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See detailInsulin Sensitivity Variability during Hypothermia
Sah Pri, Azurahisham; Chase, J. Geoffrey; Pretty, Christopher et al

in Proceedings of the 19th IFAC Conference (2014, August)

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See detailInsulin Sensitivity, Its Variability and Glycemic Outcome: A model-based analysis of the difficulty in achieving tight glycemic control in critical care
Chase, J. Geoffrey; Le Compte, Aaron J.; Preiser, Jean-Charles et al

in 18th World Congress of the International Federation of Automatic Control (IFAC) (2011)

Effective tight glycemic control (TGC) can improve outcomes in intensive care unit (ICU) <br />patients, but is difficult to achieve consistently. Glycemic level and variability, particularly early in a ... [more ▼]

Effective tight glycemic control (TGC) can improve outcomes in intensive care unit (ICU) <br />patients, but is difficult to achieve consistently. Glycemic level and variability, particularly early in a <br />patient’s stay, are a function of variability in insulin sensitivity/resistance resulting from the level and <br />evolution of stress response, and are independently associated with mortality. This study examines the <br />daily evolution of variability of insulin sensitivity in ICU patients using patient data (N = 394 patients, <br />54019 hours) from the SPRINT TGC study. Model-based insulin sensitivity (SI) was identified each hour <br />and hour-to-hour percent changes in SI were assessed for Days 1-3 individually and Day 4 Onward, as <br />well as over all days. Cumulative distribution functions (CDFs), median values, and inter-quartile points <br />(25th and 75th percentiles) are used to assess differences between groups and their evolution over time. <br />Compared to the overall (all days) distributions, ICU patients are more variable on Days 1 and 2 (p < <br />0.0001), and less variable on Days 4 Onward (p < 0.0001). Day 3 is similar to the overall cohort (p = 0.74). <br />Absolute values of SI start lower and rise for Days 1 and 2, compared to the overall cohort (all days), (p < <br />0.0001), are similar on Day 3 (p = .72) and are higher on Days 4 Onward (p < 0.0001). ICU patients have <br />lower insulin sensitivity (greater insulin resistance) and it is more variable on Days 1 and 2, compared to <br />an overall cohort on all days. This is the first such model-based analysis of its kind. Greater variability <br />with lower SI early in a patient’s stay greatly increases the difficulty in achieving and safely maintaining <br />glycemic control, reducing potential positive outcomes. Clinically, the results imply that TGC patients will <br />require greater measurement frequency, reduced reliance on insulin, and more explicit specification of <br />carbohydrate nutrition in Days 1-3 to safely minimise glycemic variability for best outcome. [less ▲]

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

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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See detailInsulin-like growth factor (IGF) family and prostate cancer
Gennigens, Christine ULg; Menetrier-Caux, C.; Droz, J. P.

in Critical Reviews in Oncology/Hematology (2006), 58(2), 124-145

There is abundant in vitro, animal and epidemiologic evidence to suggest that the Insulin-Like Growth Factor (IGF) family is a multicomponent network of molecules which is involved in the regulation of ... [more ▼]

There is abundant in vitro, animal and epidemiologic evidence to suggest that the Insulin-Like Growth Factor (IGF) family is a multicomponent network of molecules which is involved in the regulation of both physiological and pathological growth processes in prostate. The IGF family plays a key role in cellular metabolism, differentiation, proliferation, transformation and apoptosis, during normal development and malignant growth. This family also seem essential in prostate cancer bone metastases, angiogenesis and androgen-independent progression. Therapeutic alternatives in men with progressive prostate cancer after androgen ablation are very limited. More effective therapies are needed for these patients. Pharmacologic interventions targeting the IGF family are being devised. Such strategies include reduction of IGF-I levels (growth hormone-releasing hormone antagonists, somatostatin analogs), reduction of functional IGF-I receptor levels (antisense oligonucleotides, small interfering RNA), inhibition of IGF-IR and its signalling (monoclonal antibodies, small-molecule tyrosine kinase inhibitors) and Insulin-Like Growth Factor Binding Proteins. (c) 2005 Elsevier Ireland Ltd. All rights reserved. [less ▲]

