Effects of Telmisartan on Insulin Resistance in Japanese Type 2 Diabetic Patients

Objective PPARγ agonists are widely used in type 2 diabetic patients to reduce insulin resistance. Recently, telmisartan, an AT1 receptor antagonist, was reported to function as a partial agonist of PPARγ based on in vitro experiments. The aim of the present study was to investigate whether the PPAR...

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Veröffentlicht in:Internal Medicine 2010, Vol.49(17), pp.1843-1847
Hauptverfasser: Watanabe, Masaki, Inukai, Kouichi, Sumita, Takashi, Ikebukuro, Kaori, Ito, Daisuke, Kurihara, Susumu, Ono, Hiraku, Awata, Takuya, Katayama, Shigehiro
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container_end_page 1847
container_issue 17
container_start_page 1843
container_title Internal Medicine
container_volume 49
creator Watanabe, Masaki
Inukai, Kouichi
Sumita, Takashi
Ikebukuro, Kaori
Ito, Daisuke
Kurihara, Susumu
Ono, Hiraku
Awata, Takuya
Katayama, Shigehiro
description Objective PPARγ agonists are widely used in type 2 diabetic patients to reduce insulin resistance. Recently, telmisartan, an AT1 receptor antagonist, was reported to function as a partial agonist of PPARγ based on in vitro experiments. The aim of the present study was to investigate whether the PPARγ enhancing activity of telmisartan is exerted clinically in diabetic patients. Methods We compared the effects of telmisartan with those of candesartan, on insulin sensitivity, the serum levels of various adipocytokines and oxidative stress. Patients In total, 85 Japanese type 2 diabetic patients with hypertension, maintained on 8 mg per day of candesartan, were randomly assigned to the TM group (candesartan switched to 40 mg of telmisartan, n=38) or the CD group (no treatment change, n=47). Results After 3 months, oxidized lipids were significantly decreased only in the TM group. Although the homeostasis assessment model of insulin resistance (HOMA-R) tended to be improved and serum concentrations of HDL-cholesterol and HMW adiponectin tended to be increased only in the TM group, these alterations were too small to be significant by unpaired t-test. Interestingly, in subgroup analysis, the alterations of HOMA-R, serum concentrations of oxidized lipids, and HMW adiponectin were more apparent in obese TM group subjects and the changes reached statistical significance. Conclusion Switching from candesartan to telmisartan in obese subjects increases serum adiponectin and improves both insulin resistance and oxidative stress, while these effects were not statistically apparent in the total patient population. These results support the idea that telmisartan exerts its PPARγ enhancing activity clinically in obese type 2 diabetic patients.
doi_str_mv 10.2169/internalmedicine.49.3189
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Recently, telmisartan, an AT1 receptor antagonist, was reported to function as a partial agonist of PPARγ based on in vitro experiments. The aim of the present study was to investigate whether the PPARγ enhancing activity of telmisartan is exerted clinically in diabetic patients. Methods We compared the effects of telmisartan with those of candesartan, on insulin sensitivity, the serum levels of various adipocytokines and oxidative stress. Patients In total, 85 Japanese type 2 diabetic patients with hypertension, maintained on 8 mg per day of candesartan, were randomly assigned to the TM group (candesartan switched to 40 mg of telmisartan, n=38) or the CD group (no treatment change, n=47). Results After 3 months, oxidized lipids were significantly decreased only in the TM group. Although the homeostasis assessment model of insulin resistance (HOMA-R) tended to be improved and serum concentrations of HDL-cholesterol and HMW adiponectin tended to be increased only in the TM group, these alterations were too small to be significant by unpaired t-test. Interestingly, in subgroup analysis, the alterations of HOMA-R, serum concentrations of oxidized lipids, and HMW adiponectin were more apparent in obese TM group subjects and the changes reached statistical significance. Conclusion Switching from candesartan to telmisartan in obese subjects increases serum adiponectin and improves both insulin resistance and oxidative stress, while these effects were not statistically apparent in the total patient population. These results support the idea that telmisartan exerts its PPARγ enhancing activity clinically in obese type 2 diabetic patients.