Insulin therapy improves insulin-stimulated endothelial function in patients with type 2 diabetes and ischemic heart disease

Blunted insulin-stimulated endothelial function may be a mechanism for the development of atherothrombotic disease in type 2 diabetes, but it is unkno wn whether hypoglycemic drug therapy can modulate this abnormality. We stud ied patients with type 2 diabetes and stable ischemic heart disease (n = 28 ) and lean, healthy control subjects (n = 31). Forearm blood flow was measu red by venous occlusion plethysmography during dose-response studies of ace tylcholine (ACh) and sodium nitroprusside (SNP) infused into the brachial a rtery. In the patients and 10 healthy control subjects, ACh was repeated af ter intrabrachial infusion of insulin. Patients were restudied after 2 mont hs of insulin therapy with four daily subcutaneous injections (treatment gr oup, n = 19) or without hypoglycemic drug therapy (time control group, n = 9). Insulin infusion raised venous serum insulin in the forearm to high phy siological levels (133 +/- 14.6 mU/l in patients) with a minor increase in systemic venous serum insulin. This increased the ACh response by 149 +/- 4 7, 110 +/- 33, 100 +/- 45, and 106 +/- 44% during the four ACh doses in hea lthy control subjects (P < 0.0001) but had no effect in patients (P = 0.3). After 2 months, HbA(1c) in the treatment group had decreased from 10.0 +/- 0.4 to 7.5 +/- 0.2%. Although neither the ACh response (P = 0.09) nor the SNP response (P = 0.4) had changed significantly, insulin stimulation had a significant effect, as the ACh response increased by 58 +/- 25, 84 +/- 66, 120 +/- 93, and 69 +/- 36% (P = 0.0002). In the time control group, insuli n stimulation remained without effect after 8 weeks (P = 0.7). In conclusio n, insulin therapy partly restores insulin-stimulated endothelial function in patients with type 2 diabetes and ischemic heart disease.