title: Targeting nocturnal hypertension in type 2 diabetes mellitus.
abstract: Several studies in different populations have suggested that nighttime blood pressure (BP) is a stronger predictor of cardiovascular events than daytime BP. Consequently, treatment strategies to target nighttime BP have come into focus. The aim of the present study was to investigate the effect of change of administration time of antihypertensive drugs. We included 41 patients with type 2 diabetes mellitus and nocturnal hypertension (nighttime systolic BP >120 mm Hg) in an open-label, crossover study. Patients were randomized to 8 weeks of either morning or bedtime administration of all of the individual's once-daily antihypertensive drugs, followed by 8 weeks of switched dosing regimen. Bedtime administration of antihypertensive drugs resulted in a significant reduction in nighttime (7.5 mm Hg; P<0.001) and 24-hour (3.1 mm Hg; P=0.014) systolic BP, with a nonsignificant reduction in daytime (1.3 mm Hg; P=0.336) systolic BP. We did not find morning BP surge to be different between dosing regimens. Levels of C-reactive protein were significantly lower with bedtime administration, which may indicate an effect on low-grade inflammation. We found no difference in urinary albumin excretion, regardless of albuminuria status. Urinary sodium/creatinine was significantly increased and urinary osmolality significantly reduced with bedtime administration, which can be interpreted as increased nocturnal natriuresis. In patients with type 2 diabetes mellitus and nocturnal hypertension, administration of once-daily antihypertensive drugs at bedtime may be favorable. The increased nocturnal natriuresis may reflect increased effect of bedtime-administered thiazides and renin-angiotensin system inhibitors, suggesting a potential mechanism of the observed effects on BP with chronotherapeutic intervention.
authors.affiliation: From the Department of Medicine, Silkeborg Regional Hospital, Silkeborg, Denmark (N.B.R., K.W.H.); and Department of Endocrinology and Internal Medicine (N.B.R., S.T.K., E.E., P.L.P.), Medical Research Laboratory (J.F.), and Department of Clinical Biochemistry (A.-M.H.), Aarhus University Hospital, Aarhus, Denmark. niklas.rossen@rm.dk.
authors.forename: Niklas Blach
authors.initials: NB
authors.lastname: Rossen
authors.affiliation: From the Department of Medicine, Silkeborg Regional Hospital, Silkeborg, Denmark (N.B.R., K.W.H.); and Department of Endocrinology and Internal Medicine (N.B.R., S.T.K., E.E., P.L.P.), Medical Research Laboratory (J.F.), and Department of Clinical Biochemistry (A.-M.H.), Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Søren Tang
authors.initials: ST
authors.lastname: Knudsen
authors.affiliation: From the Department of Medicine, Silkeborg Regional Hospital, Silkeborg, Denmark (N.B.R., K.W.H.); and Department of Endocrinology and Internal Medicine (N.B.R., S.T.K., E.E., P.L.P.), Medical Research Laboratory (J.F.), and Department of Clinical Biochemistry (A.-M.H.), Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Fleischer
authors.affiliation: From the Department of Medicine, Silkeborg Regional Hospital, Silkeborg, Denmark (N.B.R., K.W.H.); and Department of Endocrinology and Internal Medicine (N.B.R., S.T.K., E.E., P.L.P.), Medical Research Laboratory (J.F.), and Department of Clinical Biochemistry (A.-M.H.), Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Anne-Mette
authors.initials: AM
authors.lastname: Hvas
authors.affiliation: From the Department of Medicine, Silkeborg Regional Hospital, Silkeborg, Denmark (N.B.R., K.W.H.); and Department of Endocrinology and Internal Medicine (N.B.R., S.T.K., E.E., P.L.P.), Medical Research Laboratory (J.F.), and Department of Clinical Biochemistry (A.-M.H.), Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Eva
authors.initials: E
authors.lastname: Ebbehøj
authors.affiliation: From the Department of Medicine, Silkeborg Regional Hospital, Silkeborg, Denmark (N.B.R., K.W.H.); and Department of Endocrinology and Internal Medicine (N.B.R., S.T.K., E.E., P.L.P.), Medical Research Laboratory (J.F.), and Department of Clinical Biochemistry (A.-M.H.), Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Per Løgstrup
authors.initials: PL
authors.lastname: Poulsen
authors.affiliation: From the Department of Medicine, Silkeborg Regional Hospital, Silkeborg, Denmark (N.B.R., K.W.H.); and Department of Endocrinology and Internal Medicine (N.B.R., S.T.K., E.E., P.L.P.), Medical Research Laboratory (J.F.), and Department of Clinical Biochemistry (A.-M.H.), Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Klavs Würgler
authors.initials: KW
authors.lastname: Hansen
mesh_terms: D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002097:C-Reactive Protein / Q000378:metabolism; D002940:Circadian Rhythm / Q000502:physiology*; D015897:Comorbidity; D003404:Creatinine / Q000652:urine; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D012964:Sodium / Q000652:urine; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D002097:C-Reactive Protein; D012964:Sodium; D003404:Creatinine
keywords: blood pressure monitoring, ambulatory; chronotherapy; diabetes mellitus, type 2; hypertension