Abstract
Background
Diabetes mellitus (DM) remains a major cause of morbidity and mortality. Poor glycaemic control is a key determinant of diabetes-related complications, and vitamin D deficiency has emerged as a potential contributor to impaired glycaemic control. End-stage renal disease is one of the most severe complications of DM, imposing substantial individual and public health burdens. This study aimed to determine the prevalence and risk factors of vitamin D deficiency among patients with type 2 diabetes mellitus (T2DM) and to evaluate its association with glycaemic control and renal function.
Methods
In this cross-sectional study, 100 patients with T2DM and 100 age- and sex-matched controls were recruited. Ethical approval was obtained, and informed consent was provided by all participants. Clinical data were collected, and physical examinations were performed. Blood samples were analysed for serum vitamin D, fasting blood glucose, 2-hour postprandial glucose, serum creatinine, lipid profile, albumin, calcium, and phosphate. Nephropathy was assessed using the urinary albumin–creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR). Data were analysed using SPSS version 23.
Results
The mean age of patients and controls was 53.0 ± 10.3 years and 52.9 ± 11.2 years, respectively (p = 0.933), with comparable sex distribution. Chronic kidney disease (stage ≥ 3) was present in 12.0% of T2DM patients and 4.0% of controls. Among T2DM patients, 14.0% had vitamin D deficiency (25(OH)D ≤ 20 ng/mL) and 31.0% had insufficiency (20–<30 ng/mL), compared with 5.0% and 20.0%, respectively, among controls. Vitamin D deficiency was more frequent in older participants and in males. A higher proportion of T2DM patients with vitamin D deficiency had nephropathy (93%) compared with those without deficiency. Independent predictors of vitamin D deficiency included increasing age (aOR = 1.086, 95% CI: 1.011–1.167; p = 0.024), male sex (aOR = 12.282, 95% CI: 2.661–56.688; p = 0.001), and higher glycated haemoglobin levels (aOR = 2.438, 95% CI: 1.511–3.934; p < 0.001).
Conclusions
Vitamin D deficiency is common among individuals with T2DM and is associated with male sex, advancing age, poor glycaemic control, and nephropathy.
Clinical trial number
Not applicable.
Keywords: Nephropathy, Type 2 diabetes mellitus, Vitamin D insufficiency, Vitamin D deficiency, Chronic kidney disease
Introduction
Prevalence of diabetes mellitus (DM) is on the rise in both developed and developing worlds, and this is attributed to the increasing prevalence of obesity, westernization of lifestyles, and economic development [1, 2]. Years of poorly controlled glycaemia lead to vascular and non-vascular complications that affect many organ systems [3].
Of all the chronic complications that affect individuals with diabetes, end-stage kidney disease (ESKD) probably takes the greatest toll [3]. It is associated with a profound economic burden, especially in developing countries where the resources and infrastructure to provide universal renal replacement therapy remain a challenge [3]. Diabetic nephropathy (DN) is the most common renal complication of DM; it occurs in 20–40% of patients with DM and is the leading cause of ESKD worldwide [3]. Efforts to reduce the burden of diabetes and its complications have led to screening for both traditional and novel risk factors that have an impact on glycemic control. Among these novel factors is serum vitamin D.
Population studies have provided support for the hypothesis that vitamin D deficiency is associated with impaired B-cell function, insulin resistance, impaired glucose tolerance, and poor glycaemic control [4, 5]. Some of the determinants of vitamin D deficiency in patients with DM include inadequate skin synthesis from dark skin, old age, continuous use of sunscreen, and skin covering for various religious or cultural reasons [6–8]. Limited intake of dietary sources, such as oily fish and fish-liver oil, low intake of fortified foods; strict vegans and non-milk drinkers are also at risk for vitamin D deficiency.
