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ABSTRACT: BACKGROUND & AIMS: Glutamine is a potent gluconeogenic precursor and stimulates insulin secretion. Glutamine's effect on glucose metabolism in Duchenne muscular dystrophy (DMD) has never been studied. To determine plasma glucose and insulin concentrations measured during and after glutamine administration in DMD boys. We hypothesized that glutamine can modulate whole body glutamine-glucose metabolism in DMD, a genetically determined disease. METHODS: As secondary endpoints of a randomized crossover trial in 30 prepubertal DMD boys, we measured fasting blood glucose, insulin and the Homeostasis Model Assessment (HOMA) index after daily oral glutamine (0.5 g kg(-1) d(-1)) for 4 months versus placebo. In a separate time series trial in 6 prepubertal DMD boys, we measured the same endpoints as well as plasma glutamine and whole body glucose turnover (Ra,glc) (primed continuous i.v. infusion of d-[6,6-(2)D]glucose), while participants received acute oral glutamine (0.5 g kg(-1) d(-1)) continuously for 5 h. RESULTS: In the randomized trial, baseline measurements of HOMA correlated with age (r = 0,51, p = 0.007) and percent fat estimated by bioelectrical impedance analysis (BIA) (r = 0.39, p = 0.047). After 4 months glutamine supplementation, we observed no treatment or order effect on HOMA or insulin. During acute glutamine for 5 h (time series trial), plasma glutamine doubled and was associated with increased plasma insulin concentration (10.42 ± 2.54 vs 7.32 ± 1.86, p = 0.05) with no effect on plasma glucose, HOMA or Ra,glc. CONCLUSIONS: Acute glutamine transiently stimulates insulin secretion in DMD boys, which could be mediated by plasma glutamine concentrations. Fasting insulin concentration and HOMA might provide quantifiable indices of disease progression.
Clinical nutrition (Edinburgh, Scotland) 09/2012; · 3.27 Impact Factor
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ABSTRACT: The purpose of this review is to provide a critical appraisal of the literature on Glutamine (Gln) supplementation in various conditions or illnesses that affect children, from neonates to adolescents. First, a general overview of the proposed mechanisms for the beneficial effects of Gln is provided, and subsequently clinical studies are discussed. Despite safety, studies are conflicting, partly due to different effects of enteral and parenteral Gln supplementation. Further insufficient evidence is available on the benefits of Gln supplementation in pediatric patients. This includes premature infants, infants with gastrointestinal disease, children with Crohn's disease, short bowel syndrome, malnutrition/diarrhea, cancer, severe burns/trauma, Duchenne muscular dystrophy, sickle cell anemia, cystic fibrosis, and type 1 diabetes. Moreover, methodological issues have been noted in some studies. Further mechanistic data is needed along with large randomized controlled trials in select populations of sick children, who may eventually benefit from supplemental Gln.
Journal of nutrition and metabolism 01/2011; 2011:617597.
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ABSTRACT: To compare the ability of bioelectrical impedance analysis (BIA) and skinfold thickness (ST) measurements to estimate changes in body composition in Duchenne muscular dystrophy (DMD).
A secondary analysis was performed on 26 ambulatory DMD boys aged 3-11 y selected for a randomised trial of glutamine supplementation. We assessed fat free mass (FFM) and percentage fat mass (%FM) by BIA (monofrequency (50kHz) unit), ST measurements and a criterion method, dual-energy X-ray absorptiometry (DXA), and repeated these measures 5 mo later at 3 outpatient clinical investigation centers in France.
When compared with DXA reference method, ST overestimated change in FFM (P<0.01), whereas BIA estimates did not differ from DXA. Concordance plots revealed that when compared with DXA, ST overestimated the increase in FFM (mean: 0.6 kg; 95% CI: 0.17 to 0.99) which led to an underestimation in %FM change (mean: -1.4%; 95% CI: -2.6 to -0.2), whereas BIA estimated change in FFM (mean: -0.05 kg; 95% CI: -0.39 to 0.29) and %FM (mean: 1.3%; 95% CI: -0.06 to 2.7) more accurately.
BIA method can be used to follow changes in nutritional status of ambulatory DMD children or to evaluate treatment efficacy.
Clinical nutrition (Edinburgh, Scotland) 10/2010; 29(5):633-8. · 3.27 Impact Factor
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Journal of Clinical Nursing 09/2010; 19(17-18):2649-51. · 1.12 Impact Factor
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ABSTRACT: Oral glutamine decreases whole body protein breakdown in Duchenne muscular dystrophy (DMD). We evaluated the functional benefit of 4 months oral glutamine in DMD.
