Our S I values were within the range reported by Hoffman and Armstrong 21 , although our mean value was somewhat lower. Decreased S I has been demonstrated in adolescents compared with prepubertal children 16 — In the present study, S I was somewhat but not significantly higher in prepubertal children.

However, the lack of significance may be owing to the small number of subjects in each group. The brain weight of a 6- to 9-year-old is similar to that of an adolescent g in the children and g in the adolescents The greater absolute rate of glucose Ra in micromoles per minute in the adolescents is most likely because of a larger nonbrain tissue mass e.

fat and muscle. To our knowledge, these studies are the first to demonstrate that the rate of gluconeogenesis, on a body weight basis, is greater in children between the ages of 8 and 9 y than in adolescents between the ages of 14 and 16 y, whereas the fraction of glucose production derived from gluconeogenesis was essentially identical between the two groups of subjects.

The deuterium oxide method with assessment of deuterium enrichment at carbon 6 of glucose does not include the gluconeogenic contribution from glycerol 12 , However, using the information obtained by the [ 2 H 5 ] glycerol tracer, we could calculate the glycerol turnover rates, an indicator of lipolysis, as well as the minimal and maximal estimates of the fraction of glucose Ra derived from glycerol via the gluconeogenic pathway.

These estimates were also highly reproducible. We could not demonstrate any significant relationships between measures of glucose and lipid metabolism and percent body fat, energy intake and expenditure, oxidation rates, or RQ. This is not surprising, as the subjects were all healthy and nonobese, and they were studied under strict dietary and experimental conditions.

We did not compare boys and girls because of the small sample size prepubertal children, two boys, two girls; adolescents, two boys, two girls.

Except for the differences in glucose Ra and gluconeogenic rate described above, we could not demonstrate any significant differences for metabolic variables between prepubertal children and adolescents. This may be related to the small group sizes four subjects in each group , but the study was not designed to compare the two groups.

In summary, we demonstrate, using a prepacked meal strategy as described, that it is possible to maintain a consistent dietary energy intake and composition for a period of 7 d with the children carrying out their normal activities. Furthermore, using our study design, it is possible to provide highly reproducible data on a number of measures of glucose metabolism.

The power calculations performed on the basis of these data will enable us and other investigators to more precisely design studies to evaluate the impact of various treatments and dietary intervention strategies in children e. Timothy Garvey, Rachel L. Batterham, … the STEP 5 Study Group.

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Metab Endocrinol Clin North Am 28 : — Download references. The authors thank research nurse Leah Mitchell, dietitian Sandy Kattner, and the staff of the Metabolic Research Unit at the Children's Nutrition Research Center, as well as Judy Rosenberg, Reed Parson, Carlotta Williams, Jiang-Ping Wen, Anne Adolph, Maurice Puyau, Firoz Vohra, and Nitesh Mehta for excellent assistance.

Children's Nutrition Research Center, Houston, , Texas, U. Department of Electronics and Informatics, University of Padua, Padua, Italy.

You can also search for this author in PubMed Google Scholar. Correspondence to Agneta L Sunehag. This work is a publication of the U. This project was supported by grants from MARS inc. and U. Department of Agriculture Cooperative Agreement The contents of this publication do not necessarily reflect the views or policies of the U.

Department of Agriculture, nor does mention of trade names, commercial products, or organizations imply endorsement from the U. Reprints and permissions.

Sunehag, A. et al. Glucose Production, Gluconeogenesis, and Insulin Sensitivity in Children and Adolescents: An Evaluation of Their Reproducibility. Pediatr Res 50 , — Download citation. Received : 23 August Accepted : 30 January Issue Date : 01 July Anyone you share the following link with will be able to read this content:.

Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Journal of Inherited Metabolic Disease Skip to main content Thank you for visiting nature. nature pediatric research articles article. Download PDF. Abstract The prevalence of overweight and obese children has doubled, and the incidence of type 2 diabetes in children 0—19 y has increased 4-fold during the past several decades.

Measured vs estimated resting energy expenditure in children and adolescents with obesity Article Open access 14 August Total energy expenditure is repeatable in adults but not associated with short-term changes in body composition Article Open access 10 January Free fatty acids, glicentin and glucose-dependent insulinotropic polypeptide as potential major determinants of fasting substrate oxidation Article Open access 17 August Main For the past several decades, we have experienced a dramatic increase in the incidence of obesity, insulin resistance, and type 2 diabetes in children and adolescents in the United States.

