title: A Link Between Hypoglycemia and Progression of Atherosclerosis in the Veterans Affairs Diabetes Trial (VADT).
abstract: OBJECTIVE
  To determine whether a link exists between serious hypoglycemia and progression of atherosclerosis in a substudy of the Veterans Affairs Diabetes Trial (VADT) and to examine whether glycemic control during the VADT modified the association between serious hypoglycemia and coronary artery calcium (CAC) progression.
  
  
  METHODS
  Serious hypoglycemia was defined as severe episodes with loss of consciousness or requiring assistance or documented glucose <50 mg/dL. Progression of CAC was determined in 197 participants with baseline and follow-up computed tomography scans.
  
  
  RESULTS
  During an average follow-up of 4.5 years between scans, 97 participants reported severe hypoglycemia (n = 23) or glucose <50 mg/dL (n = 74). Serious hypoglycemia occurred more frequently in the intensive therapy group than in the standard treatment group (74% vs. 21%, P < 0.01). Serious hypoglycemia was not associated with progression of CAC in the entire cohort, but the interaction between serious hypoglycemia and treatment was significant (P < 0.01). Participants with serious hypoglycemia in the standard therapy group, but not in the intensive therapy group, had ∼50% greater progression of CAC than those without serious hypoglycemia (median 11.15 vs. 5.4 mm(3), P = 0.02). Adjustment for all baseline differences, including CAC, or time-varying risk factors during the trial, did not change the results. Examining the effect of serious hypoglycemia by on-trial HbA1c levels (cutoff 7.5%) yielded similar results. In addition, a dose-response relationship was found between serious hypoglycemia and CAC progression in the standard therapy group only.
  
  
  CONCLUSIONS
  Despite a higher frequency of serious hypoglycemia in the intensive therapy group, serious hypoglycemia was associated with progression of CAC in only the standard therapy group.
authors.affiliation: Phoenix VA Health Care System, Phoenix, AZ aramesh.saremi@va.gov peter.reaven@va.gov.
authors.forename: Aramesh
authors.initials: A
authors.lastname: Saremi
authors.affiliation: Cooperative Studies Program Coordinating Center, Hines, IL.
authors.forename: Gideon D
authors.initials: GD
authors.lastname: Bahn
authors.affiliation: Phoenix VA Health Care System, Phoenix, AZ aramesh.saremi@va.gov peter.reaven@va.gov.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Reaven
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000097:blood / Q000000981:diagnostic imaging* / Q000209:etiology; D001786:Blood Glucose / Q000032:analysis; D003324:Coronary Artery Disease / Q000097:blood / Q000000981:diagnostic imaging* / Q000209:etiology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D003925:Diabetic Angiopathies / Q000097:blood / Q000000981:diagnostic imaging* / Q000209:etiology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007003:Hypoglycemia / Q000097:blood* / Q000209:etiology; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D061205:Vascular Calcification / Q000097:blood / Q000000981:diagnostic imaging* / Q000209:etiology; D014728:Veterans
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents