Trends in non-coronary arterial outcomes in people with type 1 or type 2 diabetes mellitus
Authors: Michael Maeng, Christine Gyldenkerne
Journal: The Lancet Regional Health - Europe (2024)

Type 1 and type 2 diabetes mellitus are both associated with an increased risk of cardiovascular disease.1Cardiovascular disease and risk management: standards of medical care in diabetes-2022.Diabetes Care. 2022; 45: S144-S174Crossref PubMed Scopus (294) Google Scholar, 2Marx N. Federici M. Schütt K. et al.2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes.Eur Heart J. 2023; 44: 4043-4140Crossref PubMed Scopus (56) Google Scholar, 3Olesen K.K.W. Gyldenkerne C. Thim T. Thomsen R.W. Maeng M. Peripheral artery disease, lower limb revascularization, and amputation in diabetes patients with and without coronary artery disease: a cohort study from the Western Denmark Heart Registry.BMJ Open Diabetes Res Care. 2021; 9e001803Crossref PubMed Scopus (13) Google Scholar In this Issue of the Lancet Regional Health—Europe, two cohort studies investigated trends in non-coronary arterial complications in people with either type 1 (N = 34,263)4Avdic Tarik Eliasson Björn Rawshani Araz et al.Non-coronary arterial outcomes in people with type 1 diabetes mellitus: a Swedish retrospective cohort study.Lancet Reg Health Eur. 2024; 39: 100852https://doi.org/10.1016/j.lanepe.2024.100852Summary Full Text Full Text PDF Scopus (1) Google Scholar or type 2 diabetes mellitus (N = 655,250)5Rawshani Araz Eliasson Björn Jan Boren et al.Non-coronary peripheral arterial complications in people with type 2 diabetes: a nationwide observational study from Sweden.Lancet Reg Health Europe. 2024; 39: 100888https://doi.org/10.1016/j.lanepe.2024.100888Summary Full Text Full Text PDF Scopus (1) Google Scholar based on the Swedish National Diabetes Register (NDR) between 2001 and 2019. In addition, up to five age-, sex-, and county-matched individuals functioned as a general population comparison cohort. In both studies, the authors report significant decreases in incidences of extracranial large artery disease, lower extremity artery disease, and diabetic foot disease in people with type 1 or type 2 diabetes mellitus (Table 1). Yet, both types of diabetes mellitus remain strongly associated with higher incidences of extracranial large artery disease and lower extremity artery disease compared with controls. The authors also report incidences of aortic aneurism and aortic dissection, which in general were low and stable over time in people with diabetes. Furthermore, the authors examined the relative prognostic impact of cardiometabolic risk factors and elegantly demonstrated that each cardiometabolic risk factor within target was associated with a reduced relative risk of outcomes. In summary, the two papers add valuable insights to our current understanding of the risk of non-coronary arterial complications in patients with diabetes and the prognostic importance of modifiable risk factors. However, there are two main potential limitations related to the methodology used in both studies that need to be acknowledged.Table 1Non-coronary arterial outcomes in the first and last calendar periods.Age- and sex standardized incidence rates per 100,000 person-years2001–20022016/7–2019aFor patients with T2DM, the calendar period for extracranial large artery disease and lower extremity disease is 2016–2019, for all other groups the calendar period is 2017–2019.Extracranial large artery disease T1DM87bReported as 296.5 in the paper concerning type 1 diabetes mellitus, which corresponds to the calendar period 2003–2004.3 The standardized incidence rate was highest in 2003–2004 and declined gradually afterwards.84 Controls6828 T2DM17084 Controls8044Lower extremity artery disease T1DM456311 Controls6653 T2DM338190 Controls15561Diabetic foot disease T1DM81477 T2DM309226T1DM, type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus.a For patients with T2DM, the calendar period for extracranial large artery disease and lower extremity disease is 2016–2019, for all other groups the calendar period is 2017–2019.b Reported as 296.5 in the paper concerning type 1 diabetes mellitus, which corresponds to the calendar period 2003–2004.3Olesen K.K.W. Gyldenkerne C. Thim T. Thomsen R.W. Maeng