D Hypovitaminosis in Syrian Type 2 Diabetes Mellitus Patients: Lack of Relationship with Glycemic Control

 

Razan Ibrahim1*, Mohammad Imad Khayat2, Afraa Zrieki3

1Master Student in Biochemistry and Microbiology Department, Faculty of Pharmacy, Tishreen University, Lattakia, Syria.

2Assistant professor in Laboratory Medicine Department, Faculty of Medicine, Tishreen University, Lattakia, Syria.

3Doctor in Pharmaceutics and Pharmaceutical Technology Department , Faculty of Pharmacy, Tishreen University, Lattakia, Syria.

*Corresponding Author E-mail: razan-ibrahim202@hotmail.com

 

ABSTRACT:

Vitamin D is a hormone related to skeletal integrity and many other health conditions. Recent studies suggest an association between 25-hydroxyvitamin D [25(OH)D3]  and the risk of type 2 diabetes mellitus (T2DM). The aim of this study was to evaluate plasma 25(OH)D3 levels in T2DM Syrian patients in Lattakia city, and to assess the relationship between 25(OH)D3 levels and glycemic control in addition to other variables (gender, age, duration of diabetes, BMI, smoking and fast blood glucose (FBG)). A total of 75 T2DM patients were included in the study. 25(OH)D3 was measured in serum samples using radioimmunoassay (RIA) method. Glycosylated hemoglobin A1c (HbA1c) was measured in whole blood samples using fast ion-exchange resin separation method. FBG was determined in whole blood samples by commercially available biochemical kits. The SPSS 17.0 program was used for the statistical analysis. Probability (P) value less than 0.05 was considered statistically significant. Vitamin D deficiency (25(OH)D3 ˂ 20 ng/ml) was seen in 55% of T2DM patients. Uncontrolled HbA1c was seen in 61.33% of T2DM patients. There was no relationship between serum 25(OH)D3 and HbA1c or FBG (P=0.989, P=0.611 respectively). The relationship of 25(OH)D3 with gender, age, duration of diabetes, smoking were not significant (P>0.05). However, there was a significant relationship between 25(OH)D3 and BMI (P=0.042). Our findings suggests that vitamin D deficiency is common in T2DM Syrian patients in Lattakia , and Its incidence decreases with BMI, even though its role in glycosylated  hemoglobin could not be established.

 

KEYWORDS: Type 2 Diabetes Mellitus, D hypovitaminosis , and Glycosylated Hemoglobin (HbA1c).

 

 


 

1. INTRODUCTION:

Vitamin D, also called calciferol, exists in tow forms: vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol). Both forms are inactive, which are converted to the active form by tow enzymatic hydroxylation reactions, the first one in liver forming 25-hydroxyvitamin D3[25(OH)D3], which is the major circulating form of vitamin D and measured to assess a patients vitamin D status[1], and the second in kidney forming the final activated form calcitriol (1,25 dihydroxyvitamin D)[2].

 

Based on Endocrine Society’s recommendation, vitamin D deficiency should be defined as 25(OH)D3 ˂ 20 ng/ml, while vitamin D insufficiency is recognized as 25(OH)D3 of 20-29.99 ng/ml, and 25(OH)D3 ˃30 ng/ml is considered sufficient[2].

 

In addition to its important role in the calcium and phosphorus metabolism, Vitamin D has immunomodulatory, anti-inflammatory, antioxidant, antiangiogenic, and antiproliferative functions in many kinds of cells[3].

 

Type 2 diabetes mellitus, a commonly seen endocrine disorder characterized by hypoglycemia, is a significant global health care problem. Hence the prevalence of T2DM has increased in industrial countries and is expected to reach a world-wide prevalence of 4.4% by 2030[4]. Recently, there are several factors that seem to play a role in its development including genetics, lifestyle, environmental and nutritional conditions. Amongst nutritional factors, vitamin D  is likely to have an important role either in glycemic control or in attenuating diabetic complications[5,6]. Vitamin D deficiency appears to be related to the development of diabetes mellitus type 2[7], and its levels seems to affect glucose homeostasis[8]. The probable mechanisms indicating the role of vitamin D in glucose homeostasis is likely to be through beta cell dysfunction and insulin resistance in case of vitamin D deficiency[9, 10].  

