Oral Presentation ANZOS-ASLM-ICCR 2019

Systemic Inflammation and The Effect of a GLP-1 Receptor Agonist in Adults with Prader-Willi Syndrome (#74)

Jarron M Dodds 1 , Amanda Hor 2 3 4 , Lesley Campbell 2 3 4 , Alexander Viardot 2 3 4
  1. School of Medicine, The University of Notre Dame, Sydney, NSW, Australia
  2. St Vincent's Hospital, ., Sydney, NSW, Australia
  3. The University of New South Wales, ., Sydney, NSW, Australia
  4. The Garvan Institute of Medical Research, ., Sydney, NSW, Australia

Introduction: Prader - Willi syndrome (PWS) is one of the most common known genetic obesity disorders, and is associated with a reduced life expectancy due to cardiovascular disease. Increased systemic low-grade inflammation is postulated as a contributor. In non-syndromic obesity, GLP-1 receptor agonist therapy is thought to decrease cardiovascular morbidity and mortality by reducing low-grade inflammation. However, its effects have not been studied in PWS.

This project aimed to assess immune cell activation markers and circulating cytokine profile, fasting and postprandially, in PWS compared to lean and adiposity-matched obese subjects. Further, to determine the acute effect of a GLP-1 receptor agonist on immune cell activation and circulating inflammatory cytokines in PWS.

Methods: Baseline and postprandial immune cell activation markers were quantified via flow cytometry, and inflammatory cytokine levels measured via ELISA in 9 PWS adults and compared with 11 adiposity-matched obese and 10 healthy lean subjects.  In a single-blinded, crossover design, PWS and obese subjects received either a single dose of 10 mcg exenatide (Byetta) or normal saline subcutaneously 15 minutes before consuming a standardised 600 kCal meal.

Results: PWS subjects demonstrated increased fasting and postprandial innate immune cell activation, with significantly higher expression of granulocyte and monocyte cell markers. A single dose of exenatide significantly decreased innate immune cell activation markers in PWS and obese subjects. Cytokines E-selectin, MIC-1 and PAI-1 were elevated in PWS compared to lean but not different to obese. sICAM-1 levels were not different between the groups. IL-6 was higher in PWS than in Obese and Lean. A single dose GLP-1 receptor agonist did not significantly lower IL-6 response postprandially.

Conclusions - We found evidence for low-grade systemic inflammation in PWS, with increased activation of the innate immune system and raised IL-6. GLP-1 receptor agonist therapy reduced postprandial immune cell activation, but without IL-6 suppression.