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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 31  |  Issue : 4  |  Page : 669-677

Effect of vitamin D replacement on cardiometabolic risk factors and electrophysiological pattern of peripheral neuropathy in vitamin D-insufficient or deficient type 2 diabetic patients


1 Department of Internal Medicine, Faculty of Medicine, Zagazig University, Zagazig, Egypt
2 Department of Neurology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
3 Department of Rheumatology and Rehabilitation, Faculty of Medicine, Zagazig University, Zagazig, Egypt
4 Department of Cardiology, Faculty of Medicine, Zagazig University, Zagazig
5 Department of Clinical Pathology, Faculty of Medicine, Zagazig University, Zagazig, Egypt

Date of Submission15-Apr-2018
Date of Acceptance14-Jul-2019
Date of Web Publication18-Aug-2020

Correspondence Address:
MD Nearmeen M Rashad
Departments of Internal Medicine, Faculty of Medicine, Zagazig University, Zagazig, 44519
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ejim.ejim_62_19

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  Abstract 


Background Diabetic neuropathy is one of the commonest chronic complications of diabetes seen in routine healthcare and considered the most common cause of peripheral neuropathy all over the world. Vitamin D (VD) deficiency is now recognized as a pandemic disease. This study was designed to explore the levels of 25-hydroxycholecalciferol [25(OH) D] in patients with type 2 diabetes mellitus (T2DM) with peripheral neuropathy. We also aimed to clarify the effect of VD supplementation on cardiometabolic status and electrophysiological pattern of peripheral neuropathy.
Patients and methods This clinical trial enrolled 95 patients with T2DM with peripheral neuropathy. The enrolled patients were divided into three groups according to serum 25(OH) D levels. VD deficiency and insufficiency groups received VD supplements (42,000 IU oral VD per week and 500-mg calcium carbonate per day for 12 weeks). Clinical, electrophysiological pattern, and laboratory parameters were evaluated at baseline and after 12 weeks of intervention. Serum 25(OH) D levels were measured by using a competitive enzyme-linked immunosorbent assay kit.
Results Our results revealed that, among 95 patients with T2DM with peripheral neuropathy, 32 patients had VD insufficiency [20 ng/ml <25(OH) D <30 ng/ml], 50 patients had VD deficiency [25(OH) D ˂20 ng/ml], and 13 patients had VD sufficiency [25(OH) D >30 ng/ml]. Our results reported that 25(OH) D levels were negatively correlated with cardiometabolic risk factors and Toronto Clinical Scoring System. On the contrary, 25(OH) D levels were positively correlated with nerve conduction velocities (NCV). Stepwise multiple linear regression analysis revealed that glycated hemoglobin and Toronto Clinical Scoring System were the main predictors of 25(OH) D levels among other clinical and laboratory biomarkers. Logistic regression analysis observed that motor NCV and sensory NCV of median nerve and glycated hemoglobin were independent predictors of response to VD supplementation. NCV in studied groups showed that motor NCV and sensory NCV in the median, posterior tibial, and ulnar nerves were significantly decreased in both VD deficiency and insufficiency groups compared with VD sufficiency groups, and supplementation with 42 000 IU oral VD per week and 500-mg calcium carbonate per day for 12 weeks improved cardiometabolic risk factors and electrophysiological pattern of peripheral neuropathy.
Conclusion The supplementation of VD for 12 weeks to VD deficiency and insufficiency groups improved the cardiometabolic and electrophysiological pattern of peripheral neuropathy.

Keywords: cardiometabolic, deficiency, electrophysiological, insufficiency, peripheral neuropathy, type 2 diabetes mellitus, vitamin D supplementation


How to cite this article:
Rashad NM, Sabry HM, Gomaa AF, Ebaid AM, Abomandour HG, Allam RM. Effect of vitamin D replacement on cardiometabolic risk factors and electrophysiological pattern of peripheral neuropathy in vitamin D-insufficient or deficient type 2 diabetic patients. Egypt J Intern Med 2019;31:669-77

How to cite this URL:
Rashad NM, Sabry HM, Gomaa AF, Ebaid AM, Abomandour HG, Allam RM. Effect of vitamin D replacement on cardiometabolic risk factors and electrophysiological pattern of peripheral neuropathy in vitamin D-insufficient or deficient type 2 diabetic patients. Egypt J Intern Med [serial online] 2019 [cited 2020 Sep 28];31:669-77. Available from: http://www.esim.eg.net/text.asp?2019/31/4/669/292241




  Introduction Top


A preponderance of evidence suggests that the most common cause of peripheral neuropathy in Egypt is diabetes mellitus (DM). Diabetic peripheral neuropathy (DPN) is one of the microvascular complications that cause morbidity and mortality in patients with DM; 50% of diabetic patients have diabetic neuropathy [1].

