Family History of Diabetes Is a Major Determinant of Endothelial Function

• Published in: Journal of the American College of Cardiology Vol. 47; no. 12; pp. 2456 - 2461
• Main Authors: Goldfine, Allison B., Beckman, Joshua A., Betensky, Rebecca A., Devlin, Heather, Hurley, Shauna, Varo, Nerea, Schonbeck, Uwe, Patti, Mary Elizabeth, Creager, Mark A.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 20.06.2006; Elsevier Science; Elsevier Limited
• Subjects: Adult; Biological and medical sciences; Body mass index; Cardiology; Cardiology. Vascular system; Cardiovascular disease; Cholesterol; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - physiopathology; Diabetes. Impaired glucose tolerance; Drug therapy; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Endothelium, Vascular - physiopathology; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Heart Diseases - etiology; Humans; Insulin; Insulin Resistance; Male; Medical sciences; Obesity; Risk Factors; Studies; Vasodilation; HOMA-IR; FH; EIV; HbA1c; EDV; T2D; Endocrinopathy; Family study; Diabetes mellitus; Determinant; Family environment; Circulatory system; Endothelial function; Cardiology; History; Phlebology
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2006.02.045

Family History of Diabetes Is a Major Determinant of Endothelial Function Allison B. Goldfine, Joshua A. Beckman, Rebecca A. Betensky, Heather Devlin, Shauna Hurley, Nerea Varo, Uwe Schonbeck, Mary Elizabeth Patti, Mark A. Creager Nondiabetic offspring of two parents with type 2 diabetes (T2D) demonstrated impaired brachial artery flow-mediated, endothelium-dependent vasodilation (EDV) compared to with persons with no family history (FH) of disease. Glycemia, assessed as glycosylated hemoglobin (HbA1c), and FH status were important determinants of EDV, suggesting bioavailability of nitric oxide is lower in persons with a strong FH of T2D and that glycemia, even in the nondiabetic range, can importantly affect vascular function. Abnormalities of endothelial function may contribute to atherosclerosis before the development of overt diabetes. We evaluated whether endothelial dysfunction was present in nondiabetic persons with a family history (FH) of diabetes and assessed its relationship with insulin resistance and atherosclerosis risk factors. Atherosclerosis is frequently present when type 2 diabetes (T2D) is first diagnosed. Endothelial dysfunction contributes to atherogenesis. Oral glucose tolerance and brachial artery flow-mediated, endothelium-dependent vasodilation (EDV) were assessed in 38 nondiabetic subjects; offspring of two parents with T2D (FH+) or with no first-degree relative with diabetes (FH−). Although fasting glucose was higher in FH+ than FH− (5.3 ± 0.1 mmol/l vs. 4.9 ± 0.1 mmol/l, p < 0.03), glycemic burden assessed as 2-h or area-under-the-curve glucose after glucose load or glycosylated hemoglobin (HbA1c), and measures of insulin sensitivity or inflammation did not differ. Brachial artery flow-mediated EDV was reduced in FH+ (7.1 ± 0.9% vs. 11.7 ± 1.6%, p < 0.02), with no difference in nitroglycerin-induced endothelium-independent vasodilatation. In the combined cohort, only FH+ (r2= 0.12, p < 0.02) and HbA1c (r2= 0.14, p < 0.02) correlated with EDV. Insulin resistance, assessed by tertile of homeostasis model assessment of insulin resistance (HOMA-IR), was associated with impaired endothelium-dependent vasodilatation in FH− (p < 0.03, analysis of variance), but not in FH+, as even the most insulin-sensitive FH+ offspring had diminished endothelial function. In multiple regression analysis, including established cardiac risk factors, blood pressure and lipids, HbA1c, and HOMA-IR, FH remained a significant determinant of EDV (p = 0.04). Bioavailability of nitric oxide is lower in persons with a strong FH of T2D. Glycemic burden, even in the nondiabetic range, can contribute to endothelial dysfunction. Abnormalities of endothelial function may contribute to atherosclerosis before development of overt diabetes.