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Meta-Analysis
. 2023 Mar 1;46(3):643-656.
doi: 10.2337/dc22-1024.

Combination of Multiple Low-Risk Lifestyle Behaviors and Incident Type 2 Diabetes: A Systematic Review and Dose-Response Meta-analysis of Prospective Cohort Studies

Tauseef A Khan  1   2   3 , David Field  1   2   3 , Victoria Chen  2   3 , Suleman Ahmad  1   2   3 , Sonia Blanco Mejia  1   2   3 , Hana Kahleová  4   5 , Dario Rahelić  6   7   8 , Jordi Salas-Salvadó  9   10 , Lawrence A Leiter  1   2   3   11   12   13 , Matti Uusitupa  14 , Cyril W C Kendall  1   2   3   15 , John L Sievenpiper  1   2   3   11   13
Affiliations
Meta-Analysis

Combination of Multiple Low-Risk Lifestyle Behaviors and Incident Type 2 Diabetes: A Systematic Review and Dose-Response Meta-analysis of Prospective Cohort Studies

Tauseef A Khan et al. Diabetes Care. .

Abstract

Objective: Combined low-risk lifestyle behaviors (LRLBs) have been associated with a reduction in type 2 diabetes risk. This relationship has not been systematically quantified.

Research design and methods: A systematic review and meta-analysis was conducted to assess the association of combined LRLBs with type 2 diabetes. Databases were searched up to September 2022. Prospective cohort studies reporting the association between a minimum of three combined LRLBs (including healthy diet) with incident type 2 diabetes were included. Independent reviewers extracted data and assessed study quality. Risk estimates of extreme comparisons were pooled using a random-effects model. Global dose-response meta-analysis (DRM) for maximum adherence was estimated using a one-stage linear mixed model. The certainty of the evidence was assessed using GRADE (Grading of Recommendations, Assessment, Development and Evaluations).

Results: Thirty cohort comparisons (n = 1,693,753) involving 75,669 incident type 2 diabetes cases were included. LRLBs, with author-defined ranges, were healthy body weight, healthy diet, regular exercise, smoking abstinence or cessation, and light alcohol consumption. LRLBs were associated with 80% lower risk of type 2 diabetes (relative risk [RR] 0.20; 95% CI 0.17-0.23), comparing the highest with lowest adherence. Global DRM for maximum adherence to all five LRLBs reached 85% protection (RR 0.15; 95% CI 0.12-0.18). The overall certainty of the evidence was graded as high.

Conclusions: There is a very good indication that a combination of LRLBs that includes maintaining a healthy bodyweight, healthy diet, regular exercise, smoking abstinence or cessation, and light alcohol consumption is associated with a lower risk of incident type 2 diabetes.

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Conflict of interest statement

