genetic risk categories, emphasizing the benefit of entire populations adhering to a healthy lifestyle.

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Additive and Multiplicative Interactions Between Genetic Risk Score and Family History and Lifestyle in Relation to Risk of Type 2 Diabetes

American Journal of Epidemiology ◽

10.1093/aje/kwz251 ◽

2019 ◽

Vol 189 (5) ◽

pp. 445-460 ◽

Cited By ~ 3

Author(s):

Ming Ding ◽

Shafqat Ahmad ◽

Lu Qi ◽

Yang Hu ◽

Shilpa N Bhupathiraju ◽

...

Keyword(s):

Type 2 Diabetes ◽

Family History ◽

Risk Score ◽

Genetic Risk ◽

Healthy Lifestyle ◽

Genetic Risk Score ◽

European Ancestry ◽

Health Study ◽

Public Health Implication

Abstract We examined interactions between lifestyle factors and genetic risk of type 2 diabetes (T2D-GR), captured by genetic risk score (GRS) and family history (FH). Our initial study cohort included 20,524 European-ancestry participants, of whom 1,897 developed incident T2D, in the Nurses’ Health Study (1984–2016), Nurses’ Health Study II (1989–2016), and Health Professionals Follow-up Study (1986–2016). The analyses were replicated in 19,183 European-ancestry controls and 2,850 incident T2D cases in the Women’s Genome Health Study (1992–2016). We defined 2 categories of T2D-GR: high GRS (upper one-third) with FH and low GRS or without FH. Compared with participants with the healthiest lifestyle and low T2D-GR, the relative risk of T2D for participants with the healthiest lifestyle and high T2D-GR was 2.24 (95% confidence interval (CI): 1.76, 2.86); for participants with the least healthy lifestyle and low T2D-GR, it was 4.05 (95% CI: 3.56, 4.62); and for participants with the least healthy lifestyle and high T2D-GR, it was 8.72 (95% CI: 7.46, 10.19). We found a significant departure from an additive risk difference model in both the initial and replication cohorts, suggesting that adherence to a healthy lifestyle could lead to greater absolute risk reduction among those with high T2D-GR. The public health implication is that a healthy lifestyle is important for diabetes prevention, especially for individuals with high GRS and FH of T2D.

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Type 2 Diabetes Genetic Risk Scores Are Associated With Increased Type 2 Diabetes Risk Among African Americans by Cardiometabolic Status

Clinical Medicine Insights Endocrinology and Diabetes ◽

10.1177/1179551417748942 ◽

2018 ◽

Vol 11 ◽

pp. 117955141774894 ◽

Cited By ~ 7

Author(s):

Jill Layton ◽

Xiaochen Li ◽

Changyu Shen ◽

Mary de Groot ◽

Leslie Lange ◽

...

Keyword(s):

Type 2 Diabetes ◽

African Americans ◽

Genetic Risk ◽

Genetic Risk Score ◽

Diabetes Risk ◽

Risk Scores ◽

Genetic Risk Scores ◽

Normal Ranges ◽

Increased Risk

The relationship between genetic risk variants associated with glucose homeostasis and type 2 diabetes risk has yet to be fully explored in African American populations. We pooled data from 4 prospective studies including 4622 African Americans to assess whether β-cell dysfunction (BCD) and/or insulin resistance (IR) genetic variants were associated with increased type 2 diabetes risk. The BCD genetic risk score (GRS) and combined BCD/IR GRS were significantly associated with increased type 2 diabetes risk. In cardiometabolic-stratified models, the BCD and IR GRS were associated with increased type 2 diabetes risk among 5 cardiometabolic strata: 3 clinically healthy strata and 2 clinically unhealthy strata. Genetic risk scores related to BCD and IR were associated with increased risk of type 2 diabetes in African Americans. Notably, the GRSs were significant predictors of type 2 diabetes among individuals in clinically normal ranges of cardiometabolic traits.

