Epidemiology

Diabetes prevalence is increasing worldwide, compounded by both population growth and aging.[3] 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] Worldwide, 536.6 million adults had diabetes in 2021, and projections estimate that 783.2 million adults will have diabetes by 2045.[1] Total diabetes prevalence, especially among older adults, primarily reflects type 2 diabetes, which in 2021 accounted for 96% of diabetes cases.[5]

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] CVD is the leading cause of hospital admission for people with diabetes, with CAD as the predominant subtype.[7] 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]

Globally, it is estimated that 50% of deaths among patients with type 2 diabetes are due to CVD.[9] In 2014, death due to CVD was 1.7 times higher among adults with diabetes than in adults without diabetes.[10] 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] 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] 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]

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][15] 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]

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][18] Mortality from MI is about 1.5- to 2-fold greater in people with diabetes than in people without diabetes.[19] 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] 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]

Heart failure

Although not as frequent as MI, hospitalization for heart failure is a common event in patients with type 2 diabetes.[22] 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] Greater levels of insulin resistance and dysglycemia are associated with increased risk of heart failure in patients with newly diagnosed type 2 diabetes.[23][24] 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]

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] 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]

Cerebrovascular disease (stroke and transient ischemic attack)

The risk of stroke is increased 1.5- to 4-fold in patients with diabetes.[25][26] Diabetes is associated with a significantly increased risk of stroke recurrence.[27] Stroke outcomes, including in-hospital and long-term mortality, are worse in people with diabetes.[26] 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]

Peripheral arterial disease (PAD)

Cigarette smoking and diabetes are the two major risk factors for PAD.[28] 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] 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] Diabetes is associated with increased risk of critical lower extremity ischemia and major amputation in patients with PAD.[30]

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