Hyperglycaemic clamp test for diabetes risk assessment in IA-2-antibody-positive relatives of type 1 diabetic patients |
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Authors: | E Vandemeulebroucke B Keymeulen K Decochez I Weets C De Block F Féry U Van de Velde I Vermeulen P De Pauw C Mathieu D G Pipeleers F K Gorus |
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Institution: | 1. Diabetes Research Center, Brussels Free University-VUB, Laarbeeklaan 103, 1090, Brussels, Belgium 2. Department of Endocrinology, University of Antwerp, Antwerp, Belgium 3. Department of Endocrinology, Université Libre de Bruxelles-ULB, Brussels, Belgium 4. Department of Endocrinology, Catholic University of Leuven, Leuven, Belgium
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Abstract: | 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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