European Journal of Cardiovascular Prevention and Rehabilitation
In Belgium, regulations restrict the reimbursement of statins to patients with total serum choles... more In Belgium, regulations restrict the reimbursement of statins to patients with total serum cholesterol above 250 mg/dl (6.41 mmol/l) after a three-month lipid-lowering diet. We investigated the possible impact of these regulations on characteristics of Belgian patients receiving a lipid-lowering drug. From 1998 to 2000, standard questionnaires on coronary risk factors and treatments with lipid-lowering drugs were completed by 301 GPs sampled at random in the 11 Belgian Provinces. Questionnaires had to be completed for 18 consecutive patients 35 years old or more attending GPs' practices, irrespective of the underlying motive for attendance. Of the 5511 patients included in the study, 1519 (28%) had established coronary disease or diabetes mellitus, or > or = 2 non-cholesterol coronary risk factors. Most (70%) of these patients were not treated with a lipid-lowering drug. Only 22% of patients with established coronary disease, 10% of patients with diabetes mellitus and 9% of p...
We examined whether a very-low-energy all- protein diet (VLED) would produce detectable changes i... more We examined whether a very-low-energy all- protein diet (VLED) would produce detectable changes in iron as well as in other trace elements. Twenty-five obese patients con- sumed for 2 wk a VLED containing 70 g protein after a l-wk period during which total daily energy intake was progressively reduced to 1.26 MJ. Serum iron fell sharply by "50% (P <
Refers to Finan, B. et al. A rationally designed monomeric peptide triagonist corrects obesity an... more Refers to Finan, B. et al. A rationally designed monomeric peptide triagonist corrects obesity and diabetes in rodents. Nat. Med. 21, 27-36 (2015) An innovative strategy that uses a well-balanced monomeric peptide triagonist to target three metabolically related hormone receptors has been developed. This strategy seems to be the most effective pharmacological approach to reverse obesity and its metabolic comorbidities in rodents and could open new ways to tackle the dual burden of obesity and diabetes mellitus in humans.
There is a growing body of evidence to suggest that chronic silent inflammation is a key feature ... more 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. The article covers novel strategies, using either small molecules or monoclonal antibodies. These strategies include: approaches targeting IKK-b-NF-kB (salicylates, salsalate), TNF-α (etanercept, infliximab, adalimumab), IL-1β (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. The available data supports the concept that targeting inflammation improves insulin sensitivity and β-cell function; it also ameliorates glucose control in insulin-resistant patients with inflammator...
The two most widely used methods for studying insulin sensitivity in man are the euglycaemic hype... more The two most widely used methods for studying insulin sensitivity in man are the euglycaemic hyperinsulinaemic clamp and the intravenous glucose tolerance test with minimal model assessment. The glucose clamp is the reference method, well validated and easy to interpret, which allows various extensions to the basic experimental procedure in order to obtain more valuable information on the specific effects of insulin on the various aspects of glucose metabolism. However, it is time-consuming and labour-intensive. In contrast, the intravenous glucose tolerance test is easier to perform, but its interpretation is much more difficult and requires a modeling approach called the "minimal model". If the intravenous glucose tolerance test probably represents a good screening test, mainly on a population basis, the glucose clamp still remains the gold standard method to study insulin sensitivity in man.
International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity, 1995
Impaired glucose tolerance and overt diabetes are more frequent in presence than in absence of ob... more Impaired glucose tolerance and overt diabetes are more frequent in presence than in absence of obesity. In obese subjects, glucose tolerance can be maintained within the normal range by compensating for insulin resistance by peripheral hyperinsulinism, the latter resulting from both increased insulin secretion and reduced insulin clearance. Impaired glucose tolerance is observed when insulin resistance is associated to impaired first-phase insulin response, which results in a significant increase in plasma glucose levels and a late insulin hyperresponsiveness. Both hyperinsulinaemia and hyperglycaemia are then able to overcome peripheral insulin resistance and impaired glucose disposal. When a more marked defect in insulin secretion is present, hyperglycaemia progresses, probably due to an additional participation of impaired suppression of hepatic glucose output. Overt diabetes then occurs with persistent post-absorptive hyperglycaemia. All these abnormalities can be reversed after...
