Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes
Open accessAbstract
BACKGROUND: Intensive diabetes therapy aimed at achieving near normoglycemia reduces the risk of microvascular and neurologic complications of type 1 diabetes. We studied whether the use of intensive therapy as compared with conventional therapy during the Diabetes Control and Complications Trial (DCCT) affected the long-term incidence of cardiovascular disease. METHODS: The DCCT randomly assigned 1441 patients with type 1 diabetes to intensive or conventional therapy, treating them for a mean of 6.5 years between 1983 and 1993. Ninety-three percent were subsequently followed until February 1, 2005, during the observational Epidemiology of Diabetes Interventions and Complications study. Cardiovascular disease (defined as nonfatal myocardial infarction, stroke, death from cardiovascular disease, confirmed angina, or the need for coronary-artery revascularization) was assessed with standardized measures and classified by an independent committee. RESULTS: During the mean 17 years of follow-up, 46 cardiovascular disease events occurred in 31 patients who had received intensive treatment in the DCCT, as compared with 98 events in 52 patients who had received conventional treatment. Intensive treatment reduced the risk of any cardiovascular disease event by 42 percent (95 percent confidence interval, 9 to 63 percent; P=0.02) and the risk of nonfatal myocardial infarction, stroke, or death from cardiovascular disease by 57 percent (95 percent confidence interval, 12 to 79 percent; P=0.02). The decrease in glycosylated hemoglobin values during the DCCT was significantly associated with most of the positive effects of intensive treatment on the risk of cardiovascular disease. Microalbuminuria and albuminuria were associated with a significant increase in the risk of cardiovascular disease, but differences between treatment groups remained significant (P< or =0.05) after adjusting for these factors. CONCLUSIONS: Intensive diabetes therapy has long-term beneficial effects on the risk of cardiovascular disease in patients with type 1 diabetes.
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In the DCCT cohort, there was a significant reduction in CV outcomes (42%), nonfatal myocardial infarct (MI), stroke and CV death (57%), as well as all-cause mortality (33%) in previously intensively treated participants compared with those who were previously in the standard arm.
“In the DCCT cohort, there was a significant reduction in CV outcomes (42%), nonfatal myocardial infarct (MI), stroke and CV death (57%), as well as all-cause mortality (33%) in previously intensively treated participants compared with those who were previously in the standard arm (17)(18)(19).”
From Targets for Glycemic Control (2018) · cites this paper as [17]
Split into 2 atoms — 1 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredHyperglycemia plays a central role in the microvascular and macrovascular complications of diabetes.
“Because hyperglycemia plays a central role in the microvascular and macrovascular complications of diabetes, 3,5,6 it is possible that interventions that prevent or delay hyperglycemia may effectively prevent or delay these long-term complications.”
From Pioglitazone for Diabetes Prevention in Impaired Glucose Tolerance (2011) · cites this paper as [6]
In the opening results passage (page unavailable), the paper says hyperglycemia plays a central role in microvascular complications of type 1 diabetes. A later results passage says differences in glycosylated hemoglobin accounted for much of the cardiovascular benefit of intensive therapy, supporting a role in macrovascular disease. The claim extends these type 1 findings to diabetes generally and states the macrovascular role more definitively than the paper does. (LLM, conf=0.83)
Experimental — accuracy not yet measuredThe benefits of more-stringent glycemic control compared with less-stringent glycemic control manifest over many years of treatment.
“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 [249]
The Results (page not available in our copy) report that about 6.5 years of intensive treatment, compared with conventional treatment, reduced cardiovascular events during long-term follow-up in people with type 1 diabetes. This supports a benefit observed over many years, but the claim generalizes beyond that population and outcome and implies the benefit requires many years of ongoing treatment; the paper also reports that treatment differences largely dissipated during follow-up. (LLM, conf=0.83)
Experimental — accuracy not yet measuredIn secondary interventions, individual therapy with aspirin, antihypertensive agents, and lipid-lowering drugs each reduced the relative risk of cardiovascular events by about 25%, and the effects appeared to be additive.
