International Journal of Current Research and Review
ISSN: 2231-2196 (Print)ISSN: 0975-5241 (Online)
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IJCRR - 10(7), April, 2018

Pages: 12-17

Date of Publication: 14-Apr-2018

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Cognitive Functions in Patients of Type 2 Diabetes Mellitus with Peripheral Neuropathy, An Observational Cross Sectional Study Done in India

Author: Shubhra Bhardwaj, Sunita Mondal, Rajiv Bandhu, Debasish Chaudhury, Ekta Malik Debnath, Gaurav Swami, Madhulika Monga, Mukul Adlakha

Category: Healthcare

Abstract:Background: Peripheral neuropathy and cognitive decline both are very common in diabetics but relationship between them is yet unclear. Hence, this study aimed at assessing the cognitive functions in patients of type 2 diabetes mellitus (T2DM) with diabetic peripheral neuropathy (DPN) and compare them with that of patients of T2DM without DPN and apparently healthy controls.
Materials and Methods: In this observational cross sectional study eligible T2DM patients were divided into two groups with DPN (25) and without DPN (25) by Nerve conduction velocity (NCV). 25 apparently healthy controls were taken. Cognitive functions were tested by using P300 event related potential.
Result: P300 latency on Pz was significantly delayed in the T2DM with DPN as compared to T2DM without DPN (p < 0.05) and controls (p < 0.01). The average latency was also significantly delayed in T2DM with DPN as compared to controls(p < 0.05).A positive correlation between duration of diagnosis of T2DM (r= 0.3339, p= 0.0178*) with P300 Latency Fz was observed.
Conclusion: Cognitive functions are impaired in T2DM with DPN. Duration of illness is positively correlated to decline of cognitive functions.

Keywords: T2DM, DPN, P300, Cognitive functions

DOI: 10.7324/IJCRR.2018.1073

Full Text:


The term diabetes mellitus (DM) is used for a group of common metabolic disorders that share the common phenotype of hyperglycaemia1.

T2DM has assumed more importance due to its attendant long termmicro2‚3 and macro-vascular4 complications.Diabetic peripheral neuropathy (DPN) is one of the most common long term complications of DM. It is progressive and irreversible with an incidence rate of about 50% .T2DM patients are also at increased risk of developing dementia and number of patients of T2DM demonstrating cognitive decline is also on the rise 6

Cognitive impairments can be detected by event related potentials using P300. Cognitive event-related evoked potentials (EREPs) are long-latency potential. P300 is an index of cognitive processing time and has been shown to be prolonged in dementia 7.

Conflicting results have been reported regarding the relationship between any association of the long term complications like DPN and cognitive decline. In some studies diabetic patients with DPN have shown a decrease in cognitive and executive functions as compared with those without DPN8‚9.

Whereas, no relationship between cognitive functions and neuropathy in diabetic patients was observed in another study10. In India, studies showing correlation between DPN and cognitive decline are scanty.

In view of these discordant findings, the fact remains unclear that whether the microvascular complications like DPN provide an early evidence of cognitive decline beyond what is observed in diabetic patients free from such complications.

Moreover, development of cognitive dysfunction has an important bearing on the management and further progression of complications in diabetes. Therefore there is a strong need for documenting any such association in T2DM patients.


To find out -

1. Differences in cognitive function between T2DM patients with DPN as compared to T2DMpatients without DPN.

2. Relationship between the duration of diagnosis T2DM and cognitive functions.


This present study was an observational cross sectional study carried out in department of Physiology in association with department of Medicine, Lady Hardinge Medical College and associated Smt. Sucheta Kriplani Hospital conducted between November2014 to March2016.

The ethical clearance was obtained from the Institutional Ethics committee for Human Research. Written and informed consent was taken from all study participants. The study protocol was carried out as per declaration of Helsinki.

Inclusion criteria:

For Diabetics-Comprised of 50 new or already diagnosed cases of T2DM either gender (as per ADA criteria 11) in the age group 40 to 60 years. They were then divided into two groups based on presence or absence of DPN (as per minimal criteria given by Tesfaye et al.12

For Controls-v Apparently healthy volunteers in the age group 40 to 60 years which were age, gender, BMI, socioeconomic status (SES) 13 and educational status (ES) matched.

Exclusion criteria:

Individuals having history of neuropsychiatric illness, type 1 diabetes mellitus14, presence of any significant impairment in communication , pre diabetics 15(as per ADA criteria 11) and  history or examination suggestive  of  any other  risk factors known to cause cognitive impairment .

