Glycemic Control Over Multiple Decades and Dementia Risk in People With Type 2 Diabetes

Author:

Moran Chris1234,Lacy Mary E.56,Whitmer Rachel A.57,Tsai Ai-Lin5,Quesenberry Charles P.5,Karter Andrew J.5,Adams Alyce S.58,Gilsanz Paola59

Affiliation:

1. National Centre for Healthy Ageing, Melbourne, Australia

2. Peninsula Clinical School, Monash University, Melbourne, Australia

3. Department of Geriatric Medicine, Peninsula Health, Melbourne, Australia

4. School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia

5. Kaiser Permanente Division of Research, Oakland, California

6. College of Public Health, Department of Epidemiology, University of Kentucky, Lexington

7. Division of Epidemiology, School of Medicine, University of California, Davis

8. Department of Epidemiology and Population Health and Health Policy, School of Medicine, Stanford University, Stanford, California

9. Department of Epidemiology and Biostatistics, University of California, San Francisco

Abstract

ImportanceThe levels of glycemic control associated with the lowest risk of dementia in people with type 2 diabetes are unknown. This knowledge is critical to inform patient-centered glycemic target setting.ObjectiveTo examine the associations between cumulative exposure to various ranges of glycated hemoglobin (HbA1c) concentrations with dementia risk across sex and racial and ethnic groups and the association of current therapeutic glycemic targets with dementia risk.Design, Setting, and ParticipantsThis cohort study included members of the Kaiser Permanente Northern California integrated health care system with type 2 diabetes who were aged 50 years or older during the study period from January 1, 1996, to September 30, 2015. Individuals with fewer than 2 HbA1c measurements during the study period, prevalent dementia at baseline, or less than 3 years of follow-up were excluded. Data were analyzed from February 2020 to January 2023.ExposuresTime-updated cumulative exposure to HbA1c thresholds. At each HbA1c measurement, participants were categorized based on the percentage of their HbA1c measurements that fell into the following categories: less than 6%, 6% to less than 7%, 7% to less than 8%, 8% to less than 9%, 9% to less than 10%, and 10% or more of total hemoglobin (to convert percentage of total hemoglobin to proportion of total hemoglobin, multiply by 0.01).Main Outcomes and MeasuresDementia diagnosis was identified using International Classification of Diseases, Ninth Revision codes from inpatient and outpatient encounters. Cox proportional hazards regression models estimated the association of time-varying cumulative glycemic exposure with dementia, adjusting for age, race and ethnicity, baseline health conditions, and number of HbA1c measurements.ResultsA total of 253 211 participants were included. The mean (SD) age of participants was 61.5 (9.4) years, and 53.1% were men. The mean (SD) duration of follow-up was 5.9 (4.5) years. Participants with more than 50% of HbA1c measurements at 9% to less than 10% or 10% or more had greater risk of dementia compared with those who had 50% or less of measurements in those categories (HbA1c 9% to <10%: adjusted hazard ratio [aHR], 1.31 [95% CI, 1.15-1.51]; HbA1c≥10%: aHR, 1.74 [95% CI, 1.62-1.86]). By contrast, participants with more than 50% of HbA1c concentrations less than 6%, 6% to less than 7%, or 7% to less than 8% had lower risk of dementia (HbA1c<6%: aHR, 0.92 [95% CI, 0.88-0.97]; HbA1c 6% to <7%: aHR, 0.79 [95% CI, 0.77-0.81]; HbA1c 7% to <8%: aHR, 0.93 [95% CI, 0.89-0.97]).Conclusions and RelevanceIn this study dementia risk was greatest among adults with cumulative HbA1c concentrations of 9% or more. These results support currently recommended relaxed glycemic targets for older people with type 2 diabetes.

Publisher

American Medical Association (AMA)

Subject

Neurology (clinical)

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