title: The effect of oral glucose loads on tissue metabolism during angiotensin II receptor and beta-receptor blockade in obese hypertensive subjects.
abstract: AT1 receptor blockers and ACE inhibitors decrease the risk for new onset diabetes mellitus. The phenomenon could be related to a direct angiotensin II effect on tissue metabolism. To address the issue, we recruited eighteen obese hypertensive patients. Patients were randomized to double-blind treatment with either valsartan (n = 8) or atenolol (n = 10) for thirteen weeks. They underwent an oral glucose tolerance test before and during active treatment, while metabolism was monitored through subcutaneous and intramuscular microdialysis and indirect calorimetry. After glucose ingestion, venous glucose and insulin concentrations increased rapidly while systemic free fatty acid concentrations were suppressed. Dialysate glucose and lactate concentrations increased briskly in adipose tissue and in skeletal muscle. Dialysate glycerol decreased profoundly in both tissues. Respiratory quotient increased markedly after glucose ingestion. These responses were identical at baseline and during active treatment either drug. We conclude that AT1 receptor blockade in obese hypertensive patients has no effect on interstitial glucose supply, lipolysis, and substrate oxidation. One possible explanation is that angiotensin II levels in obese hypertensives are not sufficient to elicit the metabolic changes that have been observed after direct angiotensin II application. The exact mechanism by which inhibition of the renin-angiotensin-aldosterone system decreases the diabetes risk remains unresolved and requires further study.
authors.affiliation: Franz-Volhard Clinical Research Center, Charité Campus Buch and HELIOS Klinikum, Berlin, Berlin, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Boschmann
authors.forename: U
authors.initials: U
authors.lastname: Kreuzberg
authors.forename: S
authors.initials: S
authors.lastname: Engeli
authors.forename: F
authors.initials: F
authors.lastname: Adams
authors.forename: G
authors.initials: G
authors.lastname: Franke
authors.forename: S
authors.initials: S
authors.lastname: Klaua
authors.forename: J
authors.initials: J
authors.lastname: Scholze
authors.forename: G
authors.initials: G
authors.lastname: Weidinger
authors.forename: F C
authors.initials: FC
authors.lastname: Luft
authors.forename: A M
authors.initials: AM
authors.lastname: Sharma
authors.forename: J
authors.initials: J
authors.lastname: Jordan
mesh_terms: D000273:Adipose Tissue / Q000737:chemistry; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D001262:Atenolol / Q000008:administration & dosage; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000517:prevention & control; D004311:Double-Blind Method; D000431:Ethanol / Q000032:analysis; D005230:Fatty Acids, Nonesterified / Q000032:analysis / Q000097:blood; D005260:Female; D005947:Glucose / Q000008:administration & dosage* / Q000032:analysis; D005951:Glucose Tolerance Test; D005990:Glycerol / Q000032:analysis; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D007328:Insulin / Q000097:blood; D007700:Kinetics; D019344:Lactic Acid / Q000032:analysis; D008055:Lipids / Q000097:blood; D008297:Male; D008660:Metabolism / Q000187:drug effects*; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000737:chemistry; D009765:Obesity / Q000150:complications*; D013777:Tetrazoles / Q000008:administration & dosage; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068756:Valsartan
chemical_list: D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D008055:Lipids; D013777:Tetrazoles; D019344:Lactic Acid; D000431:Ethanol; D001262:Atenolol; D000068756:Valsartan; D014633:Valine; D005947:Glucose; D005990:Glycerol