Effects of insulin and oral anti-diabetic agents on glucose metabolism, vascular dysfunction and skeletal muscle inflammation in type 2 diabetic subjects

Background To test potential differences between the actions of antidiabetic medications, we examined the effects of oral hypoglycaemic agents versus glargine-apidra insulin therapy in T2DM. Methods T2DM subjects were randomized to either oral hypoglycaemic agents (pioglitazone, metformin and glipizide, n = 9) or insulin therapy (n = 12) for 6 months. Carotid intimal media thickness, vascular reactivity (flow-mediated vasodilatation; percent change in brachial artery basal diameter post-ischaemia) and sublingual nitrate were measured with ultrasonography. Euglycemic hyperinsulinemic (80 mU/m(2)) clamp with [3]-3H-glucose and muscle biopsies were performed. Results Fasting plasma glucose (similar to 257 to similar to 124 mg/dL, oral hypoglycaemic agents and similar to 256 to similar to 142 mg/dL, IT) and HbA(1c) (similar to 10.3 to similar to 6.4%, OHA and similar to 10.7 to similar to 7.1%, IT) improved comparably. Endogenous glucose production (similar to 2.1 to similar to 1.7 mg/kg/min, oral hypoglycaemic agents and similar to 2.3 to similar to 2.0 mg/kg/min, insulin therapy) and endogenous glucose production suppression by insulin (similar to 0.4 to similar to 0.3 mg/kg min, oral hypoglycaemic agents and similar to 0.5 to similar to 0.7 mg/kg min, insulin therapy) were different. Total glucose disposal x 100 increased in the oral hypoglycaemic agents group (similar to 5.2 to similar to 8.1; p = 0.03), but not in insulin therapy (similar to 6.0 to similar to 5.4 mg/kg/min/mu U/mL x 100). OHA reduced CIMT (similar to 0.080 to similar to 0.068 cm; p < 0.05), whereas insulin therapy did not (similar to 0.075 to similar to 0.072 cm). After sublingual nitrate, brachial artery basal diameter increased in the OHA group (similar to 8.7 to similar to 18.2%), but not in insulin therapy (similar to 11.2 to similar to 15.0%; p < 0.02). Except for plasma adiponectin (similar to 7 to similar to 15, oral hypoglycaemic agents versus similar to 6 to similar to 10, IT), changes in inflammatory markers in the circulation and in muscle (I kappa B alpha, super-oxidase dismutase 2, monocyte-chemo-attractant protein 1, p-ERK and JNK) were equivalent. Conclusions Oral hypoglycaemic agents and insulin therapy treated patients achieved adequate glycemic control and the effects on circulating and muscle inflammatory biomarkers were similar, but only oral hypoglycaemic agents improved insulin sensitivity, vascular function and carotid intimal media thickness. These findings in a small sample suggest that the use of oral hypoglycaemic agents provides additional benefits to patients with T2DM. Copyright (C) 2011 John Wiley & Sons, Ltd.