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 Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 8  |  Issue : 2  |  Page : 32-36

Relationship between vitamin D levels and glycaemic control in Type 2 diabetes mellitus patients in Lagos, Nigeria


1 Department of Internal Medicine, Federal Medical Centre, Owerri, Nigeria
2 Department of Medicine, College of Medicine, University of Lagos, Lagos University Teaching Hospital, Lagos, Nigeria
3 Department of Pharmacy, Faculty of Pharmaceutical Sciences, College of Medicine, University of Lagos, Lagos, Nigeria

Date of Web Publication11-Oct-2017

Correspondence Address:
Anyanwu Anthony Chinedu
Department of Medicine, Endocrinology Unit, Federal Medical Centre, PMB 1010, Owerri, Imo State
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jod.jod_17_17

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  Abstract 


Background: Studies have reported a relationship between Vitamin D deficiency and type 2 diabetes mellitus (T2DM). There is no information on the Vitamin D status or relationship between Vitamin D and glycaemia in Nigerian patients with T2DM. The objective of this study was to determine the relationship between serum Vitamin D levels and glycaemic control, as determined by glycated haemoglobin (HbA1c) in adult patients with T2DM. Methods: This was a cross-sectional analytical study involving T2DM participants attending the Diabetes Clinic of the Lagos University Teaching Hospital. The study participants consisted of 114 T2DM and sixty healthy controls. Levels of serum Vitamin D, fasting glucose, insulin, HbA1c, calcium, albumin, phosphate, creatinine and alanine transaminase were determined. Insulin resistance and beta cell function were estimated with the homeostasis model assessment (HOMA-IR and HOMA-B, respectively). Statistical analysis was done using Statistical Package for Social Sciences, Version 20. Results: The mean age of the study participants was 52 ± 7.6 years for T2DM patients and 50 ± 8.4 years for controls. The female to male ratio in both T2DM and healthy controls was 3:2. The mean HbA1c was 7.3 ± 1.8%. Poor glycaemic control (HbA1c >6.5%) was present in 67 (58.8%) T2DM controls; forty-five (39.5%) subjects had both low Vitamin D levels and poor glycaemic control. There was a significant inverse correlation between serum Vitamin D concentration and HbA1c levels in T2DM patients (rs= −0.185; P < 0.05) A non-significant inverse association was seen between serum Vitamin D level and HOMA-IR. Conclusion: This study shows an inverse association between serum levels of Vitamin D and glycaemic control, as determined by HbA1c. T2DM patients with poor glycaemic control may need to be assessed for serum Vitamin D levels and possibly treated for Vitamin D deficiency.

Keywords: Glycaemic control, glycated haemoglobin, type 2 diabetes mellitus, Vitamin D


How to cite this article:
Chinedu AA, Fasanmade O A, Coker H, Ohwovoriole A E. Relationship between vitamin D levels and glycaemic control in Type 2 diabetes mellitus patients in Lagos, Nigeria. J Diabetol 2017;8:32-6

How to cite this URL:
Chinedu AA, Fasanmade O A, Coker H, Ohwovoriole A E. Relationship between vitamin D levels and glycaemic control in Type 2 diabetes mellitus patients in Lagos, Nigeria. J Diabetol [serial online] 2017 [cited 2017 Dec 15];8:32-6. Available from: http://www.journalofdiabetology.org/text.asp?2017/8/2/32/216459




  Introduction Top


A relationship between Vitamin D deficiency and type 2 diabetes mellitus (T2DM) has been reported.[1] Globally, evidence indicates a high prevalence of Vitamin D deficiency.[2] Consistent with the hypothesis that Vitamin D deficiency and diabetes are related, areas with high prevalence of Vitamin D insufficiency and deficiency have been associated with a higher prevalence of diabetes.[3] Reported the prevalence of Vitamin D deficiency among patients with T2DM ranges from 63.5% to 91.1%.[4],[5]

Adolescents in the National Health and Nutrition Examination Survey (NHANES III) with serum 25-hydroxyvitamin D(25(OH)D) levels <15 ng/dl were more likely to have elevated blood glucose levels than those with 25(OH)D levels >26 ng/dl.[6] This suggests a mechanistic link among serum Vitamin D concentrations, glucose homeostasis and the evolution of diabetes in a large segment of the US adults at the population level. These findings also highlight the need to consider screening for Vitamin D insufficiency in individuals with elevated glycated haemoglobin (HbA1c) level and vice versa. This is important in populations at high risk for both conditions (T2DM and Vitamin D deficiency), such as the obese and racial/ethnic minorities. Whether Vitamin D supplementation can delay the onset of diabetes remains to be established.[6]

Several studies on the glycaemic control of patients with diabetes mellitus, done in various regions in Nigeria, have shown that poor glycaemic control is common among Nigerian diabetes.[7],[8],[9],[10] In Benin, poor glycaemic control was seen in as many as 46% of the subjects,[7] while in Calabar and Ilorin, 63% and 64% of the subjects respectively had poor glycaemic control.[8],[9] In Lagos, a mean HbA1c of 10.5% was documented among T2DM patients.[10] Poor glycaemic state among diabetes patients has been attributed to several factors, among which is Vitamin D deficiency.[4],[7]

There is no information on the Vitamin D status or relationship between Vitamin D and glycaemia in Nigerian subjects with T2DM. Information on the relationship between Vitamin D and diabetes is needed in making decisions on the recommendation of Vitamin D treatment in T2DM patients with Vitamin D deficiency in Nigeria; hence, the need for this study.