The minimum values of nerve conduction velocity for diagnosing peripheral neuropathy were as follows:


Conduction  Velocity

Median motor nerve 7

Median sensory nerve 7

Peroneal nerve 7

Sural nerve 16

54.44 m/sec





Study procedure

1. A detailed history taking and examination was done. For screening the CBC, LFT, KFT, serum electrolytes, blood urea, serum creatinine, chest X ray and ECG were done. Nerve conduction studies were done on all.

They were then divided into the following groups

Group I a: 25 patients of T2DM with DPN

Group I b: 25 patients of T2DM without DPN

Group II: 25 apparently healthy individuals as controls

2. Age and anthropometric measurements were recorded.

3. P 300 Recording -

Cognitive evoked potential P300 was tested by using a machine SCHWARZER TOPAS EMG neurophysiological measuring system provided by NATUS, Europe.

P300 is endogenous or event related potential (ERP) recorded in response to external stimulus or event7. P300 latency was recorded as per standard guidelines17.

Patients were asked to report with a clean and oil free scalp18 and to avoid anti-histaminics on the day of testing. The procedure was explained and it was emphasized that he/she should remain alert and still during the test7???????.

Gold cup electrodes were applied by 10-20 system for calculating sites for placement 19.Electrode impedance was kept below 10 K ohms7.

Auditory stimuli were delivered bilaterally using odd ball paradigm .Target and non target stimuli were used (that comprised 20 % and 80  of total stimuli respectively).Target stimuli (4000 Hz) were presented randomly. Non target stimuli (1000 Hz) appeared at fixed interval of time.7 Intensity of stimuli was kept at 65 dB SPL.


The data was submitted for statistical evaluation using Graph Pad Prism software version 6.Mean and Standard error of mean (Mean ± SEM) of all the variables were calculated. After testing for normal Gaussian distribution, intergroup comparison was done using ANOVA and Tukey's post-hoc test was applied for multiple comparisons. Chi square test and Mann - Whitney test were applied as per requirement. Correlation was assessed using the Spearman’s correlation coefficient.


Table 1 illustrates socio-demographic characteristics of study population. They were age, BMI, WC, sex distribution, SES and ES matched.

Table 2 shows the treatments being received by the diabetics of the two groups. There was a statistically significant difference in number of patients receiving Insulin, Metformin and Statins.

Table 3 shows -P300 latency on Pz was significantly delayed in the T2DM with DPN as compared to T2DM without DPN (p < 0.05)v and controls (p < 0.01)as shown in Fig.1. The average latency is also significantly delayed in T2DM with DPN as compared to controls (p < 0.05) as shown in Fig.2.

A positive correlation between years since diagnosis of T2DM(r= 0.3339, p= 0.0178*) and P300 Latency Fz was observed as shown in Fig .3.


In our study it was observed that the P300 latency on Pz is significantly higher in T2DM with DPN as compared to the T2DM without DPN and controls.  The average P300 latency is also significantly higher in T2DM with DPN as compared to the controls.

These above findings suggest that cognitive functions as shown by P300 latency are delayed in diabetics with neuropathy as compared to the diabetics without neuropathy as well as controls. This is similar to study conducted by Ryan et al where they showed relationship between neuropathy and cognitive dysfunctions in diabetics9, however, this study was done in T1DM patients..In an another study conducted by Dey et al no relationship between peripheral neuropathy and cognitive functions was observed in T2DM patients10.Ryan et al hypothesized that peripheral neuropathy could be a marker for a metabolically mediated “central neuropathy” which too, may be a consequence of a long history of hyperglycaemia9.

A positive correlation of years since diagnosis of T2DM with P300 Latency Fz.(P=0.0178,r= 0.3339) was found .This suggests that as the duration of illness increases ,there is a cognitive decline. Our finding is similar to that of Ryan et al where they have observed a significant decline in cognitive functions in T1DM patients over period of time as compared to controls 20.Worall G. et al also found similar observation between duration of T2DM   and cognition 21.

Thus, our study is also consistent with the work done by Perlmuter et al where they observed that peripheral neuropathy is associated with cognitive impairment T2DMpatients and in contrast to other study done by Lawson et al 22 where they observed no such association.

