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Assessment of Executive Function in Type 2 Diabetes Mellitus – A Case Control Study

1,3 Assistant Professor, 2 Associate Professor Institute of Mental Health, Kilpauk, Chennai: 10 Corresponding Author Dr V.Sabitha Associate Professor, Institute of Mental Health, Kilpauk, Chennai: 10 ABSTRACT There is growing evidence that adults with type 2 Diabetes mellitus exhibit deficits in executive function. Primary purpose of this study was to assess executive function in type 2 DM patients. The age group studied was between 40-50 years and it was compared with the healthy controls. This is a cross sectional case control study, where in 50 consenting patients attending diabetology Outpatient department fulfilling the inclusion criteria were randomly chosen as cases and 50 consenting age, sex, education matched non diabetics were taken as controls. After screening with General Health Questionaire – 12 for psychiatric symptoms, Executive function was assessed with Digit Span Test, Verbal fluency test, Trail making test, Wisconsin Card Sorting Test and Stroop Test. In our study we found that here was no significant difference between diabetic and non-diabetic group in case digit span, verbal fluency, stroop test and WCST. There was a statistically significant difference between case and control group in Trail Making Test (p = 0.01). There was average difference of 8 seconds between diabetic and nondiabetics. The Stroop test showed a similar slowing in diabetics of 3 seconds but it was not statistically significant. Executive functioning in diabetics was comparable to that of control group. Though Trail making test, showed a statistical difference between diabetics and non-diabetic, it was still within the normative range for the particular age group.


Introduction
T2DM is a major public health problem all over the world 1 . The socio-economic cost of Type 2 diabetes mellitus is exorbitant, mainly due to number of associated problems that accompany diabetes mellitus, like micro and macro vascular diseases and their increased susceptibility for cognitive impairment 2,3 .
Executive function is a primary domain of cognition that involves a broad set of cognitive abilities like attention, working memory, organization, and persistence that are necessary for orchestrating complex, goal-directed activities 1 . Executive function appears to be orchestrated and mediated by frontal cortex along with its networks in cerebrum and sub-cortical regions of brain 4 . Recent studies and evolving data categorically suggest that executive dysfunction is causatively associated with poor glycemic control 2,5 i.e it is one of the major risk factor. The effect of Type 2 diabetes mellitus on executive function is associated with inherent micro-vascular disease affecting frontal sub-cortical function 1 . Executive function is a major domain of cognition that plays a pivotal role in allowing the execution of daily management tasks including exercise, blood glucose monitoring and drug intake, which are essential for glycemic control 1 . Executive Dysfunctions are implicated in decreased self care capacity, poor adherence to diabetic medication, decreased levels of autonomy and a decrease in ability to make essential decision, for instrumental activities of daily living, as well as resistance to proper medical care 1,5 Suggested causes of hyperglycemia induced Executive dysfunction are 1. Diabetic vasculopathy, 2. hyper-lipidemia, 3. hypertension, 4. Insulin resistance 5. hyper-insulinemia 6. dysregulation of limbic-hypothalamicadrenal pituitary axis (LHPA) 7. chronic hyperglycemia induced direct cytotoxicity on neuronal cells. 8. advanced glycation products 9. Inflammatory mediators like cytokines 10. oxidative stress 11. diabetes related depression The purpose of this study is to assess executive function in patients with type 2 Diabetes mellitus in comparison to normal subjects.

Aim
To assess executive functioning in type 2 diabetic patients compared to normal subjects NULL HYPOTHESIS There is no difference in performance, of the study and control groups, in tests of executive function.

Ethics Committee
The study was approved by the Institutional Ethical Committee, Madras Medical College. All subjects (both patients and control group) gave informed consent for participation in written form.

Digit Span Test
In digit span test the subject is instructed to repeat a series of numbers in the same order as said to JMSCR Vol||05||Issue||06||Page 23237-23246||June 2017 them. The evaluator continues to keep on increasing the series of numericals in order of one every time and then asking the subject to repeat them back to the evaluator as a long as the answers are correct and stops when a response is incorrect. Similarly in the backward digit span task the participant needs to reverse the order of the numbers.

