Hepatic insulin resistance in obese non-diabetic subjects and in type 2 diabetic patients.

in Obesity Research (2002), 10(3), 129-34

OBJECTIVE: Obese non-diabetic patients are characterized by an extra-hepatic insulin resistance. Whether obese patients also have decreased hepatic insulin sensitivity remains controversial. RESEARCH ... [more ▼]

OBJECTIVE: Obese non-diabetic patients are characterized by an extra-hepatic insulin resistance. Whether obese patients also have decreased hepatic insulin sensitivity remains controversial. RESEARCH METHODS AND PROCEDURES: To estimate their hepatic insulin sensitivity, we measured the rate of exogenous insulin infusion required to maintain mildly elevated glycemia in obese patients with type 2 diabetes, obese non-diabetic patients, and lean control subjects during constant infusions of somatostatin and physiological low-glucagon replacement infusions. To account for differences in insulin concentrations among the three groups of subjects, an additional protocol was also performed in healthy lean subjects with higher insulin infusion rates and exogenous dextrose infusion. RESULTS: The insulin infusion rate required to maintain glycemia at 8.5 mM was increased 4-fold in obese patients with type 2 diabetes and 1.5-fold in obese non-diabetic patients. The net endogenous glucose production (measured with 6,6-(2)H(2)-glucose) and total glucose output (measured with 2-(2)H(1)-glucose) were approximately 30% lower in the patients than in the lean subjects. Net endogenous glucose production and total glucose output were both markedly increased in both groups of obese patients compared with lean control subjects during hyperinsulinemia. DISCUSSION: Our data indicate that both obese non-diabetic and obese type 2 diabetic patients have a blunted suppressive action of insulin on glucose production, indicating hepatic and renal insulin resistance. [less ▲]

Comment j'explore ... Le risque d'un patient d'evoluer vers un diabete de type 2.

in Revue Médicale de Liège (2002), 57(2), 113-5

Both the prevalence and the incidence of type 2 diabetes are increasing rapidly. Effective prevention measures, including lifestyle or drug prescription, have been recently reported. It is thus important ... [more ▼]

Both the prevalence and the incidence of type 2 diabetes are increasing rapidly. Effective prevention measures, including lifestyle or drug prescription, have been recently reported. It is thus important to detect at risk individuals in order to provide appropriate diet and exercise recommendations or even pharmacological treatment. We summarize the most useful indices based on anamnesis, clinical examination and biological assays that can help to detect subjects at high risk of progression towards type 2 diabetes. [less ▲]

L'hyperglycemie post-prandiale. II. Approches therapeutiques medicamenteuses.

in Revue Médicale de Liège (2002), 57(4), 196-201

Besides dietary approaches, various pharmacological means have been recently developed in order to better control postprandial hyperglycaemia. This objective may be obtained: 1) by slowing down the ... [more ▼]

Besides dietary approaches, various pharmacological means have been recently developed in order to better control postprandial hyperglycaemia. This objective may be obtained: 1) by slowing down the intestinal absorption of carbohydrates; 2) by insuring a better insulin priming soon after the meal; and 3) by inhibiting post-prandial glucagon secretion or action. Some hormones (amylin, glucagon-like peptide-1) can slow gastric emptying while alpha-glucosidase inhibitors (acarbose, miglitol) retard intestinal digestion and resorption of complex carbohydrates. A more physiological post-meal profile of insulin may be obtained in type 2 diabetes by using new insulin secretagogues of the glinide family (repaglinide, nateglinide) with an earlier and shorter insulinotropic action or, mainly in type 1 diabetes but also in type 2 diabetes, by using short-acting insulin analogues (lispro. Asp B28) or inhated insulin the action of which is faster than that of subcutaneous insulin. Post-prandial glucagon secretion can be inhibited by amylin. GLP-1 or insulin while other glucagon antagonists are currently in development. [less ▲]

Les régimes d’épargne protéique dans le traitement de l’obésité

in Nutrition Clinique et Metabolisme (2001), 15

Effets benefiques de l'activite physique sur les facteurs de risque cardio-vasculaire.