The mechanisms responsible for glucocorticoid-induced insulin resistance remain unclear. Glucocor... more The mechanisms responsible for glucocorticoid-induced insulin resistance remain unclear. Glucocorticoids show several interactions with the sympatho-adrenal system which may contribute to this decrease in insulin sensitivity: they enhance the synthesis and actions of catecholamines, but abolish insulin-induced activation of muscle sympathetic nerve activity. The present study was performed in order to investigate the effects of the interactions between glucocorticoids and the sympatho-adrenal system on insulin sensitivity. Basal and insulin-stimulated glucose metabolism was measured in healthy human subjects during four 2-h clamp studies as follows: control (C); after taking oral dexamethasone (2 mg daily) for 2 days (D); after taking oral ephedrine sulphate (40 mg daily) for 2 days (E); and after taking dexamethasone+ephedrine (D+E). Glucose uptake, production and oxidation were calculated from plasma 13C glucose and exhaled 13CO2 during constant tracer infusion of U-13C glucose. B...
Aptitude physique versus adiposité : aspects physiopathologiques et impacts cardio-métaboliques c... more Aptitude physique versus adiposité : aspects physiopathologiques et impacts cardio-métaboliques chez le sujet adulte non diabétique Fitness versus fatness: Pathophysiological aspects and metabolic consequences in non-diabetic adults Résumé L'excès de masse grasse (adiposité), surtout abdominale, induit des effets cardiométaboliques néfastes, alors que l'exercice musculaire et une bonne aptitude physique exercent globalement une influence favorable. Les effets délétères d'un excès de masse grasse (fatness) pourraient donc être contrecarrés par la pratique régulière d'exercices aboutissant à une bonne forme physique (fitness). Cet article analyse d'abord les différents mécanismes physiopathologiques par lesquels l'exercice physique produit des effets bénéfiques chez la personne avec excès pondéral et fait le distinguo entre la pratique d'une activité physique (exercice musculaire) stricto sensu et aptitude physique (fitness). Ensuite, il décrit les études les plus importantes ayant analysé les relations entre le niveau d'aptitude physique et le degré d'adiposité chez le sujet adulte en surpoids ou obèse non diabétique et leurs influences respectives sur le risque de survenue de troubles métaboliques (syndrome métabolique) et sur la mortalité, en particulier cardiovasculaire.
Free fatty acids (FFAs) are metabolic intermediates that may be obtained through the diet or synt... more Free fatty acids (FFAs) are metabolic intermediates that may be obtained through the diet or synthesized endogenously. In addition to serving as an important source of energy, they produce a variety of both beneficial and detrimental effects. They play essential roles as structural components of all cell membranes and as signaling molecules regulating metabolic pathways through binding to nuclear or membrane receptors. However, under conditions of FFAs overload, they become toxic, inducing ROS production, ER stress, apoptosis and inflammation. SFAs (saturated fatty acids), unlike UFAs (unsaturated fatty acids), have recently been proposed as triggers of the NLRP3 inflammasome, a molecular platform mediating the processing of IL-1β in response to infection and stress conditions. Interestingly, UFAs, especially ω-3 FAs, inhibit NLRP3 inflammasome activation in various settings. We focus on emerging models of NLRP3 inflammasome activation with a special emphasis on the molecular mechanisms by which FFAs modulate the activation of this complex. Taking into consideration the current literature and FFA properties, we discuss the putative involvement of mitochondria and the role of cardiolipin, a mitochondrial phospholipid, proposed to be sensed by NLRP3 after release, exposure and/or oxidation. Finally, we review how this SFA-mediated NLRP3 inflammasome activation contributes to the development of both insulin resistance and deficiency associated with obesity/type 2 diabetes. In this context, we highlight the potential clinical use of ω-3 FAs as anti-inflammatory compounds.
Aims: This study was undertaken to determine the effects of a short-term dexamethasone treatment ... 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−1during 180 min, then at a rate of 1.5 ng/kg−1/min−1during 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 μmol/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 μmol/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.
