Endocrine Abstracts

Introduction: Over the past decades diabetes emerged as epidemic dimension due to person’s genetic pre disposition and environmental condition. Despite significant advancement in the development of oral hypoglycemic agents, an ideal drug for treating T2DM and its complication is still a distant reality. Hyperglycemia has a variety of toxic effects, including elevated generation of ROS nitrosative stress and inflammation. This work attempts to explore the role of oxidative and nitrosative stress for the electron leakage in the mitochondria initiating cardiovascular disease pathogenesis. Apart from classical risk factors, elevated serum concentration of Hcy is closely associated with the increased risk of atherosclerosis. Here we report, how Hcy upregulation may be controlled in diabetic patients administered with hypoglycemic agent, metformin.

Methods: Metformin administered and placebo T2DM subjects participated in the study.

Results: Metformin treatment diminished ROS production, MMP, inflammation and restore nitric oxide production in diabetic subjects. Homocysteine level is higher in metformin administered patients (16.2+3.5 vs 14.5+2.9 μmol/l). Vitamin B12 level is greatly reduced in metformin treated patients compared to placebo (P=0.001). The mean values of Hcy level for genotypes (677C>T MTHFR)11, 12 and 22 are 14.76, 23.37 and 29.12 μmol/l respectively.

Conclusion: Greater reduction of ROS, AOPP, CRP and pentosidine level and restoration of NO from baseline were achieved in metformin administered patients, elucidating that metformin extends added protection to combat the disease pathogenesis. Metformin treatment balance mitochondrial homeostasis by normalizing the ion transport. Enhanced Hcy production is not related with metformin treatment rather it is a drug independent phenomena and depend greatly on polymorphism in MTHFR 677 C>T phenotype. These information will be beneficial for the emergence of new pharmacogenomic initiatives.

ROS generation (1a,1c-baseline,1b-metformin administered,1d-placebo) and hyperpolarisation of mitochondrial membrane (3a,3b,3e,3f-baseline,3c,3d-metformin administered 3g,3h-placebo) reduced in metformin administered subjects in comparison to placebo. Nitric oxide production (2a,2c-baseline,2b-metformin administered,2d-placebo) is restored in metformin treated subjects.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however, funding details unavailable.