Comparison of extracellular and net glucose oxidation measured isotopically and by indirect calorimetry during high and low glucose turnover

To determine the extent to which glucose oxidation measured by indirect calorimetry reflects glucose oxidation measured isotopically, subjects were studied during a 6-h hyperinsulinemic euglycemic clamp (1 mU.kg-1.min-1) and during infusion of saline. [6-14C]glucose was infused on both occasions. Breath was collected for determination of the specific activity of carbon dioxide, oxygen consumption, and carbon dioxide production. Glucose turnover during hyperinsulinemia was approximately eightfold higher than during saline infusion. During the final 1.5 h of the hyperinsulinemic glucose clamp, oxidation measured isotopically remained slightly but consistently lower (P less than 0.05) than that measured by indirect calorimetry (13.8 +/- 1.1 vs 16.5 +/- 1.7 mumol.kg-1.min-1, respectively). In contrast, during the saline infusion, glucose oxidation measured isotopically did not differ from that measured by indirect calorimetry (8.3 +/- 0.6 vs 7.2 +/- 2.8 mumol.kg-1.min-1, respectively). We conclude that although net glucose oxidation measured isotopically was slightly lower than that measured by indirect calorimetry, both techniques provide similar estimates of glucose oxidation over a wide range of glucose disposal.     

Increased insulin sensitivity in iron-deficient rats

Iron deficient (ID) and control (C) rats were studied to determine if severe iron deficiency alters insulin-stimulated glucose disposal. Euglycemic hyperinsulinemic glucose clamps were conducted by infusing insulin (2 m mu.kg-1.min-1, constant rate) for 120 min while maintaining euglycemia. In a 12-h fasted state, ID rats were hyperglycemic (109.4 +/- 4.0 mg.dL-1 arterial plasma glucose, x +/- SEM) when compared with C rats (86.9 +/- 3.4 mg.dL-1) (P less than 0.05). Even though insulin was infused identically on a per kilogram body weight basis for both groups, the resulting hyperinsulinemia was higher in ID rats (3.1 +/- 0.27 ng.mL-1) compared with C rats (2.3 +/- 0.4 ng.mL-1) at the end of the clamp. Glucose infusion rates required to maintain euglycemia were twofold higher in ID rats (27.0 +/- 5.4 mg.kg-1.min-1) versus C rats (13.1 +/- 3.3 mg.kg-1.min-1) (P less than 0.05). Circulating lactic acid increased in both groups, and the concentrations in ID rats (3.2 +/- 0.4 mmol.L-1) were significantly higher than those in C rats (1.8 +/- 0.5 mmol.L-1) at the end of the clamp. When the efficiency of insulin to dispose glucose was evaluated by calculating the glucose disposal divided by the prevailing insulinemia, ID rats could dispose of almost twice the glucose per unit of insulin [9.0 +/- 0.6 (mg.kg-1.min-1)/(ng.mL-1)] when compared with C rats [5.6 +/- 0.9 (mg.kg-1.min-1)/(ng.mL-1)] (P less than 0.05). The data indicate that insulin sensitivity is increased in ID rats and that ID rats cannot metabolize exogenous insulin as well as C rats.     

