The DOI matches its Crossref record; 26 of the 26 references it cites were found in a registry or an index.
Multifactorial Intervention and Cardiovascular Disease in Patients with Type 2 Diabetes
Open accessAbstract
BACKGROUND: Cardiovascular morbidity is a major burden in patients with type 2 diabetes. In the Steno-2 Study, we compared the effect of a targeted, intensified, multifactorial intervention with that of conventional treatment on modifiable risk factors for cardiovascular disease in patients with type 2 diabetes and microalbuminuria. METHODS: The primary end point of this open, parallel trial was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, revascularization, and amputation. Eighty patients were randomly assigned to receive conventional treatment in accordance with national guidelines and 80 to receive intensive treatment, with a stepwise implementation of behavior modification and pharmacologic therapy that targeted hyperglycemia, hypertension, dyslipidemia, and microalbuminuria, along with secondary prevention of cardiovascular disease with aspirin. RESULTS: The mean age of the patients was 55.1 years, and the mean follow-up was 7.8 years. The decline in glycosylated hemoglobin values, systolic and diastolic blood pressure, serum cholesterol and triglyceride levels measured after an overnight fast, and urinary albumin excretion rate were all significantly greater in the intensive-therapy group than in the conventional-therapy group. Patients receiving intensive therapy also had a significantly lower risk of cardiovascular disease (hazard ratio, 0.47; 95 percent confidence interval, 0.24 to 0.73), nephropathy (hazard ratio, 0.39; 95 percent confidence interval, 0.17 to 0.87), retinopathy (hazard ratio, 0.42; 95 percent confidence interval, 0.21 to 0.86), and autonomic neuropathy (hazard ratio, 0.37; 95 percent confidence interval, 0.18 to 0.79). CONCLUSIONS: A target-driven, long-term, intensified intervention aimed at multiple risk factors in patients with type 2 diabetes and microalbuminuria reduces the risk of cardiovascular and microvascular events by about 50 percent.
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“Although HRV testing is largely confined to the research setting, the CV reflex tests that assess changes in HRV during standardized clinical challenges such as deep breathing, Valsalva maneuver and supine-to-standing position remain the gold standard tests and are available for clinical care as well.547,614,626”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [626]
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“In addition to traditional risk factors, hyperglycemia, hyperinsulinemia, and oxidative stress contribute to endothelial damage, leading to poor arterial function and greater susceptibility to atherogenesis ( 45 , 82 , 289 ).”
From Exercise and Type 2 Diabetes (2010) · cites this paper as [82]
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“In addition, studies in people with T2D and early CKD demonstrated the long-term bene fi t of multifactorial intervention on the development of microvascular and macrovascular complications and mortality.”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [9]
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“Results from several randomized controlled trials revealed that more intensive treatment of risk factors in people with increased levels of natriuretic peptides reduces the risk for symptomatic heart failure, heart failure hospitalization, and newly diagnosed left ventricular dysfunction (222,227,228).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [227]
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“Results from several randomized controlled trials revealed that more intensive treatment of risk factors in people with increased levels of natriuretic peptides reduces the risk for symptomatic heart failure, heart failure hospitalization, and newly diagnosed left ventricular dysfunction (211,216,217).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [216]
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“For people who already have diabetes, lifestyle modification and pharmacological treatment, as well as blood pressure and cholesterol control, can delay progression to complications and reduce mortality, or even help with remission, especially if started early.1,2,58–62”
From Worldwide trends in diabetes prevalence and treatment from 1990 to 2022: a pooled analysis of 1108 population-representative studies with 141 million participants (2024) · cites this paper as [58]
Experimental — accuracy not yet measuredIn the citing paper
“The benefit of the intensive multifactorial intervention was demonstrated by a significant reduction in the incidence of microvascular complications after 4 years, and a significant 53% risk reduction in macrovascular complications after 8 years.455”
From European Guidelines on cardiovascular disease prevention in clinical practice (version 2012) (2012) · cites this paper as [455]
In the citing paper
“Angiotensin-converting enzyme inhibitors812), angiotensin Ⅱ receptor blockers813), and calcium channel antagonists814) have been reported to be effective for preventing cardiovascular events in patients with DM.”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [813]
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Metadata
- Authors
- Gæde, P., Vedel, P., Larsen, N., Jensen, G. V. H., Parving, H.-H., & Pedersen, O.
- Affiliations
- Steno Diabetes Center Copenhagen (DK)
- Herlev Hospital (DK)
- Roskilde Sygehus (DK)
- Aarhus University (DK)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2003-01-30
- Volume
- 348
- Issue
- 5
- Pages
- 383-393
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2139634859
- Cited by
- 4,378
- References
- 26
- Citations by year
- 2026: 47 · 2025: 71 · 2024: 108 · 2023: 110 · 2022: 102 · 2021: 137 · 2020: 142 · 2019: 133 · 2018: 171 · 2017: 143 · 2016: 158 · 2015: 169 · 2014: 198 · 2013: 184 · 2012: 235
- FWCI
- 178.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- type 2 diabetes, cardiovascular disease, multifactorial intervention, microalbuminuria, tight glycemic control, hyperglycemia, hypertension, dyslipidemia, aspirin, myocardial infarction, stroke, kidney disease, retinopathy, autonomic neuropathy
- MeSH terms
- Amputation, Surgical, Angiotensin II, Angiotensin-Converting Enzyme Inhibitors, Antihypertensive Agents, Hypolipidemic Agents, Cardiovascular Diseases, Combined Modality Therapy, Diabetes Mellitus, Diabetes Mellitus, Type 2, Female, Humans, Hyperlipidemias, Hypertension, Hypoglycemic Agents, Male, Middle Aged, Myocardial Infarction, Obesity, Risk Factors, Vitamins, Exercise, Smoking Cessation, Diet, Fat-Restricted, Stroke
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