title: Change in albuminuria and eGFR following insulin sensitization therapy versus insulin provision therapy in the BARI 2D study.
abstract: OBJECTIVE
  In the Bypass Angioplasty Revascularization Investigation 2 Diabetes randomized trial, glycemic control with insulin-sensitization therapy was compared with insulin-provision therapy in patients with type 2 diabetes and coronary artery disease. This study examined differences in albumin excretion and renal function in the insulin-sensitization group versus the insulin-provision group over 5 years.
  
  
  METHODS
  In total, 1799 patients with measurements of creatinine and urine albumin/creatinine ratio at baseline and at least two follow-up visits were included. Management of BP, lipids, and lifestyle counseling was uniform. Progression of albuminuria was defined as doubling of baseline albumin/creatinine ratio to at least 100 mg/g or worsening of albumin/creatinine ratio status on two or more visits. Worsening renal function was defined as >25% decline in estimated GFR and annualized decline of >3 ml/min per 1.73 m(2) per year.
  
  
  RESULTS
  By 6 months and thereafter, the mean glycated hemoglobin levels were lower in the insulin-sensitization group compared with the insulin-provision group (P<0.002 for each time point; absolute difference=0.4%). Albumin/creatinine ratio increased over time in the insulin-sensitization group (P value for trend<0.001) and was stable in the insulin-provision group. Risk for progression of albumin/creatinine ratio was higher in the insulin-sensitization group compared with the insulin-provision group (odds ratio, 1.59; 95% confidence interval, 1.25 to 2.02; P=0.02). Over 5 years, albumin/creatinine ratio increased from 11.5 (interquartile range=5.0-46.7) to 15.7 mg/g (interquartile range=6.2-55.4) in the insulin-sensitization group (P<0.001) and from 12.1 (interquartile range=5.3-41.3) to 12.4 mg/g (interquartile range=5.8-50.6) in the insulin-provision group (P=0.21). Estimated GFR declined from 75.0±20.6 to 66.3±22.6 ml/min per 1.73 m(2) in the insulin-sensitization group (P<0.001) and from 76.1±29.5 to 66.8±22.1 ml/min per 1.73 m(2) in the insulin-provision group (P<0.001).
  
  
  CONCLUSIONS
  Over 5 years, despite lower glycated hemoglobin levels, the insulin-sensitization treatment group had greater progression of albumin/creatinine ratio compared with the insulin-provision treatment group. Decline in estimated GFR was similar.
authors.affiliation: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors.forename: Phyllis
authors.initials: P
authors.lastname: August
authors.forename: Regina M
authors.initials: RM
authors.lastname: Hardison
authors.forename: Fadi G
authors.initials: FG
authors.lastname: Hage
authors.forename: Oscar C
authors.initials: OC
authors.lastname: Marroquin
authors.forename: Janet B
authors.initials: JB
authors.lastname: McGill
authors.forename: Yves
authors.initials: Y
authors.lastname: Rosenberg
authors.forename: Michael
authors.initials: M
authors.lastname: Steffes
authors.forename: Barry M
authors.initials: BM
authors.lastname: Wall
authors.forename: Mark
authors.initials: M
authors.lastname: Molitch
mesh_terms: D000368:Aged; D000419:Albuminuria / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood / Q000652:urine; D003324:Coronary Artery Disease / Q000150:complications; D003404:Creatinine / Q000097:blood / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D003404:Creatinine; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; C517652:hemoglobin A1c protein, human