Effect of glycemic control on early diabetic renal lesions

A 5-year randomized controlled clinical trial of insulin-dependent diabetic kidney transplant recipients

Jose Barbosa, Michael W. Steffes, David E R Sutherland, John E. Connett, K. Venkateswara Rao, S. Michael Mauer

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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. Design. - 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. Setting. - University of Minnesota Hospital and Clinic and the Clinical Research Center and Hennepin County Medical Center, Minneapolis. Patients. - Type I diabetics with terminal diabetic renal failure undergoing renal transplantation. Forty-eight patients randomized to maximized or standard control completed the trial. Intervention. - 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<.001). Main Outcome. - 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.

Original languageEnglish (US)
Pages (from-to)600-606
Number of pages7
JournalJournal of the American Medical Association
Volume272
Issue number8
DOIs
StatePublished - Aug 24 1994

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Randomized Controlled Trials
Insulin
Kidney
Allografts
Diabetic Nephropathies
Transplants
Glomerular Basement Membrane
Transplant Recipients
Hypoglycemic Agents
Hyperglycemia
Kidney Transplantation
Renal Insufficiency
Electron Microscopy
Hemoglobins
Biopsy
Control Groups
Incidence
Therapeutics
Research

Cite this

@article{fbdedbefb0d14351835a24c19eb0c4e5,
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. Design. - 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. Setting. - University of Minnesota Hospital and Clinic and the Clinical Research Center and Hennepin County Medical Center, Minneapolis. Patients. - Type I diabetics with terminal diabetic renal failure undergoing renal transplantation. Forty-eight patients randomized to maximized or standard control completed the trial. Intervention. - 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<.001). Main Outcome. - 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.",
author = "Jose Barbosa and Steffes, {Michael W.} and Sutherland, {David E R} and Connett, {John E.} and Rao, {K. Venkateswara} and Mauer, {S. Michael}",
year = "1994",
month = "8",
day = "24",
doi = "10.1001/jama.272.8.600",
language = "English (US)",
volume = "272",
pages = "600--606",
journal = "JAMA - Journal of the American Medical Association",
issn = "0098-7484",
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TY - JOUR

T1 - Effect of glycemic control on early diabetic renal lesions

T2 - A 5-year randomized controlled clinical trial of insulin-dependent diabetic kidney transplant recipients

AU - Barbosa, Jose

AU - Steffes, Michael W.

AU - Sutherland, David E R

AU - Connett, John E.

AU - Rao, K. Venkateswara

AU - Mauer, S. Michael

PY - 1994/8/24

Y1 - 1994/8/24

N2 - 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. Design. - 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. Setting. - University of Minnesota Hospital and Clinic and the Clinical Research Center and Hennepin County Medical Center, Minneapolis. Patients. - Type I diabetics with terminal diabetic renal failure undergoing renal transplantation. Forty-eight patients randomized to maximized or standard control completed the trial. Intervention. - 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<.001). Main Outcome. - 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.

AB - 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. Design. - 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. Setting. - University of Minnesota Hospital and Clinic and the Clinical Research Center and Hennepin County Medical Center, Minneapolis. Patients. - Type I diabetics with terminal diabetic renal failure undergoing renal transplantation. Forty-eight patients randomized to maximized or standard control completed the trial. Intervention. - 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<.001). Main Outcome. - 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.

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