Blood Glucose Control a Factor in Diabetes Fracture Risk

Nancy A. Melville

January 29, 2019

Blood glucose control appears to play a role in the known risk of fracture in diabetes; however, the effect is only significant in type 1 diabetes, suggesting insulin deficiency and poor glycemic control earlier in life could take a toll on bone mass among these patients.

"We investigated the association between the degree of glycemic control and fracture risk by using a large cohort of newly diagnosed type 1 and type 2 diabetes patients," explained lead author Janina Vavanikunnel, MD, of the University Hospital Basel, Switzerland, in a press statement from the Endocrine Society.

"Both types of diabetes are associated with fragility fracture, and we showed that poor glycemic control is associated with an increased risk of fracture in type 1 diabetes," she said.

The overall greater fracture risk in diabetes has been well documented, with an important study showing the risk of hip fracture, in particular, is increased two- to threefold in patients with type 2 diabetes compared to the general population, and by as much as sixfold in the less-common type 1 diabetes.

Less is known, however, about whether the degree of glycemic control, specifically, plays a role in the fracture risk associated with diabetes.

To take a closer look at the issue, Vavanikunnel and colleagues evaluated data on primary care patients newly diagnosed with diabetes between 1995 and 2015 enrolled in the UK Clinical Practice Research Datalink.

Increased Fracture Risk in Patients With Type 1 Diabetes and Poor Glycemic Control

In the study, published online January 19 in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism, the authors identified 3329 patients with type 1 diabetes, including 672 patients with a recorded low-trauma fragility fracture after diagnosis, and 44,275 patients with type 2 diabetes, including 8859 cases of fracture.

The study is unique, say researchers, because it evaluated a much larger patient population than past research and examined average HbA1c values over 3 years. On average, nine HbA1c measurements for patients with type 1 diabetes and 11 measurements for patients with type 2 diabetes were recorded.

The risk of a fragility fracture — defined as any fall from standing height or lower that resulted in a broken bone — was increased in patients with type 1 diabetes who had a mean HbA1c > 8.0% compared to patients with type 1 diabetes and "good" control (mean HbA1c ≤ 7.0%) (adjusted odds ratio [OR], 1.39).

In patients with type 1 diabetes, certain comorbidities related to vascular complications were also associated with an increased risk of fracture, such as diabetic retinopathy (OR, 1.29) and chronic renal failure (OR, 2.24).

There was no significant relationship between glycemic control and fracture rates in type 2 diabetes.

Independent of glycemic control, an increased risk of fracture was seen in patients with type 2 diabetes currently taking pioglitazone (OR, 1.36) or rosiglitazone (OR, 1.32) compared with nonusers of thiazolidinediones. This drug class has been shown in clinical studies to adversely affect bone metabolism.

Different Mechanisms at Play in Different Types of Diabetes

In both diabetes groups, the first fragility fracture occurred relatively early in the disease course, within a mean 4.5 years of diabetes diagnosis.

Overall, patients with type 2 diabetes had better glycemic control, with a mean 3-year HbA1c of 7.3% compared to patients with type 1 diabetes, who had a mean HbA1c of 8.7%.

Poorly controlled blood glucose with a much earlier onset of type 1 diabetes, typically in youth, may increase fracture risk in those patients because of the interaction of insulin and bone, considering that as much as 50% to 60% of peak bone mass is accrued during puberty, the authors speculate.

"Insulin as an anabolic hormone is thought to have a stimulatory effect on osteoblast function," they explain. "Therefore, insulin deficiency in type 1 diabetes may cause a reduction in osteoblast cell numbers, resulting in impaired peak bone mass."

The authors note they did not evaluate the risk of fracture in patients with type 2 diabetes overall compared to patients with no diabetes, but state that "our findings support the notion that the risk of fracture in patients with type 2 diabetes might be related to risk factors independent of glycemic control."

And they stress that the higher risk of broken bones in type 2 diabetes is still very important, as second author Sarah Charlier, MSc, also of University Hospital Basel, observed: "Fracture risk in type 2 diabetes is of clinical relevance as well, as it is a major health concern worldwide due to its high prevalence."

The research was supported by the Swiss National Science Foundation.

J Clin Endocrinol Metab. Published online January 16, 2019. Abstract

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