Deciphering the molecular mechanisms underlying NLRP3 inflammasome activation by saturated fatty acids
Gianfrancesco, Marco ; ; et al
Poster (2015, September)Detailed reference viewed: 14 (3 ULg)
COMPARISON OF DIABETES CONTROL ONE YEAR AFTER GASTRIC BYPASS AND MAGENSTRASSE AND MILL PROCEDURES
SCHLECK, Michael ; KOHNEN, Laurent ; DE FLINES, Jenny et al
Poster (2015, May)
Bariatric surgery has become a main therapy of type 2 diabetes in the obese population. The best surgical procedure to achieve diabetes control remains debated. Gastric bypass would be the preferred ... [more ▼]
Bariatric surgery has become a main therapy of type 2 diabetes in the obese population. The best surgical procedure to achieve diabetes control remains debated. Gastric bypass would be the preferred option according to its incretin stimulating potential. We compared in this study gastric bypass surgery to a pure restrictive procedure in terms of diabetes control at 1 year. [less ▲]Detailed reference viewed: 41 (2 ULg)
Caractéristiques des sujets obèses métaboliquement anormaux (MUO) versus métaboliquement sains (MHO) soumis à la chirurgie bariatrique
BECK, Emmanuel ; DE FLINES, Jenny ; KOHNEN, Laurent et al
Poster (2015, April)Detailed reference viewed: 30 (5 ULg)
Caractéristiques initiales et effets de la dérivation gastrique chez 84 patients obèses diabétiques de type 2
BECK, Emmanuel ; DE FLINES, Jenny ; KOHNEN, Laurent et al
Poster (2015, April)Detailed reference viewed: 53 (5 ULg)
Cholestérol haut, cholestérol bas: quels sont les risques en gériatrie ?
ANCION, Arnaud ; PAQUOT, Nicolas ; et al
Scientific conference (2015, March 19)Detailed reference viewed: 23 (1 ULg)
Actualisation 2015 du traitement de l'hyperglycemie dans le diabete de type 2.
Scheen, Andre ; Paquot, Nicolas
in Revue medicale suisse (2015), 11(483), 15181520-5
The strategy for the management ot type 2 diabetes, summarized by a group of European and American experts, has been updated early 2015. A patient-centered approach is recommended and the first drug ... [more ▼]
The strategy for the management ot type 2 diabetes, summarized by a group of European and American experts, has been updated early 2015. A patient-centered approach is recommended and the first drug choice is metformin combined with lifestyle improvement. After failure of metformin monotherapy, the selection of a second drug should be based on the efficacy, safety and cost of each pharmacological class. When compared to the position statement of 2012, the most important changes are the possible addition of a gliptin to a dual oral therapy or even to insulin, the commercialization of sodium-glucose cotransporters type 2 (SGLT2) inhibitors (gliflozins, to be used in dual or triple therapy, even in combination with insulin) and the possible combination of a glucagon-like peptide-I receptor agonist together with a basal insulin. [less ▲]Detailed reference viewed: 23 (0 ULg)
Inflammatory markers and cardiometabolic diseases.