Differential effects of amino acid and ketoacid on protein metabolism in humans

We examined the effects of insulin, amino acid (AA), and branched-chain ketoacid (KA) availability on leucine kinetics in eight healthy volunteers (age = 22 +/- 2 y, body mass index = 24 +/- 1 kg) by using the euglycemic insulin clamp and [1-14C] leucine turnover techniques. Four experimental conditions were studied: study I, hyperinsulinemia; study II, hyperinsulinemia with maintenance of basal plasma AA and branched-chain KA concentrations; study III, hyperinsulinemia with hyperaminoacidemia and basal plasma branched-chain KA concentrations; and study IV, hyperinsulinemia plus basal plasma AA concentrations and elevated branched-chain KA levels. Basal endogenous leucine flux (ELF) averaged 1.20 +/- 0.05 (mumol.kg-1.min-1, mean +/- SE); basal leucine oxidation (LOX) was 0.25 +/- 0.01; and basal non-oxidative leucine disposal (NOLD) was 0.95 +/- 0.04. ELF significantly decreased in study I (0.77 +/- 0.06 mumol.kg-1.min-1, P < 0.01 versus basal). When plasma AA and branched-chain KA were either maintained at their basal levels (study II) or increased above baseline values (studies III and IV), ELF declined further (0.64 +/- 0.05, 0.66 +/- 0.02, and 0.66 +/- 0.03 mumol.kg-1.min-1, respectively; all Ps < 0.01 versus basal and P < 0.01 versus study I). LOX declined in study I (0.12 +/- 0.02 mumol.kg-1.min-1, P < 0.01 versus basal) but increased significantly in studies II, III, and IV (0.31 +/- 0.04, 0.37 +/- 0.03, and 0.40 +/- 0.03 mumol.kg-1.min-1, respectively, all Ps < 0.01 versus basal, P < 0.05 study IV versus study II, and P < 0.05 study III versus study II). NOLD declined in study I (0.65 +/- 0.05 mumol/kg.min, P < 0.01 versus basal), whereas neither the maintenance of basal plasma AA/branched-chain KA levels (study II; 0.89 +/- 0.2 mumol.kg-1.min-1) nor the elevation of plasma branched-chain KA concentration (study IV; 0.96 +/- 0.1 mumol.kg-1.min-1) increased NOLD above baseline level. A stimulation of NOLD was observed only when plasma AA levels were increased (study III; 1.23 +/- 0.03 mumol/kg.min, P < 0.01 versus basal). In conclusion, the present data do not support the concept of a direct anabolic action of ketoanalogs but do provide additional evidence for the pivotal role of AA availability in the stimulation of whole-body protein synthesis.     

Stimulation of thermogenesis in men after combined glucose-long-chain triglyceride infusion

The effect of combined long-chain triglyceride infusion (Intralipid 20%) with graded doses of insulin/glucose on energy expenditure was examined in 17 healthy young male volunteers by using the euglycemic insulin clamp technique in combination with indirect calorimetry. Intralipid was infused for 90 min at a constant rate of 0.23 g/min; plasma free fatty acids increased from base-line values of 380 +/- 8 mumol/l to steady state levels of 650 +/- 12 mumol/l. After 90 min the Intralipid was continued and insulin was infused at three rates (0.5, 2, and 4 mU/kg . min) to achieve steady state hyperinsulinemic plateaus of 63 +/- 4, 167 +/- 10, and 410 +/- 15 microU/ml. Plasma glucose concentration was maintained constant at basal euglycemic levels (insulin clamp technique) by infusing glucose at 0.24, 0.48, and 0.59 g/min, respectively. Glucose storage during the insulin clamp (ie, glucose uptake minus glucose oxidation) was 0.13, 0.33, and 0.40 g/min for each group and exogenous lipid storage was 0.17, 0.18, and 0.19 g/min, respectively. The net increment in energy expenditure was 0.15, 0.24, and 0.26 kcal/min, respectively, which represents 8.5% of the energy content of the total amount of glucose and lipid stored. The experimentally determined value (approximately 9%) for the cost of storing both glucose and lipid was found to be significantly greater than predicted by stoichiometric calculations. However, the experimental value for the combined infusion was less than that observed for glucose storage alone (12%). This finding provides support for the use of combined glucose/fat infusions in parenteral nutrition as it is used more economically than when glucose is infused alone.     

Effects of sucrose vs starch diets on in vivo insulin action, thermogenesis, and obesity in rats

High intake of simple sugars is generally seen as a detrimental factor in the etiology of both obesity and insulin resistance. To examine possible deleterious effects of sucrose, independent of changes in energy intake, rats were fed equal amounts of high-sucrose or high-starch diets over 4 wk. Energy expenditure was assessed by open-circuit respirometry and carcass analysis. In vivo insulin action in individual tissues was assessed with the hyperinsulinemic (1 nmol/L), euglycemic clamp combined with tracer glucose and 2-deoxyglucose administration. Whole-body glucose disposal was impaired by sucrose feeding (clamp glucose infusion rate of 77 +/- 4 vs 124 +/- 6 mumol/[kg.min], p less than 0.001, for sucrose and starch, respectively) because of a major impairment of insulin action at the liver with a smaller contribution from peripheral tissues. Sucrose feeding affected neither basal or stimulated energy expenditure nor accumulation of body fat. In conclusion, sucrose feeding produces a major impairment of insulin action, predominantly because of an effect at the liver.     

