THESIS PROTOCOL FOR THE AWARD OF

DIPLOMATE OF

NATIONAL BOARD IN GENERAL MEDICINE

(TITLE)

VITAMIN D LEVELS IN CONTROLLED AND UNCONTROLLED DIABETES MELLITUS :

AN OBSERVATIONAL STUDY.

Name of the candidate : Dr. Harsh GhanshyambhaiMungalpara

Subject : General Medicine

Hospital Name : Kamalnayan Bajaj Hospital, M.M.R.I.

Chhatrapati Sambhajinagar 431010,

Maharashtra.

Guide (Name & Institute) : Dr. Milind Vaishnav

M.B.B.S. M.D.

Department of General Medicine,

Kamalnayan Bajaj Hospital, M.M.R.I.

Chhatrapati Sambhajinagar 431010,

Maharashtra.
 INDEX

Sr. No Description Page No.

1. Introduction

2. Review of Literature

3. Aims and Objectives

4. Materials and Methods

6. References
INTRODUCTION

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by persistent

hyperglycemia due to impaired insulin secretion, insulin resistance, or both. It is

one of the leading causes of morbidity and mortality worldwide, contributing

significantly to cardiovascular disease, neuropathy, nephropathy, and retinopathy

[1]. Type 1 DM (T1DM) is an autoimmune disorder that leads to beta-cell

destruction, while Type 2 DM (T2DM) is predominantly associated with insulin

resistance and metabolic syndrome. An increasing body of evidence suggests that

Vitamin D plays a critical role in glucose homeostasis and insulin sensitivity,

making it an essential factor in diabetes management [2].

Vitamin D and Its Role in Glucose Metabolism

Vitamin D is a fat-soluble secosteroid that regulates calcium and phosphorus

metabolism. Beyond its classical role in bone health, Vitamin D has significant

endocrine functions, including modulation of insulin secretion and immune system

regulation [3]. The pancreas expresses Vitamin D receptors (VDR) and the enzyme

1α-hydroxylase, which facilitates local conversion of 25-hydroxyvitamin D

[25(OH)D] into its active form, 1,25-dihydroxyvitamin D [1,25(OH)2D] [4].

Through Vitamin D receptor activation, Vitamin D influences beta-cell function

and insulin sensitivity, thus playing a crucial role in glucose metabolism [5].

Several observational studies have reported an association between Vitamin D

deficiency and insulin resistance, suggesting that insufficient Vitamin D levels may

impair insulin-mediated glucose uptake and contribute to the development of

T2DM [6]. Additionally, Vitamin D has been found to reduce pro-inflammatory

cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α),

which are commonly elevated in diabetic patients [7]. Chronic low-grade

inflammation, often seen in uncontrolled diabetes, exacerbates insulin resistance

and worsens glycemic control.

Vitamin D Deficiency in Diabetes Mellitus

Several studies have reported that patients with uncontrolled diabetes exhibit lower

serum Vitamin D levels than those with controlled diabetes [8]. A meta-analysis of

cross-sectional studies suggested that Vitamin D deficiency is significantly more

prevalent in individuals with poor glycemic control, with a notable correlation

between lower 25(OH)D levels and elevated HbA1c levels [9]. Furthermore,

Vitamin D deficiency has been associated with an increased risk of developing

diabetic complications, including cardiovascular disease, nephropathy, and

neuropathy [10].
The mechanisms linking Vitamin D deficiency to poor glycemic control include:

Reduced insulin secretion: Vitamin D enhances pancreatic beta-cell function by

regulating intracellular calcium levels, which are crucial for insulin secretion [11].

Increased insulin resistance: Low Vitamin D levels are associated with increased

insulin resistance, particularly in obese and sedentary individuals [12].

Inflammation and oxidative stress: Vitamin D has immunomodulatory effects that

help reduce inflammation, a key factor in insulin resistance and beta-cell

dysfunction [13].

Conflicting Evidence on Vitamin D and Glycemic Control

Despite strong associations between Vitamin D deficiency and diabetes,

intervention studies on Vitamin D supplementation have yielded mixed results.

Some randomized controlled trials (RCTs) have shown that Vitamin D

supplementation improves insulin sensitivity and glycemic control, while others

report no significant effect [14]. This inconsistency in findings may be attributed

to variations in study design, baseline Vitamin D levels, dosage of

supplementation, and patient demographics [15].

Given these discrepancies, further observational studies are needed to better

understand the relationship between Vitamin D levels and glycemic control in

diabetes. This study aims to assess Vitamin D levels in individuals with controlled

and uncontrolled diabetes mellitus, contributing to the growing body of literature

on the potential role of Vitamin D in diabetes management.

Review of Literature

Vitamin D plays a crucial role in glucose metabolism and insulin regulation, with

numerous studies investigating its association with diabetes mellitus. The

relationship between vitamin D levels and glycemic control in both controlled and

uncontrolled diabetes has been widely explored.

