Article (Scientific journals)
Hyperglycaemic clamp test for diabetes risk assessment in IA-2-antibody-positive relatives of type 1 diabetic patients
Vandemeulebroucke, E.; Keymeulen, B.; Decochez, K. et al.
2010In Diabetologia, 53, p. 36-44
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Keywords :
Autoantibodies/*blood C-Peptide/blood; C-Peptide/blood MH - Diabetes Mellitus/*epidemiology/genetics MH - Diabetes Mellitus, Type 1/genetics/immunology MH - MH - Risk Assessment; Reference Values; Medical History Taking; Insulin/blood; Hyperglycemia; Humans; HLA-DQ Antigens/genetics; Glucose Clamp Technique; diabtes mellitus Type 1/genetics/immunology
Abstract :
[en] 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
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
Vandemeulebroucke, E.
Keymeulen, B.
Decochez, K.
Weets, I.
De Block, C.
Féry, F.
Van de Velde, U.
Vermeulen, I.
De Pauw, P.
Mathieu, C.
Pipeleers, D. G.
Paquot, Nicolas ;  Université de Liège - ULiège > Services généraux (Faculté de médecine) > Relations académiques et scientifiques (Médecine)
Gorus, F. K.
More authors (3 more) Less
Language :
English
Title :
Hyperglycaemic clamp test for diabetes risk assessment in IA-2-antibody-positive relatives of type 1 diabetic patients
Publication date :
January 2010
Journal title :
Diabetologia
ISSN :
0012-186X
eISSN :
1432-0428
Publisher :
Springer Verlag, Berlin, Germany
Volume :
53
Pages :
36-44
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 13 May 2011

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