Change in albuminuria and eGFR following insulin sensitization therapy versus insulin provision therapy in the BARI 2D study

Clin J Am Soc Nephrol. 2014 Jan;9(1):64-71. doi: 10.2215/CJN.12281211. Epub 2013 Oct 31.

Abstract

Background and objectives: 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.

Design, setting, participants & measurements: 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).

Conclusion: 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.

Trial registration: ClinicalTrials.gov NCT00006305.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Albuminuria / diagnosis
  • Albuminuria / drug therapy*
  • Albuminuria / etiology
  • Albuminuria / physiopathology
  • Biomarkers / blood
  • Biomarkers / urine
  • Coronary Artery Disease / complications
  • Creatinine / blood
  • Creatinine / urine
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetic Nephropathies / diagnosis
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / etiology
  • Diabetic Nephropathies / physiopathology
  • Disease Progression
  • Female
  • Glomerular Filtration Rate / drug effects*
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / therapeutic use*
  • Kidney / drug effects*
  • Kidney / physiopathology
  • Linear Models
  • Logistic Models
  • Male
  • Middle Aged
  • Odds Ratio
  • Risk Factors
  • Time Factors
  • Treatment Outcome

Substances

  • Biomarkers
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • hemoglobin A1c protein, human
  • Creatinine

Associated data

  • ClinicalTrials.gov/NCT00006305