While local data on the effect of vitamin D deficiency on diabetes control and complications of type 2 diabetes mellitus (T2DM) are scarce, low serum 25-hydroxyvitamin D [25(OH)D] status is common in patients with chronic kidney disease (CKD), even at the early stages, and the severity of deficiency increases with the progression of kidney disease [9]. Studies have shown improvement in glycaemia and proteinuria with the correction of hypovitaminosis D [10–12].
The primary objective of this study was to examine the relationship between vitamin D status, glycaemia, and diabetic nephropathy among patients with type 2 diabetes mellitus attending Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria. We hypothesised that there would be no difference in vitamin D status between individuals with type 2 diabetes mellitus and apparently healthy controls; that vitamin D status would not influence glycaemic control; and that vitamin D status would not be associated with renal function in patients with type 2 diabetes mellitus.
We compared the vitamin D status of Nigerian patients with type 2 diabetes mellitus with that of apparently healthy age- and sex-matched controls. In addition, we evaluated the associations between vitamin D status, glycaemic control, and renal function among adult patients with type 2 diabetes mellitus.
Materials and methods
Subjects recruitment
The study was a comparative cross-sectional hospital-based study among T2DM patients as well as age- and sex-matched healthy controls. This study was conducted in accordance with the Declaration of Helsinki. Ethical approval was obtained from the Ethics and Research Committee of the Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria (IRB/IEC/0004553). This study was conducted and reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. Participants were counselled, and written informed consent was obtained. This study was conducted at a tertiary health care centre in the southwestern geopolitical zone of Nigeria. Like every other Southwestern area of Nigeria, the rainy season starts from April and extends to October, while the dry season lasts from November to March [13]. Due to the important effect of sunlight on vitamin D levels, the lowest levels of 25(OH)D are expected during the rainy season and the highest levels in the dry season [5]. To minimize the seasonal variability in the mean level of vitamin D, all samples were collected during the dry season (one season), that is, between November and January.
The subject group consisted of consecutive 100 patients between the ages of 18 and 75 years being managed for T2DM and who had been on anti-diabetic drugs for at least three months. The controls were 100 healthy non-diabetic adult hospital staff and their relatives who volunteered for the study. The sample size was estimated using the Leslie Kish formula [14]:
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where Z = the precision value at 95% confidence level (1.96); p= Prevalence of Vitamin D deficiency in DM nephropathy (92%) [15]; q = (1-p) = 0.07; d=Margin of error at 5%.
People who were unwilling to participate, pregnant women or lactating mothers, patients with chronic liver disease, those using vitamin D or calcium supplements, or drugs which inhibit the action of vitamin D-hydroxylase (Phenytoin, carbamazepine, rifampin, cimetidine), or cause fat malabsorption (orlistat) were excluded. In addition, control subjects with a history of diabetes or abnormal fasting blood glucose (FBG) on screening were excluded.
Clinical variables
An interviewer-administered, structured proforma was administered to those who consented. Details of demographic data, including age, tribe, gender, marital status, area of usual residence, etc., were obtained. Sunlight exposure was defined as adequate if estimated hand and face exposure was ≥ 30 min per day [16]. Dietary history was taken, regarding intake of rich sources of vitamin D, like mackerel fish, herring fish, egg yolk, and fortified milk. Physical examinations, including weight, height, waist circumference, etc., were done following standard protocols. Body mass index (BMI) was calculated.
Laboratory assessment
After an overnight fast, 10 ml of blood was collected for the estimation of fasting blood glucose (FBG), glycated haemoglobin (HbA1c), serum vitamin D [25(OH)D] assay, calcium phosphate, creatinine and albumin, and fasting lipid profile. Serum 25(OH)D was using high-performance liquid chromatography (HPLC) on a Waters system (Water 616), based on the method described by Aksnes [17].
Nephropathy was evaluated using two modalities: the albumin creatinine ratio (ACR) in urine and the estimated glomerular filtration rate (eGFR) derived using both the Cockroft-Gault and the Modification of Diet in Renal Disease (MDRD) formulae.
Vitamin D Status was defined according to the.
