Effect of renin-angiotensin antihypertensive medication use on cognitive function in diabetes mellitus with obesity or overweight: An ancillary study to the Action for Health in Diabetes (Look AHEAD) Trial

• Type of Material: Article
• Authors: Whitney Wharton, Emory University; Andrea Anderson, Wake Forest School of Medicine; Kathleen M. Hayden, Wake Forest School of Medicine; Owen T. Carmichael, Pennington Biomedical Research Center; Jeanne M. Clark, Johns Hopkins University; José A. Luchsinger, Columbia University; Mark Espeland, Wake Forest School of Medicine; Sevil Yasar, Johns Hopkins University
• Language: English
• Date: 2022-09-05
• Publisher: John Wiley and Sons
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2022 John Wiley & Sons Ltd.
• Final Published Version (URL): https://doi.org/10.1111/dom.14838
• Title of Journal or Parent Work: Diabetes, Obesity and Metabolism
• Volume: 24
• Issue: 12
• Start Page: 2443
• End Page: 2453
• Grant/Funding Information: This research was funded by two diversity supplements to the Action for Health in Diabetes Extension Study Biostatistics Research Center (3U01DK057136-19S1 and 3 U01DK057136-19S2). The funding for the parent award is from U01DK057136. The Action for Health in Diabetes is supported through the following cooperative agreements from the National Institutes of Health: DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, and DK56992. The Look AHEAD Brain MRI ancillary study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services: DK092237-01 and DK092237-02S2. The Look AHEAD Movement and Memory ancillary study was supported by the National Institute on Aging, National Institutes of Health, Department of Health and Human Services, R01AG03308701. The Look AHEAD Mind ancillary study was funded by R01AG058571. The following federal agencies have contributed support: National Institute of Diabetes and Digestive and Kidney Diseases; National Heart, Lung, and Blood Institute; National Institute of Nursing Research; National Center on Minority Health and Health Disparities; Office of Research on Women’s Health; the Centers for Disease Control and Prevention; and the Department of Veterans Affairs. 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 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); Frederic C. Bartter General Clinical Research Center (M01RR01346); and the Wake Forest Alzheimer’s Disease Core Center (P30AG049638-01A1). The following organizations have made major contributions to Look AHEAD: FedEx Corporation; Health Management Resources; LifeScan, Inc., a Johnson & Johnson Company; OPTIFAST® of Nestle HealthCare Nutrition, Inc.; Hoffmann-La Roche Inc.; Abbott Nutrition; and Slim-Fast Brand of Unilever North America.
• Keywords: renin angiotensin system; overweight; cognitive impairment; antihypertensive medications; type 2 diabetes; dementia; obesity; cognitive decline
• Research Categories: Health Sciences, Public Health; Health Sciences, Pharmacology

Abstract

Aim There are no studies evaluating the long-term effects of antihypertensive medication on cognitive function and risk for impairment in a population with type 2 diabetes mellitus (T2DM) who have overweight or obesity. We aimed to determine whether antihypertensive medication (AHM) acting through the renin angiotensin system (RAS-AHM) compared to Other-AHM can mitigate these risks in people with T2DM. Materials and Methods This secondary analysis of the randomized controlled Action for Health in Diabetes (Look AHEAD) study included 712 community-dwelling participants who were followed over 15 years. Logistic regression was used to relate RAS-AHM use to cognitive impairment, and linear regression was used to relate RAS-AHM use to domain-specific cognitive function after adjusting for potential confounders. Results 563 reported RAS-AHM and 149 Other-AHM use during the study. RAS-AHM users have college or higher education (53%), higher baseline hemoglobin A1C (7.4), and reported higher diabetes medication use (86%), while Other-AHM users were more likely to be white (72%), obese (25%) and have cardiovascular history (19%). RAS-AHM use was not associated with a reduced risk of dementia compared to Other-AHM users. We did observe better executive function (Trail Making Test, part B, p<0.04), processing speed (Digit Symbol Substitution Test, p<0.004), verbal memory (Rey Auditory Verbal Learning Test-delayed recall, p<0.005) and Composite score (p<0.008) among RAS-AHM users compared to Other-AHM users. Conclusion In this sample of adults with T2DM, free of dementia at baseline, we observed a slower decline in processing speed, executive function, verbal memory, and composite score among RAS-AHM users.