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Abstract MP16: Adherence to Healthy Lifestyle Factors is Associated With a Lower Risk of Death Among US Male Physicians With Type 2 Diabetes

Circulation ◽

10.1161/circ.131.suppl_1.mp16 ◽

2015 ◽

Vol 131 (suppl_1) ◽

Author(s):

Andrew B Petrone ◽

J. Michael Gaziano ◽

Luc Djousse

Keyword(s):

Type 2 Diabetes ◽

Body Mass Index ◽

Lower Risk ◽

Healthy Lifestyle ◽

Lifestyle Factors ◽

Hazard Ratios ◽

Risk Of Mortality ◽

All Cause Mortality ◽

Reduced Risk

Background: Previous studies have suggested that adherence to a healthy lifestyle is associated with reduced risk of type 2 diabetes, cardiovascular disease, and mortality. However, it is unknown whether a combination of healthy lifestyle after the diagnosis of diabetes is associated with reduced risk of all-cause mortality. Objective: To test the hypothesis that healthy modifiable lifestyle factors are associated with a lower risk of all-cause mortality in people diagnosed with type 2 diabetes. Methods: A prospective cohort study of 1,160 male physicians from the Physicians’ Health Study with prevalent type 2 diabetes. Smoking habits, body mass index, exercise frequency, and alcohol consumption were assessed via questionnaire, and diet was assessed via a food frequency questionnaire between 1999 and 2002. Death was ascertained by an endpoint committee. Healthy lifestyle factors were defined as: 1) never or past smoking, 2) body mass index <25 kg/m 2 , 3) vigorous physical activity 1+ days/week, alcohol consumption of 1-2 drinks/day, and 5) being in the top two quintiles of the Alternative Healthy Eating Index score. We used Cox regression to estimate multivariable adjusted hazard ratios of death according to each lifestyle factor, and total number of healthy lifestyle factors met. Results: During a median follow-up of 9.2 years, there were 248 deaths. The mean age at baseline was 68.9 ± 8.2 years. Healthy diet score was associated with a 40% (95% CI: 20-55%) lower risk of mortality. Multivariable adjusted hazard ratios (95% CI) for mortality were: 1.0 (ref), 0.58 (0.42-0.80), 0.58 (0.41-0.81), and 0.55 (0.35-0.87) for meeting 0 or 1, 2, 3, and 4+ healthy lifestyle factors, respectively. Conclusions: Our data are consistent with an inverse association between the number of healthy lifestyle factors and risk of mortality in US male physicians with type 2 diabetes.

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Interaction between dietary branched-chain amino acids and genetic risk score on the risk of type 2 diabetes in Chinese

Genes & Nutrition ◽

10.1186/s12263-021-00684-6 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Weiqi Wang ◽

Haiyang Jiang ◽

Ziwei Zhang ◽

Wei Duan ◽

Tianshu Han ◽

...

Keyword(s):

Type 2 Diabetes ◽

Genetic Predisposition ◽

Genetic Risk ◽

Odds Ratio ◽

Regression Models ◽

Fasting Glucose ◽

Genetic Risk Score ◽

Branched Chain Amino Acids ◽

Branched Chain

Abstract Background and objectives Previous studies have found the important gene-diet interactions on type 2 diabetes (T2D) incident but have not followed branched-chain amino acids (BCAAs), even though they have shown heterogeneous effectiveness in diabetes-related factors. So in this study, we aim to investigate whether dietary BCAAs interact with the genetic predisposition in relation to T2D risk and fasting glucose in Chinese adults. Methods In a case-control study nested in the Harbin Cohort Study on Diet, Nutrition and Chronic Non-Communicable Diseases, we obtained data for 434 incident T2D cases and 434 controls matched by age and sex. An unweighted genetic risk score (GRS) was calculated for 25 T2D-related single nucleotide polymorphisms by summation of the number of risk alleles for T2D. Multivariate logistic regression models and general linear regression models were used to assess the interaction between dietary BCAAs and GRS on T2D risk and fasting glucose. Results Significant interactions were found between GRS and dietary BCAAs on T2D risk and fasting glucose (p for interaction = 0.001 and 0.004, respectively). Comparing with low GRS, the odds ratio of T2D in high GRS were 2.98 (95% CI 1.54–5.76) among those with the highest tertile of total BCAA intake but were non-significant among those with the lowest intake, corresponding to 0.39 (0.12) mmol/L versus − 0.07 (0.10) mmol/L fasting glucose elevation per tertile. Viewed differently, comparing extreme tertiles of dietary BCAAs, the odds ratio (95% CIs) of T2D risk were 0.46 (0.22–0.95), 2.22 (1.15–4.31), and 2.90 (1.54–5.47) (fasting glucose elevation per tertile: − 0.23 (0.10), 0.18 (0.10), and 0.26 (0.13) mmol/L) among participants with low, intermediate, and high genetic risk, respectively. Conclusions This study indicated that dietary BCAAs could amplify the genetic association with T2D risk and fasting glucose. Moreover, higher BCAA intake showed positive association with T2D when genetic predisposition was also high but changed to negative when genetic predisposition was low.

