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Table of Contents
ORIGINAL ARTICLE
Year : 2019  |  Volume : 10  |  Issue : 2  |  Page : 95-98

Insulin resistance as a predictor of sensory neuropathy in prediabetes


1 Department of Medicine, Medical College, New Delhi, India
2 Department of Biochemistry, PGIMER, Dr. RMLH, Medical College, New Delhi, India
3 Lady Hardinge, Medical College, New Delhi, India

Date of Submission26-Dec-2018
Date of Decision13-Mar-2019
Date of Acceptance27-Mar-2019
Date of Web Publication24-May-2019

Correspondence Address:
Dr. Ajay Chauhan
PGIMER, Dr. RMLH, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/INJMS.INJMS_41_18

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  Abstract 


Objective: The aim of this study is to assess the association of insulin resistance with sensory neuropathy in prediabetes. Materials and Methods: Fasting serum insulin levels were measured and the homeostatic model assessment of insulin resistance (HOMA-IR) was calculated in all patients. These were compared in prediabetic patients having sensory neuropathy to those who did not have sensory neuropathy as determined by vibration perception thresholds (VPTs) measured using Digital Biothesiometer. Furthermore, direct correlation between insulin resistance and VPTs was checked. Results: A total of 60 prediabetic cases were included in this study. Among the study population, the age distribution ranged from 35 years to 60 years with the mean age of 48.68 years. Male and female formed 65% and 35% of the study population, respectively. The maximum fasting serum insulin levels were 21.8 mIU/L, and the minimum fasting serum insulin levels were 3.5 mIU/L, with the mean value being 10.61 ± 4.99 mIU/L. The maximum HOMA-IR was 6.4, and the minimum was 0.986, with the mean value being 2.81 ± 1.37. Among all the prediabetic patients, 43.3% of patients had neuropathy according to VPTs measured using Biothesiometer. T-test analysis suggests that mean fasting serum insulin levels (P = 0.026) and HOMA-IR (P = 0.032) were significantly higher in patients with neuropathy than patients without neuropathy. VPTs were found to have statistically significant positive correlation with fasting serum insulin levels (Pearson correlation coefficient = 0.317 [R], 0.296 [L];P = 0.013 [R], 0.022 [L]) and HOMA-IR (Pearson correlation coefficient = 0.299 [R], 0.281 [L];P = 0.02 [R], 0.03 [L]). Conclusion: Insulin resistance, quantified with the help of the index, HOMA-IR, has an important role in the development of this sensory neuropathy.

Keywords: Insulin resistance, neuropathy, prediabetes


How to cite this article:
Singh A, Chauhan A, Goyal P, Kaur J, Ramesh P. Insulin resistance as a predictor of sensory neuropathy in prediabetes. Indian J Med Spec 2019;10:95-8

How to cite this URL:
Singh A, Chauhan A, Goyal P, Kaur J, Ramesh P. Insulin resistance as a predictor of sensory neuropathy in prediabetes. Indian J Med Spec [serial online] 2019 [cited 2019 Oct 19];10:95-8. Available from: http://www.ijms.in/text.asp?2019/10/2/95/258991




  Introduction Top


Diabetic neuropathy is the most prevalent complication of diabetes mellitus (DM), affecting as many as 50% of patients with type 1 and type 2 DM.[1] Prediabetes is a high-risk state for developing diabetes that is defined by various blood glucose variables that are higher than the normal values, but lower than diabetes cutoffs.[2] Various studies have shown that long-term complications of diabetes, including microvascular and macrovascular complications might also be at increased risk in prediabetes. In a study done in India in 2014, neuropathy was detected in 32.8% of patients with impaired glucose tolerance (prediabetes). Thus, the peripheral neuropathy may be much more common in prediabetics than previously thought.[3] In another study done in 2015, the prevalence of peripheral neuropathy was 29%, 49%, and 50% for normal glycemia, prediabetes, and new-onset diabetes, respectively.[4] There is a strong link between increased insulin resistance and poor microvascular outcomes in diabetes. Prediabetes is also a state of increased insulin resistance to a level not enough to produce diabetes. Insulin resistance might play an important role in the development of peripheral neuropathy in prediabetes also. However, few data about the influence of insulin resistance on peripheral neuropathy are available. Han et al., in their study, reported in 2015 that insulin resistance might play an important role in the development of peripheral neuropathy in metabolic syndrome.[5] Many other studies have implicated that microvascular complications start occurring as early as in prediabetes phase. However, its pathogenesis is not completely understood. The aim of the present study is to assess insulin resistance as a predictor of the occurrence of sensory neuropathy in prediabetes.


  Materials and Methods Top


Place of study

The study was conducted in the Departments of Medicine and Biochemistry at PGIMER and Dr. Ram Manohar Lohia Hospital, New Delhi, India, during the study period between November 2016 and March 2018.

Study design

A cross-sectional observational study was performed.

Sample size

A total of 60 prediabetic (as defined by the American Diabetes Association) patients were evaluated.

