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Table of Content Volume 16 Issue 1 - October 2020

 

Study of relationship between serum 25 (OH) vitamin D and insulin resistance in prediabetic patients

 

Basavaraj GT1, Sharan Nandyal2*

 

1,2Assistant Professor Department of General Medicine Basveahwar Teaching and General Hospital Sedam Road Kalaburgi, Karnataka State India 585105.

Email: Basavgt8@Gmail.Com ,sharannandyal@gmail.com

 

Abstract              Background: Prediabetes is an intermediate stage between normal glucose levels and the clinical entity of type 2 diabetes. Indian population have one of the highest number of individuals with pre-diabetes and diabetes among all major ethnic groups. Deficiency of Vitamin D may have negative effects on glucose intolerance, insulin secretion. In patients with diabetes, administration of vitamin-D has been shown to decrease insulin resistance.8 However similar observation among individuals with prediabetes has not been documented. The aim of present study was to find out the relationship between Serum 25 (OH) Vitamin D and insulin resistance among prediabetic individuals. Material and Methods:Present study was a cross-sectional, observational study carried out in the Department of Medicine at XXXX medical college and Hospital, XXXX. 50 Prediabetic individuals, 25-50 years with fasting blood glucose between 100 – 125 mg/dl and/or 2-hour post-OGTT blood glucose of 140 - 199 mg/dl were included as cases and other 50 individuals with normal glucose tolerance were included as controls. Vitamin D levels among the two groups were compared by unpaired student t test. Association between vitamin D status and insulin resistance in individuals with prediabetes was studied using Pearson’s correlation co-efficient. p-value < 0.05 was considered significant. Results: Total 100 patients were studied, 50 prediabetic cases and 50 healthy controls. Age (in years), gender and BMI (kg/m2) were comparable in both groups. 66% prediabetic individuals had hypovitaminosis D as compare to 16% of healthy controls. A statistically significant difference was noted for Fasting Plasma Glucose, 2-hour Plasma Glucose, Insulin, HOMA-IR and 25 (OH) vitamin D values between prediabetic cases and healthy controls. A statistically significant correlation was noted between 25 (OH) vitamin D values with HOMA-IR and fasting insulin levels. Conclusion: The findings of the present study indicate that serum 25 (OH) vitamin D deficiency is common in prediabetic state and serum 25 (OH) vitamin D deficiency is associated with insulin resistance among adults with prediabetes.

Key Words: Vitamin-D deficiency, insulin resistance, prediabetes.

 

INTRODUCTION

Prediabetes is an intermediate stage between normal glucose levels and the clinical entity of type 2 diabetes (T2D), defined as Impaired Fasting Glucose (IFG) (Fasting plasma glucose 100 - 125 mg/dl) and Impaired Glucose Tolerance (IGT) [2 hr plasma glucose ≥140 and ≤199 mg/dl] after ingesting 75 g of glucose (OGTT); or a combination of both.1 Indian population have one of the highest number of individuals with pre-diabetes and diabetes among all major ethnic groups2, and the conversion from prediabetes to diabetes occurs more rapidly in this population than other ethnic groups.3 Pre-diabetic individuals are at increased risk of abdominal obesity, insulin resistance, non-alcoholic fatty liver disease and metabolic syndrome, and future risk for developing T2DM and cardiovascular disease.2 Prediabetes is considered a harbinger of overt type 2 diabetes mellitus with annual rate of progression to diabetes ranging from 2.5% (Diabetes Prevention Trial) to 18% (Indian Diabetes Prevention Programme-1).4 According to Indian Council of Medical Research report in 2011, prevalence of diabetes in Indian population was about 62.4 million and of prediabetes was about 77.2 million.5 Preventive efforts in prediabetic stage have been shown to be effective in delaying or preventing the onset of diabetes. Recent research on prevention of diabetes highlights the importance of modifiable risk factors and nutritional factors. One such factor is vitamin D, which is gaining lot of importance. Vitamin D has positive effects on insulin secretion and sensitivity and on inflammation. While deficiency of Vitamin D may have negative effects on glucose intolerance, insulin secretion, either directly via Vitamin D receptor (VDR) activation or indirectly via calcemic hormones and also via inflammation.6 A decreased serum 25(OH)D, calcitriol can increase intracellular calcium in adipocytes, which can stimulate lipogenesis predisposing a patient to further weight gain and thus increasing the risk of diabetes.7 In patients with diabetes, administration of vitamin-D has been shown to decrease insulin resistance.8 However similar observation among individuals with prediabetes has not been documented. The aim of present study was to find out the relationship between Serum 25 (OH) Vitamin D and insulin resistance among prediabetic individuals.

