Kidney Disease and Related Findings in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study

Diabetes care (Impact Factor: 8.57). 01/2014; 37(1):24-30. DOI: 10.2337/dc13-2113
Source: PubMed

Kidney disease manifests clinically as elevated albumin excretion rate (AER), impaired glomerular filtration rate (GFR), or both, and is a cause of substantial morbidity and mortality in type 1 diabetes (T1D). The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study tested whether intensive diabetes therapy (INT) aimed at lowering glucose concentrations as close as safely possible to the normal range reduces the risks of kidney disease and other diabetes complications.RESEARCH DESIGN AND METHODS
In the DCCT, 1,441 participants with T1D were randomly assigned to INT or conventional diabetes therapy (CON) for a mean duration of 6.5 years. Subsequently, participants have been followed for 18 years in the ongoing observational EDIC. Standardized longitudinal measurements of AER, estimated GFR, and blood pressure were made throughout the DCCT/EDIC.RESULTSDuring the DCCT, INT reduced the risks of incident microalbuminuria (AER 40 mg/24 h) and macroalbuminuria (AER 300 mg/24 h) by 39% (95% CI 21-52%) and 54% (29-74%), respectively. During EDIC years 1-8, participants previously assigned to DCCT INT continued to experience lower rates of incident microalbuminuria and macroalbuminuria, with risk reductions of 59% (39-73%) and 84% (67-92%), respectively. Beneficial effects of INT on the development of impaired GFR (sustained estimated GFR <60 mL/min/1.73 m(2)) and hypertension became evident during combined DCCT/EDIC follow-up, with risk reductions of 50% (18-69%) and 20% (6-21%), respectively, compared with CON.CONCLUSIONS
In the DCCT/EDIC, INT resulted in clinically important, durable reductions in the risks of microalbuminuria, macroalbuminuria, impaired GFR, and hypertension.

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    ABSTRACT: Although microalbuminuria is considered as an early marker of nephropathy in diabetic adults, available information in diabetic adolescents is limited. The aim of this study was to investigate prevalence and frequency of regression of microalbuminuria in type 1 (T1DM) and type 2 diabetes mellitus (T2DM) patients with childhood onset. One hundred and nine adolescents (median, 18.9 years; interquartile range (IQR), 16.5-21.0 years) with T1DM and 18 T2DM adolescents (median, 17.9 years; IQR, 16.8-18.4 years) with repeated measurements of microalbuminuria (first morning urine microalbumin/creatinine ratios) were included. The median duration of diabetes was 10.1 (7.8-14.0) years and 5.0 (3.5-5.6) years, respectively, and follow-up period ranged 0.5-7.0 years. Growth parameters, estimated glomerular filtration rate, glycosylated hemoglobin (HbA1c) and lipid profiles were obtained after reviewing medical record in each subject. The prevalence of microalbuminuria at baseline and evaluation were 21.1% and 17.4% in T1DM, and 44.4% and 38.9% in T2DM. Regression of microalbuminuria was observed in 13 T1DM patients (56.5%) and 3 T2DM patients (37.5%), and progression rate was 10.5% and 20% in T1DM and T2DM respectively. In regression T1DM group, HbA1c at baseline and follow-up was lower, and C-peptide at baseline was higher compared to persistent or progression groups. In T2DM, higher triglyceride was observed in persistent group. Considerable regression of microalbuminuria more than progression in diabetes adolescents indicates elevated urinary microalbumin excretion in a single test does not imply irreversible diabetic nephropathy. Careful monitoring and adequate intervention should be emphasized in adolescents with microalbuminuria to prevent rapid progression toward diabetic nephropathy.
    03/2015; 20(1):13-20. DOI:10.6065/apem.2015.20.1.13
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    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, 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 1·73m2 (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.
  • Nature Reviews Nephrology 01/2015; DOI:10.1038/nrneph.2014.249 · 8.37 Impact Factor


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