METABOLIC CHANGES IN HUNTINGTON'S DISEASE

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 109-133-GHRH, GH & IGF Biology & Signaling
Bench to Bedside
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-133
Rajasree Nambron*1, Edina Silajdzic2, Eirini Kalliolia3, Nathan Hill4, Peter Christopher Hindmarsh5, Maria Bjorkqvist2 and Thomas Treharne Warner3
1Gundersen Lutheran Medical Center, La Crosse, WI, 2Lund University, Lund, Sweden, 3UCL, London, United Kingdom, 4Oxford University, Oxford, United Kingdom, 5Univ College London, London, United Kingdom
Background: Several published studies indicate that many features of HD such as weight loss and skeletal muscle wasting may be related to peripheral expression of mutant Huntingtin and may be independent from neurological dysfunction. To confirm this hypothesis we looked at 24 hour blood profiles from 2 cohorts of carefully characterized cohort of HD mutation carriers (pre-manifest and moderate HD patients) to closely look at their central and peripheral hormones and compared to a control cohort.

Aims: To investigate metabolic factors over specified period on  HD mutation carriers who were either pre manifest or had  moderate stage II/III HD and comparing with controls

Methods: Control (n=15), pre-manifest (n=14) and stage II/III (n=13) participants were studied with blood and plasma sampling over a standardized 24-h period at various points and a battery of clinical tests including neurological rating and function scales were performed.Blood samples were taken from an intravenous cannula, immediately centrifuged and plasma/serum extracted and stored at −80°C. IGF,GHRF and IGFBP3 were measured at three time points (fasting 3 pm and 11 pm). Insulin and Glucose were measured for and extended glucose tolerance test. Leptin and ghrelin were measured pre and post standardized meal. Plasma samples for amino acids were drawn fasting.

Results: There was no correlation between IGFBP3 and GHRF with CAG (disease burden).Contrary to other studies that show 10-25% (Farrer 1985) of patients with HD develop altered glucose metabolism, our study did not demonstrate an increased incidence of impaired glucose tolerance when compared to  controls, pre manifest or moderates. Fasting ghrelin levels show a significant negative association with disease burden (p=0.009) and there is a significant positive association between fasting leptin levels, body mass index and scapular fat pad thickness.

Conclusions: Fasting ghrelin levels negatively correlated with progression of HD and this may be the cause of weight loss and other peripheral manifestations of HD. Further work is required to understand the underlying mechanism and its potential as an HD biomarker.

Nothing to Disclose: RN, ES, EK, NH, PCH, MB, TTW

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: CHDI Foundation, Inc 350 Seventh Ave.Suite 601 New York, NY 10001 grant awarded to Professor Warner
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