; Paquot, Nicolas ; Scheen, André
in Acta clinica Belgica (2015), 70(3), 193-9
OBJECTIVES: A growing body of evidence emerges that obesity, metabolic syndrome, type 2 diabetes and cardiovascular disease are intimately related to chronic inflammation. METHODS: A narrative review ... [more ▼]
OBJECTIVES: A growing body of evidence emerges that obesity, metabolic syndrome, type 2 diabetes and cardiovascular disease are intimately related to chronic inflammation. METHODS: A narrative review summarizing the most recent data of the literature describing the pathological implications of inflammation in obese patients with cardiometabolic disorders. RESULTS: Besides high-sensitive C-reactive protein, various circulating or in situ inflammatory markers have been identified, presumably reflecting the presence of inflammation in various key-organs (visceral adipose tissue, skeletal muscle, pancreatic islets, liver, intestine, arterial wall). Available data support the concept that targeting inflammation, not only reduces systemic inflammatory markers, but also improves insulin sensitivity and ameliorates glucose control in insulin-resistant patients, thus potentially reducing the risk of cardiovascular complications. CONCLUSION: These observations confirm the role of inflammation in cardiometabolic diseases and support the development of pharmacological strategies that aim at reducing inflammation, especially in patients with type 2 diabetes. [less ▲]Detailed reference viewed: 13 (0 ULg)
De la médecine factuelle à la médecine personnalisée : l’exemple du diabète de type 2
in Revue Médicale de Liège (2015), 70(5-6), 299-305
Type 2 diabetes represents a major medical and public health problem due to its huge heterogeneity, the alarming rise of its incidence worldwide and bits associated vascular complications, which impair ... [more ▼]
Type 2 diabetes represents a major medical and public health problem due to its huge heterogeneity, the alarming rise of its incidence worldwide and bits associated vascular complications, which impair quality of life and reduce life expectancy. At the present time, a patient-centered approach is recommended for the management of type 2 diabetes patients. However, these recommendations are not easy to implement because we only have little objective evidence to establish individualized strategies. Following the recent introduction of new drug classes, a large number of combinations is offered to clincicians, but we do not have high quality interventional studies comparing these different therapeutic possibilities. Moreover, the response to pharmacological treatment can vary greatly from one subject to the other Pharmacogenetics might be a useful tool to better characterize the patient. However, despite some progress, the evidence we have now are very preliminary and should not allow to significantly improve the individual management of type 2 diabetes in the near future. [less ▲]Detailed reference viewed: 52 (2 ULg)
Inhibiting or Antagonizing Glucagon: A Progress in Diabetes Care ?
LEFEBVRE, Pierre ; Paquot, Nicolas ; Scheen, André
in Diabetes, obesity & metabolism (2015)
Absolute or relative hyperglucagonemia has been recognized for years in all experimental or clinical forms of diabetes. It has been suggested that excess secretion of glucagon by the islet alpha-cells is ... [more ▼]
Absolute or relative hyperglucagonemia has been recognized for years in all experimental or clinical forms of diabetes. It has been suggested that excess secretion of glucagon by the islet alpha-cells is a direct consequence of intra-islet insulin secretory defects. Recent studies have demonstrated that knock-out of the glucagon receptor or administration of a monoclonal specific glucagon receptor antibody make insulin deficient type 1 diabetic rodents thrive without insulin. These observations suggest that glucagon plays an essential role in the pathophysiology of diabetes and that targeting the alpha-cell and glucagon are innovative approaches in the management of diabetes. Despite active research and identification of promising compounds, no one selective glucagon antagonist is presently used in the treatment of diabetes. Interestingly, besides insulin, several drugs used today in the management of diabetes appear to exert their effects in part by inhibiting glucagon secretion (GLP-1 receptor agonists, DPP-4 inhibitors, alpha glucosidase inhibitors and, maybe, sulfonylureas) or glucagon action (metformin). The potential risks associated with total glucagon suppression include alpha-cell hyperplasia, increased mass of the pancreas, increased susceptibility to hepatosteatosis and hepatocellular injury and increased risk of hypoglycaemia and should be considered in the search and development of new compounds reducing glucagon receptor signalling. In conclusion, more than 40 years after its initial description, the hyperglucagonemia of diabetes can no longer be ignored or minimized and its correction represents an attractive way for improving diabetes management. [less ▲]Detailed reference viewed: 23 (2 ULg)
Obesity: A new paradigm for treating obesity and diabetes mellitus.
Scheen, André ; Paquot, Nicolas
in Nature reviews. Endocrinology (2015), 11(4), 196-198Detailed reference viewed: 26 (2 ULg)
Antidiabetic agents: Potential anti-inflammatory activity beyond glucose control.