Duality of Interest. T.A.K. has received research support from the National Honey Board and International Life Sciences Institute (ILSI North America). D.R. has served as principal investigator or coinvestigator in clinical trials of AstraZeneca, Eli Lilly, MSD, Novo Nordisk, Sanofi Aventis, Solvay, and Trophos. He received honoraria for speaking or advisory board engagements and consulting fees from Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Lifescan–Johnson and Johnson, Novartis, Novo Nordisk, MSD, Merck Sharp and Dohme, Pfizer, Pliva, Roche, Salvus, Sanofi Aventis, and Takeda. J.S.S. reports receiving grant support through his institution from the International Nut and Dried Fruit Council and reports serving on the board of the International Nut and Dried Fruit Council and the Eroski Foundation and serving on the Executive Committee of the Instituto Danone Spain and on the Scientific Committee of the Danone International Institute. He has received research support from the California Walnut Commission (Sacramento, CA) Patrimonio Comunal Olivarero, Spain, La Morella Nuts, Spain, and Borges S.A., Spain. J.S.S. reports receiving consulting fees or travel expenses from Danone, the California Walnut Commission, the Eroski Foundation, Instituto Danone–Spain, Nuts for Life, the Australian Nut Industry Council, Nestlé, Abbot Laboratories, and Font Vella Lanjarón. C.W.C.K. has received grants or research support from the Advanced Food Materials Network, the Almond Board of California, American Pistachio Growers, Barilla, the California Strawberry Commission, the Calorie Control Council, the Canola Council of Canada, Loblaw Brands Ltd., Pulse Canada, Saskatchewan Pulse Growers, and Unilever. He has received in-kind research support from the Almond Board of California, the California Walnut Council, the American Peanut Council, Barilla, Unilever, Unico/Primo, Loblaw Companies, Quaker, Pristine Gourmet, Kellogg Canada, and WhiteWave Foods. He has received travel support and/or honoraria from the American Peanut Council, American Pistachio Growers, Barilla, Bayer, the California Walnut Commission, the Canola Council of Canada, General Mills, the International Tree Nut Council, Loblaw Brands Ltd., the Nutrition Foundation of Italy, Oldways Preservation Trust, Orafti, Paramount Farms, the Peanut Institute, Pulse Canada, Sabra Dipping Co., Saskatchewan Pulse Growers, Sun-Maid, Tate and Lyle, Unilever, and WhiteWave Foods. He has served on the scientific advisory board for the International Tree Nut Council, McCormick Science Institute, Oldways Preservation Trust, Paramount Farms and Pulse Canada. He is a member of the ICQC, Executive Board Member of the DNSG of the EASD, is on the Clinical Practice Guidelines Expert Committee for Nutrition Therapy of the EASD, and is a Director of the Toronto 3D Knowledge Synthesis and Clinical Trials foundation. J.L.S. has received research support from the International Nut and Dried Fruit Council (INC) Foundation, National Honey Board (U.S. Department of Agriculture [USDA] honey “Checkoff” program), Institute for the Advancement of Food and Nutrition Sciences (IAFNS; formerly ILSI North America), Pulse Canada, Quaker Oats Center of Excellence, The United Soybean Board (USDA soy “Checkoff” program), The Tate and Lyle Nutritional Research Fund at the University of Toronto, The Glycemic Control and Cardiovascular Disease in Type 2 Diabetes Fund at the University of Toronto (a fund established by the Alberta Pulse Growers), The Plant Protein Fund at the University of Toronto (a fund which has received contributions from IFF), and The Nutrition Trialists Network Fund at the University of Toronto (a fund established by an inaugural donation from the Calorie Control Council). He has received food donations to support randomized controlled trials from the Almond Board of California, California Walnut Commission, Peanut Institute, Barilla, Unilever/Upfield, Unico/Primo, Loblaw Companies, Quaker, Kellogg Canada, Danone, Nutrartis, Soylent, and Dairy Farmers of Canada. He has received travel support, speaker fees and/or honoraria from Danone, Dairy Farmers of Canada, FoodMinds LLC, Nestlé, Abbott, General Mills, Nutrition Communications, International Food Information Council (IFIC), Calorie Control Council, International Sweeteners Association, International Glutamate Technical Committee, Phynova, and Brightseed. He has or has had ad hoc consulting arrangements with Perkins Coie LLP, Tate & Lyle, and Inquis Clinical Research. He is a former member of the European Fruit Juice Association Scientific Expert Panel and former member of the Soy Nutrition Institute (SNI) Scientific Advisory Committee. He is on the Clinical Practice Guidelines Expert Committees of Diabetes Canada, European Association for the study of Diabetes (EASD), Canadian Cardiovascular Society (CCS), and Obesity Canada/Canadian Association of Bariatric Physicians and Surgeons. He serves or has served as an unpaid member of the Board of Trustees and an unpaid scientific advisor for the Carbohydrates Committee of IAFNS. He is a member of the International Carbohydrate Quality Consortium (ICQC), Executive Board Member of the Diabetes and Nutrition Study Group (DNSG) of the EASD, and Director of the Toronto 3D Knowledge Synthesis and Clinical Trials foundation. His spouse is an employee of AB InBev. H.K. is Director of Clinical Research at the Physicians Committee for Responsible Medicine, a nonprofit organization that provides nutrition education and research. She is an Executive Board Member of the DNSG of the EASD. No other potential conflicts of interest relevant to this article were reported.

Figures

None
Graphical abstract
Figure 1
Figure 1
Systematic search and article selection.
Figure 2
Figure 2
Forest plot of the association of multiple low-risk lifestyle behaviors with type 2 diabetes incidence with highest number (three or more) vs. lowest number of behaviors (three or less). The individual study relative risk (RR) estimates are indicated by blue squares; the size is proportional to its weight. The blue horizontal lines represent CIs. The overall pooled estimate is represented by the green diamond. Estimates <1.0 indicate protective association and RRs >1.0 indicate an adverse association. Comparison is between highest vs. lowest number of LRLBs. EPIC, European Prospective Investigation into Cancer and Nutrition; E3N, Etude Epidémiologique Auprès des Femmes de la Mutuelle Générale de l’Education Nationale; FINRISK, Finland Cardiovascular Risk Study; NIH-AARP, National Institutes of Health–American Association of Retired Persons; M, males/men; F, females/women.
Figure 3
Figure 3
Dose-response plot of the association of the number of LRLBs with incident type 2 diabetes. The black boxes with vertical bars represent the aggregate relative risks (RRs) and 95% CIs for each LRLBs. Compared with adherence to no LRLBs, the estimated RRs were 0.70 (95% CI 0.64–0.78) for adherence to one LRLB, 0.49 (95% CI 0.42–0.57) for two combined LRLBs, 0.33 (95% CI 0.28–0.40) for three combined LRLBs, 0.22 (95% CI 0.19–0.27) for four-combined LRLBs, and 0.15 (95% CI 0.12–0.18) for all five combined LRLBs (global DRM at the highest adherence to global range of scores).
Figure 4
Figure 4
Subgroup analyses by sex, number of participants, duration of follow-up, number of LRLBs, exclusion of alcohol, NOS score, predominant race/ethnicity, continent, funding source, age, dietary assessment type, and time of exposure measurement with the relative risk of incident type 2 diabetes. Estimates at each subgroup level (red circles) indicate pooled effect estimates. The pooled effect estimate for the overall analysis is represented by the green diamond. Interstudy heterogeneity unexplained by the subgroup is represented by the residual I2 value.
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