Effects of co-administration of candesartan with pioglitazone on inflammatory parameters in hypertensive patients with type 2 diabetes mellitus: a preliminary report

Abstract

BackgroundAngiotensin 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.MethodsWe 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.ResultsAfter 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.ConclusionsOur 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.Trial registrationUMIN-CTR: UMIN000010142

Renoprotective effects of berberine as adjuvant therapy for hypertensive patients with type 2 diabetes mellitus: Evaluation via biochemical markers and color Doppler ultrasonography

“…Among the complex mechanisms leading to DN or HN, inflammation plays a key role, and anti-inflammation managements have been demonstrated to be effective against DN and HN (41). Increased levels of the inflammatory factors VCAM-1 and CRP are associated with the vascular complications of diabetes and hypertension (8,9,42). Renoprotective effects have been exhibited by treatments that decrease these inflammatory factors (43)(44)(45)(46).…”

“…that hypertension and diabetes are inflammatory conditions. Previous studies suggest that the levels certain inflammatory factors, such as vascular cell adhesion molecule 1 (VCAM-1) and C-reactive protein (CRP), are increased in patients with hypertension and diabetes (8,9). Elevated inflammatory factors are hypothesized to be involved in the pathogenesis of renal damage, and treatments targeted at controlling these factors have shown therapeutic effects on cardiovascular complications.…”

Inflammatory biomarkers in type 2 diabetic patients: effect of glycemic control and impact of ldl subfraction phenotype

“…Interestingly, lifestyle and pharmacological interventions in T2D such as statins, angiotensin receptor blockers and glitazones have demonstrated a beneficial effect on markers of inflammation [12-15]. However, the correlation between inflammatory markers and glycemic control is significant in some studies [16,17] but not in others [18], and available information about the effect of an improvement of glycemic control on inflammatory markers is very scarce [19,20].…”

AT1-receptor-deficiency induced atheroprotection in diabetic mice is partially mediated via PPARγ

“…Tham et al analysed the effects of AT1 receptor activation in respect to PPARγ expression in vitro and in vivo and reported a downregulation of PPARγ expression following stimulation with Ang II [19]. This mutual interaction is stressed by clinical observations in patients with metabolic syndrome defined by the coincidence of arterial hypertension and impaired glucose homeostasis [20]. Hypertension and the development of diabetes mellitus might interfere much closer than presently anticipated and the suggested interlocking regulation of PPARy and the AT1 receptor might be the key factor in this respect.…”