References of "Diabetes Research & Clinical Practice"
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See detailPossible survivorship bias rather than reverse causality in EMPA-REG OUTCOME.
Scheen, André ULiege

in Diabetes Research & Clinical Practice (2017), (May),

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See detailCardiovascular outcome studies with incretin-based therapies: Comparison between DPP-4 inhibitors and GLP-1 receptor agonists.
Scheen, André ULiege

in Diabetes Research & Clinical Practice (2017), 127

Dipeptidyl peptidase-4 inhibitors (DPP-4is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) represent two distinct classes of incretin-based therapies used for the treatment of type 2 diabetes ... [more ▼]

Dipeptidyl peptidase-4 inhibitors (DPP-4is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) represent two distinct classes of incretin-based therapies used for the treatment of type 2 diabetes. Non-inferiority versus placebo was shown in large prospective cardiovascular outcome trials in patients with high cardiovascular risk: SAVOR-TIMI 53 (saxagliptin), EXAMINE (alogliptin), and TECOS (sitagliptin); ELIXA (lixisenatide), LEADER (liraglutide) and SUSTAIN 6 (semaglutide). The promises raised by meta-analyses of phase 2-3 trials with DPP-4is were non confirmed as no cardiovascular protection could be evidenced. However, LEADER showed a significant reduction in major cardiovascular events, myocardial infarction, cardiovascular and all-cause mortality in patients treated by liraglutide compared to placebo. These positive results contrasted with the non-inferiority results with lixisenatide in ELIXA. They were partially confirmed with semaglutide in SUSTAIN 6 despite the absence of reduction in cardiovascular mortality. Hospitalisation for heart failure was not increased except with saxagliptin in SAVOR-TIMI 53. The reasons for different outcomes between trials remain largely unknown as well as the precise underlying mechanisms explaining the cardiovascular protection by liraglutide. The clinical relevance of results with DPP-4is and GLP-1RAs is discussed. Ongoing trials with linagliptin and several once-weekly GLP-1RAs should provide new insights into remaining fundamental questions. [less ▲]

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See detailEffects of reducing blood pressure on cardiovascular outcomes and mortality in patients with type 2 diabetes: Focus on SGLT2 inhibitors and EMPA-REG OUTCOME.
Scheen, André ULiege

in Diabetes Research & Clinical Practice (2016), 121

Empagliflozin, a sodium-glucose cotransporter type 2 (SGLT2) inhibitor, has shown a remarkable reduction in cardiovascular and all-cause mortality in patients with type 2 diabetes (T2D) and antecedents of ... [more ▼]

Empagliflozin, a sodium-glucose cotransporter type 2 (SGLT2) inhibitor, has shown a remarkable reduction in cardiovascular and all-cause mortality in patients with type 2 diabetes (T2D) and antecedents of cardiovascular disease in the EMPA-REG OUTCOME trial. This effect has been attributed to a hemodynamic rather than a metabolic effect, partly due to the osmotic/diuretic effect of empagliflozin and to the reduction in arterial blood pressure. The present review will: (1) summarize the results of specific studies having tested the blood pressure lowering effects of SGLT2 inhibitors; (2) describe the results of meta-analyses of trials having evaluated the effects on mortality and cardiovascular outcomes of lowering blood pressure in patients with T2D, with a special focus on baseline and target blood pressures; (3) compare the cardiovascular outcome results in EMPA-REG OUTCOME versus other major trials with antihypertensive agents in patients with T2D; and (4) evaluate post-hoc analyses from EMPA-REG OUTCOME, especially subgroups of patients of special interest regarding the blood pressure lowering hypothesis. Although BP reduction associated to empagliflozin therapy may partly contribute to the benefits reported in EMPA-REG OUTCOME, other mechanisms most probably play a greater role in the overall CV protection and reduction in mortality observed in this trial. [less ▲]

