Glucose fluxes during OGTT in adolescents assessed by a stable isotope triple tracer method

Virtually no information is available on glucose fluxes during a meal or glucose ingestion in adolescents. AIM: To use a triple tracer approach to measure rates of appearance of ingested glucose (Ra(ogtt)), endogenous glucose production (EGP) and glucose disappearance (Rd) following an oral glucose bolus in adolescents. METHODS: Eleven adolescents (4 M/7 F, 15 +/- 1 yr; 67.3 +/- 4.7 kg; 24 +/-2 kg/m2) underwent a frequent sampled oral glucose tolerance test (OGTT) (labelled with [6,6-2H2]glucose) combined with intravenous infusion of [1-(13)C]glucose and [U-(13)C6]glucose following an overnight fast. Formulas were developed to estimate glucose fluxes using one- or two-compartment models. RESULTS: During the 7 h following the OGTT bolus, 9.8 +/- 2.3% of the ingested glucose was extracted by the liver, EGP was suppressed by 45 +/- 4% and Rd increased by 21 +/- 5%. CONCLUSIONS: The triple tracer method provided accurate assessment of Ra(ogtt), EGP and Rd fluxes during an OGTT in adolescents. Thus, this method might provide novel insight on postprandial glucose fluxes in children/adolescents under various conditions

Short-term high dietary fructose intake had no effects on insulin sensitivity and secretion or glucose and lipid metabolism in healthy, obese adolescents

There is virtually no information on the metabolic impact of dietary fructose intake in adolescents despite their high fructose consumption, particularly via sweetened beverages. AIM: To determine the short-term metabolic effects of dietary fructose intake in obese adolescents. METHODS: Six volunteers (3 M/3 F; 15.2 +/- 0.5 yr; 35 +/- 2 kg/m2; 39 +/- 2% body fat) were studied twice following 7 d of isocaloric, isonitrogenous high carbohydrate (60% CHO; 25% fat) diets with fructose accounting for 6% and 24% of total energy intake, respectively (random order). Insulin sensitivity and secretion were analyzed by the stable labeled intravenous glucose tolerance test and glucose and lipid kinetics using GCMS. RESULTS: A fourfold increase in dietary fructose intake did not affect insulin sensitivity or secretion, glucose kinetics, lipolysis or glucose, insulin, C-peptide, triglycerides, HDL- and LDL-cholesterol concentrations. CONCLUSIONS: In the short term, when energy intake is constant, dietary fructose per se is not a contributor to insulin resistance and hypersecretion in obese adolescents

Aerobic Exercise Increases Peripheral and Hepatic Insulin Sensitivity in Sedentary Adolescents.

CONTEXT: Data are limited on the effects of controlled aerobic exercise programs (without weight loss) on insulin sensitivity and glucose metabolism in children and adolescents. OBJECTIVE: To determine whether a controlled aerobic exercise program (without weight loss) improves peripheral and hepatic insulin sensitivity and affects glucose production (GPR), gluconeogenesis and glycogenolysis in sedentary lean and obese Hispanic adolescents. PATIENTS AND DESIGN: Twenty-nine post-pubertal adolescents (14 lean: 15.1 +/- 0.3 y; 20.6 +/- 0.8 kg/m(2); 18.9+/-1.5% body fat and 15 obese: 15.6 +/- 0.4 y; 33.2 +/- 0.9 kg/m(2); 38.4 +/- 1.4% body fat) (mean +/- SE), completed a 12 wk aerobic exercise program (4 x 30 min/week at >or=70% of VO(2) peak). Peripheral and hepatic insulin sensitivity and glucose kinetics were quantified using GCMS pre- and post-exercise. RESULTS: No weight loss occurred. Lean and obese participants complied well with the program ( approximately 90% of the exercise sessions attended, resulting in approximately 15% increase in fitness in both groups). Peripheral and hepatic insulin sensitivity were higher in lean than obese adolescents but increased in both groups; peripheral insulin sensitivity by 35 +/- 14% (lean) (p < 0.05) and 59 +/- 19% (obese) (p < 0.01) and hepatic insulin sensitivity by 19 +/- 7% (lean) (p < 0.05) and 23 +/- 4% (obese) (p < 0.01). GPR, gluconeogenesis and glycogenolysis did not differ between the groups. GPR decreased slightly, 3 +/- 1% (lean) (p < 0.05) and 4 +/- 1% (obese) (p < 0.01). Gluconeogenesis remained unchanged, while glycogenolysis decreased slightly in the obese group (p < 0.01). CONCLUSION: This well accepted aerobic exercise program, without weight loss, is a promising strategy to improve peripheral and hepatic insulin sensitivity in lean and obese sedentary adolescents. The small decrease in GPR is probably of limited clinical relevance

Glucose production, gluconeogenesis and insulin sensitivity in children and adolescents: an evaluation of their reproducibility

