Family History of Diabetes Is a Major Determinant of Endothelial Function

Allison B. Goldfine, Joshua A. Beckman, Rebecca Betensky, Heather Devlin, Shauna Hurley, Nerea Varo, Uwe Schonbeck, Mary Elizabeth Patti, Mark A. Creager

Research output: Contribution to journalArticle

Abstract

Objectives: 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. Background: Atherosclerosis is frequently present when type 2 diabetes (T2D) is first diagnosed. Endothelial dysfunction contributes to atherogenesis. Methods: 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-). Results: 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). Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)2456-2461
Number of pages6
JournalJournal of the American College of Cardiology
Volume47
Issue number12
DOIs
StatePublished - Jun 20 2006

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Vasodilation
Endothelium
Insulin Resistance
Atherosclerosis
Type 2 Diabetes Mellitus
Brachial Artery
Glucose
Homeostasis
Nitroglycerin
Glycosylated Hemoglobin A
Glucose Tolerance Test
Biological Availability
Area Under Curve
Fasting
Analysis of Variance
Nitric Oxide
Regression Analysis
Insulin
Blood Pressure
Inflammation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Goldfine, A. B., Beckman, J. A., Betensky, R., Devlin, H., Hurley, S., Varo, N., ... Creager, M. A. (2006). Family History of Diabetes Is a Major Determinant of Endothelial Function. Journal of the American College of Cardiology, 47(12), 2456-2461. https://doi.org/10.1016/j.jacc.2006.02.045

Family History of Diabetes Is a Major Determinant of Endothelial Function. / Goldfine, Allison B.; Beckman, Joshua A.; Betensky, Rebecca; Devlin, Heather; Hurley, Shauna; Varo, Nerea; Schonbeck, Uwe; Patti, Mary Elizabeth; Creager, Mark A.

In: Journal of the American College of Cardiology, Vol. 47, No. 12, 20.06.2006, p. 2456-2461.

Research output: Contribution to journalArticle

Goldfine, AB, Beckman, JA, Betensky, R, Devlin, H, Hurley, S, Varo, N, Schonbeck, U, Patti, ME & Creager, MA 2006, 'Family History of Diabetes Is a Major Determinant of Endothelial Function', Journal of the American College of Cardiology, vol. 47, no. 12, pp. 2456-2461. https://doi.org/10.1016/j.jacc.2006.02.045
Goldfine, Allison B. ; Beckman, Joshua A. ; Betensky, Rebecca ; Devlin, Heather ; Hurley, Shauna ; Varo, Nerea ; Schonbeck, Uwe ; Patti, Mary Elizabeth ; Creager, Mark A. / Family History of Diabetes Is a Major Determinant of Endothelial Function. In: Journal of the American College of Cardiology. 2006 ; Vol. 47, No. 12. pp. 2456-2461.
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abstract = "Objectives: 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. Background: Atherosclerosis is frequently present when type 2 diabetes (T2D) is first diagnosed. Endothelial dysfunction contributes to atherogenesis. Methods: 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-). Results: 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). Conclusions: 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.",
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T1 - Family History of Diabetes Is a Major Determinant of Endothelial Function

AU - Goldfine, Allison B.

AU - Beckman, Joshua A.

AU - Betensky, Rebecca

AU - Devlin, Heather

AU - Hurley, Shauna

AU - Varo, Nerea

AU - Schonbeck, Uwe

AU - Patti, Mary Elizabeth

AU - Creager, Mark A.

PY - 2006/6/20

Y1 - 2006/6/20

N2 - Objectives: 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. Background: Atherosclerosis is frequently present when type 2 diabetes (T2D) is first diagnosed. Endothelial dysfunction contributes to atherogenesis. Methods: 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-). Results: 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). Conclusions: 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.

AB - Objectives: 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. Background: Atherosclerosis is frequently present when type 2 diabetes (T2D) is first diagnosed. Endothelial dysfunction contributes to atherogenesis. Methods: 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-). Results: 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). Conclusions: 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.

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