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Intensive Diabetes Therapy and Glomerular Filtration Rate in Type 1 Diabetes
Open accessAbstract
BACKGROUND: An impaired glomerular filtration rate (GFR) leads to end-stage renal disease and increases the risks of cardiovascular disease and death. Persons with type 1 diabetes are at high risk for kidney disease, but there are no interventions that have been proved to prevent impairment of the GFR in this population. METHODS: In the Diabetes Control and Complications Trial (DCCT), 1441 persons with type 1 diabetes were randomly assigned to 6.5 years of intensive diabetes therapy aimed at achieving near-normal glucose concentrations or to conventional diabetes therapy aimed at preventing hyperglycemic symptoms. Subsequently, 1375 participants were followed in the observational Epidemiology of Diabetes Interventions and Complications (EDIC) study. Serum creatinine levels were measured annually throughout the course of the two studies. The GFR was estimated with the use of the Chronic Kidney Disease Epidemiology Collaboration formula. We analyzed data from the two studies to determine the long-term effects of intensive diabetes therapy on the risk of impairment of the GFR, which was defined as an incident estimated GFR of less than 60 ml per minute per 1.73 m(2) of body-surface area at two consecutive study visits. RESULTS: Over a median follow-up period of 22 years in the combined studies, impairment of the GFR developed in 24 participants assigned to intensive therapy and in 46 assigned to conventional therapy (risk reduction with intensive therapy, 50%; 95% confidence interval, 18 to 69; P=0.006). Among these participants, end-stage renal disease developed in 8 participants in the intensive-therapy group and in 16 in the conventional-therapy group. As compared with conventional therapy, intensive therapy was associated with a reduction in the mean estimated GFR of 1.7 ml per minute per 1.73 m(2) during the DCCT study but during the EDIC study was associated with a slower rate of reduction in the GFR and an increase in the mean estimated GFR of 2.5 ml per minute per 1.73 m(2) (P<0.001 for both comparisons). The beneficial effect of intensive therapy on the risk of an impaired GFR was fully attenuated after adjustment for glycated hemoglobin levels or albumin excretion rates. CONCLUSIONS: The long-term risk of an impaired GFR was significantly lower among persons treated early in the course of type 1 diabetes with intensive diabetes therapy than among those treated with conventional diabetes therapy. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; DCCT/EDIC ClinicalTrials.gov numbers, NCT00360815 and NCT00360893.).
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“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 [53]
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“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 [191]
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“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 [191]
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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 (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 [55]
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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 (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 [53]
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“However, the bene fi ts of more-stringent glycemic control (i.e., lower HbA1c targets) compared with less-stringent glycemic control (i.e., higher HbA1c targets) manifest over many years of treatment. 191,248,249”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [191]
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“In randomized clinical trials, it has taken a number of years for bene fi ts of intensive glycemic control to manifest as improved clinical outcomes. 190,191,234,245,246,248,256”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [191]
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Metadata
- Authors
- The DCCT/EDIC Research Group
- Affiliations
- University of Washington (US)
- Corresponding author
- The DCCT/EDIC Research Group
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2011-12-22
- Volume
- 365
- Issue
- 25
- Pages
- 2366-2376
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC3270008
- OpenAlex
- W2141495158
- Cited by
- 568
- References
- 28
- Citations by year
- 2026: 4 · 2025: 24 · 2024: 20 · 2023: 34 · 2022: 29 · 2021: 32 · 2020: 40 · 2019: 27 · 2018: 35 · 2017: 35 · 2016: 45 · 2015: 54 · 2014: 58 · 2013: 65 · 2012: 61
- FWCI
- 46.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Research Portal (Queen's University Belfast) (submittedVersion)
- Funders
- Abbott Laboratories
- Eli Lilly and Company
- Sanofi
- Northwestern University
- University of Washington
- Novo Nordisk
- Genentech
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK087726, RC4DK090766, R01DK088762)
- National Center for Research Resources
- Division of Diabetes, Endocrinology, and Metabolic Diseases
- 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 therapy, glomerular filtration rate, diabetic nephropathy, end-stage renal disease, glycemic control, HbA1c, albuminuria, chronic kidney disease
- MeSH terms
- Adult, Creatinine, Diabetes Mellitus, Type 1, Diabetic Nephropathies, Female, Follow-Up Studies, Glomerular Filtration Rate, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Insulin, Insulin Infusion Systems, Kidney Failure, Chronic, Male, Middle Aged
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