Type 2 Diabetes Frailty Index Predicts Poor Outcomes: BP and Glucose Interventions Can Mitigate Them

A clinical doctor going over some test results with an elderly patient at the hospital.
The researchers’ goal was to develop a frailty index and explore the relationship of frailty to subsequent adverse outcomes among participants with type 2 diabetes in the ADVANCE trial.

A newly developed frailty index (FI) for patients with type 2 diabetes (T2D) identified individuals at high risk for poorer outcomes. These findings were published in Diabetes Care.

Data from the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial were analyzed in this secondary post hoc study by researchers in Australia and elsewhere around the world. The frailty index comprised 34 age-related health variables valued from 0 to 1. The frailty index was retrospectively calculated, and risk for mortality and macrovascular and microvascular events was assessed.

ADVANCE participants (N=11,140) had a mean age of 65.8 years at baseline and 42.5% were women. The frailty index was normally distributed, ranging from 0 to 0.53 (mean, 0.17; SD, 0.08).

A cutoff point for frailty was determined to be 0.21, indicating 25.7% of the population was frail. There was an age interaction, in which more patients who were 65 years and older were frail (hazard ratio [HR], 2.16; 95% CI, 1.93-2.41) compared with those younger than 65 years (HR, 1.61; 95% CI, 1.39-1.87; P =.01).

Patients who were frail at baseline had increased rates of cardiovascular mortality (adjusted HR [aHR], 3.01; 95% CI, 2.55-3.57), major macrovascular events (aHR, 2.31; 95% CI, 2.05-2.59), all-cause mortality (aHR, 2.18; 95% CI, 1.93-2.47), major microvascular events (aHR, 1.60; 95% CI, 1.42-1.81), and severe hypoglycemic events (aHR, 1.57; 95% CI, 1.20-2.06).

The blood pressure (BP)-lowering intervention decreased risk for combined macrovascular and microvascular events among nonfrail (HR, 0.86; 95% CI, 0.77-0.97) and frail (HR, 0.97; 95% CI, 0.83-1.13) patients. Decreased all-cause mortality among nonfrail (HR, 0.79; 95% CI, 0.66-0.94) and frail (HR, 0.95; 95% CI, 0.78-1.16) groups was also observed.

Intensive glucose control interventions decreased the risk for combined macrovascular and microvascular events among nonfrail (HR, 0.84; 95% CI, 0.75-0.94) and frail (HR, 1.03; 95% CI, 0.90-1.18) patients. Decreased all-cause mortality among the nonfrail (HR, 0.83; 95% CI, 0.71-0.98) and frail (HR, 1.11; 95% CI, 0.92-1.34) cohorts was also observed.

This study was limited by the number of variables collected that could be incorporated into the frailty index calculation.

The study authors concluded the frailty index identified individuals at higher risk for poorer clinical outcomes and that BP-lowering and intensive glucose control interventions had some effect at mitigating poor outcomes.

Disclosure: Some authors declared affiliations with biotech, pharmaceutical, and/or device manufacturers. Please see the original reference for a full list of authors’ disclosures.


Nguyen TN, Harris K, Woodward M, et al. The impact of frailty on the effectiveness and safety of intensive glucose control and blood pressure-lowering therapy for people with type 2 diabetes: results from the ADVANCE Trial. Diabetes Care. Published online May 25, 2021. doi:10.2337/dc20-2664