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Correlation Between Fasting Blood Glucose and Hba1c With Vitamin D in Diabetes Mellitus

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ORIGINAL ARTICLE

Correlation Between Fasting Blood Glucose and Hba1c with Vitamin


D in Diabetes Mellitus
AKHMAD RAUMULFARO AKBAR1, EDWARD KURNIASETIAWANLIMIJADI2, MEITA HENDRIANINGTYAS2,
K. HERINUGROHO H.S3
1
Faculty of Medicine, Diponegoro University, Semarang, Indonesia
2
Department of Clinical Pathology, Faculty of Medicine, Diponegoro University, Semarang, Indonesia
3
Department of Internal Medicine, Faculty of Medicine, Diponegoro University, Semarang, Indonesia
Jl. Prof. Soedharto SH, Tembalang, Semarang, Central Java, Indonesia, 50275
Correspondence to Edward Kurnia Setiawan Limijadi, Email :edwardksl@fk.undip.ac.id

ABSTRACT
Background: Diabetes Mellitus (DM) is one of the largest health problems in the world. The prevalence of DM in
human population has increased globally. Fasting blood glucose and HbA1c is one of parameters for diagnosing
and monitoring DM. Vitamin D is a fat-soluble vitamin that has a role in glucose tolerance through its effect on
insulin secretion and sensitivity in DM and the vitamin D deficiency condition sometime happened. Further more,
the relation between fasting blood glucose and HbA1c with vitamin D in DM need to be investigated
Aim: To determine the correlation of fasting blood glucose and HbA1c with vitamin D in DM.
Methods: An observational analytic study with cross sectional approach in 46 subjects suitable with the inclusion
and exclusion criterias. This study was conducted from April to September 2019 in Rumah Sakit Nasional
Diponegoro (RSND) Semarang. Variables of this study were fasting blood glucose (FBG), HbA1c levels, and
vitamin D (25(OH)D). Data were analyzed by Spearman and Pearson correlation.Test was significant if p<0,05.
Result: Mean±SDof fasting blood glucose, HbA1c and vitamin D (25(OH)D) were 168,78 ±86,21mg/dL, 8,46±2,20
%, and 15,85±8,75 ng/mL. The correlation between fasting blood glucose and vitamin D were not significant with
p=0,193; r=0,195 and neither the correlation between HbA1c and vitamin D withp=0,153; r=0.214. Conclusion:
Assessment of vitamin D deficiency base on the measurement of the vitamin D in diabetes melitus and this
parameter don’t have correlation with FBG and HbA1c levels.
Keywords: Fasting blood glucose, HbA1c, Vitamin D, Diabetes Mellitus

INTRODUCTION microvascular (retinopathy, nephropathy and


neuropathy)6,7.
Diabetes Mellitus (DM) is one of the largest problems in the The latest guidance from scientific bodies around the
world. In recent years,prevalence of DM in human world recommends measuring 25 (OH) D serum as the test
population has been increased globally1. It has been of choice for assessing vitamin D status.8Serum 25 (OH) D
reported in “Riset Kesehatan Dasar” that the prevalence of levelis the best indicator for assessing vitamin D status
DM in Indonesia for population with aged ≥ 15 years has because 25 (OH) D level reflects the production of skin
increasedfrom 6,9% in 2013 to 8,5& in 20182. vitamin D3 and vitamin D (D2 and D3) from food. 25 (OH)
Diabetes mellitus is defined as a group of metabolic D also has a long half-life in circulation which is 3-4 weeks.
diseases characterized by chronic hyperglycemia caused Although the active metabolite of vitamin D is 1.25 (OH)
by damage of insulin secretion, insulin action or both, 2D, measurement of serum 1.25 (OH) 2D level is not
causing abnormalities in the metabolism of carbohydrates, recommended to determine vitamin D status because the
lipids, and proteins3. half-life in short circulation is 4-6 hours and its level in
The condition of hyperglycemia in DM increases serum is very low when compared with a level of 25 (OH)
reactive oxygen species (ROS) which induces oxidative D. When vitamin D deficiency occurs, parathyroid hormone
stress in pancreatic β cells. This oxidative stress increase secretion will increase as a compensatory response that
the production and release of pro-inflammatory mediators will stimulate the kidneys to increase production of 1.25
(cytokines and chemokines) which activate CYP27B1 (1α- (OH) D so that when vitamin D deficiency occurs, 25 (OH)
hydroxylase), an enzyme that cause 25 (OH) D to be D level are decreased, while level of 1.25 ( OH) 2D is
converted to 1.25 (OH) D, thereby reducinglevel of 25 (OH) maintained at normal or even elevated level9.
D OH) D and increasinglevel of 1,25 (OH) D4,5. Until now then, research on the relationship of fasting
Fasting blood glucose (FBG)was used as a parameter blood glucose and HbA1c level with vitamin D (25 (OH) D)
to distinguish diabetes mellitus patients from non-mellitus levels in diabetes mellitus especially in Indonesia is still
diabetes patients because fasting blood glucose has high limited, and also there were differences in previous studies
specificity. World Health Organization also recommends between these variables. Therefore, it needs advanced
measurement of HbA1c level to diagnose diabetes, HbA1c investigations.
tends to be stable in the blood for a longer period and the
examination can be done at any time without special
preparation. According to Metcalf PA, et al (2017), HbA1c
MATERIALS AND METHODS
has correlation with macrovascular complications An observational study with cross sectional approach was
(cardiovascular disease and ischemic stroke) and conducted in Rumah Sakit Nasional Diponegoro (RSND)
Semarang on April to September 2019. The subjects of the