Endocrine Society criteria [16] as follows:
Vitamin D sufficiency was defined as serum 25(OH)D concentration of greater than or equal to 30 ng/mL (75 nmol/L); Vitamin D insufficiency as serum 25(OH)D of 20 to 29.9 ng/mL (50 to 75 nmol/L); Vitamin D deficiency as serum 25(OH)D of less than or equal to 20 ng/mL (50 nmol/L) and Vitamin toxicity as serum 25(OH)D of more than or equal to 150 ng/mL (375 nmol/L).
Statistical analysis
Data were entered and analysed using IBM statistical package for the social sciences (SPSS) 23 Statistics. Categorical variables were summarized using frequencies and percentages, and presented in tables and charts. Continuous variables were assessed for normality using the Shapiro–Wilk test. Variables that did not significantly deviate from normality were analysed using parametric methods, while non-parametric methods were applied to variables that significantly deviated from normality. Normally distributed continuous variables were summarized using mean and standard deviation, and comparisons between groups were performed using the independent samples t-test. Non-normally distributed continuous variables were summarized using median and interquartile range (IQR), and differences between groups were assessed using the Mann–Whitney U test. Linear regression analysis was used to assess the relationship between vitamin levels and eGFR and HbA1c. Statistical significance was set at a p-value < 0.05, and 95% confidence intervals were reported where appropriate.
Multivariable logistic regression analysis was performed to identify factors independently associated with vitamin D deficiency. Variables with significant difference between groups in univariate analysis, as well as those of clinical relevance, were included in the model to control for potential confounding factors.
Results
A total of 244 participants (124 people with type 2 diabetes mellitus and 120 healthy control subjects) were invited to participate in this study. Of the 120 controls, 20 were excluded on account of having FBG in the impaired or diabetic range. Of the 124 T2DM patients invited, 24 were excluded (on calcium supplements, being managed for chronic liver disease, or on carbamazepine tablets). Hence, 100 participants with diabetes and 100 controls who met the inclusion criteria and consented were recruited.
Demographic characteristics
The mean age of the T2DM and control groups was 53.0 ± 10.3 years and 52.9 ± 11.2 years, respectively (p-value 0.933). There were more males than females in both groups (56.0% versus 44.0%). The majority of the participants in both cases and controls (86.0% versus 88.0%) were Yoruba, which is the main ethnic group in the study area. There was no statistically significant difference between the two groups in terms of their educational, religious, and employment statuses.
History of diet, exposure to sunlight and social factors
All the participants reported adequate exposure to sunlight. About half to two-thirds of the participants reported regular intake of dietary sources of vitamin D (Table 1).
Table 1.
Social and dietary characteristics of study participants
| Variable | Diabetic group | Non-Diabetic group | p-value | ||
|---|---|---|---|---|---|
| n | % | n | % | ||
| Cigarette smoking | |||||
| Yes | 14 | 14.0 | 18 | 18.0 | |
| No | 86 | 86.0 | 82 | 82.0 | 0.133 |
| Alcohol intake | |||||
| Yes | 24 | 24.0 | 23 | 23.0 | |
| No | 76 | 76.0 | 67 | 67.0 | 0.747 |
| Dietary Sources of Vitamin D | |||||
| Mackerel fish | |||||
| Often | 90 | 90.0 | 88 | 88.0 | |
| Occasional | 10 | 10.0 | 10 | 10.0 | |
| Never | 0 | 0 | 2 | 2.0 | 0.340 |
| Herring fish | |||||
| Often | 78 | 78.0 | 70 | 70.0 | |
| Occasional | 22 | 22.0 | 28 | 28.0 | 0.600 |
| Egg-yolk | |||||
| Often | 38 | 38.0 | 43 | 43.0 | |
| Occasional | 46 | 46.0 | 41 | 41.0 | |
| Never | 16 | 16.0 | 13 | 13.0 | 0.650 |
| Milk intake | |||||
| Often | 44 | 44.0 | 50 | 50.0 | |
| Occasional | 52 | 52.0 | 45 | 45.0 | |
| Never | 4 | 4.0 | 2 | 2.0 | 0.650 |
Clinical characteristics
Duration of diagnosis of DM among the T2DM group ranged between 3 months and 367 months, with a median duration of 36.0 months. Sixty-eight per cent (68.0%) of the patients were on monotherapy (oral anti-diabetic medications), 18% on a combination of insulin and oral anti-diabetic drugs, and 16% on insulin therapy only.
