Diabetes prevalence is increasing worldwide, compounded by both population growth and aging.[3]NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants. Lancet. 2016 Apr 6;387(10027):1513-30.
https://www.doi.org/10.1016/S0140-6736(16)00618-8
http://www.ncbi.nlm.nih.gov/pubmed/27061677?tool=bestpractice.com
In the US, 29.3 million adults (10.6% of the population) had diagnosed diabetes between 2017 and 2020, while a further 9.7 million (3.5% of the population) had undiagnosed diabetes.[4]Martin SS, Aday AW, Almarzooq ZI, et al. 2024 Heart disease and stroke statistics: a report of US and global data from the American Heart Association. Circulation. 2024 Feb 20;149(8):e347-913.
https://www.ahajournals.org/doi/full/10.1161/CIR.0000000000001209
http://www.ncbi.nlm.nih.gov/pubmed/38264914?tool=bestpractice.com
Worldwide, 536.6 million adults had diabetes in 2021, and projections estimate that 783.2 million adults will have diabetes by 2045.[1]International Diabetes Federation. IDF diabetes atlas. 10th ed. Brussels, Belgium: International Diabetes Federation; 2021.
https://diabetesatlas.org/atlas/tenth-edition
Total diabetes prevalence, especially among older adults, primarily reflects type 2 diabetes, which in 2021 accounted for 96% of diabetes cases.[5]GBD 2021 Diabetes Collaborators. Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021. Lancet. 2023 Jul 15;402(10397):203-34.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10364581
http://www.ncbi.nlm.nih.gov/pubmed/37356446?tool=bestpractice.com
Diabetes confers a two- to fourfold excess lifetime risk of developing cardiovascular disease ([CVD]; coronary artery disease [CAD], stroke, heart failure, atrial fibrillation, and peripheral artery disease), independent of other risk factors.[6]Marx N, Federici M, Schütt K, et al. 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. Eur Heart J. 2023 Oct 14;44(39):4043-140.
https://academic.oup.com/eurheartj/article/44/39/4043/7238227
http://www.ncbi.nlm.nih.gov/pubmed/37622663?tool=bestpractice.com
CVD is the leading cause of hospital admission for people with diabetes, with CAD as the predominant subtype.[7]Feleke BE, Sacre J, Tomic D, et al. Hospital admissions among people with diabetes: a systematic review. Diabet Med. 2024 Jan;41(1):e15236.
http://www.ncbi.nlm.nih.gov/pubmed/37811704?tool=bestpractice.com
Data from the CALIBER UK cohort show the most common initial CVD complications for those with diabetes to be PAD (16.2%) and heart failure (14.1%), followed by stable angina (11.9%), nonfatal myocardial infarction (MI) (11.5%), and stroke (10.3%).[8]Shah AD, Langenberg C, Rapsomaniki E, et al. Type 2 diabetes and incidence of cardiovascular diseases: a cohort study in 1·9 million people. Lancet Diabetes Endocrinol. 2015 Feb;3(2):105-13.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4303913
http://www.ncbi.nlm.nih.gov/pubmed/25466521?tool=bestpractice.com
Globally, it is estimated that 50% of deaths among patients with type 2 diabetes are due to CVD.[9]Cosentino F, Verma S, Ambery P, et al. Cardiometabolic risk management: insights from a European Society of Cardiology Cardiovascular Round Table. Eur Heart J. 2023 Oct 14;44(39):4141-56.
https://academic.oup.com/eurheartj/article/44/39/4141/7224026
http://www.ncbi.nlm.nih.gov/pubmed/37448181?tool=bestpractice.com
In 2014, death due to CVD was 1.7 times higher among adults with diabetes than in adults without diabetes.[10]Leon BM, Maddox TM. Diabetes and cardiovascular disease: epidemiology, biological mechanisms, treatment recommendations and future research. World J Diabetes. 2015 Oct 10;6(13):1246-58.
https://www.wjgnet.com/1948-9358/full/v6/i13/1246.htm
http://www.ncbi.nlm.nih.gov/pubmed/26468341?tool=bestpractice.com
While there was an overall decrease in cardiovascular (CV) mortality from 1998 to 2014, decreases were smaller for adults with type 2 diabetes compared with adults without diabetes.[11]Rawshani A, Rawshani A, Franzén S, et al. Mortality and cardiovascular disease in type 1 and type 2 diabetes. N Engl J Med. 2017 Apr 13;376(15):1407-18.
