Effect of intensive diabetes treatment on albuminuria in type 1 diabetes: long-term follow-up of the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications study

Abstract

Background: Intensive diabetes treatment reduces the risk of developing albuminuria in individuals with type 1 diabetes. Effects on the long-term clinical course of kidney disease remain to be defined. We aimed to compare the long-term effects of intensive versus conventional treatment on incident albuminuria.

Methods: For this long-term follow-up study of the Diabetes Control and Complications Trial (DCCT) we assessed the effect of intensive diabetes treatment on albuminuria during 18 years after the completion of the trial. During the DCCT (1983-1993), 1441 participants with type 1 diabetes were randomly assigned to receive either intensive treatment (with the goal of achieving levels of glycaemia as close to the non-diabetic range as safely possible) or conventional treatment (aimed at prevention of symptoms of hyperglycaemia and hypoglycaemia). At the end of the DCCT, all participants were instructed in intensive treatment, and all participants were invited to join the observational Epidemiology of Diabetes Interventions and Complications (EDIC) study. Mean HbA1c during the EDIC study was similar in the two groups of patients who differed in their treatment assignment during the DCCT. Albumin excretion rate was measured every other year during the EDIC study. Microalbuminuria was defined as an albumin excretion rate of 30 mg per 24 h or higher on two consecutive study visits and macroalbuminuria as an albumin excretion rate of 300 mg per day or higher. We estimated glomerular filtration rate from annual serum creatinine measurements throughout DCCT and the EDIC study. The DCCT is registered with ClinicalTrials.gov, number NCT00360815, and the EDIC study, with number NCT00360893.

Findings: During years 1-18 of EDIC, we noted 191 new cases of microalbuminuria (71 in the group receiving intensive treatment during DCCT and 120 in the group receiving conventional treatment during DCCT; risk reduction 45%, 95% CI 26-59) and 117 new cases of macroalbuminuria (31 intensive, 86 conventional; 61%, 41-74). At year 17-18 of EDIC, the prevalence of albumin excretion rate of 30 mg per 24 h or higher was 18·4% in participants assigned to intensive treatment during the DCCT, compared with 24·9% in participants assigned to conventional treatment (p=0·02). During years 1-18 of EDIC, we recorded 84 cases of sustained estimated glomerular filtration rate lower than 60 mL/min per 1·73m(2) (31 intensive, 53 conventional; risk reduction 44%, 95% CI 12-64).

Interpretation: In individuals with type 1 diabetes, intensive diabetes treatment yields durable renal benefits that persist for at least 18 years after its application. Ultimately, such benefits should result in fewer patients requiring renal replacement therapy.

Funding: National Institute of Diabetes and Digestive and Kidney Disease.

Figure 1. Cumulative incidence of microalbuminuria and macroalbuminuria during years 1–18 in the EDIC study

(A) Cumulative incidence of microalbuminuria (sustained albumin excretion rate ≥30 mg per 24 h). (B) Cumulative incidence of macroalbuminuria (albumin excretion rate ≥300 mg per 24 h). (C) Hazard rate of microalbuminuria. (D) Hazard rate of macroalbuminuria. *In units of number per patient-year.

Figure 2. Prevalence of albuminuria by DCCT treatment group and EDIC study year

Albumin excretion rate is classified into four mutually exclusive categories. End-stage renal disease was used for any participant who was treated with dialysis or underwent kidney transplantation irrespective of whether urine was collected or albumin excretion rate was measured. DCCT=Diabetes Control and Complications Trial. EDIC=Epidemiology of Diabetes Interventions and Complications. I=DCCT intensive diabetes treatment. C=DCCT conventional diabetes treatment. RAS=renin-angiotensin system.