Coronary Vasomotor Function Is Abnormal in First-Degree Relatives of Patients With Type 2 Diabetes
- Kumiko Hirata, MD1,
- Amudha Kadirvelu, MB, PHD2,
- Marco Di Tullio, MD1,
- Shunichi Homma, MD, FACC1,
- Anna Maria Choy, MB, FRCP, FACC13 and
- Chim C. Lang, MD, FRCP, FACC13
- 1Department of Medicine, Columbia University, New York, New York
- 2Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia
- 3Department of Medicine and Therapeutics, Ninewells Hospital and Medical School, Dundee, Scotland, U.K.
- Address correspondence and reprint requests to Professor Chim C. Lang, MD, FRCP, FACC, Division of Medicine and Therapeutics, Ninewells Hospital and Medical School, Dundee DD1 9SY, Scotland, U.K. E-mail: c.c.lang{at}dundee.ac.uk
- CFVR, coronary flow velocity reserve
- CVD, cardiovascular disease
- FMD, forearm-mediated dilatation
- IGT, impaired glucose tolerance
- IL-6, interleukin-6
- OGTT, oral glucose tolerance test
- sICAM-1, soluble intercellular adhesion molecule-1
Nondiabetic first-degree relatives of patients with type 2 diabetes are at increased risk of developing diabetes (1) and cardiovascular disease (CVD) (2). Endothelial dysfunction is regarded as an early step in the development of atherosclerosis (3). Abnormal peripheral endothelial dysfunction detected by flow-mediated, endothelium-dependent, forearm-mediated dilatation (FMD) has been reported in first-degree relatives (4,5). The abnormal FMD could not be explained by confounding variables including age, sex, ethnicity, obesity, lipids, blood pressure, glycemia, or insulin resistance (5). However, endothelial dysfunction detected in brachial arteries may not reflect the condition of the coronary vasculature, as brachial and coronary circulations differ in terms of the microvascular architecture, pattern of blood flow, their metabolic regulation, and the pathways that are activated to induce hyperemia (6). Coronary flow reserve measurement has been considered to be a useful physiologic index for coronary circulation (6). In this study, we report for the first time impaired coronary flow reserve in young nonobese normoglycemic first-degree relatives compared with healthy control subjects.
RESEARCH DESIGN AND METHODS—
The study subjects were healthy volunteers recruited by advertisements for the University of Malaya. All gave written informed consent to participate in the study, which was approved by the local ethics committee. To be eligible as a first-degree relative, subjects had to have one or more parent with type 2 diabetes. To avoid any confounding influence on endothelial function, subjects were excluded if they had a history of smoking, manifest type 2 diabetes, hypertension, hypercholesterolemia (serum cholesterol ≥6.5 mmol/l), and concurrent CVD, including current or previous history of myocardial infarction and angina. None were on regular medication. At the screening visit, …