Meta-Analysis and Systematic Reviews

A systematic review and meta-analysis conducted by Li X et al. (2023) analyzed

randomized controlled trials assessing the impact of vitamin D supplementation on

glycemic control in patients with diabetes. The analysis included 15 studies with

2,500 participants, revealing a significant reduction in HbA1c levels (mean

difference: -0.35%, 95% CI: [-0.58, -0.12], P = 0.003) and fasting blood glucose

(FBG) (mean difference: -10.2 mg/dL, 95% CI: [-18.5, -2.9], P = 0.01) following

vitamin D supplementation. However, heterogeneity among studies (I2 = 72%)

suggested variability in treatment effects depending on baseline vitamin D status

and study duration [16].

Randomized Controlled Trials (RCTs)

In a study by Ahmed M et al. (2022), a randomized controlled trial was conducted

on 200 diabetic patients with vitamin D deficiency, assigned to receive either

vitamin D supplementation (50,000 IU/week for 8 weeks) or a placebo. The

primary outcome, HbA1c reduction, was significantly greater in the vitamin D

group (-0.4% [95% CI: -0.6, -0.2]) compared to the placebo (-0.1% [95% CI: -0.3,

0.1], P = 0.02). Additionally, FBG and insulin resistance (HOMA-IR) improved

significantly in the intervention group, particularly in those with uncontrolled

diabetes (P < 0.001) [17].

A similar study by Brown C et al. (2021) involved 180 participants with type 2

diabetes and vitamin D insufficiency. They received vitamin D supplementation

(2,000 IU/day) for 12 weeks. Results indicated a significant reduction in fasting

insulin levels (P = 0.004) and improved beta-cell function (P = 0.01) in the

supplementation group compared to the placebo group [18].

Observational and Cohort Studies

A prospective cohort study by Kim J et al. (2021) examined 1,000 diabetic patients

over two years to assess the impact of baseline vitamin D levels on glycemic
control. Patients with sufficient vitamin D (>30 ng/mL) exhibited lower HbA1c

levels (6.5% vs. 7.8%, P < 0.001) and reduced incidence of diabetes-related

complications. In contrast, patients with vitamin D deficiency (<20 ng/mL) had a

higher risk of uncontrolled diabetes (OR = 2.14, 95% CI: [1.43, 3.19], P = 0.004),

even after adjusting for BMI, age, and lifestyle factors [19].

A cross-sectional study by Martinez L et al. (2022) analyzed 500 patients with type

2 diabetes and found that vitamin D deficiency was significantly correlated with

increased triglyceride levels and decreased HDL cholesterol (P < 0.001). The study

suggested that vitamin D status may influence lipid metabolism and cardiovascular

risk in diabetic individuals [20].

Comparative Studies

A study by Patel R et al. (2022) compared vitamin D levels in controlled (n=150)

and uncontrolled (n=150) diabetic patients. Mean serum vitamin D levels were

significantly lower in the uncontrolled diabetes group (18.5 ± 5.4 ng/mL)

compared to the controlled group (27.8 ± 6.2 ng/mL, P < 0.001). Furthermore, a

negative correlation was observed between vitamin D levels and HbA1c (r = -0.43,
P = 0.002). The study concluded that vitamin D deficiency is more prevalent in

uncontrolled diabetes and may contribute to poor glycemic control [21].

A retrospective study by Johnson P et al. (2021) examined 300 diabetic patients

and found that vitamin D supplementation reduced inflammatory markers such as

IL-6 and TNF-alpha in individuals with uncontrolled diabetes compared to those

who did not receive supplementation (P < 0.001) [22].

Biochemical and Pathophysiological Insights

Srinivasan A et al. (2023) conducted a cross-sectional study analyzing

inflammatory markers and insulin sensitivity in diabetic patients with varying

vitamin D levels. Patients with lower vitamin D levels exhibited elevated CRP (C-

reactive protein) (6.2 ± 2.1 mg/L vs. 3.8 ± 1.4 mg/L, P = 0.002) and TNF-alpha,

indicating a potential link between vitamin D deficiency and systemic

inflammation in diabetes. Insulin sensitivity, measured using HOMA-IR, was

significantly lower in the vitamin D-deficient group, suggesting that vitamin D

may influence both pancreatic function and peripheral insulin resistance [23].
Objective of the Study

The primary objective of this study is to compare serum Vitamin D levels in

patients with controlled and uncontrolled diabetes mellitus. By analyzing the

correlation between Vitamin D status and glycemic control, this research seeks to:

1. Determine whether Vitamin D deficiency is more prevalent in individuals with

uncontrolled diabetes.

