PDF, 1. Research concerning diabetes and its complications has become a public health priority. An increasing number of reports link vitamin D deficiency to diabetes; however, so far, there has only been limited and contradictory data available on the correlation between diabetic peripheral neuropathy and vitamin D. Studies of people with type 2 diabetes confirmed the relationship between vitamin D deficiency and diabetic neuropathy bmj incidence as well as the severity of the symptoms caused by neuropathy.
The latest studies are also suggesting a relationship between the incidence of plantar ulcers and vitamin D deficiency. Keywords Vitamin D. Diabetes mellitus. Neuropathy Zs. Putz and T. Martos contributed equally to this study. Introduction Today, the consequences of vitamin D deficiency are increasingly considered as a public health priority that needs to be tackled.
An increasing quantity of evidence is being published about the widespread effects of vitamin D going beyond influencing bone and calcium homeostasis.
Several studies have reported on the association of vitamin D deficiency with cardiovascular disease, tumours, autoimmune conditions and overall mortality. A recent meta-analysis of 73 cohort studies and 22 randomised controlled trials  that evaluate the correlation between vitamin D levels and the risk of cause-specific death showed a moderate, but significant, inverse association between circulating hydroxyvitamin D 25OHD concentrations and t; he risk of all-cause mortality.
This association proved more specific for deaths due to coronary disease, lymphoma, upper digestive cancer and respiratory disorders. Low vitamin D levels may be associated with higher incidence of diabetes and neurodegenerative diseases as well. Martos : N. Németh : A. Körei : Diabetic neuropathy bmj.
Vági : M. Kempler : P. Martos e-mail: timea.
Németh e-mail: nora. Körei e-mail: anna. Vági e-mail: vagiorsi gmail. Kempler e-mail: kempler.
Numerous studies have implicated vitamin D in the pathophysiology of both type 1 and type 2 diabetes; however, conclusive causal proof is yet lacking. A recent study of Wolden-Kirk et al. Human and mouse islets were exposed to IL-1β and interferon-γ in the presence or absence of active vitamin D. Cytokine exposure caused a significant increase in β-cellPage 2 of 6 apoptosis, which was almost completely prevented by active vitamin D.
In addition, vitamin D restored insulin secretion from cytokine-exposed islets. These effects may contribute to the diabetic neuropathy bmj effects of vitamin D against the induction of autoimmune diabetes. Vitamin D deficiency was examined in pre-type 1 diabetic children, following disease progression from autoantibody seroconversion until manifest diabetes .
However, vitamin D deficiency was not associated with faster progression to diabetes in autoantibody-positive children. In the Third National Health and Nutrition Examination Survey —a cross-sectional survey of a nationally representative sample of the US population was analysed .
Chronic Complications of Diabetes Mellitus Historically, chronic complications of diabetes mellitus have been divided into two categories on the basis of didactical considerations: microangiopathic and macroangiopathic complications. Within the group of microangiopathic complications, retinopathy, nephropathy and neuropathy are considered specific to the diabetic condition.
These characteristic complications only occur in patients with diabetes. Macroangiopathy presents with the various forms of atherosclerosis, which ischemic heart disease, stroke, peripheral vascular disease are well known to develop also without any link to diabetes.
Although the macroangiopathic complications occurring in diabetes do tend to show certain clinical characteristics in terms of their frequency, localisation, symptoms and course, they are not fundamentally different from the forms of their occurrence in patients without diabetes. Thus, the diseases that develop on the basis of macroangiopathy cannot be considered chronic complications specific to diabetes.
Within the chronic complications that are specific to diabetes, neuropathy is of outstanding significance, as it tends to appear—as a complication of diabetes with a bad prognosis— Curr Diab Rep in over half of the patients with type 2 diabetes. The autonomic and sensory damage belongs to the progressive forms of neuropathy, the clinical and prognostic significance of which has only become clear in the past few decades.
Follow-up studies conducted with diabetic patients confirmed that the existence of cardiovascular autonomic neuropathy increases mortality five times. Today, we consider sensory neuropathy to be the most important factor in the diabetic foot condition.
The fact that amputations of the lower leg are 15—45 times more frequent among people with diabetes than in the non-diabetic population should draw attention to the importance of this condition. In the developed industrial countries, nearly half of all lower-leg amputations of a non-traumatic origin are performed on patients with diabetes, while timely discovery and appropriate complex treatment could provide an opportunity to prevent primarily those of a neuropathic origin [6—8].
The Effects of Vitamin D on the Nervous System The role of vitamin D in preventing and treating various neurological diseases has been studied for several years. The effect of vitamin D is confirmed by VDR and CYP27B1 expression measureable in the nervous system, in the brain, in the nerve and sunna cukorbetegség kezelése the glial cells .
