|Year : 2020 | Volume
| Issue : 1 | Page : 24-28
Investigation of insulin resistance and vitamin E deficiency in chronic inflammatory demyelinatıng polyneuropathy: A 5-year retrospective study
Hilal Tastekin Toz1, Eren Gozke2
1 Department of Neurology, University of Health Sciences, Kartal Dr. Lütfi Kırdar Training and Research Hospital, İstanbul, Turkey
2 Department of Neurology, University of Health Sciences, Fatih Sultan Mehmet Training and Research Hospital, İstanbul, Turkey
|Date of Submission||02-Aug-2019|
|Date of Decision||05-Sep-2019|
|Date of Acceptance||06-Oct-2019|
|Date of Web Publication||8-May-2020|
Hilal Tastekin Toz
University of Health Sciences, Kartal Dr. Lutfi Kırdar Training and Research Hospital, Istanbul
Source of Support: None, Conflict of Interest: None
Objective: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a treatable disease; therefore, accurate diagnosis and detection of coexisting disorders are very important. Some authors have reported that CIDP was more frequently observed in patients with diabetes mellitus when compared with the population in general. Vitamin E deficiency leads to demyelinating neuropathy, and Vitamin E supplementation ensures clinical and electrophysiological recovery. In this study, identifying the association between insulin resistance, Vitamin E deficiency, and CIDP is aimed. Materials and Methods: Thirty-three patients with CIDP and forty healthy controls were evaluated. Two groups were compared in terms of insulin resistance and Vitamin E level status. Results: A statistically significant difference was not found between CIDP and control groups as for the distribution of mean ages, genders, Homeostatic Model Assessment Index values, impaired fasting glucose, and a statistically significant difference was not found between CIDP and control groups as for Vitamin E deficiency. Conclusion: Our study could not reveal any evidence about insulin resistance and Vitamin E deficiency in CIDP patients.
Keywords: Chronic inflammatory demyelinating polyneuropathy, homeostatic model assessment, insulin resistance, Vitamin E
|How to cite this article:|
Toz HT, Gozke E. Investigation of insulin resistance and vitamin E deficiency in chronic inflammatory demyelinatıng polyneuropathy: A 5-year retrospective study. Neurol Sci Neurophysiol 2020;37:24-8
|How to cite this URL:|
Toz HT, Gozke E. Investigation of insulin resistance and vitamin E deficiency in chronic inflammatory demyelinatıng polyneuropathy: A 5-year retrospective study. Neurol Sci Neurophysiol [serial online] 2020 [cited 2020 Aug 11];37:24-8. Available from: http://www.nsnjournal.org/text.asp?2020/37/1/24/283927
| Introduction|| |
Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune demyelinating polyneuropathy coursing with relapses, which may involve symmetrically both lower and upper extremities and characterized by distal and proximal weakness and impaired sensory function. Diabetes mellitus (DM) occupies an important place among potentially diseases associated with CIDP. Since CIDP is a treatable condition and considering that superimposed diabetic polyneuropathy (DPN) will increase clinical complaints its association with DM carries importance in the early diagnosis and treatment.,,,,,,
In DM, most frequently symmetric sensorimotor polyneuropathy characterized by axonal involvement is seen; however occasionally, demyelinating features may be also detected in the nerve conduction studies. Therefore, it should be differentiated from CIDP. However, the diagnosis of CIDP should be considered in treatment-refractory DPN patients, predominantly with motor symptoms who had unexpectedly severe polyneuropathy. The relationship between DM and CIDP has been reported in some studies.,,,,,,,,, Furthermore, insulin resistance and impaired glucose tolerance (IGT) are related with demyelinating neuropathy.,,,,,,
It has been reported that deficiency of Vitamin E whose strong antioxidant effects have been known for years, leads to demyelinating neuropathy, and Vitamin E supplementation ensures clinical and electrophysiological recovery.,
Besides, Vitamin E supplementation decreases oxidative stress and improves the effect of insulin.
In this study, our aim was to investigate insulin resistance and Vitamin E levels in CIDP patients.
| Materials and Methods|| |
A total of 33 patients aged between 23 and 81 years who were diagnosed with CIDP, based on the European Federation of Neurological Societies and the Peripheral Nerve Society criteria, were included in the study. Patients with DM, those under steroid therapy within the previous 3 months and multivitamin complex users, were excluded from the study. The control group consisted of forty healthy individuals without diagnoses of DM, neuropathy, migraine, cerebrovascular disease, polycystic ovarian syndrome, chronic renal failure, hypo/hyperthyroidism, and nonusers of multivitamin complex. All patients were obtained from the records between September 2011 and September 2016.
