Effect of intensive therapy on the microvascular complications of type 1 diabetes mellitus
Open accessAbstract
The purpose of this report is to summarize and integrate the findings of the Diabetes Control and Complications Trial (DCCT), a randomized controlled clinical trial, and the succeeding observational follow-up of the DCCT cohort in the Epidemiology of Diabetes Interventions and Complications (EDIC) study, regarding the effects of intensive treatment on the microvascular complications of type 1 diabetes mellitus. The DCCT proved that intensive treatment reduced the risks of retinopathy, nephropathy, and neuropathy by 35% to 90% compared with conventional treatment. The absolute risks of retinopathy and nephropathy were proportional to the mean glycosylated hemoglobin (HbA(1c)) level over the follow-up period preceding each event. Intensive treatment was most effective when begun early, before complications were detectable. These risk reductions, achieved at a median HbA(1c) level difference of 9.1% for conventional treatment vs 7.3% for intensive treatment have been maintained through 7 years of EDIC, even though the difference in mean HbA(1c) levels of the 2 former randomized treatment groups was only 0.4% at 1 year (P<.001) (8.3% in the former conventional treatment group vs 7.9% in the former intensive treatment group), continued to narrow, and became statistically nonsignificant by 5 years (8.1% vs 8.2%, P =.09). The further rate of progression of complications from their levels at the end of the DCCT remains less in the former intensive treatment group. Thus, the benefits of 6.5 years of intensive treatment extend well beyond the period of its most intensive implementation. Intensive treatment should be started as soon as is safely possible after the onset of type 1 diabetes mellitus and maintained thereafter, aiming for a practicable target HbA(1c) level of 7.0% or less.
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Subsequent observational data from long-term follow-up after termination of randomization periods of both the DCCT and UKPDS cohorts showed a persistence of significant microvascular benefits and also demonstrated an emergence of beneficial effect on CV outcomes attributed to intensive glycemic control (metabolic memory or legacy effect).
“Subsequent observational data from long-term follow up after termination of randomization periods of both the DCCT and UKPDS cohorts showed a persistence of significant microvascular benefits and also demonstrated an emergence of beneficial effect on CV outcomes attributed to intensive glycemic control.This has been termed as”
From Targets for Glycemic Control (2018) · cites this paper as [14]
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Experimental — accuracy not yet measuredACE inhibitors, ARBs, SGLT2is, GLP-1 RAs, and finerenone improve albuminuria and declining eGFR.
“Therapies shown to positively affect albuminuria and declining eGFR include ACE inhibitors, ARBs, SGLT2is, GLP-1 RAs, and the nonsteroidal mineralocorticoid antagonist finerenone.197,209,239,242,393,423–435”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [197]
The Summary of Salient DCCT Results reports reduced albuminuria with intensive insulin therapy, but no effect of that therapy on measured glomerular filtration rate. The Summary of EDIC Results likewise compares former intensive and conventional treatment groups. Searches for the named drug classes and their effects on albuminuria or eGFR found no passage addressing the therapies in the claim. (LLM, conf=0.76)
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- Authors
- The Writing Team for the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group
- Venue
- JAMA: The Journal of the American Medical Association
- Publisher
- American Medical Association (AMA)
- Published
- 2002-05-15
- Volume
- 287
- Issue
- 19
- Pages
- 2563-2569
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- 1538-3598
- PMC
- PMC2622728
- OpenAlex
- W2757208104
- Cited by
- 941
- References
- 36
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 11 · 2023: 18 · 2022: 29 · 2021: 27 · 2020: 29 · 2019: 27 · 2018: 29 · 2017: 28 · 2016: 34 · 2015: 45 · 2014: 51 · 2013: 53 · 2012: 54
- FWCI
- 22.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (n01dk062204-003)
- National Heart, Lung, and Blood Institute
- National Institute of Diabetes and Digestive and Kidney Diseases (N01 DK062204)
- National Center for Research Resources
- Division of Diabetes, Endocrinology, and Metabolic Diseases
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Education
- Keywords
- type 1 diabetes, intensive insulin therapy, glycemic control, HbA1c, microvascular complications, diabetic retinopathy, diabetic nephropathy, diabetic neuropathy, Diabetes Control and Complications Trial, early treatment initiation, HbA1c targets
- MeSH terms
- Adolescent, Adult, Albuminuria, Diabetes Mellitus, Type 1, Diabetic Angiopathies, Diabetic Nephropathies, Diabetic Neuropathies, Diabetic Retinopathy, Female, Glycated Hemoglobin, Humans, Male, Randomized Controlled Trials as Topic
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