Role of basal insulin in the regulation of protein kinetics and energy metabolism in septic patients.

We have investigated the role of basal insulin concentration on leucine kinetics (determined by means of 1-[13C]leucine) and energy metabolism (determined by indirect calorimetry) in eight septic patients by reducing insulin (and glucagon) secretion by somatostatin infusion. Basal glucagon concentration was elevated (744 +/- 381 pg/mL), and insulin concentration was normal (10 +/- 4 microU/mL). Basal resting energy expenditure (REE) was 151 +/- 8% that of predicted basal energy expenditure, and leucine appearance (Ra), oxidation, and nonoxidative disposal rates were all elevated above the normal ranges. Somatostatin infusion reduced insulin concentration by 52% and glucagon concentration by 64%. This resulted in a significant increase in the rate of leucine oxidation from 0.96 +/- 0.08 to 1.18 +/- 0.14 mumol/kg/min (p less than 0.01), and nonoxidative leucine disposal decreased from 2.95 +/- 0.18 to 2.67 +/- 0.17 mumol/kg/min (p less than 0.01). Somatostatin infusion also caused significant increases in REE and fat oxidation from 1310 +/- 100 to 1505 +/- 128 kcal/m2/day (p less than 0.05) and from 1.72 +/- 0.24 to 2.41 +/- 0.41 mg/kg/min, respectively, and a slight decrease of carbohydrate oxidation from 1.51 +/- 0.49 to 1.31 +/- 0.49 mg/kg/min. These metabolic responses can be attributed to the reduction in insulin concentration, because they are in the opposite direction of changes that would occur as a consequence of a reduction in glucagon concentration. We conclude that the basal insulin plays an important role in attenuating net protein loss and energy expenditure.     

The effects of underfeeding for 7 d on the thermogenic and physiological response to glucose and insulin infusion (hyperinsulinaemic euglycaemic clamp)

The effect of underfeeding for 7 d (at 60 kJ/kg ideal body-weight) on the thermic and physiological responses to glucose and insulin infusions (hyperinsulinaemic euglycaemic clamp) was studied in six healthy women. Underfeeding had no significant effect on baseline metabolic rate, heart rate, forearm blood flow, diastolic blood pressure, blood intermediary metabolites, plasma insulin or catecholamines, but reduced both respiratory exchange ratio (RER; control (C) 0.86 (SE 0.02), underfed (U) 0.75 (SE 0.01); P less than 0.01) and systolic blood pressure (by approximately 10 mmHg, P less than 0.01). Baseline forearm glucose uptake and oxygen consumption were similar in both states. During the final 30 min of the glucose and insulin infusion, metabolic rate rose by 0.43 (SE 0.05) kJ/min in the C state, but no rise was seen in the U state (P less than 0.01). Glucose disposal rate (C 47.9 (SE 1.8), U 47.3 (SE 4.1) mumol/kg per min) and storage rate (C 27.5 (SE 2.4), U 31.6 (SE 3.6) mumol/kg per min) were similar in both states, but glucose oxidation rate was reduced in the U state (C 20.5 (SE 1.7), U 15.4 (SE 0.7) mumol/kg per min; P less than 0.05). RER rose to a higher value in the C state than in the U state (C 0.97 (SE 0.2), U 0.80 (SE 0.01); P less than 0.01). During hyperinsulinaemia, the forearm glucose uptake and O2 consumption rose in both states. No significant differences were seen in the cardiovascular responses to hyperinsulinaemia in either state. Thus underfeeding abolishes the rise in thermogenesis and reduces glucose oxidation during glucose and insulin infusions in healthy women, but does not affect the glucose disposal or storage rates or the other measured responses.     