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. As a result we can anticipate an increased number of metabolic studies in children. There are few data on measures of glucose metabolism in normal children, and virtually none relating to their reproducibility. The aims of this study were 1) to provide new data on energy expenditure and glucose, lipid, and protein metabolism in nonobese, healthy children and adolescents; 2) to evaluate their reproducibility; and 3) on the basis of these data, to perform power calculations for metabolic studies. Eight nonobese subjects (8-16 y) were studied on two occasions, preceded by 7 d of a diet with identical energy content and macronutrient distribution. Gluconeogenesis, measured by deuterium oxide, accounted for 50% of glucose production. Insulin sensitivity, measured by the labeled minimal model, averaged 4.9 x 10(-4) mL(mU x min)(-1). Glucose appearance rate was significantly higher (p < 0.01) in the children than in the adolescents. Furthermore, we demonstrated that for energy intake and expenditure, plasma concentrations of glucose and C-peptide, and rates of appearance of glucose and leucine, a 10% difference can be detected in fewer than five subjects with a power of 80% and a type I error of 5%. Insulin concentration, gluconeogenesis, insulin secretory indices, insulin sensitivity, and glucose effectiveness were more variable, but with the above power a difference of 25% could be detected in 7-11 subjects using a paired study design

Effects of dietary macronutrient content on glucose metabolism in children

Effects of carbohydrate, fat, and fructose intake on substrate and hormone concentrations, glucose production, gluconeogenesis, and insulin sensitivity were determined in healthy, nonobese prepubertal children (n = 12) and adolescents (n = 24) using a cross-over design. In one group (12 prepubertal children and 12 adolescents), subjects were studied after 7 d of isocaloric, isonitrogenous diets providing either 60% carbohydrate and 25% fat [high carbohydrate (H(CHO))/low fat (L(F))] or 30% carbohydrate and 55% fat [low carbohydrate (L(CHO))/high fat (H(F))], and in a second group (12 adolescents) H(CHO)/L(F) diets containing either 40% or 10% fructose was used. All subjects adapted to changes in carbohydrate and fat intakes primarily by appropriately adjusting their substrate oxidation rates to match the intakes, with only minor changes in parameters of glucose metabolism. Changing from a L(CHO)/H(F) to H(CHO)/L(F) diet resulted in increased insulin sensitivity (stable labeled iv glucose tolerance test) in adolescents [from 3.2 +/- 0.7 x 10(-4) to 5.0 +/- 1.4 x 10(-4) (min(-1))/( micro U.ml(-1)) (mean +/- SE)] but not in prepubertal children [9.4 +/- 2.5 x 10(-4) to 9.9 +/- 1.5 x 10(-4) (min(-1))/( micro U.ml(-1))], whereas beta-cell sensitivity was unaffected in both groups. Insulin sensitivity was higher in prepubertal children than in adolescents (P < 0.05). The dietary fructose content did not affect any measured parameter. We conclude that in the short term, dramatic changes in fat and carbohydrate intakes (regardless of fructose content) did not adversely affect glucose and lipid metabolism in healthy nonobese children. In the adolescents, the high carbohydrate diet resulted in increased insulin sensitivity, thus facilitating insulin-mediated glucose uptake

Strength exercise improves muscle mass and hepatic insulin sensitivity in obese youth.

INTRODUCTION: Data on the metabolic effects of resistance exercise (strength training) in adolescents are limited. PURPOSE: The objective of this study was to determine whether a controlled resistance exercise program without dietary intervention or weight loss reduces body fat accumulation, increases lean body mass, and improves insulin sensitivity and glucose metabolism in sedentary obese Hispanic adolescents. METHODS: Twelve obese adolescents (age = 15.5 \ub1 0.5 yr, body mass index = 35.3 \ub1 0.8 kg\ub7m; 40.8% \ub1 1.5% body fat) completed a 12-wk resistance exercise program (two times 1 h\ub7wk, exercising all major muscle groups). At baseline and on completion of the program, body composition was measured by dual-energy x-ray absorptiometry, abdominal fat distribution was measured by magnetic resonance imaging, hepatic and intramyocellular fat was measured by magnetic resonance spectroscopy, peripheral insulin sensitivity was measured by the stable-label intravenous glucose tolerance test, and hepatic insulin sensitivity was measured by the hepatic insulin sensitivity index = 1000/(GPR 7 fasting insulin). Glucose production rate (GPR), gluconeogenesis, and glycogenolysis were quantified using stable isotope gas chromatography/mass spectrometry techniques. RESULTS: All participants were normoglycemic. The exercise program resulted in significant strength gain in both upper and lower body muscle groups. Body weight increased from 97.0 \ub1 3.8 to 99.6 \ub1 4.2 kg (P < 0.01). The major part ( 3c80%) was accounted for by increased lean body mass (55.7 \ub1 2.8 to 57.9 \ub1 3.0 kg, P 64 0.01). Total, visceral, hepatic, and intramyocellular fat contents remained unchanged. Hepatic insulin sensitivity increased by 24% \ub1 9% (P < 0.05), whereas peripheral insulin sensitivity did not change significantly. GPR decreased by 8% \ub1 1% (P < 0.01) because of a 12% \ub1 5% decrease in glycogenolysis (P < 0.05). CONCLUSIONS: We conclude that a controlled resistance exercise program without weight loss increases strength and lean body mass, improves hepatic insulin sensitivity, and decreases GPR without affecting total fat mass or visceral, hepatic, and intramyocellular fat contents