Background: Patients with anorexia nervosa (AN) are at a high risk of renal failure. Chronic kidn... more Background: Patients with anorexia nervosa (AN) are at a high risk of renal failure. Chronic kidney disease (CKD) is often missed in these patients because the serum creatinine is a poor marker of kidney function. We studied the utility of cystatin C to detect renal failure in this population. Method: Twenty-seven AN patients were studied. Glomerular filtration rates (GFR) were measured with the chromium-51 ethylenediaminetetraacetate ( 51 Cr-EDTA) method. We compared the ability of creatinine and cystatin C to detect stage 3 CKD (GFR below 60 ml/min) by ROC curve analysis. Results: In this cohort, there is no correlation between GFR and serum creatinine, but there is a significant correlation between cystatin C and GFR. By ROC analysis, the cystatin C concentration is better than the serum creatinine concentration for the detection of stage 3 CKD (area under the curve of 0.86 vs. 0.61, p = 0.05). Conclusion: Plasma cystatin C is better than serum creatinine in detecting stage 3 CKD in patients with AN.
Inhibition of tumor necrosis factor (TNF)-a results in a marked increase in insulin sensitivity i... more Inhibition of tumor necrosis factor (TNF)-a 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 6 SD age, 41 6 4 yr; body mass index, 36.1 6 4.7 kg/m2; waist to hip ratio, 0.99 6 0.11) were studied (three patients with normal glucose toler- ance and four patients with impaired glucose tolerance or mild dia- betes; all were hyperinsulinemic). Each patient underwent two con- secutive euglycemic hyperinsulinemic glucose-clamp tests: 48 h after injection of placebo and 48 h after a single iv 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 6 0.74 vs. 2.38 6 0.99 mg/kg21zmin21) and glucose metabol...
PAQUOT, NICOLAS, ANDRÉ J. SCHEEN, MIRJAM DIRLEWANGER, PIERRE J. LEFÈ BVRE, AND LUC TAPPY. Hepatic... more PAQUOT, NICOLAS, ANDRÉ J. SCHEEN, MIRJAM DIRLEWANGER, PIERRE J. LEFÈ BVRE, AND LUC TAPPY. Hepatic insulin resistance in obese non-diabetic subjects and in type 2 diabetic patients. Obes Res. 2002;10: 129 -134. Objective: Obese non-diabetic patients are characterized by an extra-hepatic insulin resistance. Whether obese patients also have decreased hepatic insulin sensitivity remains controversial.
European Journal of Cardiovascular Prevention and Rehabilitation
In Belgium, regulations restrict the reimbursement of statins to patients with total serum choles... more In Belgium, regulations restrict the reimbursement of statins to patients with total serum cholesterol above 250 mg/dl (6.41 mmol/l) after a three-month lipid-lowering diet. We investigated the possible impact of these regulations on characteristics of Belgian patients receiving a lipid-lowering drug. From 1998 to 2000, standard questionnaires on coronary risk factors and treatments with lipid-lowering drugs were completed by 301 GPs sampled at random in the 11 Belgian Provinces. Questionnaires had to be completed for 18 consecutive patients 35 years old or more attending GPs' practices, irrespective of the underlying motive for attendance. Of the 5511 patients included in the study, 1519 (28%) had established coronary disease or diabetes mellitus, or > or = 2 non-cholesterol coronary risk factors. Most (70%) of these patients were not treated with a lipid-lowering drug. Only 22% of patients with established coronary disease, 10% of patients with diabetes mellitus and 9% of p...
We examined whether a very-low-energy all- protein diet (VLED) would produce detectable changes i... more We examined whether a very-low-energy all- protein diet (VLED) would produce detectable changes in iron as well as in other trace elements. Twenty-five obese patients con- sumed for 2 wk a VLED containing 70 g protein after a l-wk period during which total daily energy intake was progressively reduced to 1.26 MJ. Serum iron fell sharply by "50% (P <
Refers to Finan, B. et al. A rationally designed monomeric peptide triagonist corrects obesity an... more Refers to Finan, B. et al. A rationally designed monomeric peptide triagonist corrects obesity and diabetes in rodents. Nat. Med. 21, 27-36 (2015) An innovative strategy that uses a well-balanced monomeric peptide triagonist to target three metabolically related hormone receptors has been developed. This strategy seems to be the most effective pharmacological approach to reverse obesity and its metabolic comorbidities in rodents and could open new ways to tackle the dual burden of obesity and diabetes mellitus in humans.