Cognitive decline in diabetes mellitus can be due to impaired neurogenesis, changes in blood brain barrier, chronic hyperglycaemia, inflammatory mechanisms, vascular dysfunction affecting neuronal functions in brain6. Hyperglycaemia may have toxic effects on neurons in the brain through osmotic insults and oxidative stress. Chronic high glucose level leads to the enhanced formation of advanced glycation end products (AGEs) 23. AGEs couple with free radicals and create oxidative damage, which in turn leads to neuronal injury 24. AGEs also activate microglia in the CNS .Microglia can become deleterious and damage neurons 25. The metabolic disturbances that are associated with clinically apparent distal symmetric polyneuropathy like alterations in peripheral nerve Na+-K+ ATPase activity that leads to a reduction in myo-inositol and sorbitol metabolism 26 may also cause biochemical and physiological abnormalities that disrupt cell transport of various metabolities and substrates in both the peripheral and central nervous systems.

­In our study, DPN and cognitive dysfunction may be present in same patient and a part of the same disease process.


In our study it can be concluded that T2DM patients with DPN have impaired cognition as substantiated by delayed P300 latency. This cognitive impairment may also progress as duration of T2DM increases.

LIMITATIONS-There are confounding factors in our study which could have affected the outcome.

1. Patients of both the diabetic groups were receiving Metformin and Statins. Metformin leads to an exacerbation of peripheral neuropathy27???????. Metformin also affects cognition 28‚29. Some studies on Statins have shown lower prevalence of vascular dementia and Alzheimer's disease 30‚31‚32 with use of Statins while others have shown an equivocal result 33???????.

2. Years since diagnosis of DM was also significantly different in both the diabetic groups.

Due to the small sample size in a tertiary care setting and the above said confounding factors, the study results cannot be generalized to all the diabetics in routine management.


It is necessary to carry out the study on a larger sample size involving multi-ethnic and multi-centric population.


Authors are grateful to workers whose articles and books have been cited for reference. We are also grateful to Mr. Gaurav and his team from NATUS, Europe which provided us SCHWARZER TOPAS EMG neurophysiological measuring system along required with technical help. Authors acknowledge the immense help received from the scholars whose articles are cited and included in references of this manuscript. The authors are also grateful to authors /editors /publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed.

Sources of financial support- Nil

Conflict of interest –  Nil.


