The Association Between Vitamin D Deficiency and the Level of Fasting C Peptide Among Patients With Uncontrolled Type 2 Diabetes Mellitus: A Retrospective Cohort Study

Type 2 diabetes mellitus (T2DM) is a prevalent chronic metabolic disorder characterized by insulin resistance and relative insulin deficiency, associated with complications such as cardiovascular disease, nephropathy, neuropathy, and retinopathy. Achieving and maintaining glycemic control is central to management. Vitamin D has roles in bone health, immunity, and inflammation and may influence insulin secretion and sensitivity, potentially affecting glucose metabolism and T2DM risk. C peptide, a marker of endogenous insulin secretion, reflects β-cell function and the progression of T2DM and can guide therapy. This study aims to investigate the correlation between vitamin D deficiency and uncontrolled T2DM (elevated HbA1c) and assess the association between fasting C peptide levels and uncontrolled T2DM, providing insights into potential biomarkers and therapeutic avenues.

Prior studies suggest vitamin D may modulate insulin secretion and sensitivity, linking deficiency with higher T2DM risk. Evidence in high-risk populations remains limited, underscoring the need for targeted research to inform prevention. T2DM populations frequently exhibit vitamin D deficiency, associated with worse insulin resistance and glycemic control. Fasting C peptide is a key indicator of β-cell function and can predict therapeutic needs, including insulin initiation. Despite individual importance, the combined association of vitamin D deficiency and fasting C peptide levels with uncontrolled T2DM is underexplored. Understanding their intersection could guide personalized management strategies and reduce complications.

Design: Retrospective cohort study to assess associations between exposures (vitamin D status, fasting C peptide levels) and uncontrolled T2DM. Setting and timeframe: Specialized private diabetic clinic in Abha, Saudi Arabia; April–June 2023. Participants: Adults (≥18 years) with diagnosed T2DM and available baseline vitamin D, fasting C peptide, and HbA1c data. Exclusions: Other diabetes types (type 1, gestational) and conditions affecting vitamin D metabolism. Convenience sampling from clinic attendees; 72 participants were randomly selected from those meeting criteria. Informed consent obtained. Data collection: Two visits. Baseline collected demographics (age, gender), clinical history (duration of diabetes, prior management), and measurements: serum vitamin D, fasting C peptide, BMI, systolic/diastolic blood pressure, HbA1c, serum creatinine, total cholesterol, triglycerides. Follow-up at three months repeated these measures. Primary outcome: uncontrolled T2DM defined as HbA1c > 7% over follow-up. Secondary outcomes included medication changes, diabetic complications, and healthcare utilization. Statistical analysis: Descriptive statistics (frequencies, means ± SD). Wilcoxon rank tests compared first vs second visit parameters. Binary logistic regression examined associations of vitamin D and fasting C peptide with uncontrolled T2DM at initial visit (HbA1c > 7%), using bivariate and multivariate models with odds ratios and 95% CIs. Analyses conducted in SPSS. Ethics: Approved by King Khalid University IRB (ECM#2023-1009). Data handled with confidentiality and anonymity; stored for analysis.

- Wilcoxon first-to-second visit changes: weight increased 77.194 to 78.507 kg (p = 0.010); systolic BP 133.388 to 131.647 mmHg (p = 0.370, NS); diastolic BP 75.625 to 74.295 mmHg (p = 0.236, NS); HbA1c 10.062% to 7.586% (p = 0.001); creatinine 0.7711 to 0.861 (p = 0.001); triglycerides 174.250 to 189.708 mg/dL (p = 0.001); vitamin D 21.155 to 32.047 ng/mL (p = 0.001). - Regression analysis of clinical parameters (Table 4): weight β = 1.313, p = 0.050; systolic BP β = -1.741, p = 0.250 (NS); diastolic BP β = 1.330, p = 0.150 (NS); HbA1c β = -2.476, p = 0.002; creatinine β = 0.090, p = 0.003; triglycerides β = -0.081, p = 0.002; vitamin D β = 1.354, p = 0.002. - Logistic regression for uncontrolled T2DM (HbA1c > 7%) (Table 5): vitamin D B = -0.097, p = 0.181, OR = 0.908 (NS); C peptide B = -0.222, p = 0.797, OR = 0.801 (NS). Trend suggests higher vitamin D and C peptide associated with lower odds of uncontrolled diabetes, but not statistically significant in this analysis.

Findings indicate clinically meaningful improvements in glycemic control and vitamin D status over three months, with mixed changes in other metabolic parameters. Regression analyses suggested significant associations between several physiological variables (HbA1c, creatinine, triglycerides, vitamin D) and outcome measures, highlighting their roles in diabetes management. Although logistic regression did not show statistically significant associations of vitamin D and fasting C peptide with uncontrolled T2DM at conventional levels, point estimates trend toward protective effects, aligning with biological plausibility and prior literature indicating vitamin D’s influence on insulin secretion/sensitivity and C peptide as a marker of β-cell function. Mechanistically, vitamin D receptors in β cells and insulin-sensitive tissues suggest pathways through which vitamin D may impact glycemic control; fasting C peptide reflects β-cell reserve, which declines with chronic hyperglycemia and insulin resistance. Integrating vitamin D status assessment and C peptide monitoring could inform personalized treatment, though larger studies are needed to clarify causality and effect magnitude.

Higher vitamin D and fasting C peptide levels appear to be associated with a reduced likelihood of uncontrolled T2DM (HbA1c > 7%), though associations were not statistically significant in this cohort. The study supports continued evaluation of vitamin D status and β-cell function markers in T2DM management. Future research with larger samples and longitudinal designs is needed to validate these trends, elucidate mechanisms, and inform targeted therapeutic strategies and guidelines emphasizing optimization of vitamin D for glycemic and metabolic health.

- Potential confounding not measured: dietary vitamin D intake, sunlight exposure, and vitamin supplement use, which may influence vitamin D status and glycemic control. - Retrospective cohort design limits causal inference and directionality of associations. - Single-center setting with convenience sampling may limit generalizability. - Small sample size (n = 72) limits statistical power, possibly contributing to non-significant findings in logistic regression.