| Hyperglycaemic clamp test for diabetes risk assessment in IA-2-antibody-positive relatives of type 1 diabetic patients. | |
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MedLine Citation:
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PMID: 19898832 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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AIMS/HYPOTHESIS: The aim of the study was to investigate the use of hyperglycaemic clamp tests to identify individuals who will develop diabetes among insulinoma-associated protein-2 antibody (IA-2A)-positive first-degree relatives (IA-2A(+) FDRs) of type 1 diabetic patients. METHODS: Hyperglycaemic clamps were performed in 17 non-diabetic IA-2A(+) FDRs aged 14 to 33 years and in 21 matched healthy volunteers (HVs). Insulin and C-peptide responses were measured during the first (5-10 min) and second (120-150 min) release phase, and after glucagon injection (150-160 min). Clamp-induced C-peptide release was compared with C-peptide release during OGTT. RESULTS: Seven (41%) FDRs developed diabetes 3-63 months after their initial clamp test. In all phases they had lower C-peptide responses than non-progressors (p < 0.05) and HVs (p < 0.002). All five FDRs with low first-phase release also had low second-phase release and developed diabetes 3-21 months later. Two of seven FDRs with normal first-phase but low second-phase release developed diabetes after 34 and 63 months, respectively. None of the five FDRs with normal C-peptide responses in all test phases has developed diabetes so far (follow-up 56 to 99 months). OGTT-induced C-peptide release also tended to be lower in progressors than in non-progressors or HVs, but there was less overlap in results between progressors and the other groups using the clamp. CONCLUSIONS/INTERPRETATION: Clamp-derived functional variables stratify risk of diabetes in IA-2A(+) FDRs and may more consistently identify progressors than OGTT-derived variables. A low first-phase C-peptide response specifically predicts impending diabetes while a low second-phase response may reflect an earlier disease stage. TRIAL REGISTRATION: ClinicalTrials.gov NCT00654121 FUNDING: The insulin trial was financially supported by Novo Nordisk Pharma nv. |
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Authors:
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E Vandemeulebroucke; B Keymeulen; K Decochez; I Weets; C De Block; F F?ry; U Van de Velde; I Vermeulen; P De Pauw; C Mathieu; D G Pipeleers; F K Gorus; |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-11-07 |
Journal Detail:
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Title: Diabetologia Volume: 53 ISSN: 1432-0428 ISO Abbreviation: Diabetologia Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2010-01-21 Completed Date: 2010-05-06 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0006777 Medline TA: Diabetologia Country: Germany |
Other Details:
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Languages: eng Pagination: 36-44 Citation Subset: IM |
Affiliation:
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Diabetes Research Center, Brussels Free University-VUB, 1090 Brussels, Belgium. |
| Data Bank Information | |
Bank Name/Acc. No.:
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ClinicalTrials.gov/NCT00654121 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Autoantibodies / blood* C-Peptide / blood Diabetes Mellitus / epidemiology*, genetics Diabetes Mellitus, Type 1 / genetics, immunology Family Glucose Clamp Technique HLA-DQ Antigens / genetics Humans Hyperglycemia Insulin / blood Medical History Taking Reference Values Risk Assessment Young Adult |
| Chemical | |
Reg. No./Substance:
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0/Autoantibodies; 0/C-Peptide; 0/HLA-DQ Antigens; 0/HLA-DQ2 antigen, human; 0/HLA-DQ8 antigen; 0/ICA512 autoantibody; 11061-68-0/Insulin |
