Glutamine contribution to gluconeogenesis in healthy adults fasted for 13 h, and 37 h

International audienc

Mini-dose glucagon rescue for mild hypoglycaemia in children with type 1 diabetes: The Brisbane experience

Objectives: To evaluate the use of small doses of glucagon using an insulin syringe in mild or impending hypoglycaemia in children with type 1 diabetes. Methods: Data were collected from patients attending the Paediatric Diabetes Clinic at the Queensland Diabetes Centre at the Mater Hospital, Brisbane in 2002-2004 following the institution of a new protocol for home management of mild or impending hypoglycaemia associated with inability or refusal to take oral carbohydrate. The protocol recommended the use of subcutaneous injections of glucagon using insulin syringes at a dose of two ' units ' (20 mu g) in children 2 years of age or younger, and for older children one unit per year of age up to a maximum of 15 units (150 mu g), with an additional doubled dose given if the blood glucose had not increased in 20 min. Results: Over a 2-year period, 25 children were treated with mini-dose glucagon on a total of 38 occasions. Additional doses were required for recurring hypoglycaemia on 20 (53%) occasions. The child could be managed at home on 32 (84%) of these 38 occasions, with only 6 (16%) children needing hospital treatment. Conclusions: Our study confirmed that small doses of glucagon given subcutaneously with an insulin syringe is a simple, practical and effective home treatment of mild or impending hypoglycaemia due to gastroenteritis or food refusal in children with type 1 diabetes

Apparent decreased oxidation and turnover of leucine during infusion of medium-chain triglycerides.

A potential effector of the protein-sparing adaptation to fasting could be the increased availability of endogenous long-chain fatty acids. Were this hypothesis correct, infusion of medium-chain triglycerides to increase the plasma concentration of medium-chain fatty acids might also result in protein sparing. However, in most in vitro studies in rat muscle, octanoate increases the oxidation of the essential amino acid leucine. Therefore leucine metabolism was assessed with infusions of [3H]leucine and a-[14C]ketoisocaproate ([14C]KIC) before and during an infusion of trioctanoin in conscious dogs. Plasma octanoate increased from less than 30 to 528 microM over the 3 h of infusion. Plasma leucine and KIC concentrations decreased by 65-70% (P less than 0.01) over the first 2 h of infusion. Leucine oxidation, estimated from the expired 14CO2 and the plasma [14C]KIC specific activity, as well as from an open two-pool model, decreased. By use of these isotope models, the rates of leucine coming from and going to protein decreased (P less than 0.05 to P less than 0.01). Interconversion of leucine and KIC estimated from the open two-pool model decreased by 80% (P less than 0.01). These changes were accompanied by a 36% decrease in the plasma concentration of total plasma amino acids. Within the confines of the isotope models employed, these data are consistent with the hypothesis that increased fatty acid oxidation decreases protein turnover and may spare essential amino acids

Effects of [15N]leucine infused at low rates on leucine metabolism in humans.

The present studies were carried out to determine whether infusions of [15N]leucine at low rates affect estimates of leucine oxidation and of proteolysis and protein synthesis in humans. Three groups of normal subjects were infused for 3 h with either [15N]leucine at a rate of 0.16 or 0.26 mumol X kg-1 X min-1 or saline using [2H3]leucine and alpha-[14C]ketoisocaproate as isotopic tracers of leucine metabolism. Data were analyzed at steady state using both single- and dual-isotope models. Preliminary studies were carried out to characterize the dual-isotope model in humans using infusions of [3H]leucine and alpha-[14C]ketoisocaproate. In the postabsorptive state estimates of leucine appearance, disappearance, and oxidation derived from the two isotope models were in good agreement. Infusion of stable isotope up to approximately 10% of the leucine carbon flux do not have a significant effect on leucine metabolism, but the data derived from such studies must be properly controlled and interpreted with care because these tracers are not massless

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

Regulation of whole-body leucine metabolism with insulin during mixed-meal absorption in normal and diabetic humans.

To determine the effects of insulin on dietary and endogenous leucine metabolism, five normal subjects, seven insulin-insufficient insulin-dependent (IDDM) diabetic patients, and five diabetic patients controlled with continuous subcutaneous insulin infusion (CSII) were studied before and for 8 h after ingestion of a chemically defined elemental test meal (10 cal/kg) containing crystalline amino acids. L-[1-14C]leucine was included in the meal to trace the entry and oxidation of the dietary leucine. Total (meal + endogenous) entry of leucine into the circulation was estimated with a constant infusion of [2H3]leucine. Postabsorptive and meal-related increases in the plasma leucine concentration were greater (P less than .05) in the insulin-insufficient IDDM than in the normal subjects but returned to near-normal values with CSII. Baseline leucine flux was approximately 40% greater in the insulin-insufficient IDDM than in normal subjects (2.17 +/- 0.17 vs. 1.55 +/- 0.15 mumol.kg-1.min-1, respectively; .05 less than P less than .01) but were near normal during CSII treatment (1.85 +/- 0.25 mumol.kg-1.min-1). Furthermore, total leucine entry during meal absorption was greater in the insulin-insufficient IDDM (1.41 +/- 0.10 mmol.kg-1.8 h-1) than in either normal (0.96 +/- 0.08 mmol.kg-1.8 h-1, P less than .01) or IDDM subjects during CSII treatment (1.09 +/- 0.11 mmol.kg-1.8 h-1, P less than .05). Fractional oxidation (approximately 40-50%) and entry of dietary leucine were similar in all three group

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