Hypertension was present among 58% and 39% of the T2DM and non-diabetic groups, respectively. Table 2 shows the anthropometric and blood pressure distribution among the study participants.
Table 2.
Anthropometric indices and blood pressure distribution of study participants
| Variable | Diabetic group Median (IQR) n = 100 |
Non-Diabetic group Median (IQR) n = 100 |
p-value |
|---|---|---|---|
| BMI (kg/m2) | 28.13(25.26 – 31.82) | 27.69(23.83 – 30.11) | 0.201 |
| WC (cm) | 89.0(84.0 – 95.0) | 89.0 (84.0 – 100.0) | 0.831 |
| HC (cm) | 94.0(88.0 – 100.0) | 96.0 (88.0 – 103.0) | 0.437 |
| WHR | 0.94(0.92 – 0.97) | 0.94 (0.91 – 0.96) | 0.519 |
| SBP (mmHg) | 130.0 (120.0 – 140.0) | 130.0 (120.0 – 140.0) | 0.958 |
| DBP (mmHg) | 80.0(70.0 – 90.0) | 80.0(70.0 – 90.0) | 0.580 |
BMI = body mass index; WC = waist circumference; HC – hip circumference; WHR -= waist-to-hip ratio; SBP = systolic blood pressure; DBP = diastolic blood pressure
Biochemical characteristics
The median (IQR) HbA1c of the T2DM patients was 7.0 (6.70–8.00); 59% of them had poor glycaemic control with HbA1c > 7%.
Overt proteinuria was present in 13% of T2DM participants, while 48% had microalbuminuria compared to the non-diabetic group, where 2% had overt proteinuria and 17% had microalbuminuria. Using the eGFR, chronic kidney disease was present in 12% of the T2DM group compared to 4% of the non-diabetic population. Dyslipidaemia was present in 38% of the T2DM group compared to 28% of the non-diabetic population. Asymptomatic hypocalcaemia (serum calcium < 2.1 mmol/l) was seen in 8% of T2DM patients and none in the non-diabetic group. The biochemical characteristics of the study population is shown in Table 3.
Table 3.
Biochemical characteristics of study participants
| Variable | Diabetic group Median (IQR) n=100 |
Non-Diabetic group Median (IQR) n=100 |
p-value |
|---|---|---|---|
| 25(OH)D(ng/mL) | 30.0 (27.23 – 45.58) | 41.2 (30.00 – 50.74) | <0.001 |
| FBG(mmol/L)* | 9.0 (3.82) | 5.0 (0.64) | 0.050 |
| HbAIc(%) | 7.0 (6.70 – 8.00) | NA | - |
|
Total Cholesterol* (mmol/L) |
5.6 (0.69) | 4.5 (0.34) | 0.866 |
|
HDL Cholesterol* (mmol/L) |
1.2 (0.97) | 1.1 (0.80) | 0.298 |
|
LDL Cholesterol* (mmol/L) |
2.5 (0.57) | 2.5 (0.55) | 0.422 |
|
Triglycerides* (mmol/L) |
1.2 (0.83) | 1.0 (0.37) | 0.001 |
|
Corrected calcium* (mmol/L) |
2.2 (0.04) | 2.4 (0.15) | 0.210 |
|
Serum phosphate* (mmol/L) |
2.0 (0.67) | 1.2 (0.35) | 0.517 |
| Creatinine(µmol/L) | 89.2 (74.60 – 97.00) | 74.0 (63.62 – 82.50) | <0.001 |
| eGFR(ml/min)CG | 85.0 (70.4 – 106.5) | 95.0 (72.00 – 115.00) | 0.065 |
|
eGFR(ml/min) MDRD |
90.5 (77.0 – 101.60) | 85.0 (64.00 – 97.09) | 0.044 |
