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See detailInsulin lispro (Humalog) in the treatment of diabetes mellitus: overview of belgian clinical data from global studies.
Bex, M.; Buysschaert, M.; De Leeuw, I. et al

in Acta Clinica Belgica (1999), 54(5), 241-5

Detailed reference viewed: 64 (8 ULg)
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See detailInsulin oscillations per se do not affect glucose turnover parameters in normal man.
Paolisso, G.; Scheen, André ULg; Verdin, Emeline ULg et al

in Journal of Clinical Endocrinology and Metabolism (1986), 63(2), 520-5

To compare the metabolic effects of pulsatile vs. continuous iv insulin infusion, normal men had two glucose-controlled iv glucose infusions using the Biostator for 260 min, during which endogenous ... [more ▼]

To compare the metabolic effects of pulsatile vs. continuous iv insulin infusion, normal men had two glucose-controlled iv glucose infusions using the Biostator for 260 min, during which endogenous pancreatic hormone secretion was inhibited by a somatostatin infusion and glucagon was replaced by continuous glucagon infusion. The two tests were performed at 1-week intervals, during which human insulin was infused either continuously at a constant rate of 0.2 mU kg-1 min-1 or in a pulsatile manner at a rate of 1.3 mU kg-1 min-1 with a switching on/off length of 2/11 min. Blood glucose levels and glucose infusion rates (GIR) were continuously monitored, and glucose turnover was estimated using a [3H]glucose infusion. In both tests, plasma C-peptide dropped markedly, whereas plasma glucagon levels were about twice basal values. Plasma insulin averaged 7 mU liter-1 during continuous infusion and oscillated between 1.5 and 35 mU liter-1 during pulsatile delivery. During the first 30-60 min of both tests, the glucose appearance rate and endogenous glucose production (EGP) increased, resulting in moderate hyperglycemia, which completely suppressed GIR. During the last 65 min, EGP declined, while the glucose disappearance rate and the glucose MCR increased, so that GIR increased progressively to maintain the blood glucose clamped at about 5 mmol liter-1. During this period, no significant differences were found between the two modes of insulin administration for any of the parameters studied. Thus, continuous and pulsatile insulin iv infusion, resulting in physiological peripheral plasma insulin levels, altered the glucose turnover parameters equally, in particular inhibiting EGP, which was stimulated by glucagon during the first part of the study, and stimulating peripheral glucose uptake at the end of the study period. [less ▲]

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See detailInsulin secretion and action in various populations with type 2 (non-insulin-dependant) diabetes mellitus
Scheen, André ULg; Paolisso, G.; Castillo, M. et al

in Diabetologia (1992), 16 ( suppl 1)(29), 116

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See detailInsulin secretion, clearance and action before and after gastroplasty in severely obese subjects.
Letiexhe, Michel ULg; Scheen, André ULg; Gerard, Pascale ULg et al

in International Journal of Obesity & Related Metabolic Disorders (1994), 18(5), 295-300

This study investigated the effects of a drastic weight reduction on insulin secretion rate (ISR), insulin metabolic clearance rate (MCRI) and insulin sensitivity (SI) in severely obese subjects. A ... [more ▼]

This study investigated the effects of a drastic weight reduction on insulin secretion rate (ISR), insulin metabolic clearance rate (MCRI) and insulin sensitivity (SI) in severely obese subjects. A frequently sampled intravenous glucose tolerance test (FSIVGTT, 0.3 g/kg) was performed before and 8 +/- 1 months after a vertical ring gastroplasty in 12 overnight-fasted obese non-diabetic subjects; the results were compared to those obtained in 12 lean controls matched for age and sex. ISR was derived by deconvolution of plasma C-peptide levels; MCRI was obtained by dividing the area under the curve (AUC180 min) of ISR by the corresponding AUC of plasma insulin levels (IRI); the SI and the glucose effectiveness index (SG) were calculated by Bergman's minimal model. Before gastroplasty, obese subjects showed significantly higher ISR (P < 0.02), lower MCRI (P < 0.001), lower SI (P < 0.001) but similar SG when compared to lean controls. After gastroplasty (reduction of body weight from 104.8 +/- 3.8 to 73.4 +/- 3.6 kg and of BMI from 37.9 +/- 0.8 to 26.5 +/- 0.9 kg/m2; P < 0.001), ISR only decreased from 53,125 +/- 7968 to 42,302 +/- 3716 pmol/180 min (not significant) while AUC-IRI dramatically fell from 53,626 +/- 6378 to 21,111 +/- 2584 pmol.min/l; P < 0.001); consequently, MCRI markedly increased from 526 +/- 96 to 1257 +/- 150 ml/min/m2; P < 0.01). SI significantly rose from 3.12 +/- 0.45 to 7.10 +/- 1.20 x 10(-4) l/mU/min (P < 0.005) while SG remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) [less ▲]

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See detailInsulin secretion, clearance, and action on glucose metabolism in cirrhotic patients.
Letiexhe, Michel ULg; Scheen, André ULg; Gerard, Pascale ULg et al

in Journal of Clinical Endocrinology and Metabolism (1993), 77(5), 1263-8

To study the mechanisms of glucose intolerance and hyperinsulinism in liver cirrhosis, we compared the plasma glucose, insulin, and C-peptide levels during a frequently sampled i.v. glucose tolerance test ... [more ▼]

