title: The effect of intensive glucose lowering on lipoprotein particle profiles and inflammatory markers in the Veterans Affairs Diabetes Trial (VADT).
abstract: OBJECTIVE
  Intensive 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.
  
  
  METHODS
  Standard 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.
  
  
  RESULTS
  INT 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.
  
  
  CONCLUSIONS
  INT 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.
authors.affiliation: Department of Medicine, Phoenix Veterans Affairs Health Care System, Phoenix, Arizona, USA. juraj.koska@va.gov
authors.forename: Juraj
authors.initials: J
authors.lastname: Koska
authors.forename: Aramesh
authors.initials: A
authors.lastname: Saremi
authors.forename: Gideon
authors.initials: G
authors.lastname: Bahn
authors.forename: Shizuya
authors.initials: S
authors.lastname: Yamashita
authors.forename: Peter D
authors.initials: PD
authors.lastname: Reaven
mesh_terms: D015415:Biomarkers; D001786:Blood Glucose / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000209:etiology; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000008:administration & dosage; D015850:Interleukin-6; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008687:Metformin / Q000008:administration & dosage; D008875:Middle Aged; D012307:Risk Factors; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D002784:Cholesterol; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D015850:Interleukin-6; D008074:Lipoproteins; D008687:Metformin; D000077154:Rosiglitazone; D045162:Thiazolidinediones
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