There is a growing body of evidence to suggest that chronic silent inflammation is a key feature ... more 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. The article covers novel strategies, using either small molecules or monoclonal antibodies. These strategies include: approaches targeting IKK-b-NF-kB (salicylates, salsalate), TNF-α (etanercept, infliximab, adalimumab), IL-1β (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. The available data supports the concept that targeting inflammation improves insulin sensitivity and β-cell function; it also ameliorates glucose control in insulin-resistant patients with inflammator...
The two most widely used methods for studying insulin sensitivity in man are the euglycaemic hype... more The two most widely used methods for studying insulin sensitivity in man are the euglycaemic hyperinsulinaemic clamp and the intravenous glucose tolerance test with minimal model assessment. The glucose clamp is the reference method, well validated and easy to interpret, which allows various extensions to the basic experimental procedure in order to obtain more valuable information on the specific effects of insulin on the various aspects of glucose metabolism. However, it is time-consuming and labour-intensive. In contrast, the intravenous glucose tolerance test is easier to perform, but its interpretation is much more difficult and requires a modeling approach called the "minimal model". If the intravenous glucose tolerance test probably represents a good screening test, mainly on a population basis, the glucose clamp still remains the gold standard method to study insulin sensitivity in man.
International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity, 1995
Impaired glucose tolerance and overt diabetes are more frequent in presence than in absence of ob... more Impaired glucose tolerance and overt diabetes are more frequent in presence than in absence of obesity. In obese subjects, glucose tolerance can be maintained within the normal range by compensating for insulin resistance by peripheral hyperinsulinism, the latter resulting from both increased insulin secretion and reduced insulin clearance. Impaired glucose tolerance is observed when insulin resistance is associated to impaired first-phase insulin response, which results in a significant increase in plasma glucose levels and a late insulin hyperresponsiveness. Both hyperinsulinaemia and hyperglycaemia are then able to overcome peripheral insulin resistance and impaired glucose disposal. When a more marked defect in insulin secretion is present, hyperglycaemia progresses, probably due to an additional participation of impaired suppression of hepatic glucose output. Overt diabetes then occurs with persistent post-absorptive hyperglycaemia. All these abnormalities can be reversed after...
The mechanisms responsible for glucocorticoid-induced insulin resistance remain unclear. Glucocor... more The mechanisms responsible for glucocorticoid-induced insulin resistance remain unclear. Glucocorticoids show several interactions with the sympatho-adrenal system which may contribute to this decrease in insulin sensitivity: they enhance the synthesis and actions of catecholamines, but abolish insulin-induced activation of muscle sympathetic nerve activity. The present study was performed in order to investigate the effects of the interactions between glucocorticoids and the sympatho-adrenal system on insulin sensitivity. Basal and insulin-stimulated glucose metabolism was measured in healthy human subjects during four 2-h clamp studies as follows: control (C); after taking oral dexamethasone (2 mg daily) for 2 days (D); after taking oral ephedrine sulphate (40 mg daily) for 2 days (E); and after taking dexamethasone+ephedrine (D+E). Glucose uptake, production and oxidation were calculated from plasma 13C glucose and exhaled 13CO2 during constant tracer infusion of U-13C glucose. B...
Aptitude physique versus adiposité : aspects physiopathologiques et impacts cardio-métaboliques c... more Aptitude physique versus adiposité : aspects physiopathologiques et impacts cardio-métaboliques chez le sujet adulte non diabétique Fitness versus fatness: Pathophysiological aspects and metabolic consequences in non-diabetic adults Résumé L'excès de masse grasse (adiposité), surtout abdominale, induit des effets cardiométaboliques néfastes, alors que l'exercice musculaire et une bonne aptitude physique exercent globalement une influence favorable. Les effets délétères d'un excès de masse grasse (fatness) pourraient donc être contrecarrés par la pratique régulière d'exercices aboutissant à une bonne forme physique (fitness). Cet article analyse d'abord les différents mécanismes physiopathologiques par lesquels l'exercice physique produit des effets bénéfiques chez la personne avec excès pondéral et fait le distinguo entre la pratique d'une activité physique (exercice musculaire) stricto sensu et aptitude physique (fitness). Ensuite, il décrit les études les plus importantes ayant analysé les relations entre le niveau d'aptitude physique et le degré d'adiposité chez le sujet adulte en surpoids ou obèse non diabétique et leurs influences respectives sur le risque de survenue de troubles métaboliques (syndrome métabolique) et sur la mortalité, en particulier cardiovasculaire.
