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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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 glycemic control-independent mechanisms.
Department of Endocrinology, Wolfson Med Center, Holon, Israel. marinas@wolfson.health.gov.il
Marina
M
Shargorodsky
Elena
E
Omelchenko
Zipora
Z
Matas
Mona
M
Boaz
Dov
D
Gavish
D052242:Adiponectin / Q000097:blood*; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D015536:Down-Regulation; D005234:Fatty Liver / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance; D007557:Israel; D016014:Linear Models; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D015999:Multivariate Analysis; D065626:Non-alcoholic Fatty Liver Disease; D013997:Time Factors; D016896:Treatment Outcome; D059289:Vascular Stiffness / Q000187:drug effects*
C499918:ADIPOQ protein, human; D052242:Adiponectin; D015415:Biomarkers; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D008687:Metformin