P J M H S Vol. 13, NO. 4, OCT – DEC 2019 1093


Correlation Between Fasting Blood Glucose and Hba1c with Vitamin D in Diabetes Mellitus

study were 46 diabetes mellitus patients who met inclusion Table 1. Characteristicsof subjects
and exclusion criterias by consecutive sampling. The Parameter Mean± SD
incluson criterias were diabetic patients, >18 years old, Age (years) 57,85± 11,58
normal body temperature, normal liver function test, and Gender (%)
Male 36,96
willing to be respondent, while the exclusion criterias were
Female 63,04
anemia, pregnant, smoker, consuming vitamin D Sport activity (%)
supplements, patient with history of chronic liver, patient Yes 34,78
with history of chronic kidney disease, and stroke patient. No 65,22
Data in this study were identity of the patients, weight, Blood pressure (mmHg)
height, sport activity, blood pressure, percentage of body Sistol 131,89 ± 11,73
fat, hemoglobin levels, AST, ALT, FBG, HbA1c levels, and Diastol 82,83 ± 6,08
25(OH)D levels. Blood sampling, blood presureand the Percentage of body fat (%) 32,56 ± 6,48
percentage of body fat measurement weredone at Male 26,76 ± 6,77
laboratory of RSND. The measurement of hemoglobin Female 35,56 ± 5,03
Body weight (kilograms) 63,19 ± 11,54
levels, AST, ALT, FBG, HbA1c, and 25(OH)D was done at
Height (centimeters) 156,29 ± 7,87
laboratory of RSND, GAKI laboratory faculty of medicine
Body Mass Index (kg/m2) 25,72 ± 4,15
UNDIP, and laboratory of Prodia. Hemoglobin levels (mg/dL) 13,18 ± 0,95
The percentageofbodyfatwasdonebyomron body SGOT (mg/dL) 19,37 ± 5,2
composition monitor HBF-375. Fasting blood glucose were SGPT (mg/dL) 18,65 ± 5,33
measured by GOD-PAP method on automatic clinical Fasting blood glucose (mg/dl) 168,78± 86,21
chemistry analyzer architech C-4000, normal level of FBG HbA1c levels (%) 8,46± 2,20
is ≤ 100 mg/dl. HbA1c levels were measured by high Vitamin D (25(OH)D) levels (ng/mL) 15,85± 8,75
performance liquid chromatography (HPLC) on a D-10
system, normal level of HbA1c is less than 5,7%. 25(OH)D The percentage of body fat in female is higher than
levels were measured by Enzyme-Linked Immuno Sorbent male with BMI obtained in normal to overweight range.
Assay (ELISA )method, normal level of 25(OH) is 30- Fasting blood glucose levels in this study population
100ng/mL. ranged from normal to high, where the proportion of normal
Data analysis was performed by statistical FBG level was less than those of high levels. There were
programme computer. Normality test was Saphiro-Wilk and 21 (45,65%) subjects with normal FBG and 25 (54,35%)
data that were not normally distributed carried out data subjects with increased FBG, while HbA1c levels in all
transformation. Pearson correlation test was performed to subjects of this study were found to be increasing from
test correlation of HbA1c levels with vitamin D (25(OH)D) normal. 25(OH)D levels in this study were found decreased
levels and Spearman correlation was performed to test based on normal values.
relation of fasting blood glucose with vitamin D
(25(OH)D).p>0,05 was significant. Table 2: Correlation test results
Ethical clearance was obtained from the Medical and Vitamin D (25(OH)D)
Variable
Health Research Ethics Commission (KEPK) of the Faculty r p
of Medicine, Diponegoro University. Subjects were given a HbA1c 0,214 0,153a
brief explanation of the purpose, benefits, research Fasting blood glucose 0,195 0,193b
a
protocols, and possible side effects, and written informed Pearson correlation test
b
Spearman correlation test
consent was done.
Data was analyzed by parametric Pearson correlation test
RESULT for HbA1c and vitamin D (25(OH)D) and non-parametric
The population of this study were diabetes mellitus patients Spearman correlation test for fasting glucose test and
in RumahSakit Nasional Diponegoro (RSND) Semarang. vitamin D (25(OH)D). Based on the Pearson correlation test
This study was conducted from April to September 2019 in between HbA1c and vitamin D (25(OH)D), the result shows
RSND Semarang and the samples were examined in there was no significant correlation between HbA1c and
laboratory of RSND Semarang. There were 79 subjects vitamin D (25(OH)D). Based on the Spearman correlation
who were willing to be sampled, but only 46 subjects met test between fasting blood glucose and vitamin D
the inclusion and exclusion criteria. Descriptive are shown (25(OH)D), the result shows there was no significant
in table 1. correlation between fasting blood glucose and vitamin D
The gender distribution in this study was 17 (36,96%) (25(OH)D) as shown in table 2.
males and 29 (63,04%) females. The average age of
respondents was 57.85 ± 11.58 years. The youngest age in DISCUSSION
this study was 34 years and the oldest age was 79 years.
The result of Spearman correlation test between fasting
There were 16 (34.78%) subjects who routinely did sport
activities and there were 30 (65.22%) subjects who did not blood glucose with vitamin D (25(OH)D) showed that there
routinely do sport activities. was no significant correlation. The study conducted by
Alkhatatbeh in 2018 found that there was no significant
relationship between fasting blood glucose with vitamin D
(25(OH)D) in diabetes mellitus10. Tandon in 2014 also
stated there was no significant correlation between fasting