It is a well-known fact that there is a link between the incidence of sclerosis multiplex and geography; the risk of sclerosis multiplex increases parallel to the increase in the distance from the Equator. Ample data confirm that lower serum 25OHD levels correlate with the incidence, relapses and mortality of sclerosis multiplex and with the active sclerosis multiplex lesions identified on MRI images of the brain [10—16]. Treatment involving high dosages of vitamin D slows down the progression of disability linked to multiple sclerosis .
However, the real therapeutic efficacy of vitamin D in the treatment of the disease will be revealed by the clinical trials that are currently under way . The risk role of vitamin D deficiency has also been proven in the development of neurodegenerative diseases. Another study examined the correlation between 25OHD levels and cognitive decline in Italian individuals over the age of The study of Ding et al. The Role of Diabetic neuropathy bmj D in the Development of Neuropathy Notwithstanding the numerous publications on the relationship between diabetes and vitamin D deficiency, there are few— and only contradictory—data concerning the actual correlation between vitamin D deficiency and neuropathy Table 1.
In vitro data and the outcomes of animal testing have both confirmed the role played by vitamin D analogues in stimulating and reducing the breakdown of the nerve growth factor that is crucial to the survival of sympathetic and sensory neurons.
Központi Könyvtár - Semmelweis Publikációk
A vitamin D derivative CB was examined in the study of Riaz et al. In streptozotocin-diabetic rats, deficient nerve growth factor NGF causes impaired neurotrophic support in the muscle and skin. CB stimulates the expression of NGF in both the skin and muscle of diabetic and control rats.
In sciatic nerves of diabetic rats, the depletions of nerve growth factor and its neuronal target gene products substance P and CGRP were cukorbetegség és annak kezelése otthon by CB These findings suggest that in animal models of Table 1 The main outcomes of the relevant studies examining the relationship between vitamin D supply and neuropathy Authors Type of study Number of subjects included Follow-up Main outcome periods Result Lee P et al.
Overall and specific quality-of-life measures were also improved.
Is There an Association Between Diabetic Neuropathy and Low Vitamin D Levels?
Logistic regressions demonstrate vitamin D insufficiency is associated with the adjusted composite paresthesia measure odds ratio 2. Serum OH-vitamin D levels were significantly lower in the group with neuropathy, NA not available, MPQ McGill pain questionnaire, VAS visual analogue self-report scalePage 4 of 6 diabetes, it is possible to prevent depletions of nerve growth factor and the products of its neuronal target genes by a vitamin D derivative, which could be a possible mechanism of the therapeutic effect of vitamin D in human diabetic neuropathy, as well.
After 2 months, VDR expression was significantly increased in diabetic rats, which was observed in the cytoplasm, nuclei and cell membranes of neurons, as well. This increased VDR expression was observed in all types of neurons, but it was most notable in the neurons of small diameter. According to Filipovic diabetic neuropathy bmj al. Calcium-binding protein is responsible for the transfer and availability of calcium ions in different cells.
Calcium-buffering molecules are protecting the cells from calcium overload. These effects of vitamin D, increased transcription activity of VDR-target genes, protect the neuronal cells from apoptosis and neurodegeneration. The relevance of VDRs for diabetic neurons is still uncertain; further studies are needed to investigate the role of vitamin D and VDRs in the neuronal metabolism.
The study conducted by Lee and Chen  was the first to examine the correlation between vitamin D deficiency and diabetic neuropathy. They examined 51 patients with type 2 diabetes who had deficient 25OHD serum levels and also diabetic neuropathy.
Also, in patients suffering from musculoskeletal pain of various origins, a study identified lower 25OHD levels, and with the administration of vitamin D supplements, it reported an increase in pain thresholds .
Global epidemiology of prediabetes - present and future perspectives.
In a case repot , a year-old male patient having suffered from type 1 diabetes for 27 years reported symptoms of painful lower-leg neuropathy that started 10 years earlier and have become more prominent in the past 4 years. The tricyclic antidepressant, gabapentin and pregabalin used to treat the symptoms mitigated diabetic neuropathy bmj pain only partially. As low 25OHD levels are frequent in case of both obesity and type 1 diabetes , the serum 25OHD level was determined, and it proved to be The administration of supplementary vitamin D 50, NE per week resulted in significantly reduced pain, and the dosage of pain killers could be reduced considerably.
In another trial conducted with the participation of patients with type 2 diabetes , the authors aimed to assess the correlations between neuropathy and vitamin D deficiency. Diabetic neuropathy bmj Diab Rep The study covered 87 patients of type 2 diabetes with and without neuropathy. The average serum 25OHD concentration was significantly lower among the diabetic patients having neuropathy compared to those without. In a double-blind, placebo-controlled trial, Valensi et al.
QR is a compound that contains quercetin, ascorbyl palmitate and vitamin D3. Eight percent had four to six insensate areas on their feet as determined by the Semmes-Weinstein monofilament test.
Logistic regressions demonstrate vitamin D insufficiency is associated with the adjusted composite paresthesia measure and the adjusted numbness measure. A further trial  involving patients had the objective of determining the frequency of low 25OHD levels among patients with type 2 diabetes suffering from peripheral neuropathy.
