|Year : 2019 | Volume
| Issue : 2 | Page : 79-82
Association of vitamin D with diabetic neuropathy among Sudanese patients with type 2 diabetes mellitus
Ibrahim Wagea Alla Dalia1, M Abdalla Abdelmula2, Abdelrahman Elbashir Zeinab3, A Abdrabo AbdElkarim2
1 Department of Clinical Chemistry, School of Medical Laboratory Science, Sharq Elniel College, Khartoum, North, Sudan
2 Department of Clinical Chemistry, Faculty of Medical Laboratory Science, Elneelain University, Sudan
3 Department of Internal Medicine, Faculty of Medicine, University of Khartoum, Khartoum, Sudan
|Date of Submission||03-Apr-2019|
|Date of Decision||31-Jul-2019|
|Date of Acceptance||09-Sep-2019|
|Date of Web Publication||19-Nov-2019|
Dr. Ibrahim Wagea Alla Dalia
Department of Clinical Chemistry, School of Medical Laboratory Science, Sharq El Niel College Khartoum
Source of Support: None, Conflict of Interest: None
Background: Neuropathy is a common diabetic microvascular complication which reduces quality of life; causing pain and irritation in lower limbs and may result in amputation. Several Studies documented that vitamin D deficiency have extra skeletal effects including poor glycemic control and microvascular complications. Objectives: To explore the relationship between levels of vitamin D and diabetic neuropathy in Sudanese patients with type 2 diabetes mellitus. Methods: In this cross-sectional case control and hospital based study conducted at Jabber Abu Eliz Diabetes Centre (JAEDC), from February 2015 to November 2018, Sixty diabetic patients (thirty patients with neuropathy and thirty patients without neuropathy), and sixty healthy subjects were compared in terms of levels of vitamin D, C-peptide, lipid profile, HbA1C, C-reactive protein, and MAU. SPSS software was used for analysis of clinical variables. Results: Vitamin D levels where significantly decreased in diabetic patients and also in those with neuropathy when compared to those without neuropathy (P < 0.05) Vitamin D correlated significantly with age P (0.016), insignificantly with disease duration, BMI, HbA1C and MAU (P > 0.05). 86.8% of patients with neuropathy had vitamin D deficiency and 6.6% had insufficiency. Vitamin D levels where significantly reduced with increasing severity of neuropathy (P 0.001). Conclusion: Vitamin D levels are significantly decreased in diabetic patients especially in those with neuropathy. Severity of neuropathy is significantly correlated to severity of vitamin D deficiency. Diabetic patients should be screened for vitamin D level and supplementation should be prescribed to correct the deficiency.
Keywords: Diabetic neuropathy, Sudanese patients, type 2 diabetes, Vitamin D
|How to cite this article:|
Alla Dalia IW, Abdelmula M A, Zeinab AE, AbdElkarim A A. Association of vitamin D with diabetic neuropathy among Sudanese patients with type 2 diabetes mellitus. Niger J Basic Clin Sci 2019;16:79-82
|How to cite this URL:|
Alla Dalia IW, Abdelmula M A, Zeinab AE, AbdElkarim A A. Association of vitamin D with diabetic neuropathy among Sudanese patients with type 2 diabetes mellitus. Niger J Basic Clin Sci [serial online] 2019 [cited 2020 Apr 6];16:79-82. Available from: http://www.njbcs.net/text.asp?2019/16/2/79/271005
| Introduction|| |
Diabetes mellitus is a global health problem as well as Vitamin D deficiency. Epidemiologic observations have associated low vitamin D status with an increased risk of non-musculoskeletal disease.
Diabetic peripheral neuropathy is one of the most common long-term complications of diabetes; it develops in up to half of all people with diabetes and is one of the main risk factors contributing to foot ulcerations and eventual amputation. Several studies showed possible association between vitamin D deficiency and diabetic peripheral neuropathy. Several studies on patients with type 2 diabetes confirmed the relationship between vitamin D deficiency and the incidence of neuropathy as well as symptoms caused by neuropathy.
Vitamin D deficiency was reported to be associated with neuronal calcium homeostasis, neurotrophin levels and also with neuronal differentiation. Furthermore, the nociceptor function seemed to be modulated by vitamin D. Moreover, some previous studies mentioned that treatment of vitamin D deficiency may reduce neuropathic pain.
| Methods|| |
This cross-sectional case control and hospital-based study was conducted at Jabir Abu Eliz Centre for Diabetes from February 2015 to November 2018 and was approved by Alneelain University Research Committee, the management of Jabir Abu Eliz diabetes center and Ministry of Health Khartoum, Sudan.