High-carbohydrate, high-fiber diets increase peripheral insulin sensitivity in healthy young and old adults

To examine extra-alimentary effects of high-carbohydrate, high-fiber (HCF) diets, insulin-mediated glucose disposal employing the euglycemic clamp and hepatic glucose output (HGO) employing [6,6-2H2]glucose were measured in 12 healthy young and old individuals before and after 21-28 d of an HCF diet. Diet lowered fasting concentrations of glucose from 5.3 +/- 0.2 to 5.1 +/- 0.1 mmol/L (p less than 0.01) and insulin from 66.0 +/- 7.9 to 49.5 +/- 5.7 pmol/L (p less than 0.01). Fasting serum cholesterol decreased from 5.17 +/- 0.18 to 3.80 +/- 0.20 mmol/L (p less than 0.01) in young individuals and from 6.15 +/- 0.52 to 4.99 +/- 0.49 mmol/L (p less than 0.01) in elderly individuals. Fasting serum triglyceride concentrations, basal HGO, and insulin suppression of HGO were unchanged by the diet. Glucose disposal rates increased from 18.87 +/- 1.66 before 23.87 +/- 2.78 mumol.kg-1.min-1 after the diet (p less than 0.02). Therefore, HCF diets may improve carbohydrate economy by enhanced peripheral sensitivity to insulin.     

Whole-body protein anabolic response is resistant to the action of insulin in obese women

BACKGROUND: Obesity is associated with insulin resistance of glucose and lipid metabolism. OBJECTIVE: We sought to determine the effects of obesity on the insulin sensitivity of protein metabolism. DESIGN: Whole-body [(13)C]leucine and [(3)H]glucose kinetics were measured in 9 lean and 10 obese women in the postabsorptive state and during a hyperinsulinemic, euglycemic, isoaminoacidemic clamp. RESULTS: In the postabsorptive state, the leucine endogenous rate of appearance (catabolism), normalized for fat-free mass, was 11% greater and the nonoxidative rate of disappearance (synthesis) was 8% greater in the obese than in the lean women, but net balance was 29% more negative (P < 0.05). Clamp amino acid and glucose infusion rates were significantly lower in the obese women than in the lean women (0.65 +/- 0.02 compared with 0.85 +/- 0.04 and 5.7 +/- 0.3 compared with 9.1 +/- 0.5 mg x kg fat-free mass(-1) x min(-1), respectively; P < 0.0001 for both), and their rates correlated positively (r = 0.635, P = 0.005). During hyperinsulinemia, synthesis was stimulated less and net leucine balance was much lower in the obese women than in the lean women (-0.08 +/- 0.06 and 0.30 +/- 0.03 mumol x kg fat-free mass(-1) x min(-1), respectively; P < 0.0001). The percentage change in net leucine balance correlated negatively with all adiposity indexes. Plasma free fatty acids were less suppressed and the respiratory quotient was lower in the obese women than in the lean women. CONCLUSION: Obese women show a blunted protein anabolic response to hyperinsulinemia that is consistent with resistance to the action of insulin on protein concurrent with that on glucose and lipid metabolism.     

Effect of DL-3-hydroxybutyrate infusions on leucine and glucose kinetics in burned rats receiving TPN

Whole-body leucine and plasma glucose kinetics were simultaneously measured in burned rats after 2 d of total parenteral nutrition (TPN) containing sodium DL-3-hydroxybutyrate or sodium acetate to evaluate the ketone bodies as energy substrates during stress. TPN solutions consisted of dextrose and amino acids [200 kcal/(kg . d); 13 g amino acids/(kg . d)] and contained 34.3 mEq/(kg . d) either as sodium DL-3-hydroxybutyrate (n = 8) or sodium acetate (n = 7). Whole-body leucine appearance, incorporation into protein, release from protein breakdown and oxidation rates, as measured after a constant infusion of L-[1-14C]leucine did not significantly differ between the groups. In contrast, D-[6-3H]glucose appearance rates after constant infusion of this tracer were significantly higher in rats given sodium DL-3-hydroxybutyrate [209.3 +/- 3.8 mumol/(kg body weight . min)] than in those given sodium acetate [162.4 +/- 9.7 mumol/(kg body weight . min)] (P less than 0.01). Since leucine kinetics did not differ, the results suggest that sodium DL-3-hydroxybutyrate infusions increase endogenous glucose production [61.0 +/- 4.6 mumol/(100 kg body weight . min)] by enhancing glucose recycling. However, there was no unique protein-sparing effect of ketone bodies identified during injury.     

