Circulating adiponectin levels in type 2 diabetes mellitus patients with or without non-alcoholic fatty liver disease: Results of a small, open-label, randomized controlled intervention trial in a subgroup receiving short-term exenatide

- 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.

AimDiabetes 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.MethodsDMT2 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).ResultsBaseline 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).ConclusionSupplementation 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.