Fenofibrate reduces inflammation in obese patients with or without type 2 diabetes mellitus via sirtuin 1/fetuin A axis

• This paper investigates serum sirtuin 1 levels in T2DM patients.
• Correlation between sirtuin 1 and fetuin A levels is outlined for the first time.
• Correlation between sirtuin 1 and (hs-CRP, IL-6) is also outlined.
• This paper proves that low serum siruin 1 levels are associated with T2DM.
• Fenofibrate can reduce complications of obesity and T2DM by increasing sirtuin 1.

AimsThe aim of the current study is to investigate the effect of fenofibrate alone and in combination with pioglitazone on serum sirtuin 1 and fetuin A of obese patients with Type 2 Diabetes Mellitus (T2DM).MethodsIntervention effect on inflammatory parameters was assessed before and after treatment. The study was conducted on 60 postmenopausal females of whom, only 44 patients completed the study. They were distributed as follows; obese patients without T2DM (n = 15) who administered fenofibrate (160 mg/day) once for 8 weeks, obese patients with T2DM (n = 15) who administered fenofibrate (160 mg/day) once for 8 weeks, obese patients with T2DM (n = 14) who administered fenofibrate (160 mg/day) and pioglitazone (15 mg/day) combination once for 8 weeks.We measured fasting plasma glucose, glycated hemoglobin (HbA1c), serum lipids. Inflammatory markers (high sensitivity C-reactive protein “hs-CRP”, interleukin-6 “IL-6”, fetuin A, and sirtuin 1) of patients were measured in serum using enzyme-linked immunoassay (ELISA) kits.ResultsSirtuin 1 levels in obese patients with T2DM were significantly lower than its levels in obese patients while fetuin A levels were significantly higher (P < 0.001). Fenofibrate, alone and in combination with pioglitazone, significantly decreased triacylglycerol, hs-CRP, IL-6, fetuin A and increased sirtuin 1 levels (P < 0.001) which suggests that it can be used to delay the complications of obesity and T2DM. There is a strong correlation between fetuin A, sirtuin 1, IL-6 and hs-CRP levels suggesting a shared common pathway.ConclusionsFenofibrate was shown to increase serum sirtuin 1 and decrease serum fetuin A levels in obese patients.Trial numberPACTR201407000856135