“hypertensive agents, and lipid-lowering drugs each reduced the relative risk of cardiovascular events by about 25%, and the effects appeared to be additive.21,22”
From Effect of a multifactorial intervention on mortality in type 2 diabetes (2008) · cites this paper as [22]
The Results section says that medications lowering cholesterol and blood pressure are proven interventions that reduce cardiovascular risk. It does not report a roughly 25% reduction for each drug class, address aspirin’s effect, or say the effects are additive. No page number is available in our copy. (LLM, conf=0.80)
Experimental — accuracy not yet measuredThe Epidemiology of Diabetes Interventions and Complications (EDIC) study found intensive diabetes treatment reduced the risk of cardiovascular events by 42% compared with conventional treatment.
“The Epidemiology of Diabetes Interventions and Complications (EDIC) study,109 which followed participants with type 1 diabetes for long-term complications, found intensive diabetes treatment reduced the risk of cardiovascular events by 42% compared with conventional treatment.”
From Type 1 diabetes (2014) · cites this paper as [109]
Severe insulin deficiency can cause acute hyperglycemic complications such as diabetic ketoacidosis, hyperosmolar hyperglycemic state, hypertriglyceridemia, and hypercatabolic state, which may be life-threatening.
“Absolute (or near-absolute) insulin deficiency can result in acute hyperglycemic complications, including DKA, hyperosmolar hyperglycemic state, hypertriglyceridemia, and hypercatabolic state, which can be life-threatening.1114–1120”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [1117]
The results section discusses long-term microvascular and cardiovascular complications of type 1 diabetes, while the study-procedures section describes insulin treatment and glucose targets. Searches for ketoacidosis, severe insulin deficiency, and the listed acute complications found no passage addressing the claimed life-threatening effects; page numbers were not available in our copy. (LLM, conf=0.74)
Experimental — accuracy not yet measuredDiabetic complications continue to be a major cause of morbidity and mortality in type 1 diabetes, and cardiovascular disease is the leading cause of death.
“Unfortunately, diabetic complications continue to be a major cause of morbidity and mortality in persons with T1D and cardiovascular disease (CVD) is the leading cause of death98.”
From Epidemiology of type 1 diabetes (2010) · cites this paper as [98]
The importance of intensive glycemic control for protection against microvascular complications and cardiovascular disease in people with type 1 diabetes mellitus is well established.
“Although the importance of intensive glycemic control for protection against microvascular complications and CVD in people with T1DM is well established [9, 10]”
From Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007–2017 (2018) · cites this paper as [10]
Longer follow-up documented a significant reduction in cardiovascular disease in patients with type 1 diabetes treated with intensive glycemic control.
“Longer follow-up documented a significant reduction in cardiovascular disease in patients with type 1 diabetes treated with intensive glycemic control (45).”
From Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus (2011) · cites this paper as [45]
The quality of adjustment of traditional risk factors accounts for only ∼50% of the cardio-protective effect of improved metabolic control.
“the quality of adjustment of traditional risk factors accounts for only ∼50% of the cardio-protective effect of improved metabolic control.787”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [787]
About 40% of the cardio-protective effect remains for HbA1c or elevated glucose concentrations per se.
“About 40% of the cardio-protective effect remains for HbA1c or elevated glucose concentrations per se.”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [787]
Intensive glycemic control in all major clinical trials increased the risk of severe hypoglycemia 2- to 3-fold.
“Intensive glycemic control in all major clinical trials was shown to increase the risk of severe hypoglycemia 2- to 3-fold.”
From Clinical management of stable coronary artery disease in patients with type 2 diabetes mellitus: a scientific statement from the American Heart Association (2020) · cites this paper as [193]
Similar legacy effects of early intensive glycaemic control were seen in patients with type 1 diabetes in the DCCT/EDIC trial.
“Similar legacy effects of early, intensive glycaemic control were seen in patients with type 1 diabetes in the DCCT/ EDIC trial.445”
From European Guidelines on cardiovascular disease prevention in clinical practice (version 2012) (2012) · cites this paper as [445]
Intensive glycemic management resulting in lower A1C levels has a beneficial effect on cardiovascular disease complications in type 1 diabetes.
“Intensive glycemic management resulting in lower A1C levels has also been shown to have a beneficial effect on cardiovascular disease (CVD) complications in type 1 diabetes (9,10)”
From Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy (2009) · cites this paper as [10]
Missed insulin injections impact HbA1c levels and lead to an increased risk of diabetes-related complications.
