Type 1 Diabetes and Cardiovascular Disease: Advances and Needs

In this Scientific Statement jointly sponsored by the American Heart Association (AHA) and the American Diabetes Association (ADA), de Ferranti and colleagues provide a thorough overview of cardiovascular disease (CVD) in type 1 diabetes mellitus (T1DM).¹ In 2007 the AHA and ADA published a joint scientific paper on CVD in diabetes in which it was stated that all of the recommendations listed for patients with type 2 diabetes (T2DM) appear appropriate for those with T1DM as well.² In this previous joint statement the majority of the evidence focused on T2DM, which was not surprising given that this is the predominant form of diabetes. However, T1DM is not a rare disease, affecting more than 165,000 youth less than 20 years of age in the US in 20103 and an estimated 10-20 million people worldwide. In the current Scientific Statement, data are highlighted indicating specific pathophysiologic differences and opportunities to develop therapeutic interventions for CVD in T1DM as a distinct entity from CVD in T2DM. (To support such a distinction, consider the CVD risk assessment in a lean 40-year-old diagnosed with autoimmune T1DM pre-pubertally in contrast to an obese 40-year-old diagnosed recently or any number of such comparisons with differing CVD risk factors by diabetes etiology.) The current Scientific Statement concludes with a summary of gaps in knowledge and topics on which research is needed. One important advance made by the authors is to interpret and summarize the data to justify a distinction in CVD in T1DM compared to T2DM. As such, the current statement could be considered to update the previous AHA/ADA Scientific Statement concerning CVD and T1DM. Future research and clinical guidelines likely will build upon this and focus efforts to distinguish CVD prevention by diabetes type.

Previous statements and management approaches for CVD in T1DM have been extrapolated from research and clinical experience in T2DM. However, as the authors emphasize, many differences exist in CVD risk in people with T1DM compared to those with T2DM. For example, diabetes duration is an important CVD risk factor, and people with T1DM often have longer duration of diabetes than someone with T2DM at a similar age. Another important point made in this statement is that much of the data on T1DM and CVD is from historic studies of people with T1DM in whom less intensive control was the norm; how such data apply to more recently diagnosed people with T1DM in the post-Diabetes Control and Complications Trial era of intensive control is an open question. Data from the Pittsburgh Epidemiology of Diabetes Complications study suggest a 15-year improvement in life-expectancy among those with T1DM diagnosed in 1965-80 compared to 1950-644---and further improvements could be postulated in contemporary diagnosed cohorts. Recent data on the complications of diabetes are a mixed story, with decreasing rates in a large, presumably mainly T2DM cohort that are offset by increases in the diagnosis of T2DM in the US.⁵ In T1DM similar data exist for a reduction of microvascular complications, but such improvement is less clear for CVD.⁶ This progress in care has led to the survival of people with T1DM with long duration of diabetes and created a need for optimal care in the elderly with T1DM, a population that previously was extremely rare⁷ and for whom CVD health is a priority. In contrast, concern exists as the phenotype of T1DM has evolved to have comparable rates of obesity as in the general population.^8,9 Historically, people with T1DM were not obese due in large part to an inability to achieve near euglycemia.

A thorough literature review is included with research focused on specific targets for CVD prevention in T1DM including the ABCs (glucose control or HbA1c, hypertension or blood pressure, and dyslipidemia or cholesterol), smoking, and kidney disease. Emerging data on inflammation, genetics, and insulin resistance are also included. Further studies are needed not only on outcomes in T1DM but also on the most effective use of subclinical CVD markers such as coronary artery calcification (CAC), carotid intima media thickness (CIMT), and endothelial function, among others. How best to apply these and other techniques to assess CVD burden in T1DM and to guide CVD prevention efforts is a focus of investigation. Another important aspect of CVD in T1DM is the loss of female protection from CVD events typical in the non-diabetic population. Fat distribution patterns and insulin resistance are hypothesized as explanatory factors. Both obesity and insulin resistance in T1DM are the topic of active investigation with the potential for targeted therapies to improve glycemic control and CVD health.¹⁰ Race/ethnicity differences also exist in T1DM,^11,12 although this may not be a diabetes-specific effect; the authors emphasize that further research is needed on racial disparities in outcomes in T1DM.ttention focuses on the need for primary prevention of CVD in T1DM and specifies that the atherosclerotic process begins in childhood with subclinical CVD abnormalities evident during adolescence. From a pediatric perspective, the current Scientific Statement will be expanded upon in an upcoming AHA/ADA Scientific Statement that focuses on CVD in Youth with Diabetes.¹³

The authors do a service to the field by including a clearly delineated section on “opportunities for advances.” Improved understanding of the cellular and molecular mechanisms underlying CVD in T1DM, distinguishing contributors to micro- versus macro-vascular disease, and the pathophysiologic process of the atherosclerotic lesion are all topics of interest. Novel pathways and targets for therapeutic intervention are required in addition to more successful translation of known science to clinical care. A helpful list of specific questions and comments about CVD and T1DM is provided that identifies key gaps in knowledge as is a summary of areas where future research should be focused to improve understanding of pathophysiology, epidemiology and risk prevention, and treatment. These sections should serve to inform on-going research efforts to advance the care of cardiovascular health in people with T1DM. Readers should also be aware of the useful summary of information included in the on-line supplemental tables with the following data in T1DM: (1) prevalence and incidence of CVD (coronary heart disease and stroke); (2) peripheral arterial disease; (3) CIMT and CAC; and (4) genetic associations of clinical and subclinical CVD.

Although much remains to be discovered to prevent and improve care of CVD in T1DM, this joint Scientific Statement provides an important first step by identifying distinct pathophysiologic differences in CVD in T1DM. As CVD pathophysiology specific to T1DM is better understood, the opportunity to tailor therapy to prevent and treat CVD will improve. The authors of this statement clarify the unique aspects of CVD in T1DM, which will advance the field by focusing research and therapy to achieve needed improvements in care and clinical outcomes for people with T1DM.