Christine Fedou

Grape Polyphenols Prevent Fructose- Induced Oxidative Stress and Insulin Resistance in First-Degree Relatives of Type 2 Diabetic Patients

OBJECTIVE To assess the clinical efficacy of nutritional amounts of grape polyphenols (PPs) in counteracting the metabolic alterations of high-fructose diet, including oxidative stress and insulin resistance (IR), in healthy volunteers with high metabolic risk. RESEARCH DESIGN AND METHODS Thirty-eight healthy overweight/obese first-degree relatives of type 2 diabetic patients (18 men and 20 women) were randomized in a double-blind controlled trial between a grape PP (2 g/day) and a placebo (PCB) group. Subjects were investigated at baseline and after 8 and 9 weeks of supplementation, the last 6 days of which they all received 3 g/kg fat-free mass/day of fructose. The primary end point was the protective effect of grape PPs on fructose-induced IR. RESULTS In the PCB group, fructose induced 1) a 20% decrease in hepatic insulin sensitivity index (P < 0.05) and an 11% decrease in glucose infusion rate (P < 0.05) as evaluated during a two-step hyperinsulinemic-euglycemic clamp, 2) an increase in systemic (urinary F2-isoprostanes) and muscle (thiobarbituric acid–reactive substances and protein carbonylation) oxidative stress (P < 0.05), and 3) a downregulation of mitochondrial genes and decreased mitochondrial respiration (P < 0.05). All the deleterious effects of fructose were fully blunted by grape PP supplementation. Antioxidative defenses, inflammatory markers, and main adipokines were affected neither by fructose nor by grape PPs. CONCLUSIONS A natural mixture of grape PPs at nutritional doses efficiently prevents fructose-induced oxidative stress and IR. The current interest in grape PP ingredients and products by the global food and nutrition industries could well make them a stepping-stone of preventive nutrition.

Relationships between fibrinogen and insulin resistance.

A relationship between plasma fibrinogen levels and insulinemia, as well as the different parameters of the insulin resistance syndrome has been described. The aim of the present paper was to investigate whether plasma fibrinogen concentrations were linked to plasma insulin levels or to the degree of insulin resistance. For this purpose, 62 nondiabetic, nonhypertensive patients, 30 men and 32 women, with body mass indexes (BMIs) and ages ranging from 18.6 to 50.2 kg/m(2) and from 19 to 60 years, respectively, were studied. Insulin sensitivity was quantified by the minimal model procedure over a 180-min intravenous glucose tolerance test with iterative sampling. Plasma insulin was determined by radioimmunoassay without cross-reactivity to human proinsulin, and fibrinogen by the method of Clauss. Insulin sensitivity ranged from 0.009 to 23.2 min(-1)/(microU/ml)x10(-4), covering the whole range of insulin sensitivities. Fibrinogen ranged from 1.70 to 5.07 g/l. There was a significant negative correlation between fibrinogen and insulin sensitivity (r=-0.76,P<0.0001) and a positive correlation between fibrinogen and basal insulin (r=0.56,P<0.0001). After adjustment for BMI, body fat mass and waist-to-hip ratio, these two relationships remained significant. In addition, a multiple regression analysis was performed to assess the independent effect of the following related variables: fibrinogen, insulin sensitivity, insulinemia and BMI. Only insulin sensitivity appeared to account for the ability to predict fibrinogen values. Thus, we hypothesized it was likely that the state of insulin resistance rather than hyperinsulinemia per se was related to hyperfibrinogenemia. We proposed an interpretation of these data in connection with some factors like free fatty acids or tumor necrosis factor-alpha, which have been implicated in the pathogenesis of insulin resistance. Nevertheless, prospective and intervention studies are needed to assess whether there is a simple association or a causal relationship between insulin resistance and hyperfibrinogenemia.

