Liraglutide reduces oxidative stress and restores heme oxygenase-1 and ghrelin levels in patients with type 2 diabetes: a prospective pilot study

利拉鲁肽减轻氧化应激并恢复 2 型糖尿病患者的血红素加氧酶-1 和生长素释放肽水平:一项前瞻性试点研究

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作者:Manfredi Rizzo, Nicola Abate, Manisha Chandalia, Ali A Rizvi, Rosaria V Giglio, Dragana Nikolic, Antonella Marino Gammazza, Ignazio Barbagallo, Esma R Isenovic, Maciej Banach, Giuseppe Montalto, Giovanni Li Volti

Conclusions

In a 2-months prospective pilot study, the addition of liraglutide to metformin resulted in improvement in oxidative stress as well as plasma ghrelin and HO-1 concentrations in patients with T2DM. These findings seemed to be independent of the known effects of liraglutide on glucose metabolism.

Objective

We evaluated the effect of liraglutide on markers of oxidative stress, heme oxygenase-1 (HO-1), and plasma ghrelin levels in patients with type-2 diabetes mellitus (T2DM). Design and setting: A prospective pilot study of 2 months' duration has been performed at the Unit of Diabetes and Cardiovascular Prevention at University of Palermo, Italy. Patients and Intervention(s): Twenty subjects with T2DM (10 men and 10 women; mean age: 57 ± 13 y) were treated with liraglutide sc (0.6 mg/d for 2 wk, followed by 1.2 mg/d) in addition to metformin (1500 mg/d orally) for 2 months. Patients with liver disorders or renal failure were excluded. Main outcome measure(s): Plasma ghrelin concentrations, oxidative stress markers, and heat-shock proteins, including HO-1 were assessed.

Results

The addition of liraglutide resulted in a significant decrease in glycated hemoglobin (HbA1c) (8.5 ± 0.4 vs 7.5 ± 0.4%, P < .0001). In addition, plasma ghrelin and glutathione concentrations increased (8.2 ± 4.1 vs 13.6 ± 7.3 pg/ml, P = .0007 and 0.36 ± 0.06 vs 0.44 ± 0.07 nmol/ml, P = .0002, respectively), whereas serum lipid hydroperoxides and HO-1 decreased (0.11 ± 0.05 vs 0.04 ± 0.07 pg/ml, P = .0487 and 7.7 ± 7.7 vs 3.6 ± 1.8 pg/ml, P = .0445, respectively). These changes were not correlated with changes in fasting glycemia or HbA1c. Conclusions: In a 2-months prospective pilot study, the addition of liraglutide to metformin resulted in improvement in oxidative stress as well as plasma ghrelin and HO-1 concentrations in patients with T2DM. These findings seemed to be independent of the known effects of liraglutide on glucose metabolism.

Trial registration

ClinicalTrials.gov NCT01715428.

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