 

The aim of this study was to evaluate 25(OH)D3 in type 2 diabetic Syrian patients in Lattakia city, and to evaluate the relationship of 25(OH)D3 with glycosylated hemoglobin HbA1c levels as a blood glucose control marker, and with some other factors like age, gender, body mass index (BMI), smoking, duration of the diabetic and FBG.

 

2.  MATERIALS AND METHODS:

2.1. Patients and Clinical Parameters:

The present study is a cross- sectional study with informed consent signed by all patients after explaining the objectives of the study. Our study sample comprised 75 diabetic patients of both gender recruited from Diabetes Centre in Lattakia – Syria between May 2015 and July 2016. Participation was voluntary and recruitment took place during working hours. The diagnosis of T2DM was confirmed by biochemical investigations according to World Health Organization (WHO) criteria[11]. Height, body weight were measured using standard methods. BMI was calculated using the equation “BMI = weight/height2(kg/meter2)”. Smoking status was divided into 2 categories: current smokers (if the subjects smoked currently), nonsmokers (if the subjects never smoked). Patients with type 1 DM, chronic renal disease, chronic liver disease, hypertension and cardiovascular diseases, anemia, pregnant and breast feeding women were excluded from the study. Patients taking supplements, antihypertensive agents, antiepileptics or any other drug that could affect vitamin D or HbA1c were also excluded.

 

2.2.  Sample collection and handling:

Blood samples were collected by standard procedure from each participant. 2.5 ml were placed in EDTA tube and used for HbA1c analysis. Plasma was separated by centrifugation within 5 minutes at room temperature and stored at 2-8°C for no more than 7 days. 2 ml were placed in heparin tube and used for FBG analysis after plasma separation by centrifugation.

 

Another 2.5 ml of collected blood were placed in evacuated glass tube for vitamin D determination. The blood was allowed to clot at room temperature (15-20°C) and centrifuged for 10 minutes to obtain hemolysis free serum. HbA1c was measured using Fast Ion-Exchange Resin separation method (Human Diagnostics®, Wiesbaden, Germany) using semi-automated spectrophotometer (Biosystems BTS-310, Barcelona, Spain). FBG was determined in whole blood samples by commercially available biochemical kits. Vitamin D levels were measured using 25(OH)D3 pre-extraction with acetonitrile, double antibody radioimmunoassay (RIA) ( DIAsource®, Louvain-la-Neuve, Belgium)[12].

 

2.3. Classification of vitamin D levels:

Serum levels of 25(OH)D3 were stratified into sufficient (˃30 ng/ml), insufficient (20-29.99 ng/ml) and deficient (˂20 ng/ml). Subsequently, we considered all 25(OH)D3 values of ˂20 ng/ml as vitamin D deficient and  ≥20 ng/ml as non-deficient[13].

 

2.4. Statistical analysis:

The SPSS 17.0 software program was used for the statistical analysis. The Chi square test was used to compare the categorical measurements between the groups. The ANOVA test was used for comparing the means of quantitative variables between three groups or more. The Kruskal-wallis test was used for comparing three groups or more independent samples.

 

Pearson’s correlation coefficient (r) was used to analyze the degree of association between two variables.  Probability (P) value less than 0.05 was regarded as statistically significant.

 

3. RESULTS:

3.1. Characteristics of the study population:

A total of 75 T2DM Syrian patients were included in this study with mean±SD age of 54,85±8.91 years. 55% of participant were females and 52% were current smokers. Base line datas shows a trend to overweight (defined as BMI ≥ 25) in our population with mean±SD BMI of 28.28±5.29. The mean duration of  T2DM was 6.93 years ranging from 1-26. General characteristics of the patients are shown in Table 1.

 

Table 1: General clinical and biochemical characteristics of the study population

Variable

Mean ± SD

Range

Age

54.85 ± 8.91

30-82

Gender (%)

female

male

55%

45%

BMI (kg/m2)

28.28 ± 5.29

17.67 – 46.87

Smoking (%)

yes

no

52%

48%

Duration of diabetes(years)

6.93±5,63

1-26

Fast blood glucose (mg/dl)

158.55±59.30

85-370

HbA1c

6.92±1.33

4-10.9

25(OH)D3 (ng/ml)

19.9 ± 5

8-33

 

Taking HbA1c cut off value of 6.5% as marker for glycemic control, we observed that 61.33% of our study population have uncontrolled glycemy. The patients were further subdivided, according to the HbA1c cutoff values suggested by American Diabetes Association (ADA), into excellent controlled glycemy (HbA1c: 4.5-6.5) (38.67%), good controlled glycemy (HbA1c: 6.5-7) (18.67%), acceptable controlled glycemy (HbA1c: 7.1-8) (24.0%) and poor controlled glycemy (HbA1c ˃8) (18.67%) (Figure 1).