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See detailInsulin-like growth factor 1 (IGF-1) promotes interleukin 7 (IL-7) synthesis and secretion by primary cultures of human thymic epithelial cells
Goffinet, Lindsay ULg; Renard-Charlet, Chantal; Martens, Henri ULg et al

in Scandinavian Journal of Immunology (2011, April), 73

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See detailAn insulin-like growth factor 2-derived self-antigen inducing a regulatory cytokine profile after presentation to peripheral blood mononuclear cells from DQ8(+) type 1 diabetic adolescents - Preliminary design of a thymus-based tolerogenic self-vaccination
Geenen, Vincent ULg; Louis, Céline ULg; Martens, Henri ULg

in Annals of the New York Academy of Sciences (2004), 1037

This work aims to evaluate the potential use of insulin-like growth factor 2 (IGF-2) as the dominant thymic self-antigen precursor of the insulin family in designing a tolerogenic approach to type 1 ... [more ▼]

This work aims to evaluate the potential use of insulin-like growth factor 2 (IGF-2) as the dominant thymic self-antigen precursor of the insulin family in designing a tolerogenic approach to type 1 diabetes (T1D) prevention. This evaluation was primarily based on cytokine profile driven by MHC presentation of insulin and IGF-2-derived antigens to PBMC cultures derived from 16 T1D DQ8(+) adolescents. Insulin B9-23, one dominant P-cell autoantigen, and the homologous sequence B11-25 of IGF-2 display the same affinity and fully compete for binding to DQ8, a MHC-II allele conferring major genetic susceptibility to type 1 diabetes (T1D). However, compared to insulin beta 9-23, presentation of IGF-2 B11-25 elicits a suppressive/regulatory cytokine profile with a higher number of IL-10-secreting cells (P < 0.05), a much higher ratio of IL-10/IFN-gamma (P < 0.01), as well as a lower number of IL-4-secreting cells (P < 0.05). Thus, with regard to T1D prevention, administration of IGF-2-derived self-antigen(s) seems to be an efficient approach that combines both antagonism for binding to a major susceptibility MHC-II allele, as well as downstream promotion of an antigen-driven tolerogenic response. [less ▲]

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See detailInsulin-like growth factor binding proteins (IGFBPs) in camels : revelation by western ligand blotting and partial purification of insulin-like growth factor binding protein-3 (IGFBP3)
Hammadi, Mohamed; Colinet, Frédéric ULg; Khorchani, Touhami et al

in Biotechnologie, Agronomie, Société et Environnement = Biotechnology, Agronomy, Society and Environment [=BASE] (2004), 8(Special issue), 53

It's well known that Insulin-like growth factor binding proteins (IGFBPs) are important in somatotrope axis in mammals. They modulate bioactivity of Insulin-like growth factor-I/II. In this study, we ... [more ▼]

It's well known that Insulin-like growth factor binding proteins (IGFBPs) are important in somatotrope axis in mammals. They modulate bioactivity of Insulin-like growth factor-I/II. In this study, we identified IGFBPs in blood of camel by Western ligand blotting and we investigated a procedure to purify IGFBP-3 from this species. Three distinct bands are observed. By analogy to that known in mammals, they are identified as insulin-like growht factor binding-3 (IGFBP-3:40-46 kDa), insulin-like growth factor binding proteins-2 (IGFBP-2: 32 kDa) and insulin-like growth factor binding proteins-1 (IGFBP-1: 28 kDa). IGFBP-3 precipitates in 40-60% by ammonium sulfate saturation of serum. Acidification of 40-60% fraction at pH 3.0 is necessary to dissociate IGFBP-3 from tertiary complex (IGFBP-3, acid labile subunit and IGF-I/II). IGFBP-3 is partially purified by anionic ions exchange chromatography at pH 8.5. It forms a clear doublet band. [less ▲]

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See detailInsulin-like growth factor I (IGF-I) and IGF-I binding proteins levels in different breeds at various stages of lactation
Renaville, Robert ULg; Shojae, D.; Portetelle, Daniel ULg et al

in Journal of Animal Science (1990), 68(suppl 1), 447

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See detailInsulin-like growth factor-I (IGF-I), IGF-binding proteins synthesis, and thyroid status are affected by dexamethasone esters treatment in finishing calves
Bertozzi, Carlo; Massart, Serge; Prandi, Alberto et al

in Biotechnologie, Agronomie, Société et Environnement = Biotechnology, Agronomy, Society and Environment [=BASE] (1998), 2(special issue), 45