1094 P J M H S Vol. 13, NO. 4, OCT – DEC 2019


ORIGINAL ARTICLE

blood glucose with vitamin D (25(OH)D) in diabetes more frequent in women can also reduce vitamin D
mellitus11. synthesis, and also women have a higher percentage of fat
The result of this study differs from some previous than men thus they have lower concentrations of vitamin D
studies. Study conducted by Pannu in 2017 found there (25 (OH) D) than men. Furthermore, age also affects
was a negative relationship between fasting blood glucose vitamin D level due to reduced production of vitamin D in
and vitamin D (25(OH)D) in DM12. Another study in 2017 by the skin, lack of exposure to UV B sunlight, reduced food
Kanakaraju shows there was a negative relationship intake, reduced skin thickness, impaired absorption in the
between vitamin D (25(OH)D) with blood glucose intestine, and reduced hydroxylation in the liver and
parameters13. The same result was also mentioned by kidneys.In the study conducted by Al-Horani in 2016
Bhatt in 2018 there was a negative relationship between showed that there was a relationship between gender, age,
fasting blood glucose with vitamin D (25(OH)D in pre- and body mass index with vitamin D (25(OH)D) levels25.
diabetic population14. Another factors that can influence HbA1c level in this
Insignificant relationship between fasting blood study is glycation factors which can be influenced by the
glucose and vitamin D (25(OH)D) can be caused by levels of consumption of vitamin C, the levels of
several factors. One of them is the percentage of body fat. consumption of vitamin E, and alcoholism, as well as
Individuals with a high percentage of body fat can reduce Yunika (2017)9. In the study conducted by Ardekani in 2007
level of vitamin D (25(OH)D) because excess fat tissue can showed that consumption of vitamin D decreases serum
store fat-soluble vitamin D thus it reduces vitamin D is level of fasting blood glucose, LDL, and HbA1c
released in the bloodstream and serum 25(OH)D level significantly26.
become low15,16. Limitations in this study are the current study
The use of drugs such as glucocorticoid drugs,anti- subjects,they are not distinguished based on physical
hypertension may affect vitamin D (25(OH)D) level, activity, gender and age. This study also did not distinguish
glucocorticoids may affect function of osteoblasts and DM subjects based on BMI or body fat percentage.
osteoclasts thus it reduces vitamin D levels. Some Medicines were consumed by patients, where the use of
glucocorticoids also increase degradation of 25(OH)D and several drugs such as anti-hypertensive drugs,
1,25(OH)D due activation of pregnane X receptors17. In glucocorticoids, vitamin C supplements, vitamin E
addition, physical activity also affects plasma vitamin D supplements can influence the results of the study.
concentrations, a study conducted by Fernandes in 2017
showed that the concentration plasma vitamin D increases CONCLUSION
with physical activity18. Research conducted by Sakungin
2018 showed that physical activity may increases insulin Relationship between FBG and HbA1c levels with vitamin
sensitivity and increases glucose uptake by body tissues D (25(OH)D) level in diabetes mellitus patients are not
thus it reduce blood glucose level19. significant. Assessment of vitamin D deficiency base on the
The result of Pearson correlation test between HbA1c measurement of the vitamin D in diabetes melitus.The next
with vitamin D (25(OH)D) showed there was no significant study needs to be adjusted with interference factors related
correlation. The study conducted by Kumar in 2017 showed to variables detail that mention in limitation.
that diabetes mellitus could not be proven to have a
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