25(OH)D − 25-hydroxyvitamin D; FBG - Fasting blood glucose; HbA1c - Glycated haemoglobin; HDL – High-density lipoprotein; LDL – Low-density lipoprotein; eGFR-CG and eGFR-MDRD - estimated glomerular filtration rate derived from Cockroft-Gault and the Modification of Diet in Renal Disease (MDRD) formula respectively; NA-not applicable. Corrected calcium = serum calcium + 0.02 (4 – albumin)
*Mean (SD)
Pattern and prevalence of vitamin D status
Prevalence of vitamin D deficiency (25(OH)D≤20ng/mL) was 14.0% and 5.0% among the T2DM and control groups respectively, while the prevalence of vitamin D insufficiency (25(OH)D = 20-29.9 ng/mL) was 31.0% among the diabetic group, and 20.0% among the non-diabetic group (X2 = 57.747, p-value < 0.001).
Vitamin D deficiency and insufficiency were more common in older age groups. Participants aged 50 years and above constituted 70% and 100% of those with vitamin D deficiency and insufficiency in the T2DM and control groups, respectively. Among the T2DM subjects, Vitamin D deficiency was predominant among the male participants (9:5), while it was predominant among females (1:4) in the control group.
Relationship between vitamin D and HbA1c
Of the 14 diabetic subjects with 25(OH)D deficiency, 12 (86.7%) had poor control (HbA1c > 7.0%), while 21(67.7%) of the 31 diabetic patients with 25(OH)D insufficiency had poor control.
Linear regression analysis was used to determine the relationship between vitamin D status and HbA1c in the diabetic group (Fig. 1). Regression revealed a statistically significant negative relationship between the two variables, i.e., for every increase in HbA1c by 1%, the level of 25(OH)D reduces by 1.79ng/ml with a coefficient of 0.43 and p-values < 0.001.
Fig. 1.
Regression analysis showing relationship between 25(OH) D and HbA1c in the Diabetic group. Y = 1.7969x + 52.232 R2 = 0.182 r = 0.427 p = < 0.001
Vitamin D and diabetic nephropathy
Using the urine albumin/creatinine ratio, 13% of the T2DM group had frank proteinuria, 48% had microalbuminuria, while 2% of the non-diabetic group had proteinuria, and 17% had microalbuminuria. Among the 14 diabetic subjects with vitamin D deficiency, 93.0% had microalbuminuria/proteinuria.
Similarly, of the 31 diabetic subjects with insufficiency, 67.7% had microalbuminuria /proteinuria. This pattern was, however, not observed among the control group (Tables 4a and b).
Table 4a.
Albumin-creatinine (ACR) ratio and vitamin D status amongst diabetic group
| Vitamin D Grade | Normoalbuminuria | Microalbuminuria | Overt proteinuria |
Total | χ2 test | ||||
|---|---|---|---|---|---|---|---|---|---|
| n | (%) | n | (%) | n | (%) | n | (%) | ||
| Deficient | 1 | (2.6) | 6 | (12.5) | 7 | (53.8) | 14 | (14.0) |
Fisher’ = 21.06 p < 0.001 |
| Insufficient | 9 | (23.1) | 19 | (39.6) | 3 | (23.1) | 31 | (31.0) | |
| Sufficient | 29 | (74.4) | 23 | (47.9) | 3 | (23.1) | 55 | (55.0) | |
| Total | 39 | (100.0) | 48 | (100.0) | 13 | (100) | 100 | (100) | |
Table 4b.