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A Study by Tarek Elwakil et al. entitled "Led Light Photobiomodulation Effect on Wound Healing Combined with Phenytoin in Mice Model" is awarded Best Article of Vol 13 issue 02
A Study by Mohita Ray et al. entitled "Accuracy of Intra-Operative Frozen Section Consultation of Gastrointestinal Biopsy Samples in Correlation with the Final Histopathological Diagnosis" is awarded Best Article for Vol 13 issue 01
A Study by Badritdinova MN et al. entitled "Peculiarities of a Pain in Patients with Ischemic Heart Disease in the Presence of Individual Combines of the Metabolic Syndrome" is awarded Best Article for Vol 12 issue 24
A Study by Sindhu Priya E S et al. entitled "Neuroprotective activity of Pyrazolone Derivatives Against Paraquat-induced Oxidative Stress and Locomotor Impairment in Drosophila melanogaster" is awarded Best Article for Vol 12 issue 23
A Study by Habiba Suhail et al. entitled "Effect of Majoon Murmakki in Dysmenorrhoea (Usre Tams): A Standard Controlled Clinical Study" is awarded Best Article for Vol 12 issue 22
A Study by Ghaffar UB et al. entitled "Correlation between Height and Foot Length in Saudi Population in Majmaah, Saudi Arabia" is awarded Best Article for Vol 12 issue 21
A Study by Siti Sarah Binti Maidin entitled "Sleep Well: Mobile Application to Address Sleeping Problems" is awarded Best Article for Vol 12 issue 20
A Study by Avijit Singh"Comparison of Post Operative Clinical Outcomes Between “Made in India” TTK Chitra Mechanical Heart Valve Versus St Jude Mechanical Heart Valve in Valve Replacement Surgery" is awarded Best Article for Vol 12 issue 19
A Study by Sonali Banerjee and Mary Mathews N. entitled "Exploring Quality of Life and Perceived Experiences Among Couples Undergoing Fertility Treatment in Western India: A Mixed Methodology" is awarded Best Article for Vol 12 issue 18
A Study by Jabbar Desai et al. entitled "Prevalence of Obstructive Airway Disease in Patients with Ischemic Heart Disease and Hypertension" is awarded Best Article for Vol 12 issue 17
A Study by Juna Byun et al. entitled "Study on Difference in Coronavirus-19 Related Anxiety between Face-to-face and Non-face-to-face Classes among University Students in South Korea" is awarded Best Article for Vol 12 issue 16
A Study by Sudha Ramachandra & Vinay Chavan entitled "Enhanced-Hybrid-Age Layered Population Structure (E-Hybrid-ALPS): A Genetic Algorithm with Adaptive Crossover for Molecular Docking Studies of Drug Discovery Process" is awarded Best article for Vol 12 issue 15
A Study by Varsha M. Shindhe et al. entitled "A Study on Effect of Smokeless Tobacco on Pulmonary Function Tests in Class IV Workers of USM-KLE (Universiti Sains Malaysia-Karnataka Lingayat Education Society) International Medical Programme, Belagavi" is awarded Best article of Vol 12 issue 14, July 2020
A study by Amruta Choudhary et al. entitled "Family Planning Knowledge, Attitude and Practice Among Women of Reproductive Age from Rural Area of Central India" is awarded Best Article for special issue "Modern Therapeutics Applications"
A study by Raunak Das entitled "Study of Cardiovascular Dysfunctions in Interstitial Lung Diseas epatients by Correlating the Levels of Serum NT PRO BNP and Microalbuminuria (Biomarkers of Cardiovascular Dysfunction) with Echocardiographic, Bronchoscopic and HighResolution Computed Tomography Findings of These ILD Patients" is awarded Best Article of Vol 12 issue 13 
A Study by Kannamani Ramasamy et al. entitled "COVID-19 Situation at Chennai City – Forecasting for the Better Pandemic Management" is awarded best article for  Vol 12 issue 12
A Study by Muhammet Lutfi SELCUK and Fatma entitled "Distinction of Gray and White Matter for Some Histological Staining Methods in New Zealand Rabbit's Brain" is awarded best article for  Vol 12 issue 11
A Study by Anamul Haq et al. entitled "Etiology of Abnormal Uterine Bleeding in Adolescents – Emphasis Upon Polycystic Ovarian Syndrome" is awarded best article for  Vol 12 issue 10
A Study by entitled "Estimation of Reference Interval of Serum Progesterone During Three Trimesters of Normal Pregnancy in a Tertiary Care Hospital of Kolkata" is awarded best article for  Vol 12 issue 09
A Study by Ilona Gracie De Souza & Pavan Kumar G. entitled "Effect of Releasing Myofascial Chain in Patients with Patellofemoral Pain Syndrome - A Randomized Clinical Trial" is awarded best article for  Vol 12 issue 08
A Study by Virendra Atam et. al. entitled "Clinical Profile and Short - Term Mortality Predictors in Acute Stroke with Emphasis on Stress Hyperglycemia and THRIVE Score : An Observational Study" is awarded best article for  Vol 12 issue 07
A Study by K. Krupashree et. al. entitled "Protective Effects of Picrorhizakurroa Against Fumonisin B1 Induced Hepatotoxicity in Mice" is awarded best article for issue Vol 10 issue 20
A study by Mithun K.P. et al "Larvicidal Activity of Crude Solanum Nigrum Leaf and Berries Extract Against Dengue Vector-Aedesaegypti" is awarded Best Article for Vol 10 issue 14 of IJCRR
A study by Asha Menon "Women in Child Care and Early Education: Truly Nontraditional Work" is awarded Best Article for Vol 10 issue 13
A study by Deep J. M. "Prevalence of Molar-Incisor Hypomineralization in 7-13 Years Old Children of Biratnagar, Nepal: A Cross Sectional Study" is awarded Best Article for Vol 10 issue 11 of IJCRR
A review by Chitra et al to analyse relation between Obesity and Type 2 diabetes is awarded 'Best Article' for Vol 10 issue 10 by IJCRR. 
A study by Karanpreet et al "Pregnancy Induced Hypertension: A Study on Its Multisystem Involvement" is given Best Paper Award for Vol 10 issue 09

List of Awardees

A Study by Ese Anibor et al. "Evaluation of Temporomandibular Joint Disorders Among Delta State University Students in Abraka, Nigeria" from Vol 13 issue 16 received Emerging Researcher Award

A Study by Alkhansa Mahmoud et al. entitled "mRNA Expression of Somatostatin Receptors (1-5) in MCF7 and MDA-MB231 Breast Cancer Cells" from Vol 13 issue 06 received Emerging Researcher Award

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Disclaimer: International Journal of Current Research and Review (IJCRR) provides platform for researchers to publish and discuss their original research and review work. IJCRR can not be held responsible for views, opinions and written statements of researchers published in this journal.


International Journal of Current Research and Review (IJCRR) provides platform for researchers to publish and discuss their original research and review work. IJCRR can not be held responsible for views, opinions and written statements of researchers published in this journal


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