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Long-Term Effect of Intensive Treatment on Nephropathy



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Am Fam Physician. 2004 Apr 1;69(7):1764.

The Diabetes Control and Complications Trial (DCCT) results showed that intensive treatment of diabetes prevents and reduces progression of the microvascular complications of diabetes, such as retinopathy and albuminuria. At the end of this trial, patients in the intensive and conventional treatment groups were encouraged to continue or initiate intensive treatment and were followed for an average of an additional eight years in the Epidemiology of Diabetes Interventions and Complications (EDIC) Study. This study determines the ongoing impact of previous intensive glucose lowering by comparing the onset of indicators of nephropathy in patients previously treated with intensive therapy and in those who had received conventional therapy.

The cohort in the DCCT patient cohort included patients with type I diabetes mellitus who were free of advanced microvascular or macrovascular complications of diabetes and who were followed for an average of six and one half years. In the EDIC study, 1,349 participants were followed for the development of microalbuminuria, albuminuria, hypertension or treatment with antihypertensive medications, doubling of the serum creatinine concentration since the DCCT baseline level, or need for renal transplantation or dialysis.

Patients in the EDIC study had a mean age of 33 years and a mean duration of diabetes of 12 years. The difference in mean glycosylated hemoglobin (A1c) that had been maintained between treatment groups during the DCCT began to narrow throughout the EDIC study, with a mean value of 8.0 percent and 8.2 percent in the previously intensively treated group and the conventional group, respectively.

Albumin excretion rates were normal in both groups at the beginning of the EDIC study. Over eight years, there was an adjusted risk reduction in the development of albuminuria of 57 percent in the early intensive treatment group. In addition, after eight years, there was an 84 percent reduction in the risk of developing clinical albuminuria in the intensively treated group. After eight years of follow-up in the EDIC study, the prevalence of a measured creatinine clearance of less than 70 mL per minute (1.2 mL per second) per 1.73 m2 in the intensive treatment group was below 1 percent in the intensively treated group compared with 4 percent in the conventionally treated group.

The number of patients reaching a creatinine concentration of 2 mg per dL (176.8 μmol per L) or greater was significantly lower in the intensive treatment group than in the conventional treatment group. Systolic blood pressure was also significantly lower in patients in the intensively treated group after eight years. The authors suggest that all of these findings could be attributed to lower mean A1c levels during the DCCT.

During the EDIC study, only 6.8 percent of participants in the previous intensive treatment group developed microalbuminuria, and 1.4 percent developed clinical albuminuria, compared with 15.8 percent and 9.4 percent respectively in patients in the conventional treatment group. The authors conclude that these findings suggest that intensive treatment, even when it is not sustained, has a lasting beneficial effect on the development of markers of nephropathy, possibly representing delay in the development of these complications. Intensive treatment therefore should be initiated as early as possible in patients with type 1 diabetes.

The Writing Team for the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. Sustained effect of intensive treatment of type 1 diabetes mellitus on development and progression of diabetic nephropathy. The Epidemiology of Diabetes Interventions and Complications (EDIC) Study. JAMA. October 22/29, 2003;290:2159–67.


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