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HbA1c, wound healing unrelated in diabetic foot ulcers

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April 20, 2018

Nestoras Mathioudakis, MD
Nestoras Mathioudakis

Among patients with long-term diabetic foot ulcers, neither baseline HbA1c nor change in HbA1c was associated with wound healing time, according to findings from a clinic-based observational study.

“Although we know that chronic hyperglycemia leads to neuropathy and peripheral vascular disease, which are the proximal risk factors for diabetic foot ulcers, we did not see a clear association between HbA1c levels and wound healing in patients who have developed foot ulcers,” Nestoras Mathioudakis, MD, MHS, assistant professor of medicine and clinical director, division of endocrinology, diabetes and metabolism at Johns Hopkins University School of Medicine, told Endocrine Today. “It is likely that the damage induced by chronic hyperglycemia reaches a point where it cannot be reversed in a relatively short time frame to improve wound healing.”

Mathioudakis and colleagues analyzed data from 270 patients with 584 diabetic foot ulcers seen at the Johns Hopkins Multidisciplinary Diabetic Foot and Wound Clinic between July 2012 and March 2017 (40.7% women; mean age, 58 years; 63.6% black; 94.4% with type 2 diabetes ; mean diabetes duration, 15.7 years ) . Point-of-care HbA1c measurements were assessed at least every 90 days (mean baseline HbA1c , 8.1% ) . Researchers used Cox proportional hazard models to assess the association between baseline HbA1c and wound healing and the association between change in HbA1c measures and long-term wound healing ( 90 days).

In patients with long-term wounds and a baseline HbA1c of 7.5% or less, there was no association between nadir HbA1c change or mean HbA1c change from baseline and wound healing, with results persisting after adjustments for wound stage and wound intervention. In one model, however, researchers observed an association between nadir HbA1c in the highest tertile of change (0.09 to 2.4) and wound healing (HR = 1.9; 95% CI, 1.03-3.53), with the findings persisting after adjustment for insulin doses (HR = 2.07; 95% CI, 1.08-4).

“One of the surprising findings in this study was that in patients with diabetic foot ulcers who had better glycemic control at baseline, increases in HbA1c during wound treatment were paradoxically associated with accelerated long-term wound healing, even after adjusting for relevant confounders,” Mathioudakis said.In other words, relaxation of glycemic control was associated with a more favorable outcome in this subgroup. The explanation for this finding isn't entirely clear, and we need further studies to replicate this finding before drawing inferences about its clinical relevance.”


In patients with long-term wounds and baseline HbA1c at least 7.5%, researchers similarly observed no association between nadir change or mean HbA1c change and wound healing after multivariable adjustment.

Mathioudakis said the findings show that the optimal HbA1c target for patients with diabetic foot ulcers remains unclear.

“Although lower HbA1c may not improve rates of wound healing, providers still need to be mindful of the potential benefit of glycemic control on prevention of other microvascular complications in these patients,” Mathioudakis said. This study does not support the role of aggressive glycemic control expressly for wound healing and suggests that an HbA1c target of 7.5% to 8% is reasonable for most patients with diabetic foot ulcers, depending on other factors, such as age, life expectancy, comorbid conditions, and resources or support.”

Mathioudakis also noted that researchers did not account for ongoing medication changes in the cohort, and it is possible that the use of antihyperglycemia medications are confounding the association with wound healing. – by Regina Schaffer

For more information:

Nestoras Mathioudakis, MD, MHS, can be reached at Johns Hopkins University School of Medicine, Department of Endocrinology, Diabetes and Metabolism, 1830 E. Monument St., Suite 333, Baltimore, MD 21287; email:

Disclosures: Mathioudakis reports he has received consultant fees from GlucoMe and honoraria from DK Bm ed CME and Pri-Med CME as a course director for eDiabetes Review.