 

 

 

 

Figure. 1: Patients distribution  according to glycemic control level 

 

The overall mean plasma 25(OH)D3 was 19.9 ±5 ng/ml (Table 1), 41 of 75 (54.7%) of participant had vitamin D deficiency, 25OHD levels ˂ 20 ng/ml, and 28 of 75 (37.3%) had vitamin D insufficiency, 25OHD levels between 20-29.99 ng/ml (Figure 2).

 

 

Figure. 2: Patients distribution according to 25(OH)D3 levels

 

3.2. Comparison of clinical and biochemical characteristics of the study population according to 25(OH)D3 levels:

Clinical parameters such as age, gender, smoking, duration of diabetes, and biochemical parameters such as HbA1c and FBG in T2DM patients were compared between the three groups of 25(OH)D3 levels where notably no significant difference was observed as shown in table 2. There was modest but statistically significant difference of BMI in T2DM patients across the 3 different subgroups of 25(OH)D3 levels (P = 0.042) (Table 2). Increased BMI (˃25 kg/m2) was seen in 76% of T2DM patients. In unexpected manner, the highest BMI (31.2 ± 8.4) was observed in 25(OH)D3 sufficient group (25(OH)D3 ˃30 ng/ml) as opposed to BMI of 29.6 ± 5.46 in 25(OH)D3 insufficient group (25(OH)D3: 20-29.99 ng/ml), and BMI of 26.9 ± 4.2 in 25(OH)D3 deficient patients (25(OH)D3 ˂ 20 ng/ml). However, this difference was not significant when we considered all 25(OH)D3 values of ˂ 20 ng /ml as vitamin D3 deficient and ≥ 20 ng/ ml as non-deficient. The other clinical and biochemical indices (age, gender, smoking, FBG, HbA1c) are still have no difference between these 2 groups of vitamin D. However this stratification of vitamin D levels revealed a significant difference (P = 0.039) of duration of diabetes between deficient (25(OH)D3 ˂ 20 ng/ml) and non-deficient T2DM (25(OH)D3 ≥ 20 ng/ml) (Table 3).

 

 

 

 

 

 


Table 2: Comparison of clinical and biochemical characteristics of study population according to sufficient, insufficient, or deficient 25(OH)D3 levels:

Total

N=75

25(OH)D3 < 20 ng/ml

mean±SD: 16.01± 4.06

N=41        55%

25(OH)D3 :20-29,99 ng/ml

mean±SD: 23.80±2.99

N=28       37%

25(OH)D3 > 30 ng/ml

mean±SD: 31.324±0.98

N=6       8%

P value

 

Mean ± SD

Range

Mean ± SD

Range

Mean ± SD

Range

Age (years)

55.4±10.6

30-82

54.1±7

45-70

54.3±4.3

49-61

0.665

Gender

(%)

male

N=19

46%

N=12

43%

N=3

50%

0.932

female

N=22

54%

N=16

57%

N=3

50%

BMI (kg/m2)

26.9±4.2

17.7-33.9

29.6±5.6

22-44.9

31.2±8.4

22.9-46.9

0.042

Smoking (%)

yes

N=22

54%

N=16

57%

N=1

17%

0.188

no

N=19

46%

N=12

43%

N=5

83%

Duration of diabetes (years)

8.1±6.1

1-26

5.3±4.8

1-20

6.3±4.8

1-14

0.106

Fast blood glucose(mg/dl)

155.5±57.3

85-350

167.7±67.1

86-370

136.8±33.5

102-197

0.611

HbA1c

6.9±1.2

4.4-10.9

6.9±1.5

4-9.4

1.4±7

5.3-9.5

0.989

 

Table 3: Comparison of clinical and biochemical characteristics of the study population according to deficient and non-deficient 25(OH)D3 levels:

Total

N=75

25(OH)D3 ˂ 20 ng/ml

mean±SD: 16.01±4.06

N=41    55%

25(OH)D3 ≥ 20 ng/ml

mean±SD: 26.013±4.24

N=34       45%

P value

 

