title: Effects of co-administration of candesartan with pioglitazone on inflammatory parameters in hypertensive patients with type 2 diabetes mellitus: a preliminary report.
abstract: BACKGROUND
  Angiotensin receptor blockers (ARBs) are reported to provide direct protection to many organs by controlling inflammation and decreasing oxidant stress. Pioglitazone, an anti-diabetic agent that improves insulin resistance, was also reported to decrease inflammation and protect against atherosclerosis. This study aimed to evaluate the utility of combination therapy with both medicines from the viewpoint of anti-inflammatory effects.
  
  
  METHODS
  We administered candesartan (12 mg daily) and pioglitazone (15 mg daily) simultaneously for 6 months to hypertensive patients with type 2 diabetes mellitus (T2DM) and evaluated whether there were improvements in the serum inflammatory parameters of high-molecular-weight adiponectin (HMW-ADN), plasminogen activator inhibitor-1 (PAI-1), highly sensitive C-reactive protein (Hs-CRP), vascular cell adhesion molecule-1 (VCAM-1), and urinary-8-hydroxydeoxyguanosine (U-8-OHdG). We then analyzed the relationship between the degree of reductions in blood pressure and HbA1c values and improvements in inflammatory factors. Furthermore, we analyzed the relationship between pulse pressure and the degree of lowering of HbA1c and improvements in inflammatory factors. Finally, we examined predictive factors in patients who received benefits from the co-administration of candesartan with pioglitazone from the viewpoint of inflammatory factors.
  
  
  RESULTS
  After 6 months of treatment, in all patients significant improvements from baseline values were observed in HMW-ADN and PAI-1 but not in VCAM-1, Hs-CRP, and U-8-OHdG. Changes in HbA1c were significantly correlated with changes in HMW-ADN and PAI-1 in all patients, but changes in blood pressure were not correlated with any of the parameters examined. Correlation and multilinear regression analyses were performed to determine which factors could best predict changes in HbA1c. Interestingly, we found a significant positive correlation of pulse pressure values at baseline with changes in HbA1c.
  
  
  CONCLUSIONS
  Our data suggest that the pulse pressure value at baseline is a key predictive factor of changes in HbA1c. Co-administration of candesartan with pioglitazone, which have anti-inflammatory (changes in HMW-ADN and PAI-1) effects and protective effects on organs, could be an effective therapeutic strategy for treating hypertensive patients with type 2 diabetes mellitus.
  
  
  BACKGROUND
  UMIN-CTR: UMIN000010142.
authors: Department of Internal Medicine, Division of Diabetes, Metabolism and Endocrinology, Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo 105-8461, Japan.
authors: Hirofumi
authors: H
authors: Suzuki
authors: Masaya
authors: M
authors: Sakamoto
authors: Takeshi
authors: T
authors: Hayashi
authors: Hiroyuki
authors: H
authors: Iuchi
authors: Kennosuke
authors: K
authors: Ohashi
authors: Tsuyoshi
authors: T
authors: Isaka
authors: Noriko
authors: N
authors: Sakamoto
authors: Yosuke
authors: Y
authors: Kayama
authors: Katsuyoshi
authors: K
authors: Tojo
authors: Michihiro
authors: M
authors: Yoshimura
authors: Kazunori
authors: K
authors: Utsunomiya
mesh_terms: D052242:Adiponectin / Q000276:immunology; D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D001794:Blood Pressure; D002097:C-Reactive Protein / Q000276:immunology; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin; D006151:Guanosine / Q000031:analogs & derivatives / Q000652:urine; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D017395:Plasminogen Activator Inhibitor 1 / Q000276:immunology; D011446:Prospective Studies; D013777:Tetrazoles / Q000627:therapeutic use*; D045162:Thiazolidinediones / Q000627:therapeutic use*; D016896:Treatment Outcome; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology
chemical_list: D052242:Adiponectin; D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D002097:C-Reactive Protein; D006442:Glycated Hemoglobin; D006151:Guanosine; D007004:Hypoglycemic Agents; D000077205:Pioglitazone; D017395:Plasminogen Activator Inhibitor 1; D013777:Tetrazoles; D045162:Thiazolidinediones; D019010:Vascular Cell Adhesion Molecule-1; C499918:ADIPOQ protein, human; C051321:SERPINE1 protein, human; C517652:hemoglobin A1c protein, human; C046215:8-hydroxyguanosine; C081643:candesartan
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