Optimal Glycemic Control Could Slow Biological Aging in Adults with Type 2 Diabetes

Exploratory analyses of data from the Look AHEAD trial suggest maintaining an HbA1c level of 7% or less was associated with smaller increases in frailty index over the 8-year study period when compared to their counterparts with an HbA1c level of 8% or greater.

Mark Espeland, PhD, Wake Forest

Mark Espeland, PhD

An analysis of data from the landmark Look AHEAD study suggests greater glycemic control could slow biological aging among adults with type 2 diabetes.

Results of the exploratory analyses, which included data from more than 4000 participants within the Look AHEAD trial, suggest lower HbA1c levels were associated with smaller increases in frailty index scores, with results also pointing to associations between use of metformin and weight loss with slower increases in frailty index during the 8-year study period.

“Among adults with type 2 diabetes, poorer glycemic control is associated with greater frailty and worse profiles of frailty over time. Frailty progressed more slowly among individuals achieving weight loss and those treated with metformin, which may reflect slower biological aging,” wrote investigators.

A multicenter, randomized clinical trial conducted in 16 sites across the US, the Look AHEAD trial was launched with the intent of developing a more thorough understanding of the long-term effects of intensive lifestyle intervention compared with disease support and education in individuals with type 2 diabetes who were also overweight or obese. With the primary outcome of interest defined as a composite outcome including cardiovascular death, nonfatal myocardial infarction, hospitalized angina, and nonfatal stroke, the trial randomized more than 5000 participants and concluded intensive lifestyle intervention failed to reduce incidence of the primary outcome but was associated with significant weight loss and reduced the prevalence of cardiovascular risk factors.

In the current study, a team led by Mark Espeland, PhD, of Wake Forest School of Medicine, sought to describe cross-sectional and longitudinal associations between HbA1c levels and randomization arm with 8-year changes in deficit accumulation of frailty index. With this in mind, investigators identified 4169 participants with sufficient data to compute frailty index at year 8 of follow-up for inclusion in their exploratory analyses. For the purpose of analysis, analyses of variance and covariance were used to assess relationships between baseline and 8-year levels of HbA1c with changes in frailty index and associations between changes in frailty index and use of diabetes medication classes and weight changes were controlled for HbA1c levels. Investigators also pointed out inverse probability weighting was used to estimate bias associated with differential follow-up.

Upon analysis, results indicated baseline and average HbA1c levels over time of less than 7%, as compared with 8% or greater, were associated with lesser increases in frailty index scores during the 8-year follow-up period (both P ≤.002). Investigators highlighted the coloration between baseline HbA1c and frailty index was modest, and based on spline regression, was approximately linear. Investigators noted results also indicated use of metformin and weight loss of greater than 5% were independently associated with slower increases in frailty index in analyses adjusted for HbA1c levels.

“Lower HbA1c levels among individuals with diabetes are associated with slower biological aging as captured by a deficit accumulation frailty index. Strategies to control diabetes through weight loss or metformin use may also slow aging,” investigators concluded.

This study, “An Examination of Whether Diabetes Control and Treatments Are Associated With Change in Frailty Index Across 8 Years: An Ancillary Exploratory Study From the Action for Health in Diabetes (Look AHEAD) Trial,” was published in Diabetes Care.

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