|Year : 2016 | Volume
| Issue : 2 | Page : 76-80
Vitamin D deficiency and its correlation to hemoglobin A1C in adolescent and young adult type 1 diabetes mellitus patients
Amira M Elsayed1, Ghada A Mohamed2
1 Department of Internal Medicine, Benha Faculty of Medicine, Benha University, Benha, Egypt
2 Department of Internal Medicine, Assiut Faculty of Medicine, Assiut University, Assiut, Egypt
|Date of Submission||25-Feb-2016|
|Date of Acceptance||19-Apr-2016|
|Date of Web Publication||21-Oct-2016|
Ghada A Mohamed
Department of Internal Medicine, Assiut Faculty of Medicine, Assiut University, PO Box: 71511
Source of Support: None, Conflict of Interest: None
Some studies have described the relationship between autoimmune diabetes or type 1 diabetes mellitus (T1DM) and vitamin D deficiency. Few studies correlate between vitamin D deficiency and glycemic control.
This study was conducted to appraise the status of vitamin D in adolescent and young adult T1DM patients and to correlate its deficiency to glycated hemoglobin (HbA1c).
Patients and methods
Around 63 Kuwaiti patients with T1DM were recruited in a descriptive cross-sectional study in April 2015. Serum level of vitamin D [25(OH)D] was measured using enzyme-linked immunosorbent assay, and glycemic control was measured by HbA1c using autoanalyzer. The relationship between vitamin D levels and HbA1c was analyzed by Spearman’s correlation. Among the participants, 21 (33.3%) were male and 42 (66.7%) were female. The mean age was 18.41±6.19, and the mean diabetes duration was 6.98±4.99. The mean vitamin D concentration was 47.29±2.91 nmol/l, with 38.1% of participants identified to have vitamin D deficiency and 19% identified to have vitamin D insufficiency. There were high levels of HbA1c (10.08±2.28), with a significant inverse correlation between HbA1c and vitamin D (r=−0.374 and P=0.003).
Low vitamin D in T1DM is extremely highly and closely correlated to HbA1c. We recommend that evaluation of the level of vitamin D in type 1 diabetic patients is very critical, and vitamin D supplementation may improve glycemic control.
Keywords: HbA1c, type 1 diabetes mellitus, vitamin D
|How to cite this article:|
Elsayed AM, Mohamed GA. Vitamin D deficiency and its correlation to hemoglobin A1C in adolescent and young adult type 1 diabetes mellitus patients. Al-Azhar Assiut Med J 2016;14:76-80
|How to cite this URL:|
Elsayed AM, Mohamed GA. Vitamin D deficiency and its correlation to hemoglobin A1C in adolescent and young adult type 1 diabetes mellitus patients. Al-Azhar Assiut Med J [serial online] 2016 [cited 2018 May 23];14:76-80. Available from: http://www.azmj.eg.net/text.asp?2016/14/2/76/192643
| Introduction|| |
Vitamin D deficiency and diabetes mellitus are two common situations, and they are widely prevalent across all ages, races, geographical regions, and socioeconomic conditions . 1,25(OH)2D3 plays an immune-modulatory part in the prevention of type 1 diabetes mellitus (T1DM) . At the level of the pancreatic islets, 1,25(OH)2D3 decreases in-vivo and in-vitro proinflammatory chemokine and cytokine expression (e.g. interleukin-6), which are involved in the pathogenesis of T1DM, making β-cells less chemoattractive and less prone to inflammation; this results in decreased T-cell recruitment and infiltration, increased regulatory cells, and arrest of the autoimmune process.
At the level of the immune system, 1,25(OH)2D3 inhibits the differentiation and maturation of dendritic cells and stimulates their apoptosis, preventing their transformation into antigen-presenting cells, which is the first step in the initiation of an immune response . It has been demonstrated by a research study that the death of islet cells and its supplements can be easily prevented by vitamin D, which in turn will enhance the production of insulin . In addition, studies in humans have shown that vitamin D supplementation in infancy reduces the risk of T1DM during early adulthood . Many observational studies have evaluated the 25-hydroxyvitamin D [25(OH)D] level in T1DM patients and found a significantly higher prevalence of 25(OH)D deficiency in T1DM patients compared with controls, and have therefore suggested that the vitamin D levels of diabetic patients should be assessed on a regular basis, to ensure appropriate healthcare delivery ,. A decrease in the levels of 25(OH)D leads to increased levels of glucose. Similar to this, the reduced levels of 25(OH)D are also related to the increased levels of glycated hemoglobin (HbA1c) . There is a paucity of studies that assessed the relationship between HbA1c and vitamin D levels in T1DM, and thus we are trying to find out this relationship in this study.
