SLR - March 2019 - Terrence S. Park

Association of Hemoglobin A1c and Wound Healing in Diabetic Foot Ulcers

Betiel K. Fesseha, Christopher J Abularrage, Kathryn F Hines, Ronald Sherman, Priscilla Frost, Susan Langan, Joseph Canner, Kendall C. Likes, Sayed M Hosseini, Gwendolyne Jack, Caitlin W. Kicks, Swaytha Yalamanchi, and Nestoras Mathioudakis. Association of Hemoglobin A1c and Wound Healing in Diabetic Foot Ulcers. Diabetes Care. 2018 July 6; 41:1478–1485.

Scientific Literature Review

Reviewed By: Terrence S. Park, DPM
Residency Program: New York Presbyterian/Queens, Flushing, NY

Podiatric Relevance: The diabetic foot ulcer is a common condition seen and treated by podiatric surgeons and has major implications on quality of life as well as life expectancy. Notably, five-year mortality rates are as high as 55 percent for ischemic ulcers and 77 percent for those with a previous lower-limb amputation. Healing of a wound depends on many different factors, but previously published studies report no association between baseline A1c and wound healing. However, most of these studies have limitations where the measure of glycemic control was obtained prior to the initiation of the study, making it difficult to make inferences regarding the effect of the glucose control during treatment. In this study, baseline as well as prospective A1c were obtained to assess the effect of glycemic control and its effect on wound healing.

Methods: This is a retrospective study of an ongoing prospective, clinic-based study of patients with DFUs treated at an academic institution between July 2012 and March 2017 (4.7 years). Data from 584 wounds (total 270 patients) were included in this analysis. Cox proportional hazards regression model was used to assess the incidence of wound healing at any follow-up time. Criteria assessed in this study are long-term (>90 days) wound healing in relation to baseline A1c, nadir A1c change and mean A1c change from baseline, both unadjusted and adjusted for potential confounders.

Results: Overall, baseline A1c was not associated with wound healing in both univariate or fully adjusted models. A paradoxical positive association was observed with long-term wound healing in the subset of participants with baseline A1c <7.5 percent who had worse glycemic control during the treatment period; groups with a nadir A1c change from -0.29 to 0.0 (tertile 2) and a nadir A1c change of 0.09 to 2.4 (tertile 3). However, there was no association with wound healing with the mean A1c change from baseline in this group. Neither nadir A1c change or mean A1c change were associated with long-term wound healing in participants with baseline A1c >7.5 percent.

Conclusion: Contrary to the authors' initial hypothesis that tight glycemic control can enhance outcomes, a clinically meaningful correlation between wound healing in patients with DFU and their diabetes status was not found. Even more interesting was the fact that better wound healing was observed in a group with better baseline glycemic control (baseline A1c <7.5 percent) when the A1c was elevated during the study period. This paradoxical finding is counterintuitive. One of the possible explanations offered by the authors was the adverse effect of hypoglycemia on the healing process. This requires confirmation in future studies, perhaps with a design that takes account of the effect of timing and dosage of hypoglycemic agents administered during the treatment period.

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