Verbal Fluency Test
The Verbal Fluency battery includes tests for Letter and Category fluency. In Verbal fluency test the subject is evaluated for maximum number of word production , within a set time frame, and within a specific constraint, In the Letter Fluency test, the subject is give three separate one-minute trials for the letters F, A, and S. The Category Fluency test is a one-minute trial for a single category like birds which can fly, four legged animals etc. For Subjects not proficient English, 3 letter of their Vernacular language is given.

Wisconsin card sorting test
It consists of sixty four tests cards and 4 stimulus cards. Each card is a square of dimensions 8cms by 8cms. The stimuli vary in 3 attributes: color(red, green, yellow, blue), form(triangle, star, cross, circle) and number(1,2,3,4).

Stroop test
This test measures the response inhibition ability. Three cards which has 20 rows and 5 columns of either color names or symbol is presented. First card has color names printed in black color, second card has x symbol printed in different colors. And last card has color names blue, green, and red printed in different colors. The time taken to read each card (t1, t2, t3) and the number of errors made isnoted. The Stroop effect is calculated as: t3-(t1+t2 / 2).

Trail making test
Trail Making Test has two parts A and B. Each part consists of 25circles distributed over a sheet of paper. Time taken to complete the trail is noted.

Results
The study is a case control study, cases defined as Type2 Diabetes mellitus and controls as healthy unrelated subjects.
A. Socio-demographic data of cases and controls With respect to study population (cases), mean age was 45.14±1.5. Sex distribution was also equal among cases, 25 males and 25 females. With respect to control group), mean age was 44.98±1.52 Sex distribution among control was 26 (52%) male and 24 (48%) female. Comparison of socio-demographic data of cases and controls shows no significant difference. Hence the two groups are comparable with respect to age, sex distribution, education, occupation, socioeconomic status.  The mean age of onset of diabetes mellitus is 41.40 years and the mean duration of illness is < 5 years. There was no major macro / micro vascular complication.
c. Assessment of normal distribution of data Shapiro-Wilk and Kolmogorov-Smirnov test is used to assess the normal distribution of data. is the gold standard test for executive function testing. The raw scores for each parameter were noted and their corresponding standard scores entered from test manual. The overall performance was marginally better in control group compared to cases who made more number of errors (total and perseverative) and perseverative responses. So the standardized scores were marginally low in cases compared to controls.

Wisconsin card sorting test
The tests did not show statistically significance difference between the two groups. All the test were not statistically significant.

Discussion
In our study age group selected was between 40 to 50 years. This was mainly taken to avoid any age related cognitive deficits. Formal education of at least 8 th standard was applied so that the subjects could understand the tests and perform. The digit span test did not show much difference between case and control group. The verbal fluency was also within normal limits in diabetics compared to the non-diabetics. The Wisconsin card sorting test -(WCST) (perseveration), B: WCST (category) and C: WCST (conceptual responses) also did not vary significantly between diabetics group and non-diabetics. The deficits in executive function were observed in some studies 7,8,9, 15 or randomized studies such as PROSPER 16 highlighted diabetes as an independent risk factor for cognitive impairment in elderly individuals over 70 years. Our study group was between 40 -50 years age group, with a duration of disease less than or equal to five years, without any vascular complications. This study group didn't show a significant executive dysfunction compared to previous studies probably due to relatively recent onset disease and a younger population group. In elderly patients, co-morbidities are higher namely hypertension, cardio-vascular, cerebro-vascular disease, psychiatric affections and drug usage. These lead to exacerbation of the executive dysfunction in them.

Conclusion
Executive functioning in patients with Type 2 diabetes mellitus was comparable to that of control group. Though Trail making test, showed a statistical difference between the diabetic and non-diabetic, it was still within the normative range for the particular age group. Validation of this conclusion requires a larger group and prospective longitudinal study. Future follow up is essential to see how the cognitive dysfunction develop in these patients over a period of time and whether they would also develop problems in their executive functions and information processing abilities as seen in other studies.