https://www.nejm.org/doi/full/10.1056/NEJMoa1608664
http://www.ncbi.nlm.nih.gov/pubmed/28402770?tool=bestpractice.com
One Danish population-based cohort study found that from 1996 to 2015, the 5-year risk of first-time ischemic stroke was approximately halved in patients with incident type 2 diabetes mellitus and no prior atherosclerotic CVD.[12]Gyldenkerne C, Kahlert J, Olesen KKW, 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 Sep 1;45(9):2144-51.
https://diabetesjournals.org/care/article/45/9/2144/147286/Twenty-Year-Temporal-Trends-in-Risk-of-Ischemic
http://www.ncbi.nlm.nih.gov/pubmed/35876649?tool=bestpractice.com
Increased use of medication to control CV risk factors has likely influenced the decrease in CV morbidity and mortality in patients with type 2 diabetes.[13]Gyldenkerne C, Knudsen JS, Olesen KKW, et al. Nationwide trends in cardiac risk and mortality in patients with incident type 2 diabetes: a Danish cohort study. Diabetes Care. 2021;44(10):2353-60.
http://www.ncbi.nlm.nih.gov/pubmed/34380704?tool=bestpractice.com
Although the risk of CVD in patients with type 1 diabetes has also decreased over time, there remains considerable excess CV risk in this group compared with the general population.[14]de Ferranti SD, de Boer IH, Fonseca V, et al. Type 1 diabetes mellitus and cardiovascular disease: a scientific statement from the American Heart Association and American Diabetes Association. Circulation. 2014 Aug 11;130(13):1110-30.
https://www.ahajournals.org/doi/full/10.1161/CIR.0000000000000034
[15]Harjutsalo V, Pongrac Barlovic D, Groop PH. Long-term population-based trends in the incidence of cardiovascular disease in individuals with type 1 diabetes from Finland: a retrospective, nationwide, cohort study. Lancet Diabetes Endocrinol. 2021 Sep;9(9):575-85.
http://www.ncbi.nlm.nih.gov/pubmed/34303414?tool=bestpractice.com
One Finnish study found the risk of CVD to be 64.3% in patients with type 1 diabetes of duration >50 years, compared with 7.4% in individuals without diabetes.[16]Harjutsalo V, Barlovic DP, Gordin D, et al. Presence and determinants of cardiovascular disease and mortality in individuals with type 1 diabetes of long duration: the FinnDiane 50 years of diabetes study. Diabetes Care. 2021 Aug;44(8):1885-93.
https://diabetesjournals.org/care/article/44/8/1885/138863/Presence-and-Determinants-of-Cardiovascular
http://www.ncbi.nlm.nih.gov/pubmed/34162664?tool=bestpractice.com
CAD (MI, angina)
CAD is the most common manifestation of CVD in people with diabetes. In patients with established CAD, 70% to 75% have abnormal glucose regulation, with more than 30% having known diabetes, up to 20% having undiagnosed diabetes, and around 25% having impaired glucose tolerance or prediabetes.[17]Standl E, Khunti K, Hansen TB, et al. The global epidemics of diabetes in the 21st century: current situation and perspectives. Eur J Prev Cardiol. 2019 Dec;26(2 Suppl):7-14.
https://academic.oup.com/eurjpc/article/26/2_suppl/7/5925429
http://www.ncbi.nlm.nih.gov/pubmed/31766915?tool=bestpractice.com
[18]Fleg JL, Forman DE, Berra K, et al; American Heart Association. Secondary prevention of atherosclerotic cardiovascular disease in older adults: a scientific statement from the American Heart Association. Circulation. 2013 Nov 26;128(22):2422-46.
https://www.ahajournals.org/doi/full/10.1161/01.cir.0000436752.99896.22
Mortality from MI is about 1.5- to 2-fold greater in people with diabetes than in people without diabetes.[19]Klein L, Gheorghiade M. Management of the patient with diabetes mellitus and myocardial infarction: clinical trials update. Am J Med. 2004 Mar 8;116(suppl 5A):47-63S.
