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Tight glycemic targets, insulin use increase fracture risk among older men with type 2 diabetes
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Older men with type 2 diabetes and low baseline HbA1c were more likely to sustain any fracture or a hip fracture over 3 years than similar men with HbA1c between 7.5% and 8.5%, with insulin use further increasing fracture risk, according to findings published in the Journal of Bone and Mineral Research.
“Our work shows there is a significant risk [for] fractures among older men with type 2 diabetes, especially among those with tight glycemic control and insulin use,” Richard H. Lee, MD, MPH, assistant professor of medicine at Duke University in Durham, North Carolina, told Endocrine Today. “The results show the significant dangers in overtreating diabetes in older patients and the importance of avoiding hypoglycemia. As part of the management of diabetes, clinicians should incorporate a falls assessment, especially among those with diabetic complications.”
In a retrospective study, Lee and colleagues analyzed electronic medical records of 652,901 men aged at least 65 years with type 2 diabetes and an available HbA1c value who received primary care in the VA between 2000 and 2010. Researchers stratified patients by baseline HbA1c value into five categories: less than 6.5%; 6.5% to 7.5%; 7.5% to 8.5%; 8.5% to 9.5%; and at least 9.5%. Fracture outcomes of interest included any clinical fracture and hip fracture. Researchers evaluated associations of HbA1c level with fracture risk using time-to-event analysis with competing risk for death.
During mean follow-up of 3.43 years (2,272,930 person-years), researchers observed 65,211 clinical fractures, including 15,020 hip fractures. Compared with men without a fracture, men who sustained an incident fracture were older (mean age, 76.4 years vs. 73.9 years), had a lower BMI (mean, 29.9 kg/m² vs. 30.5 kg/m²) and were more likely to use insulin or sulfonylureas.
The researchers found that a baseline HbA1c of less than 6.5% was associated with a higher risk for any clinical fracture (HR = 1.08; 95% CI, 1.06-1.11) vs. an HbA1c between 7.5% and 8.5%. They observed no increase in fracture risk among men with an HbA1c of 8.5% or greater, nor among those with an HbA1c between 6.5% and 7.5%.
Men with a baseline HbA1c of less than 6.5% also appeared more likely to sustain a hip fracture than men with an HbA1c between 7.5% and 8.5% (HR = 1.13; 95% CI, 1.08-1.19), as were men with a baseline HbA1c of at least 9.5% (HR = 1.1; 95% CI, 1.02-1.2).
Insulin use was independently associated with greater risk for any fracture (HR = 1.1; 95% CI, 1.07-1.12) and for hip fracture (HR = 1.17; 95% CI, 1.12-1.22). The researchers observed an interaction between insulin use and HbA1c level (P < .001), noting that men using insulin with an HbA1c of less than 6.5% had an HR for any fracture of 1.23, whereas men using insulin with an HbA1c between 6.5% and 7.5% had an HR for any fracture of 1.15.
“Our results suggest that hypoglycemia significantly contributes to the increased fracture risk observed among older adults with diabetes,” the researchers wrote.
The researchers also found that metformin use was associated with a 12% decrease in fracture risk (HR = 0.88; 95% CI, 0.87-0.9).
“Based on the results of our current study, we recommend particular attention to those older adults treated with insulin and to those with HbA1c of at least 9.5% or less than 6.5%,” the researchers wrote. “Our findings demonstrate the importance of evaluating the fracture risk and prescribed diabetes treatment regimen and avoiding hypoglycemia for fracture prevention in older men with diabetes.” – by Regina Schaffer
For more information:
Richard H. Lee, MD, can be reached at Duke University Medical Center, P.O. Box 3470, Durham, NC 27710; email: r.lee@duke.edu.
Disclosures: The authors report no relevant financial disclosures.
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