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See detailLes Insulin-like-growth factors : structure, synthèse et fonctions
Gabriel, Annick ULg; Istasse, Louis ULg; Clinquart, Antoine ULg et al

in Annales de Médecine Vétérinaire (1990), 134

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See detailThe Insulin-Sensitive Side of SHIP2
Schurmans, Stéphane ULg

in TheScientificWorldJournal (2001), 1

A substantial and increasing proportion of death and disability in the EU (and elsewhere) is attributable to diseases associated with insulin resistance (i.e., decreased insulin sensitivity). Beside type ... [more ▼]

A substantial and increasing proportion of death and disability in the EU (and elsewhere) is attributable to diseases associated with insulin resistance (i.e., decreased insulin sensitivity). Beside type II diabetes, other diseases like obesity, hypertension, atherosclerosis, hyperlipidaemia, polycystic ovarian syndrome, and acromegaly are indeed associated with insulin resistance [less ▲]

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See detailInsulin-stimulated glucose disposal is not increased in anorexia nervosa.
Castillo, M.; Scheen, André ULg; Lefebvre, Pierre ULg et al

in Journal of Clinical Endocrinology and Metabolism (1985), 60(2), 311-4

Insulin-stimulated glucose disposal was investigated using the euglycemic hyperinsulinemic glucose clamp technique in six women with anorexia nervosa (27.3 +/- 4.9 yr old; weight, 38.8 +/- 6.6 kg) and ... [more ▼]

Insulin-stimulated glucose disposal was investigated using the euglycemic hyperinsulinemic glucose clamp technique in six women with anorexia nervosa (27.3 +/- 4.9 yr old; weight, 38.8 +/- 6.6 kg) and compared to results obtained in six normal women (22.6 +/- 1.2 yr old; weight, 58 +/- 2.5 kg) and seven obese women (26.8 +/- 7.7 yr old; weight, 92.5 +/- 13.8 kg). The glucose clamp was performed for 2 h using the Biostator and a continuous insulin infusion of 100 mU kg-1 h-1. Plasma levels of insulin were determined at 30-min intervals. Plasma levels of glucagon, FFA, glycerol, 3-hydroxy-butyrate, and alanine were measured basally. Blood glucose levels were similar in normal subjects and anorectic patients; they were slightly but significantly higher in the obese patients. The indices of insulin sensitivity measured were the MCR of glucose and the ratio of glucose infused to insulin infused (G/I). They were very similar in anorectic subjects [MCR, 13.5 +/- 2.4 (+/- SEM) ml kg-1 min-1; G/I, 5.2 +/- 0.9 mg/mU) and normal subjects (MCR, 13.5 +/- 1.7 ml kg-1 min-1; G/I, 5.2 +/- 0.4 mg/mU), but were significantly reduced in obese patients (MCR, 5.1 +/- 0.8 ml kg-1 min-1; G/I, 2.6 +/- 0.3 mg/mU; P less than 0.0025). Differences in plasma insulin among the three groups were not statistically significant. Plasma alanine levels were higher in anorectic than in normal or obese subjects, suggesting defective gluconeogenesis. Thus, insulin-stimulated glucose disposal is normal in patients with anorexia nervosa, a finding that contrasts with the previously reported increase in erythrocyte insulin receptors in this disease. [less ▲]

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See detailInsuline detemir (Levemir) dans l'etude predictive: resultats obtenus chez les patients diabetiques de type 1 de la cohorte belge.
Philips, Jean-Christophe ULg; Scheen, André ULg

in Revue Médicale de Liège (2009), 64(3), 124-30

Insulin detemir (Levemir) is a soluble human insulin analogue acylated with a 14-carbon fatty acid, which reversibly binds to albumin, thereby providing a more prolonged metabolic effect with lower ... [more ▼]

