title: Effect of glycemic control on early diabetic renal lesions. A 5-year randomized controlled clinical trial of insulin-dependent diabetic kidney transplant recipients.
abstract: OBJECTIVE
  To determine whether optimized glycemic control in type I diabetic recipients of renal allografts will prevent or delay diabetic renal lesions in the allograft.
  
  
  METHODS
  Prospective, controlled, and randomized trial of glycemic control in an inception cohort of type I diabetic renal allograft recipients. The experimental group underwent maximized glycemic control, and the standard group was treated in the same way as other patients in the transplant clinic. Patients underwent baseline (before transplant) and 5-year posttransplant allograft biopsies.
  
  
  METHODS
  University of Minnesota Hospital and Clinic and the Clinical Research Center and Hennepin County Medical Center, Minneapolis.
  
  
  METHODS
  Type I diabetics with terminal diabetic renal failure undergoing renal transplantation. Forty-eight patients randomized to maximized or standard control completed the trial.
  
  
  METHODS
  Subcutaneous insulin given several times a day or continuously (maximized group) and once or twice each day (standard group) was used throughout the trial. A significant difference for hemoglobin A1 level was maintained (mean +/- SD: standard, 0.117 +/- 0.013; maximized, 0.096 +/- 0.016; P < 0.001).
  
  
  RESULTS
  The primary end point of this trial was the difference between the groups in renal glomerular mesangial expansion as determined by electron microscopy.
  
  
  RESULTS
  There was a more than twofold increase in the volume fraction of mesangial matrix per glomerulus in the standard group (mean +/- SD, 0.043 +/- 0.034) compared with the maximized group (0.019 +/- 0.038; P = .024). The threefold increase in arteriolar hyalinosis, the greater widening of the glomerular basement membrane, and increase of volume fraction of the total mesangium in the patients who received standard treatment all approached significance (P = .10 or less). The incidence of severe hypoglycemic episodes was greater in the maximized group (1.7 per patient per year) than in the standard treatment group (< 0.1 per patient per year; P < .001).
  
  
  CONCLUSIONS
  This trial indicates a causal relationship between hyperglycemia and an important lesion of diabetic nephropathy, mesangial matrix expansion, in renal allografts transplanted into diabetic recipients. In addition, the results with other lesions central to the development of diabetic nephropathy support the major conclusion.
authors.affiliation: Department of Medicine (Division of Endocrinology and Metabolism), University of Minnesota Medical School, University of Minnesota Hospital, Minneapolis.
authors.forename: J
authors.initials: J
authors.lastname: Barbosa
authors.forename: M W
authors.initials: MW
authors.lastname: Steffes
authors.forename: D E
authors.initials: DE
authors.lastname: Sutherland
authors.forename: J E
authors.initials: JE
authors.lastname: Connett
authors.forename: K V
authors.initials: KV
authors.lastname: Rao
authors.forename: S M
authors.initials: SM
authors.lastname: Mauer
mesh_terms: D000328:Adult; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001707:Biopsy, Needle; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications / Q000601:surgery*; D003928:Diabetic Nephropathies / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D004334:Drug Administration Schedule; D005260:Female; D005920:Glomerular Mesangium / Q000473:pathology / Q000648:ultrastructure; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000150:complications / Q000517:prevention & control*; D007003:Hypoglycemia / Q000517:prevention & control; D007165:Immunosuppression Therapy; D007328:Insulin / Q000008:administration & dosage* / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000473:pathology / Q000502:physiology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D000959:Antihypertensive Agents; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007328:Insulin