Effects of pulsatile intravenous insulin therapy on the progression of diabetic nephropathy.

The purpose of this study was to assess the effects of pulsatile intravenous insulin therapy (PIVIT) on the progression of diabetic nephropathy in patients with type 1 diabetes mellitus (DM). This 18-month multicenter, prospective, controlled study involved 49 type 1 DM patients with nephropathy who were following the Diabetes Control and Complications Trial (DCCT) intensive therapy (IT) regimen. Of these, 26 patients formed the control group (C), which continued on IT, while 23 patients formed the treatment group (T) and underwent, in addition to IT, weekly PIVIT. Blood pressure in all patients was maintained below 140/90 mm Hg on antihypertensive medication, preferentially using angiotensin-converting enzyme (ACE) inhibitors. All study patients were seen in the clinic weekly for 18 months, had monthly glycohemoglobin (HbA1c), and every 3 months, 24-hour urinary protein excretion and creatinine clearance (CrCl) determinations. The HbA1c levels declined from 8.61% +/- 0.33% to 7.68% +/- 0.31% (P = .0028) in the T group and from 9.13% +/- 0.36% to 8.19% +/- 0.33% (P = .0015) in the C group during the study period. CrCl declined significantly in both groups, as expected, but the rate of CrCl decline in the T group (2.21 +/- 1.62 mL/min/yr) was significantly less than in the C group (7.69 +/- 1.88 mL/min/yr, P = .0343). We conclude that when PIVIT is added to IT in type 1 DM patients with overt nephropathy, it appears to markedly reduce the progression of diabetic nephropathy. The effect appears independent of ACE inhibitor therapy, blood pressure, or glycemic control.

[1]  T. Aoki,et al.  Effect of intensive insulin therapy on progression of overt nephropathy in patients with type 1 diabetes mellitus. , 1999, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[2]  H. Parving,et al.  Progression of diabetic nephropathy in normotensive type 1 diabetic patients. , 1999, Kidney international. Supplement.

[3]  K. Sharma,et al.  Hyperglycemia and Diabetic Kidney Disease: The Case for Transforming Growth Factor–β as a Key Mediator , 1995, Diabetes.

[4]  E. Grecu,et al.  Effect of Chronic Intermittent Intravenous Insulin Therapy on Antihypertensive Medication Requirements in IDDM Subjects With Hypertension and Nephropathy , 1995, Diabetes Care.

[5]  D. Yue,et al.  High Glucose Concentration Causes a Decrease in Mesangium Degradation: A Factor in the Pathogenesis of Diabetic Nephropathy , 1994, Diabetes.

[6]  F. Martin,et al.  Clinical and Histological Correlations of Decline in Renal Function in Diabetic Patients With Proteinuria , 1994, Diabetes.

[7]  R. Bain,et al.  The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. , 1993, The New England journal of medicine.

[8]  R. Bain,et al.  The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. , 1993 .

[9]  S. Genuth,et al.  The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. , 1993, The New England journal of medicine.

[10]  T. Aoki,et al.  Long-term intermittent intravenous insulin therapy and type 1 diabetes mellitus , 1993, The Lancet.

[11]  P. Reichard,et al.  The effect of long-term intensified insulin treatment on the development of microvascular complications of diabetes mellitus. , 1993, The New England journal of medicine.

[12]  G. Viberti,et al.  Diabetic Nephropathy: Future avenue , 1992, Diabetes Care.

[13]  M. Walser,et al.  Progression of chronic renal failure in man. , 1990, Kidney international.

[14]  H. Parving,et al.  Effect of antihypertensive treatment on kidney function in diabetic nephropathy. , 1987, British medical journal.

[15]  G. Paolisso,et al.  Greater Efficacy of Pulsatile Insulin in Type I Diabetics Critically Depends on Plasma Glucagon Levels , 1987, Diabetes.

[16]  W. Waldhäusl,et al.  Efficacy of Pulsatile Versus Continuous Insulin Administration on Hepatic Glucose Production and Glucose Utilization in Type I Diabetic Humans , 1986, Diabetes.

[17]  H. Parving,et al.  EARLY AGGRESSIVE ANTIHYPERTENSIVE TREATMENT REDUCES RATE OF DECLINE IN KIDNEY FUNCTION IN DIABETIC NEPHROPATHY , 1983, The Lancet.

[18]  R. Bilous,et al.  Long term correction of hyperglycaemia and progression of renal failure in insulin dependent diabetes , 1983, British medical journal.

[19]  R. Bilous,et al.  Monitoring glomerular function in diabetic nephropathy. A prospective study. , 1983, The American journal of medicine.

[20]  M. Jastremski,et al.  EDUCATIONAL GRAFFITI: BETTER USE OF THE LAVATORY WALL , 1982, The Lancet.

[21]  B. Myers,et al.  Slope of serial glomerular filtration rate and the progression of diabetic glomerular disease. , 1993, Journal of the American Society of Nephrology : JASN.

[22]  D. Hadden,et al.  The relationship between long-term glycaemic control and diabetic nephropathy. , 1992, The Quarterly journal of medicine.