Hyperglycaemic clamp test for diabetes risk assessment in IA-2-antibody-positive relatives of type 1 diabetic patients
; ; et al
in Diabetologia (2010), 53
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 ... [more ▼]
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 [less ▲]Detailed reference viewed: 8 (2 ULg)
Anticorps monoclonaux en diabétologie : jusqu’au bout du rêve ?
Philips, Jean-Christophe ; ; et al
in Revue Médicale de Liège (2009), 64(5-6), 3327-333
SUMMARY : Type 1 diabetes is characterized by the autoimmune- mediated destruction of the insulin-producing beta cells of the pancreatic islets of Langerhans. Several cells are potentially implicated in ... [more ▼]
SUMMARY : Type 1 diabetes is characterized by the autoimmune- mediated destruction of the insulin-producing beta cells of the pancreatic islets of Langerhans. Several cells are potentially implicated in the selective destruction of beta cells, including the beta cells themselves, and T-lymphocytes and B- lymphocytes that are working as antigen-presenting cells. Both types of lymphocytes play also a role in the progressive loss of graft function after islet transplantation. Therefore, immunotherapy may represent a great opportunity to prevent, treat or even cure type 1 diabetes, and the input of monoclonal antibodies (mAb) appears crucial in such a strategy. The concept has first been validated in various animal models, especially the classical one of the NOD mouse. During recent years, promising results of a few clinical trials have been published with the administration of anti-CD3 mAbs targeting T lymphocytes at the time of diagnosis of type 1 diabetes. Results showed a more sustained residual insulin secretion during the following months associated with a reduction in insulin needs. Interesting results may also be expected from the use of anti-CD20 mAbs targeting B lymphocytes. Finally, when considering immunosuppressive therapies after beta-cell transplantation, mAbs, especially those blocking interleukin-2, are already used in clinical practice, but new trials are expected with mAbs targeting T or B lymphocytes. Thus, mAbs might be efficacious in a near future in the prevention (when administered early in the natural course of the disease, in high risk patients) and the treatment of type 1 diabetes, and therefore could avoid, or at least minimize, the constraints of intensive subcutaneous insulin therapy. [less ▲]Detailed reference viewed: 163 (3 ULg)
Insulin lispro (Humalog) in the treatment of diabetes mellitus: overview of belgian clinical data from global studies.
; ; et al
in Acta Clinica Belgica (1999), 54(5), 241-5Detailed reference viewed: 58 (8 ULg)