CLINICAL STUDY OF EARLY INSULIN THERAPY COMPARED TO ORAL HYPOGLYCEMIC AGENTS IN NEWLY DETECTED TYPE 2 DIABETES MELLITUS- A HOSPITAL BASED STUDY

1. Associate Professor, Department of Medicine, Jorhat Medical College & Hospital(JMCH),Jorhat-1, Assam. 2. Assistant Professor, Department of Medicine, Jorhat Medical College & Hospital,(JMCH), Jorhat-1, Assam. 3. Assistant Professor,Department of Medicine, Assam Medical College & Hospital (AMCH), Dibrugarh-2, Assam. .................................................................................................................. Manuscript Info Abstract ......................... ........................................................................ Manuscript History Received: 18 February 2020 Final Accepted: 20 March 2020 Published: April 2020


ISSN: 2320-5407
Int. J. Adv. Res. 8(04), 1050-1055 1051 with the largest number of diabetes in the world. The major chunk of diabetes in India is type2 diabetes (96% of diabetes in India is type 2 as compared to above 85% worldwide) 4 .
As the type 2 diabetes progresses, the ability of the pancreas to produce insulin may become impaired, and the body does not have enough insulin to move glucose into cells .The oral medications become less effective, and more than a third of people must add insulin injections to their treatment regimen. New research is now challenging this treatment approach, suggesting that adding insulin earlier can greatly improve blood glucose control. (Diabetes Special Report, Johns Hopkins Health Alerts2005).
In this background it has become necessary to study the efficacy of insulin as an early therapeutic measure in newly detected type 2 diabetes mellitus of this region where no such study has been conducted before. Therefore this study was undertaken with following aims and objectives-Aims and Objectives:- 1. To study the efficacy of early insulin therapy in newly detected type 2 DM in relation to immediate glycemic control and glycemic control at the end of six months. 2. To study the compliance among the patients treated with oral hypoglycemic agents and Insulin. 3. To study the adverse effects if any of the two modalities of treatment.

Materials and Methods:-
The study was conducted for a duration of one year on newly detected type 2 diabetes mellitus patients diagnosed according to ADA criteria, attending diabetic clinic, out-patient and in-patient department of different medicine units of a tertiary care teaching hospital in North East India after clearance of institutional ethics committee. Patients were selected randomly and informed consent was obtained from all the subjects. The selected patients were evaluated on the basis of detailed history and clinical examination and investigations with special attention to the glycemic status. Patients were assigned randomly into two groups (A&B) with equal number of patients in each group .Group A was treated with oral hypoglycemic agents. (Both single drug and combination therapy according to the guidelines).Group B was put on insulin, a combination of short acting and intermediate acting insulin. Dose administration frequency, dose adjustment and administration of other drugs were done according to the ADA guidelines 5 . Each case was followed up for 6 months after starting treatment with FBS, PPBS during weekly visit and HbAlc was monitored at the time of diagnosis and after 6 months of follow up. HbAlc was estimated by using cation exchange HPLC system D in the same laboratory.All the patients were also monitored for the adverse effects like hypoglycemia, infection, weight gain, drug overdose, angina, cardiac failure etc.The paired t test was performed and standard deviation and p values of both the groups were calculated. One way analysis of variance (ANOVA) was used to know the difference in the two groups.

Results and Observations:-
A total of 80 patients were selected randomly in two groups .Group A was treated with oral hypoglycemic agents and Group B was put on insulin. Out of the 80 patients 56 were followed up till the completion of six months. The majority of the patients were from the 40 to <50 years age group. The mean baseline HbAlc were 11.55% in group A (male 11.62% and female 11.44%) and 11.38 % in group B (male 11.28% and female 11.53%). The mean HbAlc after six month of therapy were 10.76% in group A (male 10.74% and female 10.77%) and 10.64% in group B (male 10.65% and female 10.63%).  There was no significant difference in the base line FBS, PPBS and HbAlc values in the two groups. However after one month there were significant (p < 0.001) decrease in mean FBS and PPBS in both the groups .Regarding HbA1c ,though there was fall in mean value after six months, statistically it was not significant (p > 0.05). (Table: 1&2). On comparing the two groups, the decrease in FBS and PPBS after one month and HbAlc after six months were also not significant (p > 0.05) (Table: 2)

Discussion:-
The primary aim of the study was to assess the efficacy of early insulin therapy in newly detected type 2 diabetes mellitus versus oral hypoglycemic agents as a part of the conventional treatment regime and to find out the compliance and adverse effects in the two groups.