</description><identifier>ISSN: 0918-2918</identifier><identifier>EISSN: 1349-7235</identifier><identifier>DOI: 10.2169/internalmedicine.49.3189</identifier><identifier>PMID: 20823643</identifier><language>eng</language><publisher>Japan: The Japanese Society of Internal Medicine</publisher><subject>adiponectin ; Adiponectin - blood ; Aged ; Angiotensin II Type 1 Receptor Blockers - pharmacology ; Angiotensin II Type 1 Receptor Blockers - therapeutic use ; Antihypertensive Agents - pharmacology ; Antihypertensive Agents - therapeutic use ; Benzimidazoles - pharmacology ; Benzimidazoles - therapeutic use ; Benzoates - pharmacology ; Benzoates - therapeutic use ; Cholesterol, HDL - blood ; Diabetes Mellitus, Type 2 - complications ; Diabetes Mellitus, Type 2 - drug therapy ; Diabetes Mellitus, Type 2 - physiopathology ; Female ; Homeostasis ; Humans ; Hypertension - complications ; Hypertension - drug therapy ; insulin resistance ; Insulin Resistance - physiology ; Japan ; Lipoproteins, LDL - analysis ; Male ; Metabolic Syndrome - drug therapy ; Metabolic Syndrome - physiopathology ; Middle Aged ; Obesity - complications ; Oxidative Stress ; PPAR gamma - agonists ; PPARγ ; Telmisartan ; Tetrazoles - pharmacology ; Tetrazoles - therapeutic use</subject><ispartof>Internal Medicine, 2010, Vol.49(17), pp.1843-1847</ispartof><rights>2010 by The Japanese Society of Internal Medicine</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c583t-3f9e881d9b039a3c6693f9ee94e270300e038f39fbb3b86535ac552f3c26eb263</citedby><cites>FETCH-LOGICAL-c583t-3f9e881d9b039a3c6693f9ee94e270300e038f39fbb3b86535ac552f3c26eb263</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,1883,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20823643$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Watanabe, Masaki</creatorcontrib><creatorcontrib>Inukai, Kouichi</creatorcontrib><creatorcontrib>Sumita, Takashi</creatorcontrib><creatorcontrib>Ikebukuro, Kaori</creatorcontrib><creatorcontrib>Ito, Daisuke</creatorcontrib><creatorcontrib>Kurihara, Susumu</creatorcontrib><creatorcontrib>Ono, Hiraku</creatorcontrib><creatorcontrib>Awata, Takuya</creatorcontrib><creatorcontrib>Katayama, Shigehiro</creatorcontrib><title>Effects of Telmisartan on Insulin Resistance in Japanese Type 2 Diabetic Patients</title><title>Internal Medicine</title><addtitle>Intern. Med.</addtitle><description>Objective PPARγ agonists are widely used in type 2 diabetic patients to reduce insulin resistance. Recently, telmisartan, an AT1 receptor antagonist, was reported to function as a partial agonist of PPARγ based on in vitro experiments. The aim of the present study was to investigate whether the PPARγ enhancing activity of telmisartan is exerted clinically in diabetic patients. Methods We compared the effects of telmisartan with those of candesartan, on insulin sensitivity, the serum levels of various adipocytokines and oxidative stress. Patients In total, 85 Japanese type 2 diabetic patients with hypertension, maintained on 8 mg per day of candesartan, were randomly assigned to the TM group (candesartan switched to 40 mg of telmisartan, n=38) or the CD group (no treatment change, n=47). Results After 3 months, oxidized lipids were significantly decreased only in the TM group. Although the homeostasis assessment model of insulin resistance (HOMA-R) tended to be improved and serum concentrations of HDL-cholesterol and HMW adiponectin tended to be increased only in the TM group, these alterations were too small to be significant by unpaired t-test. Interestingly, in subgroup analysis, the alterations of HOMA-R, serum concentrations of oxidized lipids, and HMW adiponectin were more apparent in obese TM group subjects and the changes reached statistical significance. Conclusion Switching from candesartan to telmisartan in obese subjects increases serum adiponectin and improves both insulin resistance and oxidative stress, while these effects were not statistically apparent in the total patient population. 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Inukai, Kouichi ; Sumita, Takashi ; Ikebukuro, Kaori ; Ito, Daisuke ; Kurihara, Susumu ; Ono, Hiraku ; Awata, Takuya ; Katayama, Shigehiro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c583t-3f9e881d9b039a3c6693f9ee94e270300e038f39fbb3b86535ac552f3c26eb263</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>adiponectin</topic><topic>Adiponectin - blood</topic><topic>Aged</topic><topic>Angiotensin II Type 1 Receptor Blockers - pharmacology</topic><topic>Angiotensin II Type 1 Receptor Blockers - therapeutic use</topic><topic>Antihypertensive Agents - pharmacology</topic><topic>Antihypertensive Agents - therapeutic use</topic><topic>Benzimidazoles - pharmacology</topic><topic>Benzimidazoles - therapeutic use</topic><topic>Benzoates - pharmacology</topic><topic>Benzoates - therapeutic use</topic><topic>Cholesterol, HDL - blood</topic><topic>Diabetes Mellitus, Type 2 - complications</topic><topic>Diabetes Mellitus, Type 2 - drug therapy</topic><topic>Diabetes Mellitus, Type 2 - physiopathology</topic><topic>Female</topic><topic>Homeostasis</topic><topic>Humans</topic><topic>Hypertension - complications</topic><topic>Hypertension - drug therapy</topic><topic>insulin resistance</topic><topic>Insulin Resistance - physiology</topic><topic>Japan</topic><topic>Lipoproteins, LDL - analysis</topic><topic>Male</topic><topic>Metabolic Syndrome - drug therapy</topic><topic>Metabolic Syndrome - physiopathology</topic><topic>Middle Aged</topic><topic>Obesity - complications</topic><topic>Oxidative Stress</topic><topic>PPAR gamma - agonists</topic><topic>PPARγ</topic><topic>Telmisartan</topic><topic>Tetrazoles - pharmacology</topic><topic>Tetrazoles - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Watanabe, Masaki</creatorcontrib><creatorcontrib>Inukai, Kouichi</creatorcontrib><creatorcontrib>Sumita, Takashi</creatorcontrib><creatorcontrib>Ikebukuro, Kaori</creatorcontrib><creatorcontrib>Ito, Daisuke</creatorcontrib><creatorcontrib>Kurihara, Susumu</creatorcontrib><creatorcontrib>Ono, Hiraku</creatorcontrib><creatorcontrib>Awata, Takuya</creatorcontrib><creatorcontrib>Katayama, Shigehiro</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Internal Medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Watanabe, Masaki</au><au>Inukai, Kouichi</au><au>Sumita, Takashi</au><au>Ikebukuro, Kaori</au><au>Ito, Daisuke</au><au>Kurihara, Susumu</au><au>Ono, Hiraku</au><au>Awata, Takuya</au><au>Katayama, Shigehiro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of Telmisartan on Insulin Resistance in Japanese Type 2 Diabetic Patients</atitle><jtitle>Internal Medicine</jtitle><addtitle>Intern. Med.</addtitle><date>2010-01-01</date><risdate>2010</risdate><volume>49</volume><issue>17</issue><spage>1843</spage><epage>1847</epage><pages>1843-1847</pages><issn>0918-2918</issn><eissn>1349-7235</eissn><abstract>Objective PPARγ agonists are widely used in type 2 diabetic patients to reduce insulin resistance. Recently, telmisartan, an AT1 receptor antagonist, was reported to function as a partial agonist of PPARγ based on in vitro experiments. The aim of the present study was to investigate whether the PPARγ enhancing activity of telmisartan is exerted clinically in diabetic patients. Methods We compared the effects of telmisartan with those of candesartan, on insulin sensitivity, the serum levels of various adipocytokines and oxidative stress. Patients In total, 85 Japanese type 2 diabetic patients with hypertension, maintained on 8 mg per day of candesartan, were randomly assigned to the TM group (candesartan switched to 40 mg of telmisartan, n=38) or the CD group (no treatment change, n=47). Results After 3 months, oxidized lipids were significantly decreased only in the TM group. Although the homeostasis assessment model of insulin resistance (HOMA-R) tended to be improved and serum concentrations of HDL-cholesterol and HMW adiponectin tended to be increased only in the TM group, these alterations were too small to be significant by unpaired t-test. Interestingly, in subgroup analysis, the alterations of HOMA-R, serum concentrations of oxidized lipids, and HMW adiponectin were more apparent in obese TM group subjects and the changes reached statistical significance. Conclusion Switching from candesartan to telmisartan in obese subjects increases serum adiponectin and improves both insulin resistance and oxidative stress, while these effects were not statistically apparent in the total patient population. These results support the idea that telmisartan exerts its PPARγ enhancing activity clinically in obese type 2 diabetic patients.</abstract><cop>Japan</cop><pub>The Japanese Society of Internal Medicine</pub><pmid>20823643</pmid><doi>10.2169/internalmedicine.49.3189</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record>
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subjects adiponectin
Adiponectin - blood
Aged
Angiotensin II Type 1 Receptor Blockers - pharmacology
Angiotensin II Type 1 Receptor Blockers - therapeutic use
Antihypertensive Agents - pharmacology
Antihypertensive Agents - therapeutic use
Benzimidazoles - pharmacology
Benzimidazoles - therapeutic use
Benzoates - pharmacology
Benzoates - therapeutic use
Cholesterol, HDL - blood
Diabetes Mellitus, Type 2 - complications
Diabetes Mellitus, Type 2 - drug therapy
Diabetes Mellitus, Type 2 - physiopathology
Female
Homeostasis
Humans
Hypertension - complications
Hypertension - drug therapy
insulin resistance
Insulin Resistance - physiology
Japan
Lipoproteins, LDL - analysis
Male
Metabolic Syndrome - drug therapy
Metabolic Syndrome - physiopathology
Middle Aged
Obesity - complications
Oxidative Stress
PPAR gamma - agonists
PPARγ
Telmisartan
Tetrazoles - pharmacology
Tetrazoles - therapeutic use
title Effects of Telmisartan on Insulin Resistance in Japanese Type 2 Diabetic Patients
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