Original article 309 Diurnal correlation of ambulatory blood pressure and interstitial glucose in patients with normal glucose tolerance Nikolaos A. Zakopoulos, Konstantinos J. Dolianitis, Michael J. Theodorakis, Efstathios D. Manios, Maria Alevizaki, Kimon S. Stamatelopoulos, Eleni A. Koroboki, Ioanna Spiliopoulou, Eleni Anastasiou, Myron Mavrikakis and Spyridon D. Moulopoulos Objective Among the physiological variables whose diurnal profile is governed by circadian rhythmicity, plasma glucose concentrations, and arterial blood pressure constitute key elements of the physiological regulation of energy homeostasis. Evidence on their diurnal association derived from frequent measurements of both variables is, however, lacking in humans. Methods We investigated the relationship between blood pressure levels recorded by an ambulatory device and interstitial glucose concentrations on an outpatient basis, in patients with normal glucose tolerance (N = 20), either normotensive (group A; N = 10), or newly diagnosed with essential hypertension (group B; N = 10). Results In the population throughout the 24-h monitoring period, there was a significant positive correlation between interstitial glucose concentrations and systolic, diastolic, and mean 24-h blood pressure levels, which was retained in patients with hypertension compared with normotensive patients. In patients with newly diagnosed hypertension, interstitial glucose concentrations exhibit significant correlation to systolic blood pressure levels during the 24-h period, but no association with diastolic and mean blood pressure during the night, whereas the reverse is the case in patients with normal glucose tolerance and normal blood pressure. Conclusion Diurnal variations of continuously monitored interstitial glucose concentrations significantly associate with blood pressure levels in both normotensive and hypertensive humans, indicating a common pathway of circadian autoregulation, probably stemming from both central mechanisms and peripheral inputs. Such a pathway might underlie similar pathophysiological aberration in disease states such as the metabolic syndrome. Blood Press Monit 13:309–317  c 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins. Blood Pressure Monitoring 2008, 13:309–317 Keywords: ambulatory blood pressure, circadian variation, interstitial glucose concentration Department of Clinical Therapeutics, University of Athens School of Medicine, Alexandra Hospital, Athens, Greece Correspondence to Dr Efstathios D. Manios, Department of Clinical Therapeutics 80 Vas, Alexandra Hospital, Sofias Ave, 115 28 Athens, Greece Tel: +30 210 338 1392; fax: +30 210 777 0473; e-mail: stathismanios@yahoo.gr Received 18 November 2007 Revised 22 May 2008 Accepted 24 May 2008 Introduction Circadian rhythmicity underlies most of the fundamental physiological processes governed by homeostatic and autoregulatory mechanisms in humans [1,2] and a pivotal role has been attributed to the suprachiasmatic nucleus of the hypothalamus [3,4] for acting as a neuroendocrine clock mechanism both through direct neuronal influence as well as by means of circadian control of hormone secretion [5,6]. In normal conditions, plasma glucose homeostasis is tightly controlled so that an elegant balance exists between glucose delivery and its utilization by peripheral tissues, in order for critical metabolic fueling to be constantly optimized and matched to demand [7]. It has been well established that the characteristics of normal glucose regulation vary signifi- cantly across the 24-h cycle and that temporal variation in glucose tolerance is at least partially under the influence of a central pacemaker but also modulated by counter- regulatory hormones [8,9]. Similarly, blood pressure (BP) as well as heart rate (HR) exhibits normal diurnal variation, with higher daytime than nighttime levels, primarily caused by the combined effects of physical activity, postural changes, and the sleep–wake transitions [10,11]. In addition, the effects of psychological and behavioral anticipation of meal presentation and ingestion per se on daytime BP variability are consistent with an increase in systolic BP (SBP) that is directly related to the amount of insulin secreted, in normotensive patients with normal glucose tolerance [12]. The coexistence of diabetes mellitus and hypertension has been found to double the risk of cardiovascular 1359-5237  c 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins DOI: 10.1097/MBP.0b013e32830d4b4a Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.