Diabetes mellitus and 24-hour ambulatory blood pressure monitoring: broadening horizons of risk assessment.

Given the increase in prevalence of obesity, survival to older age, and urbanization, the projected global number of people with diabetes mellitus will double within decades (http://www.eatlas.idf.org/Prevalence). Physicians care for an ever-increasing load of elderly patients with diabetes mellitus. As a matter of fact, quality of care of patients with diabetes mellitus has become a measure of quality in internal medicine, and diabetes mellitus practice improvement modules are part of the American Board of Internal Medicine recertification program (http://www.abms.org/Maintenance of Certification). Recently it became clear that a major (and most reachable) intersection on the road to improving prognosis of patients with diabetes mellitus is the successful lowering of their blood pressure to levels well below those previously considered the goal for subjects without diabetes mellitus. The vast body of research regarding blood pressure of patients with (as well as without) diabetes mellitus relies on office blood pressure measurements. However, it is now clear that 24-hour ambulatory blood pressure (ABP) monitoring provides data that are more closely linked to patients’ daily behavior.1 Compared with office blood pressure, the 24-hour ABP average may be closer to the individual’s “true” blood pressure. This is the basis for the overall stronger links of the latter with target organ damage, cardiovascular events, and, ultimately, survival. Can we apply the vast knowledge generated from hypertensive and general populations with 24-hour ABP monitoring to patients with diabetes mellitus? Are 24-hour ABP monitoring patterns such as white coat effect, masked hypertension, nocturnal hypertension, and nondipping (the lack of the sleep-associated blood pressure or heart rate decline) represented in patients with diabetes mellitus as in the general hypertensive population? Surprisingly there are relatively few data to answer such questions. Nevertheless, there is good reason to suspect that some of the established patterns of 24-hour ABP monitoring might be different in patients with diabetes mellitus. For instance, the American Heart Association proposed 3 different definitions for normal ABP, 1 for 24-hour average; 1 for daytime (presumably awake) average; and 1 for nighttime (presumably sleep) average.1 We have found, among 4000 subjects referred for monitoring of 24-hour ABP, that there is some discordance between these cutoff definitions: a sizable minority ( 17%) with apparently normal 24-hour ABP have nocturnal hypertension.2 Subjects with diabetes mellitus are frequently nondippers,3 and at a given office blood pressure they have been shown to have increased odds for sleep hypertension and masked hypertension.4 What are the mechanisms for the attenuated blood pressure decline during sleep in diabetes mellitus? The lack of definite answers to this question in part reflects our incomplete understanding of the sleep-associated dipping phenomenon, but we do have some clues. Subjects with diabetes mellitus may be more likely to have obesity-associated obstructive sleep apnea, a recognized cause for nondipping; orthostatic hypotension because of autonomic neuropathy might negate blood pressure changes induced by circadian and sleep-wake cycles; and diabetic nephropathy, heart failure, and perhaps a more general form of salt retention might dampen the blood pressure reductions expected during sleep-related sympathetic withdrawal.5 Subjects with diabetes mellitus are also more prone to nocturia, because of osmotic diuresis, advanced nephropathy with concentrating defects, obstructive sleep apnea, urinary tract infections, neurogenic bladder, misuse of diuretics, heart failure with central compartmentalization of volume when supine, gastrointestinal motility disorders with delayed fluid absorption, and prostatic hypertrophy, which is common in these generally older patients. Nocturnal awakenings and getting out of bed to urinate elevate night blood pressure and heart rate to daytime levels, and when repeated may give appearance of nondipping if these measurements are captured and calculated within the night’s average.6 Notwithstanding issues of measurement, in subjects with diabetes mellitus, sleep is genuinely accompanied by a lesser decline of blood pressure, as observed during a relatively brief, uninterrupted, daytime sleep.7 This confirms that the roots of nondipping in diabetes mellitus lie beyond disturbed sleeping patterns. In this issue of Hypertension, Palmas et al3 describe predictors of mortality in a large multiethnic cohort of elderly subjects with diabetes mellitus. They used 24-hour ABP monitoring and have several interesting findings. A surprising negative finding is that neither office nor ABP was independently related to mortality. This is difficult to comprehend, The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association. From the Department of Internal Medicine (M.B.), Mount Scopus Campus, Jerusalem, Israel; and Nephrology and Hypertension Service (I.Z.B.-D.), Hadassah-Hebrew University Medical Centers, Jerusalem, Israel. Correspondence to Michael Bursztyn, Hypertension Unit, Department of Medicine, Hadassah-Hebrew University Medical Center, Mount-Scopus, PO Box 24035, Jerusalem 91240, Israel. E-mail [email protected] (Hypertension. 2009;53:110-111.) © 2009 American Heart Association, Inc.