Decreased hypoglycemic effect of insulin at night in insulin-dependent diabetes mellitus and healthy subjects.

Diurnal variations in insulin-induced hypoglycemia and in plasma counterregulatory hormone concentrations were explored in eight insulin-dependent diabetic and six healthy subjects during a 100-min iv insulin infusion performed at 0300 h and 1500 h. In healthy subjects, plasma glucose concentrations (mean +/- SD) fell by 35 +/- 2% during the daytime test and by 26.5 +/- 2% during the nocturnal test (P less than 0.01). Plasma cortisol, GH, and epinephrine concentrations increased more during the daytime than during the nocturnal test. In contrast, plasma glucagon concentrations rose more during the nocturnal tests. In insulin-dependent diabetes mellitus patients, insulin infusion had to be interrupted in three subjects because plasma glucose fell below 1.9 mmol/L 80 min after the beginning of the test. In the other five patients plasma glucose fell by 34 +/- 5% during the daytime test while no significant decrease in plasma glucose was observed in any of the eight patients during the nighttime test. Counterregulatory hormone concentrations were consistent with the results of plasma glucose, with no change during the nocturnal test and significant increases in cortisol, GH, and epinephrine during the daytime test. These results show that insulin sensitivity is decreased at night in comparison to midafternoon in healthy subjects and that in insulin-dependent diabetes mellitus patients this phenomenon is exaggerated, even in patients with defective counterregulation to hypoglycemia.

Acute effect of glyburide on insulin sensitivity in type I diabetic patients.

Possible extrapancreatic effects of glyburide on insulin action were studied in six patients with insulin-dependent diabetes mellitus. Each patient was studied on two separate occasions with continuous iv infusions of either glyburide (0.3 mg/h after a 1-mg iv bolus dose) or NaCl. During the studies blood glucose concentrations were controlled by a glucose-controlled infusion system (Biostator). The study included the 12-h period after the evening meal, followed by a 4-h period during which euglycemic hyperinsulinemic clamp studies were performed at two rates of insulin infusion: 1 and 10 mU/kg.min. During the glyburide infusion, the Biostator-determined insulin delivery rate was similar to that during the NaCl infusion for the first 6 h after the meal, but it decreased by 32% between the 6th and 12th hours after the meal. During the hyperinsulinemic clamp studies, glucose was delivered at a significantly higher rate when glyburide was infused; this was true for both rates of insulin infusion [5.6 +/- 1.9 (+/- SD) vs. 3.6 +/- 1.4 mg/kg.min and 12.1 +/- 2.4 vs. 9.1 +/- 2.1 mg/kg.min; P less than 0.05, glyburide vs. NaCl, respectively]. Plasma C-peptide was undetectable in all patients during both studies. These results indicate that 1) glyburide has an acute effect on insulin action in insulin-dependent diabetic patients; and 2) this effect occurs at physiological as well as pharmacological insulin concentrations.

Serum bone Gla protein: a marker of bone turnover in hyperthyroidism.

Serum bone Gla protein (BGP) concentrations were measured in 24 hyperthyroid patients before and after treatment. Before treatment, the mean concentration was higher [11.8 +/- 3.4 ( +/- SD) ng/ml] in the patient group than in a group of 12 age-matched normal subjects (6.1 +/- 1.7 ng/ml; P less than 0.001); 16 of the 24 patients had a value above the normal range. Serum BGP concentrations in the patients correlated significantly with serum T3 (r = 0.65; P less than 0.001) and T4 concentrations (r = 0.56; P less than 0.01). Other biochemical markers of bone metabolism (serum alkaline phosphatase, serum and urinary calcium, and urinary hydroxyproline) did not correlate with circulating thyroid hormone levels. Serum BGP also was measured after the patients had become euthyroid; 23 measurements were made on 16 patients at various times after the start of treatment. All values were normal after 16 weeks; before this period, most of the values were still above the normal range despite normal plasma thyroid hormone concentrations in all patients. These results suggest that BGP is a sensitive marker of bone metabolism alterations during hyperthyroidism.

RU 486 prevents the acute effects of cortisol on glucose and leucine metabolism.

