In summary, patients with type 2 diabetes exhibited impaired endothelium-dependent vasodilation in vivo, elevated serum triglycerides, decreased LDL size, and normal antioxidant capacity. Of these parameters, LDL size was significantly correlated with endothelial function.

Background-It is unknown whether LDL particle size is, independent of other lipids and lipoproteins, associated with endothelial dysfunction in vivo. Methods and Results-We determined in vivo endothelial function in 34 healthy men by measuring forearm blood flow responses to intrabrachial artery infusions of acetylcholine (ACh, an endothelium-dependent vasodilator) and sodium nitroprusside (an endothelium-independent vasodilator). LDL peak particle size was measured with gradient gel electrophoresis. Men with small LDL particles (LDL diameter Յ25.5 nm, nϭ10) had a 39% lower blood flow response to ACh than men with large LDL particles (LDL diameter Ͼ25.5 nm, nϭ24, blood flow 6.9Ϯ3.6 versus 11.4Ϯ5.1 mL/dL ⅐ min, Pϭ0.006).

Abstract-A total of 75 in vivo endothelial function tests (intrabrachial artery infusions of endothelium-dependent[acetylcholine] and -independent [sodium nitroprusside] vasoactive agents) were performed in 18 type 2 diabetic patients (aged 58Ϯ2 years, body mass index 28.5Ϯ0.6 kg/m 2 , and fasting plasma glucose 229Ϯ11 mg/dL) and 27 matched normal subjects. These tests were performed before and 6 months after combination therapy with insulin and metformin and before and 6 months after metformin therapy only. Before insulin therapy, blood flow responses to acetylcholine (15 g/min) were significantly blunted in type 2 diabetic patients (7.5Ϯ0.7 mL ⅐ dL Ϫ1 ⅐ min Ϫ1) compared with normal subjects (11.6Ϯ0.9 mL ⅐ dL Ϫ1 ⅐ min Ϫ1 , PϽ0.01). During insulin therapy, the acetylcholine response increased by 44% to 10.8Ϯ1.6 mL ⅐ dL Ϫ1 ⅐ min Ϫ1 (PϽ0.05). Insulin therapy also significantly increased the blood flow responses to both low and high doses of sodium nitroprusside. We conclude that insulin therapy improves endothelium-dependent and -independent vasodilatation. These data support the idea that insulin therapy has beneficial rather than harmful effects on vascular function.

Although nateglinide and glibenclamide increase postprandial insulin secretion and attenuate hyperglycemia, they do not alleviate postprandial lipemia in subjects with type 2 diabetes and good glycemic control. Although small LDL particle size is associated with chronic hypertriglyceridemia, LDL size does not change during acute postprandial hypertriglyceridemia.

on behalf of the DAIS GroupBackground-The Diabetes Atherosclerosis Intervention Study showed that treatment with fenofibrate decreases progression of coronary atherosclerosis in subjects with type 2 diabetes. We determined whether on-treatment plasma lipid concentrations and LDL particle size contribute to the favorable effect of fenofibrate on the progression of coronary artery disease (CAD). Methods and Results-A total of 418 subjects with type 2 diabetes were randomly assigned to 200 mg micronized fenofibrate daily or placebo. The mean follow-up time was 39.6 months. LDL peak particle diameter (LDL size) was determined by polyacrylamide gradient gel electrophoresis from 405 subjects at baseline and at the end of the study.