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Mitigation of Venous Thromboembolism Risk through Favorable Lifestyle: The ARIC Study

Blood ◽

10.1182/blood-2019-131290 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1151-1151

Author(s):

Christina Evans ◽

Ching-Png Hong ◽

Aaron R Folsom ◽

Susan Heckbert ◽

Nicholas Smith ◽

...

Keyword(s):

Venous Thromboembolism ◽

Genetic Risk ◽

Genetic Risk Score ◽

Lifestyle Factors ◽

Normal Weight ◽

Common Disease ◽

High Genetic Risk ◽

Optimal Health ◽

Aric Study ◽

The Impact

Background: Venous thromboembolism (VTE) is a common disease with a strong genetic basis. Unhealthy lifestyle factors contribute to risk, but it is unknown whether healthier lifestyle can mitigate the risk for VTE in those at high genetic risk. We studied whether greater adherence to the American Heart Association's (AHA's) cardiovascular health metric called Life's Simple 7 (LS7) is associated with a lower rate of VTE in individuals with high genetic risk score (GRS) for VTE. Methods: We followed 9,026 middle-aged white participants from the Atherosclerosis Risk in Communities (ARIC) Study, a prospective cohort of 15,792 individuals enrolled in 1987-89. A validated GRS was used, comprising 5 well known genetic conditions associated with VTE (factor V Leiden, prothrombin 20210A, non-O blood group, factor XI rs4241824, and fibrinogen gamma FGG rs2066865). Only white participants were included, as the GRS did not predict VTE in others. AHA's LS7 categories of inadequate, average, and optimal health were determined based on smoking status, body mass index, physical activity, diet, total cholesterol, blood pressure, and fasting glucose. VTE events were adjudicated by expert medical record review. We calculated hazard ratios (HRs) and 95% confidence intervals (CI) of incident VTE by LS7 categories, stratified by GRS (low, intermediate, high), adjusting for age, sex, and education. HRs were also calculated for individual LS7 components stratified by GRS. Results: There were 466 incident VTE over 22.8 years of follow-up. Compared to those with optimal health, those with inadequate LS7 score had higher rates of VTE (5.7% vs. 3.9%). In Figure 1, compared to the high GRS / inadequate LS7 group, the HR of VTE in the low GRS group with optimal health was lowest at 0.39 (95% CI 0.25-0.61), but moreover, the HR in the high GRS group with optimal health was also attenuated to 0.65 (95% CI 0.48-0.89). The pattern of association was similar for provoked and unprovoked VTE. Of the LS7 components, obesity was most strongly related to VTE. In Figure 2, compared to obese / high GRS participants, the HR of VTE with normal weight / low GRS was 0.36 (95% CI 0.23-0.57), while the HR in high GRS / normal weight participants was reduced by 45%, at 0.55 (95% CI 0.4-0.76). Conclusion: Among all participants, even those at high genetic risk, healthier lifestyle factors, particularly obesity, were associated with decreased incidence of VTE. Further studies should determine the impact of lifestyle change among patients at high genetic risk of VTE, such as in thrombophilic families. Disclosures Heckbert: National Institutes of Health: Other: Grants.

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