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Type 2 Diabetes Subgroups, Risk for Complications, and Differential Effects Due to an Intensive Lifestyle Intervention

posted on 11.03.2021, 08:33 by Michael P. Bancks, Haiying Chen, Ashok Balasubramanyam, Alain G. Bertoni, Mark A. Espeland, Steven Kahn, Scott Pilla, Elizabeth Vaughan, Lynne E. Wagenknecht, the Look AHEAD Research Group
Objective: We re-evaluated the Action for Health in Diabetes (Look AHEAD) intervention, incorporating diabetes subgroups, to identify whether intensive lifestyle intervention (ILI) is associated with differential risk for cardiovascular disease (CVD) by diabetes subgroup.

Research Design and Methods: Look AHEAD randomized 5145 participants, aged 45-76 years, with type 2 diabetes (T2D) and overweight or obesity, to 10 years of ILI or a control condition of diabetes support and education. ILI focused on weight loss through decreased caloric intake and increased physical activity. To characterize diabetes subgroups, we applied k-means clustering to data for age of diabetes diagnosis, body mass index, waist circumference, and glycated hemoglobin. We examined whether relative intervention effects on the trial’s prespecified CVD outcomes varied among diabetes subgroups.

Results: We characterized four subgroups related to older age at diabetes onset (42% of sample), poor glycemic control (14%), severe obesity (24%), and younger age at onset (20%). We observed interactions (all p<0.05) between intervention and diabetes subgroup for three separate composite cardiovascular outcomes. Randomization to ILI was associated with increased risk for each cardiovascular outcome only among the poor glucose control subgroup (hazard ratios, HR >1.32). Among the three other diabetes subgroups, ILI was not associated with increased risk for CVD.

Conclusion: Among overweight and obese adults with T2D, a lifestyle intervention was associated with differential risk for CVD that was dependent on diabetes subgroup. Diabetes subgroups may be important to identify the patients who would achieve benefit and avoid harm from an intensive lifestyle intervention.


This study used data from the Look AHEAD trial intervention phase which was funded by the National Institutes of Health through cooperative agreements with the National Institute of Diabetes and Digestive and Kidney Diseases: DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, and DK56992. Additional funding was provided by the National Heart, Lung, and Blood Institute; National Institute of Nursing Research; National Center on Minority Health and Health Disparities; NIH Office of Research on Women’s Health; and the Centers for Disease Control and Prevention. This research was supported in part by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. The Indian Health Service (I.H.S.) provided personnel, medical oversight, and use of facilities. The opinions expressed in this paper are those of the authors and do not necessarily reflect the views of the I.H.S. or other funding sources. Additional support was received from The Johns Hopkins Medical Institutions Bayview General Clinical Research Center (M01RR02719); the Massachusetts General Hospital Mallinckrodt General Clinical Research Center and the Massachusetts Institute of Technology General Clinical Research Center (M01RR01066); the Harvard Clinical and Translational Science Center (RR025758-04); the University of Colorado Health Sciences Center General Clinical Research Center (M01RR00051) and Clinical Nutrition Research Unit (P30 DK48520); the University of Tennessee at Memphis General Clinical Research Center (M01RR0021140); the University of Pittsburgh General Clinical Research Center (GCRC) (M01RR000056), the Clinical Translational Research Center (CTRC) funded by the Clinical & Translational Science Award (UL1 RR 024153) and NIH grant (DK 046204); the VA Puget Sound Health Care System Medical Research Service, Department of Veterans Affairs; and the Frederic C. Bartter G