Exploring the link between Vitamin D deficiency and prediabetes in the Ibb Governorate, Yemen: the prevalence and impact of high-dose Vitamin D supplementation

Abstract

Prediabetes and vitamin D deficiency are interrelated public health concems, especially in low-resource regions with high metabolic risk. This study aimed to determine the prevalence of prediabetes among adults in Ibb governorate, Yemen, assess vitamin D status in ADA-defined prediabetic individuals, and evaluate the effects of high-dose vitamin D supplementation on glycaemic parameters, insulin resistance, B-cell function, inflammatory markers, lipid profile, and endothelial function. This two-phase study, conducted from July 2024 to May 2025, included a community-based cross-sectional study followed by a randomized controlled trial involving 1,045 adults aged 18-60 years. Prediabetes was defined using American Diabetes Association criteria based on fasting blood glucose (FBG), 2-hour postprandial plasma glucose (2HPP), or glycated hemoglobin (HbA1c). Of 266 adults with ADA-defined prediabetes, 151 who had vitamin D deficiency were randomised to receive weekly oral cholecalciferol 50,000 IU or placebo for 16 weeks. Vitamin D status was categorized as deficient (<20 ng/mL), insufficient (20-30 ng/mL), or sufficient (>30 ng/mL). Primary outcomes were prediabetes prevalence, vitamin D deficiency among prediabetics, and changes in glycaemic parameters and insulin indices (FBG, 2HPP, HbA1c, HOMA-IR, and HOMA-ẞ). Secondary outcomes included hs-CRP, IL-6, lipid profile, and endothelial function measured by flow-mediated dilation (FMD). Prediabetes prevalence was 23.4% (n=245) (FBG), 14.7% (n=154) (2HPP), and 26.4% (n=276) (HbA1c). Among 266 prediabetics, 74.1% (n=197) were vitamin D deficient, 19.2% (n=51) insufficient, and 6.7% (n=18) sufficient. Post-intervention, 25(OH)D level increased significantly in the vitamin D group compared with placebo (31.13 ± 6.42 vs. 10.64 ± 4.87 ng/mL; p<0.001). Vitamin D supplementation significantly reduced FBG (94 ± 8.1 vs. 100 ± 9.3 mg/dL; p<0.001), improved B-cell function (HOMA-ẞ: 94.79 ± 22.6 vs. 72.16 ± 19.4; p=0.028) and endothelial function (FMD: 15.47 ± 3.2% vs. 2.72 ± 1.1%; p<0.001) compared with placebo. No significant differences were observed for HbA1c, 2HPP, HOMA-IR IL-6, hs-CRP, or lipid parameters between groups. In conclusion, prediabetes and vitamin D deficiency are highly prevalent in Ibb governorate. High- dose vitamin D supplementation improves fasting glycemia, B-cell function, and endothelial function, supporting its potential role as an adjunct strategy for early metabolic and vascular risk modification in vitamin D-deficient prediabetics.