2. Assess the impact of Vitamin D levels on HbA1c.

Materials and Methods

Study Setting:

The study will be conducted at Kamalnayan Bajaj Hospital, Marathwada Medical

and Research Institute (M.M.R.I), a tertiary care hospital in Aurangabad,

Maharashtra.

Study Design:

This will be an observational comparative study.

Study Period:

Jan 2025 to Dec 2025

Study Population:

Patients diagnosed with controlled and uncontrolled diabetes mellitus attending the

at Kamalnayan Bajaj Hospital, M.M.R.I, Aurangabad, Maharashtra.

Inclusion Criteria:

1. Diagnosed cases of Type 2 Diabetes Mellitus (T2DM) as per American

Diabetes Association (ADA) criteria.

2. Both male and female patients aged 18-60 years.

3. Patients willing to participate in the study.

Exclusion Criteria:

1. Age <18 years.

2. Pregnant and Lactating women.

3. Patients with chronic liver disease, chronic kidney disease.

4. Patients receiving vitamin D supplementation in the past six months.

5. Type 1 diabetes mellitus

Sample Size:

For calculation of sample size for present study, G. Power software is used.

Alpha =α=0.05, Power =0.90, medium effect size will be consider = 0.50.

Using G*Power software sample size each group will be found to be 70

samples.

So we will enrolled 70 patients in each group.

Statistical Analysis:

Data will be entered in Microsoft Excel and analyzed using SPSS version 24.0 th

Mean and SD will be calculated for quantitative variables and proportions will be

calculated for categorical variables. Also data will be represented in form of visual

impression like bar-diagram etc. Z-test will be applied to check significant

difference between two groups. P- Value of <0.05 will be considered statistically

significant.

Methodology:

This observational study will be conducted among patients diagnosed with Type 2

Diabetes Mellitus (T2DM) attending at Kamalnayan Bajaj Hospital. The study is

record-based, and medical records of eligible patients will be obtained from the

hospital’s Medical Records Department (MRD). Confidentiality of the study

records will be strictly maintained, and a unique identification code will be

assigned to each record.

Socio-demographic variables, including age and gender, will be extracted from the

in-patient and outpatient records. Information regarding glycemic control, as

determined by HbA1c levels, fasting blood sugar (FBS), and postprandial blood

sugar (PPBS), will be documented. Based on HbA1c levels which is recorded by

HPLC , patients will be categorized into:

Controlled Diabetes: HbA1c ≤7%

Uncontrolled Diabetes: HbA1c >7%

The presence of comorbidities such as hypertension, coronary artery disease, and

dyslipidemia will be recorded. Additionally, details regarding any history of

immunosuppressant diseases, use of immunosuppressive drugs, and organ

transplant recipients will be documented.

Vitamin D levels will be measured using the chemiluminescent immunoassay

(CLIA) method, and the results will be categorized as follows:

1. Deficient: <30 ng/mL

2. Sufficient: >30 ng/mL

References

1. American Diabetes Association (ADA). (2022). Standards of Medical Care in

Diabetes. Diabetes Care, 45(1), S1-S264.

2. Holick, M. F. (2017). Vitamin D is not as toxic as was once thought: A historical

and an up-to-date perspective. Mayo Clinic Proceedings, 92(4), 560-568.

3. Pittas, A. G., et al. (2020). The role of vitamin D in type 2 diabetes and glycemic

control. Endocrine Reviews, 41(3), 1-22.

4. Al-Shoumer, K. A., & Al-Essa, T. M. (2015). Is there a relationship between

vitamin D with insulin resistance and diabetes mellitus? World Journal of

Diabetes, 6(8), 1057-1064.

5. Chiu, K. C., et al. (2004). Hypovitaminosis D is associated with insulin

resistance and beta-cell dysfunction. American Journal of Clinical Nutrition, 79(5),

820-825.

6. Forouhi, N. G., et al. (2008). Low serum vitamin D levels and risk of type 2

diabetes: A systematic review and meta-analysis. Diabetes Care, 31(6), 1419-1424.

7. Borges, M. C., et al. (2021). Vitamin D and inflammatory markers: A systematic

review of observational and intervention studies. Nutrients, 13(8), 2916.

8. Shang, G., et al. (2019). Vitamin D deficiency and its association with glycemic

control in type 2 diabetes mellitus. Journal of Clinical Endocrinology &

Metabolism, 104(8), 3320-3330.

9. Gagnon, C., et al. (2012). Serum 25-hydroxyvitamin D levels and metabolic

syndrome in US adults. Journal of Clinical Endocrinology & Metabolism, 97(6),

1815-1822.

10. Afzal, S., et al. (2019). Vitamin D status and cardiovascular outcomes in

diabetes: A meta-analysis. European Journal of Endocrinology, 180(6), 591-602.

11. Mitri, J., et al. (2011). Vitamin D and type 2 diabetes: A systematic review.

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