 

MATERIAL AND METHODS

Present study was a cross-sectional, observational study carried out in the Department of General Medicine Basveahwar Teaching and General Hospital Sedam Road Kalaburgi. Study period was 6 months (from October 2018 to March 2019). Institutional ethical committee clearance was taken prior to the study. Relatives/attendants of patients coming to our diabetic outpatient department, from age group of 25 - 50 years were screened for present study. Fasting blood glucose estimation (following overnight 8 hours fast) was done, following which patients underwent 75 gm Oral Glucose Tolerance Test. Patients were ask to take 75 gm glucose solution and blood glucose was estimated after 2-hour post-glucose ingestion.

 

Inclusion criteria

  • Prediabetic individuals with fasting blood glucose between 100 – 125 mg/dl (impaired fasting glucose) and/or 2-hour post-OGTT blood glucose of 140 - 199 mg/dl (impaired glucose tolerance) (As per ADA criteria)10

Exclusion criteria

  • History of any oral antidiabetic medications or insulin
  • Associated disorders like primary hyperparathyroidism, chronic kidney disease, liver disease, any chronic illness, malignancy,
  • History of chronic drug use like antiepileptic agents, oral contraceptive pills, steroids ( can interfere with Vitamin-D metabolism)
  • History of calcium or vitamin D supplementation in the last one year

After applying inclusion and exclusion criteria, total 50 prediabetes individuals were included in the study as cases. Other 50 individuals with normal glucose tolerance were included as controls.

Study was explained in local language and a informed written consent from the participants was taken. Demographic data was collected. Body mass index (kg/m2) was calculated as weight (in kilograms) divided by height (in meter squares). Routine biochemical blood investigations routine investigations (including complete blood count, renal and liver function tests, serum calcium and phosphate levels) and special blood investigations including serum vitamin D levels and insulin levels were done. Fasting serum insulin level was measured by commercially available Insulin IRMA kit (Immune-radiometric assay). Insulin resistance was measured using Homeostasis Model Assessment Insulin Resistance (HOMAIR):

HOMA-IR = Insulin (μIU/L) X Glucose (mmol/l)/22.5.

Serum 25 (OH) vitamin D levels were measured using commercially available DiaSorin 25 (OH) vitamin D 125I

RIA (radioimmune assay) Kit (DiaSorin, Stillwater, Minnesota 55082 - 0285, USA). The plasma 25 (OH) vitamin D concentrations were expressed in nano-gram per ml (ng/ml).

Data was analysed by SPSS Software. The vitamin D levels among the two groups were compared by unpaired student t test. Association between vitamin D status and insulin resistance in individuals with prediabetes was studied using Pearson’s correlation co-efficient. p-value < 0.05 was considered significant.


 

 

 

 

RESULTS

Total 100 patients were studied, 50 prediabetic cases and 50 healthy controls. Age (in years), gender and BMI (kg/m2) were comparable in both groups as shown in table 1. 66% prediabetic individuals had hypovitaminosis D as compare to 16% of healthy controls.

 

Table 1: Characteristics of prediabetic cases and controls.

Characteristics

Cases (n=50)

No. (%)

Controls (n=50)

No. (%)

Total (n=100)

Age group in years

25-40

19 (38%)

21 (42%)

40

41-50

31 (62%)

29 (58%)

60

Gender

Male

32 (64%)

30 (60%)

62

Female

18 (36%)

20 (40%)

38

Body mass index

≤ 25 kg/m2

20 (40%)

28 (56%)

48

> 25 kg/m2

30 (60%)

22 (44%)

52

Vitamin D levels (ng/ml)

Less than 20

33 (66%)

8 (16%)

41

20-29.9

10 (20%)

19 (38%)

29

More than 30

7 (14%)

23 (46%)

30

A statistically significant difference was noted for Fasting Plasma Glucose, 2-hour Plasma Glucose, Insulin, HOMA-IR and 25 (OH) vitamin D values between prediabetic cases and 50 healthy controls.