Mean ± SD

Range

Mean ± SD

Range

Age (years)

55±10.6

30-82

54.2±6.6

45-70

0.556

Gender

 (%)

male

Female

0.758

19.9±5.3

20±4.8

BMI (kg/m2)

26.9±4.2

17.7-33.9

29.9±6.1

22-46.9

0.060

Smoking (%)

yes

N=22

53.7%

N=17

50%

0.752

no

N=19

46.3%

N=17

50%

Duration of diabetes (years)

8.1±6.1

1-26

5.5±4.8

1-20

0.039

Fast blood glucose(mg/dl)

155.5±57.3

85-350

162.2±63.2

86-370

0.702

HbA1c

6.9±1.2

4.4-10.9

6.9±1.5

4-9.4

0.936

 


 


 

Vitamin D


Figure. 3: correlation between 25(OH)D3 and HbA1c and FBG levels

 


Results from correlation analysis indicates that continues values of HbA1c (r = 0.052, P = 0.66 ) and FBG  (r = 0.072, P = 0.539) did not have any statistically significant correlation with overall continues plasma 25(OH)D3 levels (Figure 3).

 

Similarly, no significant association was detected of the both parameters with 25(OH)D3 levels through the 3 subgroups of 25(OH)D3 levels, deficiency (˂ 20 ng/ml) (HbA1c: r = 0.052 , P = 0.749 , FBG: r = 0.277 , P = 0.08), insufficiency (20-29.99 ng/ml) (HbA1c: r = 0.145 , P = 0.462 , FBG: r = 0.112 , P = 0.571), or sufficiency (˃ 30 ng/ml) (HbA1c: r = 0.0228, P = 0.966, FBG: r = 0.055 , P = 0.917) (Figure 4).


 

 

Figure. 4: Relationship between vitamin D and HbA1c and FBG in deficient, insufficient, and sufficient 25(OH)D3 T2DM patients

 


Additionally, results of correlation analysis between 25(OH)D3 levels and other clinical indices did not reveal any correlation of age, BMI, and duration of diabetes with vitamin D deficiency, insufficiency, and sufficiency (Table 4).


 

Table 4: Correlation of (age, BMI, and duration of diabetes) with 25(OH)D3 levels:

Vit D (ng/ml)

25(OH)D3 ˂ 20 ng/ml

25(OH)D3 :20-29,99 ng/ml

25(OH)D3 > 30 ng/ml

r

P

r

P

r

P

Age(years)

-0.01

0.949

-0.25

0.202

0.03

0.951

BMI

-0.02

0.907

-0.18

0.364

-0.08

0.086

Duration of diabetes

-0.09

0.580

0.18

0.356

0.75

0.086

 


Finally the mean serum concentration of 25(OH)D3 was again not statistically different between male and female (19.9±5.3, 20±4.8 ) respectively (P=0,758), neither between smoker and non smoker T2DM patients (19.1± 3.6, 20.8 ± 6)  respectively ( P = 0.324).

 

4. DISCUSSION:

Vitamin D deficiency is considered a worldwide  health issue[14]. The diverse effect of vitamin D on glucose and calcium homeostasis has made it an ideal factor to know its role in glycemic control in T2DM[12,15-19]. We hypothesized that vitamin D deficiency may be prevalent in a population of T2DM patients and that vitamin D may be related to glucose control in this group of patients. So, the aim of our study was to evaluate levels of 25(OH)D3 and the relationship between 25(OH)D3 levels and glycemic control represented by HbA1c level.

 

The first notable point in our study was the high prevalence (55%) of vitamin D deficiency defined as   (˂ 20ng/ml) with mean±SD of 16.01±4.06. Syria is considered a sunny country, and it is expected that sufficient sun light is received throughout the year. This high prevalence of D hypovitaminosis  highlights the need for larger controlled study in order to evaluate the prevalence of vitamin D deficiency in Syrian population.