Insulin detemir (Levemir) is a soluble human insulin analogue acylated with a 14-carbon fatty acid, which reversibly binds to albumin, thereby providing a more prolonged metabolic effect with lower variability as compared to NPH insulin taken as reference. Thanks to this pharmacokinetic and pharmacodynamic profile, insulin detemir is essentially used within a basal-bolus regimen. We report the results obtained in 232 type 1 diabetic patients recruited in Belgium in the frame of the international observational, open, prospective PREDICTIVE study. In patients initially treated with either NPH insulin or glargine, followed for 26 weeks, the shift to insulin detemir did not change HbA1c levels, but significantly reduced both the mean and the variability of fasting blood glucose levels while diminishing the risk of hypoglycaemic episodes, especially at night. Therefore, insulin detemir was associated with significantly improved quality of life. These changes were obtained with a slight increase in daily insulin doses but without weight gain. [less ▲]

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See detailInsuline glargine et cancer: une tempete dans un verre d'eau?
Scheen, André ULg; Lefebvre, Pierre ULg

in Revue Médicale de Liège (2009), 64(9), 440-5

Insulin glargine is widely used as basal insulin in the treatment of type 1 and type 2 diabetes mellitus. However, this insulin analogue has been recently suspected to be associated with an increased risk ... [more ▼]

Insulin glargine is widely used as basal insulin in the treatment of type 1 and type 2 diabetes mellitus. However, this insulin analogue has been recently suspected to be associated with an increased risk of cancer, especially breast cancer, in patients with type 2 diabetes. The present article aims at briefly presenting the state of the art based upon currently available data. We will first summarize the observations reported in recent publications, then we will present a critical analysis of these in fact non-conclusive findings, and finally we will conclude with some practical recommendations. [less ▲]

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See detailLes insulinosensibilisateurs.
Scheen, André ULg; Paquot, Nicolas ULg

in Revue Médicale de Liège (2005), 60(5-6), 409-13

Insulin resistance has a genetic background and its phenotypic expression is triggered by fat diet, lack of physical activity and obesity. It provokes a stress on B cells, tends to increase blood glucose ... [more ▼]

Insulin resistance has a genetic background and its phenotypic expression is triggered by fat diet, lack of physical activity and obesity. It provokes a stress on B cells, tends to increase blood glucose levels, is intimately associated with the metabolic syndrome and represents a major cardiovascular risk factor. Insulin resistance may be favourably influenced by simple life-style changes. If necessary, drugs may be prescribed, such as metformin, the first choice antidiabetic oral agent in overweight individuals, or thiazolidinediones (glitazones), new insulin sensitizers with promising effects. New molecules are currently developed, especially PPAR alpha/gamma or pan-agonists. Targeting insulin resistance has several objectives: reducing hyperglycaemia in type 2 diabetic patients, protecting B cells in order to prevent type 2 diabetes in at risk individuals and limiting the progressive metabolic deterioration in diabetic patients, finally, and perhaps most importantly, ameliorating the global cardiovascular prognosis. [less ▲]

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See detailL'insulinotherapie dans le diabete de type 2.
Philips, Jean-Christophe ULg; Scheen, André ULg

in Revue Médicale de Liège (2005), 60(5-6), 419-23

As compared to type 1 diabetes, type 2 diabetes usually requires insulin at a late stage, after secondary failure to oral antidiabetic drugs. However, it should be pointed out that insulin therapy should ... [more ▼]

As compared to type 1 diabetes, type 2 diabetes usually requires insulin at a late stage, after secondary failure to oral antidiabetic drugs. However, it should be pointed out that insulin therapy should not be delayed in patients not well controlled on oral agents. Type 2 diabetic patients failing to oral antidiabetic medications need insulin. Nevertheless, insulin therapy in type 2 diabetic patients is less standardized than in those with type 1 diabetes. Several clinical trials tried to investigate what is the most appropriate initial insulin therapy in type 2 diabetic patients, with the main objectives of reaching almost normoglycaemia without increased risk of frequent or severe hypoglycaemic episodes. However, there is no agreement upon optimal mode of initiating insulin. The most important factors leading to adequate metabolic control are a global educational approach together with a intensified follow up, independently of the insulin regimen. [less ▲]

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