http://www.ncbi.nlm.nih.gov/pubmed/15019863?tool=bestpractice.com
In the UK Prospective Diabetes Study (UKPDS), the odds ratio for acute MI case fatality was 1.17 per 1% increase in hemoglobin A1c (HbA1c).[20]Stevens RJ, Coleman RL, Adler AI, et al. Risk factors for myocardial infarction case fatality and stroke case fatality in type 2 diabetes: UKPDS 66. Diabetes Care. 2004 Jan;27(1):201-7.
http://care.diabetesjournals.org/content/27/1/201.full
http://www.ncbi.nlm.nih.gov/pubmed/14693990?tool=bestpractice.com
Additionally, patients with diabetes who are admitted with high-risk non-ST elevation MI are known to have worse early outcomes, including mortality, compared with patients without diabetes who present similarly.[21]Giraldez RR, Clare RM, Lopes RD, et al. Prevalence and clinical outcomes of undiagnosed diabetes mellitus and prediabetes among patients with high-risk non-ST-segment elevation acute coronary syndrome. Am Heart J. 2013 Jun;165(6):918-25.
http://www.ncbi.nlm.nih.gov/pubmed/23708162?tool=bestpractice.com
Heart failure
Although not as frequent as MI, hospitalization for heart failure is a common event in patients with type 2 diabetes.[22]Sacre JW, Magliano DJ, Shaw JE. Incidence of hospitalization for heart failure relative to major atherosclerotic events in type 2 diabetes: a meta-analysis of cardiovascular outcomes trials. Diabetes Care. 2020 Oct;43(10):2614-23.
https://diabetesjournals.org/care/article/43/10/2614/35990/Incidence-of-Hospitalization-for-Heart-Failure
http://www.ncbi.nlm.nih.gov/pubmed/32958618?tool=bestpractice.com
People with type 2 diabetes are twice as likely to develop heart failure than those without type 2 diabetes and the prevalence of heart failure in people with type 2 diabetes in the US is estimated to be as high as 22%.[23]Pandey A, Khan MS, Patel KV, et al. Predicting and preventing heart failure in type 2 diabetes. Lancet Diabetes Endocrinol. 2023 Aug;11(8):607-24.
http://www.ncbi.nlm.nih.gov/pubmed/37385290?tool=bestpractice.com
Greater levels of insulin resistance and dysglycemia are associated with increased risk of heart failure in patients with newly diagnosed type 2 diabetes.[23]Pandey A, Khan MS, Patel KV, et al. Predicting and preventing heart failure in type 2 diabetes. Lancet Diabetes Endocrinol. 2023 Aug;11(8):607-24.
http://www.ncbi.nlm.nih.gov/pubmed/37385290?tool=bestpractice.com
[24]Wamil M, Coleman RL, Adler AI, et al. Increased risk of incident heart failure and death is associated with insulin resistance in people with newly diagnosed type 2 diabetes: UKPDS 89. Diabetes Care. 2021 Aug;44(8):1877-84.
https://diabetesjournals.org/care/article/44/8/1877/138817/Increased-Risk-of-Incident-Heart-Failure-and-Death
http://www.ncbi.nlm.nih.gov/pubmed/34162666?tool=bestpractice.com
Type 2 diabetes duration has also been identified as an independent risk factor for heart failure, with each 5-year increase associated with a 17% increased risk.[23]Pandey A, Khan MS, Patel KV, et al. Predicting and preventing heart failure in type 2 diabetes. Lancet Diabetes Endocrinol. 2023 Aug;11(8):607-24.
http://www.ncbi.nlm.nih.gov/pubmed/37385290?tool=bestpractice.com
Women appear to be more at risk of heart failure than men, potentially due to a greater burden of cardiometabolic risk factors such as increased body mass index and systolic blood pressure at the time of diabetes diagnosis, therapeutic inertia that disproportionately affects women, and distinct hormone profiles.[23]Pandey A, Khan MS, Patel KV, et al. Predicting and preventing heart failure in type 2 diabetes. Lancet Diabetes Endocrinol. 2023 Aug;11(8):607-24.
http://www.ncbi.nlm.nih.gov/pubmed/37385290?tool=bestpractice.com
Similarly, racial disparities have been reported in the type 2 diabetes-associated risk of heart failure, with black individuals at higher risk than those of other races; these differences largely seem to be driven by a higher burden of adverse social determinants of health, including lower income and lower access to health care.[23]Pandey A, Khan MS, Patel KV, et al. Predicting and preventing heart failure in type 2 diabetes. Lancet Diabetes Endocrinol. 2023 Aug;11(8):607-24.