Several lines of evidence confirmed the DPN complications, of particular interest, foot amputation owing to painless foot ulcers, and diabetic autonomic neuropathy may be associated with life-threatening conditions such as sudden death and silent myocardial ischemia [2]

Vitamin D (VD) is a fat-soluble vitamin that is naturally present in very few foods and is available as a dietary supplement. It is a steroid hormone with pleiotropic effects. In addition to the main effects of VD on bone and calcium metabolism, it has other roles in the body, including modulation of cell growth, neuromuscular and immune function, and reduction of inflammation [3].

VD deficiency is now recognized as a pandemic disease. Its prevalence varies according to geographic location, season, ethnicity, and the standard laboratory value, of what is considered normal, deficient, and insufficient. VD deficiency is a risk factor for hypertension, diabetes, and various cancers [4]. Accumulating evidence suggests that VD deficiency contributes significantly to the pathogenesis of the two types of diabetes by impairing insulin secretion from pancreatic beta cells [5] and increasing insulin resistance [6]. Extensive data support a major role of VD deficiency in pathogenesis of diabetic neuropathies [7],[8]. Therefore, the aim of the current study was to measure the levels of 25-hydroxycholecalciferol [25(OH) D] in patients with type 2 diabetes mellitus (T2DM) with peripheral neuropathy. We also aimed to clarify the effect of VD supplementation on cardiometabolic status and electrophysiological pattern of peripheral neuropathy.


  Patients and methods Top


Patients

This clinical trial was conducted in the outpatient clinics of diabetes and endocrinology of Internal Medicine Department at Zagazig University Hospital. This study included 95 patients with T2DM with peripheral neuropathy. The diagnosis of diabetes was according to ADA 2017; the enrolled diabetic patients were classified into three groups according to estimated serum 25(OH) D levels. VD deficiency was defined as serum 25(OH) D concentration of less than 20 ng/ml, insufficiency as 20 ng/ml less than 25(OH) D less than 30 ng/ml, and sufficiency was defined as 25(OH) D higher than 30 ng/ml [9]. The enrolled patients were subjected to full clinical assessment and neurological examination. There is no gold standard for the diagnosis of peripheral neuropathy. The expert panel of San Antonio conference recommends that it should be made on the basis of neuropathic symptoms, signs, and nerve conduction studies (NCS) [10].

Neurological examination was performed in the outpatient clinic of Neurology Department using the 10-g Semmes-Weinstein monofilament, applying the test on nine different sites on the plantar surface of the foot and diagnosing sensory neuropathy when less than seven sites were felt by the patient. Vibration perception threshold (VPT) was also measured, using a biothesiometer, to define the presence of diabetic neuropathy with a cutoff vibration perception threshold of more than 25 V for the diagnosis of loss of protective sensation.

Anthropometric variables including BMI were calculated as weight (kg)/height (m2) and waist circumference (cm)/hip circumference (cm) ratio was measured. Body weight had to be stable for at least 3 months before study. All participants were on an unrestricted diet and were instructed not to modify their usual eating patterns.

Exclusion criteria included current psychiatric disorder that might affect the reliability of their response to the study questionnaire. The patients whose serum calcium was more than 10.4 mg/dl or those taking multivitamin supplementation or having hepatic, renal, or metabolic bone disorders (including parathyroid-related problems) were excluded from the study. Moreover, those patients with use of glucocorticoids or anti-seizure medications in the previous 6 months or those patients having history of malabsorption syndromes such as celiac disease or active malignancy or with active infection were excluded from the study. Patients with any neuropathic pain of nondiabetic origin including but not limited to lower back or neck pain (radiculopathy), postherpetic neuralgia, cancer-related pain, spinal-cord injury pain, multiple sclerosis pain, carpal tunnel syndrome pain, phantom pain, trigeminal neuralgia, or fibromyalgia were excluded from the study. In addition, we excluded pregnant patients.