The study group comprised of 60 Sudanese patients with type 2 diabetes mellitus, 30 of which had neuropathy and 30 patients without microvascular complications (control group 2). As control, 60 healthy volunteers (age and sex matched) with normal physical examination and lab findings were selected (control group 1). All patients signed an informed consent form to allow in their information to be used for this study. An interview administered questionnaire was used to obtain the demographic and clinical data of each participant.
A physician carried out the classification of the participants into study and control groups based on clinical history and examination findings.
Peripheral neuropathy was defined by abnormalities in 10 g monofilament testing and tuning fork. Four Neurological Examination Scoring systems were selected on the basis of ease of performance and common use which include Diabetic Neuropathy Symptoms score (DNS), Diabetic Neuropathy Examination score (DNE), Modified Neuropathy Symptoms Score (NSS) and Modified Neuropathy Disability Score., All patients were graded based on each of the above scores. Patients with acute complications, clinical history of renal disease or hypertension originating from causes other than diabetes, patients with end stage renal disease; cancer, autoimmune disorders, liver disorders, patients on vitamin D supplementation; patients that had any type of neuropathy diagnosed or suspected, acute or chronic musculoskeletal disorder, patients on drugs that may improve, mask or aggravate the normal course of neuropathy and pregnant women, were excluded from this study.
Blood samples after overnight fasting were collected in Ethylene Diamine Tetra-acetic Acid (EDTA) container for estimation of glycated hemoglobin (HbA1C) and lithium heparin container for estimation of 25(OH) vitamin D level, Connecting peptide (C-peptide), C-reactive protein (CRP), and lipid profile. Also, on-the spot urine sample was collected, for quantification of microalbumin (MA), from each participant in the study.
Total cholesterol was determined using cholesterol oxidase method, triglycerides determined by glycerol kinase peroxidase method, and direct method were used for determination of high-density lipoprotein (HDL) and low-density lipoprotein (LDL). All these parameters were estimated using mindary BS 200 autoanlyzer. The level of 25(OH) vitamin D were measured using Euroimmun 25(OH) vitamin D ELIZA kit based on competitive principle by using ELISA reader (Human Germany). C-peptide levels were measured by flurometeric enzyme immunoassay (Tosho-India) with detection range of 0.1–sd1000 ng/ml.
HbA1C, CRP and urine for microalbumin (MAU) were determined by using a fluorescence immunoassay (FIA) based on sandwich principle by commercial kit from Boditech Med Incorporated 43 Republic of Korea using i-chroma reader.
The precision and accuracy of the techniques used in this study were checked each time a batch was analysed by including commercially prepared control sera (two levels of control material normal and pathological) from Mindray, EUROIMMUN, Tosoh and Boditech Med Incorporated were analysed with each batch of sample to verify the performance of measurement procedure. These controls serve as internal controls for the reliability of the test procedure.
SPSS software (version 23) was used for analysis of data and expressed as Mean ± SD P value of <0.05 was considered significant. T-test method was used to compare variables between the diabetic groups and Pearson's correlation was used to assess correlation between vitamin D and HbA1c, age, duration of diabetes, body mass index (BMI), CRP and microalbumin, respectively.
| Results|| |
As illustrated in [Table 1], there is a significant increase in BMI, SBP, Total Cholesterol, Triglycerides and CRP P = (0.02,0.02,0.01,0.02 and 0.009 respectively). There was a significant decrease in 25(OH) vitamin D and C-peptide in diabetic group when compared with control group 1P (0.001 and 0.001, respectively). Also, there was insignificant increase in DBP, LDL P = (0.31, 0.6 respectively). The HDL was insignificantly decreased P = 0.063.
|Table 1: Demographic and clinical data of the study group and their control 1 group|
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As laid out in [Table 2], in patients with diabetic neuropathy there was significant increase in HbA1c, (9.79 ± 2.29 vs. 8.53 ± 1.66, P = 0.01). In addition, there was significant decrease in 25(OH) vitamin D and C-peptide (12.33 ± 8.53 vs. 20.40 ± 11.12, P = 0.001 and 1.22 ± 0.37 vs 1.67 ± 0.50, P = 0.001, respectively). The Table shows insignificant increase in CRP and the results were (10.17 ± 5.02 vs. 8.05 ± 3.90, P = 0.07, respectively). There was insignificant decrease in MAU and the results were (8.10 ± 4.49 vs. 8.53 ± 2.24, P = 0.63, respectively).
