publication . Article . 2013

Metabolite Profiling Reveals Normal Metabolic Control in Carriers of Mutations in the Glucokinase Gene (MODY2)

Spégel, Peter; Ekholm, Ella; Tuomi, Tiinamaija; Groop, Leif; Mulder, Hindrik; Filipsson, Karin;
Open Access English
  • Published: 01 Jan 2013 Journal: DIABETES, volume 62, issue 2, pages 653-661 (issn: 0012-1797, eissn: 1939-327X, Copyright policy)
  • Publisher: AMER DIABETES ASSOC
Abstract
Mutations in the gene encoding glucokinase (GCK) cause a mild hereditary form of diabetes termed maturity-onset diabetes of the young (MODY)2 or GCK-MODY. The disease does not progress over time, and diabetes complications rarely develop. It has therefore been suggested that GCK-MODY represents a metabolically compensated condition, but experimental support for this notion is lacking. Here, we profiled metabolites in serum from patients with MODY1 (HNF4A), MODY2 (GCK), MODY3 (HNF1A), and type 2 diabetes and from healthy individuals to characterize metabolic perturbations caused by specific mutations. Analysis of four GCK-MODY patients revealed a metabolite patte...
Subjects
free text keywords: Genetics/Genomes/Proteomics/Metabolomics
Related Organizations
Funded by
EC| CEED3
Project
CEED3
Collaborative European effort to Develop Diabetes Diagnostics
  • Funder: European Commission (EC)
  • Project Code: 223211
  • Funding stream: FP7 | SP1 | HEALTH
51 references, page 1 of 4

1 Gat-Yablonski G Shalitin S Phillip M Maturity onset diabetes of the young—review. Pediatr Endocrinol Rev 2006;3(Suppl. 3):514–520 17551475 [PubMed]

2 Fajans SS Bell GI MODY: history, genetics, pathophysiology, and clinical decision making. Diabetes Care 2011;34:1878–1884 21788644 [OpenAIRE] [PubMed]

3 Osbak KK Colclough K Saint-Martin C Update on muta tions in glucokinase (GCK), which cause maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemic hypoglycemia. Hum Mutat 2009;30:1512–1526 19790256 [PubMed]

4 Velho G BlanchéH Vaxillaire M Identification of 14 new glucokinase mutations and description of the clinical profile of 42 MODY-2 families. Diabetologia 1997;40:217–224 9049484 [PubMed]

5 Stride A Hattersley AT Different genes, different diabetes: lessons from maturity-onset diabetes of the young. Ann Med 2002;34:207–216 12173691 [PubMed]

6 Timsit J Bellanné-Chantelot C Dubois-Laforgue D Velho G Diagnosis and management of maturity-onset diabetes of the young. Treat Endocrinol 2005;4:9–18 15649097 [PubMed]

7 Mitchell F Diabetes: extended genetic testing improves MODY diagnosis. Nat Rev Endocrinol 2012;8:319

8 Schnyder S Mullis PE Ellard S Hattersley AT Flück CE Genetic testing for glucokinase mutations in clinically selected patients with MODY: a worthwhile investment. Swiss Med Wkly 2005;135:352–356 16059790 [OpenAIRE] [PubMed]

9 Owen KR Skupien J Malecki MT CEED3 Consortium The clinical application of non-genetic biomarkers for differential diagnosis of monogen ic diabetes. Diabetes Res Clin Pract 2009;86(Suppl. 1):S15–S21 20115926 [PubMed]

10 Zhang GF Sadhukhan S Tochtrop GP Brunengraber H Metabolomics, pathway regulation, and pathway discovery. J Biol Chem 2011;286:23631–23635 21566142 [OpenAIRE] [PubMed]

11 Pasikanti KK Ho PC Chan ECY Gas chromatography/mass spectrometry in metabolic profiling of biological fluids. J Chromatogr B Analyt Technol Biomed Life Sci 2008;871:202–211 18479983 [PubMed]

12 Wishart DS Computational approaches to metabolomics. Methods Mol Biol 2010;593:283–313 19957155 [PubMed]

13 Ekholm E, Shaat N, Holst JJ. Characterization of beta cell and incretin function in patients with MODY1 (HNF4A MODY) and MODY3 (HNF1A MODY) in a Swedish patient collection. Acta Diabetol. 16 July 2011 [Epub ahead of print]

14 Spégel P Danielsson APH Bacos K Metabolomics analysis of a human oral glucose tolerance test reveals fatty acids as reliable indicators of regulated metabolism. Metabolomics 2010;6:56–66

15 Danielsson APH Moritz T Mulder H Spégel P Development of a gas chromatography / mass spectrometry based metabolomics protocol by means of statistical experimental design. Metabolomics 2012;8:50–63