Fasting blood glucose (FBG), fasting insulin, and Vitamin E levels were analyzed. Individuals with fasting glucose levels between 100 and 126 mg/dl were evaluated as patients with impaired fasting glucose (IFG). Insulin resistance was determined using the Homeostasis Model Assessment (HOMA) Index (FBG mg/dl × fasting insulin [μU/ml]/405) formula, and ≥2.5 were accepted as abnormal. Normal range for Vitamin E levels was considered to vary between 0.30 and 0.90 mg/dl.
In the data evaluation, the normality of distribution of the parameters was assessed by the Shapiro–Wilks test. In addition to descriptive statistical methods (Mean, Standard deviation, frequency), Student's t test was used for comparison of parameters that showed normal distribution in comparison of quantitative data, and Mann Whitney U test was used for comparison of parameters that did not show normal distribution between two groups. Fisher's exact test and Chi- square test with Yates's continuity correction are used for the comparison of qualitative data, and Pearson's correlation test was employed for the correlations. Statistical significance was evaluated at P < 0.05.
| Results|| |
A statistically significant difference was not found between CIDP and control groups as for the distribution of mean ages and genders (P > 0.05) [Table 1]. There was no statistically significant difference between CIDP and control groups as for HOMA Index values and Vitamin E levels (P > 0.05) [Table 2]. A statistically significant difference was not found between CIDP and control group as for the presence of insulin resistance, IFG, and Vitamin E deficiency (P > 0.05) [Table 3].
|Table 2: Evaluation of Homeostatic Model Assessment Index and Vitamin E levels|
Click here to view
|Table 3: Comparison between chronic inflammatory demyelinating polyneuropathy and control groups as for the presence of insulin resistance, impaired fasting glucose, and Vitamin E deficiency|
Click here to view
There was no statistically significant difference in the patient and control groups between the study participants aged ≤40 and >40 years as for the presence of insulin resistance and decreased Vitamin E levels (P > 0.05) [Table 4].
Seven (17.5%) cases among all forty patients with CIDP who were followed up in our clinic had definitive diagnosis of diabetes, which did not statistically significantly differ from the incidence of diabetes in Turkey (13.5%) (P > 0.05).
| Discussion|| |
As a critical issue, CIDP should be accurately diagnosed and discriminated from other demyelinating peripheral polyneuropathies because it responds better to the treatment., Among diseases concurrently seen with CIDP, inflammatory, and autoimmune diseases, including DM, human immmunodeficiency virus infection, chronic active hepatitis, monoclonal gammopathy of undetermined significance, temporal arteritis, rheumatoid arthritis, systemic lupus erythematosus, and other connective tissue diseases, inflammatory bowel diseases, sarcoidosis, and thyroid diseases can be enumerated.,,,,
The relationship between DM and CIDP has been reported in many studies, although no clear conclusions have been reached.,,,,,,,,,
CIDP should be differentiated from symmetrical sensorimotor polyneuropathy seen in DM. The diagnosis of CIDP should be thought in treatment-refractory DPN, predominantly with motor symptoms and unexpectedly severe polyneuropathy.
In diabetic patients, various forms of neuropathy can be seen. Some authors have been reported that CIDP was more frequently observed in patients with DM when compared with the population in general. In a study by Sharma KR et al., 1127 patients were seen. Of these, 189 (16.8%) had DM with various neurologic disorders, including 32 patients (16.9%) with DM-CIDP. Among the remaining 938 patients without DM, 17 (1.8%) had idiopathic CIDP. The odds of occurrence of DM-CIDP were eleven times higher among diabetic than nondiabetic patients (P < 0.001). In another study in which 100 DM patients with symptomatic neuropathy were evaluated clinically and pathologically, CIDP was detected in 9% of patients and was identified as the most common nondiabetic cause of neuropathy in the study group. However, some authors advocated lack of any pathogenetic correlation between DM and CIDP. Laughlin et al. found no increase in the incidence of CIDP in the DM group as compared to the general population and concluded that DM is not a major risk factor for the development of CIDP. Chiò et al. detected DM in 9% (n = 14) of 155 CIDP patients with an incidence rate nearly similar to that observed in overall population, so they concluded that only a coincidental relationship exists between CIDP and DM.
Furthermore, in our study, DM was seen in 17.5% of CIDP patients, which does not differ statistically significantly from the relevant incidence of DM (13.5%) in Turkey.
Other disorders can be seen in conjunction with CIDP, which is an inflammatory disease. Abraham et al. detected abnormal laboratory test results in most (84%) of the patients with CIDP, and most frequently found paraproteinemia (29%), increased glycated hemoglobin (HbA1c) (28%), and creatine kinase (84%) levels. Hence, we wanted to investigate the presence of age factor and insulin resistance in CIDP patients. Studies have shown that nerve damage starts in the early stages of glucose metabolism. Sumner et al. in their study of 73 patients with idiopathic peripheral neuropathy, 56% of the patients found a disorder in OGTT; of the 41 patients with impaired OGTT, 26 were diagnosed with IGT and 15 with DM.