Free fatty acids (FFAs) are metabolic intermediates that may be obtained through the diet or synt... more Free fatty acids (FFAs) are metabolic intermediates that may be obtained through the diet or synthesized endogenously. In addition to serving as an important source of energy, they produce a variety of both beneficial and detrimental effects. They play essential roles as structural components of all cell membranes and as signaling molecules regulating metabolic pathways through binding to nuclear or membrane receptors. However, under conditions of FFAs overload, they become toxic, inducing ROS production, ER stress, apoptosis and inflammation. SFAs (saturated fatty acids), unlike UFAs (unsaturated fatty acids), have recently been proposed as triggers of the NLRP3 inflammasome, a molecular platform mediating the processing of IL-1β in response to infection and stress conditions. Interestingly, UFAs, especially ω-3 FAs, inhibit NLRP3 inflammasome activation in various settings. We focus on emerging models of NLRP3 inflammasome activation with a special emphasis on the molecular mechanisms by which FFAs modulate the activation of this complex. Taking into consideration the current literature and FFA properties, we discuss the putative involvement of mitochondria and the role of cardiolipin, a mitochondrial phospholipid, proposed to be sensed by NLRP3 after release, exposure and/or oxidation. Finally, we review how this SFA-mediated NLRP3 inflammasome activation contributes to the development of both insulin resistance and deficiency associated with obesity/type 2 diabetes. In this context, we highlight the potential clinical use of ω-3 FAs as anti-inflammatory compounds.
Aims: This study was undertaken to determine the effects of a short-term dexamethasone treatment ... 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−1during 180 min, then at a rate of 1.5 ng/kg−1/min−1during 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 μmol/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 μmol/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.
Background: Patients with anorexia nervosa (AN) are at a high risk of renal failure. Chronic kidn... more Background: Patients with anorexia nervosa (AN) are at a high risk of renal failure. Chronic kidney disease (CKD) is often missed in these patients because the serum creatinine is a poor marker of kidney function. We studied the utility of cystatin C to detect renal failure in this population. Method: Twenty-seven AN patients were studied. Glomerular filtration rates (GFR) were measured with the chromium-51 ethylenediaminetetraacetate ( 51 Cr-EDTA) method. We compared the ability of creatinine and cystatin C to detect stage 3 CKD (GFR below 60 ml/min) by ROC curve analysis. Results: In this cohort, there is no correlation between GFR and serum creatinine, but there is a significant correlation between cystatin C and GFR. By ROC analysis, the cystatin C concentration is better than the serum creatinine concentration for the detection of stage 3 CKD (area under the curve of 0.86 vs. 0.61, p = 0.05). Conclusion: Plasma cystatin C is better than serum creatinine in detecting stage 3 CKD in patients with AN.
Inhibition of tumor necrosis factor (TNF)-a results in a marked increase in insulin sensitivity i... more Inhibition of tumor necrosis factor (TNF)-a 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 6 SD age, 41 6 4 yr; body mass index, 36.1 6 4.7 kg/m2; waist to hip ratio, 0.99 6 0.11) were studied (three patients with normal glucose toler- ance and four patients with impaired glucose tolerance or mild dia- betes; all were hyperinsulinemic). Each patient underwent two con- secutive euglycemic hyperinsulinemic glucose-clamp tests: 48 h after injection of placebo and 48 h after a single iv 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 6 0.74 vs. 2.38 6 0.99 mg/kg21zmin21) and glucose metabol...
PAQUOT, NICOLAS, ANDRÉ J. SCHEEN, MIRJAM DIRLEWANGER, PIERRE J. LEFÈ BVRE, AND LUC TAPPY. Hepatic... more PAQUOT, NICOLAS, ANDRÉ J. SCHEEN, MIRJAM DIRLEWANGER, PIERRE J. LEFÈ BVRE, AND LUC TAPPY. Hepatic insulin resistance in obese non-diabetic subjects and in type 2 diabetic patients. Obes Res. 2002;10: 129 -134. Objective: Obese non-diabetic patients are characterized by an extra-hepatic insulin resistance. Whether obese patients also have decreased hepatic insulin sensitivity remains controversial.
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Papers by Nicolas Paquot