Scheen, André ; ; Paquot, Nicolas
in Diabetes & metabolism (2015)
A growing body of evidence is emerging to show that abdominal obesity, the metabolic syndrome, type 2 diabetes, cardiovascular disease and microvascular diabetic complications are intimately related to ... [more ▼]
A growing body of evidence is emerging to show that abdominal obesity, the metabolic syndrome, type 2 diabetes, cardiovascular disease and microvascular diabetic complications are intimately related to chronic inflammation. These observations pave the way to the development of new pharmacological strategies that aim to reduce silent inflammation. However, besides specific anti-inflammatory agents, glucose-lowering medications may also exert anti-inflammatory effects that could contribute to improved outcomes in diabetic patients. Most studies have used metformin, an AMP-activated protein kinase (AMPK) activator, and thiazolidinediones (TZDs), which act as peroxisome proliferator-activated receptor-gamma (PPARgamma) agonists. Both pharmacological classes (considered insulin-sparing agents or insulin sensitizers) appear to have greater anti-inflammatory activity than insulin-secreting agents such as sulphonylureas or glinides. In particular, TZDs have shown the widest range of evidence of lowered tissue (visceral fat and liver) and serum inflammation. In contrast, despite reducing postprandial hyperglycaemia, the effect of alpha-glucosidase inhibitors on inflammatory markers appears rather modest, whereas dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) and glucagon-like peptide-1 (GLP-1) receptor agonists appear more promising in this respect. These incretin-based therapies exert pleiotropic effects, including reports of anti-inflammatory activity. No human data are available so far regarding sodium-glucose cotransporter type 2 (SGLT2) inhibitors. Although they may have indirect effects due to reduced glucotoxicity, their specific mode of action in the kidneys does not suggest systemic anti-inflammatory activity. Also, in spite of the complex relationship between insulin and atherosclerosis, exogenous insulin may also exert anti-inflammatory effects. Nevertheless, for all these glucose-lowering agents, it is essential to distinguish between anti-inflammatory effects resulting from better glucose control and potential anti-inflammatory effects related to intrinsic actions of the pharmacological class. Finally, it would also be of major clinical interest to define what role the anti-inflammatory effects of these glucose-lowering agents may play in the prevention of macrovascular and microvascular diabetic complications. [less ▲]Detailed reference viewed: 26 (3 ULg)
Anti-inflammatory agents to treat or prevent type 2 diabetes, metabolic syndrome and cardiovascular disease.
Esser, Nathalie ; Paquot, Nicolas ; Scheen, André
in Expert opinion on investigational drugs (2015), 24(3), 283-307
Introduction: There is a growing body of evidence to suggest that chronic silent inflammation is a key feature in abdominal obesity, metabolic syndrome, type 2 diabetes (T2DM) and cardiovascular disease ... [more ▼]
Introduction: There is a growing body of evidence to suggest that chronic silent inflammation is a key feature in abdominal obesity, metabolic syndrome, type 2 diabetes (T2DM) and cardiovascular disease (CVD). These observations suggest that pharmacological strategies, which reduce inflammation, may be therapeutically useful in treating obesity, type 2 diabetes and associated CVD. Area covered: The article covers novel strategies, using either small molecules or monoclonal antibodies. These strategies include: approaches targeting IKK-b-NF-kB (salicylates, salsalate), TNF-alpha (etanercept, infliximab, adalimumab), IL-1beta (anakinra, canakinumab) and IL-6 (tocilizumab), AMP-activated protein kinase activators, sirtuin-1 activators, mammalian target of rapamycin inhibitors and C-C motif chemokine receptor 2 antagonists. Expert opinion: The available data supports the concept that targeting inflammation improves insulin sensitivity and beta-cell function; it also ameliorates glucose control in insulin-resistant patients with inflammatory rheumatoid diseases as well in patients with metabolic syndrome or T2DM. Although promising, the observed metabolic effects remain rather modest in most clinical trials. The potential use of combined anti-inflammatory agents targeting both insulin resistance and insulin secretion appears appealing but remains unexplored. Large-scale prospective clinical trials are underway to investigate the safety and efficacy of different anti-inflammatory drugs. Further evidence is needed to support the concept that targeting inflammation pathways may represent a valuable option to tackle the cardiometabolic complications of obesity. [less ▲]Detailed reference viewed: 37 (6 ULg)
Les inhibiteurs de la PSCK9: une innovation majeure dans le traitement des dyslipidémies ?
