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Cited by 183Chronic Kidney Disease and DiabetesDiabetes Management and ResearchDiabetes Treatment and Management

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

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·2014·The Lancet Diabetes & Endocrinology
DOI 10.1016/s2213-8587(14)70155-xPMC PMC4215637
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Abstract

Summary 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 1·73m2 (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.

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  • Intensive lowering of blood glucose with the goal of achieving near-normoglycemia has been shown in large randomized studies to delay the onset and progression of albuminuria and reduce eGFR in people with type 1 diabetes and type 2 diabetes.

    “Intensive lowering of blood glucose with the goal of achieving near-normoglycemia has been shown in large, randomized studies to delay the onset and progression of albuminuria and reduce eGFR in people with type 1 diabetes (52,53) and type 2 diabetes (1,(54)(55)(56)(57)(58)(59).”

    From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [52]

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  • Lowering blood glucose itself helps prevent CKD and its progression.

    “Insulin alone was used to lower blood glucose in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study of type 1 diabetes, while a variety of agents were used in clinical trials of type 2 diabetes, supporting the conclusion that lowering blood glucose itself helps prevent CKD and its progression.”

    From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [52]

    The Methods (page unavailable) describe insulin-based glucose lowering in the DCCT, and the Results (page unavailable) report fewer cases of albuminuria, impaired kidney filtration, and end-stage renal disease after intensive treatment in people with type 1 diabetes. The Results also report that mean HbA1c explained most or all of the treatment effect on incident albuminuria. But the Discussion > Interpretation says the long-term renal benefits in type 2 diabetes remain inconclusive, so this paper does not fully support the unqualified conclusion about preventing CKD progression across diabetes types. (LLM, conf=0.84)

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  • In RCTs, targeting lower HbA1c values using glucose-lowering medications has been proven to reduce risks of microvascular diabetes complications (kidney disease, retinopathy, neuropathy) and, in some studies, also macrovascular diabetes complications (cardiovascular events).

    “In RCTs, targeting lower HbA1c values using glucose-lowering medications has been proven to reduce risks of microvascular diabetes complications (i.e., kidney disease, retinopathy, neuropathy) and, in some studies, also macrovascular diabetes complications (i.e., cardiovascular events).”

    From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [190]

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  • In T1D or T2D, lower achieved HbA1c levels below 7% versus 8%-9% reduce the risk of overall microvascular complications, including nephropathy and retinopathy, and macrovascular complications in some RCTs.

    “In both T1D or T2D, lower achieved levels of HbA1c < 7% ( < 53 mmol/mol) versus 8% -9% (64 -75 mmol/mol) reduce risk of overall microvascular complications, including nephropathy and retinopathy, and macrovascular complications in some RCTs. 189 -193”

    From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [190]

    The Introduction and Discussion report that intensive treatment reduced albuminuria in type 1 diabetes, and the Discussion’s literature review reports albuminuria benefits in type 2 diabetes. The paper does not establish the claimed comparison of achieved HbA1c below 7% versus 8–9%, or report reductions in retinopathy and macrovascular complications. Page numbers are unavailable in our copy. (LLM, conf=0.88)

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  • Intensive lowering of blood glucose with the goal of achieving near-normoglycemia has been shown in large randomized studies to delay the onset and progression of albuminuria and reduce eGFR in people with type 1 diabetes and type 2 diabetes.

    “Intensive lowering of blood glucose with the goal of achieving near-normoglycemia has been shown in large, randomized studies to delay the onset and progression of albuminuria and reduce eGFR in people with type 1 diabetes (54,55) and type 2 diabetes (1,56,57).”

    From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [54]

    The Introduction and Results report that intensive treatment aimed at near-normal glycaemia reduced incident microalbuminuria and macroalbuminuria in people with type 1 diabetes. But the Results report fewer cases of impaired eGFR—not a reduction in eGFR itself. The type 2 diabetes portion of the citing sentence has separate citations and is not attributed to this paper. (LLM, conf=0.87)

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Venue
The Lancet Diabetes & Endocrinology
Publisher
Elsevier BV
Published
2014-10
Volume
2
Issue
10
Pages
793-800
ISSN
2213-8587 (ISSN-L)
DOI
10.1016/s2213-8587(14)70155-x
PMC
PMC4215637
OpenAlex
W2272346242
Semantic Scholar
419a300421ff9524b70f750cd1e12584323330df
Cited by
183
References
34
Citations by year
2026: 10 · 2025: 9 · 2024: 17 · 2023: 16 · 2022: 15 · 2021: 20 · 2020: 12 · 2019: 12 · 2018: 25 · 2017: 7 · 2016: 21 · 2015: 15 · 2014: 4
FWCI
12.39
Type
journal article
Language
en
Open access
Licence
Locations
  • The Lancet Diabetes & Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute of Neurological Disorders and Stroke (R01DK087726, R01DK088762)
  • National Eye Institute
  • National Institute of Diabetes and Digestive and Kidney Diseases (1982–93)
Topics
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Keywords
type 1 diabetes, intensive diabetes treatment, albuminuria, microalbuminuria, macroalbuminuria, diabetic nephropathy, urinary albumin excretion rate, glycemic control, HbA1c, glomerular filtration rate, Diabetes Control and Complications Trial, EDIC
MeSH terms
Adult, Albuminuria, Clinical Trials as Topic, Diabetes Mellitus, Type 1, Female, Follow-Up Studies, Humans, Male, Middle Aged, Risk Factors, Incidence, Proportional Hazards Models, Treatment Outcome, Young Adult

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