30 ambulant DMD boys were included in this double-blind, randomized crossover trial with 2 intervention periods: glutamine (0.5 g/kg/d) and placebo, 4 months each, separated by a 1-month wash-out, at 3 outpatient clinical investigation centers in France. Functional benefit was tested by comparing glutamine versus placebo on change in walking speed at 4 months. Secondary outcome measures were: 2-minute walk test, work, power, muscle mass (urinary creatinine), markers of myofibrillar protein breakdown (urinary 3-methyl-histidine/creatinine), serum creatine phospho-kinase, body composition (fat free mass, fat mass percentage), safety and oral nutrient intake. There was no improvement in the primary end point (walking speed) or in secondary measures of muscle function (2-minute walk test, work, power) in the glutamine group compared with placebo. However, subjects receiving glutamine or placebo showed no deterioration in functional measures over the course of the 9-month trial. No differences in muscle mass, markers of protein breakdown or serum creatine phosho-kinase were observed, except for a blunted increase in fat free mass in the glutamine group which led to a greater increase in fat mass percentage. Glutamine was safe and well-tolerated.
This trial did not identify additional benefit of 4 months oral glutamine over placebo on muscle mass or function in ambulatory DMD boys. Although apparently safe, current data cannot support routine supplementation in this population as a whole, until further research proves otherwise.
(ClinicalTrials.gov) NCT00296621.
PLoS ONE 02/2009; 4(5):e5448. · 4.09 Impact Factor
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ABSTRACT: The purpose of this work was to compare breastfeeding practices, perceptions, and infant weight change of prepregnant obese versus normal-weight mothers in the first 3 months postpartum.
For the prospective case-control study, obese mothers (prepregnant BMI > or = 30 kg/m(2)) were matched with normal-weight mothers (18.5 < or = prepregnant BMI < 25 kg/m(2)) according to initial infant feeding, parity, maternal age, ethnicity, and education. Participants completed an oral questionnaire in the hospital and a telephone interview at 1 and 3 months postpartum.
Of 1432 mothers who had given birth at a university hospital in France, 10% were obese. Breastfeeding initiation was lower for obese (48%) versus normal-weight (64%) mothers. A total of 111 of 141 obese mothers were paired with 111 normal-weight mothers. Infant birth weight was similar for newborns of obese and normal-weight mothers. Among mothers who initiated breastfeeding, infant weight gain from 0 to 1 month was lower in breastfed infants of obese mothers compared to normal-weight mothers. Obese mothers were less likely to maintain full breastfeeding at 1 month and 3 months. The percentage of mothers breastfeeding to any extent did not differ between obese and reference women. Obese mothers more often felt uncomfortable breastfeeding in public at 3 months. Fewer obese mothers perceived that their milk supply was sufficient at 1 month and 3 months. Despite greater breastfeeding difficulties, obese mothers were less likely to seek support for breastfeeding in the first 3 months postpartum.
Pediatricians and health professionals should recognize that obese mothers have different breastfeeding practices and perceptions. Extra support and intervention are needed among obese mothers during prenatal and early postnatal periods so that their children can benefit from breastfeeding.
PEDIATRICS 05/2008; 121(5):e1319-24. · 4.47 Impact Factor
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ABSTRACT: To determine whether glutamine (Gln) reduces the ratio of oxidized to total glutathione (GSSG/GSH) and extracellular signal-regulated kinase (ERK1/2) activation in dystrophic muscle. Four-week old mdx mice, an animal model for Duchenne muscular dystrophy and control (C57BL/10) received daily intraperitoneal injections of l-Gln (500 mg/kg/d) or 0.9% NaCl for 3 d. GSH and GSSG concentrations in gastrocnemius were measured using a standard enzymatic recycling procedure. Free amino acid concentrations in gastrocnemius were determined by ion exchange chromatography. Phosphorylated protein levels of ERK1/2 in quadriceps were examined using Western Blot. l-Gln decreased GSSG and GSSG/GSH (an indicator of oxidative stress). This was associated with decreased ERK1/2 phosphorylation. Muscle free Gln, glutamate (Glu), and the sum (Gln + Glu) were higher in mdx versus C57BL/10, at the basal level. Exogenous Gln decreased muscle free Glu and Gln + Glu in mdx only, whereas Gln was not affected. In conclusion, exogenous Gln reduces GSSG/GSH and ERK1/2 activation in dystrophic skeletal muscle of young mdx mice, which is associated with decreased muscle free Glu and Gln + Glu. This antioxidant protective mechanism provides a molecular basis for Gln's antiproteolytic effect in Duchenne muscular dystrophy children.
Pediatric Research 04/2008; 63(3):268-73. · 2.70 Impact Factor
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ABSTRACT: Glutamine has been shown to acutely decrease whole-body protein degradation in Duchenne muscular dystrophy (DMD).
To improve nutritional support in DMD, we tested whether oral supplementation with glutamine for 10 d decreased whole-body protein degradation significantly more than did an isonitrogenous amino acid control mixture.
Twenty-six boys with DMD were included in this randomized, double-blind parallel study; they received an oral supplement of either glutamine (0.5 g . kg(-1) . d(-1)) or an isonitrogenous, nonspecific amino acid mixture (0.8 g . kg(-1) . d(-1)) for 10 d. The subjects in each group were not clinically different at entry. Leucine and glutamine metabolisms were estimated in the postabsorptive state by using a primed continuous intravenous infusion of [1-(13)C]leucine and [2-(15)N]glutamine before and 10 d after supplementation.