in Revue Médicale de Liège (2001), 56(4), 239-43

Numerous observational (epidemiological surveys) or interventional (controlled trials) studies demonstrated that regular physical activity increases insulin sensitivity in normal subjects and decreases ... [more ▼]

Numerous observational (epidemiological surveys) or interventional (controlled trials) studies demonstrated that regular physical activity increases insulin sensitivity in normal subjects and decreases insulin resistance in patients with obesity and/or type 2 diabetes. These favourable effects are at least partially linked to a reduction in abdominal fat mass. This results in a significant improvement of lipid profile, with a decrease in the concentrations of total cholesterol, LDL cholesterol and triglycerides, associated with an increase of HDL cholesterol level. Such favourable metabolic effects related to regular physical activity probably explain the better cardiovascular prognosis observed in regularly exercising subjects as compared to sedentary individuals. These observations should motivate any practitioner to promote endurance physical exercise in every subject, especially in individuals at high cardiovascular risk. [less ▲]

Effects of glucocorticoids on hepatic sensitivity to insulin and glucagon in man.

in Clinical Nutrition (2000), 19(1), 29-34

AIMS: This study was undertaken to determine the effects of a short-term dexamethasone treatment on hepatic sensitivities to insulin and glucagon. METHODS: Eleven healthy subjects were studied during one ... [more ▼]

AIMS: This study was undertaken to determine the effects of a short-term dexamethasone treatment on hepatic sensitivities to insulin and glucagon. METHODS: Eleven healthy subjects were studied during one or several of four protocols. In all protocols, somatostatin was infused continuously to inhibit pancreatic hormone secretion. In protocol 1, basal insulin was infused over 300 min while glucagon was infused at a rate of 0.5 mg/kg(-1)/min(-1)during 180 min, then at a rate of 1.5 ng/kg(-1)/min(-1)during 150 min. In protocol 2, the same experiment was performed after a 2 day treatment with 8 mg/day dexamethasone. In protocol 3, the two-step glucagon infusion was performed during insulin infusion at a rate aimed to reproduce the hyperinsulinemia observed during protocol 2. In protocol 4, continuous basal insulin and low glucagon (0.5 mg/kg(-1)/min(-1)) were infused over 330 min. RESULTS: In protocol 1, plasma glucose rose transiently by 2.0 +/- 0.3 mmol/l when the glucagon rate was increased and glucose production increased by 1.4 +/- 0.5 micromol/kg(-1)/min(-1). In protocol 2, the insulin infusion rate (1.85 +/- 0.36 nmol/kg(-1)/min(-1)) required to maintain glycemia was 3.3-fold higher than during protocol 1. Glucagon-induced stimulation of glycemia (by 1.47 +/- 0.5 mmol/l) and endogenous glucose production (by 0.8 +/- 0.3 micromol/kg(-1)/min(-1)) were blunted, but not abolished. In protocol 3, endogenous glucose production was suppressed by 75% by hyperinsulinemia and was not stimulated when the glucagon infusion rate was increased. In protocol 4, endogenous glucose production did not change significantly with time. CONCLUSION: These results indicate that high dose glucocorticoids induce a marked hepatic insulin resistance. Stimulation of glucose production by hyperglucagonemia was maintained in spite of hyperinsulinemia which can be attributed to either hepatic insulin resistance and/or increased hepatic glucagon sensitivity. [less ▲]

Evaluation de la synthèse de glycogène par biopsie chimique du foie chez des sujets obèses non diabétiques et des sujets de poids normaux

in Diabète & Métabolisme (2000), 26(suppl 1), 43

No increased insulin sensitivity after a single intravenous administration of a recombinant human tumor necrosis factor receptor: Fc fusion protein in obese insulin-resistant patients.

in Journal of Clinical Endocrinology and Metabolism (2000), 85(3), 1316-9

Inhibition of tumor necrosis factor (TNF)-alpha results in a marked increase in insulin sensitivity in obese rodents. We investigated the influence of a TNF antagonist [Ro 45-2081, a recombinant fusion ... [more ▼]