| Objective|| |
The study aimed to evaluate the status of vitamin D in T1DM, and to assess the relation between vitamin D deficiency and glycemic control in T1DM patients.
| Patients and methods|| |
Study design and participants
We have selected a descriptive cross-sectional research design. The study recruited 63 patients with established diagnosis of T1DM. The participants were selected from the diabetic outpatient clinic of primary healthcare center in Kuwait state on April 2015. The age range of the patients was between 13 and 36 years. Data of the patients, including, age, duration of diabetes mellitus, BMI, HbA1c, and serum 25(OH)D, were collected.
Morning venous blood samples were collected and centrifuged within 1 h and stored at −20°C until the time of batch analysis. Serum 25(OH)D was determined using a competitive binding protein assay (Immundiagnostik AG, Blenheim, Germany). Circulating levels of glycosylated hemoglobin (HbA1c), a clinical indicator of blood glucose control, were measured by Hitachi 911 autoanalyzer (Hitachi Co. Ltd., Tokyo, Japan).
According to HbA1c, the participants were divided into three categories that include good glycemic control (HA1c≤7%), moderate glycemic control (HA1c 7.1–9%), and poor glycemic control (HbA1c>9%). The study divided the participants into three groups according to The US Institute of Medicine (IOM) recommendations for vitamin D :
- Group I included patients with serum 25(OH)D less than 30 nmol/l, named as the ‘deficient amount group’.
- Group II included patients with serum 25(OH)D of 30–50 nmol/l, named as the ‘insufficient amount group’.
- Group III included patients with serum 25(OH)D more than 50 nmol/l, named as the ‘sufficient amount group’.
Patients having malnutrition, liver disease, end-stage renal disease, and those on current vitamin therapy were excluded from the study.
Collected data were reviewed and analyzed using the statistic package for social science, version 19 (SPSS Inc., Chicago, Illinois, USA). Values are expressed as percentages and mean±SD. The χ2-test was used to compare qualitative data, and Mann–Whitney test was used for non-normally distributed continuous variables. Correlations were performed using the Spearman bivariate correlation. The level of significance was taken at a P value less than or equal to 0.05.
| Results|| |
The study selected 63 young adult diabetic patients as participants: 42 (66.7%) were female and 21 (33.3%) were male. [Table 1] presents complete information about the demographic and laboratory data of selected participants. The findings of this study have also shown that 24 (38.1%) diabetic patients were suffering from the condition of vitamin D deficiency. It was also estimated that 19% of the diabetic participants had an insufficient amount of vitamin D in their human body. However, 42.9% of the diabetic participants had normal levels of vitamin D. Therefore, it can be said that 57.1% of the diabetic patients had reduced levels of vitamin D. Our laboratory results showed high levels of HbA1c (10.08±2.28) with significant inverse correlation between HbA1c and vitamin D among the selected diabetic patients (r=−0.374 and P=0.003) ([Figure 1]). In comparison between the three groups of vitamin D status, we found a significant difference in glycemic control (P=0.003), but not in age, sex, and duration of diabetes. In addition, our result showed that 48 (76.2%) out of 63 had poor metabolic control (HbA1c>9%); of them, 22 (45.8%) T1DM patients had vitamin D deficiency, 12 (25%) patients had vitamin D insufficiency, and 14 (29.2%) patients had normal level of vitamin D ([Table 2]).