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See detailPrecision medicine: The future in diabetes care?
Scheen, André ULiege

in Diabetes Research & Clinical Practice (2016), 117

Personalized medicine aims at better targeting therapeutic intervention to the individual to maximize benefit and minimize harm. Type 2 diabetes (T2D) is a heterogeneous disease from a genetic ... [more ▼]

Personalized medicine aims at better targeting therapeutic intervention to the individual to maximize benefit and minimize harm. Type 2 diabetes (T2D) is a heterogeneous disease from a genetic, pathophysiological and clinical point of view. Thus, the response to any antidiabetic medication may considerably vary between individuals. Numerous glucose-lowering agents, with different mechanisms of action, have been developed, a diversified armamentarium that offers the possibility of a patient-centred therapeutic approach. In the current clinical practice, a personalized approach is only based upon phenotype, taking into account patient and disease individual characteristics. If this approach may help increase both efficacy and safety outcomes, there remains considerable room for improvement. In recent years, many efforts were taken to identify genetic and genotype SNP's (Single Nucleotide Polymorphism's) variants that influence the pharmacokinetics, pharmacodynamics, and ultimately the therapeutic response of oral glucose-lowering drugs. This approach mainly concerns metformin, sulphonylureas, meglitinides and thiazolidinediones, with only scarce data concerning gliptins and gliflozins yet. However, the contribution of pharmacogenetics and pharmacogenomics to personalized therapy still needs to mature greatly before routine clinical implementation is possible. This review discusses both opportunities and challenges of precision medicine and how this new paradigm may lead to a better individualized treatment of T2D. [less ▲]

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See detailCoûts de soins de malades diabétiques hospitalisés en court séjour à Lubumbashi : Etude descriptive transversale
Mundongo Tshamba, Henri; Kaj Malonga, Françoise; Ditend, Grévisse et al

in Diabetes Research & Clinical Practice (2014), 103(Supplement 1), 32

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See detailInflammation as a link between obesity, metabolic syndrome and type 2 diabetes
ESSER, Nathalie ULiege; Legrand, Sylvie ULiege; Piette, Jacques ULiege et al

in Diabetes Research & Clinical Practice (2014)

It is recognized that a chronic low-grade inflammation and an activation of the immune system are involved in the pathogenesis of obesity-related insulin resistance and type 2 diabetes. Systemic ... [more ▼]

It is recognized that a chronic low-grade inflammation and an activation of the immune system are involved in the pathogenesis of obesity-related insulin resistance and type 2 diabetes. Systemic inflammatory markers are risk factors for the development of type 2 diabetes and its macrovascular complications. Adipose tissue, liver, muscle and pancreas are themselves sites of inflammation in presence of obesity. An infiltration of macrophages and other immune cells is observed in these tissues associated with a cell population shift from an anti-inflammatory to a pro-inflammatory profile. These cells are crucial for the production of pro-inflammatory cytokines, which act in an autocrine and paracrine manner to interfere with insulin signaling in peripheral tissues or induce β-cell dysfunction and subsequent insulin deficiency. Particularly, the pro-inflammatory interleukin-1β is implicated in the pathogenesis of type 2 diabetes through the activation of the NLRP3 inflammasome. The objectives of this review are to expose recent data supporting the role of the immune system in the pathogenesis of insulin resistance and type 2 diabetes and to examine various mechanisms underlying this relationship. If type 2 diabetes is an inflammatory disease, anti-inflammarory therapies could have a place in prevention and treatment of type 2 diabetes. [less ▲]

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See detailOutcomes and lessons from the PROactive study.
SCHEEN, André ULiege

in Diabetes Research & Clinical Practice (2012), epub ahead of print

Beyond improvement of glucose control, thiazolidinediones exert pleiotropic effects, which may contribute to some cardiovascular protection. PROactive ("PROspective pioglitAzone Clinical Trial In ... [more ▼]

