Type 1 Diabetes Mellitus and Cardiovascular Disease: A Scientific Statement From the American Heart Association and American Diabetes Association

Perspective:

The following are 10 points to remember from this Scientific Statement on type 1 diabetes mellitus (T1DM) and cardiovascular disease (CVD):

1. Despite the known higher risk of CVD in individuals with T1DM, the pathophysiology underlying the relationship between cardiovascular events, CVD risk factors, and T1DM is not well understood.

2. T1DM is characterized by an absolute insulin deficiency caused by T-cell–mediated autoimmune destruction of pancreatic β-cells, which frequently begins with an intercurrent infection that may be a trigger. It is the predominant form of DM during childhood and adolescence, and can present in adults with the typical symptoms of polyuria, polydipsia, and weight loss and ketoacidosis. T1DM in adults may represent milder forms with enough residual β-cell function to avoid dependence on insulin for many years.

3. The age-adjusted relative risk (RR) for CVD in T1DM is ≈10 times that of the general population, and the cause of death in >3% per year after 20 years. Most studies report cumulative incidences of ≈15% over ≈15 years, whereas stroke rate is about 2x the general population.

4. By 65 years of age, the cumulative probability of lower-extremity amputation in a Swedish cohort was 11% for women with T1DM and 20.7% for men. Predictors of all types of peripheral arterial disease (PAD) include classic risk factors, history of foot lesions or ulcers, diastolic blood pressure, hemoglobin A1c (HbA1c), DM duration, albumin excretion rate, glomerular filtration rate, and retinopathy. A 1% increase in HbA1c increases the risk of PAD by 18%, but aggressive glycemic control to lower the HbA1c did not appear to reduce rates of PAD in the DCCT/EDIC study.

5. Endothelial function is abnormal at an early stage of T1DM including in children, and the extent of endothelial dysfunction correlates significantly with blood glucose levels. Adults with endothelial dysfunction are more likely to develop coronary heart disease (CHD). Preclinical atherosclerosis is more common in T1DM than the general population including coronary artery calcification (CAC), and carotid intima-media thickness and plaque that are increased in children, adolescents, and adults. Preclinical atherosclerosis is associated with the traditional and glycemia-related risk factors.

6. Compared to T2DM, coronary atherosclerosis in the setting of T1DM is characterized by more inflammation, tighter stenoses, multiple vessel involvement, and more distal disease with more soft and fibrous and concentric location of lesions, but similar age/sex-adjusted coronary calcium scores. The extent of atherosclerosis by intravascular ultrasound in T1DM correlated with HbA1c; a 1% increase in mean HbA1c was associated with a 6.4% increase in coronary vessel stenosis. Several studies did not show an association between HbA1c and clinical CHD after adjustment for other CVD risk factors.

7. Epidemiological studies have identified factors important to the incidence and prevalence of CVD in T1DM which could be targets for risk reduction and include hypertension, proteinuria, obesity, HbA1c, lipid levels, smoking, exercise, and diet.

8. Recommendations for CVD risk factor treatment in adults with T1DM include the American Diabetes Association diet for all; insulin targeting HbA1c to <7%; angiotensin-converting enzyme inhibitor for microalbumin and chronic kidney disease; statins without CVD to goal low-density lipoprotein cholesterol <100 mg/dl and with CVD <70 mg/dl; blood pressure treatment begins at >140/80 mm Hg with goal <130/80 mm Hg; and adults with CVD should be treated with aspirin.

9. As in the general population, guidelines recommend additional testing for CHD for any patient (including those with T1DM) with symptoms suggestive of CHD, an abnormal resting electrocardiogram (ECG), or clustering of CVD risk factors that yields an intermediate or high global risk estimate. For patients able to walk, exercise treadmill testing alone is indicated because of its high cost-effectiveness.

10. In persons not able to exercise or with ECG abnormalities of left ventricular hypertrophy, vasodilator myocardial perfusion imaging or pharmacological stress echocardiography may be required. The diagnostic accuracy of these noninvasive testing modalities may differ in T1DM compared with the general population. It is reasonable to apply the current guidelines for the use of CAC assessment in T1DM, as recommended for the general population.

Clinical Topics: Dyslipidemia, Noninvasive Imaging, Prevention, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Lipid Metabolism, Nonstatins, Echocardiography/Ultrasound, Nuclear Imaging, Diet, Hypertension, Smoking

Keywords: Hypertrophy, Left Ventricular, Myocardial Perfusion Imaging, Proteinuria, Peripheral Arterial Disease, Blood Pressure, Electrocardiography, Aspirin, Albumins, Vasodilator Agents, Hemoglobin A, Glycosylated, Cholesterol, Cause of Death, Obesity, Amputation, Diabetes Mellitus, Type 1, Hypertension, Inflammation, Stroke, Insulin, Carotid Intima-Media Thickness, Risk Reduction Behavior, Weight Loss, Echocardiography, Stress, Polydipsia, Angiotensin-Converting Enzyme Inhibitors, American Heart Association, Constriction, Pathologic, Smoking, Ulcer, Polyuria, Blood Glucose, Ketosis, Glomerular Filtration Rate, Diet, Renal Insufficiency, Chronic


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