Highlights
- •DMT2 with concomitant NAFLD is associated with a greater decrease in adiponectin.
- •Adiponectin concentration was found to correlate negatively with the degree of ALT.
- •Exenatide was effective in inducing weight loss and non-inferior in lowering HbA1c.
- •Exenatide proved equally effective in increasing adiponectin levels.
- •Increases of adiponectin were attributable to weight loss, glucose control and CRP.
Abstract
Aim
Diabetes mellitus type 2 (DMT2) and non-alcoholic fatty liver disease (NAFLD) are
both characterized by decreased circulating adiponectin. Recently, glucagon-like peptide-1
receptor agonists have been shown to induce adiponectin's expression. However, their
interaction on clinical grounds needs to be further elucidated.
Methods
DMT2 patients with abnormal aminotransferases were screened for NAFLD and subjected
to liver biopsy (group A, n = 17). A subgroup of patients (n = 110), after assessed for eligibility criteria, was blindly randomized to receive either
6-month exenatide supplementation on glargine insulin (group B) or intense, self-regulated,
insulin therapy alone (group C).
Results
Baseline patient characteristics: 49(38.6%) males, aged 63.1 ± 7.5 years-old, BMI 32.9 ± 4.9 kg/m2, HbA1c 8.1 ± 1.2% (65 ± 14 mmol/mol), median ALT 23 U/L (range 5–126), AST 20 U/L (7–72). Group A had biopsy-proven NAFLD with a median Activity Score of 5 and
fibrosis stage 3. Presence of NAFLD was accompanied by a significant decline in adiponectin
(p < 0.001), which was negatively correlated with the degree of ALT in all groups (Spearman's
correlation, rs = −0.644, p < 0.001). In the subgroup intervention trial, adiponectin was significantly raised in
both groups B and C (t-Student for paired samples, p = 0.001) by Δ= +24.2% (interquartile range 14.8–53.2%). This elevation was not associated with the
type of intervention but with weight loss, glycemic control and reduction of C-reactive
protein (one-way ANCOVA).
Conclusion
Supplementation of exenatide to glargine insulin compared to standard insulin was:
(i) effective in inducing weight loss, (ii) non-inferior in lowering HbA1c and (iii)
non-inferior in increasing circulating adiponectin. Higher adiponectin was associated
with lower ALT, suggesting a hepato-protective role for this cytokine.
Keywords
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Article info
Publication history
Published online: January 08, 2016
Accepted:
December 27,
2015
Received in revised form:
October 19,
2015
Received:
July 10,
2015
Identification
Copyright
© 2016 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