Selection of the study population

The target population consisted of patients of prediabetes either admitted as inpatient or visiting the outpatient department between November 2016 and March 2018. Sixty consecutive patients fulfilling all inclusion and exclusion criteria were included in the study.

Inclusion criteria

  • Age of 30–60 years
  • Fasting plasma glucose between 100 and 125 mg/dL or
  • 2-h postprandial plasma glucose between 140 and 199 mg/dL (were included in the study only after reconfirming with standard 2-h oral glucose tolerance test [after 75 g of glucose solution ingestion]) or
  • Glycated hemoglobin = 5.7%–6.4%.


Exclusion criteria

  • Cerebrovascular accidents
  • Hypothyroidism
  • Chronic alcoholics
  • Patients on anti-tubercular treatment and other drugs known to cause neuropathy
  • Smokers
  • Patients on chemotherapy and/or radiotherapy
  • Systemic lupus erythematosus
  • Leprosy
  • Vasculitis
  • Malignancy
  • Neurological disorders such as Guillain-Barré syndrome, multiple sclerosis
  • Human immunodeficiency virus positive patients
  • Chronic glucocorticoid therapy
  • Vitamin B12 deficiency.


Levels of fasting serum insulin levels and vibration perception thresholds (VPTs)[6] were measured. Serum Insulin levels were measured using the enzyme-linked immunosorbent assay kit (DRG Insulin ELISA EIA-2935) on the EVOLIS™ Twin Plus System (Bio-Rad). The basal state insulin resistance of the individual was calculated using the homeostatic model assessment of insulin resistance (HOMA-IR). The HOMA-IR used is available on the Internet at www.dtu.ox.ac.uk/homacalculator.

VPTs were measured using Digital Biothesiometer (Vibrotest) using the PLANTAR method [Figure 1], and the average value was calculated in both feet. Biothesiometer is a useful diagnostic tool for quantitatively grading the neuropathy, manufactured by Diabetik Foot Care India Pvt Ltd. Patients with average VPT of >15 V on either side were considered to have neuropathy.
Figure 1: Areas to measure vibration perception thresholds in PLANTAR method

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Data were analyzed for statistical correlation of fasting serum insulin levels and HOMA-IR with VPTs.

Data analysis

The data obtained was entered into Microsoft Excel Worksheet. Statistical analysis was performed using statistical software package statistical package for the social sciences (SPSS) version 22.0 (IBM Corporation, Armonk, New York, United States). Data are represented as mean ± standard deviation, mean value of the continuous variable was compared using t-test. The Pearson's correlation coefficient was calculated to assess the correlation between two continuous variables. Value of P < 0.05 was considered as statistically significant.


  Results Top


A total of 60 prediabetic cases were included in this study. Among the study population, the age distribution ranged from 35 years to 60 years, with the mean age of 48.68 years. Male and female formed 65% and 35% of the study population, respectively. The maximum fasting serum Insulin levels were 21.8 mIU/L and the minimum was 3.5 mIU/L, with the mean value being 10.61 ± 4.99 mIU/L. The maximum HOMA-IR was 6.4 and the minimum was 0.986, with the mean value being 2.81 ± 1.37 [Table 1]. Among all the prediabetic patients, 43.3% of patients had neuropathy according to VPTs measured by Biothesiometer. T-test analysis suggests that mean fasting serum insulin levels (P = 0.026) and HOMA-IR (P = 0.032) were significantly higher in patients with neuropathy than patients without neuropathy [Table 2].
Table 1: Baseline characteristics of study population (n=60)

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Table 2: Comparison of biochemical parameters in patients with or without neuropathy

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VPTs were found to have statistically significant positive correlation with fasting serum insulin levels (Pearson correlation coefficient = 0.317 [right foot (R)], 0.296 [left foot (L)]; P = 0.013 [R], 0.022 [L]) and HOMA-IR (Pearson correlation coefficient = 0.299 [R], 0.281 [L]; P = 0.02 [R], 0.03 [L]) [Table 3] and [Table 4].
Table 3: Correlation of vibration perception thresholds (right side) with serum insulin levels and HOMA-IR (n=60)

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Table 4: Correlation of vibration perception thresholds (left side) with serum insulin levels and HOMA-IR (n=60)

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  Discussion Top


Prediabetes is considered to be a precursor phase of DM in which blood sugar levels are higher than normal but not high enough to meet the criteria of DM. Thus, this intermediate stage is often referred to as the gray area or gray zone between normoglycemia and overt diabetes. Prediabetic neuropathy is a new emerging entity. There is a paucity of literature pertaining to peripheral neuropathy in prediabetes, especially from India. Therefore, this study was designed to understand the role of insulin resistance in sensory neuropathy in prediabetes.

Patients were assessed for the occurrence of neuropathy by measuring VPTs using Biothesiometer. Statistical correlations of neuropathy in prediabetic patients with fasting serum insulin levels and HOMA-IR were studied.

