RESUMEN
Metformin, a cheap and safe biguanide derivative, due to its ability to influence metabolism, is widely used as a first-line drug for type 2 diabetes (T2DM) treatment. Therefore, the aim of this review was to present the updated biochemical and molecular effects exerted by the drug. It has been well explored that metformin suppresses hepatic glucose production in both AMPK-independent and AMPK-dependent manners. Substantial scientific evidence also revealed that its action is related to decreased secretion of lipids from intestinal epithelial cells, as well as strengthened oxidation of fatty acids in adipose tissue and muscles. It was recognized that metformin's supra-therapeutic doses suppress mitochondrial respiration in intestinal epithelial cells, whereas its therapeutic doses elevate cellular respiration in the liver. The drug is also suggested to improve systemic insulin sensitivity as a result of alteration in gut microbiota composition, maintenance of intestinal barrier integrity, and alleviation of low-grade inflammation.
RESUMEN
BACKGROUND: Research evidence indicates that vitamin D deficiency is involved in the pathogenesis of insulin resistance (IR) and associated metabolic disorders including hyperglycemia and dyslipidemia. It also suggested that vitamin D deficiency is associated with elevated levels of oxidative stress and its complications. Therefore, the aim of our study was to determine the effect of vitamin D supplementation on DNA damage and metabolic parameters in vitamin D deficient individuals aged >45 with metabolic disorders. Material and Methods: Of 98 initially screened participants, 92 subjects deficient in vitamin D were included in the study. They were randomly assigned to the following group: with vitamin D supplementation (intervention group, n = 48) and without supplementation (comparative group, n = 44). The patients from both groups were divided into two subgroups according to the presence or absence of type 2 diabetes (T2DM). The intervention group was treated with 2000 International Unit (IU) cholecalciferol/day between October and March for three months. At baseline and after three-month supplementation vitamin D concentration (25-OH)D3 and endogenous and oxidative DNA damage were determined. In addition, fast plasma glucose (FPG), fasting insulin, HbA1c and lipid fraction (total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), triglyceride (TG)), as well as anthropometric measurements (weight, height) were gathered. The following IR-related parameters were calculated Homeostatic Model Assesment - Insulin Resistance (HOMA-IR) and TG/HDL ratio. Results: Three-month vitamin D supplementation increased the mean vitamin D concentration to generally accepted physiological level independently of T2DM presence. Importantly, vitamin D exposure decreased the level of oxidative DNA damage in lymphocytes of patients of intervention group. Among studied metabolic parameters, vitamin D markedly increased HDL level, decreased HOMA-IR, TG/HDL ratio. Furthermore, we found that HbA1c percentage diminished about 0.5% in T2DM patients supplemented with vitamin D. Conclusion: The current study demonstrated that daily 2000I U intake of vitamin D for three months decreased the level of oxidative DNA damage, a marker of oxidative stress, independently on T2DM presence. Furthermore, vitamin D reduced metabolic parameters connected with IR and improved glucose and lipid metabolism. Therefore, our results support the assertion that vitamin D, by reducing oxidative stress and improving of metabolic profile, may decrease IR and related diseases.