Albumin-creatinine ratio (ACR) and Vitamin D status amongst non-diabetic group
| Vitamin D Grade | Normo-albuminuria | Microalbuminuria | Overt proteinuria |
Total | χ2 test | ||||
|---|---|---|---|---|---|---|---|---|---|
| n | (%) | n | (%) | n | (%) | n | (%) | ||
| Deficient | - | - | - | - | - | - | - | - |
Fisher’ = 1.721 P = 1.000 |
| Insufficient | 2 | (2.5) | 0 | (0.0) | 0 | (0.0) | 2 | (2.0) | |
| Sufficient | 79 | (97.5) | 17 | (100.0) | 2 | (100.0) | 98 | (98.0) | |
| Total | 81 | (100.0) | 17 | (100.0) | 2 | (100.0) | 100 | (100.0) | |
Using the CG and MDRD formulae for calculation of eGFR, 12.0% of the T2DM patients had chronic kidney (stage 3 and above) compared to 4.0% of the non-diabetic group.
There was a positive correlation between 25(OH)D levels and eGFR using both the CG formula and the MDRD formula, respectively (Fig. 2a and b). That is, for every unit rise in serum Vitamin D level, the GFR increases by 0.848 and 0.614 with the C-G formula and MDRD formula, respectively, with a coefficient of correlation of r = 0.265 and r = 0.270, respectively (p-values < 0.05). No significant difference was found in eGFR levels using the C-G formula or the MDRD formula.
Fig. 2a.
Vitamin D versus e-GFR (C-G formula) - Linear regression analysis
Fig. 2b.
Vitamin D versus e-GFR (MDRD formula) - Linear regression analysis
Risk factors for vitamin D deficiency
A binary logistic regression analysis was performed to assess the association between eGFR (using MDRD) and vitamin D deficiency while adjusting for age, gender, duration of diabetes, serum creatinine, and glycated hemoglobin (HbA1c) (Table 5). In the adjusted model, eGFR was not significantly associated with vitamin D deficiency (adjusted odds ratio [aOR] = 0.986, 95% CI: 0.946–1.028; p = 0.512). Age was independently associated with vitamin D deficiency, with increasing age corresponding to higher odds (aOR = 1.086, 95% CI: 1.011–1.167; p = 0.024). Gender was also significantly associated with the outcome, with male participants having a higher odds of vitamin D deficiency compared to the female participants (aOR = 12.282, 95% CI: 2.661–56.688; p = 0.001). Higher HbA1c levels were strongly associated with increased odds of vitamin D deficiency (aOR = 2.438, 95% CI: 1.511–3.934; p < 0.001). Duration of diabetes (aOR = 0.994, 95% CI: 0.987–1.000; p = 0.054), and serum creatinine (aOR = 0.984, 95% CI: 0.928–1.043; p = 0.583) were not significantly associated with vitamin D deficiency.
Table 5.
Adjusted logistic regression analysis of factors associated with vitamin D deficiency
| Variable | B | SE | p-value | Adjusted OR (95% CI) |
|---|---|---|---|---|
| eGFR (MDRD) | -0.014 | 0.021 | 0.512 | 0.986 (0.946–1.028) |
| Age (years) | 0.083 | 0.036 | 0.024 | 1.086 (1.011–1.167) |
| Gender (Male) | 2.508 | 0.780 | 0.001 | 12.282 (2.661–56.688) |
| Duration of diabetes | -0.006 | 0.003 | 0.054 | 0.994 (0.987–1.000) |
| Serum creatinine | -0.016 | 0.030 | 0.583 | 0.984 (0.928–1.043) |
| HbA1c | 0.891 | 0.244 | <0.001 | 2.438 (1.511–3.934) |
eGFR (MDRD): estimated glomerular filtration rate based on Modification of Diet Renal Disease equation. HbA1c: glycated haemoglobin
Discussion
Vitamin D deficiency has been linked with a myriad of chronic systemic diseases, including DM. This study, therefore, sets out to determine the serum levels of vitamin D among T2DM patients as well as age and sex-matched controls and to correlate it with glycaemic control and nephropathy.