 

This vitamin D deficiency is likely to be due to low exposure to direct sunlight, low mobility, dietary habits, or malabsorption[20]. Life style factors, especially in-door working or working in close environment with minimum sun exposure is likely to explain the high prevalence of vitamin D deficiency in our population. Maximum sun exposure required for conversion of 7-dehydrocholestrol to pre-vitamin D3 is between 11 am and 2 pm[21]. However, normal office hours in Syria are usually from 8 am to 3 pm forcing most of worker people to stay indoor during this time with restriction of sun light exposure. Though the observational studies cannot demonstrate the cause and effects related to vitamin D, lower vitamin D status might be a reflect of sedentary lifestyle and chronic non-specific illness. Our finding is consistent with previously published studies demonstrating high prevalence of vitamin D deficiency in T2DM patients. in one study, 74.6%  of patients with T2DM had D hypovitaminosis[22]. In another published study from Kashmir, vitamin D deficiency was found in 91% of patients with diabetes and 58 % of the healthy control[23]. In another similar study done by Sheth et.al, vitamin D deficiency (˂20 ng/ml) was a common finding affecting  approximately 91.4% and 93.0% of T2DM cases and control subjects respectively[24]. However, a study done by Yaturu et.al showed lower incidence (31%) of vitamin D deficiency in T2DM[25]. This marked variation in prevalence of vitamin D deficiency might be due to the structure of the study population (ex. the age of subjects), study design, the variability of ethnicity, geographical environment, duration of diabetes (diagnosis vs. follow up) and glycemic control.

 

Vitamin D deficiency is thought to influence the insulin resistance and the pathogenesis of T2DM by affecting either insulin sensitivity, β cell function, or both[26,27]. However, we have found no significant difference in FBG, HbA1c in groups of T2DM patients with D hypovitaminosis ( insufficiency, deficiency 25(OH)D3) versus patients with normal vitamin D status (Table2 ). Similar findings have been reported previously[12,24,28]. However other studies revealed contrast results[12,29,30].

 

The design of our study was cross-sectional not focused on monitoring the impact of vitamin D itself on glycemic control. Therefore, we did not measure the glycemic parameters before and after vitamin D supplementation.

 

We have found no correlation between 25(OH)D3 values with FBG or HbA1c. Luo et.al. also showed that within T2DM subjects, regardless of common finding of vitamin D deficiency, low vitamin D was not associated with glycemic control[15]. Although a number of epidemiological studies and meta analysis showed an association between low serum  25(OH)D3 and impaired glycemia[31,32], Vitamin D intervention trials have had inconsistent results.

 

In a recent study by Davidson et.al. on subjects unknown to have diabetes failed to demonstrate the effect of vitamin D supplementation to predict the development of diabetes in pre-diabetic and those with low vitamin D level compared to placebo group[33]. Further, Kampmann et.al. and Witham et.al. showed that improvement in vitamin D status may increasee insulin secretion but did not improve insulin resistance or HbA1c in patients with T2DM[34, 35].

 

Therefore, it is uncertain whether vitamin D deficiency and poor glycemic control are causally inter related or they represent two independent features of T2DM. The height prevalence of D hypovitaminosis in T2DM patients highlights the need for prospective studies in order to evaluate the impact of vitamin D supplementation on glucose metabolism.

 

We evaluated the relationship between vitamin D levels and some clinical variables: age, gender, BMI, smoking in addition to duration of diabetes. We did not found statistically significant different in the mean of age cross different subgroups of vitamin D levels ( P=0.665). Mauss et.al revealed the same result[36]. Similarly no significant difference was observed in vitamin D levels according to gender ( P=0.758) or current smoking status (P=0.188) which is consistent with many previous studies[12,37]. However, in the study of Mauss et.al. deficiency of 25(OH)D3  was associated with female gender,  which was explained by the relation to postmenopausal effects as the mean age of female in their study was 51.8 years. In our study  55 % of our population was female with a mean age of 53.7 years[36].

 

Taking a 25(OH)D3 ˂ 20 ng/ml as cut off for vitamin D deficiency we have observed a statistically significant difference in diabetes duration between deficient (˂ 20 ng/ml) and non-deficient (≥ 20 ng/ml) vitamin D subgroups. Similar results was detected by Sheth et.al[24] while  the study of  Laway et.al. showed contrast results[12]. It has been previously demonstrated that β-cells reserve attenuates with the progression in the duration of T2DM[38]. Furthermore, vitamin D receptors have been found in pancreatic β-cells[39], which additionally have been found to express the enzyme 1-α-hydroxylase[40]. It has been also demonstrated that vitamin D facilitates the secretion of insulin from pancreatic β-cells, thus appearing to regulate insulin secretion[41]. These information mentioned above could explain the relationship between vitamin D deficiency and duration of diabetes, where  the number of β-cell decreases by extended duration of diabetes. However, it is not possible to determine any causal conclusion about the direction of the effects in this relationship we observed, and regardless of our results concerning  the absence of association between vitamin D deficiency and glycemic control. This is possibly because the inflammatory  mechanisms are extremely stimulated by the diabetic milieu or the β-cell dysfunction, and insulin resistance is more severe and less reversible by extended duration of diabetes as explained by Luo et.al [15].

