“Effect of Fenofibrate and Pioglitazone on Fetuin A and Sirtuin 1 in Obese Patients with Type 2 Diabetes Mellitus”

Abstract

Type 2 diabetes mellitus (T2DM) is a serious disease that can predispose to various complications especially when complicated with obesity. Those complications can lead to morbidity and mortality and can greatly affect the quality of life. These complications include diabetic nephropathy, retinopathy, neuropathy, stroke, microalbuminuria, Alzheimer’s disease and many others. Some inflammatory markers were identified to play a key role in diabetes and obesity- associated inflammation and can consequently lead to these complications. One of those biomarkers was found to be fetuin A. Other biomarkers were found to guard against inflammation and development of complications. The most important player in this category is sirtuin 1, which was found to be the Holy Grail that can guard against low and high-grade inflammations and has anti-cancer and anti-aging effects. Fenofibrate attracted researchers attention in recent years due to its antiinflammatory effects, which appeared to be independent from its hypolipidemic effects. The exact mechanism by which this anti-inflammatory effect takes place is still unknown. While the main and most disseminated use for pioglitazone is as a hypoglycemic drug, literature establishes pioglitazone as a powerful antiinflammatory drug that is directly involved in the expression of inflammatory biomarkers. Our aim was to investigate the potential protective effect that fenofibrate, alone and in combination with pioglitazone, can exert on the serum levels of sirtuin 1 and fenofibrate A and consequently on the development of complications Summary and Conclusion 93 associated with obesity and T2DM The effect of fenofibrate, alone and in combination with pioglitazone, on other well-established inflammatory markers like C-reactive protein (CRP) and interleukin-6 (IL-6) was also investigated together with the relation between all the assayed biomarkers. In order to fullfil our aim, this study was conducted on 44 subjects divided into the following three groups, all of them included only postmenopausal females: c) Group 1: consisted of 15 obese subjects without T2DM who were administered fenofibrate (160 mg) single dose per day for 8 weeks. d) Group 2: consisted of 15 obese subjects with T2DM who were administered fenofibrate (160 mg) single dose per day for 8 weeks. e) Group 3: consisted of 15 obese subjects with T2DM who were administered fenofibrate (160 mg) single dose and pioglitazone (15 mg) single dose per day for 8 weeks. Main outcome measures: Before and after treatment, we measured fasting plasma glucose, glycated hemoglobin (HbA1c), serum lipids. Serum inflammatory markers (hs-CRP, IL-6, fetuin A, and sirtuin 1) were assessed for all patients using enzyme-linked immunoassay (ELISA) commercial kits. Results of the current study can be summarized as follows: (1) Decreased sirtuin 1 serum levels were observed in obese subjects with T2DM when compared to obese subjects without T2DM. (2) Moreover, there was a significant increase in fetuin A serum levels in obese subjects with T2DM when compared to obese subjects without T2DM. This shows that T2DM is responsible for elevated fetuin A and lower sirtuin 1 levels.