The Effect of Intensive Glucose Lowering on Lipoprotein Particle Profiles and Inflammatory Markers in the Veterans Affairs Diabetes Trial (VADT)

Abstract

OBJECTIVEIntensive glucose-lowering therapy (INT) did not reduce macrovascular events in the recent randomized trials, possibly because it did not improve or worsen other traditional or novel cardiovascular risk factors.RESEARCH DESIGN AND METHODSStandard plasma lipids, cholesterol content of lipoprotein subfractions, and plasma inflammatory and prothrombotic markers were determined in a subgroup of the Veterans Affairs Diabetes Trial (VADT) participants (n = 266) at baseline and after 9 months of INT or standard therapy.RESULTSINT lowered glycated hemoglobin (by a median of 2% vs. a median of 0.7% by standard treatment; P < 0.0001); increased BMI (4 vs. 1%; P < 0.001), total HDL (9 vs. 4%; P < 0.05), HDL2 (14 vs. 0%; P = 0.009), LDL2 (36 vs. 1%; P < 0.0001), and plasma adiponectin (130 vs. 80%; P < 0.01); and reduced triglycerides (−13 vs. −4%; P = 0.02) and small, dense LDL4 (−39 vs. −13%; P < 0.001), but had no effect on levels of plasma apolipoproteins B-100 and B-48, C-reactive protein, interleukin-6, lipoprotein-associated phospholipase A2, myeloperoxidase, fibrinogen, and plasminogen activator inhibitor 1. Incident macrovascular events were associated with baseline interleukin-6 (hazard ratio per each quartile increase 1.33 [95% CI 1.06–1.66]), total LDL (1.25 [1.01–1.55]), apolipoprotein B-100 (1.29 [1.01–1.65]), and fibrinogen (1.26 [1.01–1.57]) but not changes in any cardiovascular risk factors at 9 months.CONCLUSIONSINT was associated with improved adiponectin, lipid levels, and a favorable shift in LDL and HDL subfractions after 9 months. These data suggest that the failure of INT to lower cardiovascular outcomes occurred despite generally favorable changes in standard and novel risk factors early in the study.

Disialylated apolipoprotein C-III proteoform is associated with improved lipids in prediabetes and type 2 diabetes

“…ACT NOW participants included more by the Friedewald equation. In the RACED study samples, standard lipids and lipoprotein subclass concentrations were measured by the Vertical Auto Profile II method (VAP II; Atherotech, Inc., Birmingham, AL), as previously described (32). Total plasma apoC-III concentrations were measured in baseline samples from the RACED study by sandwich ELISA using an antiapoC-III antibody (identical Academy Biomedical antibody as in the MSIA) and apoC-III protein standard obtained from Academy Biomedical, as previously described (33).…”

Update on Prevention of Cardiovascular Disease in Adults With Type 2 Diabetes Mellitus in Light of Recent Evidence

“…Thus, targeting changes in LDL size to reduce CVD risk is not indicated. 186 Moreover, although an elevated LDL-C level generally is not recognized as the major lipid abnormality in patients with type 2 diabetes mellitus, clinical trials amply demonstrate that statin treatment will reduce the risk for major coronary events.…”

Association of Blood Glucose Control and Lipids With Diabetic Retinopathy in the Veterans Affairs Diabetes Trial (VADT)

“…In addition, another VADT substudy examined blood from a subset of patients during the first year of the trial. They also reported more favorable changes in lipid fractions in the cohort of patients assigned to the INT arm (37). If one assumes that what is damaging to the macrovasculature is damaging to the microvasculature as well, the interaction between INT and lipids on DR progression may be because INT reduces the atherogenicity of lipid particles.…”