|Table 2: Comparison of HbA1C, 25(OH) vitamin D, C-peptide, MAU and CRP levels in diabetic group with neuropathy and diabetic group without neuropathy (control 2 group)|
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As shown in [Table 3], in patients with neuropathy, there were significant correlations between 25(OH) vitamin D and patients' age (r = -0.434 P = 0.02). Also, there was insignificant correlation between 25(OH) vitamin D and disease duration, BMI, HbA1C and MAU (r = 0.096 P = 0.62, r = -0.273 P = 0.15, r = -0.247 P = 0.14 and r = -0.168 P = 0.38, respectively).
|Table 3: Correlation between 25(OH) vitamin D level and age, disease duration, BMI, HbA1C, and MAU in diabetic patients with neuropathy. Pearson's correlation was used for analysis|
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In [Figure 1], 86.8% of patients with neuropathy had 25(OH) vitamin D deficiency (less than 20 ng/ml), 6.6% of the patients had insufficiency (20 ng/ml to less than 30 ng/ml) and 6.6% had sufficient 25(OH) vitamin D levels (30 ng/ml and less than 70 ng/ml).
|Figure 1: Distribution of patients according to level of 25(OH) vitamin D in the study groups. Deficiency (less than 20 ng/ml), Insufficiency (20 ng/ml and less than 30 ng/ml), Sufficiency (30 ng/ml and less than 70 ng/ml)|
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In [Figure 2], according to the severity of the neuropathy, vitamin D levels were significantly decreased with values ranging from 29.25 ± 10.21 ng/ml in mild cases, 13.54 ± 2.26 ng/ml in moderate cases, and 5.92 ± 1.75 ng/ml in severe cases of neuropathy (P = 0.001).
|Figure 2: The level of 25(OH) vitamin D according to the Severity of neuropathy in the study group|
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| Discussion|| |
In the group of patients with diabetes, the study showed a significant decrease in the level of 25(OH) vitamin D in patients with microvascular complications when compared to those without microvascular complications. A link between hypovitaminosis D and microvascular complications in patients has been explored by Fiscella et al., who found that 25(OH) vitamin D levels were lower in diabetic patients with microvascular complications compared to those without microvascular complications.
In patients with neuropathy in our study, 25(OH) vitamin D levels are significantly lower than in those without microvascular complication, which agrees with the study done by Ahmadieh et al. who reported that the prevalence of diabetic neuropathy increases with decrease in 25(OH) vitamin D levels. The percentage of neuropathy increased in patients with 25(OH) vitamin D levels below 20 ng/ml. In addition, 25(OH) vitamin D levels were lower in patients with diabetic neuropathy compared with those without neuropathy. There is emerging evidence that vitamin D is a neurotrophic substance, but its role in diabetic neuropathic pain is uncertain. It has been suggested that vitamin D deficiency may potentiate diabetic nerve damage and may impair nociceptor function, resulting in pain at a threshold of serum 25(OH) vitamin D higher than that in the non-diabetic population. Lee, and Chen showed that vitamin D supplementation over 3 months improved neuropathic symptoms by 50% in diabetic patients with vitamin D deficiency at baseline.
Diabetic neuropathy is the most common microvascular complication. In the study carried out by Lee et al., an association was detected between hypovitaminosis D and diabetic neuropathy. The researches indicated that neuropathic pain decreased after vitamin D replacement therapy. Another study demonstrated a link between hypovitaminosis D and neuropathy. In contrast, in the study done by Simesk et al. no differences in vitamin D levels were found between diabetic patients with or without microvascular complication.
The result of our study shows that, in patients with neuropathy, 25(OH) vitamin D correlates significantly with patients' age, but this disagrees with the result obtained by Lanlan et al., who reported that there was no correlation between 25(OH) Vitamin D levels and age. In this study, 25(OH) vitamin D is insignificantly correlated with the duration of neuropathy, which disagrees with the results of Lanlan et al., who found a negative correlation between 25(OH) Vitamin D level and the course of the disease. The current study found insignificant negative correlation between 25(OH) vitamin D and BMI in patients with neuropathy. This result agrees with the result of Lanlan et al. who found no correlation between 25(OH) Vitamin D level and BMI. In patients with neuropathy, the present study found an insignificant negative correlation of 25(OH) vitamin D with HbA1C, this is consistent with Lanlan et al. whose result found that there was no correlation between 25(OH) Vitamin D level and HbA1c.
