Telmisartan improves insulin sensitivity in nondiabetic patients with essential hypertension.
Hypertension is a cardiovascular risk factor commonly associated with insulin resistance, the metabolic syndrome, and type 2 diabetes mellitus. Recent in vitro data indicate that certain angiotensin receptor antagonists, for example, telmisartan, activate peroxisome proliferator-activated receptor gamma (PPAR-gamma) and increase adiponectin protein content in adipocytes. By this means, they may improve insulin sensitivity in vivo. To investigate the effect of antihypertensive treatment on insulin sensitivity and fasting adiponectin serum levels, 37 nondiabetic patients with essential hypertension were randomized to receive telmisartan, the calcium channel blocker nisoldipine, or their combination for 6 weeks in a prospective, parallel group study. Fasting serum glucose, insulin, and adiponectin were evaluated before, 3 weeks (low dose), and 6 weeks (high dose) after initiation of treatment. Furthermore, the effect of telmisartan on PPAR-gamma receptor activity was investigated in vitro using a PPAR-gamma reporter gene assay. As reported previously, telmisartan significantly enhanced PPAR-gamma receptor activity in vitro. At baseline, a positive correlation between insulin serum levels and body mass index of investigated subjects was observed, whereas body mass index and serum adiponectin levels were negatively associated. High-dose treatment with telmisartan but not with nisoldipine reduced serum insulin levels as well as the homeostasis model assessment of insulin resistance, but did not affect serum adiponectin levels. In conclusion, in our study cohort of nondiabetic patients with essential hypertension, telmisartan improved insulin sensitivity by mechanisms apparently not involving adiponectin induction. Future studies will demonstrate whether these telmisartan-induced effects may contribute to a blood pressure-independent reduction in cardiovascular morbidity.
Benndorf
Ralf A
RA
Department of Clinical Pharmacology, Institute of Experimental and Clinical Pharmacology and Toxicology, University Hospital Hamburg-Eppendorf, D-20246 Hamburg, Germany. benndorf@uke.uni-hamburg.de
Rudolph
Tanja
T
Appel
Daniel
D
Schwedhelm
Edzard
E
Maas
Renke
R
Schulze
Friedrich
F
Silberhorn
Elisabeth
E
Böger
Rainer H
RH
D052242:Adiponectin / Q000097:blood; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D001565:Benzoates / Q000008:administration & dosage / Q000494:pharmacology*; D015992:Body Mass Index; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000209:etiology; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D015737:Nisoldipine / Q000008:administration & dosage / Q000494:pharmacology; D047495:PPAR gamma / Q000378:metabolism; D000077333:Telmisartan
D052242:Adiponectin; D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001565:Benzoates; D002121:Calcium Channel Blockers; D047495:PPAR gamma; D015737:Nisoldipine; D000077333:Telmisartan