METHODS Subjects The protocol was approved by the Institutional Review Board for Human Subject Research for Baylor College of Medicine and affiliated hospitals. Table 1 Subjects Full size table.

RESULTS Subject characteristics, including age, weight, height, BMI, and percent fat, are depicted in Table 1 , and the dietary intakes in Table 2. Table 3 Plasma concentrations of substrates and hormones during steady state study h 2.

Table 4 Isotopic enrichments during steady state study h 2. Table 5 Glucose Ra equivalent to GPR , gluconeogenesis, glycerol Ra, and leucine Ra during steady state study h 2. Figure 1. Full size image. Similar content being viewed by others.

Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial Article Open access 10 October Effects of dietary fibre on metabolic health and obesity Article 07 February The genetics of obesity: from discovery to biology Article 23 September Abbreviations BMI: body mass index BMR: basal metabolic rate CV: coefficient of variation GC: gas chromatography GCMS: gas chromatography mass spectrometry GPR: glucose production rate HMT: hexamethylenetetramine IVGTT: intravenous glucose tolerance test KIC: α-ketoisocaproic acid RQ: respiratory quotient Ra: rate of appearance S I : insulin sensitivity S G : glucose effectiveness.

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J Pediatr : — Article CAS PubMed Google Scholar Rosenbloom AL, Joe JR, Young RS, Winter WE Emerging epidemic of type 2 diabetes in youth. Diabetes 26 : — Article CAS PubMed Google Scholar Kalhan SC, Savin SM, Adam PAJ Estimation of glucose turnover with stable tracer glucose 13 C.

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J Biol Chem : — Article CAS PubMed Google Scholar Landau BR, Wahren J, Chandramouli V, Schumann WC, Ekberg K, Kalhan SC Use of Use of 2 H2O for estimating rates of gluconeogenesis. J Clin Invest 95 : — Article CAS PubMed PubMed Central Google Scholar Cobelli C, Ruggeri A A reduced sampling schedule for estimating the parameters of the glucose minimal model from a labeled IVGTT.

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Diabetes 48 : — Article CAS PubMed Google Scholar Katz J, Tayek JA Gluconeogenesis and the Cori cycle in , , and h-fasted humans. Am J Physiol :E CAS PubMed Google Scholar Hellerstein MK, Neese RA, Linfoot P, Christiansen M, Turner S, Letscher A Hepatic gluconeogenic fluxes and glycogen turnover during fasting in humans: a stable isotope study.

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Download references. This work was supported by grants from the National Institutes of Health to L. was the recipient of a post-doctoral fellowship and a Junior Faculty Award from the American Diabetes Association.

Departments of Medicine and Molecular Pharmacology, Diabetes Research and Training Center, Albert Einstein College of Medicine, Bronx, New York, USA. Merck Research Laboratories, Rahway, New Jersey, USA.

You can also search for this author in PubMed Google Scholar. Correspondence to Luciano Rossetti. is employed by the Merck Research Laboratories, and Cpd1 was originally reported by their group. has a consultation agreement in unrelated areas with Merck Research Laboratories.

Reprints and permissions. Hypothalamic insulin signaling is required for inhibition of glucose production. Nat Med 8 , — Download citation. Received : 17 April Accepted : 21 October Published : 11 November Issue Date : 01 December Anyone you share the following link with will be able to read this content:.

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Skip to main content Thank you for visiting nature. nature nature medicine articles article. Abstract Circulating insulin inhibits endogenous glucose production. Access through your institution. Buy or subscribe. Change institution.

Learn more. Figure 1: Effect of ICV administration of insulin and insulin mimetic on glucose uptake and production. Figure 2: Antagonism of hypothalamic insulin action in the presence of peripheral hyperinsulinemia. Figure 3: Effect of ICV administration of insulin antagonists on peripheral and hepatic insulin action.

Figure 4: Effect of hypothalamic K ATP channels or melanocortin receptors blockade on peripheral and hepatic insulin action. References Taylor, S. Article CAS PubMed Google Scholar Sindelar, D. Article CAS PubMed Google Scholar Boden, G. Article Google Scholar Lewis, G. Article Google Scholar Rebrin, K.

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