|Reference : Hyperglycaemic clamp test for diabetes risk assessment in IA-2-antibody-positive relativ...|
|Scientific journals : Article|
|Human health sciences : Endocrinology, metabolism & nutrition|
|Hyperglycaemic clamp test for diabetes risk assessment in IA-2-antibody-positive relatives of type 1 diabetic patients|
|Vandemeulebroucke, E. [ > > ]|
|Keymeulen, B. [ > > ]|
|Decochez, K. [ > > ]|
|Weets, I. [ > > ]|
|De Block, C. [ > > ]|
|Féry, F. [ > > ]|
|Van de Velde, U. [ > > ]|
|Vermeulen [ > > ]|
|De Pauw, P. [ > > ]|
|Mathieu, C. [ > > ]|
|Pipeleers, D. G. [ > > ]|
|Paquot, Nicolas [Université de Liège - ULg > Services généraux (Faculté de médecine) > Relations académiques et scientifiques (Médecine) >]|
|Gorus, F. K. [ > > ]|
|Yes (verified by ORBi)|
|[en] 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|
|[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
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