A significant effect of time was observed on estimates of whole-body protein degradation. A significant (P < 0.05) decrease in the rate of leucine appearance (an index of whole-body protein degradation) was observed after both glutamine and isonitrogenous amino acid supplementation [x +/-SEM: 136 +/- 9 to 124 +/- 6 micromol . kg fat-free mass (FFM)(-1) . h(-1) for glutamine and 136 +/- 6 to 131 +/- 8 micromol . kg FFM(-1) . h(-1) for amino acids]. A significant (P < 0.05) decrease in endogenous glutamine due to protein breakdown was also observed (91 +/- 6 to 83 +/- 4 micromol . kg FFM(-1) . h(-1) for glutamine and 91 +/- 4 to 88 +/- 5 micromol . kg FFM(-1) . h(-1) for amino acids). The decrease in the estimates of whole-body protein degradation did not differ significantly between the 2 supplemental groups.
Oral glutamine or amino acid supplementation over 10 d equally inhibits whole-body protein degradation in DMD.
American Journal of Clinical Nutrition 05/2006; 83(4):823-8. · 6.67 Impact Factor
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ABSTRACT: We present here evidence for the enhancement of an inositol 1,4,5-trisphosphate (IP3) mediated calcium signaling pathway in myotubes from dystrophin-deficient cell lines (SolC1(-)) as compared to a cell line from the same origin but transfected with mini-dystrophin (SolD(+)). With confocal microscopy, we demonstrated that calcium rise, induced by the perifusion of a solution containing a high potassium concentration, was higher in SolC1(-) than in SolD(+) myotubes. The analysis of amplitude and kinetics of the calcium increase in SolC1(-) and in SolD(+) myotubes during the exposure with SR Ca2+ channel inhibitors (ryanodine and 2-APB) suggested the presence of two mechanisms of SR calcium release: (1) a fast SR calcium release that depended on ryanodine receptors and (2) a slow SR calcium release mediated by IP3 receptors. Detection analyses of mRNAs (reverse transcriptase [RT]-PCR) and proteins (Western blot and immunolocalization) demonstrated the presence of the three known isoforms of IP3 receptors in both SolC1(-) and SolD(+) myotubes. Furthermore, analysis of the kinetics of the rise in calcium revealed that the slow IP3-dependent release may be increased in the SolC1(-) as compared to the SolD(+), suggesting an inhibitory effect of mini-dystrophin in this signaling pathway. Upon incubation with pertussis toxin (PTX), an inhibitory effect similar to that of the IP3R inhibitor (2-APB) was observed on K+-evoked calcium release. This result suggests the involvement of a Gi protein upstream of the IP3 pathway in these stimulation conditions. A hypothetical model is depicted in which both Gi protein and IP3 production could be involved in K+-evoked calcium release as well as a possible interaction with mini-dystrophin. Our findings demonstrate the existence of a potential relationship between mini-dystrophin and SR calcium release as well as a regulatory role of mini-dystrophin on intracellular signaling.
The Journal of General Physiology 03/2006; 127(2):171-82. · 3.84 Impact Factor
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ABSTRACT: Duchenne muscular dystrophy (DMD) is often associated with obesity, which worsens the handicap early in the course of the disease. Nutritional assessment, however, can be difficult and often misleading in DMD.
Two methods of estimating body composition in DMD, skinfold-thickness (ST) measurement and bioelectrical impedance analysis (BIA), were compared with a reference method, labeled water dilution (WD).
Body composition was estimated by using ST measurements and BIA (50 kHz, 800 mAmp), as well as the WD method (1 mL H2(18)O/kg) in 11 DMD patients with a mean (+/-SD) age of 10.0 +/- 2.5 y.
When compared with the WD method, ST measurement significantly (P < 0.01) overestimated fat-free mass (FFM) (mean +/- SD ST: 24.5 +/- 5.9 kg; mean +/- SD WD: 18.2 +/- 2.5 kg), which led to an underestimation of the percentage of fat mass (%FM) (ST: 23.3 +/- 10.4%; WD: 40.1 +/- 17.1%; P < 0.05). In contrast, estimates obtained with BIA (FFM: 21.5 +/- 4.5 kg; %FM: 31.3 +/- 13.9%) did not differ from those obtained with WD. The difference from the reference method was less for BIA (mean: 3.3 kg; 95% CI: 0.8, 4.9 kg) than for ST (6.3 kg; 2.2, 8.6 kg). WD and BIA defined 73% and 55%, respectively, of the children as obese (%FM associated with body mass index cutoffs for obesity), whereas ST measurements defined 9% as obese (P < 0.01).
Body-composition estimates by BIA are closer to those by WD than are those by ST measurement. Early detection of fat accumulation and longitudinal monitoring of nutritional care are 2 relevant applications of BIA to prevent obesity and hence lessen the burden of DMD.
American Journal of Clinical Nutrition 01/2006; 83(1):65-9. · 6.67 Impact Factor
