Predictors of fracture in middle-aged and older adults with type 2 diabetes and overweight or obesity.

CONTEXT Persons with type 2 diabetes have increased fracture risk that existing fracture risk assessment tools underestimate. OBJECTIVE Identify fracture predictors in persons with type 2 diabetes and overweight or obesity, considering traditional and diabetes-related risk factors. DESIGN Secondary analysis of the Look AHEAD: Action for Health in Diabetes randomized clinical trial, with randomization from 2001-2004 and fracture follow-up until 2015. SETTING Multicenter U.S. study. PARTICIPANTS Men and women 45-75 years old with type 2 diabetes and body mass index≥25 kg/m2. EXPOSURES Potential fracture predictors ascertained at randomization included traditional and diabetes-related risk factors (diabetes duration, diabetic neuropathy, antidiabetic medication use, hemoglobin A1c, and renal function). Total hip bone mineral density (BMD) was measured in a subcohort. MAIN OUTCOME MEASURE All incident clinical fractures, ascertained by self-report and centrally adjudicated with medical records review. RESULTS Over a median 12.2 years follow-up, 649 of the 4,703 participants experienced at least one clinical fracture. Thiazolidinedione use [hazard ratio (HR):1.22, 95% confidence interval (CI):1.02-1.46] and insulin use [HR:1.34, 95% CI:1.08-1.66] were significant diabetes-related predictors of all clinical fractures. When measured in a subcohort (n=1,285), total hip BMD was the strongest modifiable predictor of all clinical fractures [Per 1 standard deviation (SD)=0.1 g/cm2 increase, HR:0.47, 95% CI:0.39-0.58]. CONCLUSIONS Thiazolidinedione and insulin use predict clinical fracture in middle-aged and older persons with type 2 diabetes and overweight or obesity. Evaluating BMD is advisable if these medications are prescribed. Fracture risk prediction tools may consider including thiazolidinedione and insulin use to refine prediction in this population.