 

The most surprising results of our study is that vitamin D status showed positive relationship with BMI (P = 0.042), but this relation was not significant after considering all 25(OH)D3 levels ˃ 20 ng/ml as non-deficient. Our finding regarding BMI is contrary to most of the present literature. Several studies have shown that patients with D hypovitaminosis had higher prevalence of over weights or obesity when compared to patients with normal 25(OH)D3 status[22,36,42,43]. However the study of Sheth et.al. showed as well no significant difference in BMI between vitamin D deficient (25(OH)D3 ˂ 20 ng/ml) and non- deficient (25(OH)D3 ≥ 20 ng/ml) subgroups. Furthermore, it is important to notice that in our T2DM population the BMI in the 3 subgroups of vitamin D status was above 25 kg/m2. So, the higher BMI observed in vitamin D sufficiency group of our population could be related to their life style factors, especially dietary regimens. It is common in our country that T2DM patients try to avoid sugar and carbohydrate content in their meals and replace them by protein or fat rich foods, which are a good sources of lipid soluble vitamin D. Therefore, more the patient eat fatty food, more he would got weight and have higher vitamin D level.

 

Several mechanisms have been hypothesized to clarify this reverse relationship between 25(OH)D3 levels and BMI. One of the most discussed mechanisms is explained by low bioavailability of vitamin D when height content of body fat acts as a reservoir for lipid soluble vitamin D and increase its sequestration[44]. Furthermore, the synthesis of 25(OH)D3 may be decreased in obese subjects because hepatic steatosis[45,46].  In addition, low sun exposure and limited cutaneous vitamin D synthesis in obese patients may also play a role[47]. Total body fat includes both peripheral adipose at the hip and thigh, with beneficial metabolic effects in both men and women[48], as well as less healthy upper body and central fat depots[49]. The opposing effects of these adipose depots could possibly weaken or inverse any correlation of BMI with vitamin D levels. However, in the study of  Mcgill et.al.2008, although an inverse relation between BMI and vitamin D was revealed, no relationship of fat % with vitamin D was found reflecting the influence of fat- free compartments of bone, muscle and abdominal organ (liver, kidney, gut)[50]. This idea had further confirmed in the study of Raska et.al.where they observed a significant negative association between 25(OH)D3 level and total body lean mass[51]. This come in line with animal studies, which reported that 25(OH)D3 status are distributed in the body fat and also in muscle tissue[52]. Therefore, it is attempting to speculate that muscle can create another reservoir of vitamin D also in human.

 

When interpreting our findings, several limitation must be taken into consideration. First, small size and cross sectional design. It is an observational study carried out on a population of T2DM patients without comparison with control group. Second, it is an observational study, with cross-sectional design, so it is not possible to draw any causal conclusion about the direction of effects in the relationships we observed. Third, we did not assess anti-diabetic medication of participants. Finally, it would be worthwhile to see the effect prevention or delaying of vitamin D supplementation on the onset of new diabetes in well-designed controlled prospective studies.

 

5. CONCLUSION:

Our study has revealed that vitamin D deficiency is prevalent in T2DM subjects in Lattakia, Syria (55%), which emphasize the need for routine screening for 25(OH)D3 levels. Low serum vitamin D was related to BMI and duration of diabetes but not to age or gender. However, the relationship of vitamin D deficiency with glycemic control in T2DM could not be confirmed in our population. This is potentially an important finding for public health, demonstrating that improvement of vitamin D status is not the only factor responsible for better health of the individuals but life style and dietary changes seem to play a role which will improve the overall health including hemoglobin glycation along with vitamin D levels.                 

 

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Received on 24.06.2018          Modified on 05.07.2018

Accepted on 30.07.2018        © RJPT All right reserved

Research J. Pharm. and Tech 2018; 11(12): 5319-5326.

DOI: 10.5958/0974-360X.2018.00968.X