Family History of Diabetes Is a Major Determinant of Endothelial Function
Allison B. Goldfine, MD*, ,*,
Joshua A. Beckman, MD ,
Rebecca A. Betensky, PhD ,
Heather Devlin*,
Shauna Hurley ,
Nerea Varo, PhD ,
Uwe Schonbeck, PhD ,
Mary Elizabeth Patti, MD* and
Mark A. Creager, MD
* Joslin Diabetes Center, Boston, Massachusetts
Brigham and Women's Hospital, Boston, Massachusetts
Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts.

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Figure 1 Endothelium-dependent vasodilatation is impaired in offspring of two diabetic parents (FH+) compared to with persons without family history of diabetes (FH). Endothelium-independent vasodilatation is not impaired.
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Figure 2 The whole cohort was divided into tertiles of homeostasis model assessment of insulin resistance (HOMA-IR), such that the lowest tertile is most insulin sensitive and the highest tertile most resistant. The same levels of HOMA-IR were then applied to define the subgroups within positive family history (FH+) and negative family history (FH) groups. There was reduced endothelium-dependent vasodilation (EDV) in the most resistant persons of the whole cohort, and in the most insulin-resistant FH group as compared to with either of the two more sensitive subgroups; however, there was no relationship between HOMA-IR and EDV in FH+, such that even the most insulin-sensitive offspring had attenuated EDV. *p < 0.05.
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Figure 3 Simple linear regression is demonstrated between endothelium-dependent vasodilatation (EDV) and glycosylated hemoglobin (HbA1c), demonstrating within normal range higher glycemic burden associates with attenuated EDV. Individual data are presented for subjects with a family history of diabetes (FH+) (solid circles) and subjects without a family history of diabetes (FH) (open circles).
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Figure 4 Simple linear regression is demonstrated with endothelium-dependent vasodilation as the dependent variable and cholesterol high-density lipoprotein (HDL) and systolic blood pressure (BP) as independent variables in subjects with a family history of diabetes (FH+) and subjects without a family history of diabetes (FH). Individual data are presented for FH+ (solid circles) and FH (open circles). Positive family history subjects demonstrate blunted endothelial dilation across the range of cholesterol and systolic pressure.
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