Serum endothelin-1 in obesity: the effect of weight reduction

Recent studies have shown that endothelin-1 [ET-1] is implicated in avariety of pathological conditions including obesity, diabetes mellitus, essential hypertension and astherosclerosis. The aim of the present work was to examine the relationship between ET-1 with some anthropometric and metabolic variables characteristic of insulin resistance syndrome The effects of energy restriction either alone or in combination with metformin on serum ET-1, some anthropometric and metabolic variables characteristic of insulin resistance syndrome were also studied. The study included 40 obese female patients with age ranging from 47 to 53 years. They were divided into two groups. Group I included 30 obese female patients with either IGT or newly diagnosed type 2 diabetes with insulin resistance syndrome, group II included 10 obese females without IRS and were taken as a control. Both groups were matched in age, and BML. Patients in group I was divided into two groups. Group I received LCD [1200 kcal/day] alone, Group 2 received low calorie diet plus metformin ,[850mg twice daily]. The study continued for 6 months. All patients were subjected to thorough history taking and clinical examination stressing on weight, height, BMI, WHR and blood pressure. Fasting 2 hour postprandial plasma glucose, HBAIc, HOMA-IR lipogram and ET-1 were also assessed. These parameters were also evaluated after dietary intervention and metformin treatment. From this study, we found that patients with IRS were obese, BMI [33.57 +/- 1.7] with significant increase in WHR compared to obese controls, Also there was significant increase in SBP, DBP, fasting postprandial plasma glucose, fasting insulin insulin, HOMA-IR, total cholesterol, LDL-C, TG and significant reduction in HDL-C in obese patients with IRS in comparison with obese controls. Also resum ET-1 were significantly increased in obese patients with IRS compared to controls. Also, there was significant correlations between serum ET-1 and some parameters present in IRS e.g. BMI, WHR, SBP, DI3P, fasting and postprandial plasma glucose, HbAlc, fasting insulin, HOMA-IR and lipid profile. The following results were obtained after dietary intervention and metformin treatment: Significant decrease in BMI, WHR, blood pressure, fasting, postprandial blood glucose, HbAlc, HOMA-IR, total cholesterol, LDL-c in both groups with more reduction in LCD+metformin group HDL-C also significantly increased in both groups with more significant increase in LCD+metformin group. ET-1 were significantly reduced in LCD metformin group. We can conclude that insulin resistance syndrome is a constellation of clinical and biochemical anomalies clustering in subjects with upper body fat distribution. ET-1 also may be involved in. the pathogenesis of many components of IRS e.g. insulin resistance, hypertension dyslipidaemia. Insulin ET-1 production and ET-1 decreased insulin sensitivity so, ET-1 may play another key underlying role in IRS through its close relation with insulin resistance. LCD and metformin are effective and safe measures in the management of obese patients with IRS as they improve many components of this syndrome. Their effects may be explained partly by their effect on insulin resistance and plasma ET-1

Subclinical hypothyrodism, is it mild thyroid failure to treat or acompansated state?

Subclinical hypothyroidism "SCH" affects of general 5-15% of general population, however the need of lifelong L-thyroxin "LT4" therapy is still controversial. As the serum lipids and myocardium are main targets of thyroid hormone action, we investigate whether SCH induces serum lipids and cardiovascular alterations and we evaluate the effect of L-T4 replacement therapy on clinical symptoms, serum lipids and echocardiographic parameters in patients with SCH. We studied 20 premenopausal women with subclinical hypothyroidism with age ranging from 18-45 years and 20 premenopausal euthyroid women as control group matched to SCH patients for age and body mass index [BMI]. Patients were randomly classified into two sub-group each included 10 women, one group received L-T4 therapy and the other group receive placebo for the same period. All were subjected to through clinical assessment, assessment of tissues hypothyroidism using zulewski Score, serum total cholesterol [TC] law density lipoprotein cholesterol "LDL-C", high density lipoprotein cholesterol "HDL-C" and triglycerides "TG" also echocardiography 2D, M-Mode and Doppler study. Our study revealed significant elevation of total cholesterol and LDL-C in SCH patients than control and after L-T4 therapy, there was significant improvement of both clinical score and serum lipids. Also SCH patients had significantly higher isovolumetric relaxation time "IVRT' and peak A value than control moreover preejection period "PEP" as well as PEP/ET were significantly longer in patients than controls and these changes fully reversed after L-T4 therapy. SCH patients has negative clinical metabolic and echocardiographic effects and these negative effects are fully reversible after LT4 therapy. Therefore subclinical hypothyroidism is better considered a condition of minimal tissues hypothyroidism than a compensated state. Indeed, L-T4 replacement therapy should be advised for these patients with the aim to prevent both the progression to frank hypothyroidism and the development of clinically significant myocardial dysfunction