Beyond improvement of glucose control, thiazolidinediones exert pleiotropic effects, which may contribute to some cardiovascular protection. PROactive ("PROspective pioglitAzone Clinical Trial In macroVascular Events") has provided valuable, although controversial, information on the impact of pioglitazone on cardiovascular outcomes in a high-risk population of patients with type 2 diabetes and established macrovascular disease. Since 2005, there has been much debate on the relative value of the statistically non-significant 10% reduction in the quite challenging primary composite endpoint (combining cardiovascular disease-driven and procedural events in all vascular beds) versus the statistically significant 16% decrease in the more robust and conventional main secondary endpoint (all-cause mortality, myocardial infarction, and stroke) observed with pioglitazone. Revisiting PROactive deserves much interest following the report of inconclusive results on cardiovascular efficacy and safety of rosiglitazone in RECORD, the withdrawal (limitation) of rosiglitazone because of cardiovascular safety concern, the recent publication of a statement positioning pioglitazone in type 2 diabetes and the near availability of cheaper generics of pioglitazone. Although subanalyses may have more limited value from a statistical viewpoint, they nonetheless can provide valuable information on the drug efficacy/safety profile and clinical insights into which patients might benefit most (in terms of cardiovascular outcomes) from pioglitazone therapy. [less ▲]

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See detailThymus and type 1 diabetes: An update
Geenen, Vincent ULiege

in Diabetes Research & Clinical Practice (2012)

Type 1 diabetes (T1D) is a chronic disease resulting from the selective autoimmune destruction of pancreatic islet ß cells. The absence and/or breakdown of immune selftolerance to islet ß cells is now ... [more ▼]

Type 1 diabetes (T1D) is a chronic disease resulting from the selective autoimmune destruction of pancreatic islet ß cells. The absence and/or breakdown of immune selftolerance to islet ß cells is now recognized as the essential cause for the development of the diabetogenic autoimmune response. For a long time, a failure in peripheral tolerogenic mechanisms was regarded as the main source of an inappropriate immune process directed against insulin-secreting ß cells. While defective peripheral self-tolerance still deserves to be further investigated, the demonstration that all members of the insulin gene family are transcribed in thymic epithelial cells (TECs) of different species under the control of the AutoImmune REgulator (AIRE) gene/protein has highlighted the importance of central self-tolerance to insulin-secreting islet b cells. Moreover, there is now evidence that a primary or acquired failure in thymus-dependent central self-tolerance to ß cells plays a primary role in T1D pathogenesis. This novel knowledge is currently translated into the development of innovative tolerogenic/regulatory approaches designed to reprogram the specific immune self-tolerance to islet ß cells. [less ▲]

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See detailInsulin versus insulin plus sulfonylureas in type 2 diabetic patients with secondary failure to sulfonylureas.
Scheen, André ULiege; Lefebvre, Pierre ULiege

in Diabetes Research & Clinical Practice (1989), 6(4), 33-4242-3

According to the modern pathophysiological understanding of type 2 diabetes and the mechanisms of sulfonylurea action, combined insulin-sulfonylurea therapy appears to be an interesting alternative for ... [more ▼]

According to the modern pathophysiological understanding of type 2 diabetes and the mechanisms of sulfonylurea action, combined insulin-sulfonylurea therapy appears to be an interesting alternative for treating diabetic patients with secondary failure to sulfonylureas. From its revival in the early 1980s, combination therapy has been shown to have a positive effect on blood glucose control although initially published clinical studies, generally open and uncontrolled, have been widely criticized. Several recent well-designed studies confirmed these favorable results, with better glucose profiles and/or decreased insulin needs, which were shown to persist after 1 year or more. Most of the studies investigating the mechanism of action indicate that the effect is mainly due to stimulation of the residual insulin secretion with minimal or no effect on insulin sensitivity. The risk of hypoglycemic episodes is rather small when insulin doses are adapted at the beginning of the combined therapy. Effects on lipid metabolism are minimal and controversial. Thus, insulin-sulfonylurea treatment may be a safe and effective solution in type 2 diabetic patients with secondary failure to sulfonylureas, particularly in those with significant residual endogenous insulin secretion. The additional cost of such combined therapy should be weighed against the potential advantages of better metabolic control. [less ▲]

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