Synergistic Association of Glycemic Variability and Severe Vitamin D Deficiency with Proliferative Diabetic...

Background: Oscillating hyperglycemia (glycemic variability) and vitamin D deficiency each damage the retinal microvasculature, yet their combined effect on sight-threatening proliferative diabetic retinopathy (PDR) is uncertain. Objective: To determine whether high GV and severe vitamin D deficiency independently, and additively, associate with retinal neovascularization in adults with diabetes. Materials and Methods: We conducted a cross-sectional study between January 2025 and June 2025 in 58 adults with diabetes at Constanța County Emergency Hospital, Romania. GV was classified as high (coefficient of variation > 36% or SMBG-SD > 50 mg/dL) or low. Serum 25-hydroxy-vitamin D [25(OH)D] was measured; severe deficiency < 10 ng/mL. Dilated funduscopy graded retinopathy as non-proliferative (NPDR) or proliferative (PDR). Multivariable logistic regression adjusted for HbA1c, diabetes duration, BMI, smoking, triglycerides and therapy. Results: From 58 adults (mean ± SD 59 ± 11 years), high GV characterized 29/58 participants (50%). Severe vitamin D deficiency was more frequent in the GV-high group (45% vs. 31%). PDR prevalence was 48% in GV-high and 31% in GV-low patients. After adjustment, high GV (adjusted OR 2.31, 95% CI 1.05-5.09) and severe vitamin D deficiency (OR 2.04, 95% CI 0.98-4.25) each predicted PDR. Concomitant exposure to both stressors conferred 3.9-fold higher odds of PDR (OR 3.88, 95% CI 1.35-11.1). No interaction term reached significance (p = 0.21), indicating additive effects. Conclusions: High GV and severe vitamin D deficiency independently and additively associate with PDR. Screening for both parameters may enhance risk stratification of PDR. Within adults with diabetes, high glycemic variability and severe vitamin D deficiency were each associated with higher odds of PDR after adjustment for HbA1c, diabetes duration, BMI, smoking, triglycerides, and treatment pattern; their effects appeared additive rather than multiplicative. These findings reflect associations within diabetes and do not imply that vitamin D deficiency produces retinopathy in euglycemic individuals.