51 references, page 1 of 4
Abstract
Mutations in the gene encoding glucokinase (GCK) cause a mild hereditary form of diabetes termed maturity-onset diabetes of the young (MODY)2 or GCK-MODY. The disease does not progress over time, and diabetes complications rarely develop. It has therefore been suggested that GCK-MODY represents a metabolically compensated condition, but experimental support for this notion is lacking. Here, we profiled metabolites in serum from patients with MODY1 (HNF4A), MODY2 (GCK), MODY3 (HNF1A), and type 2 diabetes and from healthy individuals to characterize metabolic perturbations caused by specific mutations. Analysis of four GCK-MODY patients revealed a metabolite patte...
Subjects
free text keywords: Genetics/Genomes/Proteomics/Metabolomics
Related Organizations
Funded by
EC| CEED3
Project
CEED3
Collaborative European effort to Develop Diabetes Diagnostics
  • Funder: European Commission (EC)
  • Project Code: 223211
  • Funding stream: FP7 | SP1 | HEALTH
51 references, page 1 of 4

1 Gat-Yablonski G Shalitin S Phillip M Maturity onset diabetes of the young—review. Pediatr Endocrinol Rev 2006;3(Suppl. 3):514–520 17551475 [PubMed]

2 Fajans SS Bell GI MODY: history, genetics, pathophysiology, and clinical decision making. Diabetes Care 2011;34:1878–1884 21788644 [OpenAIRE] [PubMed]

3 Osbak KK Colclough K Saint-Martin C Update on muta tions in glucokinase (GCK), which cause maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemic hypoglycemia. Hum Mutat 2009;30:1512–1526 19790256 [PubMed]

4 Velho G BlanchéH Vaxillaire M Identification of 14 new glucokinase mutations and description of the clinical profile of 42 MODY-2 families. Diabetologia 1997;40:217–224 9049484 [PubMed]

5 Stride A Hattersley AT Different genes, different diabetes: lessons from maturity-onset diabetes of the young. Ann Med 2002;34:207–216 12173691 [PubMed]

6 Timsit J Bellanné-Chantelot C Dubois-Laforgue D Velho G Diagnosis and management of maturity-onset diabetes of the young. Treat Endocrinol 2005;4:9–18 15649097 [PubMed]

7 Mitchell F Diabetes: extended genetic testing improves MODY diagnosis. Nat Rev Endocrinol 2012;8:319

8 Schnyder S Mullis PE Ellard S Hattersley AT Flück CE Genetic testing for glucokinase mutations in clinically selected patients with MODY: a worthwhile investment. Swiss Med Wkly 2005;135:352–356 16059790 [OpenAIRE] [PubMed]

9 Owen KR Skupien J Malecki MT CEED3 Consortium The clinical application of non-genetic biomarkers for differential diagnosis of monogen ic diabetes. Diabetes Res Clin Pract 2009;86(Suppl. 1):S15–S21 20115926 [PubMed]

10 Zhang GF Sadhukhan S Tochtrop GP Brunengraber H Metabolomics, pathway regulation, and pathway discovery. J Biol Chem 2011;286:23631–23635 21566142 [OpenAIRE] [PubMed]

11 Pasikanti KK Ho PC Chan ECY Gas chromatography/mass spectrometry in metabolic profiling of biological fluids. J Chromatogr B Analyt Technol Biomed Life Sci 2008;871:202–211 18479983 [PubMed]

12 Wishart DS Computational approaches to metabolomics. Methods Mol Biol 2010;593:283–313 19957155 [PubMed]

13 Ekholm E, Shaat N, Holst JJ. Characterization of beta cell and incretin function in patients with MODY1 (HNF4A MODY) and MODY3 (HNF1A MODY) in a Swedish patient collection. Acta Diabetol. 16 July 2011 [Epub ahead of print]

14 Spégel P Danielsson APH Bacos K Metabolomics analysis of a human oral glucose tolerance test reveals fatty acids as reliable indicators of regulated metabolism. Metabolomics 2010;6:56–66

15 Danielsson APH Moritz T Mulder H Spégel P Development of a gas chromatography / mass spectrometry based metabolomics protocol by means of statistical experimental design. Metabolomics 2012;8:50–63

51 references, page 1 of 4
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publication . Article . 2013

Metabolite Profiling Reveals Normal Metabolic Control in Carriers of Mutations in the Glucokinase Gene (MODY2)

Spégel, Peter; Ekholm, Ella; Tuomi, Tiinamaija; Groop, Leif; Mulder, Hindrik; Filipsson, Karin;