THE EFFECT OF EZETIMIBE ON GLYCEMIC PARAMETER IN IRAQI WOMEN WITH METABOLIC SYNDROME

Ali K. Hushi Allami 1 , Prof. Dr. Faruk H Al-Jawad 2 , Asst. Prof. Yaseen O.Yaseen 3 and M. Haider F. Shamikh Alsaedi 4 . 1. Al-Nahrain University/College of Medicine /Pharmacology Department. 2. ‎Al‎‏-Yarmook ‏University collegel / Pharmacology Department. 3. Missan University/College of Medicine / Medicine Department. 4. ‎Missan University/College of Pharmacy / Pharmacology Department. ...................................................................................................................... Manuscript Info Abstract ......................... ........................................................................ Manuscript History

Metabolic syndrome is multiple clinical component that leads development of Type 2 Diabetes Mellitus, atherosclerosis and various diseases. The study included 90 female with metabolic syndrome according to International Diabetic Federation (IDF) criteria. They divided into three groups (30 patients in each group) First group put on diet restriction and physical exercise, the second group put on metformin 750 mg extended release once daily while the third group given ezetimibe 10 mg tab plus diet restriction and physical exercise.The duration of study 12 weeks ,samples taken from each patients at zero time to determine baseline level and after 12 weeks including measurements of WC,BMI,FBS,FIHOMA-IRHbA1c ,TG and HDL. Results:-Show significant changes in the measured parameter in the first group while highly significant changes in ezetimibe and metformin group Conclusion:-From these noticeable changes in the patients taken ezetimibe we conclude that ezetimibe have effect in improving glycemic parameter in Iraqi metabolic syndrome women.

Introduction:-
The metabolic syndrome is a clustering of components including hyperglycemia/insulin resistance, obesity and dyslipidemia (Putnam, Shoemaker et al. 2012) . Metabolic syndrome also known as syndrome x, Reavansyndrome , insulin resistance syndrome andcrdiometabolic syndrome (Ninomiya,L'Italienetal.2004). Historically In 1988, Gerald Reaven hypothesized that insulin resistance could be the underlying factor conjugating this constellation of abnormalities, which called -syndrome X (Das 2010).

Inflammation and role of cytokines in insulin resistance
In the state of central obesity(increase in number and size of adipocyte), various inflammatory mediators(cytokines) like Tumar Necrosis Factor -alpha ,C-reactive protein are produced and involved in theproduction of insulin resistance (Wisse 2004).
Ezetimibe:-Ezitimibeinhibits intestinal and excreted in bile absorption of cholesterol also phytosterol (Sudhop, 2002). A transport protein, Niemann-Pick C1-like 1NPC1L1 which found in the apical of enterocyte of intestine also liver , is the target of the drug. It is effective in the absence of dietary cholesterol because it also inhibits reabsorption of cholesterol excreted in the bile (Katzung, Masters et al. 2009).
In animal studyEZM decrease fatty live r and improve insulin signaling (Jenkins, Toth et al. 2014). Also ezitimbe used to treat NAFL by decrease hepatic fat content(Ahmed, 2010 )

Patients and Method:-
In this study 90 patients with metabolic syndrome included in the study according to (IDF) criteria ,for each group 30 patients enrolled:-1. control group ,patients put only on diet restriction and physical exercise. 2. metformin group ,patients received metformin 750 mg extended release (gluophage XR) R formulationdiet orally once daily at night in addition to diet restriction and physical exercise. 3. Ezetimibe group, in which patients receive ezitimibe10mg tab orally 1hr before breakfast in addition to diet restriction and physical exercise.The following parameters measured for all participant starting from zero time(baseline level) and continued for 12 weeks,10 ml venous blood sampling and they should be fasting overnight for 12 hr. waist,Body Mass Index (BMI),FBS, FI, HOM-IR ,HbAlc, TG and HDL.

Results:-
Using paired t-test statistically for results analysis C and biliary cholesterol. The effect of ezetimibe on insulin resistance recognized by changes in fasting insulin and fasting blood sugar ,this effect produce changing in HOMA-IR and HbA1c, and this related to incease free fatty acid and TG elevation which lead to insulin resistance and hyperinsulinemia which vicious cycle, so treatment with ezetimibe lead to reduction in insulin level and fasting blood sugar . (Deushi, Nomura et al. 2007)hypothesized that ezetimibe could directly affect insulin signaling in liver, and showed that ezetimibe dramatically enhanced insulin signaling (i.e., phosphorylation of IR, IRS-1, and Akt-1) in hepatocyte in vitro on in in obese rat model of metabolic syndrome.

Conclusion:-
From this study,the obivous improving effect of ezetimibe on both lipid and hyperglycemic parameters of patient with metabolic syndrom.