Pioglitazone increases circulating adiponectin levels and subsequently reduces TNF‐α levels in Type 2 diabetic patients: a randomized study

SummaryAldosterone production causes vascular injury and may occur despite the long-term administration of angiotensin converting enzyme-inhibitors (ACE-I) (ie, aldosterone breakthrough). The angiotensin II receptor blocker (ARB) telmisartan can function as a ligand for peroxisome proliferator-activated receptor (PPAR) γ. Stimulation of PPAR γ has been demonstrated to raise adiponectin production and suppress angiotensin II type 1 receptor expression. Thus, we investigated the effect of the ACE-I perindopril erbumin (perindopril) and the ARB telmisartan on plasma levels of aldosterone and adiponectin.Patients with essential hypertension were randomly assigned to receive 48 weeks of perindopril (2-8 mg/d) or telmisartan (20-80 mg/d). We measured adiponectin, aldosterone, angiotensin II, and renin at weeks 0, 8, 24, and 48.A total of 53 subjects were randomized. Data on 51 subjects (25 in the perindopril group and 26 in the telmisartan group; mean age, 65.1 years) were available for analyses. Plasma aldosterone decreased significantly in both the telmisartan (69.9 ± 5.6 to 58.1 ± 5.4 pg/mL) and perindopril (74.1 ± 4.7 to 64.7 ± 5.3 pg/mL) groups at 8 weeks, but returned toward the baseline in the perindopril group (67.9 ± 4.1 pg/mL) at 24 weeks. Plasma glycated hemoglobin levels or urine albumin did not change significantly after the treatment in either group.Telmisartan seemed to be more effective at suppressing aldosterone and raising adiponectin levels than perindopril; however, improvements in insulin sensitivity and albuminuria were not detected. These results are consistent with the idea that the use of an ARB with PPAR γ stimulating activity is equivalent to ACE-I for the treatment of hypertension. (Int Heart J 2009; 50: 501-512)

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“…13,33) The lack of effect of telmisartan on circulating leptin levels in our study is consistent with these clinical data.…”

Section: Discussionsupporting

confidence: 81%

Effects of ARB or ACE-Inhibitor Administration on Plasma Levels of Aldosterone and Adiponectin in Hypertension

et al. 2009

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“…In general, improvement of glycemic controls by diet, exercise or medical interventions does not always lead to increase in serum AdN concentrations. In fact, there are some studies reporting negative effects of anti-diabetic agents on serum AdN levels, including glibenclamide [17], voglibose [18] and metformin [24,25]. To our knowledge, this is the first clinical report of AdNincreasing effect of any α-glucosidase inhibitors.…”

Section: Discussionmentioning

confidence: 81%

“…Interestingly, this gene effect was not observed after acarbose treatment [23], which raises a possibility that adiponectin is involved in clinical effects of acarbose. There have been described virtually no studies that examined the effect of α-glucosidase inhibitors on the circulating levels of AdN except for negative reports that voglibose does not change serum AdN concentrations [15,18]. Thus, in the present study, we investigated the effect of treatment with acarbose, and with pioglitazone as a positive control, on the serum levels of adiponectin in patients with type 2 diabetes.…”

mentioning

confidence: 98%

“…have the highest capacity of increasing the circulating AdN levels indirectly by inducing "bad" large adipocytes into "good" small adipocytes [12,13] and/or by directly inducing adiponectin gene transcription through PPARγ [14]. Pioglitazone, the only thiazolidine derivative clinically available in Japan, is no exception: it has been shown to increase blood levels of AdN, particularly its high molecular weight isoform (HMWAdN) [15][16][17][18], raising a possibility that anti-diabetic and anti-atherogenic effects of pioglitazone may partly be mediated by increased AdN.…”

mentioning

confidence: 99%

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Acarbose Treatment Increases Serum Total Adiponectin Levels in Patients with Type 2 Diabetes

et al. 2008

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Abstract. Adiponectin is an anti-diabetic and anti-atherogenic adipokine that serves as a major determinant of insulin sensitivity. Thiazolidine derivatives increase circulating adiponectin, particularly the high molecular weight isoform, which has been shown to well correlate with amelioration of insulin resistance by thiazolidines in diabetic patients. α-glucosidase inhibitors are another class of anti-diabetic agents that specifically reduce postprandial blood glucose elevations, but its effect on adiponectin is largely unknown. In the present study we investigated effect of an α-glucosidase inhibitor, acarbose, together with pioglitazone, the only thiazolidine derivative available in Japan, on serum concentrations of adiponectin. Seventeen patients with type 2 diabetes were treated with acarbose and sixteen with pioglitazone for three months. Treatment with acarbose and pioglitazone decreased HbA1c values by 0.49% and 0.63%, respectively. Pioglitazone, as expected, increased serum levels of total adiponectin by 2.1 fold and its high molecular weight isoform by 3.6 fold. We found that acarbose also caused a small but significant increase in serum concentrations of total adiponectin. However, in contrast to pioglitazone, no appreciable changes were observed in the levels of high molecular weight adiponectin. In conclusion, acarbose increases serum concentrations of total adiponectin without preference of the high molecular weight isoform in type 2 diabetic patients. Clinical relevance of the increased adiponectin to the acarbose effects remains to be elucidated.

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“…Activation of PPAR-␥ stimulates differentiation to insulin-sensitive smaller adipocytes 11 and redistributes fat from visceral to subcutaneous depots, a pattern that has been associated with lower CVD risk, 12 supported by improved adipocytokine profiles following treatment with thiazolidinediones such as increased adiponectin and decreased tissue necrosis factor-␣. 13 In addition, thiazolidinediones reduce circulating free fatty acids, likely via potentiation of antilipolytic effects of insulin and upregulation of adipocyte free fatty acid transporters, 14 with potential favorable effects on liver and skeletal muscle metabolism, 7 ␤-cell function, 15 vascular inflammation and endothelial function, 16 and myocardial viability. 17 Thus, the net effect of thiazolidinedione treatment is an increased mass of small, insulin-sensitive subcutaneous adipocytes with decreased lipolytic activity, resulting in decreased circulating free fatty acids and improved adipocytokine profiles.…”

Section: Metabolic Effects Adipogenesismentioning

confidence: 99%

New Drugs for the Treatment of Diabetes Mellitus

2008

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Pioglitazone increases circulating adiponectin levels and subsequently reduces TNF‐α levels in Type 2 diabetic patients: a randomized study

Abstract: In summary, pioglitazone caused an immediate increase in circulating adiponectin levels, followed by a reduction of TNF-alpha. The observed increase in circulating adiponectin could be related to decreases in both systolic and diastolic blood pressure.

Cited by 46 publications

References 27 publications

Effects of ARB or ACE-Inhibitor Administration on Plasma Levels of Aldosterone and Adiponectin in Hypertension

Effects of ARB or ACE-Inhibitor Administration on Plasma Levels of Aldosterone and Adiponectin in Hypertension

Acarbose Treatment Increases Serum Total Adiponectin Levels in Patients with Type 2 Diabetes

New Drugs for the Treatment of Diabetes Mellitus

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