In patients with diabetic neuropathy, the level of 25(OH) vitamin D was decreased in severe cases of neuropathy compared to those with mild and moderate cases. The decline in vitamin D levels between the groups was found to be significant. This result agreed with the results obtained from Shehab et al. and Bilir et al. Their studies have strongly suggested an inverse relationship between vitamin D level and diabetic peripheral neuropathy in diabetes mellitus.,
| Conclusion|| |
Vitamin D levels are significantly decreased in diabetic patients especially those with neuropathy. Severity of neuropathy is significantly correlated to severity of vitamin D deficiency. Diabetic patients should be screened for vitamin D level and supplementation should be prescribed to correct the deficiency.
Limitations of the study
The limitation of this study could be summarised in two points first in the small number of subjects, second limited in conclude that vitamin D status is directly related to pathogenesis of neuropathy.
| Recommendation|| |
Further studies with larger number of subjects are needed to determine whether vitamin D status is a casual factor in neuropathy or rather a consequence of disease. Moreover, supplementations of vitamin D are recommended to the patients with neuropathy to determine its effects in prevention the development of neuropathy.
Authors are grateful to the staff of Jaber Abu Eliz Diabetes Centre, Sudan and all people from who samples were taken.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Gabbay L, Dib S, Carvalho E. Vitamin D and diabetes mellitus: Un update. Arq Bras Endocrinol Metabol 2014;58:1-8.
Gow D, Moore P. Assessing diabetic peripheral neuropathy in primary care. Best Pract J2014;61:36-47.
Usluogullari C, Balkan F, Caner S, Ucler R, Kaya C, Ersoy R, et al.
The relationship between microvascular complications and vitamin D deficiency in type 2 diabetes mellitus. BMC Endocr Disord 2015;15:33.
Putz Z, Martos T, Nemeth N, Korei A, Vagi O, Kempler M, et al
. Is there an association between diabetic neuropathy and low vitamin D levels? Curr Diab Rep 2014;14:573.
Bell D. Reversal of the symptoms of Diabetic Neuropathy through correction of Vitamin D deficiency in a type 1 diabetic patient. Case Rep Endocrinol2012;2012:165056. doi: 10.1155/2012/165056.
Shehab D, Al-Jarallah K, Abdella N, Mojiminiyi O, Al Mohamedy H. Prospective evaluation of the effect of short-term oral vitamin D supplementation on peripheral neuropathy in type 2 diabetes mellitus. Med Princ Pract 2015;24:250-6.
England J, Gronseth G, Franklin G, Miller R, Asbury A, Carter GT, et al.
Distal symmetric polyneuropathy: A definition for clinical research; report of American Academy Electrodiagnostic Medicine and the American Academy of Physical Medicine and Rehabilitation. Neurology 2005;64:199-207.
Mallik A, Weir A. Nerve conduction studies: Essentials and pitfalls in practice. J Neurol Neurosurg Psychiatry 2005;76:S23-31.
Fiscella K, Winters P, Ogedegbe G. Vitamin D and racial disparity in albuminuria: NHANES 2001–2006. Am J Hypertens 2011;24:1114-20.
Ahmadieh H, Azar S, Lakkis N, Arabi A. Hypovitaminosis D in patients with type 2 diabetes mellitus: A relation to disease control and complications. ISRN Endocrinol2013;2013:641098. doi: 10.1155/2013/641098.
Simsek Y, Kucukler F, Arduc A, Guler S. Is there an association between vitamin D level and microvascular complications of type 2 diabetes mellitus? WIMJ Open 2015;2:138-41.
Naveilhan P, Neveu I, Wion D, Brachet P. 1,25-Dihydroxyvitamin D3, an inducer of glial cell line-derived neurotrophic factor. NeuroReport1996;7:2171-5.
Lee P, Chen R. Vitamin D as an analgesic for patients with type 2 diabetes and neuropathic pain. Arch Intern Med2008;1680:771-2.
Lee J, OKeefe J, Bell D, Hensrud D, Holick M. Vitamin D deficiency an important, common, and easily treatable cardiovascular risk factor? J AM Coll Cardiol 2008;52:1949-56.
Lanlan Y, XuMa Z, Dong X, Tian F, Man R. Correlation between 25-hydroxy-Vitamin-D and senile diabetic peripheral neuropathy in type 2 diabetes. Biomed Res2017;28:6286-9.
Shehab D, Al-Jarallah K, Mojiminiyi O, Al Mohamedy H, Abdella N. Does vitamin D deficiency play a role in peripheral neuropathy in Type 2 diabetes? Diabet Med2012;29:43-9.
Bilir B, Tulubas F, Bilir B, Atile N, Kara S, Yildirim T, et al.
The association of vitamin D with inflammatory cytokines in diabetic peripheral neuropathy. J Phys Ther Sci 2016;28:2159-63.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]