Insulin Resistance - Treatment Options
METFORMIN
Metformin has been shown to improve muscle insulin sensitivity measured with the euglycaemic insulin clamp in type 2 diabetics. Metformin also improves insulin sensitivity and normalises glycogen synthesis in the muscle in insulin resistant normoglycaemic first degree relatives of individuals with type 2 diabetes mellitus. Metformin may activate AMP kinase leading to enhanced basal and insulin stimulated glucose transport in muscle
Metformin improves hepatic insulin sensitivity. Basal HGP was decreased by 20% in T2DM treated with metformin- interestingly despite a reduction in fasting plasma insulin. Metformin does this by improving insulin receptor tyrosine phosphorylation and enhances glucose transport. Activation of AMP kinase in liver causes inhibition of hepatic glucose production and decreased expression of a number of genes involved in hepatic free fatty acid and VLDL synthesis. The VLDL synthesis reduction may also be partly mediated through a decrease in acetyl Co A carboxylase activity. All these could be involved in the efficacy of metformin in retarding the progression of IGT to T2DM as shown in the DPP study. Combating insulin resistance with decreased FFA and VLDL synthesis could explain the cardiovascular mortality reduction in obese diabetics demonstrated in the UKPDS.
Metformin improves hepatic insulin sensitivity. Basal HGP was decreased by 20% in T2DM treated with metformin- interestingly despite a reduction in fasting plasma insulin. Metformin does this by improving insulin receptor tyrosine phosphorylation and enhances glucose transport. Activation of AMP kinase in liver causes inhibition of hepatic glucose production and decreased expression of a number of genes involved in hepatic free fatty acid and VLDL synthesis. The VLDL synthesis reduction may also be partly mediated through a decrease in acetyl Co A carboxylase activity. All these could be involved in the efficacy of metformin in retarding the progression of IGT to T2DM as shown in the DPP study. Combating insulin resistance with decreased FFA and VLDL synthesis could explain the cardiovascular mortality reduction in obese diabetics demonstrated in the UKPDS.