OBJECTIVEIn mice, 4F, an apolipoprotein A-I mimetic peptide that restores HDL function, prevents diabetes-induced atherosclerosis. We sought to determine whether HDL function is impaired in type 2 diabetic (T2D) patients and whether 4F treatment improves HDL function in T2D patient plasma in vitro.RESEARCH DESIGN AND METHODSHDL anti-inflammatory function was determined in 93 T2D patients and 31 control subjects as the ability of test HDLs to inhibit LDL-induced monocyte chemotactic activity in human aortic endothelial cell monolayers. The HDL antioxidant properties were measured using a cell-free assay that uses dichlorofluorescein diacetate. Oxidized fatty acids in HDLs were measured by liquid chromatography–tandem mass spectrometry. In subgroups of patients and control subjects, the HDL inflammatory index was repeated after incubation with L-4F.RESULTSThe HDL inflammatory index was 1.42 ± 0.29 in T2D patients and 0.70 ± 0.19 in control subjects (P < 0.001). The cell-free assay was impaired in T2D patients compared with control subjects (2.03 ± 1.35 vs. 1.60 ± 0.80, P < 0.05), and also HDL intrinsic oxidation (cell-free assay without LDL) was higher in T2D patients (1,708 ± 739 vs. 1,233 ± 601 relative fluorescence units, P < 0.001). All measured oxidized fatty acids were significantly higher in the HDLs of T2D patients. There was a significant correlation between the cell-free assay values and the content of oxidized fatty acids in HDL fractions. L-4F treatment restored the HDL inflammatory index in diabetic plasma samples (from 1.26 ± 0.17 to 0.71 ± 0.11, P < 0.001) and marginally affected it in healthy subjects (from 0.81 ± 0.16 to 0.66 ± 0.10, P < 0.05).CONCLUSIONSIn patients with T2D, the content of oxidized fatty acids is increased and the anti-inflammatory and antioxidant activities of HDLs are impaired.

No abstract

Despite the evidence in experimental animal models that insulin, or GIK (glucose-insulin-potassium), improves left ventricular function and perfusion during both acute and chronic ischaemia, clinical studies have generated conflicting results. We tested the hypothesis that pretreatment with GIK attenuates the vascular and functional effects of stress-induced myocardial ischaemia in humans. Twenty-two patients with evidence of inducible myocardial ischaemia were enrolled; 11 patients with normal ventricular function underwent two dipyridamole echocardiography tests, and 11 with regional contractility defects from previous myocardial infarction were submitted to two ECG exercise tests combined with 201Tl myocardial perfusion scintigraphy; the tests were preceded by 60 min of either normal saline or an isoglycaemic GIK infusion. On a stress echocardiogram, a 30% reduction in the severity of ischaemia was observed. On ECG ergometry, GIK infusion slightly increased the time to ischaemia (+0.6 min, P=0.07); however, the higher workload (+8%, P=0.07) was achieved at a similar rate-pressure plateau. On scintigraphy, an increase in ischaemic segments (+48%, P<0.001) was imaged mainly at the expense of viable (but non-ischaemic) and non-viable segments, which were reduced by 60%. GIK affected stress-induced left ventricular underperfusion only marginally (GIK: 39.7+/-2.5 compared with saline: 35.4+/-2.2 units, P<0.05), but significantly improved its acute reversibility (-42+/-4 compared with -25+/-4%, P<0.001). We conclude that GIK pretreatment attenuates the effect of ischaemia on myocardial contractility, slightly improves exercise tolerance and causes a more rapid and diffuse recovery of post-ischaemic reperfusion.

ED, as detected by PAT in a population enriched with subjects at risk for CVD neither reflects the burden of classical risk factors (under treatment) nor the severity of atherosclerosis. Aside from central obesity and HDL cholesterol, most of the factors responsible for this ED remain unknown.

Physiological hyperinsulinemia has no effect on endothelium-dependent vasodilatation in conduit vessels of healthy individuals, but it induces a slight decline in endothelium-independent vasodilatation, which is entirely explained by the insulin-induced noradrenergic activation.