in ABD- le supplément du médecin (2014), 57(6), 6-7Detailed reference viewed: 28 (3 ULg)
LAPAROSCOPIC MAGENSTRASSE AND MILL GASTROPLASTY. FIRST RESULTS OF A PROPECTIVE STUDY
DE ROOVER, Arnaud ; KOHNEN, Laurent ; DE FLINES, Jenny et al
in Obesity Surgery (2014), 25
Abstract Background TheMagenstrasse and Mill (M&M) procedure is a vertical gastroplasty creating a tubular pouch extending from the cardia to the antrum. This “incomplete sleeve” avoids gastric resection ... [more ▼]
Abstract Background TheMagenstrasse and Mill (M&M) procedure is a vertical gastroplasty creating a tubular pouch extending from the cardia to the antrum. This “incomplete sleeve” avoids gastric resection or band placement. In this paper, we report our experience of the laparoscopic approach of the technique in a selected obese population excluding prominent grazer and/or sweet eaters. Material and Methods One hundred patients (39 males, 61 females) underwent the procedure in a prospective trial.Mean age was 40 years (range 18–68). Mean preoperative BMI was 43.2 kg/m2 (range 35–62). Results The procedure was performed by laparoscopy starting with the creation of a circular opening at the junction of antrum and corpus followed by a vertical stapling to the angle of Hiss. Mean duration of the procedure was 67 (range 40– 122) min. No intraoperative complication occurred. Mean hospital stay (SD) was 2.5 (0.9) days. The single postoperative complication consisted in a mild stenosis that responded to endoscopic dilatation. After a mean follow-up of 15 months (range 9–24), mean percentage of excess body weight loss (SD) was 48(14), 59(18) and 68(24)%, respectively at 3, 6, and 12 months. Quality of life appeared satisfactory with a low incidence of gastroesophageal reflux. The procedure was associated with improvement or resolution of diabetes, arterial hypertension, and dyslipemia at 1 year. Conclusions Our experience demonstrated that the M&M procedure could be performed safely laparoscopically. The satisfactory results on weight loss, obesity-associated mordities, and quality of life will need to be confirmed on longer follow-up. [less ▲]Detailed reference viewed: 25 (3 ULg)
Free fatty acids as modulators of the NLRP3 inflammasome in obesity / type 2 diabetes
Legrand-Poels, Sylvie ; Esser, Nathalie ; L'Homme, Laurent et al
in Biochemical Pharmacology (2014)Detailed reference viewed: 50 (10 ULg)
Comment gérer la nutrition artificielle chez un patient diabétique ?
PAQUOT, Nicolas ; DE FLINES, Jenny ; PREISER, Jean-Charles
in Nutrition Clinique et Metabolisme (2014)
Hyperglycaemia in patients receiving enteral or parenteral nutrition is a major problem due to its high prevalence and possible consequences interms of morbidity and mortality. However, the management of ... [more ▼]
Hyperglycaemia in patients receiving enteral or parenteral nutrition is a major problem due to its high prevalence and possible consequences interms of morbidity and mortality. However, the management of diabetes/stress hyperglycaemia during artificial nutrition remains largely unknown,especially in non-critically ill patients. The indications and access routes for artificial nutrition are not different in patients with diabetes/stressdiabetes than in non-diabetics. We do not recommend using enteral formulas designed for patients with diabetes. The glycaemic objective mustbe individualized. We recommend a preprandial blood glucose levels between 100 and 140 mg/dL (5.5 and 7.8 mmol/L) and postprandial levelsbetween 140 and 180 mg/dL (7.8 and 10 mmol/L). A frequent monitoring of capillary glycaemias is mandatory. The best drug treatment for treatinghyperglycaemia/diabetes is insulin and we recommend to adapt the theoretical insulin action to the nutrition infusion regimen. The managementof these patients needs the help of a multidisciplinary experimented staff. [less ▲]Detailed reference viewed: 38 (10 ULg)
Le diabete du sujet age: du defi epidemiologique a une approche personnalisee.
Scheen, André ; Paquot, Nicolas ;
in Revue medicale de Liege (2014), 69(5-6), 323-8
Diabetes mellitus is a common chronic disease in the elderly, being either a known disease with a long history (type 1 or even more often type 2 diabetes) and then frequently associated with various ... [more ▼]
Diabetes mellitus is a common chronic disease in the elderly, being either a known disease with a long history (type 1 or even more often type 2 diabetes) and then frequently associated with various diabetic complications, or a recently diagnosed diabetes that may, however, have been ignored for a rather long time. In this latter case, diabetes may present as the occurrence or aggravation of one or several geriatric syndromes that overall result in a loss of autonomy. The global geriatric assessment, the estimation of life expectancy and the justification of glucose-lowering treatments should be performed at regular intervals in elderly diabetic people as they determine the right choice of glucose target levels and the best selection of glucose-lowering agents. Medications that can induce hypoglycaemia should ideally be avoided, especially in the frailty older population. The benefit-risk ratio of the proposed therapies should be analyzed first, and then regularly reassessed because of a potentially rapidly progressing condition. The recommended approach is a tailored management of diabetes that should integrate the clinical, functional and psycho-social aspects of elderly individuals. [less ▲]Detailed reference viewed: 79 (12 ULg)
Inflammasome NLRP3 et graisse viscerale.