Insulin resistance in nondiabetic morbidly obese patients: effect of bariatric surgery

OBJECTIVE: To evaluate insulin action on substrate use and insulinemia in nondiabetic class III obese patients before and after weight loss induced by bariatric surgery. RESEARCH METHODS AND PROCEDURES: Thirteen obese patients (four men/nine women; BMI = 56.3 +/- 2.7 kg/m2) and 13 lean subjects (five men/eight women; BMI = 22.4 +/- 0.5 kg/m2) underwent euglycemic clamp, oral glucose tolerance test, and indirect calorimetry. The study was carried out before (Study I) and after ( approximately 40% relative to initial body weight; Study II) weight loss induced by Roux-en-Y Gastric bypass with silastic ring surgery. RESULTS: The obese patients were insulin resistant (whole-body glucose use = 19.7 +/- 1.5 vs. 51.5 +/- 2.4 micromol/min per kilogram fat-free mass, p < 0.0001) and hyperinsulinemic in the fasting state (332 +/- 86 vs. 85 +/- 5 pM, p < 0.0001) and during the oral glucose tolerance test compared with the lean subjects. Fasting plasma insulin normalized after weight loss, whereas whole-body glucose use increased (35.5 +/- 3.7 micromol/min per kilogram fat-free mass, p < 0.05 vs. Study I). The higher insulin clearance of obese did not change during the follow-up period. Insulin-induced glucose oxidation and nonoxidative glucose disposal were lower in the obese compared with the lean group (all p < 0.05). In Study II, the former increased slightly, whereas nonoxidative glucose disposal reached values similar to those of the control group. Fasting lipid oxidation was higher in the obese than in the control group and did not change significantly in Study II. The insulin effect on lipid oxidation was slightly improved (p = 0.01 vs. Study I). DISCUSSION: The rapid weight loss after surgery in obese class III patients normalized insulinemia and improved insulin sensitivity almost entirely due to glucose storage, whereas fasting lipid oxidation remained high.     

Protein metabolism in obesity: effects of body fat distribution and hyperinsulinemia on leucine turnover

To examine whether moderate obesity and differences in body fat distribution are associated with abnormalities of protein metabolism, leucine turnover was measured in three groups of age-matched premenopausal women. Ten upper-body-obese (UB Ob), 10 lower-body-obese (LB Ob), and 10 nonobese (Non Ob) women were studied in an overnight postabsorptive condition (basal) and again during an infusion of low physiologic amounts of insulin (insulin clamp). Results showed that basal leucine carbon flux was greater (P less than 0.05) in UB Ob and LB Ob women than in Non Ob women (2.96 +/- 0.08 vs 3.14 +/- 0.16 vs 2.68 +/- 0.08 mumol.kg lean body mass-1.min-1, respectively; mean +/- SEM). Leucine carbon flux was not suppressed during the insulin-clamp study in UB Ob women but was in the LB Ob and Non Ob women. We conclude that moderate obesity is associated with increased proteolysis and that insulin's antiproteolytic actions are impaired in upper-body obesity. These findings could have implications for future studies of and treatment of obesity.     

Body composition, energy utilization, and nitrogen metabolism with a 4.25-MJ/d low-energy diet supplemented with pyruvate.

We measured body composition, energy deficit, and nitrogen metabolism in 14 obese women housed in a metabolic ward, who consumed a 4.25-MJ/d liquid diet (68% carbohydrate, 22% protein) for 21 d with or without pyruvate (PY; n = 7) partially, isoenergetically substituted for glucose (placebo; n = 7). Body composition and leucine oxidation and turnover were determined before and after weight loss. Energy deficit was calculated from resting metabolic rates. Subjects fed pyruvate showed a greater weight loss (PY = 5.9 +/- 0.7 kg, placebo = 4.3 +/- 0.3 kg, P less than 0.05), fat loss (PY = 4.0 +/- 0.5 kg, placebo = 2.7 +/- 0.2 kg, P less than 0.05), kg wt loss/4.25-MJ deficit (PY = 0.22 +/- 0.01 kg, placebo = 0.17 +/- 0.01 kg, P less than 0.05, and kg fat loss/4.25-MJ deficit (PY = 0.15 +/- 0.01 kg, placebo = 0.11 +/- 0.01 kg, P less than 0.05). Nitrogen balance (urine and stool) and leucine oxidation and turnover were similar in both groups. We conclude that the dietary modification whereby the three-carbon compound pyruvate is isoenergetically substituted for the six-carbon compound glucose in a 4.25-MJ/d, low-energy diet will increase fat and weight loss.     

