A triple-blinded crossover study to evaluate the short-term safety of sweet manioc starch for the treatment of glycogen storage disease type Ia

Vaneisse C L Monteiro, Bibiana M de Oliveira, Bruna B Dos Santos, Fernanda Sperb-Ludwig, Lilia F Refosco, Tatiele Nalin, Terry G J Derks, Carolina F Moura de Souza, Ida V D Schwartz, Vaneisse C L Monteiro, Bibiana M de Oliveira, Bruna B Dos Santos, Fernanda Sperb-Ludwig, Lilia F Refosco, Tatiele Nalin, Terry G J Derks, Carolina F Moura de Souza, Ida V D Schwartz

Abstract

Background: Glycogen storage disease type 1a (GSD Ia) is characterized by severe fasting hypoglycemia. The clinical management includes the administration of uncooked cornstarch (UCCS). Although such a diet approach is effective in achieving euglycemia, its impact on the quality of life of patients should be considered. In vitro analyses suggest a longer release of glucose when using sweet manioc starch (SMS).

Methods: We compared the efficacy and safety of the administration of SMS and UCCS during a short-fasting challenge in patients with GSD Ia in a randomized, triple-blind, phase I/II, cross-over study. GSD Ia patients aged ≥ 16 years and treated with UCCS were enrolled. Participants were hospitalized for two consecutive nights, receiving UCCS or SMS in each night. After the administration of the starches, glucose, lactate and insulin levels were measured in 1-h interval throughout the hospitalization period. The procedures were interrupted after 10 h of fasting or in a hypoglycemic episode (< 3.88 mmol/L).

Results: Eleven individuals (mean age: 21.6 ± 4.3 years; all presenting body mass index > 25 kg/m2) participated in the study. The average fasting period was 8.2 ± 2.0 h for SMS and 7.7 ± 2.3 h for UCCS (p = 0.04). SMS maintained euglycemia for a greater period over UCCS. Increased lactate concentrations were detected even in absence of hypoglycemia, not being influenced by the different starches investigated (p = 0.17). No significant difference was found in total cholesterol, HDL, triglycerides and uric acid levels in both arms. None of the patients showed severe adverse events.

Conclusions: SMS appears to be non-inferior to UCCS in the maintenance of euglycemia, thus emerging as a promising alternative to the treatment of GSD Ia.

Keywords: Cornstarch; Dietary treatment; Hepatic glycogen storage disease; Inborn errors of metabolism; Sweet manioc starch; Treatment strategies.

Conflict of interest statement

TN is currently an employee of Ultragenyx Farmacêutica Brasil LTDA and hold stock in Ultragenyx Pharmaceutical Inc. All other authors declare no conflicts of interest.

Figures

Fig. 1
Fig. 1
Kaplan Meier curve indicating test durations for each starch load performed (n = 11). UCCS: uncooked cornstarch and SMS: sweet manioc starch
Fig. 2
Fig. 2
Blood concentrations of glucose and lactic acid after UCCS or SMS throughout the study period. A Glucose level for each starch load performed (n = 11), normal range: > 3.88 mmol/L; B Lactic acid levels for each starch load performed (n = 11), normal range: 0.5 to 2.2 mmol/L. UCCS (uncooked cornstarch load) or SMS (sweet manioc starch)
Fig. 3
Fig. 3
Study design. *refers to blood collection for the evaluation of glucose, lactic acid, insulin, total cholesterol, triglyceride and uric acid levels. **refers to blood collection for the glucose, lactic acid and insulin levels. GSD Ia: glycogen storage disorder type Ia; UCCS: uncooked cornstarch and SMS: sweet manioc starch

