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Left Ventricular Mass Increases With Deteriorating Glucose Tolerance, Especially in Women: Independence of Increased Arterial Stiffness or Decreased Flow-Mediated Dilation

The Hoorn Study

¹ Institute for Research in Extramural Medicine, VU University Medical Center, Amsterdam, the Netherlands
² Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, the Netherlands
³ Department of Cardiology, VU University Medical Center, Amsterdam, the Netherlands
⁴ Department of Clinical Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, the Netherlands
⁵ Department of Endocrinology, VU University Medical Center, Amsterdam, the Netherlands
⁶ Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands

Address correspondence and reprint requests to Professor C.D.A. Stehouwer, MD, PhD, Department of Internal Medicine, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, Netherlands. E-mail: cda.stehouwer{at}vumc.nl

OBJECTIVE—Type 2 diabetes and impaired glucose metabolism (IGM) are associated with an increased cardiovascular disease (CVD) risk. Increased left ventricular mass (LVM) is thought to increase CVD risk through several unfavorable cardiac changes. Type 2 diabetes and IGM are associated with increased LVM, but the underlying mechanism is unclear. We investigated the association between glucose tolerance status (GTS) and LVM and explored whether any such association could be mediated through increased arterial stiffness, impaired endothelial function, or the presence of atherosclerosis.

RESEARCH DESIGN AND METHODS—We used ultrasound to measure LVM, carotid and femoral stiffness, carotid-femoral transit time, and flow-mediated vasodilation (FMD) and tonometry to estimate compliance and augmentation index. The study population (n = 780) consisted of 287 individuals with normal glucose metabolism (NGM), 179 with IGM, and 314 with type 2 diabetes, and the mean age was 68.4 years.

RESULTS—In women, after adjusting for age, height, BMI, and mean arterial pressure, LVM increased significantly with deteriorating GTS (LVM 157 g in NGM, 155 g in IGM, and 169 g in type 2 diabetes; P for trend <0.018). Additional adjustment for arterial stiffness, FMD, or the presence of atherosclerosis did not materially alter the results, even though these variables were significantly associated with both GTS and LVM. Indexes of hyperglycemia/-insulinemia or insulin resistance explained at most 7% of the association between GTS and LVM. In men, no statistically significant associations were observed.

CONCLUSIONS—Our data expand the conceptual view of the pathogenesis of GTS-related changes in LVM because we show that the increase in LVM in women is independent of increased arterial stiffness, impaired FMD, or the presence of atherosclerosis. In addition, we show that this increase in LVM is only minimally explained by indexes of hyperglycemia/-insulinemia or insulin resistance. Our data may, in part, explain the increased CVD risk seen in women with deteriorating GTS.

Abbreviations: CVD, cardiovascular disease • EDD, end-diastolic diameter • FMD, flow-mediated vasodilation • GTS, glucose tolerance status • IGM, impaired glucose metabolism • IVS, interventricular septum thickness • LVM, left ventricular mass • NGM, normal glucose metabolism • RWT, relative wall thickness

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