VPT results have been found to have good correlation with nerve conduction velocity study (NCV) findings. Klima et al. reported comparison of VPT values, based on whether or not evoked sensory and motor responses were obtained in NCV, indicated that mean VPTs were consistently higher among patients in whom these evoked responses were not elicited.[7] Martin et al. reported that VPT was a sensitive predictor of distal symmetric polyneuropathy (DSPN), with the highest sensitivity noted for confirmed clinical neuropathy (87%). The sensitivity of VPT to predict definite clinical neuropathy and abnormal nerve conduction was 80% and 75%, respectively.[8] Jayaprakash et al. quoted that VPT is considered as a gold standard for the diagnosis of diabetic peripheral neuropathy.[9] Hence, VPTs can reliably detect sensory neuropathy and serve as a useful, less time-consuming, and less painful alternative to nerve conduction studies.

Insulin resistance is strongly associated with microvascular complications of diabetes and is a very important target of intervention as increased insulin sensitivity leads to improved microvascular outcomes. It is hypothesized that higher insulin levels accelerate hyperglycemia-mediated microvascular damage due to increased oxidative stress.[10] Recently, several studies showed that the components of metabolic syndrome had an obvious impact on the pathogenesis of peripheral neuropathy. Insulin resistance is the core feature of metabolic syndrome. Data have accumulated to suggest that neurons could also develop insulin resistance, resulting in neuronal injury. The components of metabolic syndrome and insulin resistance both might play an important role in the development of peripheral neuropathy.[5]

Serum insulin levels and HOMA-IR were found to be significantly higher in prediabetics with neuropathy (P< 0.05) in this study. Their values also significantly correlated with sensory neuropathy in prediabetic patients (P< 0.05). This is well supported in a study by Han et al. in 2015 which showed that insulin resistance might play an important role in the development of peripheral neuropathy in metabolic syndrome.[5] However, this biochemical parameter has not been previously studied for its role in sensory neuropathy in prediabetes per se, and our study is first to underscore the significance of insulin resistance in neuropathy in prediabetes. Although the occurrence of neuropathy in prediabetes has been studied, as per our knowledge, there are no published studies, in the Indian medical literature dwelling on the roles of the probable causative factors of sensory neuropathy in prediabetes.


  Conclusion Top


To sum it all up, sensory neuropathy, like in diabetes, also occurs in the prediabetic stage. Insulin resistance, as confirmed by the HOMA-IR and fasting serum insulin levels, has a role to play in the development of this sensory neuropathy.

Financial support and sponsorship

None.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Diabetic Neuropathy: Practice Essentials, Background, Anatomy; 2016. Available from: http://www.emedicine.medscape.com/article/1170337-overview. [Last accessed on 2016 August 26].  Back to cited text no. 1
    
2.
Tabák AG, Herder C, Rathmann W, Brunner EJ, Kivimäki M. Prediabetes: A high-risk state for diabetes development. Lancet 2012;379:2279-90.  Back to cited text no. 2
    
3.
Kannan MA, Sarva S, Kandadai RM, Paturi VR, Jabeen SA, Borgohain R. Prevalence of neuropathy in patients with impaired glucose tolerance using various electrophysiological tests. Neurol India 2014;62:656-61.  Back to cited text no. 3
[PUBMED]  [Full text]  
4.
Lee CC, Perkins BA, Kayaniyil S, Harris SB, Retnakaran R, Gerstein HC, et al. Peripheral neuropathy and nerve dysfunction in individuals at high risk for type 2 diabetes: The PROMISE cohort. Diabetes Care 2015;38:793-800.  Back to cited text no. 4
    
5.
Han L, Ji L, Chang J, Wen J, Zhao W, Shi H, et al. Peripheral neuropathy is associated with insulin resistance independent of metabolic syndrome. Diabetol Metab Syndr 2015;7:14.  Back to cited text no. 5
    
6.
Maffei L, Premrou V, Roldan P, Copetti M, Pellegrini F, Rossi MC, et al. Vibration perception threshold in the screening of sensorimotor distal symmetric polyneuropathy: The need of more accurate age-specific reference values. J Diabetes Sci Technol 2014;8:621-2.  Back to cited text no. 6
    
7.
Klima RR, Weigand AH, DeLisa JA. Nerve conduction studies and vibration perception thresholds in diabetic and uremic neuropathy. Am J Phys Med Rehabil 1991;70:86-90.  Back to cited text no. 7
    
8.
Martin CL, Waberski BH, Pop-Busui R, Cleary PA, Catton S, Albers JW, et al. Vibration perception threshold as a measure of distal symmetrical peripheral neuropathy in type 1 diabetes: Results from the DCCT/EDIC study. Diabetes Care 2010;33:2635-41.  Back to cited text no. 8
    
9.
Jayaprakash P, Bhansali A, Bhansali S, Dutta P, Anantharaman R, Shanmugasundar G, et al. Validation of bedside methods in evaluation of diabetic peripheral neuropathy. Indian J Med Res 2011;133:645-9.  Back to cited text no. 9
[PUBMED]  [Full text]  
10.
Groop PH, Forsblom C, Thomas MC. Mechanisms of disease: Pathway-selective insulin resistance and microvascular complications of diabetes. Nat Clin Pract Endocrinol Metab 2005;1:100-10.  Back to cited text no. 10
    


    Figures

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    Tables

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



 

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