Socio-demographic attributes such as ethnic group, religion, education status, employment status, alcohol intake, and cigarette smoking were similar between the two groups, removing the role of socio-demographic factors as confounders.
The prevalence of vitamin D deficiency of 14% was found to be higher among T2DM participants compared to the controls (5%). However, these values were lower than what was reported in Lagos, Nigeria [11]. The reason a lower rate was seen in Ile-Ife compared to Lagos could be attributed to the seasonal variation in serum vitamin D level, which may not have been considered in previous studies in Lagos. This study was done during the dry season when exposure to sunshine is expected to be optimal. A supportive study from Toronto showed an increase in the prevalence of vitamin D deficiency from 9% in the fall to 18% in the spring [18]. Also, individuals residing in rural areas tend to have more outdoor activity and sunlight exposure than individuals in the city. Ile Ife, being a semi-urban community, probably has more utilitarian walking distance than most urban areas, which could probably contribute to the lower prevalence of vitamin D deficiency observed in this study.
Another probable theory for the difference in prevalence between Ile-Ife and Lagos is the effect of environmental pollution. Lagos, a south-western cosmopolitan city in Nigeria, is an industrialized emerging megacity in Nigeria, subject to the negative impacts of changing climatic conditions partly caused by ubiquitous air pollution [19]. Atmospheric pollution has been suggested to be a cause of reduced vitamin D synthesis in the skin. Agarwal et al. [20] demonstrated that the higher the atmospheric pollution, the lower the amount of UVB light reaching ground level. Prevalence rates reported from a community-based study in Nigeria by Glew et al. [21] amongst 51 nomadic Fulanis revealed that 83% of the women and 45% of the men had serum 25-hydroxyvitamin D levels in the hypovitaminosis D range. The high prevalence was attributed to poor dietary sources of vitamin D among the nomads and the concealing dressing habits of the women.
Medd et al. [22] reported a prevalence of 47.6% of hypovitaminosis D in a healthy cohort of 389 adults from Tunisia. Allali et al. [23] reported a prevalence of vitamin D insufficiency (< 30 ng/mL) of 91% in a cohort of 415 women from Morocco. Lack of exposure to sunlight and veiled clothing style were the most important factors that influenced hypovitaminosis D in these studies [22, 23].
A higher proportion of vitamin D deficiency was found among the older age group, and this is similar to the study in Lagos [10]. Among elderly patients, multiple factors contribute to vitamin D inadequacy, including decreased cutaneous synthesis of vitamin D3. Also, with increasing age, there is decreased renal conversion of 25 OH vitamin D to the active form [24]. There is also the additional burden of age-related lactose intolerance with reduced intake of fortified dairy products [24].
Vitamin D deficiency was found to be associated with the male gender in the study. Previous studies [25, 26] suggest that low vitamin D levels are associated with reduced testosterone in middle-aged men, potentially improved through supplementation. However, conflicting evidence exists, requiring further research to clarify the impact of vitamin D supplementation on testosterone levels. A review of the literature reported a higher prevalence of vitamin D deficiency among females, which is attributed to increased frequency of obesity, clothing style, multiparity, and menopause among other features [22, 23, 27]. The difference in this study could be due to our environmental differences and the slightly more male subjects recruited in this study.
Obesity did not explain the occurrence of vitamin D deficiency in this study, contrary to other studies [8, 24], which reported an inverse relationship between obesity and vitamin D insufficiency. Lower concentrations of serum 25(OH)D levels in obese subjects may be explained by enhanced uptake by adipose tissue, increased metabolic clearance, and the sedentary lifestyle of obese subjects could be associated with less outdoor activity and less exposure to sunlight.
All the study participants reported adequate exposure to sunlight; there was no use of sunscreen creams. The availability of vitamin D for individuals was heavily influenced by exposure to sunlight, as vitamin D is mostly produced in the skin. With trends towards less sun exposure and routine use of sunscreen, several studies have identified these additional risk factors. However, this was not the case in this study [7, 27]. The study participants are Nigerians who are dark-skinned. They have melanin-rich skin, which provides protection against harmful UV radiation but can also inhibit vitamin D synthesis in response to sunlight exposure [27, 28].