M. Peripheral artery disease, lower limb revascularization, and amputation in diabetes patients with and without coronary artery disease: a cohort study from the Western Denmark Heart Registry.BMJ Open Diabetes Res Care. 2021; 9e001803Crossref PubMed Scopus (13) Google Scholar The standardized incidence rate was highest in 2003–2004 and declined gradually afterwards. Open table in a new tab T1DM, type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus. First, participants were allowed to contribute observation time for several calendar periods if they did not experience an event. Thus, a person with diabetes entered into the Swedish NDR in 2001 could contribute observation time in the 2001–2002 study period and, if not censored due to an event, would continue to contribute with observation time in the 2003–2004, 2005–2006, etc, calendar periods if no events occurred. As acknowledged by the authors, this leads to "a sequential accumulation of healthier individuals in each period. As a result, this may result in a cohort that progressively comprise individuals at lower risk."4Avdic Tarik Eliasson Björn Rawshani Araz et al.Non-coronary arterial outcomes in people with type 1 diabetes mellitus: a Swedish retrospective cohort study.Lancet Reg Health Eur. 2024; 39: 100852https://doi.org/10.1016/j.lanepe.2024.100852Summary Full Text Full Text PDF Scopus (1) Google Scholar This issue is likely more influential for people with type 1 diabetes mellitus who were much younger when entering the Swedish NDR than people with type 2 diabetes mellitus (mean age 33 years for the former vs 64 years for the latter).4Avdic Tarik Eliasson Björn Rawshani Araz et al.Non-coronary arterial outcomes in people with type 1 diabetes mellitus: a Swedish retrospective cohort study.Lancet Reg Health Eur. 2024; 39: 100852https://doi.org/10.1016/j.lanepe.2024.100852Summary Full Text Full Text PDF Scopus (1) Google Scholar,5Rawshani Araz Eliasson Björn Jan Boren et al.Non-coronary peripheral arterial complications in people with type 2 diabetes: a nationwide observational study from Sweden.Lancet Reg Health Europe. 2024; 39: 100888https://doi.org/10.1016/j.lanepe.2024.100888Summary Full Text Full Text PDF Scopus (1) Google Scholar Well-treated, compliant people with type 1 diabetes mellitus have a low risk for many years and such patients will likely contribute observation time for many of the examined calendar periods. In contrast, non-compliant people with type 1 diabetes mellitus will have a high risk of events and thus a lower risk of contributing observation time to several calendar periods. Thus, it is unclear how much of the reported lower incidence of outcomes over time that may be due to the study design. It is noteworthy that the incidences of extracranial large artery disease and lower extremity artery disease also decreased in the matched controls. Consequently, the reported decline in both types of artery diseases could possibly either reflect the accumulation of healthier individuals or be due to a general risk reduction in both people with diabetes and the matched controls. This should be addressed in future studies with adequate study designs. Second, the studies included participants with large variations in the duration of diabetes rather than starting follow-up when diagnosed with diabetes.6Gyldenkerne C. Knudsen J.S. Olesen K.K.W. et al.Nationwide trends in cardiac risk and mortality in patients with incident type 2 diabetes: a Danish cohort study.Diabetes Care. 2021; https://doi.org/10.2337/dc21-0383Crossref PubMed Google Scholar, 7Gyldenkerne C. Kahlert J. Olesen K.K.W. et al.Twenty-year temporal trends in risk of ischemic stroke in incident type 2 diabetes: a Danish population-based cohort study.Diabetes Care. 2022; 45: 2144-2151Crossref PubMed Scopus (3) Google Scholar, 8Gyldenkerne C. Mortensen M.B. Kahlert J. et al.10-year cardiovascular risk in patients with newly diagnosed type 2 diabetes mellitus.J Am Coll Cardiol. 