 

Table 2: Comparison of Glycaemic parameters, insulin levels, HOMA-IR and vitamin D levels

Variable

Cases (n = 50)

Controls (n = 50)

p-value

Significance

Fasting Plasma Glucose (mg/dl)

100.24 ± 9.18

84.27 ± 7.44

<0.001

Significant

2-hour Plasma Glucose (mg/dl)

153.87 ± 13.56

124.38 ± 11.46

<0.001

Significant

Insulin(uIU/ml)

18.26 ± 12.14

10.81 ± 8.29

<0.001

Significant

HOMA-IR

5.32 ± 2.96

2.31 ± 2.01

<0.001

Significant

25 (OH) vitamin D (ng/ml)

14.88 ± 11.36

22.16 ± 8.47

0.032

Significant

We compared 25 (OH) vitamin D values with Fasting Plasma Glucose, 2-hour Plasma Glucose, Insulin, HOMA-IR with help of Pearson’s Correlation co-efficient. A statistically significant correlation was noted between 25 (OH) vitamin D values with HOMA-IR and fasting insulin levels.

 

Table 3: Correlation between vitamin-D status and other parameters in prediabetes individuals.

Correlation variables

Pearson’s Correlation co-efficient

p-value

Significance

Parameter 1

Parameter 2

25(OH)D

HOMA-IR

-0.275

0.038

Significant

25(OH)D

Fasting insulin

-0.268

0.029

Significant

25(OH)D

Fasting Plasma Glucose (mg/dl)

-0.92

0.071

Non-significant

25(OH)D

2-hour Plasma Glucose (mg/dl)

-0.132

0.075

Non-significant

 


DISCUSSION

The International Diabetes Federation (IDF) has considered pandemics of vitamin D deficiency and diabetes worldwide.9 Individuals with IFG and/or IGT have been referred to as having pre-diabetes, indicating the relatively high risk for the future development of diabetes.10 The risk of progression to diabetes depends mainly on the degree of insulin resistance, deficiency of insulin secretion while other factors are age, family history, overweight or obesity or history of gestational diabetes or PCOS. Prediabetes is associated with increased risk of progressing to overt diabetes and its complications, according to an ADA expert panel, up to 70% of individuals with prediabetes will eventually develop diabetes.11 Vitamin D deficiency is largely due to inadequate cutaneous production and to a lesser extent from low dietary intake. The production of vitamin D in the body is dependent upon exposure to sunlight which in turn depends on the seasonal changes, latitude, clothing, skin pigmentation and use of sunscreens. In this study, vitamin D deficiency was the predominant vitamin D status among adults with prediabetes. This high prevalence of hypovitaminosis D in our cases group (66%) is in concordance with various other Indian studies who also reported prevalence of hypovitaminosis D in prediabetic individuals.12,13 Dutta et al. in their study among individuals with prediabetes, they noted that those having severe vitamin D deficiency (< 10 ng/ml), had the worst insulin resistance (HOMA2-IR) as compared to those having higher levels, with an inverse correlation between vitamin-D status and insulin resistance.14 Manju. M et al..15 noted a strong negative correlation between Vit D levels and insulin resistance, HOMA 2 IR in prediabetic individuals. Similar results were noted in present study. Studies have demonstrated an inverse relationship between serum 25(OH)D and diabetes, metabolic syndrome, insulin resistance, and beta cell function.16 The changing lifestyle, urbanization and modernization of Indian population has led to possible reduction of people being exposed to direct sunlight and inadequate intake of dietary vitamin D, thereby leaving the population at increased risk of vitamin D Deficiency and type 2 diabetes. Studies have also explored the possibility of intervention with vitamin D and prevention of progression towards diabetes. Pittas et al.. reported a significant reduction in fasting plasma glucose (FPG) and HOMAIR with supplementation of calcium and Vitamin D over a period of 3 years in people with prediabetes, but not in those with normal glucose tolerance.17 Indian studies by Harinarayan et al..18 noted improvement of insulin resistance and metabolism indexes in nondiabetic subjects with vitamin D deficiency after supplementation of Vitamin D. While Dutta et al. noted that vitamin D supplementation improved the glycemic control and insulin sensitivity in prediabetic individuals.19 Limitations of present study were small sample size, cross-sectional study, so our results cannot establish cause and effective relationship between vitamin D and prediabetes. Also a recent meta-analysis failed to show a positive effect of vitamin D supplementation on HOMA-IR and 2-hour plasma glucose after oral glucose tolerance test, but showed significant lowering of FPG and HbA1c in patients with pre-diabetes.20 So a population based; large sample sized prospective studies are required to assess role of vitamin D in prediabetic, role of supplementation of vitamin D in prevention of diabetes, halting progression from prediabetes to T2DM, and improving glycemic control.

 

CONCLUSION

The findings of the present study indicate that serum 25 (OH) vitamin D deficiency is common in prediabetic state and serum 25 (OH) vitamin D deficiency is associated with insulin resistance among adults with prediabetes.

 

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