Go to: References 1. Prediabetes: a high-risk state for diabetes development. Diabetes Prevention Program Research Group The prevalence of retinopathy in impaired glucose tolerance and recent-onset diabetes in the diabetes prevention program.
A Hz calibrated tuning fork and a g SemmesWeinstein monofilament were used to examine neuropathy. Neuropathy was confirmed in Diabetic patients suffering from peripheral diabetic neuropathy were older The level of serum 25OHD was significantly lower in the group of diabetics with neuropathy than in the group not suffering from diabetic neuropathy bmj Ahmadieh et al.
Mean 25OHD levels were lower in subjects with diabetic neuropathy compared to those without diabetic neuropathy. After adjustment for HbA1c, age, smoking, BMI and duration of diabetes in diabetes insipidus natrium urine logistic regression model, diabetes duration and 25OHD levels were significant predictors of diabetic neuropathy.
The inverse correlation between serum 25OHD level diabetic neuropathy bmj cardiovascular mortality was shown by Chowdbury et al. In diabetic neuropathy bmj to this increased cardiovascular risk, Ziegler et al. If vitamin D deficiency has a causal role in the development of diabetic neuropathy, vitamin D deficiency and neuropathy together could confer a multiplicative increase in cardiovascular risk in diabetic patients. Vitamin D stimulates cell differentiation, which is crucial to the healing of wounds.
Vitamin D enhances the protective immune response against infections at several points . The study covered diabetic patients without diabetic neuropathy bmj with plantar ulcers.
Lower 25OHD levels were found in patients with diabetes having plantar ulcers than in those without 6. However, further clinical trials must be conducted to confirm these data. The effect of vitamin D on the glucose control in diabetes is another aspect of the connection between vitamin D and microvascular complications. HbA1c level is a well-known risk factor of diabetic neuropathy. The Tromso Study is a longitudinal population-based study initiated in Almost 13, subjects aged 30—87 years participated in the study.
This association remained significant in a multiple linear regression model after adjustment for confounding factors. In a sub-analysis on diabetic neuropathy bmj with diabetes, the association between serum 25OHD and HbA1c appeared to be even stronger with a difference in HbA1c of 0. Zoppini et al. Page 5 of 6, This relation maintained its independence in the multivariate analysis after adjusting for age, sex, BMI, treatment and duration of diabetes and nephropathy.
Ennek haemodynamicai magyarázata főképp az, hogy az egyes nephronokban a vas efferens mérsékelt szűkülete, a vas afferens tágulata jön létre, ezáltal megnő az intraglomerularis nyomás és az ultrafiltratum mennyisége. A fokozott filtratio és glomerulus permeabilitás következtében megnövekszik a filtrált és ürített albumin mennyisége is. Mindez a glomerulus basalmembrán és endothel között elhelyezkedő mesangialis matrix kóros felhalmozódásához vezet, aminek végeredménye a glomerulosclerosis, a következményes, lassú glomerulus pusztulás.
Conclusion Based on the above suggestive data, administration of vitamin D supplements may prove to be a beneficial adjuvant therapy in mitigating neuropathic pain as well as in blocking the progression of neuronal destruction. These results may also lead us to conclude that vitamin D deficiency could have a partial role in diabetic neuropathy bmj development of diabetic plantar ulcers. Identifying the benevolent and malignant immune mediators having an impact on the development of plantar ulcers and also in the process of wound healing might be important, as later on these could become the focal points of targeted therapy.
However, the exact role of vitamin D in these processes requires further investigations. Until then, in the event of distal symmetric neuropathy symptoms and also in neuropathy without any clinical signs, vitamin D deficiency should definitely be estimated and, if present, diabetic neuropathy bmj D supplementation should be considered. Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.
Vitamin D and risk of cause specific death: systematic review and meta-analysis of observational cohort and randomised intervention studies.
International Diabetes Federation. IDF Diabetes Atlas 6th edn. Brussels: International Diabetes Federation; Discovery of molecular pathways mediating 1, dihydroxyvitamin D3 protection against cytokine-induced inflammation and damage of human and male mouse islets of Langerhans.
Prevalence of vitamin D deficiency diabetic neuropathy bmj pre-type 1Page 6 of 6 5. Diabetes Care. A distalis típusú, sensoros neuropathia diagnosztikája a diabetológiai gyakorlatban. Diabetologia Hungarica. Diabetes specifikus szövődmények prediabetesben. Vetőmag len kezelés cukorbetegség vélemények Hetil.
Ziegler D. Diabetic cardiovascular autonomic neuropathy: prognosis, diagnosis and treatment. Diabetes Metab Rev. Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain.
J Chem Neuroanat. Mortality from multiple sclerosis and exposure to residential and occupational solar radiation: a case—control study based on death certificates.
Diabetic neuropathy bmj Environ Me. Serum hydroxyvitamin D levels and risk of multiple sclerosis.