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 early diagnosis and treatment^[1-7].

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, 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^[8-17]. Also insulin resistance and impaired glucose tolerance are related with demyelinating neuropathy^[18-24].

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^[25,26].

Besides, vitamin E supplementation decreases oxidative stress, and improves the effect of insulin^[27].

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 23-81 years who were diagnosed as CIDP based on EFNS/PNS (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. Control group consisted of 40 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 records between the years 2011-2016.

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 HOMA (Homeostasis Model Assessment) index [FBG mg/dl x fasting insulin (µU/ml)/405] formula, and values ≥ 2.5 were accepted as abnormal. Normal range for vitamin E levels was considered to vary between 0.30-0.90 mg/dl.

In the data evaluation, the normality of distribution of the parameters was assessed by Shapiro Wilks test. In addition to descriptive statistical methods (mean, standard deviation, frequency), in the comparison of quantitative data for parameters with normal distribution Student t test, and for parameters without normal distribution Mann-Whitney U test were used. For comparison of qualitative data Fisher’s exact test, and chi- square test with Yates’s continuity correction, and for correlations Pearson correlation test were employed. Statistical significance was evaluated at p < 0.05.

Results

A statistically significant difference was not found between CIDP, and control groups as for 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, impaired fasting glucose (IFG) and vitamin E deficiency (p > 0.05) (Table 3).

Table 1: Demographic data of groups

¹Student t test ²Chi- square test with Yates’s continuity correction

Table 2: Evaluation of HOMA index and vitamin E levels

¹Student t test, ²Mann Whitney U Test

HOMA: The Homeostasis Model Assessment

Table 3: Comparison between CIDP and control groups as for the presence of insulin resistance, impaired fasting glucose (IFG) and vitamin E deficiency

Chi- square test with Yates’s continuity correction

There was no statistically significant difference in the patient and control groups between study participants aged ≤ 40, and > 40 years as for the presence of insulin resistance, and decreased vitamin E levels (p > 0.05) (Tables 4).

Table 4: Evaluation of insulin resistance according to age groups

Fisher’s Exact test

Seven (17.5%) cases among all 40 patients with CIDP who were followed up in our clinic had definitive diagnosis of diabetes which did not statistically significantly differ from incidence of diabetes in Turkey (13.5%) (p > 0.05).

Discussion

As a critical issue chronic inflammatory demyelinating polyneuropathy should be accurately diagnosed, and discriminated from other demyelinating peripheral polyneuropathies because it responds better to treatment^[1,2]. Among diseases concurrently seen with CIDP, inflammatory, and autoimmune diseases including DM, Human Immmuno Deficiency Virus (HIV) infection, chronic active hepatitis, IgM Monoclonal Gammopathy (MGUS), temporal arteritis, rheumatoid arthritis, Systemic Lupus Erythematosus (SLE), and other connective tissue diseases, inflammatory bowel diseases, sarcoidosis, and thyroid diseases can be enumerated^[3-7].

The relationship between DM and CIDP has been reported in many studies, although no clear conclusions have been reached^[8-17].

CIDP should be differentiated from symmetrical sensory motor polyneuropathy seen in DM. 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 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 was 11 times higher among diabetic than nondiabetic patients (P < 001)(15). 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^[16]. However some authors advocated lack of any pathogenetic correlation between DM, and CIDP. Laughin et al. found no increase in the incidence of CIDP in the DM group compared to the general population and conclude that DM is not a major risk factor for the development of CIDP^[12]. Chio 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^[8].

Also 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 HbA1c (28%), and creatine kinase (84%) levels^[18]. So 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. ın 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^[19].

In 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%^[20].

Dunnigan et al. and Haq et al. detected that CIDP + DM patients were relatively older. They indicated that despite similarities in electrophysiologic patterns of demyelination, their etiologies differ with higher probability^[13,14]. 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 general population, 36% of the patients in the CIDP group, while 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. And 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 play 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 anti-inflammatory effects by modifying inflammatory response. Vitamin E deficiency leads to demyelinating neuropathy, and vitamin E supplementation ensures clinical and electrophysiologic recovery^[25,26].

Puri V 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^[25].

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 are far behind the other group and never reached normal^[26].

In our study, we did not find any significant difference in vitamin E levels in the CIDP group 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 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^[27].

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

In conclusion, though 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.

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