The ethical committee of Faculty of Medicine, Zagazig University, approved our study protocol, and all participants signed a written informed consent before starting the study.

Severity of neuropathy

The severity of neuropathy was graded according to Toronto Clinical Scoring System (TCSS): 1–5 points for no neuropathy, 6–8 points for mild neuropathy, 9–11 points for moderate neuropathy, and 12–19 points for severe neuropathy. Symptom, reflex, and sensory tests, including pinprick, temperature, light touch, vibration, and position sensation, were performed as part of the TCSS [11].

Nerve conduction study

NCS in the median, ulnar, peroneal, tibial, and sural nerves were carried out for all participants with the Micromed machine in the neurology outpatient clinic. Motor conduction studies were carried out with surface disk electrodes, with the active electrode inserted on the muscles and supramaximal stimulation of the corresponding nerves. Sensory NCS were performed. The parameters were compared between patients and controls. Individual values of conduction velocities, latencies, or amplitude were considered abnormal when outside the mean±2 SD of controls [12]. If two or more nerves had at least one abnormal parameter compared with the age-matched controls, it is electrophysiologically considered peripheral neuropathy.

Intervention

All VD insufficiency and deficiency patients received VD supplements 42 000 IU oral VD per week and 500-mg calcium carbonate per day for 12 weeks to reach 25(OH) D above 30 ng/ml and the maintenance dose of 1500–2000 IU per days.

Dietary intake

Dietary intakes of VD and calcium were ensured through 1-day 24-h dietary recall at the baseline and end of the eighth week of the study.

Blood sampling

Blood samples were drawn from all participants after an overnight fast and divided into three portions: 1 ml of whole blood was collected into evacuated tubes containing EDTA, for glycated hemoglobin (HbA1c), 1 ml of whole blood was collected into evacuated tubes containing potassium oxalate and sodium fluoride (2 : 1) for fasting plasma glucose (FPG), and serum was separated immediately from the remaining part of the sample and stored at −20°C until analysis.

Biochemical analysis

We determined FPG levels using the glucose oxidase method (Spinreact, Girona, Spain). Total cholesterol, high-density lipoprotein-cholesterol, and triglycerides levels were measured by routine enzymatic methods (Spinreact). The low-density lipoprotein-cholesterol level was calculated using the Friedewald formula [13].

Determination of serum vitamin D levels

Serum concentrations of 25(OH) D were tested using enzyme-linked immunosorbent assay (Cat No. EQ. 6411–9601; Euroimmun Medizinische Labordiagnostika AG, Germany). Current recommendations define VD deficiency as serum 25(OH) D levels less than 20 ng/ml and VD insufficiency less than 30 ng/ml [14].

Statistical analysis

Statistical analyses were performed using the Statistical Package for the Social Sciences for Windows (version 21.0; SPSS Inc., Chicago, Illinois, USA). Data were expressed using descriptive statistic (mean±SD) and were analyzed using one-way analysis of variance, followed by least significance difference test for multiple comparisons between groups. Pearson correlation coefficient was used to assess the association between serum 25(OH) D levels with anthropometric measures as well as electrophysiological parameters in the patients. A stepwise multiple linear regression analysis was done to detect the main predictors of serum 25(OH) D in T2DM group. Logistic regression analysis was performed to determine the predictor biomarker associated with VD supplementation among patients with T2DM. We considered P to be significant at less than 0.05, with a 95% confidence interval.


  Results Top


Among 95 patients with T2DM with peripheral neuropathy, 32 patients had VD insufficiency [20 ng/ml <25(OH) D <30 ng/ml], 50 patients had VD deficiency [25(OH) D ˂20 ng/ml], and 13 patients had VD sufficiency [25(OH) D >30 ng/ml].

Clinical, laboratory, and electrophysiological characteristics of the studied groups at baseline

VD insufficiency (n=32) and deficiency (n=50) patients had significantly long duration of diabetes and higher values of triglycerides, total cholesterol, low-density lipoprotein, FPG, HbA1c, PO4, and TCSS compared with VD sufficiency (n=13) group. Furthermore, VD deficiency patients had significantly higher values of systolic blood pressures compared with VD sufficiency (P<0.001). On the contrary, VD insufficiency and deficiency patients had significantly lower values of high-density lipoprotein and serum calcium compared with VD sufficiency group ([Table 1]).
Table 1 Clinical, laboratory, and electrophysiological characteristics of the studied groups at baseline

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Electrophysiological tests of the studied groups

Nerve conduction velocities (NCV) in the studied group showed that motor nerve conduction velocities (MNCV) in median, ulnar, and posterior tibial (PT) nerves were significantly decreased in both VD insufficiency and deficiency patients compared with VD sufficiency group. Moreover, sensory nerve conduction velocities (SNCV) in median, ulnar, sural, and PT nerves were significantly decreased in VD insufficiency and deficiency patients, with P value less than 0.001 ([Table 1]).

Regarding amplitudes, compound muscle action potential (CMAP) amplitudes in median, ulnar, and PT were significantly decreased in both obese patients with or without peripheral neuropathy compared with the control group. Sensory nerve conduction potential (SNAP) amplitudes in median, PT, and sural nerves were significantly decreased in decreased in VD insufficiency and deficiency patients compared with VD sufficiency group, with P value less than 0.001 ([Table 1]).

Correlations between serum 25-hydroxycholecalciferol levels with Toronto Clinical Scoring System as well as electrophysiological parameters in patients

Our results reported that 25(OH) D levels were negatively correlated with cardiometabolic risk factors ([Figure 1],[Figure 2],[Figure 3],[Figure 4]) and TCSS. On the contrary, 25(OH) D levels were positively correlated with electrophysiological tests: MNCV (median, ulnar, and PT nerves), SNCV (median, ulnar, and PT nerves), CMAP amplitude (median, ulnar, and PT nerves), and SNAP amplitude (median, sural, ulnar, and PT nerve) ([Table 2]).
Figure 1 Correlations between serum 25(OH) D levels and TCSS. 25(OH) D, 25-hydroxycholecalciferol; TCSS, Toronto Clinical Scoring System.

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Figure 2 Correlations between serum 25(OH) D levels and HbA1c. 25(OH) D, 25-hydroxycholecalciferol; HbA1c, glycated hemoglobin.

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Figure 3 Correlations between serum 25(OH) D levels and BMI. 25(OH) D, 25-hydroxycholecalciferol.

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Figure 4 Correlations between serum 25(OH) D levels and TG. 25(OH) D, 25-hydroxycholecalciferol; TG, triglycerides.

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Table 2 Pearson correlation between serum 25-hydroxycholecalciferol and electrophysiological parameters in patients with type 2 diabetes mellitus

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Linear regression analyses in patients with type 2 diabetes mellitus to assess the main independent parameters associated with serum 25-hydroxycholecalciferol levels

Linear regression analysis test revealed that serum 25(OH) D levels were independently correlated with HbA1c and TCSS (P<0.001) ([Table 3]).
Table 3 Linear regression analyses in type 2 diabetes mellitus to test the influence of the main independent variables against serum 25-hydroxycholecalciferol (ng/ml) levels (dependent variable) in patients with type 2 diabetes mellitus

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The effect of vitamin D supplementations on clinic-metabolic status and electrophysiological parameters of vitamin D deficiency and insufficiency groups

All VD insufficiency and deficiency patients received VD supplements 42 000 IU oral VD per week and 500-mg calcium carbonate per day for 12 weeks to reach 25(OH) D above 30 ng/ml.

