Association between hemoglobin A1c, Vitamin C, and microbiome in diabetic foot ulcers and intact skin: A cross-sectional study

Diabetic foot ulcers (DFUs) add billions of dollars to the direct annual costs associated with diabetes. Despite various treatments, many DFUs do not heal and become infected. Both skin-associated microbial communities and glycemic control are believed to be important in nonhealing DFUs. Recent studies have linked serum Vitamin C levels with glycemic control and DFUs. This cross-sectional study assessed skin microbiome in DFUs, intact diabetic skin, and nondiabetic skin to identify correlations between hemoglobin A1c (HbA1c), Vitamin C, and microbial community structure. Correlations between Vitamin C, HbA1c, wound size, and ulcer duration were also determined.


Participants had their DFUs or intact skin culture swabbed. HbA1c was obtained via point-of-care fingerstick testing and serum Vitamin C was obtained via venipuncture. All participants completed a dietary questionnaire. Participants with ulcers were stratified into the controlled (≤8.0%) or uncontrolled (>8.0%) HbA1c group. Analysis of microbial communities was performed via 16S ribosomal RNA (rRNA) gene amplicon sequencing and bacterial load was measured by the domain-level quantitative polymerase chain reaction of the 16S rRNA gene.


Forty-two patients were recruited over 6 months. Bacteria from the genera Staphylococcus and Stenotrophomonas were present in all samples and often dominant, but a shift towards anaerobic pathogenic taxa was observed in ulcers. No global significant differences were observed for HbA1c and Vitamin C levels in the microbial community structure (R < 0.013/p > 0.375). Bacterial loads were 4–5 orders of magnitude higher in ulcers than in intact skin samples. Bacterial load was not significantly higher in the uncontrolled HbA1c group (p = 0.67). Larger wound sizes (p = 0.46) were observed in the uncontrolled HbA1c group compared to the control. Lower Vitamin C levels (p = 0.002) were observed in the uncontrolled HbA1c group compared to nondiabetic controls.


Understanding the link between Vitamin C and HbA1c and DFU microbiome may aid in new therapies.



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Published: 03 Aug 2022

Health Science Reports; DOI: