Glycemic control and diabetic foot ulcer outcomes: A systematic review and meta-analysis of observational studies

To evaluate the association between glycemic control (hemoglobin A1C, fasting glucose, and random glucose) and the outcomes of wound healing and lower extremity amputation (LEA) among patients with diabetic foot ulcers (DFUs).

Medline, EMBASE, Cochrane Library, and Scopus were searched for observational studies published up to March 2019. Five independent reviewers assessed in duplicate the eligibility of each study based on predefined eligibility criteria and two independent reviewers assessed risk of bias. Ameta-analysis was performed to calculate a pooled odds ratio (OR) or hazard ratio (HR) using random effects for glycemic measures in relation to the outcomes of wound healing and LEA. Subgroup analyses were conducted to explore potential source of heterogeneity between studies. The study protocol is registered with PROSPERO (CRD42018096842).

Of 4572 study records screened, 60 observational studies met the study eligibility criteria of which 47 studies had appropriate data for inclusion in one or more meta-analyses(n = 12,604 DFUs). For cohort studies comparing A1C >7.0 to 7.5% vs. lower A1C levels, the pooled OR for LEA was 2.04 (95% CI, 0.91, 4.57) and for studies comparing A1C ≥ 8% vs. <8%, the pooled OR for LEA was 4.80 (95% CI 2.83, 8.13). For cohort studies comparing fasting glucose ≥126 vs. <126 mg/dl, the pooled OR for LEA was 1.46 (95% CI, 1.02, 2.09). There was no association with A1C category and wound healing (OR or HR). There was high risk of bias with respect to comparability of cohorts as many studies did not adjust for potential confounders in the association between glycemic control and DFU outcomes.

Our findings suggest that A1C levels ≥8% and fasting glucose levels ≥126 mg/dl are associated with increased likelihood of LEA in patients with DFUs. A purposively designed prospective study is needed to better understand the mechanisms underlying the association between hyperglycemia and LEA.