Nondipping in Nocturnal Blood Pressure in Diabetes: An Indicator of Autonomic Nervous Dysfunction?

Several reports showed that the nondipping status of a fall in nocturnal blood pressure (BP) is an independent risk factor for silent and clinically overt cardiovascular disease,1,2 but it is unclear whether nondipping is a cause or a consequence of target organ damage. In this issue of the American Journal of Hypertension,3 Pistrosch et al describe an interesting cross-sectional study of the association between diurnal variation of BP and that of blood glucose in hypertensive patients with Type 2 diabetes. Diabetic nondippers exhibited a higher postprandial glucose excursion than did dippers, whereas the levels of fasting glucose and glycohemoglobin were comparable between the two groups. Nondippers also had a higher excretion of urinary albumin than did dippers. Because the postprandial excursion was reported to be an independent risk factor for cardiovascular events, the finding of Pistrosch et al3 is in accordance with a previous clinical observation that diabetic nondippers have a poorer cardiovascular prognosis.4 The association between diurnal variation of BP and postprandial glucose should be confirmed in nonmedicated diabetic patients in earlier stages. As shown in their Fig. 1, not only the postprandial glucose level, but also the preprandial glucose level, remains higher in nondippers than in dippers. In addition, nondippers tend to exhibit a higher level of glycohemoglobin than do dippers, although the difference between the two groups did not reach statistical significance. Thus, diabetic nondippers in this study may have had more advanced target organ damage because of poorly controlled glucose than did dippers. Antihypertensive and antidiabetic medications would affect the dipping status in nocturnal BP and the diurnal variation in glucose. The future study using a glucose tolerance test to detect the postprandial peak of glucose in patients with impaired glucose tolerance or with mild diabetes mellitus seems to be interesting to detect the association with dipping status in nocturnal BP. In addition, the mechanistic linkage between abnormal, nocturnal BP dipping status and abnormal glucose metabolism remains unclear. Autonomic dysfunction and endothelial-cell dysfunction may be a missing link between glucose abnormality and nondipping status in diabetes. There is an interesting prospective study of the association between dipping patterns and microalbuminuria in Type 1 diabetes, which showed that the earliest abnormality is a loss of the normal nocturnal dipping of BP, and that microalbuminuria comes later.5 Nondipping is closely associated with various types of autonomic dysfunction such as orthostatic BP dysregulation and disrupted diurnal variation of the sympathetic and parasympathetic balance.6,7 Nondippers tend to show orthostatic hypotension, whereas extreme dippers show orthostatic hypertension.7 Patients with Type 1 diabetes often have autonomic nervous dysfunction, and both types of these orthostatic BP dysregulations are frequently found.8 The nondipping pattern of a nocturnal fall in BP may develop in parallel with autonomic nervous dysfunction and precede the development of other manifestations of target organ damage. In the future, the associations between abnormal diurnal variation in BP and that of glucose should be confirmed in a prospective study of target organ damage and autonomic nervous dysfunction in diabetic patients. See related article on page 541.