According to the study of Farhad et al., 32.7% of patients with idiopathic neuropathy remained idiopathic, whereas the most common causes were impaired glucose metabolism (DM and prediabetes) with a rate of 25.3% and CIDP with a rate of 20%.
Dunnigan et al. and Haq et al. detected that CIDP + DM patients were relatively older. They indicated that despite similarities in electrophysiological patterns of demyelination, their etiologies differ with higher probability., In our study, in the CIDP group, insulin resistance was seen in 37.5% of the cases aged ≤40 years and 36% of the cases above 40 years of age without a statistically significant intergroup difference. However, in the control group, in accordance with the opinion which asserts that rates of insulin resistance increase with age, insulin resistance was seen in 25% of the cases aged ≤40 years, and 42.9% of the patients aged >40 years without any statistically significant intergroup difference. When patients aged ≤40 years in the CIDP, and control groups were compared, though not statistically significant, insulin resistance was seen more frequently in the CIDP group (37.5% vs. 25% in the control group). However, in the group aged >40 years, probably related to an increase in insulin resistance in the general population, 36% of the patients in the CIDP group, whereas in 42.9% of the cases in the control group, insulin resistance was detected without any statistically significant intergroup difference.
As a result; ın our study, there was no significant difference in insulin resistance including age factor in both groups. Moreover, there is no similar study in the literature investigating insulin resistance in CIDP patients.
Many recent studies have shown that oxidative stress resulting in increased free radical formation, and a defect in antioxidant defense mechanisms plays a role in the development of neurodegenerative diseases and complications of DM. Antioxidants inhibit the harmful effect of free radicals.
Vitamin E has been studied as for its potent antioxidant effects for years, and also, we have benefited from its therapeutic potency. It has been thought that alpha-tocopherol exerts its antiinflammatory effects by modifying the inflammatory response. Vitamin E deficiency leads to demyelinating neuropathy, and Vitamin E supplementation ensures clinical and electrophysiological recovery.,
Puri et al. found a low serum Vitamin E level in a 22-year-old male patient with demyelinating neuropathy. Sural nerve biopsy revealed loss of large myelinated fibers with evidence of remyelination. Vitamin E supplementation led to clinical and electrophysiological recovery of sensory conduction and evoked potentials. Motor nerve conduction, however, showed only partial recovery.
In a study examining the sciatic nerve healing of animals with low and normal Vitamin E levels, it was found that myelin production of low Vitamin E animals is far behind the other group and never reached normal.
In our study, we did not find any significant difference in Vitamin E levels in the CIDP group as compared to the control group. There were no studies in the literature on CIDP and Vitamin E assessment.
Vitamin E can also increase insulin sensitivity with a resultant decrease in insulin resistance. Vitamin E supplementation increases both insulin sensitivity and insulin release in population. Lower serum α-tocopherol concentrations have been associated with increased insulin resistance and increased incidence of Type 2 DM.
We looked for a link between Vitamin E and insulin resistance in CIDP and control groups. We found no correlation between Vitamin E, HbA1c levels, and insulin resistance in CIDP and control groups. In addition, we could not find another study in the literature investigating insulin resistance in CIDP patients.
| Conclusion|| |
Although the relationship between CIDP, insulin resistance, and DM has attracted attention in clinical practice, our study could not reveal relevant evidence favoring this finding. Besides any correlation between CIDP and Vitamin E deficiency was not observed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Lewis RA. Chronic inflammatory demyelinating polyneuropathy. Curr Opin Neurol 2017;30:508-12.
Cornblath DR, Gorson KC, Hughes RA, Merkies IS. Observations on chronic inflammatory demyelinating polyneuropathy: A plea for a rigorous approach to diagnosis and treatment. J Neurol Sci 2013;330:2-3.
Saperstein DS, Katz JS, Amato AA, Barohn RJ. Clinical spectrum of chronic acquired demyelinating polyneuropathies. Muscle Nerve 2001;24:311-24.
Said G. Chronic inflammatory demyelinating polyneuropathy. Neuromuscul Disord 2006;16:293-303.
Hughes RA, Bouche P, Cornblath DR, Evers E, Hadden RD, Hahn A, et al
. European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society. Eur J Neurol 2006;13:326-2.