Effects of oral zinc gluconate on glucose effectiveness and insulin sensitivity in humans

Zinc improves both insulin secretion and insulin sensitivity, and exerts insulin-like effects. We investigated its acute effects on the parameters of glucose assimilation determined with the minimal model technique from frequent sampling intravenous glucose tolerance test (FSIVGTT) in seven healthy volunteers. FSIVGTTs (0.5 g/kg of glucose, followed by 2 U insulin iv injection at 19 min) were performed after the subjects had taken 20 mg zinc gluconate twice (the evening before and 30 min before the beginning of the test) or placebo pills (simple blind randomized protocol). Glucose assimilation was analyzed by calculating Kg (slope of the exponential decrease in glycemia), glucose effectiveness Sg (i.e., ability of glucose itself to increase its own disposal independent of insulin response), and SI (insulin sensitivity, i.e. the effect of increases in insulinemia on glucose disposal). The two latter parameters were calculated by fitting the experimental data with the two equations of Bergman’s “minimal model”. Zinc increased Kg (p<0.05) and Sg (p<0.05), whereas SI and insulin first-phase secretion did not significantly increase. This study suggests that zinc improves glucose assimilation, as evidenced by the increase in Kg, and that this improvement results mainly from an increase in glucose effectiveness (insulin-like effect), rather than an action on insulin response or insulin sensitivity.

The effects of intensive training on insulin-like growth factor I (IGF-I) and IGF binding proteins 1 and 3 in competitive cyclists: relationships with glucose disposal.

Abstract The aim of the present study was to determine whether 4 months of intensified training would result in modified plasma insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 1 (IGFBP-1) or IGFBP-3 in eight competitive cyclists and eight sedentary individuals and to define the relationships of these factors with glucose disposal. Insulin sensitivity and glucose effectiveness — that is, the fractional disappearance of glucose independent of any change in insulinaemia — were measured with the minimal model (mathematical analysis of frequently sampled intravenous glucose tolerance test). Both glucose effectiveness and insulin sensitivity were higher in the cyclists than in the sedentary individuals, but did not increase further with training. IGF-I was higher in the cyclists than in the sedentary group only after training (P<0.05). Plasma IGFBP-1 and IGFBP-3 increased after training (38 and 20%, respectively; P<0.05) in the cyclists and were higher than in the sedentary individuals (P<0.05). IGF-I was negatively correlated with insulin sensitivity before and after training (r=−0.66 and −0.67, respectively; P<0.05) and IGFBP-1 was negatively correlated with glucose effectiveness before and after training (r=−0.68 and −0.77, respectively; P<0.05). Our results show that strenuous endurance training improves the somatotrope axis (growth hormone—IGF) and that IGFBP-1 may be involved in glucose homeostasis, possibly by limiting the exercise-induced increase in glucose disposal, in competitive cyclists.

Serum zinc in highly trained adolescent gymnasts

Serum zinc was measured in 20 adolescent gymnasts (9 boys, 11 girls, age 12–15 yr) explored for detecting possible adverse effects of intense training on pubertal maturation and growth. They had low serum zinc (0.599±0.026 mg/L) when compared to matched control sedentary children (n=118 mean 0.81±0.014p<0.001). Girls had lower zinc than boys (0.557±0.023 vs 0.651±0.044p<0.001). Zinc was correlated to isometric adductor strength (r=0.468p<0.05). Children with serum zinc <0.6 mg/L had lower insulin-like growth factor binding protein 3 than others (2.326±0.264 vs 2.699±0.12p<0.01). Thus, zinc is lowered in trained adolescent gymnasts and even lower in females. This reduction could play some role in abnormalities of puberty, growth, or muscular performance.

Serum levels of insulin-like growth factor-I (IGF-I), and IGF-binding proteins-1 and -3 in middle-aged and young athletes versus sedentary men: Relationship with glucose disposal

