Risk Factors for Cardiovascular Disease in Youth With Type 1 Diabetes

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Substantial gaps exist in the knowledge and understanding of the safety and efficacy of cardiovascular disease therapies in children and adolescents with type 1 diabetes.
Substantial gaps exist in the knowledge and understanding of the safety and efficacy of cardiovascular disease therapies in children and adolescents with type 1 diabetes.

Early treatment of cardiovascular disease risk factors such as dyslipidemia, hypertension, obesity, and glycemic control in youth diagnosed with type 1 diabetes (T1D) may have beneficial long-term benefits such as decreased risk for acquiring cardiovascular disease, lower healthcare costs, and prolonged life, according to a study published in the Lancet.

Researchers conducted a review of the literature to determine the strongest risk factors for developing cardiovascular disease in individuals diagnosed with T1D, and to summarize the pediatric data that currently exist in the literature regarding the identification and treatment of cardiovascular risk factors as recommended by current evidence-based guidelines.

The risk factors observed during the literature review in this study were noted to be hyperglycemia, hypertension, dyslipidemia, and diabetic kidney disease. 

Hyperglycemia was found in multiple adult studies to be associated with promoting endothelial dysfunction and arterial stiffness, which contributes to cardiovascular disease in individuals with T1D. However, the data from studies regarding the association between hyperglycemia and glycemic control and its effect on cardiovascular disease in pediatrics was found to be weak. 

Youth with T1D were noted in the literature to have higher rates of hypertension at 4% to 7% compared with 1% to 5% in youth not diagnosed with T1D.  When these high blood pressures were decreased to less than 120/70 mm Hg, the risk for adverse renal outcomes was found to be substantially lower in one study compared with individuals with blood pressure ≤130/80 mm Hg. The literature suggests that target organ damage caused by hypertension may begin during youth, since hypertension has been linked to arterial stiffness and increased carotid intima media thickness. Study data in both adults and children recommend a target blood pressure at or above the 90th percentile for age, sex, and height.

It is widely reported in both adult and pediatric literature that dyslipidemia is highly prevalent in youth with T1D, as hypercholesterolemia was found to be present in 28.6% of children, adolescents, and young adults with T1D. Dyslipidemia was also associated with arterial fatty streaks and low-density lipoprotein (LDL)-cholesterol concentrations. It is recommended that individuals reach targeted levels of LDL-cholesterol concentrations of <100mg/dL, high-density lipoprotein (HDL)-cholesterol concentrations >35 mg/dL, and triglycerides <150 mg/dL. Dyslipidemia is a modifiable risk factor for cardiovascular disease, with LDL-concentrations above the recommended threshold found to place an individual at a significantly higher risk for cardiovascular disease.

Finally, diabetic kidney disease is preceded by a significant period of time without signs or symptoms of disease, but is a major cause of end-stage renal disease, dialysis, and a crucial risk factor for cardiovascular disease. Study results found microalbuminuria to be an early clinical marker for diabetic kidney disease, yet it is undertreated in youth who present with increased albumin excretion with T1D, as only 36% were found to be treated with renin-angiotensin-aldosterone system inhibitors. Therefore, clinicians should routinely check for microalbuminuria and begin early treatment with the use of an angiotensin-converting enzyme (ACE) inhibitor.

Obesity in youth was found to increase the overall lifetime risk for early death as a result of cardiovascular disease. The prevalence of youth with T1D is increasing, and likely as a result of the fear of hypoglycemia, there is reduced exercising and increased carbohydrate intake. Clinicians should emphasize to youth the importance of exercising not only for glycemic control, but also to reduce the risk for cardiovascular disease and early death. Insulin resistance was found to predict incident cardiovascular disease, but the mechanisms remain unclear. 

Other lifestyle factors related to cardiovascular disease include exercise, diet, smoking sleep, stress, and depression. Regular exercise was associated with improved cardiovascular health related to reducing glycated hemoglobin (HbA1c) concentrations, triglycerides, and total cholesterol levels.  Smoking rates in youth with T1D were noted in one study to be 20% and found to be associated with coronary artery calcification. Altered sleep, poor sleep quality, and stress were associated with hypoglycemia, while general parental anxiety was found to be linked to depressive symptoms and led to worse glycemic control in youth. Clinicians should screen for depression in youth as it is important in glycemic management in youth with T1D.

Researchers found that youth with T1D had worse vascular function and increased arterial stiffness compared with youth without T1D, which emphasizes the importance of clinicians monitoring vascular function in this population. Unfortunately, despite hyperglycemia, blood pressure, and dyslipidemia being known major risk factors for cardiovascular disease, pediatric providers may not be familiar with the medications to treat these risk factors. Clinicians, especially pediatricians, should become comfortable with and follow standardized protocols for medications proven to be safe in adolescents with T1D as the earlier the introduction of these medications — such lipid-lowering agents — the greater the long-term benefit. Further, clinicians should strongly encourage and discuss achievable goals regarding lifestyle changes, as well as a pharmacotherapy plan if lifestyle changes fail.

Reference

Bjornstad P, Donaghue KC, Maahs DM. Macrovascular disease and risk factors in youth with type 1 diabetes: time to be more attentive to treatment? [published online February 20, 2018]. Lancet Diabetes Endocrinol. doi:10.1016/S2213-8587(18)30035-4

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