Age distribution:
In the present study maximum numbers of patients (38.88%) were from the 40 to 50 years age group. The mean age at diagnosis was 46.40 years for all type 2 DM patients, (46.62 years for male and 46.06 years for female). The National Rural Diabetes Survey (1989)(1990)(1991) found the mean age of subjects with diabetes to be 52.3 years. 6, 7. Tripathy and Kar found that onset of diabetic cases were above 50 years. 8 V. Mohan et al found mean age at diagnosis to be around 45 years 9. .King H et al found that the peak age at diagnosis was 40-45 years in developing countries compared to >60 years in developed countries 10,11 .
The overall male: female ratio in the present study was found to be 1

HbAlc:
The mean baseline HbAlc in group A was 11.55% (male 11.62% and female 11.44%) and in group B was 11.38% (male 11.28% and female 11.53%) After six month of therapy, the mean HbAlc in group A was 10.76% (male (4% and female 10.77%) and in group B was 10.64% (male 10.65% and female 10.63%). The mean decrease in HbAlc in group A was 0.79% and in group B was 0.74% after six months of therapy.
The decrease in mean FBS and PPBS in both the groups after one month of therapy were significant (p < 0.0001), but though there was fall in mean HbA1c value after six months, statistically it was not significant (p > 0.05). In Rury R et al 13 study about the efficacy of complex insulin regimens in type 2 diabetes mellitus found that the decrease in mean FBS was 50 ± 47 and decrease in mean PPBS was 61 ± 58. In the present study the glycemic status achieved after one month of follow up in both the groups in terms of decrease mean FBS and PPBS were comparable with the above study.
In a 48 weeks study carried out by Meneghini et al on 551 patients found that mean decrease in HbA1c was 2.6% and 2.3% in insulin and OHA groups respectively 14 .Another 24 weeks multicentre, open level, parallel study carried out by Rosenstock et al found that the HbAlc improvement from base line in both insulin and OHA groups were similar (mean decrease in HbAlc 1.7% and 1.5% in insulin and OHA groups respectively). 15 In our study the probable reason for not able to find a significant difference in early glycemic status among the two groups is short duration of follow up and small number of patient.

Adverse event:
At the time of diagnosis the mean body weight in group A was 64.57 ±9.28 kg and in group B was 60.85 ±8.84 kg with a p value 0.1458 (p>0.05). The mean weight gain after six months of therapy in group A was -1,05 +0.3 and in group B was 2.3± 0.5 with a p value of 0.034 (p<0.05).Infection was more in group A (32.14%) than in group B (17.85%). Hypoglycemia was seen in 7.14% cases in group A and in 10.00% cases in group B. Meneghini et al study also found that hypoglycemic events were slightly more in the insulin group 14.

Compliance:
In the present study, out of the total 24 follow up loss 6 patients were (25.00%) from group A and 18 patients were (75.00%) from group B. During follow up 17.86% patients in group A skipped 10% or more OHA doses and 57.14% patients in group B skipped 10% or more insulin doses (p<0.05). Rury R et al 13 found mean increase in weight 5.7±0.5kg in biphasic insulin group after 3 years of follow up.

Summary:
The majority of the patients (44.46%) were from the 40 to 50 years age group. The mean age at diagnosis was 46.40 years for all Type 2 DM patients with a male: female ratio was 1.67:1.
The base line FBS, PPBS and HbA1c were similar in both the groups without any significant difference (p>0.05). Though there was significant (p <0.001) the decrease in mean FBS and PPBS in both the groups after one month of therapy the fall in mean HbAlc value after six months, was not significant (p > 0.05). On comparing the two groups, the decrease in FBS and PPBS after one month and HbAlc after six months was also not significant (p > 0.05).
There was significant weight gain in group B (p<0.05) who were on insulin. Hypoglycemia occurs more commonly in this group (7.14% cases in group A and in 10.00% cases in group B).Infection was more in group A who were on oral hypoglycaemic agent (32.14% Vs 17.85%).
Compliance to the therapy was better in those patients who were on oral hypoglycaemic agent .Follow up loses were much more in insulin treated group as compared to OHA treated group (75% Vs 25 %.). In group B who were receiving insulin 25.00% patient skipped 20% or more doses of insulin during follow up. 1055

Conclusion:-
Improvements in the glycemic status in patients with type 2 diabetes mellitus treated with oral hypoglycemic agents and insulin was almost identical (p>0.05). Patients on insulin showed high incidence of weight gain (P<0.05). The compliance was better with oral hypoglycemic agents. Overall, in the present setting insulin is not better than oral hypoglycemic agents in newly diagnosed type 2 diabetes mellitus patients. Further studies with large number of patients with prolong duration are needed to arrive at a more clear cut conclusion regarding glycemic efficacy of early initiation of insulin specially in newly diagnosed type 2 diabetes mellitus .