In VD insufficiency group (n=32), after 12 weeks of trial, our results revealed significantly improvements of TCSS and MNCV (median, ulnar, and PT nerves), SNCV (median, ulnar, and PT nerves), CMAP amplitude (median, ulnar, and PT nerves), and SNAP amplitude (median, sural, ulnar, and PT nerve), with P value less than 0.001 ([Table 4]).
Table 4 Effect of vitamin D supplementation on clinical, laboratory, and electrophysiological characteristics of vitamin D deficiency and insufficiency groups

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Considering the effect of VD supplementation in VD deficiency group on cardiometabolic risks, our results revealed significantly improvement of glycemic and lipid profiles as well as calcium hemostasis. Moreover, TCSS and MNCV (median, ulnar, and PT nerves), SNCV (median, ulnar, and PT nerves), CMAP amplitude (median, ulnar, and PT nerves) and SNAP amplitude (median, sural, ulnar, and PT nerves) significantly improved after VD supplementations for 12 weeks, with P value less than 0.001 ([Table 4]).

Assessment of the power of vitamin D supplementation to improve cardiometabolic risk and electrophysiological parameters

Logistic regression analysis was performed to detect the main predictors of cardiometabolic biomarkers associated with VD supplementation among patients with T2DM. Our findings revealed that among clinical and laboratory features, MNCV and SNCV of median nerve as well as HbA1c were independent predictors of improvement to VD supplementation, with odds ratios of 0.457, 2.123, and 520.042, respectively ([Table 5]).
Table 5 Logistic regression analysis evaluating the association of cardiometabolic risk and electrophysiological with vitamin D supplementation among patients with type 2 diabetes mellitus

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  Discussion Top


Despite attempts to increase awareness of the deleterious health consequences associated with T2DM and its complications, there continues to be a significant increase in the T2DM population worldwide. A growing body of evidence has corroborated that patients with T2DM are at high risk of microvascular complications including DPN, which has a bad effect on the quality of life, and it is associated with high mortality [15]. Substantial evidence assesses the prevalence of neuropathy in Egypt, and it found that the prevalence of neuropathy ranged from 21.9% in hospital outpatient clinics to 60% in hospital inpatients [16].

Past decades have witnessed a spurt in research activity that has shown a key role of VD in the pathogenesis of DPN. In fact, experimental studies demonstrated the associations between VD deficiency and low levels of nerve growth factors (neurotrophins), which are required for the development and survival of both sympathetic and sensory neurons and cause defective neuronal calcium homeostasis [14]. Decrease in neurotrophins and defective calcium homeostasis increase nerve damage by toxins including hyperglycemia; in addition, VD receptor modulates neuronal cells differentiation and function [17]. In this study, we aimed to explore the levels of 25(OH) D in patients with T2DM with peripheral neuropathy. We also aimed to clarify the effect of VD supplementation on cardiometabolic status and electrophysiological pattern of peripheral neuropathy.

The current study revealed that among 95 patients with T2DM with peripheral neuropathy, 32 patients had VD insufficiency [20 ng/ml <25(OH) D <30 ng/ml], 50 patients had VD deficiency [25(OH) D ˂20 ng/ml], and 13 patients had VD sufficiency [25(OH) D >30 ng/ml].

In another Egyptian study conducted on Egyptian patients with or without DPN, the results revealed the mean serum levels of 25(OH) VD in patients with DPN were lower than that in patients without DPN. Moreover, we found that 87.6% of patients with DPN had VD deficiency [25(OH) D ≤28.3 ng/ml] compared with patients without DPN, whereas in their study, there were 45% who had VD deficiency [18].

The diverse results summarized before could be owing to different 25(OH) D cutoffs, as in our study, we classified our patients with T2DM with DPN as follows: VD deficiency was defined as serum 25(OH) D concentration of less than 20 ng/ml, insufficiency as 20 ng/ml less than 25(OH) D less than 30 ng/ml, and sufficiency was defined as 25(OH) D higher than 30 ng/ml.

Omics studies have indeed demonstrated that patients with DN had significant lower levels of VD than that in patient without DN, whereas there were similar values of VDBP and VDR in two groups of diabetic patients with and without DN [19].

Our results reported that 25(OH) D levels were negatively correlated with cardiometabolic risk factors and TCSS. On the contrary, 25(OH) D levels were positively correlated with NCV. Stepwise multiple linear regression analysis revealed that HbA1c and TCSS were the main predictors of 25(OH) D levels among other clinical and laboratory biomarkers. Logistic regression analysis observed that MNCV and SNCV of median nerve and HbA1c were independent predictors of response to VD supplementation.

