Dysregulation of immunoglobulins and complement proteins in diabetic foot infections

Abstract

Background: Diabetic foot infections (DFIs) continue to be a substantial contributor to morbidity, disability, and limb loss in resource-limited nations. Hyperglycemia is associated with impaired wound healing; however, the relationship between immune dysregulation and metabolic glitches in diabetic foot infections remains imperfectly characterized.

Methods: This cross-sectional analytical investigation recruited 55 patients with diabetic foot infections from a specialist diabetes care center in Eastern Sudan (2024–2025). Clinical factors, ulcer intensity (SINBAD score), fasting blood sugar (FBS), and glycated hemoglobin (HbA1c) were recorded. Plasma immunoglobulins (IgA, IgG, IgM) and complement (C3,C4) levels were measured and compared with reference values. Associations among immunological markers, glycemic indices, and ulcer intensity were analyzed using chi-square tests, correlation analyses, and regression models.

Results: The study consisted of 60% males and 40% females, with a mean age of 50.4±16.0 years and an average diabetes duration of 10.3±6.9 years. The majority exhibited advanced ulceration, with 52.7% receiving a SINBAD score of 6. The mean FBS and HbA1c levels were 191.0±71.9 mg/dl and 9.12±2.25%, respectively. Relative to reference values, IgA, C3, and C4 exhibited elevation (P<0.001), whereas IgM was reduced (P<0.001). Low IgM showed a linkage with increased HbA1c (P=0.030), whereas C3 was linked to FBS (P=0.049).

Conclusions: DFIs in Sudanese patients are accompanied by immune dysregulation, reduced IgM, and persistent complement signaling, linked to hyperglycemia. Assessing immunological markers alongside glycemic indices may expand the practical utility of prognostic evaluation in resource-limited settings.