The goal of this study was to characterize the respective effects of aging and endurance training on serum insulin-like growth factor I (IGF-I), as well as IGF-binding proteins (IGFBP)-1 and -3 in relationship with glucose disposal. Thirty-two subjects (16 middle-aged men: 8 cyclists and 8 sedentary men; and 16 young men: 8 cyclists and 8 sedentary men) were compared in this study. Insulin sensitivity (SI) and glucose effectiveness (Sg) were assessed by the minimal model. Endurance training increased SI, Sg, and IGFBP-1 and -3 in both age groups (P<.05), but the older group showed a greater increase in SI and IGFBP-1 than the younger group (P<.05). IGF-I was increased only in the middle-aged trained men (P<.05). An effect of aging was found in the sedentary subjects, who presented lower IGF-I and SI (P<.05) when older. This effect disappeared with training since IGF-I and SI were nearly identical in young and middle-aged trained subjects. SI was correlated with IGFBP-1 (P<.01). These data suggest that (1) endurance training increases SI, Sg, and IGFBP-1 and -3 in men and, for SI and IGFBP-1, this increase becomes more pronounced with age; (2) endurance training may attenuate the aged-related decline in SI and IGF-I; and (3) IGFBP-1 may protect against the risk of hypoglycemia by counteracting the hypoglycemic effect of IGF-I in such situations of high SI.

Exploration de gymnastes adolescents de classe sportive: Quel suivi médical pour la croissance et la puberté?

Resume Un bilan endocrinien approfondi, incluant une epreuve deffort submaximale de 15 minutes, a ete realise a lautomne (debut de saison dentrainement) chez 30 gymnastes de classe sportive (18 filles et 12 garcons, âge : 9–15 ans), afin detudier leurs caracteristiques metaboliques et hormonales et de proposer un suivi biologique adapte a cette population. Un suivi longitudinal a ete possible chez 21 dentre eux, explores une seconde fois au printemps, apres 6 mois dentrainement gymnique. La taille et le poids etaient comparables entre les gymnastes et un groupe de 11 temoins apparies, et la croissance se poursuivait de facon normale pendant lentrainement. Les gymnastes de sexe masculin avaient une moindre adiposite que les temoins ( p ). Le pourcentage de masse grasse augmentait significativement chez les filles pendant lentrainement ( p ). Les gymnastes se distinguaient par une plus grande force de prehension ( p ). Les variations de leur capacite aerobie (W 170 ) pendant le suivi etaient negativement correlees a celles du score de surentrainement ( r = − 0,604, p ). Sur le plan hormonal, il existait une augmentation significative des concentrations destradiol ( p ) et de testosterone ( p ) entre les deux visites chez les gymnastes en cours de puberte. Les concentrations plasmatiques basales de GH etaient plus faibles chez les gymnastes que chez les temoins en debut de saison ( p ), mais augmentait significativement au printemps ( p ). La reponse de la GH a lexercice tendait a etre plus elevee chez les gymnastes mais netait pas influencee par la periode dentrainement. LIGF-I et lIGFBP-1 etaient identiques dans les deux groupes. LIGFBP-3 etait abaissee de 25 % chez les gymnastes en debut de saison ( p ). LIGF-I sabaissait de 24 % au printemps ( p ). Chez les gymnastes en cours de puberte, lIGFBP-1 ( p ) et lIGFBP-3 ( p ) sabaissaient egalement pendant la saison gymnique. LIGFBP-3 chez les gymnastes etait correle a la force de prehension sur lensemble des deux visites ( r = 0,550, p ). Laxe corticotrope presentait plusieurs particularites : la reponse de lACTH a lexercice etait significativement plus faible chez les gymnastes ( p s 0,01 ). Il en etait de meme pour le cortisol plasmatique ( p ). Au contraire, les valeurs basales de β-endorphine etaient trois fois plus elevee ( p s 0,01 ) chez les sportifs et restaient significativement superieures pendant lexercice. Ceci conduisait a une alteration tres importante du rapport molaire entre ACTH et β-endorphine, tres abaisse chez les gymnastes au repos comme a lexercice. Les valeurs de creatine kinase et de myosine plasmatiques etaient significativement plus elevees chez les gymnastes ( p p s 0,05 respectivement). La troponine I squelettique, mesuree uniquement chez les gymnastes avait augmente de 240 % pendant le suivi ( p ). Les taux de ferritine et de zinc serique etaient plus faibles chez les sujets sportifs. Cette etude montre que lentrainement gymnique pratique par des adolescents a un niveau national est bien tolere en ce qui concerne les parametres physiques de croissance et de maturation sexuelle. En revanche, il existe chez ces jeunes sportifs des modifications tres nettes des fonctions somatotropes et opio-adrenocorticotrope et dautres marqueurs peu habituels qui pourraient avoir un interet en medecine sportive.

