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Effects of omega-3 in type 2 diabetic patients – new mechanisms for targeted therapy (concluded project)


Minor dietary components with proven biological effects play an important role in the complex treatment strategy of obesity-related diseases, however our knowledge regarding the mechanisms of their action is relatively limited. The aim of this project is to identify novel mechanisms behind the beneficial effects of omega-3 in patients with type 2 diabetes mellitus (DM), i.e. the only dietary component with clearly demonstrated beneficial effects on dyslipidemia and cardiovascular mortality and morbidity in the diabetic patients. 

Based on our results in a mouse model of metabolic syndrome (Kuda et al. 2009. DiabetologiaHorakova et al. 2012. PLoS OneKus et al. 2011. PLoS One), and by taking advantage of available clinical  data and biological materials (plasma, adipose and muscle tissue) collected during the previous randomized, placebo-controlled, intervention study in DM patients treated with metformin (6-month-long intervention; groups, n=15: placebo, omega-3, placebo+pioglitazone, omega-3+pioglitazone), we focus on:

  1. novel regulatory mechanisms (adipokines/cytokines, lipid mediators, endocannabinoids), through which omega-3 affect lipid metabolism and mitigate low-grade chronic inflammation and accumulation of adipose tissue
  2. mechanisms, which differentiate the effects of  omega-3 and pioglitazone on insulin sensitivity in patients; and possible improvements of glucose homeostasis in response to a modulation of incretin system by omega-3
  3. identification of novel markers of sensitivity to treatment, based on targeted metabolomic analysis in plasma of patients.

 

Project will help to understand the mechanisms, by which omega-3  normalize lipid metabolism and mitigate low-grade inflammation in patients with DM, specifically in those treated with metformin (or metformin + pioglitazone). The results will help to

  1. rationalize the use of omega-3 in the treatment of DM patients and in the prevention of cardiovascular diseases in these patients
  2. establish a personalized treatment of the patients.

 

Supported by the Ministry of Health of the Czech Republic (NT13763-4;  2012-2015; PI: Jan Kopecký, MD, DSc;  collaborator: prof. Terezie Pelikánová, MD, DSc, Diabetes Centre, IKEM, Prague).