Risk factors, mortality, and cardiovascular outcomes in patients with type 2 diabetes
Open accessAbstract
BACKGROUND: Patients with diabetes are at higher risk for death and cardiovascular outcomes than the general population. We investigated whether the excess risk of death and cardiovascular events among patients with type 2 diabetes could be reduced or eliminated. METHODS: In a cohort study, we included 271,174 patients with type 2 diabetes who were registered in the Swedish National Diabetes Register and matched them with 1,355,870 controls on the basis of age, sex, and county. We assessed patients with diabetes according to age categories and according to the presence of five risk factors (elevated glycated hemoglobin level, elevated low-density lipoprotein cholesterol level, albuminuria, smoking, and elevated blood pressure). Cox regression was used to study the excess risk of outcomes (death, acute myocardial infarction, stroke, and hospitalization for heart failure) associated with smoking and the number of variables outside target ranges. We also examined the relationship between various risk factors and cardiovascular outcomes. RESULTS: The median follow-up among all the study participants was 5.7 years, during which 175,345 deaths occurred. Among patients with type 2 diabetes, the excess risk of outcomes decreased stepwise for each risk-factor variable within the target range. Among patients with diabetes who had all five variables within target ranges, the hazard ratio for death from any cause, as compared with controls, was 1.06 (95% confidence interval [CI], 1.00 to 1.12), the hazard ratio for acute myocardial infarction was 0.84 (95% CI, 0.75 to 0.93), and the hazard ratio for stroke was 0.95 (95% CI, 0.84 to 1.07). The risk of hospitalization for heart failure was consistently higher among patients with diabetes than among controls (hazard ratio, 1.45; 95% CI, 1.34 to 1.57). In patients with type 2 diabetes, a glycated hemoglobin level outside the target range was the strongest predictor of stroke and acute myocardial infarction; smoking was the strongest predictor of death. CONCLUSIONS: Patients with type 2 diabetes who had five risk-factor variables within the target ranges appeared to have little or no excess risk of death, myocardial infarction, or stroke, as compared with the general population. (Funded by the Swedish Association of Local Authorities and Regions and others.).
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When all major cardiovascular risk factors are treated to within target ranges, people with type 2 diabetes have risk of death, MI, or stroke similar to that of the general population.
“when all major cardiovascular risk factors are treated to within the target ranges, people with type 2 diabetes have risk of death, MI, or stroke similar to that of the general population (6).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [6]
The Discussion (p. 7) reports that patients with type 2 diabetes whose five selected risk factors were within target ranges had, at most, marginally higher risks of death, myocardial infarction, and stroke than the general population. But the paper’s limitations (p. 11) say it did not distinguish patients medically treated to reach those ranges from patients already within them without treatment. The comparison is supported; attributing it specifically to treatment is not. (LLM, conf=0.88)
Experimental — accuracy not yet measuredAmong persons with type 2 diabetes, cardiovascular risk and mortality are dependent on the number of uncontrolled risk factors.
“Among persons with type 2 diabetes (T2D), cardiovascular risk and mortality are dependent on the number of uncontrolled risk factors.”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [6]
A large cohort study confirmed no or only marginally increased mortality, MI, and stroke risk compared with the general population when all major cardiovascular risk factors are managed to goal levels in people with type 2 diabetes.
“In addition to the evidence from prospective intervention studies to support comprehensive ASCVD risk factor reduction, a large cohort study confirmed no or only marginally increased mortality, MI, and stroke risk compared with the general population when all major cardiovascular risk factors are managed to goal levels in people with type 2 diabetes (6).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [6]
Hypertriglyceridemia is indirectly linked to changes in HDL-C and LDL-C composition that promote accelerated atherogenesis.
“Hypertriglyceridemia is indirectly linked with changes in HDL-C and LDL-C composition that are conducive to accelerated atherogenesis.”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [313]
The Discussion (p. 7) links LDL-cholesterol levels to cardiovascular risk, but does not discuss changes in LDL-C or HDL-C composition. Searches for hypertriglyceridemia, triglycerides, and lipoprotein composition found no passage addressing the proposed mechanism of accelerated atherogenesis. (LLM, conf=0.76)
Experimental — accuracy not yet measuredAll apo B-containing particles are potentially atherogenic.
“In persons with fasting triglycerides of 200 to 499 mg/dL, despite tight adherence to a healthy diet (to include reduced intake of simple carbohydrates and avoidance of fruit juices and alcohol) and optimized glycemia control, prescribe statin therapy to the maximum tolerated dose to achieve goals for non-HDL-C or apo B, since all apo B–containing particles are potentially atherogenic.”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [313]
The Discussion (p. 7) links LDL cholesterol levels with cardiovascular outcomes in patients with type 2 diabetes, but it does not address whether all apo B–containing particles are potentially atherogenic. Searches for that phrase and for apolipoprotein B, non-HDL cholesterol, and atherogenic particles found no passage making the attributed point. (LLM, conf=0.75)
Experimental — accuracy not yet measured
Apart from icosapent ethyl, fish oil therapy has not been shown to prevent cardiovascular adverse events.
