Metabolic rate and vascular function are reduced in women with a family history of type 2 diabetes mellitus Jennifer L. Olive a, ⁎ , Kevin D. Ballard a , James J. Miller b , Beth A. Milliner b a Department of Health and Sport Sciences, University of Louisville, Louisville, KY, USA b School of Medicine, University of Louisville, Louisville, KY, USA Received 24 September 2007; accepted 22 January 2008 Abstract Metabolic and vascular abnormalities have been found in individuals with type 2 diabetes mellitus (T2D). Family history is often associated with increased risk of the development of T2D. We sought to determine if young, sedentary, insulin-sensitive individuals with a family history of T2D (FH+) have a reduced resting energy expenditure (REE) and vascular endothelial function compared with individuals who have no family history of T2D (FH-). The REE was determined in 18 FH+ individuals and 15 FH- individuals using indirect open- circuit calorimetry. Vascular endothelial function was measured via flow-mediated dilation (FMD) of the brachial artery. C-reactive protein and interleukin-6 were also measured to look at vascular inflammation. Body composition was measured via bioelectrical impedance analysis to determine fat-free mass and fat mass for each individual. Insulin resistance was calculated using the homeostasis model assessment equation and fasting insulin and glucose concentrations. Subjects (n = 42) were approximately 26 years old and had normal fasting serum insulin or glucose concentrations. The REE normalized for body weight (kilocalories per day per kilogram body weight) was significantly reduced in the FH+ women compared with FH- women (P b .001) but not in the men. The FMD was significantly reduced (34.3%) in the FH+ group compared with the FH- in women (P = .002). However, no between-group difference in FMD was present in male subjects (P = .376). Young, healthy, insulin-sensitive women with a family history of T2D have reduced whole-body metabolic rate and vascular endothelial function compared with those with no family history of disease. These differences in whole-body metabolic rate and vascular endothelial function were not present in male subjects. © 2008 Elsevier Inc. All rights reserved. 1. Introduction Individuals who have at least one parent with type 2 diabetes mellitus (T2D) have a 50% increased chance of developing T2D independent of other risk factors such as obesity and inactivity [1]. The development of T2D is often associated with environmental determinants, but recent research suggests that inherited mitochondrial defects may also play a role [2]. Individuals with T2D have many adverse health outcomes that make early diagnosis and treatment critical. In recent years, high-risk groups for T2D have been targeted to determine if physiological changes occur before the onset of disease. A recent study found that women in their mid-30s with a family history (FH) of T2D have a reduced whole-body metabolism [3]. This reduction in whole-body metabolism may lead to increased fat deposition, thereby leading to insulin resistance [2]. Other work has found that individuals with an FH of T2D also have impaired vascular function years before the development of the disease [4,5]. Brachial artery flow-mediated dilation (FMD) was impaired in middle-aged normoglycemic subjects with an FH of T2D compared with healthy control subjects [4,5]. Interestingly, subjects who had an FH of T2D had a similar reduction in vascular function as individuals who were glucose intolerant [4]. These studies demonstrate that abnormalities in metabolic rate and vascular function may be present in some subjects at risk for T2D before the development of insulin resistance and T2D. The research is limited because it has not measured both metabolic and vascular function in a young, healthy, FH for T2D population and has not taken into account physical activity, which affects metabolic and vascular function. Available online at www.sciencedirect.com Metabolism Clinical and Experimental 57 (2008) 831 – 837 www.metabolismjournal.com ⁎ Corresponding author. Tel.: +1 253 301 4283, +1 502 216-6807 (cell). E-mail address: jloliv05@gwise.louisville.edu (J.L. Olive). 0026-0495/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.metabol.2008.01.028