To study the mechanisms of glucose intolerance and hyperinsulinism in liver cirrhosis, we compared the plasma glucose, insulin, and C-peptide levels during a frequently sampled i.v. glucose tolerance test (0.3 g glucose/kg BW) in nine compensated cirrhotic patients and nine healthy volunteers well matched for age, sex, and body weight. The insulin secretion rate was derived by the deconvolution of plasma C-peptide levels, insulin sensitivity was calculated using Bergman's minimal model method, and insulin clearance was estimated by dividing the 0-180 min area under the curve of insulin secretion rate by that of peripheral plasma insulin levels. The cirrhotic patients were characterized during the frequently sampled i.v. glucose tolerance test by a 60% greater insulin secretion rate (P < 0.05), a markedly reduced insulin sensitivity index (SI; 2.82 +/- 0.75 vs. 5.86 +/- 0.68 x 10(-4) min/mU.L; P < 0.01) and a 40% reduced insulin clearance (725 +/- 169 vs. 1165 +/- 99 mL/min.m-2; P < 0.05). The reduction of insulin clearance was significantly correlated with the amplitude of the portosystemic shunt, measured using an isotopic method (r = 0.75; P < 0.02). In conclusion, cirrhosis is characterized by an important peripheral hyperinsulinism, resulting from both a higher insulin secretion rate and a reduced insulin hepatic clearance; the severe insulin resistance explains the glucose metabolism alterations. [less ▲]

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See detailInsulin secretion, metabolism and sensitivity before and after a protein-sparing modified fast in obese subjects.
Paquot, Nicolas ULg; Scheen, André ULg; juchmes, Jacques et al

in Diabetologia (1990), 33(suppl), 216

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See detailInsulin Sensitivity during Hypothermia in Critically Ill Patients
Sah Pri, Azurahisham; Chase, J. Geoffrey; Le Compte, Aaron J. et al

Poster (2013, September)

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See detailInsulin sensitivity in anorexia nervosa: a mirror image of obesity?
Scheen, André ULg; Castillo, M.; Lefebvre, Pierre ULg

in Diabetes/Metabolism Reviews (1988), 4(7), 681-90

Although, in many respects and from a metabolic point of view, obesity and AN are clearly two opposite pathological conditions, the available data concerning insulin sensitivity in these two syndromes are ... [more ▼]

Although, in many respects and from a metabolic point of view, obesity and AN are clearly two opposite pathological conditions, the available data concerning insulin sensitivity in these two syndromes are not so obviously opposite. Indeed, whereas everybody is convinced that obesity is characterized by an increased insulin resistance, the papers reporting insulin sensitivity parameters in AN contain some apparently contradictory results. The observations of simultaneously low fasting blood glucose and plasma-insulin levels in anorectic patients could suggest increased insulin sensitivity in AN. However, if this is the case, it would be present despite other metabolic and hormonal changes (increased plasma concentrations of free fatty acids, cortisol, and growth hormone) which are known factors of insulin resistance. During an oral glucose-tolerance test, an impaired glucose-tolerance occurring despite sustained insulin response to glucose is usually found in anorectic patients before treatment; these abnormalities are, at least partially, reversed after successful refeeding. From these results, such conclusive, if indirect, evidence exists for relative insulin insensitivity in untreated AN. Similar results were initially reported with the intravenous glucose-tolerance test. Typically, the coefficient of glucose assimilation K was reduced in anorectic patients before treatment and increased after realimentation. This seemed to occur despite a relative increase in insulin response to glucose, which again may be related to insulin resistance in these undernourished subjects. However, more recent data demonstrated that the early insulin response is significantly lower in anorectic patients than in controls and that more than half of these patients have normal glucose-tolerance despite decreased peripheral plasma insulin levels. These latter observations, on the contrary, suggest an increased insulin sensitivity, at least in some patients with AN. Only the recently developed minimal model method allows us to discriminate between changes in insulin secretion and action after intravenous glucose injection and thus to infer accurately the sensitivity of the tissues to insulin. Unfortunately, this technique has not been applied to anorectic patients, until now, to solve the controversy. The simplest way to assess the action in vivo of insulin is to perform an intravenous insulin-tolerance test. However, the initial findings with this test, which showed exaggerated fall in plasma-glucose values and delayed return to basal levels after intravenous injection of insulin in AN, do not necessarily mean increased insulin sensitivity in these self-starved patients.(ABSTRACT TRUNCATED AT 400 WORDS) [less ▲]

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See detailInsulin sensitivity modulates the growth response during the first year of high-dose growth hormone treatment in short prepubertal children born small for gestational age.
Gies, Inge; Thomas, Muriel; Tenoutasse, Sylvie et al

in Hormone research in paediatrics (2012), 78(1), 24-30

AIM: To study the relationship between insulin sensitivity and growth response in short children born small for gestational age (SGA) treated with growth hormone (GH). METHODS: Randomized, open-label, 24 ... [more ▼]

AIM: To study the relationship between insulin sensitivity and growth response in short children born small for gestational age (SGA) treated with growth hormone (GH). METHODS: Randomized, open-label, 24-month intervention study in 40 short prepubertal SGA children [age (mean +/- SD) 5.3 +/- 1.5 years], who either remained untreated (n = 20) or were treated with GH (66 microg/kg/day; n = 20). Changes in fasting glucose, insulin, quantitative insulin sensitivity check index (QUICKI), IGF-1 and leptin after 1 and 2 years were studied. RESULTS: Mean height SDS increased from -3.3 +/- 0.7 to -2.3 +/- 0.7 after 1 year, and to -1.9 +/- 0.7 after 2 years of treatment. QUICKI decreased significantly (p = 0.008) in the first year of GH treatment and stabilized in the second year. Baseline QUICKI was positively associated (r = 0.40; p < 0.05) with the change in height SDS in the first year. CONCLUSION: Higher insulin sensitivity at the start of GH therapy is associated with greater first-year growth response to GH, and could be a promising parameter in selecting prepubertal short SGA children for GH treatment. However, this finding needs to be confirmed in larger studies. [less ▲]

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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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