Similar results were observed by Alamdari et al. [13]. They found that the serum 25(OH) D was significantly inversely correlated with the intensity of NCV impairment.

Against our results, Kheyami [20] demonstrated that VD has analgesic effect in patients with painful DPN, but VD deficiency does not more associate with painful neuropathy than painless neuropathy.

The results presented herein are innovative, as this study performs a robust estimation of NCV in patients with T2DM in relation to serum 25(OH) D. Even more importantly, our study evaluated the effect of VT supplementation on electrophysiological pattern. The results presented here are innovative, as we found that MNCV and SNCV in the median, PT, and ulnar nerves were significantly decreased in both VD deficiency and insufficiency groups compared with VD sufficiency groups, and after supplementation with 42 000 IU oral VD per week and 500-mg calcium carbonate per day for 12 weeks, the cardiometabolic risk factors and electrophysiological pattern of peripheral neuropathy improved.Similar results were described in Putz et al. [21] who recommended VD supplementation in patients with diabetic neuropathy.

In earlier published studies conducted in our region, that is, Middle East, Zhang et al. [22] observed low VD in diabetes and the possible mechanisms for this association may include the presence of VD receptors in pancreatic beta cells to which circulating VD binds [23]. In addition, VD has been well recognized for its role in regulating extracellular calcium flux, and insulin secretion is known as a calcium-dependent process [24].


  Conclusion Top


Our study observed that MNCV and SNCV in the median, PT, and ulnar nerves were significantly decreased in both VD deficiency and insufficiency groups compared with VD sufficiency group, and after supplementation with 42 000 IU oral VD per week and 500-mg calcium carbonate per day for 12 weeks, it improved cardiometabolic risk factors and electrophysiological pattern of peripheral neuropathy.

Acknowledgements

The authors thank all the participants of the study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Lv WS, Zhao WJ, Gong SL, Fang DD, Wang B, Fu ZJ et al. Serum 25-hydroxyvitamin D levels and peripheral neuropathy in patients with type 2 diabetes: a systematic review and meta-analysis. J Endocrinol Invest 2015; 38:513–518.  Back to cited text no. 1
    
2.
Boulton AJM, Vinik AI, Arezzo JC, Bril V, Feldman EL, Freem R et al. Diabetic neuropathies. Diabetes Care 2005; 28:956–962.  Back to cited text no. 2
    
3.
Holick MF. Vitamin D. the underappreciated D-lightful hormone that is important for skeletal and cellular health. Curr Opin Endocrinol Diabetes 2002; 9:87–98.  Back to cited text no. 3
    
4.
Hilger J, Friedel A, Herr R, Rausch T. A systematic review of vitamin D status in populations worldwide. Br J Nutr 2014; 111:23–45.  Back to cited text no. 4
    
5.
Reis AF, Hauache OM, Velho G. Vitamin D endocrine system and the genetic susceptibility to diabetes, obesity and vascular disease. A review of evidence. Diabetes Metab 2005; 31(4 Part 1):318–325.  Back to cited text no. 5
    
6.
Knekt P, Laaksonen M, Mattila C, Harkanen T, Marniemi J, Heliovaara M et al. Serum vitamin D and subsequent occurrence of type 2 diabetes. Epidemiology 2008; 19:666–671.  Back to cited text no. 6
    
7.
Bell DSH. Reversal of the symptoms of diabetic neuropathy through correction of vitamin D deficiency in a type 1 diabetic patient. Case Rep Endocrinol 2012; 2012:165056.  Back to cited text no. 7
    
8.
Shehab D, Al-Jarallah K, Mojiminiyi OA, Al Mohamedy H, Abdella NA. Does vitamin D deficiency play a role in peripheral neuropathy in type 2 diabetes? Diabet Med 2012; 29:43–49.  Back to cited text no. 8
    
9.
Daga RA, Laway BA, Shah ZA, Mir SA, Kotwal SK, Zargar AH. High prevalence of vitamin D deficiency among newly diagnosed youth-onset diabetes mellitus in north India. Arq Bras Endocrinol Metabol 2012; 56:423–428.  Back to cited text no. 9
    
