A study of effect of insulin therapy on the endothelial dysfunction in the type II diabetic patients at tertiary health care centre

Abstract               Background: Diabetes is an independent risk factor for cardiovascular disease¹. Hyperglycemia² and insulin resistance Aims and Objectives: To Study effect of insulin therapy on the endothelial dysfunction in the type II diabetic patients at tertiary health care centre. Methodology:  This was a cross-sectional study carried out in the department Medicine of a tertiary health care centre in the type II diabetic patients during the one year period i.e. June 2017 to June 2018 , all the diabetic patients either on oral hypoglycemic drugs or oral hypoglycemic drugs were randomly selected, oral hypoglycemic drugs (OH) were 35 and oral hypoglycemic drugs and insulin(OH+I) 15, The statistical analysis done by unpaired t-test and analyzed by SPSS 19 version.  Result:  In our study we have seen that the majority of the patients were in the age group of 50-60 were 27.78% followed by 40-50 were 25.93%, >60 were 20.37%, 30-40 were 16.67%, 20-30 were 9.26%. The majority of the patients were Male i.e. 59.26% and Female were 40.74% . The patients in the Oral Hypoglycemic (OH) were 35 (64.81) and OH+ Insulin (OH + I) were 19 (35.19). The levels of MDA   (Mean ±SD)   were significantly lower i.e. 1.93 ± 0.92 and 3.12 ± 1.34 (t=3.36,df=48,p<0.0001),  FRAP  (Mean ±SD) -0.82 ± 0.38   and 0.45 ± 0.15  (t=4.56,df=48,p<0.001),  NO   (Mean ±SD) - 18.23 ± 3.42    and 13.34 ± 4.21   (t=5.24,df=48,p<0.001) respectively in the OH  and  OH + I   groups. Conclusion:  It can be concluded from our study that the patients on the insulin treatment were significantly less NO level and more in the oxidative stress, enzymes like FRAP and MDA level are low. Hence it indicated that insulin treatment group is having more endothelial dysfunction and more oxidative stress.

Key Word: oral hypoglycemic drugs (OH), FRAP, MDA, oxidative stress.

INTRODUCTION

Diabetes is an independent risk factor for cardiovascular disease¹. Hyperglycemia² and insulin resistance³ are the characteristics of type 2 diabetes most often attributed a causal relation with atherosclerosis. Their possible influence on vascular endothelial function may explain the particular risk of diabetic vascular disease, because endothelial dysfunction is one of the earliest events identified in the pathogenesis of atherosclerosis and thrombosis⁴. Impaired endothelium-dependent vasodilation is associated with insulin resistance⁵, and this association may be represented in the vasculature by abnormalities in insulin stimulated endothelial function. Thus, insulin induces vasorelaxation mediated by endothelium-derived nitric oxide (NO) in isolated rat skeletal muscle arterioles⁶, and in healthy humans, insulin has a stimulating effect on NO dependent basal blood flow^7,8 and on agonist-stimulated endothelium-dependent vasodilation^9,10. However, these effects are blunted in patients with obesity-associated insulin resistance or type 2 diabetes^10,12

METHODOLOGY

This was a cross-sectional study carried out in the department Medicine of a tertiary health care centre in the type II diabetic patients during the one year period i.e. June 2017 to June 2018, all the diabetic patients either on oral hypoglycemic drugs and insulin drugs were randomly selected with the written  and explained consent during the one year so during the one year the treatment group selected for study were oral hypoglycemic drugs (OH) were 35 and oral hypoglycemic drugs and insulin(OH+I) 15 . All the patients in the study were undergone biochemical analysis regarding the enzymes responsible for the endothelial functioning i.e. MDA was manually estimated by thiobarbituric acid reactive substances (TBARS) method and antioxidant capacity was estimated as FRAP. NO was measured by using kinetic cadmium reduction method. The statistical analysis done by unpaired t-test and analyzed by SPSS 19 version.

RESULT                                  

Table 1: Distribution of the patients as per the age

The majority of the patients were in the age group of 50-60 were 27.78% followed by 40-50 were 25.93%, >60 were 20.37%, 30-40 were 16.67%, 20-30 were 9.26%.

Table 2: Distribution of the patients as per the sex

The majority of the patients were Male i.e. 59.26% and Female were 40.74%

Table 3: Distribution of the patients as per the treatment group

The patients in the Oral Hypoglycemic (OH) were 35 (64.81) and OH+ Insulin (OH + I) were 19 (35.19).

Table 4: Distribution of the patients as per the endothelial function

The levels of MDA (Mean ±SD) significantly lower i.e. 1.93 ± 0.92 and 3.12 ± 1.34 (t=3.36,df=48,p<0.0001),  FRAP  (Mean ±SD) -0.82 ± 0.38   and 0.45 ± 0.15  (t=4.56,df=48,p<0.001),  NO   (Mean ±SD) - 18.23 ± 3.42    and 13.34 ± 4.21   (t=5.24,df=48,p<0.001) respectively in the OH  and  OH + I   groups.

DISCUSSION

Type 2 diabetic subjects are more prone to cardiovascular diseases in the worldwide population. Even though the subjects undergo anti-diabetic treatment, the complications are more in these cases. Insulin is not a treatment for type 2 diabetic subjects, but in uncontrolled condition, insulin is required. Earlier studies have been reported that hyperinsulin emia itself is a risk factor in causing vascular complications.^13,14,15 However, endothelial dysfunction is an initial stage of developing vascular complications. Endothelial dysfunction (ED) is an imbalance between vasoconstriction and vasodilatation in vascular tissues. Endothelial function is mainly regulated by endothelial-1, NO, and prostacyclin.¹⁶ The most common soluble markers to analyze endothelial function include NO, vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), E-selectin and von Willebrand factor (vWF) etc.^17,18 Among these, NO is an important marker to assess vascular endothelial function and its impairment. Reduced availability of nitric oxide indicates impaired endothelial function and also an initiator for the development and progression of atherosclerosis.¹⁹ In our study we have seen that the majority of the patients were in the age group of 50-60 were 27.78% followed by 40-50 were 25.93%, >60 were 20.37%, 30-40 were 16.67%, 20-30 were 9.26%. The majority of the patients were Male i.e. 59.26% and Female were 40.74%. The patients in the Oral Hypoglycemic (OH) were 35 (64.81) and OH+ Insulin (OH + I) were 19 (35.19). The levels of MDA   (Mean ±SD)   were significantly lower i.e. 1.93 ± 0.92    and 3.12 ± 1.34 (t=3.36,df=48,p<0.0001),  FRAP  (Mean ±SD) -0.82 ± 0.38   and 0.45 ± 0.15  (t=4.56,df=48,p<0.001),  NO   (Mean ±SD) - 18.23 ± 3.42    and 13.34 ± 4.21   (t=5.24,df=48,p<0.001) respectively in the OH  and  OH + I   groups. These findings are similar with Siva P Palem ²⁰ et al they found a significantly lower level of NO in OHDI group than OHD group and healthy controls. Slightly lower level of NO was observed in subjects with OHD alone compared to healthy control.

CONCLUSION

It can be concluded from our study that the patients on the insulin treatment were significantly less NO level and more in the oxidative stress, enzymes like FRAP and MDA levels are low. Hence it indicated that insulin treatment group is having more endothelial dysfunction and more oxidative stress.

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