Diabetes and Risk of Frailty and Its Potential Mechanisms: A Prospective Cohort Study of Older Adults
Background: There is emerging evidence of the role of diabetes as a risk factor for frailty. However, the mechanisms of this association are uncertain. Methods: Prospective cohort study of 1750 non-institutionalized individuals aged ≥60 years recruited in 2008-2010. At baseline, information was obtained on health behaviors, morbidity, cardiometabolic biomarkers, and antidiabetic treatments. Individuals were considered diabetic if they reported a physician-diagnosis or had fasting serum glucose ≥126 mg/dl. Study participants were followed-up through 2012 to assess incident frailty, defined as at least three of the five Fried criteria. Results: At baseline, the cohort included 346 individuals with diabetes and 1404 without it. Over a mean 3.5-year follow-up, 115 cases of incident frailty were ascertained. After adjustment for age, sex and education, participants with diabetes showed an increased risk of frailty (odds ratio [OR]: 2.18; 95% confidence interval [CI]: 1.42-3.37). Additional adjustment for health behaviors and abdominal obesity yielded a 29.7% reduction in the OR (OR: 1.83; 95%CI: 1.16-2.90). Subsequent adjustment for morbidity produced an additional 8.4% reduction (OR: 1.76; 95%CI: 1.10-2.82), and for cardiometabolic biomarkers, a further 44% reduction (OR: 1.32; 95% 0.70-2.49). In particular, adjustment for HbA1c, lipoproteins and triglycerides accounted for the greatest reductions. Finally, additional adjustment for oral antidiabetic medication reduced the OR to 1.01 (95%CI: 0.46-2.20), while adjustment for nutritional therapy increased it to 1.64 (95%CI: 0.77-3.49). Conclusions: Diabetes mellitus is associated with higher risk of frailty; this association is partly explained by unhealthy behaviors and obesity and, to a greater extent, by poor glucose control and altered serum lipid profile among diabetic individuals. Conversely, diabetes nutritional therapy reduces the risk of frailty ; Baseline data collection was funded by Sanofi-Aventis. Data collection during follow-up was funded by the Spanish Government FIS grants 09/1626 and 09/0104 (Instituto de Salud Carlos III). Funding specific for this analysis was obtained from the Spanish Government FIS grant 12/1166 (Instituto de Salud Carlos III) and the FP7-HEALTH-2012-Proposal No: 305483–2 (FRAILOMIC Initiative).