10.
Meijer WG, Bosma E, Lefrandt JD, Links TP, Smit AJ, Van Der Hoeven JH, Hoogenberg K. Clinical diagnosis of diabetic polyneuropathy with the diabetic neuropathy symptom and diabetic neuropathy examination scores. Diabetes Care 2003; 26:697–701.  Back to cited text no. 10
    
11.
Sachedina S, Toth C. Association of comorbidities with increasing severity of peripheral neuropathy in diabetes mellitus. World J Diabetes 2013; 4:135–144.  Back to cited text no. 11
    
12.
Dyck PJ, Carter RE, Litchy WJ. Modeling nerve conduction criteria for diagnosis of diabetic polyneuropathy. Muscle Nerve 2011; 44:340–345.  Back to cited text no. 12
    
13.
Alamdari A, Mozafari R, Tafakhori A, Faghihi-Kashani S, Hafezi-Nejad N, Sheikhbahaei S et al. An inverse association between serum vitamin D levels with the presence and severity of impaired nerve conduction velocity and large fiber peripheral neuropathy in diabetic subjects. Neurol Sci 2015; 36:1121–1126.  Back to cited text no. 13
    
14.
Bos M, Agyemang C. Prevalence and complications of diabetes mellitus in Northern Africa, a systematic review. BMC Public Health 2013; 13:387.  Back to cited text no. 14
    
15.
El Badawy AA, GFE S, Fahmy HH, Demitry SR, Sherif NA, Badawy SAE. Vitamin D status and some related factors among a sample of females living in rural area of Sharkia Governorate. Cairo: Egypt Osteoporosis Prevention Society Conference; 2009.  Back to cited text no. 15
    
16.
Raman R, Gupta A, Krishna S, Kulothungan V, Sharma T. Prevalence and risk factors for diabetic microvascular complications in newly diagnosed type II diabetes mellitus. SankaraNethralaya Diabetic Retinopathy Epidemiology and Molecular Genetic Study (SN-DREAMS, report 27). J Diabetes Complications 2012; 26:123–128.  Back to cited text no. 16
    
17.
Riaz S, Malcangio M, Miller M, Tomlinson DR. A vitamin D (3) derivative (CB1093) induces nerve growth factor and prevents neurotrophic deficits in streptozotocin-diabetic rats. Diabetologia 1999; 42:1308–1313.  Back to cited text no. 17
    
18.
Abdelsadek SE, El Saghier EO, Abdel Raheem SI. Serum 25(OH) vitamin D level and its relation to diabetic peripheral neuropathy in Egyptian patients with type 2 diabetes mellitus. Egypt J Neurol Psychiatry Neurosurg 2018; 54:36.  Back to cited text no. 18
    
19.
Celikbilek A, Gocmen AY, Tanik N, Borekci E, Adam M, Celikbilek M. Decreased serum vitamin D levels are associated with diabetic peripheral neuropathy in a rural area of Turkey. Acta Neurol Belg 2015; 115:47–52.  Back to cited text no. 19
    
20.
Kheyami A. Vitamin D and diabetic neuropathy [thesis]. Submitted to the University of Manchester for the degree of MPhil in the Faculty of Medical and Human Sciences, 2014. p. 227782.  Back to cited text no. 20
    
21.
Putz Z, Martos T, Németh N, Körei AE, Szabó M, Vági O et al. Vitamin D and neuropathy. Orv Hetil 2013; 154:2012–2015.  Back to cited text no. 21
    
22.
Zhang FF, Al Hooti S, Al Zenki S, Alomirah H, Jamil KM, Rao A et al. Vitamin D deficiency is associated with high prevalence of diabetes in Kuwaiti adults: results from a national survey. BMC Public Health 2015; 16:100.  Back to cited text no. 22
    
23.
Bland R, Markovic D, Hills CE, Hughes SV, Chan SL, Squires PE et al. Expression of 25-hydroxyvitamin D3-1alpha-hydroxylase in pancreatic islets. J Steroid Biochem Mol Biol 2004; 89-90:121–125.  Back to cited text no. 23
    
24.
Milner RD, Hales CN. The role of calcium and magnesium in insulin secretion from rabbit pancreas studied in vitro. Diabetologia 1967; 3:47–49.  Back to cited text no. 24
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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