In the assessment of vitamin D deficiency/insufficiency, patients should be questioned about their consumption and timing of calcium-containing medications and meals. This is because certain supplements are absorbed better when taken with food, while others are more effective on an empty stomach. The timing of these medications with meals is essential for evaluating vitamin D deficiency. It also impacts the efficacy of calcium supplementation and should be considered alongside vitamin D status [29]. In this study, however, people taking Vitamin D or calcium supplements were excluded. Hence, the use of these supplements is not expected to impact the outcome of this study.
Higher HbA1c levels were strongly associated with vitamin D deficiency, supporting evidence of a link between poor glycemic control and low vitamin D status. This is similar to the findings from earlier reports [10, 30, 31]. It is believed that vitamin D may assist in improving glycaemic control by improving insulin production and secretion and reducing insulin peripheral resistance, while chronic hyperglycemia may adversely affect vitamin D metabolism, suggesting a bidirectional relationship [12, 32].
The observed 93% co-occurrence between vitamin D deficiency and nephropathy is notable; however, it should be interpreted with caution. This association is likely influenced by shared underlying risk factors, such as chronic illness, malnutrition, or kidney disease affecting vitamin D metabolism, rather than reflecting a direct causal relationship. Nevertheless, the finding may have relevant clinical implications, particularly in resource-limited settings. Vitamin D deficiency could potentially serve as a pragmatic risk marker to prompt further evaluation for nephropathy, and vice versa, although it is not suitable as a standalone diagnostic indicator. Its principal utility may lie in informing targeted, tiered screening strategies designed to optimize case detection while maintaining cost-effectiveness.
Our study demonstrated a positive correlation between vitamin D levels and nephropathy, measured using eGFR, although this association was no longer significant after adjusting for confounding variables in regression analysis. The proportion of the T2DM subjects with vitamin D deficiency who had nephropathy assessed with ACR was higher compared to those with insufficiency and normal serum vitamin D, respectively (93.0% versus 67.7% versus 47.3%). The difference was statistically significant and similar to other studies [9]. Vitamin D deficiency in renal insufficiency may be caused by dysregulation of vitamin D metabolism and loss of reno-protective actions of vitamin D [33].
This study has some limitations. Its cross-sectional design precludes causal inference and prevents assessment of the temporal relationship between vitamin D deficiency and chronic hyperglycaemia; prospective studies are therefore warranted. Moreover, the moderate sample size, including relatively few participants with vitamin D deficiency, may limit the statistical power of subgroup analyses and compromise the stability of estimates, particularly for renal outcomes.
Conclusion
A high prevalence of vitamin D deficiency and insufficiency was seen in individuals with diabetes in this study, and age, and male sex were the identified risk factors. This study also showed that vitamin D deficiency is associated with poor glycemic control and renal function deterioration.
Acknowledgements
The authors wish to acknowledge the contributions of the residents of the Endocrine Unit of the hospital for their support in recruiting participants for this study.
Author contributions
ATL and RTI contributed to the conceptualization, methodology, writing, reviewing, and editing; DOS contributed to the methodology, writing, reviewing, and editing; ANF and BAK contributed to writing, reviewing, and editing. All authors contributed to the interpretation of data and approved the final version of the manuscript.
Funding
This study received no external funding.
Data availability
The datasets used during this study are available on request.
Declarations
Ethical approval
This study was conducted in accordance with the principles outlined in the Declaration of Helsinki. Ethical approval was obtained from the Ethics and Research Committee of the Obafemi Awolowo University Teaching Hospital (IRB/IEC/0004553).
Consent to participate
Written informed consent was obtained from willing participants after counselling before enrolment in the study.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets used during this study are available on request.