Glucocorticoids have deleterious effects on glucose and protein metabolism. RU 486 is an antiprogestin with antiglucocorticoid activity, which could be used to prevent the undesirable metabolic effects of glucocorticoids. A randomized, controlled, double blind study was performed in eight healthy male volunteers who were tested four times: during the iv infusion of cortisol (2 micrograms/kg.min for 5 h) after the oral ingestion of RU 486 (600 mg) or a placebo, and during the infusion of a normal saline solution with placebo or RU 486 ingestion. During each test, a primed continuous iv infusion of D-[6,6-2H]glucose and [1-13C-]leucine was given for the calculation of hepatic glucose production and plasma leucine appearance rate. 13CO2 enrichment in breath was measured for the calculation of leucine oxidation. Plasma concentrations of cortisol, ACTH, insulin, C-peptide, glucagon, and GH were measured at regular intervals. Compared to saline, cortisol infusion increased plasma glucose 5.5 +/- 0.6 vs. 4.7 +/- 0.4 mmol/L; P < 0.01) and leucine (179 +/- 35 vs. 155 +/- 35 mumol/L; P < 0.01) concentrations as well as the leucine appearance rate (2.24 +/- 0.3 vs. 2.0 +/- 0.28 mumol/kg.min; P < 0.05) and oxidation (0.51 +/- 0.22 vs. 0.39 +/- 0.06 mumol/kg.min; P < 0.01), and there was no change in hepatic glucose production. None of the metabolic changes induced by cortisol were seen when cortisol was administered after the ingestion of RU 486. When RU 486 was given before normal saline infusion, plasma glucose concentrations were transiently lower than those after placebo ingestion, as was the hepatic glucose production. No change in insulin, C-peptide, or glucagon was seen between tests. GH concentrations were higher during cortisol infusion, but not when cortisol was administered after the ingestion of RU 486. The following conclusions were reached. 1) RU 486 can suppress the effects of acute hypercortisolemia on glucose and protein metabolism and GH secretion in man. Long term studies are warranted to explore the potential of antiglucocorticoid molecules as preventive agents of the deleterious effects of chronic glucocorticoid administration. 2) RU 486 is useful molecule for studying the metabolic effects of cortisol in man.

PIP: In Montreal, Quebec, a randomized, double blind study was conducted in eight healthy men at Hotel-Dieu Hospital during administration of cortisol (2 mcg/kg per minute for 5 h) with RU-486 (600 mg), during cortisol administration with a placebo, during 0.9% saline administration with RU-486, and during normal saline administration with a placebo. Clinicians administered a primed continuous infusion of D-[6,6-2H]glucose and [1-13C-]leucine during each test to determine hepatic glucose production and plasma leucine appearance rate. Continuous infusion of labeled bicarbonate in four men was also conducted to calculate the recovery factor of carbon dioxide in their breath. Researchers wanted to examine glucose and protein metabolism during hypercortisolemia with or without RU-486 and the effects of RU-486 on the metabolic effects of acute cortisol deficiency. Among men receiving the placebo, plasma glucose levels were higher during cortisol infusion than saline infusion (5.5 vs. 4.7 mmol/l; p 0.01). The leucine appearance rate was also higher during cortisol infusion than saline infusion (2.24 vs. 2 mcmol/kg per min; p 0.05) as well as leucine oxidation (0.51 vs. 0.31 mcmol/kg; p 0.01). Hepatic glucose production did not change in either placebo group. Cortisol did not induce the same metabolic changes when it was administered after RU-486. Normal saline infusion after RU-486 induced a short-term lower plasma glucose level and hepatic glucose production. Insulin, C-peptide, or glucagon did not change. Cortisol induced increased growth hormone (GH) levels (e.g., at 240 min, 5.9 vs. 1.7 mcg/l; p 0.01) while GH levels did not change when cortisol was administered after RU-486. These findings show that RU-486 suppresses the effects of acute hypercortisolemia on glucose and protein metabolism and GH secretion in males. Long-term studies could reveal the potential of RU-486 to prevent the adverse effects of chronic glucocorticoid administration. RU-486 allows researchers to study the metabolic effects of cortisol in males.

Intragastric vs oral feeding: effect on the thermogenic response to feeding in lean and obese subjects.

The aim of this study was to observe the effects of oropharyngeal stimulation on thermogenic response to feeding (TRF) in obese and healthy individuals. Resting energy expenditure was measured in eight normal-weight (BMI, in kg/m2: 22.9 +/- 1.7) and nine obese subjects (BMI: 36.5 +/- 7.2), once after the ingestion of a standardized meal and once after the intragastric administration of the same, blenderized meal. In control subjects, TRF was lower after intragastric than after oral feeding: 5.6 +/- 1.4% vs 8.0 +/- 1.8% of the ingested energy for intragastric vs oral feeding, respectively (P < 0.01), but in obese subjects no difference occurred (6.5 +/- 3.0% vs 6.1 +/- 2.0%). In obese subjects the response over 6 h after the oral meal was lower than in/control subjects (P < 0.01). Intragastric TRF was not different between the two groups. This study confirms our previous observation that TRF has two components in humans, and suggests that oropharyngeal stimulation elicits a greater TRF in normal-weight than in obese individuals.

Effects of marginally negative energy balance on insulin binding to erythrocytes of normal men.

