Cardiovascular Disease and Type 1 Diabetes

Event Details

Purpose of the Workshop

Cardiovascular disease remains the leading cause of death for people with type 1 diabetes, despite improvements in the control of glucose, blood pressure, and lipid levels. The pathophysiology, risk factors, and clinical course of cardiovascular disease in type 1 diabetes have features that are different from those for cardiovascular disease in people with type 2 diabetes or without diabetes, yet most of the clinical recommendations for people with type 1 diabetes are based on studies of these other populations. The goals of the workshop are the following:

• Review the pathophysiology of atherosclerosis and myocardial infarction in people with type 1 diabetes.
• Compare and contrast risk factors for cardiovascular disease that are general, diabetes-specific, and type 1 diabetes-specific.
• Review the clinical presentation and course for acute coronary syndrome and stroke in type 1 diabetes.
• Discuss and prioritize research questions for cardiovascular disease and type 1 diabetes.
• Review and discuss the approaches and resources needed to address the high-priority research questions.

Workshop Organizing Committee

Robert H. Eckel, M.D., University of Colorado (Co-chair)
David M. Nathan, M.D., Massachusetts General Hospital (Co-chair)
Judith E. Fradkin, M.D., NIDDK
Larissa Aviles-Santa, M.D., M.P.H., NHLBI
Denise Bonds, M.D., M.P.H., NHLBI
Teresa L.Z. Jones, M.D., NIDDK
Barbara Linder, M.D., Ph.D., NIDDK
Peter J. Savage, M.D., NIDDK

Agenda

October 8, 2014

What do we know and don't we know about cardiovascular disease and type 1 diabetes?

8:00 a.m.

Welcoming Remarks
Dr. Griffin P. Rodgers, Director, NIDDK
Dr. Gary H. Gibbons, Director, NHLBI
Workshop Co-chairs: Dr. Robert H. Eckel and Dr. David M. Nathan

8:10 a.m.

Cardiovascular Results from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study (DCCT/EDIC)
Moderator: Dr. Nathan

Analysis of Risk Factors for Cardiovascular Disease
Dr. John Lachin

Discussion: How do these results compare to other type 1 diabetes cohorts and type 2 diabetes populations? How well did the surrogate end-points predict cardiovascular events?

(30 min talk; 20 min discussion)

9:00 a.m.

The Pathophysiology of Atherosclerosis and Myocardial Infarction in Type 1 Diabetes
Moderator: Dr. Eckel

Post-mortem Studies
Dr. Renu Virmani

Magnetic Resonance Imaging and Intravascular Ultrasound Findings
Dr.  Anne Sofie Astrup

Vascular Calcification
Dr. Janet Snell-Bergeon

Inflammation and Macrophages
Dr. Karin Bornfeldt

Leukocytosis
Dr. Edward Fisher

Glyoxylase and Oxidative Metabolism
Dr. Michael Brownlee

Protective Factors
Dr. George King

Autoimmunity and Myocardial Infarction
Dr. Myra Lipes

Discussion: What mechanisms are unique or prevalent in type 1 diabetes? How is the development of atherosclerotic plaques similar and different among type 1 and type 2 diabetes and non-diabetes? What are promising targets for biomarker and therapy development?

(12 min per talk; 35 min discussion; 15 min break)

11:30 a.m.

Risk Factors – General, Diabetes-specific and Type 1 Diabetes-specific
Moderator: Dr. Eckel

Traditional Risk Factors (hypertension, tobacco use, exercise, obesity, gender)
Dr. Helen Colhoun

Dyslipidemia
Dr. John Brunzell

Thrombosis
Dr. Guenther Boden

Hyperglycemia
Dr. David Maahs

Insulin Resistance
Dr. Marian Rewers

Hypoglycemia
Dr. Mikhail Kosiborod

Chronic Kidney Disease
Dr. Daniel Gordin

Cardiac Autonomic Neuropathy
Dr. Rodica Pop-Busui

Haptoglobin and Other Genetic Factors (hand-out)
Dr. Trevor Orchard

Heavy Metal Exposure (Trial to Assess Chelation Therapy)
Dr. Ana Navas-Acien and Dr. Gervasio Lamas

Discussion: Are we ready to build a risk calculator for type 1 diabetes? What would be the components? How might it differ from the clinical situation without diabetes or with type 2 diabetes? Are we missing important components? How good are the biomarkers to assess risk for individual patients and for stratification for clinical trials?

(60 min per group; 30 min general discussion; 60 min lunch)

4:00 p.m.

Acute Coronary Syndrome and Stroke

Panel discussion on the presentation, clinical course, and long-term outcomes from myocardial infarction and stroke in type 1 diabetes
Dr. Mikhail Kosiborod and Dr. Darren McGuire

4:45 p.m.

Day 1 wrap-up
Moderators: Dr. Eckel and Dr. Nathan

Discussion: What areas need more basic mechanistic studies in animal models or humans? What areas need better epidemiologic data? What research questions are ready for pilot clinical trials? What research questions are ready for phase II or III clinical trials? In which area(s) could we make the biggest impact on patient health? Consensus development on the top five research questions that will be the basis of discussion on Day 2.

5:30 p.m.

Adjournment Day 1

October 9, 2014

How do we proceed with the top five research questions?

8:00 a.m.

Introduction
Moderator: Dr. Nathan

For the research questions that depend on preclinical and translational work, what resources or tools are needed?
Panel: Dr. Karin Bornfeldt, Dr. Michael Brownlee, Dr. George King, and Dr. Ann Marie Schmidt (30 min)

For these research questions, are there alternative ways to conduct clinical trials than the traditional randomized trial? (60 min)

How could the Patient-Centered Outcomes Research Network (PCORnet) be applied to these research questions?
Dr. Robert Califf

What are the appropriate outcome measures for the clinical research questions? Do we have adequate surrogate end-points for pilot clinical trials?
Panel: Dr. Anne Sofie Astrup, Dr. Darren McGuire, Dr. Trevor Orchard, and Dr. John Spertus (30 min)

What recruitment strategies can be employed effectively for these research questions in type 1 diabetes adolescents and adults? How can we best involve the type 1 diabetes patient community?
Panel: Dr. George King, Dr. David Maahs, Dr. John Petrie and Dr. Rodica Pop-Busui (30 min)

How could registries, cohorts and biorepositories be used to answer these research questions? The program book will include summaries of cohorts and registries.
Panel: Dr. Helen Colhoun, Dr. Daniel Gordin, and Dr. Trevor Orchard

(30 min per panel; 15 min break)

11:30 a.m.

Day 2 Wrap-up
Moderators: Dr. Nathan and Dr. Eckel

12:00 p.m.

Adjournment Day 2