Rentzos M, Anyfanti C, Kaponi A, Pandis D, Ioannou M, Vassilopoulos D. Chronic inflammatory demyelinating polyneuropathy: A 6-year retrospective clinical study of a hospital-based population. J Clin Neurosci 2007;14:229-35.
Allen JA, Lewis RA. CIDP diagnostic pitfalls and perception of treatment benefit. Neurol 2015;85:498-504.
Chiò A, Plano F, Calvo A, Leone M, Mutani R, Cocito D, et al
. Comorbidity between CIDP and diabetes mellitus: Only a matter of chance? Eur J Neurol 2009;16:752-4.
Fatehi F, Nafissi S, Basiri K, Amiri M, Soltanzadeh A. Chronic inflammatory demyelinating polyneuropathy associated with diabetes mellitus. J Res Med Sci 2013;18:438-41.
Lotan I, Hellman MA, Steiner I. Diagnostic criteria of chronic inflammatory demyelinating polyneuropathy in diabetes mellitus. Acta Neurol Scand 2015;132:278-83.
Dunnigan SK, Ebadi H, Breiner A, Katzberg HD, Barnett C, Perkins BA, et al
. The characteristics of chronic inflammatory demyelinating polyneuropathy in patients with and without diabetes – An observational study. PLoS One 2014;9:e89344.
Laughlin RS, Dyck PJ, Melton LJ 3rd
, Leibson C, Ransom J, Dyck PJ. Incidence and prevalence of CIDP and the association of diabetes mellitus. Neurol 2009;73:39-45.
Dunnigan SK, Ebadi H, Breiner A, Katzberg HD, Lovblom LE, Perkins BA, et al
. Comparison of diabetes patients with “demyelinating” diabetic sensorimotor polyneuropathy to those diagnosed with CIDP. Brain Behav 2013;3:656-63.
Haq RU, Pendlebury WW, Fries TJ, Tandan R. Chronic inflammatory demyelinating polyradiculoneuropathy in diabetic patients. Muscle Nerve 2003;27:465-70.
Sharma KR, Cross J, Farronay O, Ayyar DR, Shebert RT, Bradley WG. Demyelinating neuropathy in diabetes mellitus. Arch Neurol 2002;59:758-65.
Lozeron P, Nahum L, Lacroix C, Ropert A, Guglielmi JM, Said G. Symptomatic diabetic and non-diabetic neuropathies in a series of 100 diabetic patients. J Neurol 2002;249:569-75.
Chiò A, Cocito D, Bottacchi E, Buffa C, Leone M, Plano F, et al
. Idiopathic chronic inflammatory demyelinating polyneuropathy: An epidemiological study in Italy. J Neurol Neurosurg Psychiatry 2007;78:1349-53.
Abraham A, Albulaihe H, Alabdali M, Qrimli M, Breiner A, Barnett C, et al
. Frequent laboratory abnormalities in CIDP patients. Muscle Nerve 2016;53:862-5.
Sumner CJ, Sheth S, Griffin JW, Cornblath DR, Polydefkis M. The spectrum of neuropathy in diabetes and impaired glucose tolerance. Neurol 2003;60:108-11.
Farhad K, Traub R, Ruzhansky KM, Brannagan TH 3rd
. Causes of neuropathy in patients referred as “idiopathic neuropathy”. Muscle Nerve 2016;53:856-61.
Singleton JR, Smith AG, Bromberg MB. Painful sensory polyneuropathy associated with impaired glucose tolerance. Muscle Nerve 2001;24:1225-8.
Smith AG, Singleton JR. Impaired glucose tolerance and neuropathy. Neurol 2008;14:23-9.
Singleton JR, Smith AG, Bromberg MB. Increased prevalence of impaired glucose tolerance in patients with painful sensory neuropathy. Diabetes Care 2001;24:1448-53.
Ince H, Taşdemir HA, Aydin M, Ozyürek H, Tilki HE. Evaluation of nerve conduction studies in obese children with insulin resistance or impaired glucose tolerance. J Child Neurol 2015;30:989-99.
Puri V, Chaudhry N, Tatke M, Prakash V. Isolated vitamin E deficiency with demyelinating neuropathy. Muscle Nerve 2005;32:230-5.
Cecchini T, Cuppini R, Ciaroni S, Del Grande P. Effect of vitamin E-deficiency on regeneration of the sciatic nerve. Arch Ital Anat Embriol 1990;95:155-65.
Mayer-Davis EJ, Costacou T, King I, Zaccaro DJ, Bell RA; Insulin Resistance and Atherosclerosis Study (IRAS). Plasma and dietary vitamin E in relation to incidence of type 2 diabetes: The Insulin resistance and atherosclerosis study (IRAS). Diabetes Care 2002;25:2172-7.
[Table 1], [Table 2], [Table 3], [Table 4]