The objective of this study was to determine the relationship between serum Vitamin D levels and glycaemic control in patients with T2DM.


  Methods Top


This was a cross-sectional analytical study involving T2DM participants attending the Diabetes Clinic of the Lagos University Teaching Hospital (LUTH). The study was carried out over a period of 5 months. Nigerian patients with T2DM attending the diabetes clinic of LUTH were chosen as study participants, and apparently healthy controls from among LUTH members of staff and the general outpatient department.

Informed consent was obtained from all the study participants, both in English and in vernacular languages. Ethical clearance was obtained before data collection from the local institutions (LUTH) health and ethics committee.

Sample size determination

The sample size was calculated using the Kish formula.[11]



Where,

N = Desired sample size,

Z =Standard deviation (SD) set at 1.96 corresponding to 95% confidence interval (CI),

P =Population in the target population estimated to have a population characteristics (prevalence of Vitamin D deficiency) =91.1%,

q = 1.0 – P,

d = degree of accuracy required set at 0.05 (5%).





= 112

Control participants

The ratio of the controls to T2DM participants was 1:2. Hence, the estimated number of control participants was 56.

The total calculated sample size was 168 (112 T2DM and 56 control participants). To allow for a dropout rate of about 10%, 184 participants were estimated to be recruited for this study (T2DM participants = 122; and controls = 62).

Inclusion and exclusion criteria for the study participants Inclusion criteria

The following groups of persons were eligible for recruitment into the study:

  1. Type 2 diabetes mellitus participants


    • Participants aged 35–65 years with type 2 diabetes mellitus and on oral antidiabetics
    • Participants who gave informed consent


  2. Control participants


    • Apparently, healthy participants aged 35–65 years who gave informed consent.


Exclusion criteria

Those who were excluded from the study were:

  • Participants below 35 years or above 65 years
  • Participants with type 1 DM
  • T2DM participants on insulin (due to influence of insulin antibodies on serum insulin assay)
  • Pregnant women (serum Vitamin D levels are generally low in pregnancy)
  • Participants with chronic diseases including renal insufficiency (glomerular filtration rate <30 ml/min), history of chronic liver disease or alanine aminotransferase >5 times upper reference limit, tuberculosis, diarrhoeal or malabsorption state.


Levels of serum Vitamin D were assayed using the Agilent series 1120 high-performance liquid chromatography (HPLC) system with quaternary pump. Marker of glycaemic control, HbAIc, was analysed through the boronate affinity chromatography technique, using the automated Glycohemoglobin analyser (In2it A1c analyser, Bio-rad, USA) and the Trinder (glucose-oxidase) method employed for assay of fasting plasma glucose. Serum insulin levels were determined using the enzyme-linked immunosorbent assay method (Diagnostic Automation/Cortez Diagnostics, Inc., USA). Serum calcium, albumin, phosphate, creatinine and alanine transaminase were measured using standardised and automated assays.

Insulin resistance (IR) and beta cell function (B) were estimated with the homeostasis model assessment (HOMA).[12]

HOMA-IR defined as the product of fasting serum insulin (μU/ml) and fasting blood glucose, fasting plasma glucose (FBG) (mmol/L) divided by 22.5. A score of ≥2 defined IR.[13]

HOMA-B insulin secretion (IS) defined as the product of twenty and fasting insulin (μU/ml) divided by FBG (mmol/L) minus 3.5. A score of <100 defined reduced IS (B).[13]

Statistical analysis was done using Statistical Package for Social Sciences Version 20 (Chicago, IL, USA). Data distribution (normality) was investigated using the D' Agostino-Pearson Omnibus normality test for appropriate statistical analysis. Summary description of data was listed as mean, SDs, median, CIs, proportions and tables.

Student's t-test, Wincoxon inferential statistical test, Chi-test and Spearman's rank correlation coefficient tests were used where applicable. P < 0.05 was considered statistically significant.


  Results Top


Characteristics of study participants

Clinical and anthropometric characteristics of study participants

The mean age of the study participants was 52 ± 7.6 years for T2DM patients and 50 ± 8.4 years for controls. There were 45 (39.5%) males and 69 (60.5%) females in the T2DM group and 24 (40%) males and 36 (60%) females in the control group (χ2 = 0.005; P = 0.94). The female to male ratio in both T2DM and healthy controls was 3:2. There were similar age and sex distributions in both groups; so also were the body mass index and blood pressure. However, the waist circumference and waist-hip ratio were significantly higher in the diabetic group. The median duration of T2DM was 4 years. [Table 1] shows the anthropometric and clinical characteristics of the T2DM and controls.
Table 1: Anthropometric and clinical characteristics of study participants

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Biochemical characteristics of study participants

The median (95% CI) fasting plasma glucose was 144 mg/dl (133–154) in T2DM patients and 85 mg/dl (81–89) in controls, P < 0.001. HOMA-IR values in T2DM was 4.9 (3.6–6.2) and 1.9 (0.6–3.2) in the healthy control group, P < 0.001. The median pancreatic HOMA-B, (%) was 101 (73–128.7) in T2DM patients and 239 (156–454) in controls, P < 0.001.