Six healthy male volunteers were confined to a metabolic unit for 105 days. Energy intake (EI) and energy expenditure (EE) were varied in order to achieve either a marginally negative (-15%) or an equilibrated energy balance (EB), in different metabolic periods (MP) as follows: MP I: EE = 1, EI = 1, EB = 0; MP II: EE = 1, EI = 0.85, EB = -15%; MP III: EE = 0.85, EI = 0.85, EB = 0; MP IV: EE = 0.85, EI = 0.70, EB = -15%; MP VI: EE = 1.15, EI = 1.15, EB = 0; MP VII: EE = 1.15, EI = 1, EB = -15%. An egg protein formula diet was fed throughout the study. The amount given in MP I was sufficient to maintain body weight constant. Assigned physical activity consisted of regulated walking and cycling. During MP I, this physical activity accounted for 15% of the energy intake. Serum insulin, insulin binding to erythrocytes and body fat content were determined at the end of each MP. No significant changes were found in serum insulin level throughout the study, but specific insulin binding did change significantly. Binding increased with increased physical activity by 23% at the end of MP VI and an additional 35% at the end of MP VII. The maximum percentage of insulin binding to erythrocytes correlated inversely with the percentage of body fat in each MP. These data suggest that insulin binding to erythrocytes, in normal men, is sensitive to a small change in energy balance, and especially to physical activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Hormonal changes in normal men under marginally negative energy balance.

Six men were confined to a metabolic unit for 105 days. Their assigned work and energy intake were varied throughout six metabolic periods in order to create either a marginally negative (-15%) or an equilibrated energy balance. They were fed a defined diet providing a constant amount of protein. At each metabolic period, T4, T3, reverse T3(rT3), free T3, free reverse T3, thyroid-stimulating hormone, cortisol, cortisol-binding globulin, testosterone, and testosterone/estradiol-binding globulin were measured. Free urinary cortisol was measured daily. Results show that serum thyroid hormones are sensitive to marginal changes in energy intake, expenditure, and balance. The ratio T4/T3 appears to be more sensitive to the balance itself, with the ratio T3/rT3 being more sensitive to the intake and expenditure level at which this balance is established. Regulations of T3 and rT3 production are probably distinct. Urinary cortisol did not show any variation that could be related to the energy balance. However, daily urinary cortisol was correlated to daily urinary nitrogen excretion. No change in serum testosterone was found.

Milk- and soy-protein ingestion: acute effect on serum uric acid concentration.

Acute effect of the ingestion of 80 g each of casein, lactalbumin, and soybean isolate on serum and urinary uric acid concentrations was investigated in 10 healthy subjects. Serum and urinary uric acid concentrations were measured before and after the ingestion of proteins. Serum uric acid decreased significantly 3 h after ingestion of lactalbumin and casein but increased after soybean consumption. Urate clearance was significantly increased after ingestion of each of the three proteins. Multivariate analysis of urate clearance during lactalbumin and casein loads showed that independent correlation was obtained for serum alanine and urea concentration. These results demonstrate that, in addition to their known uricosuric effect, milk proteins acutely decrease serum uric acid concentration. Analysis of the effects of lactalbumin and casein on urinary uric acid elimination suggests that the uricosuric effect of proteins is a multifactorial phenomenon.

No change in glucose tolerance and substrate oxidation after a high-carbohydrate, low-fat diet.

Possible changes in glucose tolerance and substrate oxidation after a high-carbohydrate, low-fat diet were studied in seven healthy volunteers. Each subject consumed two experimental diets for 1 week after 1 week on a stabilization diet; diet no. 1 11% fat and 64% carbohydrates, and diet no. 2 30% fat and 45% carbohydrates. At the end of each experimental week, plasma levels of glucose, insulin, and free fatty acids were measured before and every 30 minutes for 6 hours after a 75-g oral glucose challenge. At the same time, energy expenditure and substrate oxidation were measured by indirect calorimetry. Plasma lipid and lipoprotein levels were measured at the end of one stabilization period and at the end of each diet. Plasma glucose concentrations and areas under the curve of glucose concentrations were identical after the two experimental periods; the means +/- standard deviation for the values at 120 minutes were 6.4 +/- 0.3 and 6.4 +/- 0.6 mmol/L after diets no. 1 and 2, respectively, and areas under the curve were 1,853 +/- 115 and 1,862 +/- 211 mmol.min/L after diets no. 1 and 2, respectively. Similarly, plasma concentrations of insulin and free fatty acids after glucose ingestion were unaffected by the dietary changes. Energy expenditure increased after glucose administration, and this thermic effect of glucose was identical after the two experimental diets at 4.2% +/- 1.4%, and 3.9% +/- 1.4% of ingested energy for diets no. 1 and 2, respectively. Substrate oxidation rates were also identical for both the fasted and post-glucose periods after the two diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of moderate physical training on prednisone-induced protein wasting: a study of whole-body and bone protein metabolism.

