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 anti-diabetic 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/m²) clamp with [3]-3H-glucose and muscle biopsies were performed. Results: Fasting plasma glucose (~257 to ~124 mg/dL, oral hypoglycaemic agents and ~256 to ~142 mg/dL, IT) and HbA_1c (~10.3 to ~6.4%, OHA and ~10.7 to ~7.1%, IT) improved comparably. Endogenous glucose production (~2.1 to ~1.7 mg/kg/min, oral hypoglycaemic agents and ~2.3 to ~2.0 mg/kg/min, insulin therapy) and endogenous glucose production suppression by insulin (~0.4 to ~0.3 mg/kg min, oral hypoglycaemic agents and ~0.5 to ~0.7 mg/kg min, insulin therapy) were different. Total glucose disposal × 100 increased in the oral hypoglycaemic agents group (~5.2 to ~8.1; p = 0.03), but not in insulin therapy (~6.0 to ~5.4 mg/kg/min/μU/mL × 100). OHA reduced CIMT (~0.080 to ~0.068 cm; p < 0.05), whereas insulin therapy did not (~0.075 to ~0.072 cm). After sublingual nitrate, brachial artery basal diameter increased in the OHA group (~8.7 to ~18.2%), but not in insulin therapy (~11.2 to ~15.0%; p < 0.02). Except for plasma adiponectin (~7 to ~15, oral hypoglycaemic agents versus ~6 to ~10, IT), changes in inflammatory markers in the circulation and in muscle (IκBα, 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.