Inhibition of tumor necrosis factor (TNF)-alpha results in a marked increase in insulin sensitivity in obese rodents. We investigated the influence of a TNF antagonist [Ro 45-2081, a recombinant fusion protein that consists of the soluble TNF-receptor (p55) linked to the Fc portion of human IgG1] on insulin sensitivity of patients with android obesity. Seven patients (five women and two men; mean +/- SD age, 41 +/- 4 yr; body mass index, 36.1 +/- 4.7 kg/m2; waist to hip ratio, 0.99 +/- 0.11) were studied (three patients with normal glucose tolerance and four patients with impaired glucose tolerance or mild diabetes; all were hyperinsulinemic). Each patient underwent two consecutive euglycemic hyperinsulinemic glucose-clamp tests: 48 h after injection of placebo and 48 h after a single i.v. injection of 50 mg Ro 45-2081. In both tests, steady-state plasma glucose and insulin levels were similar. Insulin-mediated glucose disposal (2.23 +/- 0.74 vs. 2.38 +/- 0.99 mg/kg(-1) x min(-1)) and glucose metabolic clearance rate (2.28 +/- 0.85 vs. 2.48 +/- 1.03 mL/kg(-1) x min(-1)) were similar after placebo and after the drug. Indirect calorimetry showed no difference in substrate oxidation rates between the two experimental conditions. In conclusion, under the conditions of this study, no improvement in insulin sensitivity was observed in obese insulin-resistant patients following a single i.v. administration of a recombinant TNF receptor: Fc fusion protein. [less ▲]

Faut-il instaurer un traitement en prévention primaire chez la femme hypercholestérolémique?

in Revue Médicale de Liège (1999), 54(4), 240-3

Limited data are available in women from randomized trials of lipid-lowering therapy for primary prevention of coronary heart disease (CHD). In women with isolate hypercholesterolemia but no clinical ... [more ▼]

Limited data are available in women from randomized trials of lipid-lowering therapy for primary prevention of coronary heart disease (CHD). In women with isolate hypercholesterolemia but no clinical symptoms of CHD and no other risk factors, there is no evidence that lipid-lowering therapy is of benefit. In postmenopausal women with hypercholesterolemia and other risk factors (particularly diabetes and family history of CHD), lipid-lowering therapy may be of benefit. In those women, hormone replacement therapy may be proposed in the treatment of postmenopausal hypercholesterolemia. [less ▲]

Non oxidative fructose disposal is not inhibited by lipids in humans.

in Diabètes & Métabolism (1999), 25(3), 233-40

Elevated free fatty acid concentrations are known to decrease insulin-mediated glucose uptake, glucose oxidation and glycogen synthesis. In order to determine whether free fatty acids inhibit glycogen ... [more ▼]

Elevated free fatty acid concentrations are known to decrease insulin-mediated glucose uptake, glucose oxidation and glycogen synthesis. In order to determine whether free fatty acids inhibit glycogen synthesis at the level of liver cells, the effects of an infusion of lipids on carbohydrate metabolism were investigated in healthy subjects during a two-step (16.7 and 33.4 mumol/(kg.min) 13C-fructose infusion. Fructose infusion dose-dependently stimulated fructose (measured from 13CO2 production) and net carbohydrate oxidation (measured with indirect calorimetry). It also stimulated systemic 13C glucose appearance, indicating a dose-dependent stimulation of gluconeogenesis. Net glucose output (measured with 6,6 2H glucose) was however not altered. Lipid infusion significantly reduced fructose oxidation (measured from 13CO2 production) at both rates of fructose infusion, but did not alter plasma fructose or lactate concentrations, nor plasma 13C glucose appearance or net glucose production. Non oxidative fructose disposal was increased by 31% (p < 0.05) at the lowest, and by 18% (p < 0.01) at the highest infusion rate. Since nonoxidative fructose disposal corresponds mainly to liver glycogen deposition, these results suggest that lipid infusion increased hepatic glycogen synthesis, and hence that hepatic glycogen synthase is not inhibited by fatty acids. [less ▲]