; Legrand-Poels, Sylvie ; Piette, Jacques et al
in Revue medicale de Liege (2014), 69 Spec No
It is recognized that abdominal obesity is accompanied by a chronic low-grade inflammation that is involved in the pathogenesis of insulin resistance and type 2 diabetes. Metabolic syndrome and type 2 ... [more ▼]
It is recognized that abdominal obesity is accompanied by a chronic low-grade inflammation that is involved in the pathogenesis of insulin resistance and type 2 diabetes. Metabolic syndrome and type 2 diabetes are associated with an abnormal production of pro-inflammatory cytokines, an increased level of acute-phase proteins and an activation of inflammatory signalling pathways. These pro-inflammatory cytokines, mainly produced by adipose tissue macrophages, are involved in development of obesity-associated insulin resistance and in the progression from obesity to type 2 diabetes. Particularly, the interleukin-1 beta may play a key role through the activation of the NLRP3 inflammasome. Adipose tissue topography, more than the total amount of fat, may play an important pathogenic role. Indeed, the presence of metabolic abnormalities in obesity is associated with a deleterious immunological and inflammatory profile of visceral adipose tissue and with an increased activation of the NLRP3 inflammasome in macrophages infiltrating visceral adipose tissue. Targeting inflammation, especially NLRP3 inflammasome, may offer potential novel therapeutic perspectives in the prevention and treatment of type 2 diabetes. [less ▲]Detailed reference viewed: 30 (4 ULg)
Metabolic effects of SGLT-2 inhibitors beyond increased glucosuria: A review of the clinical evidence.
Scheen, André ; Paquot, Nicolas
in Diabetes & metabolism (2014), 40(6 Suppl 1), 4-11
Sodium-glucose cotransporter type 2 (SGLT-2) inhibitors (canagliflozin, dapagliflozin, empagliflozin) are new glucose-lowering agents that exert their therapeutic activity independently of insulin by ... [more ▼]
Sodium-glucose cotransporter type 2 (SGLT-2) inhibitors (canagliflozin, dapagliflozin, empagliflozin) are new glucose-lowering agents that exert their therapeutic activity independently of insulin by facilitating glucose excretion through the kidneys. However, this simple renal mechanism that results in sustained glucose urinary loss leads to more complex indirect metabolic effects. First, by reduction of chronic hyperglycaemia and attenuation of glucose toxicity, SGLT-2 inhibitors can improve both insulin secretion by beta cells and peripheraltissue insulin sensitivity. In the case of canagliflozin, because of low-potency SGLT1 inhibition, a non-renal (intestinal) effect may also be considered, which may contribute to better control of postprandial hyperglycaemia, although this contribution remains to be better analyzed in humans. Second, chronic glucose loss most probably leads to compensatory mechanisms. One of them, although not well evidenced in humans, might involve an increase in energy intake, an effect that may limit weight loss in the long run. Another could be an increase in endogenous glucose production, most probably driven by increased glucagon secretion, which may somewhat attenuate the glucoselowering effect. Nevertheless, despite these compensatory mechanisms and most probably because of the positive effects of the reduction in glucotoxicity, SGLT-2 inhibitors exert clinically relevant glucose-lowering activity while promoting weight loss, a unique dual effect among oral antidiabetic agents. Furthermore, the combination of SGLT-2 inhibitors with other drugs that either have anorectic effects (such as incretin-based therapies) or reduce hepatic glucose output (like metformin) and, thus, may dampen these two compensatory mechanisms appears appealing for the management of type 2 diabetes mellitus. [less ▲]Detailed reference viewed: 19 (3 ULg)