| Investigator | |
Investigator/Affiliation:
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P Abrams / ; C Algoet / ; P Arnouts / ; S Ayoubi / ; A Bachy / ; J Baeyens / ; E Balasse / ; G Bataille / ; D Beckers / ; V Beckers / ; H Becq / ; A Beirinckx / ; J Beirinckx / ; M Bex / ; A Bocquet / ; A Bodson / ; F Bosly / ; H Bossaert / ; R Bouillon / ; M S Bouquegneau / ; J Bourguignon / ; H Brussaard / ; M Buysschaert / ; M Cardon / ; A Carlier / ; K Casteels / ; E Cavatorta / ; A Chachati / ; A Claessens / ; C Claeys / ; L Claeys / ; M Claeys / ; M Cnop / ; P Cochez / ; M Coeckelberghs / ; V Col / ; M Colin / ; J L Coolens / ; P Coremans / ; B Corvilain / ; F Coucke / ; W Coucke / ; E Couturier / ; A Crap? / ; L Crenier / ; P Damoiseaux / ; N Daoudi / ; C Daper / ; C Daubresse / ; J C Daubresse / ; M De Backer / ; C De Block / ; I De Feyter / ; E De Groot / ; R De Hauwere / ; K De Keyser / ; I De Leeuw / ; J De Schepper / ; K De Schynkel / ; K De Waele / ; G De Wasch / ; J A Decerf / ; K Decochez / ; P Decraene / ; F Defoer / ; R Demaeseneer / ; L Derdelinckx / ; S Deweer / ; L Dooms / ; H Dorchy / ; S Driessens / ; M Du Caju / ; J Ducobu / ; V Dumasy / ; E Duvivier / ; F Duyck / ; A Dysseleer / ; L Emsens / ; W Engelen / ; C Ernould / ; V Ers / ; C Evenepoel / ; A Eykens / ; N Favere / ; F Fery / ; R Fils / ; L Frankart / ; N Gaham / ; E Galopin-Vanderstappen / ; K Garmijn / ; J Gerard / ; I Geronooz / ; P Gillard / ; C Gillet / ; M Giri / ; F Gorus / ; J Guiot / ; A Haemers / ; S Haemers / ; C Hendrieckx / ; C Herbaut / ; G Heremans / ; F Heureux / ; E Heyns / ; R Hilbrands / ; A Huard / ; G Hubermont / ; J Huyghe / ; V Immegeers / ; B Jandrain / ; P Jopart / ; J Kaufman / ; B Keymeulen / ; M Kin-Willems / ; P Kleynen / ; Y Kockaerts / ; G Krzentowski / ; K Laga / ; E Lagasse / ; G Lamberigts / ; E Lambrecht / ; M C Lebrethon / ; P Lefebvre / ; F Lienart / ; T Lim Tjin / ; C Litvine / ; K Logghe / ; J Louis / ; M Maes / ; W Maes / ; M Marchal / ; P Marien / ; G Massa / ; C Mathieu / ; Z Mathijs / ; D Mattelaer / ; Y Maus / ; K Mekeirele / ; F Merahli / ; J Mockel / ; J Monballyu / ; G Moorkens / ; T Moureau / ; E Muls / ; W Musch / ; P Nachtegaele / ; K Naudts / ; I Neven / ; D Nicolaij / ; F Nobels / ; A Nollet / ; F Paciorkowski / ; N Paquot / ; I Paris / ; C Peeters / ; F Peiffer / ; M C Pelckmans / ; H Penninckx / ; O Peters / ; J C Philips / ; M Pieron / ; D Pipeleers / ; K Platteau / ; L Poelmans / ; M Ponchon / ; A Purnode / ; C Remy / ; B Renneboog / ; C Righes / ; D Rocour-Brumioul / ; M P Roggemans / ; R Rooman / ; R Rottiers / ; J Ruige / ; D Scarniere / ; A Scheen / ; E Schils / ; I Schoemaker / ; L Schrijvers / ; M Schuerman / ; J Schutyser / ; P Selvais / ; N Seret / ; K Spincemaille / ; M P Stassen / ; M Strivay / ; M Struelens / ; P Taelman / ; S Tenoutasse / ; L Terriere / ; J Teuwen / ; G Thenaers / ; G Thiry-Counson / ; J Tits / ; G Tsibuabua / ; G Tsjoen / ; C Tuyttens / ; J Unger / ; K Van Acker / ; E Van Aken / ; S Van Aken / ; P Van Belle / ; P Van Crombrugge / ; A Van Den Bruel / ; J Van Den Saffele / ; B Van der Auwera / ; J Van Doorn / ; E Van Fleteren / ; L Van Gaal / ; L Van Garsse / ; D Van Gijsegem / ; M Van Helvoirt / ; S Van Imschoot / ; E Van Kerchove / ; C Van Parijs / ; I Van Pottelbergh / ; P Van Rooy / ; C Van Winghem / ; J Vanbesien / ; X Vande Mergel / ; H Vandecauter / ; E Vandemeulebroucke / ; M Vandenbroucke / ; E Vandenbussche / ; A Vandergheynst / ; M Vanderijst / ; H Vanderstappen / ; G Vanhaverbeke / ; S Vanneste / ; D Vannimmen / ; J Vanuytsel / ; R Verbiest / ; C Vercammen / ; P Vergauwe / ; A Verhaegen / ; G Verhaert / ; V Verjans / ; R Verniest / ; J Verschuere / ; B Vets / ; G Vieillevoye / ; J Vinckx / ; S Vinken / ; C Warnotte / ; P Watillon / ; E Weber / ; I Weemaes / ; I Weets / ; L Winne / |
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