Context: Dysregulation of glucose metabolism in metabolic syndrome (METS) is allegedly due to the disruption of insulin as the main pathway in cellular metabolism. Green tea and green coffee are known to have potential benefit in METS therapy. Aims: To evaluate the effect of therapy using decaffeinated green tea-green coffee extract as metformin's add-on in the risk factors of METS and its effect on the cardiac insulin-gene-related pathway, such as IRS1, PI3Kr1, and GLUT4. Methods: METS model rats were divided into five groups. The rats' level of body weight (BW), fasting blood glucose (FBG), triglycerides (TG), high-density lipoprotein (HDL), insulin (INS), and homeostatic model assessment for insulin resistance (HOMA-IR) were measured periodically. After nine weeks of treatment, the rats were euthanized, and the heart was isolated for measurement of IRS1, PI3Kr1, and GLUT4 gene expression by reverse-transcriptase polymerase chain reaction. Results: This study found that there was a decrease in BW, FBG, TG and an increase in HDL in METS model rats given therapy with metformin and green tea-green coffee extract (COMB) (p<0.0001). There is also improvement in insulin resistance by reducing HOMA-IR in the COMB group (p = 0.0434 for INS and p<0.0001 for HOMA-IR). This study found that IRS1, PI3K, and GLUT4 gene expression increased in the COMB group. The five groups differ significantly, with a p = 0.000. Conclusions: Therapy using a combination of decaffeinated green tea and green coffee extract as an add-on of metformin improved METS risk factor via a significant reduction in BW, FBG, TG, increasing HDL and improving insulin resistance. It also increased the IRS1, PI3Kr1, and GLUT4 gene expression as markers of cardiac insulin-gene-related pathways.
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