 Vitamine D et diabèteCAVALIER, Etienne  ; Conference (2012, March 22) Detailed reference viewed: 22 (0 ULg) Cardiovascular risk factors and complications associated with impaired renal function and albuminuria in insulin-treated type 2 diabetes; SCHEEN, André ; et alin Diabetologia (2011) Detailed reference viewed: 4 (0 ULg)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)Poor glycaemic control in secondary care insulin treated patients correlates with bad process indicators; ; et al in Diabetologia (2010), 53(s407), 1018 Detailed reference viewed: 8 (0 ULg)Anticorps monoclonaux en diabétologie : jusqu’au bout du rêve ?Philips, Jean-Christophe ; ; et alin 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) Polymorphisms in innate immunity genes predispose to bacteremia and death in the medical intensive care unit; ; et al in Critical Care Medicine (2009), 37(1), 192-2011-3 OBJECTIVE: Critically ill patients are at risk of sepsis, organ failure, and death. Studying the impact of genetic determinants may improve our understanding of the pathophysiology and allow ... [more ▼] OBJECTIVE: Critically ill patients are at risk of sepsis, organ failure, and death. Studying the impact of genetic determinants may improve our understanding of the pathophysiology and allow identification of patients who would benefit from specific treatments. Our aim was to study the influence of single nucleotide polymorphisms in selected genes involved in innate immunity on the development of bacteremia or risk of death in patients admitted to a medical intensive care unit. DESIGN, SETTING, AND PATIENTS: DNA was available from 774 medical intensive care unit patients. We selected 31 single nucleotide polymorphisms in 14 genes involved in host innate immune defense. Serum levels of MASP2 and chemotactic capacity, phagocytosis, and killing capacity of monocytes at admission were quantified. Univariate Kaplan-Meier estimates with log-rank analysis and multivariate logistic regression were performed. Bootstrap resampling technique and ten-fold cross-validation were used to assess replication stability, prognostic importance of the variables, and repeatability of the final regression model. MAIN RESULTS: Patients with at least one NOD2 variant were shown to have a reduced phagocytosis by monocytes (p = 0.03) and a higher risk of bacteremia than wild-type patients (p = 0.02). The NOD2/TLR4 combination was associated with bacteremia using survival analyses (time to bacteremia development, log-rank p < 0.0001), univariate regression (p = 0.0003), and multivariate regression analysis (odds ratio [OR] 4.26, 95% confidence interval [CI] 1.85-9.81; p = 0.0006). Similarly, the same combination was associated with hospital mortality using survival analysis (log-rank p = 0.03), univariate regression (p = 0.02), and multivariate regression analysis (OR 2.27, 95% CI 1.09-4.74; p = 0.03). Also variants in the MASP2 gene were significantly associated with hospital mortality (survival analysis log-rank-p = 0.003; univariate regression p = 0.02; multivariate regression analysis OR 2.35, 95% CI 1.38-3.99; p = 0.002). CONCLUSIONS: Functional polymorphisms in genes involved in innate immunity predispose to severe infections and death, and may become part of a risk model, allowing identification of patients at risk, who could benefit from early introduction of specific preventive or therapeutic interventions. [less ▲] Detailed reference viewed: 10 (2 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), 241-5 Detailed reference viewed: 58 (8 ULg)A promoter element active in run-off transcription controls the expression of two cistrons of nad and rps genes in Nicotiana sylvestris mitochondria; ; et al in Nucleic Acids Research (1996), 24(23), 4798-4804 The expression of two mitochondrial gene clusters (orf87-nad3-nad1/A and orf87-nad3-rps 12) was studied in Nicotiana sylvestris. 5' and 3' termini of transcripts were mapped by primer extension and ... [more ▼] The expression of two mitochondrial gene clusters (orf87-nad3-nad1/A and orf87-nad3-rps 12) was studied in Nicotiana sylvestris. 5' and 3' termini of transcripts were mapped by primer extension and nuclease S1 protection. Processing and transcription initiation sites were differentiated by in vitro phosphorylation and capping experiments. A transcription initiation site, present in both gene clusters, was found 213 nucleotides upstream of orf87. This promoter element matches the consensus motif for dicotyledonous mitochondrial promoters and initiates run-off transcription in a pea mitochondrial purified protein fraction, Processing sites were identified 5' of nad3, nad1/A and rps12 respectively. These results suggest that (i) the expression of the two cistrons is only controlled by one duplicated promoter element, and (ii) multiple processing events are required to produce monocistronic nad3, nad1/A and rps12 transcripts. [less ▲] Detailed reference viewed: 8 (0 ULg) |
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