http://www.ncbi.nlm.nih.gov/pubmed/37385290?tool=bestpractice.com
Cerebrovascular disease (stroke and transient ischemic attack)
The risk of stroke is increased 1.5- to 4-fold in patients with diabetes.[25]Chen R, Ovbiagele B, Feng W. Diabetes and stroke: epidemiology, pathophysiology, pharmaceuticals and outcomes. Am J Med Sci. 2016 Apr;351(4):380-6.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5298897
http://www.ncbi.nlm.nih.gov/pubmed/27079344?tool=bestpractice.com
[26]Idris I, Thomson GA, Sharma JC. Diabetes mellitus and stroke. Int J Clin Pract. 2006 Jan;60(1):48-56.
http://www.ncbi.nlm.nih.gov/pubmed/16409428?tool=bestpractice.com
Diabetes is associated with a significantly increased risk of stroke recurrence.[27]Zhang L, Li X, Wolfe CDA, et al. Diabetes as an independent risk factor for stroke recurrence in ischemic stroke patients: an updated meta-analysis. Neuroepidemiology. 2021;55(6):427-35.
https://karger.com/ned/article/55/6/427/828639/Diabetes-As-an-Independent-Risk-Factor-for-Stroke
http://www.ncbi.nlm.nih.gov/pubmed/34673640?tool=bestpractice.com
Stroke outcomes, including in-hospital and long-term mortality, are worse in people with diabetes.[26]Idris I, Thomson GA, Sharma JC. Diabetes mellitus and stroke. Int J Clin Pract. 2006 Jan;60(1):48-56.
http://www.ncbi.nlm.nih.gov/pubmed/16409428?tool=bestpractice.com
Diabetes increases the risk of ischemic stroke to a greater degree than hemorrhagic stroke. Lacunar infarcts are more common in patients with diabetes, who are more likely to develop silent lacunar infarcts. However, transient ischemic attacks are less common in people with diabetes than in those without diabetes. The risk of stroke increases with worsening glycemic control. In the UKPDS, the odds ratio for stroke case fatality was 1.37 per 1% increase in HbA1c.[20]Stevens RJ, Coleman RL, Adler AI, et al. Risk factors for myocardial infarction case fatality and stroke case fatality in type 2 diabetes: UKPDS 66. Diabetes Care. 2004 Jan;27(1):201-7.
http://care.diabetesjournals.org/content/27/1/201.full
http://www.ncbi.nlm.nih.gov/pubmed/14693990?tool=bestpractice.com
Peripheral arterial disease (PAD)
Cigarette smoking and diabetes are the two major risk factors for PAD.[28]Writing Committee Members, Gornik HL, Aronow HD, et al. 2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS guideline for the management of lower extremity peripheral artery disease: a report of the American College of Cardiology/American Heart Association Joint Committee on clinical practice guidelines. J Am Coll Cardiol. 2024 Jun 18;83(24):2497-604.
https://www.sciencedirect.com/science/article/pii/S0735109724003814
http://www.ncbi.nlm.nih.gov/pubmed/38752899?tool=bestpractice.com
Risk factors associated with an increased risk for PAD in people with diabetes include increased age, hypertension, dyslipidemia, poor glycemic control, longer duration of diabetes, neuropathy, retinopathy, and a prior history of CVD.[29]American Diabetes Association. Standards of care in diabetes - 2024. Diabetes Care 2024 Jan 1;47(suppl 1):S1-321.
https://diabetesjournals.org/care/issue/47/Supplement_1
Of symptomatic patients with PAD, 20% are known to have diabetes; however, most patients with PAD are asymptomatic. Up to two-thirds of people with asymptomatic PAD have been shown to have comorbid diabetes.[29]American Diabetes Association. Standards of care in diabetes - 2024. Diabetes Care 2024 Jan 1;47(suppl 1):S1-321.
https://diabetesjournals.org/care/issue/47/Supplement_1
Diabetes is associated with increased risk of critical lower extremity ischemia and major amputation in patients with PAD.[30]Barnes JA, Eid MA, Creager MA, et al. Epidemiology and risk of amputation in patients with diabetes and peripheral artery disease. Arterioscler Thromb Vasc Biol. 2020 Aug;40(8):1808-17.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377955
http://www.ncbi.nlm.nih.gov/pubmed/32580632?tool=bestpractice.com