|Table 1: Demographic and laboratory characteristics of the studied groups|
Click here to view
|Table 2: Characteristics of the studied groups according to vitamin D status|
Click here to view
| Discussion|| |
It is important for those young adults with established type 1 diabetes (T1D) to be aware of the high prevalence of vitamin D inadequacy and its adverse effect on glycemic control and skeletal health. In our sample, 57.1% of the diabetic patients had reduced levels of vitamin D; of them, 19% had insufficient levels and 38.1% were deficient for vitamin D. Numerous retrospective and observational studies have demonstrated a high prevalence of 25(OH)D deficiency in patients with T1D, therefore suggesting a contributory role in the pathogenesis of T1D. In a North Indian case–control study, 58% of T1D patients had 25(OH)D deficiency . A cross-sectional study from Switzerland reported 60–84% of T1D patients to be 25(OH)D deficient . Another study conducted by Al-Agha et al.  supported the findings of our study and stated that 77% of the diabetic patients had reduced levels of vitamin D. The previous study further described that 28.8% of the patients had insufficient levels; however, 48.2% of the patients were deficient in vitamin D. Al-Daghri et al.  found that 100% (60 patients) of the DMT1 Saudi patients and 78% of the healthy children were vitamin D deficient. Despite these observations, a study in Florida (a state famous for its tropical sun and warm temperature) found no difference in 25(OH)D levels in diabetes patients compared with the controls . Discrepancies in the studies regarding the prevalence of vitamin D deficiency in T1DM patients might be explained by the differences in the dietary intake, geographical location, sun avoidance behaviors, skin color, or genetic predisposition.
This research study discovered that only 57.1% of the boys were vitamin D deficient in comparison with 28.6% of the girls. However, results of a similar past study affirmed that the girls have more tendency of coping up with the deficiency of it in comparison with boys .
The current study has identified high mean HbA1c and significant inverse correlation between vitamin D and HbA1c among the participants (r=−0.374 and P=0.003). In accordance with our result, a study conducted by Desy Wulandari et al.  stated a significant difference in HbA1c levels in T1DM compared with controls, and also described a significant negative correlation between HbA1c levels in T1DM and levels of vitamin D (P=0.000 and r=−0.871). Two investigational projects have reported that reduced serum 25(OH)D levels had a close relationship with improper metabolic control among diabetic patients ,. In contrast to our study, a previous study had not described any difference between vitamin D and HbA1c levels among diabetic children. Again El Baba et al.  found no correlation between diabetes control and variation of vitamin D level in a population of Lebanese with T1DM. Sakineh et al. reported that treatment with vitamin D3 causes better glycemic control in patients with T1DM. Moreover, vitamin D3 supplement causes the improvement of HbA1C in all groups of glycemic control, including poor, fair, and good ones.
In our study, there were several mechanisms explaining vitamin D deficiency and poor glycemic control. First, patients who were included in the study spent most of the day indoors, with decreased outdoor activities and exercise especially in summer season because of excessively hot weather. Subsequently, deterioration of the glycemic control occurs, as well as low exposure to the sun. Second, insulin resistance plays a large role in T1D disease process than is generally known. The onset of T1D is often heralded by an antecedent disease and/or the onset of puberty, both situations associated with insulin resistance . Clinically, insulin resistance in patients with T1D is commonly recognized by high insulin requirements . In insulin-responsive tissues, such as skeletal muscle and adipose tissue, calcium is crucial for insulin-mediated intracellular processes. Indeed, a narrow range of intracellular calcium is needed for optimal function. Vitamin D improves insulin sensitivity by stimulating the expression of insulin receptors and/or by activating peroxisome proliferator-activated receptor-δ. The indirect effect of vitamin D is exerted by regulating calcium flux through the cell membrane and intracellular calcium by rapid responses . Therefore, it is possible that subsets of people with mild manifestations of the type 1 autoimmune disease process could benefit from treatments aimed at improving the insulin-resistant state . Third, the urinary loss of vitamin D-binding protein secondary to reduced function or availability of megalin or low-density lipoprotein-related protein 2 correlated with proteinuria . Fourth, there was a relative decrease in 1,25(OH)2D3 plasma concentration and an increase in 24,25(OH)D levels in diabetics .
| Conclusion|| |
The present study revealed that vitamin D deficiency occurs in adolescent and young adults with T1DM. In addition, vitamin D deficiency is associated with poor glycemic control. Therefore, it can be concluded that gauging the level of vitamin D deficiency in diabetic patients is very critical and vitamin D supplementation may improve glycemic control. Further studies are required to find out the relationship between vitamin D as immune modulator and other autoimmune diseases that are commonly associated with T1DM.
Limitations of the study
Small sample size and seasonal variation of vitamin D are limitations to this current study. In addition, we did not evaluate the effect of vitamin D supplementations on glycemic control of the patients.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Griz LH, Bandeira F, Gabbay MA, Dib SA, Carvalho EF. Vitamin D and diabetes mellitus: an update 2013. Arq Bras Endocrinol Metabol 2014; 58:1–8.
van Etten E, Mathieu C. Immunoregulation by 1,25-dihydroxyvitamin D3: basic concepts. J Steroid Biochem Mol Biol. 2005; 97:93–101.