Dietary fat content alters insulin-mediated glucose metabolism in healthy men

BACKGROUND: A high dietary fat intake is involved in the pathogenesis of insulin resistance. OBJECTIVE: The aim was to compare the effect of different amounts of dietary fat on hepatic and peripheral insulin sensitivity. DESIGN: Six healthy men were studied on 3 occasions after consuming for 11 d diets with identical energy and protein contents but different percentages of energy as fat and carbohydrate as follows: 0% and 85% [low-fat, high-carbohydrate (LFHC) diet], 41% and 44% [intermediate-fat, intermediate-carbohydrate (IFIC) diet], and 83% and 2% [high-fat, low-carbohydrate (HFLC) diet]. Insulin sensitivity was quantified by using a hyperinsulinemic euglycemic clamp (plasma insulin concentration: approximately 190 pmol/L). RESULTS: During hyperinsulinemia, endogenous glucose production was higher after the HFLC diet (2.5 +/- 0.3 micromol x kg(-1) x min(-1); P < 0.05) than after the IFIC and LFHC diets (1.7 +/- 0.3 and 1.2 +/- 0.4 micromol x kg(-1) x min(-1), respectively). The ratio of dietary fat to carbohydrate had no unequivocal effects on insulin-stimulated glucose uptake. In contrast, insulin-stimulated, nonoxidative glucose disposal tended to increase in relation to an increase in the ratio of fat to carbohydrate, from 14.8 +/- 5.1 to 20.6 +/- 1.9 to 26.2 +/- 2.9 micromol x kg(-1) x min(-1) (P < 0.074 between the 3 diets). Insulin-stimulated glucose oxidation was significantly lower after the HFLC diet than after the IFIC and LFHC diets: 1.7 +/- 0.8 compared with 13.4 +/- 2.1 and 19.0 +/- 2.1 micromol x kg(-1) x min(-1), respectively (P < 0.05). During the clamp study, plasma fatty acid concentrations were higher after the HFLC diet than after the IFIC and LFHC diets: 0.22 +/- 0.02 compared with 0.07 +/- 0.01 and 0.05 +/- 0.01 mmol/L, respectively (P < 0.05). CONCLUSION: A high-fat, low-carbohydrate intake reduces the ability of insulin to suppress endogenous glucose production and alters the relation between oxidative and nonoxidative glucose disposal in a way that favors storage of glucose.     

Glucose metabolism in advanced lung cancer patients.

Although it is generally accepted that altered nutrient intake and metabolism are responsible for the progressive loss of body weight observed in most advanced cancer patients, there is still considerable controversy regarding the contributory role of changes in both resting energy expenditure (REE) and glucose metabolism. Several studies suggest increases in both REE and glucose appearance in advanced cancer patients compared with healthy control subjects, whereas others revealed no changes in either metabolic parameter. We measured REE with indirect calorimetry and glucose kinetics with a primed constant infusion of D-[U-14C]glucose and D-[6-3H]glucose over the last 4 h of a 24-h fast in 32 advanced lung cancer patients immediately after diagnosis and before any chemotherapy or radiotherapy and in 19 healthy volunteer subjects. REE for the lung cancer group was not significantly different from that in the control group (1535.8 +/- 78.0 vs. 1670.2 +/- 53.9 kcal/day, respectively, p = 0.151). When REE was expressed as a function of body weight, or lean body mass, no differences between the two groups were observed. The rate of glucose appearance was 9.88 +/- 0.36 mumol.kg-1.min-1 in the cancer patients and 10.15 +/- 0.53 mumol.kg-1.min-1 in control subjects (p = 0.667), of which 50.4 versus 58.2%, respectively, was oxidized. The amount of glucose recycled was 13.54 +/- 1.22% in cancer patients and 15.08 +/- 0.99% in control subjects (p = 0.394). The amount of VCO2 from direct oxidation of glucose was 23.39 +/- 0.74% in cancer patients and 27.45 +/- 1.36% in control subjects (p = 0.006).(ABSTRACT TRUNCATED AT 250 WORDS)     

