ESA-SRB-AOTA 2019

Systemic inflammation and The Effect of a GLP-1 Agonist in Adults with Prader-Willi Syndrome  (#534)

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

Introduction:

Prader – Willi syndrome (PWS) is one of the most common known genetic obesity disorders. Individuals with PWS have reduced life expectancy due to cardiovascular disease. Increased systemic low-grade inflammation is postulated to contribute. Whilst increased systemic inflammation is associated with excess adiposity, increased visceral fat mass and decreased insulin sensitivity in obesity, an overactivation of the innate immune system has been reported in PWS independent of central adiposity and insulin resistance. This chronic inflammatory process could present a novel treatment target to reduce cardiovascular morbidity and mortality in PWS.

Aims:

  1. To assess circulating cytokine profile, fasting and postprandially, to estimate systemic immune activation in PWS, compared to lean and adiposity-matched obese subjects.
  2. To determine the acute effect of a GLP-1 receptor agonist on systemic inflammation in PWS.

 

Methods:

Baseline and postprandial inflammatory cytokine levels were measured in 9 PWS adults and compared with 11 adiposity-matched obese, and 10 healthy lean subjects.  In a single-blinded, crossover design, 6 PWS and 11 obese subjects, received either a single dose of 10 mcg exenatide  (Byetta) or normal saline subcutaneously 15 minutes before a 600kCAl test meal. IL-6, the only cytokine high in PWS compared to control subjects, was measured at baseline and for 240 min after the test meal.

 

Results:

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. Single dose GLP-1 agonist did not significantly lower IL-6 response post-prandially.

 

Conclusion:

There was no generally increased immune activation observed in PWS. However, the increased IL-6 levels fasting and post-prandially appears to be specific to PWS and merits further investigation regarding its possible contribution to the cardiovascular risk.