January 18, 2019
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Influence of HbA1c on fracture risk differs in type 1, type 2 diabetes

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Adults with type 1 diabetes and an HbA1c of at least 8% were more likely to sustain a low-trauma fracture in the 4 years after diabetes diagnosis than similar adults with an HbA1c of less than 7%, according to findings from a case-control study.

In an analysis of more than 47,000 adults, researchers did not observe the same fracture association for adults with type 2 diabetes; however, the risk for fracture was elevated in adults with type 2 diabetes prescribed rosiglitazone (Avandia, GlaxoSmithKline) or pioglitazone, independent of glycemic control.

“In patients diagnosed with [type 1 diabetes] during adolescence and early adulthood, deficiencies in insulin and insulin-like growth factor I seem to impair osteoblast function leading to lower bone mass, smaller bone size and alterations in bone microstructure,” Janina Vavanikunnel, MD, a research fellow in the division of endocrinology, diabetes and metabolism at University Hospital Basel, Switzerland, and colleagues wrote in the study background. “In contrast, patients with [type 2 diabetes], who usually suffer from obesity-related insulin resistance and hyperinsulinemia, present[ed] with normal to increased bone mass and preserved or even increased trabecular bone volume, but with increased cortical porosity. This pattern is found particularly in patients with fractures and microvascular complications.”

Vavanikunnel and colleagues analyzed data from adults with type 1 (n = 3,329) or type 2 diabetes (n = 44,275) diagnosed between 1995 and 2015, using data from the United Kingdom-based Clinical Practice Research Datalink. Cases were defined as patients with a low-trauma fracture sustained after diabetes onset (n = 9,531). Researchers matched each case with four controls by age, sex, general practice, fracture date and diabetes type and duration (n = 38,073). Exposure of interest was glycemic control after diabetes onset, defined by HbA1c levels. Researchers used conditional logistic regression analysis to assess the association between HbA1c values and the risk for low-trauma fractures, expressed as odds ratios.

Among patients with type 1 diabetes, 672 sustained a fracture after diagnosis during a median of 4.5 years (46% women). Researchers found that patients with 3-year mean HbA1c levels of at least 8% were 39% more likely to sustain a fracture vs. those with 3-year mean HbA1c levels of less than 7% (adjusted OR = 1.39; 95% CI, 1.06-1.83). Researchers did not observe an association between HbA1c and fracture risk in adults with type 1 diabetes and moderate glycemic control, defined as an HbA1c between 7% and 8% (aOR = 0.99; 95% CI, 0.72-1.35).

Among patients with type 2 diabetes, 8,859 sustained a fracture after diagnosis during a median of 4.5 years (71% women). In these patients, glycemic control was not associated with fracture risk; however, researchers observed increased fracture risk when patients were stratified by antidiabetes therapies. Compared with nonusers, adults prescribed pioglitazone (OR = 1.36; 95% CI, 1.25-1.49) or rosiglitazone (OR = 1.32; 95% CI, 1.2-1.46) were more likely to sustain a low-trauma fracture, independent of glycemic control, according to researchers.

“The impact of glycemic control on the risk of nonvertebral low-trauma fractures differed in [type 1 diabetes] and [type 2 diabetes] patients with short-term disease,” the researchers wrote. “While poor glycemic control elevated the risk of fracture in [type 1 diabetes] patients, we observed no such association in patients with [type 2 diabetes]. This might be attributed to a protective effect of insulin resistance in early disease.” – by Regina Schaffer

Disclosures: The Swiss National Science Foundation supported this study. The authors report no relevant financial disclosures.