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01.12.2012 | Original investigation | Ausgabe 1/2012 Open Access

Cardiovascular Diabetology 1/2012

Relation between augmentation index and adiponectin during one-year metformin treatment for nonalcoholic steatohepatosis: effects beyond glucose lowering?

Cardiovascular Diabetology > Ausgabe 1/2012
Marina Shargorodsky, Elena Omelchenko, Zipora Matas, Mona Boaz, Dov Gavish
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1475-2840-11-61) contains supplementary material, which is available to authorized users.

Competing interests

The corresponding author and all of the authors have no conflicts of interest or financial or other contractual agreements that might cause conflicts of interest.

Authors’ contributions

MS and DG contributed to the study conception and design. EO was responsible for the data acquisition. MB performed the analysis and interpretation of data. ZM carried out the immunoassays. MS was responsible for review the existing literature and for writing the first draft of the paper. All authors performed a critical revision of the manuscript for important intellectual content. All authors read and approved the final manuscript.



Insulin resistance (IR) is the major driving force behind development and progression of atherosclerosis in patients with nonalcoholic fatty liver disease (NAFLD). Therefore, correction of IR is a relevant therapeutic target.
We performed the current trial to evaluate whether 12- month metformin therapy improves vascular stiffness in patients with NAFLD and to assess if this improvement is associated with change in glucose control, insulin resistance or circulating adiponectin.


In randomized, placebo controlled study, 63 patients with NAFLD were assigned to one of two groups: Group 1 received daily metformin; Group 2 received placebo. Central aortic augmentation index (AI) was performed using SphygmoCor (version 7.1, AtCor Medical, Sydney, Australia) at baseline, at 4-and 12-month treatment period. Metabolic parameters, insulin resistance markers and serum adiponectin levels were determined.


In placebo group: AI did not improve during the treatment period. Liver function and adiponectin levels did not change during the study.
In multiple linear regression analysis, the independent predictors of arterial stiffness improvement were metformin treatment and increase in circulating adiponectin levels.
Among metformin treated patients: AI decreased significantly during the study. ALP and ALT decreased during initial 4-month treatment period, however raised to the pretreatment levels after 12 months. Serum adiponectin level tended to increase during treatment period with metformin.


Metformin treatment was associated with significant decrease in AI during one year treatment in NAFLD patients. These beneficial vascular effects was associated with exposure to metformin per se as well as change in adiponectin levels suggesting that metformin may mediate its vascular effects via glicemic control-independent mechanisms.

Trial registry

no: NCT01084486
Authors’ original file for figure 1
Authors’ original file for figure 2
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