The mean (SD) HbA1c was 7.3% ±1.8%; poor glycaemic control (HbA1c >6.5%) was present in 67 (58.8%) T2DM patients. Forty-five (39.5%) T2DM patients had both low Vitamin D concentration and poor glycaemic control. [Table 2] shows the other biochemical characteristics of the study participants.
Table 2: Biochemical characteristics of study participants

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Relationships between Vitamin D3 levels, beta-cell function and anthropometric indices

There was a significant negative correlation between serum Vitamin D concentration and HbA1c concentrations in T2DM patients (rs= −0.185; P < 0.05). A non-significant inverse association was seen between serum Vitamin D concentration and HOMA-IR in T2DM subjects. There was no significant correlation with pancreatic HOMA-B in both groups. Correlations matrixes for other indices are as shown in [Table 3] and [Table 4].
Table 3: Interrelationship variables among Type 2 diabetes participants

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Table 4: Interrelationship variables among control participants

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  Discussion Top


The objective of this study was to determine the relationship between serum Vitamin D concentration and glycaemic control among persons with T2DM.

Vitamin D may influence IS and sensitivity through several mechanisms. The presence of Vitamin D receptors in beta cells and Vitamin D response element in human insulin gene support a direct effect of Vitamin D on insulin synthesis and secretion; Vitamin D stimulates the expression of the insulin receptor in peripheral tissues and thereby increasing glucose transport. Vitamin D attenuates the expression of pro-inflammatory cytokines involved in IR such as interleukin (IL)-1, IL-6, tumour necrosis factor-a, also downregulates nuclear factor-Kb activity.[14],[15]

Summary of key findings

The proportion of females in this study was higher than the male counterpart in contrast to some previous documented reports of an overall higher prevalence of diabetes in males than females. A possible explanation for this might be due to the higher life expectancy in females.[16] In part, this finding may be a reflection of the female to male sex distribution of the diabetes patients attending the diabetes clinic of the LUTH where this study was carried out, which was put at 1.8. Greater use of hospital facility by women or lack of time to visit hospital by employed males may also be a reason.

The mean HbA1c found in this study was lower compared to the previous report of a mean HbA1c of 10.5% among T2DM patients in this centre. The reason for this could be due to an improvement in patients care. The proportion of subjects with poor glycaemic control seen in this study is similar to reports in other centres across the country, which ranged from 46% to 64%.[7],[8],[9],[10]

This study found a significant inverse association between serum Vitamin D concentration and glycaemic control as measured by HbA1c levels in persons with T2DM. This finding is similar to the report of cross-sectional analyses of data from 9,773 adults who participated in the 2003–2006 NHANES, which found that serum 25(OH) D concentration was inversely associated with Hba1c level in individuals 35–74 years old, but not among the younger or older adults.[6]

Yu et al. also reported that high levels of HbA1c were independently associated with Vitamin D deficiency in T2DM patients.[17] In a study of 250 overweight and obese adults age 18 years in New Zealand, investigators observed a weak, inverse relation between HbA1c and Vitamin D levels.[18] A study of 7,198 British Caucasians showed a non-linear inverse relationship between Vitamin D and A1C.[19]

However, no significant relationship was observed between serum Vitamin D levels, IR and pancreatic B in this study.

Study strengths and limitations

The HPLC method, which is considered Gold standard, was employed in the assay of Vitamin D. Furthermore, the measurement of glycaemic control, HbA1c, was done using the boronate affinity chromatographic method, which is one of the most favoured.

However, this study has important limitations. The sample size is relatively small, and the cross-sectional design makes it difficult to establish a causal relationship between Vitamin D and HbA1c levels. Furthermore, the analysis derives from only a single measurement of HbA1c and Vitamin D levels.


  Conclusion Top


This study findings support an inverse association between serum level of Vitamin D and glycaemic control (HbA1c) in persons with T2DM. There may be need to screen persons with T2DM with poor glycaemic control for Vitamin D deficiency.

Further studies on this subject, as well as those on Vitamin D supplementation in T2DM patients are needed.

Acknowledgement

Dr. Odeniyi I. Department of Medicine, Endocrinology unit, LUTH, Lagos, Nigeria.

Dr. Iwuala Sandra. Department of Medicine, Endocrinology unit, LUTH, Lagos, Nigeria.

Mr. Olajide. Department of Pharmacy, College of Medicine, University of Lagos, Nigeria.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Kish L. A procedure for objective respondent selection within the household. J Am Stat 1949;44:380-7.  Back to cited text no. 11
    
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Pittas AG, Lau J, Hu FB, Dawson-Hughes B. The role of Vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. J Clin Endocrinol Metab 2007;92:2017-29.  Back to cited text no. 15
    
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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