References

    1. Wolfsdorf JI, Weinstein DA. Glycogen storage diseases. Rev Endocr Metab Disord. 2003;4(1):95–102. doi: 10.1023/a:1021831621210.
    1. Koeberl DD, Kishnani PS, Chen YT. Glycogen storage disease types I and II: treatment updates. J Inherit Metab Dis. 2007;30(2):159–164. doi: 10.1007/s10545-007-0519-9.
    1. Brody LC, Abel KJ, Castilla LH, et al. Construction of a transcription map surrounding the BRCA1 locus of human chromosome 17. Genomics. 1995;25(1):238–247. doi: 10.1016/0888-7543(95)80131-5.
    1. Grinshpun A, Condiotti R, Waddington SN, et al. Neonatal gene therapy of glycogen storage disease type Ia using a feline immunodeficiency virus-based vector. Mol Ther. 2010;18(9):1592–1598. doi: 10.1038/mt.2010.119.
    1. Froissart R, Piraud M, Boudjemline AM, et al. Glucose-6-phosphatase deficiency. Orphanet J Rare Dis. 2011;6:27. doi: 10.1186/1750-1172-6-27.
    1. Bali DS, Chen YT, Austin S, Goldstein JL. Glycogen Storage Disease Type I. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews(®). University of Washington, Seattle. Copyright © 1993–2020, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.; 1993.
    1. Laforêt P, Weinstein D, Smit P. Inborn metabolic diseases: diagnosis and treatment In: Saudubray J, van den Berghe G, Walter J, eds. 2012:115–139:chap The glycogen storage diseases and related disorders.
    1. Kishnani PS, Austin SL, Abdenur JE, et al. Diagnosis and management of glycogen storage disease type I: a practice guideline of the American College of Medical Genetics and Genomics. Genet Med. 2014;16(11):e1. doi: 10.1038/gim.2014.128.
    1. NCT0397027. Long-term follow-up to evaluate the safety and efficacy of adeno associated virus (AAV) serotype 8 (AAV8)-mediated gene transfer of glucose-6-phosphatase (G6Pase) in adults with glycogen storage disease type Ia (GSDIa). NCT0397027. Accessed Apr 7, 2021.
    1. Bhattacharya K, Orton RC, Qi X, et al. A novel starch for the treatment of glycogen storage diseases. J Inherit Metab Dis. 2007;30(3):350–357. doi: 10.1007/s10545-007-0479-0.
    1. Li S, Cui Y, Zhou Y, Luo Z, Liu J, Zhao M. The industrial applications of cassava: current status, opportunities and prospects. J Sci Food Agric. 2017;97(8):2282–2290. doi: 10.1002/jsfa.8287.
    1. Nalin T, Sperb-Ludwig F, Venema K, Derks TG, Schwartz IV. Determination of amylose/amylopectin ratio of starches. J Inherit Metab Dis. 2015;38(5):985–986. doi: 10.1007/s10545-015-9850-8.
    1. Nalin T, Venema K, Weinstein DA, et al. In vitro digestion of starches in a dynamic gastrointestinal model: an innovative study to optimize dietary management of patients with hepatic glycogen storage diseases. J Inherit Metab Dis. 2015;38(3):529–536. doi: 10.1007/s10545-014-9763-y.
    1. Rousseau-Nepton I, Huot C, Laforte D, et al. Sleep and quality of life of patients with glycogen storage disease on standard and modified uncooked cornstarch. Mol Genet Metab. 2018;123(3):326–330. doi: 10.1016/j.ymgme.2017.09.003.
    1. Thornhill C, Saavedra H, Tatevian N, et al. A Case of eosinophilic gastroenteritis in a Patient with glycogen storage disease type 1a. Open J Clin Med Case Rep. 2017;3(12):1–2.
    1. Peeks F, Boonstra WF, de Baere L, et al. Research priorities for liver glycogen storage disease: an international priority setting partnership with the James Lind Alliance. J Inherit Metab Dis. 2020;43(2):279–289. doi: 10.1002/jimd.12178.
    1. Bhattacharya K, Mundy H, Lilburn MF, Champion MP, Morley DW, Maillot F. A pilot longitudinal study of the use of waxy maize heat modified starch in the treatment of adults with glycogen storage disease type I: a randomized double-blind cross-over study. Orphanet J Rare Dis. 2015;10:18. doi: 10.1186/s13023-015-0229-6.
    1. Correia CE, Bhattacharya K, Lee PJ, et al. Use of modified cornstarch therapy to extend fasting in glycogen storage disease types Ia and Ib. Am J Clin Nutr. 2008;88(5):1272–1276. doi: 10.3945/ajcn.2008.26352.
    1. Sidbury JB, Chen YT, Roe CR. The role of raw starches in the treatment of type I glycogenosis. Arch Intern Med. 1986;146(2):370–373. doi: 10.1001/archinte.1986.00360140200029.
    1. Anderson GH, Cho CE, Akhavan T, Mollard RC, Luhovyy BL, Finocchiaro ET. Relation between estimates of cornstarch digestibility by the Englyst in vitro method and glycemic response, subjective appetite, and short-term food intake in young men. Am J Clin Nutr. 2010;91(4):932–939. doi: 10.3945/ajcn.2009.28443.
    1. Series FFaN. Maize in human nutrition. Accessed October, 2020.

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