Santilli F, Guagnano M T, Tartaro E, Simeone P, Liani R, Sborgia C, Tripaldi R, Laronga G, Leo M, Maccarone M, Angelucci E, Federico V, Pansa L, Lattanzio F M, Davi G and Consoli A
Chieti University School of Medicine and Health Sciences, Italy
Posters-Accepted Abstracts: J Diabetes Metab
Obesity, insulin resistance and beta cell deterioration are key issues in the development and progression of type 2 diabetes (T2DM). Given the concurrent effects acknowledged for GLP-1 agonists on body weight, fat mass, insulin resistance and beta cell preservation, we hypothesized that this class of drugs may exert additional actions on top of those anticipated for lifestyle intervention-mediated weight loss. Twenty-nine metformin-treated obese subjects with impaired glucose tolerance (IGT), impaired fasting glucose (IFG) or newly diagnosed T2DM, were randomized to liraglutide treatment (1.8 mg/d) or lifestyle counseling to assess whether changes in subcutaneous (SAT) and visceral (VAT) adipose tissue distribution and in degree of non-alcoholic fatty liver disease (NAFLD) (all assessed by MRI) after a modest and comparable weight loss (7% of initial body weight), might affect insulin sensitivity (Matsuda Index) and β-cell performance (by insulin secretion-sensitivity index-2 (ISSI-2)) during multiple sampling oral glucose tolerance test. SAT and NAFLD grade were significantly and comparably reduced in both treatment groups, whereas insulin sensitivity was not significantly affected by any intervention. In contrast, the liraglutide group showed a significantly greater reduction in median VAT (p=0.001), as compared to the lifestyle group (-15.3% vs. -7.3% median decrease) and a greater improvement in beta cell function (ISSI-2) (96.3% vs. 29.8%, p=0.006), which translated into a significantly more pronounced reduction in both fasting, 1-hour and 2-hour postprandial plasma glucose, despite comparably reduced HbA1c in both groups (by 7.0%). In the liraglutide arm, but not in the lifestyle arm, VAT values were significantly related to ISSI-2 (Rho=-0.60, p=0.023) and adiponectin levels (Rho=-0-589, p=0.021) throughout the intervention period. This pilot study may help establishing a cause-and-effect relationship between VAT inflammation, beta cell performance and development or progression of T2DM, unravelling as well potential mechanisms by which liraglutide may favorably impact T2DM pathogenesis.
Email: fra.santilli22@gmail.com