Caffeine ingestion increases the insulin response to an oral-glucose-tolerance test in obese men before and after weight loss

BACKGROUND: Caffeine ingestion decreases the insulin sensitivity index (ISI) for an oral-glucose-tolerance test (OGTT) and decreases insulin-induced glucose disposal in lean male subjects during a hyperinsulinemic clamp. OBJECTIVE: We examined the effects of caffeine ingestion on insulin and glucose homeostasis in obese men before and after a nutrition and exercise intervention. DESIGN: Nine sedentary, obese [body mass index (in kg/m(2)): 34.0 +/- 1.0] men who had refrained from exercise and caffeine ingestion for 48 h underwent 2 oral-glucose-tolerance tests (OGTTs). The subjects randomly received caffeine (5 mg/kg) or placebo 1 h before each OGTT. After a 12-wk nutrition and exercise intervention, during which time the subjects avoided dietary caffeine, the OGTTs were repeated. RESULTS: The intervention resulted in decreases (P < or = 0.05) in body weight (8.5 +/- 1.5 kg), percentage body fat (2.8 +/- 0.7%), and fasting glucose, insulin, and proinsulin concentrations and increases in the ISI for the placebo OGTT (P < or = 0.05). Caffeine caused a greater (P < or = 0.05) OGTT insulin response and a lower (P < or = 0.05) ISI both before and after weight loss. The proinsulin-insulin ratio indicated that neither weight loss nor caffeine affected the nature of the beta cell secretion of insulin. CONCLUSIONS: A nutrition and exercise intervention improved, whereas caffeine ingestion impaired, insulin-glucose homeostasis in obese men. The results are consistent with previous findings that caffeine ingestion contributes to insulin resistance.     

Recovery of [13C]-bicarbonate as respiratory 13CO2 in parenterally fed infants

Ten infants on continuous total parenteral nutrition (TPN) were infused with NaH13CO3 for 6 h in order to assess the amount of 13C recovered as breath 13CO2. Protein intake was 2.8 +/- 0.3 g/kg/d and non-protein energy intake 107 +/- 4 kcal/kg/d (447 +/- 18 kJ/kg/d), provided either as glucose alone or as an isoenergetic glucose-lipid mixture. In the five infants receiving glucose as the sole non-protein energy source, total CO2 production (559 +/- 50 mumol/kg/min), natural 13C abundance of breath CO2 (-11.8 +/- 0.6 delta % versus PDB) and basal 13CO2 production (6.1 +/- 0.6 mumol/kg/min) were higher than in the five infants infused the glucose-lipid mixture (465 +/- 30 mumol/kg/min, P less than 0.02; -16.1 +/- 0.5 delta %, P less than 0.01 and 5.0 +/- 0.3 mumol/kg min, P less than 0.02, respectively). There was a good agreement, in the glucose-infused infants, between the net glucose oxidation rate measured by indirect calorimetry (25.6 +/- 2 g/kg/d) and the glucose oxidation rate estimated from the 13C natural abundances of breath CO2 and infused substrates (23.5 +/- 3 g/kg/d). Steady state 13C enrichment of breath CO2 was reached in all infants after 120 min infusion and ranged from 11.0 to 21.5 delta % over baseline. Steady state 13C enrichment was negatively related to total CO2 production (r = -0.72; P less than 0.02). In contrast, steady state 13CO2 production in excess of baseline was only correlated to bicarbonate infusion rate (r = 0.95; P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of preexercise ingestion of modified cornstarch on substrate oxidation during endurance exercise

The purpose of this study was to investigate differences in substrate oxidation between dextrose (DEX) and unmodified (UAMS) and acid/alcohol-modified (MAMS) cornstarches. Seven endurance-trained men (VO2peak = 59.1 +/- 5.4 mL.kg-1.min-1) participated in 2 h of exercise (66.4% +/- 3.3% VO2peak) 30 min after ingesting 1 g/kg body weight of the experimental carbohydrate or placebo (PLA). Plasma glucose and insulin were elevated after DEX (P < 0.05) compared with UAMS, MAMS, and PLA. Although MAMS and DEX raised carbohydrate oxidation rate through 90 min of exercise, only MAMS persisted throughout 120 min (P < 0.05 compared with all trials). Exogenous-carbohydrate oxidation rate was higher in DEX than in MAMS and UAMS until 90 min of exercise. Acid/alcohol modification resulted in augmented carbohydrate oxidation with a small, sustained increase in exogenous-carbohydrate oxidation rate. MAMS appears to be metabolizable and available for oxidation during exercise.     