Chakhtoura M, Azar ST. The role of vitamin D deficiency in the incidence, progression, and complications of type 1 diabetes mellitus. Int J Endocrinol 2013; 2013:148673.
Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP et al.
Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2011; 96:1911–1930.
Hyppönen E, Läärä E, Reunanen A, Järvelin MR, Virtanen SM. Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet 2001; 358:1500–1503.
Mohr SB, Garland CF, Gorham ED, Garland FC. The association between ultraviolet B irradiance, vitamin D status and incidence rates of type 1 diabetes in 51 regions worldwide. Diabetologia 2008; 51:1391–1398.
Kositsawat J, Freeman VL, Gerber BS, Geraci S. Association of A1C levels with vitamin D status in US adults: data from the National Health and Nutrition Examination Survey. Diabetes Care 2010; 33:1236–1238.
IOM. Dietary reference intakes for calcium and vitamin D. Washington, DC: The National Academies Press; 2011.
Borkar VV, Devidayal , Verma S, Bhalla AK. Low levels of vitamin D in North Indian children with newly diagnosed type 1 diabetes. Pediatr Diabetes 2010; 11:345–350.
Janner M, Ballinari P, Mullis PE, Flück CE. High prevalence of vitamin D deficiency in children and adolescents with type 1 diabetes. Swiss Med Wkly 2010; 140:w13091.
Al-Agha AE, Ahmad IA. Association among vitamin D deficiency, type 1 diabetes mellitus and glycemic control. J Diabetes Metab 2015; 6:594.
Al-Daghri NM, Al-Attas OS, Alokail MS, Alkharfy KM, Yakout SM, Aljohani NJ et al.
Lower vitamin D status is more common among Saudi adults with diabetes mellitus type 1 than in non-diabetics. BMC Public Health 2014; 14:153.
Bierschenk L, Alexander J, Wasserfall C, Haller M, Schatz D, Atkinson M. Vitamin D levels in subjects with and without type 1 diabetes residing in a solar rich environment. Diabetes Care 2009; 32:1977–1979.
Alshamsan F, Elgabry E, Bin-Abbas B. Vitamin D deficiency is comparatively more prevalent in female children with type 1 diabetes in a high vitamin D deficiency risk country. Middle East J Fam Med 2014; 7:31.
Desy Wulandari HAC, Widjajanto E, Puryatni A. Low levels of vitamin D correlate with hemoglobin A1c and interleukin-10 levels in pediatric type 1 diabetes mellitus patients. J Trop Life Sci 2014; 4:182–186.
Svoren BM, Volkening LK, Wood JR, Laffel LM. Significant vitamin D deficiency in youth with type 1 diabetes mellitus. J Pediatr 2009; 154:132–134.
Tunc OCS, Kizilgun M. Evaluation of the relation between vitamin D and insulin requirements and frequency of osteopenia/osteoporosis in childhood with type 1 diabetes. 49th Annual Meeting of the ESPE; Prague, Czech Republic, 2010. pp. 22–25.
El Baba K, Zantout MS, Akel R, Azar ST. Seasonal variation of vitamin D and HbA(1c) levels in patients with type 1 diabetes mellitus in the Middle East. Int J Gen Med 2011; 4:635–638.
Greenbaum CJ. Insulin resistance in type 1 diabetes. Diabetes Metab Res Rev 2002; 18:192–200.
Kilpatrick ES, Rigby AS, Atkin SL. Insulin resistance, the metabolic syndrome, and complication risk in type 1 diabetes: ‘double diabetes’ in the Diabetes Control and Complications Trial. Diabetes Care 2007; 30:707–712.
Harinarayan CV. Vitamin D and diabetes mellitus. Hormones (Athens) 2014; 13:163–181.
Thrailkill KM, Jo CH, Cockrell GE, Moreau CS, Fowlkes JL. Enhanced excretion of vitamin D binding protein in type 1 diabetes: a role in vitamin D deficiency? J Clin Endocrinol Metab 2011; 96:142–149.
Rødland O, Markestad T, Aksnes L, Aarskog D. Plasma concentrations of vitamin D metabolites during puberty of diabetic children. Diabetologia 1985; 28:663–666.
[Table 1], [Table 2]