“The impact of missed insulin injections on HbA1c levels is well established,7–12 leading to an increasing risk of diabetes-related complications.13,14”
From Increased Time in Range and Fewer Missed Bolus Injections After Introduction of a Smart Connected Insulin Pen (2020) · cites this paper as [14]
Many people treated with insulin fail to reach their glycemic targets, which is known to increase the risk of microvascular and macrovascular complications, resulting in substantial morbidity and mortality.
“Many people treated with insulin fail to reach their glycemic targets, which is known to increase the risk of microvascular and macrovascular complications, resulting in substantial morbidity and mortality.13,14,24”
From Increased Time in Range and Fewer Missed Bolus Injections After Introduction of a Smart Connected Insulin Pen (2020) · cites this paper as [14]
In the 9-year post-DCCT follow-up of the EDIC cohort, participants previously randomized to the intensive arm had a significant 57% reduction in the risk of nonfatal myocardial infarction (MI), stroke, or cardiovascular death compared with those previously randomized to the standard arm.
“In the 9-year post-DCCT follow-up of the EDIC cohort, participants previously randomized to the intensive arm had a significant 57% reduction in the risk of nonfatal myocardial infarction (MI), stroke, or cardiovascular death compared with those previously randomized to the standard arm (54).”
From 6. Glycemic Targets: <i>Standards of Care in Diabetes—2023</i> (2023) · cites this paper as [54]
Nine-year post-DCCT follow-up of the cohort has shown that participants previously randomized to the intensive arm had a 42% reduction (P = 0.02) in cardiovascular disease outcomes and a 57% reduction (P = 0.02) in the risk of nonfatal myocardial infarction, stroke, or cardiovascular disease death compared with those previously in the standard arm.
“However, 9-year post-DCCT follow-up of the cohort has shown that participants previously randomized to the intensive arm had a 42% reduction (P = 0.02) in CVD outcomes and a 57% reduction (P = 0.02) in the risk of nonfatal myocardial infarction (MI), stroke, or CVD death compared with those previously in the standard arm (55).”
From Standards of Medical Care in Diabetes—2009 (2009) · cites this paper as [55]
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References 35 · Cited by 5,138
Research works printed but not linked: 2
- [3]3. Erratum, N Engl J Med 2000; 342:1376.
- [11]11. Backlund JY, Determan A, Cleary P. Validation of deaths and reported cardio- vascular cerebrovascular events. Control Clin Trials 2003;23:2S. Snedecor GW, Cochran WG. Statisti- cal methods. 7th ed. Ames: Iowa State Uni- versity Press, 1980.
- Authors
- The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study Research Group
- Corresponding author
- The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study Research Group
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2005-12-22
- Volume
- 353
- Issue
- 25
- Pages
- 2643-2653
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC2637991
- OpenAlex
- W1752045965
- Semantic Scholar
- 8b951bfff8120cd5b7ea267c32bad255f02145a6
- Cited by
- 5,138
- References
- 35
- Citations by year
- 2026: 90 · 2025: 115 · 2024: 142 · 2023: 153 · 2022: 144 · 2021: 201 · 2020: 191 · 2019: 210 · 2018: 246 · 2017: 240 · 2016: 276 · 2015: 335 · 2014: 358 · 2013: 322 · 2012: 343
- FWCI
- 147.55
- 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)
- Funders
- National Institutes of Health (n01dk062204-003)
- National Institute of Diabetes and Digestive and Kidney Diseases (N01 DK062204)
- 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, Cardiovascular Risks, and Lipoproteins
- Keywords
- type 1 diabetes, intensive diabetes therapy, cardiovascular disease, glycemic control, HbA1c, myocardial infarction, stroke, cardiovascular mortality, microalbuminuria, albuminuria, Diabetes Control and Complications Trial, long-term follow-up
- MeSH terms
- Adolescent, Adult, Cardiovascular Diseases, Diabetes Mellitus, Type 1, Female, Follow-Up Studies, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Insulin, Male, Middle Aged, Risk, Proportional Hazards Models, Treatment Outcome
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