الفهرس 
O BESITY AND I NSULIN R ESISTANCEOnly 14 pages are availabe for public view
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Abstract
ABSTRACT
Background: Obesity is a major public health problem since it is a risk factor for the development of metabolic disorders such as type 2 diabetes, cardiovascular diseases and some malignancies with pandemic evolution. Type 2 diabetes mellitus (T2DM) is a serious menace to human health. Bile acids are the end products of cholesterol catabolism and play an important role in maintaining cholesterol homeostasis. Studies suggest that bile acids may regulate glucose tolerance, insulin sensitivity, and energy metabolism, Farnesoid X receptors (FXRs) play an important role in the regulation of bile acid synthesis and hepatic glucose metabolism. The FXR ligand Obeticholic acid (OCA) is a semisynthetic derivative of the bile acid chenodeoxycholic acid. Studies were done showing that treatment with OCA had improved insulin sensitivity and reduced markers of liver inflammation and fibrosis in patients with T2DM and nonalcoholic steatohepatitis (NASH) suggesting that bile acids may represent a potential therapeutic target for T2DM.
Aim of the Work: The aim of this study was to evaluate efficacy of Obeticholic acid in obese patients with prediabetes.
Patients and Methods: We conducted a randomized single blinded placebo controlled study on 82 overweight and obese patients with prediabetes at Ain shams University hospital outpatient clinic throughout 3 months. Patients with matched age and sex were divided into two groups (41 per group) through block randomization, group (A) who received Obeticholic acid 5 mg oral tablets daily and group (B) who received placebo in form of non-sweet capsules for 3 months, 3 follow up visits were done to assure compliance and check for any developed side effects.
Results: 82 patients of matched age and sex criteria who underwent block randomization into 2 equal groups, group(A) representing cases and group(B) the placebo controlled group, with 3 months’ regular follow up showed at end of treatment statistically significant difference in weight being lower in group (A) with p-value 0.004 with decreased parameters of glycemic profile (Fasting insulin, FPG, HOMA_IR, 2h PP, HbA1c) in group(A) with p-value< 0.001 except 2hpp which p-value is 0. 006. Also ALT was much decreased in group(A) with p-value <0.001. Lipid profile didn’t show significant difference between 2 groups except for TGs which deceased in follow up in group(A) with p-value <0. 001.It is also noted there was no statistically significant difference among control group between baseline and after end of treatment data.
Conclusion: Activation of FXR by OCA leads to increased insulin sensitivity in overweight and obese patients with insulin resistance and prediabetes. OCA also caused patients to lose weight.