MECHANISMS OF NOCTURNAL HYPERTENSION IN TYPE 1 DIABETES

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Diabetes is the leading cause of end-stage renal disease (ESRD) world-wide. In susceptible individuals, the development of renal microvascular complications in type 1 diabetics often follows a uniform pattern which initially is asymptomatic with normal renal, cardiovascular and autonomic function. Progression of renal disease is then characterized by the development of nocturnal hypertension and microalbuminuria(MA). These changes are subsequently followed by the development of overt hypertension and proteinuria prior to the development of ESRD. Healthy individuals typically exhibit a fall in blood pressure at night in relation to their daytime blood pressure by approximately 10-25%. An interesting feature of type 1 diabetics is the loss of this normal circadian variation in blood pressure where blood pressure does not fall at night. The etiology of this nocturnal hypertension in type 1 diabetics has been ascribed to the loss or attenuation of the circadian changes in sympatho-vagal balance usually present in healthy individuals. This circadian sympatho-vagal axis in healthy individuals appears to be controlled through the diurnal release of catecholamines and current evidence suggests that this release may potentially be modulated by circulating levels of melatonin. To date, there is limited evidence regarding catecholamine and melatonin levels in type 1 diabetics. The question therefore arises if the altered sympatho-vagal axis of type 1 diabetics is the result of altered levels of nocturnal melatonin and catecholamine release. Specific Aim #1: To determine if type 1 diabetics with nocturnal hypertension have a significantly altered level of nocturnal melatonin release when compared to a group of type 1 diabetics without nocturnal hypertension and a group of healthy controls. Specific Aim #2: To examine the sympatho-vagal balance in these same 3 groups to test the hypothesis that decreased nocturnal melatonin secretion may be associated with increased catecholamine release and altered sympatho-vagal balance in type 1 diabetics with nocturnal hypertension as compared to type 1 diabetics without nocturnal hypertension and healthy controls. Specific Aim #3: To determine if supplemental administration of melatonin significantly changes nocturnal blood pressure when given to type 1 diabetics with nocturnal hypertension.