HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 293/5/E1378    most recent 00658.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Weghuber, D. Articles by Bischof, M. G. Search for Related Content PubMed PubMed Citation Articles by Weghuber, D. Articles by Bischof, M. G.

Characterization of hepatic and brain metabolism in young adults with glycogen storage disease type 1: a magnetic resonance spectroscopy study

D. Weghuber,^2,4 M. Mandl,¹ M. Krák,¹ M. Roden,³ P. Nowotny,¹ A. Brehm,¹ M. Krebs,¹ K. Widhalm,² and M. G. Bischof¹

¹Division of Endocrinology and Metabolism, Department of Internal Medicine III, and ²Division of Clinical Nutrition, Department of Pediatrics, University of Vienna Medical School; ³Department of Internal Medicine I, Hanusch Hospital Vienna, Austria; and ⁴Department of Pediatrics, Paracelsus Private Medical School, Salzburg, Austria

Submitted 3 December 2006 ; accepted in final form 28 August 2007

In glycogen storage disease type 1 (GSD1), children present with severe hypoglycemia, whereas the propensity for hypoglycemia may decrease with age in these patients. It was the aim of this study to elucidate the mechanisms for milder hypoglycemia symptoms in young adult GSD1 patients. Four patients with GSD1 [body mass index (BMI) 23.2 ± 6.3 kg/m, age 21.3 ± 2.9 yr] and four healthy controls matched for BMI (23.1 ± 3.0 kg/m) and age (24.0 ± 3.1 yr) were studied. Combined ¹H/³¹P nuclear magnetic resonance spectroscopy (NMRS) was used to assess brain metabolism. Before and after administration of 1 mg glucagon, endogenous glucose production (EGP) was measured with D-[6,6-²H₂]glucose and hepatic glucose metabolism was examined by ¹H/¹³C/³¹P NMRS. At baseline, GSD1 patients exhibited significantly lower rates of EGP (0.53 ± 0.04 vs. 1.74 ± 0.03 mg·kg^–1·min^–1; P < 0.01) but an increased intrahepatic glycogen (502 ± 89 vs. 236 ± 11 mmol/l; P = 0.05) and lipid content (16.3 ± 1.1 vs. 1.4 ± 0.4%; P < 0.001). After glucagon challenge, EGP did not change in GSD1 patients (0.53 ± 0.04 vs. 0.59 ± 0.24 mg·kg^–1·min^–1; P = not significant) but increased in healthy controls (1.74 ± 0.03 vs. 3.95 ± 1.34; P < 0.0001). In GSD1 patients, we found an exaggerated increase of intrahepatic phosphomonoesters (0.23 ± 0.08 vs. 0.86 ± 0.19 arbitrary units; P < 0.001), whereas inorganic phosphate decreased (0.36 ± 0.08 vs. –0.43 ± 0.17 arbitrary units; P < 0.01). Intracerebral ratios of glucose and lactate to creatine were higher in GSD1 patients (P < 0.05 vs. control). Therefore, hepatic defects of glucose metabolism persist in young adult GSD1 patients. Upregulation of the glucose and lactate transport at the blood-brain barrier could be responsible for the amelioration of hypoglycemic symptoms.

endogenous glucose production; glucose-6-phospate; intrahepatocellular lipid content; hypoglycemia