“To date, aside from icosapent ethyl, fish oil therapy has not been shown to prevent CV adverse events.”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [313]
The Discussion (p. 7) addresses cardiovascular risk factors in type 2 diabetes, but not fish oil therapy. Searches for icosapent ethyl, fish oil, and omega-3 fatty acids found no passage assessing whether they prevent cardiovascular adverse events. (LLM, conf=0.76)
Experimental — accuracy not yet measuredNo randomized controlled trial has yet been reported to investigate whether reducing severe (>500 mg/dL) or moderate (>200 mg/dL) hypertriglyceridemia prevents cardiovascular disease.
“No RCT has yet been reported to investigate the benefit of reducing severe (>500 mg/dL) or moderate (>200 mg/dL) hypertriglyceridemia to prevent CVD.”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [313]
The Discussion (p. 7) says randomized trials of multifactorial cardiovascular risk-factor interventions in type 2 diabetes are scarce, but does not address trials specifically testing triglyceride reduction. Searches for hypertriglyceridemia, triglyceride-lowering trials, and the 500 and 200 mg/dL thresholds found no passage establishing the claimed absence of such trials. (LLM, conf=0.76)
Experimental — accuracy not yet measuredDespite newer therapies, the risk of kidney failure remains high, particularly in those whose risk factors are insufficiently controlled.
“Despite these newer therapies, the risk of kidney failure remains high, particularly in those whose risk factors are insufficiently controlled.6,7”
From The Effect of Retatrutide on Kidney Parameters in Participants With Type 2 Diabetes Mellitus and/or Obesity (2025) · cites this paper as [6]
The Outcomes section (p. 2) lists death, myocardial infarction, stroke, and hospitalization for heart failure, but not kidney failure. The Discussion (p. 7) links risk factors outside target ranges to cardiovascular outcomes; it does not establish the claimed kidney-failure risk or assess whether that risk remains high despite newer therapies. Searched for kidney failure, end-stage renal disease, renal failure, and nephropathy. (LLM, conf=0.78)
Experimental — accuracy not yet measuredIn patients with advanced disease, e.g. T2DM and established microalbuminuria, an intensive, target-driven, multifactorial therapy resulted in 50% fewer microvascular and macrovascular events after 7.8 years of follow-up.
“In patients with advanced disease, e.g.T2DM and established microalbuminuria, an intensive, target-driven, multifactorial therapy (Steno-2 study; targets: HbA1c <6.5%, total cholesterol <4.5 mmol/L [175 mg/dL], and BP <130/80 mmHg) resulted in 50% fewer microvascular and macrovascular events after 7.8 years of follow-up.361”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [361]
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- Authors
- Rawshani, A., Rawshani, A., Franzén, S., Sattar, N., Eliasson, B., Svensson, A.-M., Zethelius, B., Miftaraj, M., McGuire, D. K., Rosengren, A., & Gudbjörnsdottir, S.
- Affiliations
- Uppsala University (SE)
- From the Department of Molecular and Clinical Medicine, Institute of Medicine (Aidin Rawshani, Araz Rawshani, B.E., A. Rosengren, S.G.), and the Health Metrics Unit, Sahlgrenska Academy (S.F.), University of Gothenburg, and the Swedish National Diabetes Register, Center of Registers in Region (Aidin Rawshani, Araz Rawshani, S.F., B.E., A.-M.S., M.M., S.G.), Gothenburg, and the Department of Public Health and Caring Sciences–Geriatrics, Uppsala University, and the Swedish Medical Products Agency,...
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2018-08-16
- Volume
- 379
- Issue
- 7
- Pages
- 633-644
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2887185538
- Cited by
- 1,475
- References
- 22
- Citations by year
- 2026: 158 · 2025: 172 · 2024: 178 · 2023: 175 · 2022: 197 · 2021: 219 · 2020: 210 · 2019: 141 · 2018: 20 · 2013: 1
- FWCI
- 116.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- type 2 diabetes, cardiovascular risk factors, mortality, acute myocardial infarction, stroke, heart failure hospitalization, HbA1c, LDL cholesterol, albuminuria, smoking, blood pressure, Swedish National Diabetes Register, matched cohort comparison
- MeSH terms
- Adult, Albuminuria, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Female, Glycated Hemoglobin, Humans, Hypercholesterolemia, Hypertension, Male, Middle Aged, Myocardial Infarction, Risk Factors, Smoking, Sweden, Cohort Studies, Body Mass Index, Stroke
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