Relationships between fitness and blood viscosity in untrained normal short children

18 healthy untrained children (13 boys, 5 girls) performed a 15 min submaximal incremental exercise on cycloergometer rising heart rate (HR) up to a final step (5 min) at 90% of theoretical maximal heart rate

Interactions entre la fonction somatotrope et l'activité musculaire

Resume La reponse secretoire de lhormone de croissance (GH) a lexercice depend des caracteristiques de cet exercice (charge de travail, duree, anaerobiose ou hyperlactatemie, charge thermique). Le determinisme neuroendocrinien de cette secretion semble plus une baisse de la somatostatine quune augmentation du GRF. Lexercice modulerait ainsi le tonus somatostatinergique par plusieurs influences inhibitrices : catecholamines, serotonine, dopamine, acetylcholine. Lentrainement amplifie la pulsatilite de repos de la secretion somatotrope, et amplifie egalement la reponse de GH a lexercice, malgre une litterature un peu ancienne qui suggerait linverse. Les opiaces endogenes amplifient la reponse de GH a lexercice chez lathlete entraine. Cest plutot la surcharge dactivite et le surentrainement qui deprimeraient cette reponse. Le role physiologique de la reponse de GH a lexercice pourrait resider dans un effet lipolytique direct, une activation de la neoglucogenese, la preparation metabolique de lorganisme a un exercice ulterieur (croissance et syntheses proteiques du muscle squelettique). Les travaux recents sur le deficit en GH chez ladulte et sa correction par traitement substitutif confirment bien que la GH est une hormone ergogenique, par ses actions sur la force musculaire et la performance myocardique et les compartiments hydriques (notamment la thermolyse par sudation) et, peut-etre aussi, par des effets neuroendocriniens au niveau du systeme nerveux central. Leffet anabolisant dune activite physique reguliere depend aussi de mecanismes de regulation peripherique de lIGF-1, notamment par ses proteines porteuses. IGF-1 et IGF-BP3 sont des marqueurs de lanabolisme general chez le sportif, correles a des mesures ergometriques. LIGF-BP3 semble se reduire dans les etats de surentrainement. Dans ce contexte, lexploration de la fonction somatotrope chez des sportifs (et notamment des enfants) soumis a un entrainement intensif pourrait devenir un outil interessant pour le medecin du sport, lorsque ces elements se seront mieux precises et auront permis de definir une semeiologie utilisable.

Protéines porteuses des somatomédines et force isométrique de préhension dans un groupe de gymnastes adolescents soumis à un entraînement intensif

Resume Laxe hormone de croissance - somatomedines est un des systemes anabolisants essentiels de lorganisme et sest avere en relation avec le niveau d activite physique et de performance aerobie. Nous avons etudie les relations entre la somatomedine C/IGFI serique, ses proteines porteuses IGFBPI et IGFBP3 et la force musculaire chez 37 gymnastes adolescents soumis depuis 1 a 5 ans a 18–20 heures dentrainement intensif hebdomadaire ( 13 garcons, 24 filles, âge 10–15 ans, taille 1,55 ± 0,01 m, poids 45,1 ± 1,4 kg). Le bilan nutritionnel montre que ces gymnastes consommaient environ 2 670 ± 380 kCal journalieres, se reparfissant de la sorte: 16% (+2) de protides, 39% (+3) de lipides et 45 % (+1) de glucides. Somatomedine C/IGFI et IGFBP3 restent dans lenveloppe des valeurs normales, tandis que les valeurs dIGFBPI semblent se retrouver au dessous de cette enveloppe. Au cours de la puberte lIGFBPI decroIt ( p r = 0.489 p r =0,3451 p r =−0,431 p r = 0,698 p r = −0,595 p r =−0,553 p r = −0,765 p