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Abstract
Insulin resistance can be the important mechanism by which obesity leads to the development of type II diabetes and increased risk of atherosclerotic diseases. Insulin resistance is present years before the onset of diabetes and may predict the onset of diabetes.
Insulin resistance leads to endothelial dysfunction through the frequent association with traditional cardiovascular risk factors and through some more direct novel mechanisms.
Nitric oxide is the key endothelium-derived relaxing factor that plays a pivotal role in the regulation of vascular tone and vasomotor function.
The proinflammatory cytokine TNF-α may be at the center of the processes underlying the insulin resistance, having effects on proinsulin-insulin conversion, on endothelium in various tissues, on coagulation, and on multiple additional abnormalities of the insulin resistance and potentially underlying the association between insulin resistance and vascular disease.
Intercellular adhesion molecule-1 (ICAM-1) is expressed by endothelial and other cell types and participates in inflammation and atherosclerosis ICAM-1 plays an important role in the recruitment of immune cells during the development of atherosclerotic plaque.
To give an insight into the possible relationship between insulin resistance and each of endothelial activation and inflammatory markers, and further development of atherosclerosis, we measured circulating level of nitric oxide, TNF-α, and ICAM-I in insulin resistant obese subjects and insulin resistant diabetic subjects in relation to HOMA index and correlated with CA-IMT as a marker of atherosclerosis.
This work included 70 subjects and patients. Subjects were divided into the following groups:
I. The control group (Group I):
It comprises 20 healthy subjects (12 males and 8 females). They were non obese, non diabetic, and normotensive.
II. The insulin resistance diabetic group (Group II):
It includes 30 patients with type II diabetes mellitus (16 males and 14 females). They were non obese and normotensive.
II. The insulin resistance obese group (Group III):
It consists of 20 obese first degree relatives of type II (9 males and 11 females). All of them were non diabetic.
Research investigation:
1. Determination of fasting plasma glucose.
2. Estimation of glycohemoglobin (HbA1c) in blood.
3. Measurement of serum s-ICAM-1 by ELIZA.
4. Quantification of serum TNF-α by ELIZA.
5. Estimation of fasting serum insulin by radioimmunoassay.
6. Measurements of insulin resistance by homeostasis model assessment (HOMA) index.
8. Determination of nitric oxide by Grisse method.
9. Anthropometric measures as BMI.
10. Ultrasonographic measurements of carotid intimal-medial thickness (CA-IMT).
The following results were obtained:
There was a significant increase in HOMA index in the insulin resistant diabetic group and insulin resistant obese group when compared with the control group. But there was no significant difference in the HOMA index between the diabetic group when compared with the obese group. There was a significant decrease in the NO in the diabetic group and obese group when compared with the control group. While there was insignificant difference between obese and diabetic groups.Negative significant correlation between NO and insulin resistance in diabetic group was detected. While a negative insignificant correlation between NO and insulin resistance in obese group.This research detected a significant negative correlation between CA-IMT and NO in diabetic group and an insignificant negative correlation between CA-IMT and NO in obese group.