Energy metabolism and substrate oxidation in patients with Crohn's disease

Weight loss and malnutrition are common features in patients with Crohn's disease. This study was designed to evaluate diet-induced thermogenesis and substrate oxidation in patients with Crohn's disease. Twenty-three patients (17 women, 6 men; age 34 +/- 2 y) and 17 healthy control subjects (13 women, 4 men; age 36 +/- 3 y) were studied. Resting energy expenditure and fasting substrate oxidation were measured by indirect calorimetry in the morning after an overnight fast. After a standard homogenized test meal (10 kcal/kg), indirect calorimetry was performed every 30 min for 3 h to measure the diet-induced thermogenesis and the postprandial substrate oxidation. In the fasting state, resting energy expenditure was significantly higher in patients than in control subjects (1433 +/- 43 versus 1279 +/- 53 kcal/24 h). Lipid oxidation was higher in patients with Crohn's disease than in control subjects (1.17 +/- 0. 07 versus 0.61 +/- 0.11 mg. kg(-1). min(-1), P < 0.01). Postprandially, diet-induced thermogenesis was significantly lower in patients with Crohn's disease than in control subjects (4.6% +/- 0.5 versus 6.3% +/- 0.5 of energy intake, P < 0.01). Lipid oxidation was significantly higher in patients with Crohn's disease than in control subjects (0.78 +/- 0.05 versus 0.56 +/- 0.08 mg. kg(-1). min(-1), P < 0.05), and glucose oxidation was lower in patients with Crohn's disease than in control subjects. In patients with Crohn's disease, lipid oxidation positively correlates with the disease activity evaluated by the Crohn's Disease Activity Index (r = 0.48, P150), fasting and postprandial lipid oxidation was significantly higher than in patients with inactive Crohn's disease (P < 0.05). In conclusion, patients with Crohn's disease have increased fat oxidation, which correlates with disease activity and this may explain the reduced fat stores in patients with Crohn's disease.     

Glucose metabolism and thermogenesis during glucose and insulin infusion in severely underweight patients.

This study investigates the effects of gross loss of body weight on glucose disposal (GD), storage (GS), oxidation (GO), and the thermogenic response (TR) during hyperinsulinemic euglycemic glucose infusion in 9 underweight but nourished patients (UP) and in 3 of the patients after weight gain (WGP). In UP, baseline metabolic rate (MR) was 4.1 +/- 0.2 kJ/min and respiratory exchange ratio (RER) 0.97 +/- 0.02. During the final 30 minutes of hyperinsulinemia MR rose by 0.32 +/- 0.07 kJ/min (p less than .01) and RER rose to 1.09 +/- 0.03 (p less than .01). GD was 61 +/- 3 mumol/kg per minute, GO 35 +/- 1 mumol/kg per minute, and GS 26 +/- 4 mumol/kg per minute. The energy cost of glucose storage as glycogen was 0.15 kJ/min, and as lipid was 0.2 kJ/min. In WGP baseline MR was 4.5 +/- 0.4 kJ/min and RER was 0.91 +/- 0.03. During hyperinsulinemia MR rose by 0.63 +/- 0.2 kJ/min, RER rose to 0.93 +/- 0.02, GD was 53 +/- 4 mumol/kg per minute, GO was 30 +/- 3 mumol/kg per minute, and GS was 23 +/- 1 mumol/kg per minute. The energy cost for this glucose storage was 0.22 kJ/min. Therefore, during hyperinsulinemia in UP, GD, and TR are similar, but GO is greater and GS is less than previously reported in healthy subjects. However, this TR is entirely accounted for by the energy cost of glucose storage with no evidence of facultative thermogenesis. In WGP, all responses were similar to those in healthy subjects, and the TR was in excess of that required of the energy cost of glucose storage.