2023; 82: 1583-1594Crossref PubMed Scopus (2) Google Scholar The Swedish NDR was established in 1996. Initially, this register comprised mainly people receiving care at hospital clinics, with later expansion to include an increasing number of people managed by general practitioners. People with diabetes entered early in the register were thus selected in a different way than those enrolled later. E.g., the mean age of people with type 1 diabetes mellitus was 38 years in 2001–2002, which declined to 26 years in 2013–2014, with corresponding diabetes durations being 18 years and 8 years, respectively. This is an inherent bias caused by the way the Swedish NDR was constructed. This bias can be circumvented, for example by using registries to identify people with newly diagnosed diabetes.6Gyldenkerne C. Knudsen J.S. Olesen K.K.W. et al.Nationwide trends in cardiac risk and mortality in patients with incident type 2 diabetes: a Danish cohort study.Diabetes Care. 2021; https://doi.org/10.2337/dc21-0383Crossref PubMed Google Scholar, 7Gyldenkerne C. Kahlert J. Olesen K.K.W. et al.Twenty-year temporal trends in risk of ischemic stroke in incident type 2 diabetes: a Danish population-based cohort study.Diabetes Care. 2022; 45: 2144-2151Crossref PubMed Scopus (3) Google Scholar, 8Gyldenkerne C. Mortensen M.B. Kahlert J. et al.10-year cardiovascular risk in patients with newly diagnosed type 2 diabetes mellitus.J Am Coll Cardiol. 2023; 82: 1583-1594Crossref PubMed Scopus (2) Google Scholar The most important and valid clinical implication of these two Swedish NDR papers is that non-arterial outcomes can be reduced by optimizing treatment of modifiable risk factors. Future studies should examine whether early initiation of available cardiovascular protective antidiabetic drugs, such as sodium-glucose cotransporter 2 inhibitors and particularly glucagon-like peptide 1 agonists, can further reduce the risk of noncoronary arterial outcomes. These drugs combine weight loss and glucose-lowering effects, and they have the potential to inhibit or delay the development type 2 diabetes as well as reduce the diabetes-associated risk of coronary and non-coronary arterial outcomes.1Cardiovascular disease and risk management: standards of medical care in diabetes-2022.Diabetes Care. 2022; 45: S144-S174Crossref PubMed Scopus (294) Google Scholar,2Marx N. Federici M. Schütt K. et al.2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes.Eur Heart J. 2023; 44: 4043-4140Crossref PubMed Scopus (56) Google Scholar,9Lincoff A.M. Brown-Frandsen K. Colhoun H.M. et al.Semaglutide and cardiovascular outcomes in obesity without diabetes.N Engl J Med. 2023; 389: 2221-2232Crossref PubMed Scopus (59) Google Scholar Moreover, we need additional temporal studies to confirm the observed findings accounting for the above-mentioned limitations. Dr. Maeng drafted this commentary, which subsequently was revised in collaboration with Dr. Gyldenkerne. Dr. Maeng is supported by a grant from the Novo Nordisk Foundation (grant number NNF22OC0074083); has received lecture and/or advisory board fees from AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, and Novo Nordisk, has received a travel grant from Novo Nordisk, has received institutional research grants from Bayer, Novo Nordisk and Philips, has ongoing research contracts with Janssen, Novo Nordisk, and Philips, and is a minor stockholder in Eli Lilly & Company, Novo Nordisk, and Verve Therapeutics. Dr. Gyldenkerne has no conflicts of interest. Non-coronary arterial outcomes in people with type 1 diabetes mellitus: a Swedish retrospective cohort studyPeripheral arterial complications decreased in persons with type 1 diabetes mellitus, except for aortic aneurysm which remained low. Besides glycemic control, traditional cardiovascular risk factors were associated with incident outcomes. Risk of these outcomes increased with additional risk factors present. Persons with type 1 diabetes mellitus exhibited a lower risk of aortic aneurysm compared to controls, despite presence of cardiovascular risk factors. Full-Text PDF Open AccessNon-coronary peripheral arterial complications in people with type 2 diabetes: a Swedish retrospective cohort studyThe incidence of non-coronary peripheral arterial complications has declined significantly among persons with type 2 diabetes mellitus, with the exception of aortic aneurysm. HbA1c, smoking and blood pressure demonstrated greatest relative contribution for outcomes and lower levels of cardiometabolic risk factors are associated with reduced relative risk of outcomes. Full-Text PDF Open Access