This study investigated the possibility of preventing prednisone-induced protein wasting by regular physical activity. Eight healthy untrained volunteers took prednisone (30 mg/d for nine days), once after a 4-week exercise program that consisted of jogging 2.5 miles four times a week, and once without exercise. Whole body protein turnover was measured from the 15N enrichment plateau of urinary ammonia during ingestion of 15N glycine at hourly intervals. Whole-body protein synthesis and breakdown were derived from nitrogen flux, nitrogen intake, and urinary nitrogen elimination. Muscle myofibrillar protein breakdown was explored by measuring urinary 3-methylhistidine excretion. Bone protein metabolism was studied by measuring serum bone GLA protein (BGP), a specific marker of bone protein synthesis, and urinary elimination of hydroxyproline, an index of bone resorption. Whole-body protein turnover was significantly increased by exercise and prednisone (+19% and +17%, respectively); this effect was related to increased protein synthesis during exercise training (+27%, P less than .01) and to increased protein breakdown during prednisone administration without exercise (+21%, P less than .05). In contrast, values of protein turnover, synthesis, and breakdown were not different from control when the subjects took prednisone after training. Urinary excretion of 3-methylhistidine was decreased (-15%, P less than .05) at the end of the prednisone administration period but was identical to the control value when the subjects took prednisone in association with exercise. In contrast, serum BGP was significantly decreased by prednisone, with or without exercise (-35%, P less than .001). These data suggest that moderate exercise training can prevent, at least in part, the protein loss induced by prednisone.(ABSTRACT TRUNCATED AT 250 WORDS)

Improved clinical status and length of care with low-fat nutrition support in burn patients.

BACKGROUND: The optimal amount and type of fat in the nutrition support of burned patients have not been determined. The aim of this study was to test low-fat nutritional solutions, with or without fish oil, on protein metabolism, morbidity, and length of care in severely burned adults. METHODS: In a prospective randomized clinical trial, 43 patients were assigned to one of the following groups: control (35% fat), low-fat solution (ie, 15% of total calories as fat), low-fat with fish oil, given for 30 days. Nitrogen balance, urinary 3-methylhistidine excretion, urinary cortisol, and clinical status were measured daily. Corticosteroid-binding globulin and total and free serum cortisol were measured every 3 days. RESULTS: Compared with controls, patients on low-fat support had fewer cases of pneumonia: 3/24 vs 7/13 (p = .02), better respiratory and nutrition status, and shorter time to healing: 1.2 vs 1.8 days/% burned area (p = 0.01). There was no difference in nitrogen balance between groups, and 3-methylhistidine excretion was higher and serum free cortisol was lower in log-fat--fed patients than in controls. There was no difference between the two low-fat groups in any of the parameters measured. CONCLUSIONS: This study showed that low-fat nutrition support decreases infectious morbidity and shortens length of stay in burn patients. Fish oil does not seem to add clinical benefit to low-fat solutions. In addition, this study provides the first evidence that nutrition intervention modulates cortisol-binding globulin and the concentration of free circulating cortisol after a severe stress.

Thermogenic response to feeding in severely burned patients: relation to resting metabolic rate.

Energy expenditure (EE) was measured one to five times by indirect calorimetry for 1 h after an overnight fast, and for 2 h after starting feeding in 19 severely burned patients (TBSA > 20 per cent) for a total of 36 tests. Twelve tube-fed volunteers served as controls. Thermogenic response to feeding (TRF) was calculated as the percentage of energy intake and hypermetabolism as the percentage of values obtained with the Harris-Benedict formula (%HB). Measured energy expenditure values were compared with values given by three predicting formulae. TRF was present in 10 out of the 33 measurements. Fasting EE was not different between the tests with and without TRF, but %HB was different between the two groups: 121.1 +/- 25.8 vs 157.8 +/- 32.0 per cent (tests with and without TRF, respectively (P < 0.01)). TRF was always absent when %HB was higher than 50. When TRF was present it was not statistically different from the control values. None of the three predicting formulae gave values within 10 per cent of the measured values in more than 25 per cent of the patients. We conclude that TRF is suppressed in burned patients with marked hypermetabolism, and that EE measured in the fed state reflects resting expenditure accurately in these patients. In addition, EE cannot be predicted from existing formulae.

In vitro models to study wound healing fibroblasts.

Phenotypic and contractile properties of human fibroblasts from dermis and from an experimental wound model were studied in vitro. When cultured in monolayer, dermal fibroblasts had an elongated spindle shape, were small in diameter and grew at a high rate. Wound fibroblasts grew slowly and were large, star shaped and had cytoplasmic stress fibres. Smooth muscle alpha actin was detected in 10 percent of dermal cells, whereas 20-80 per cent of wound fibroblasts contained this protein in their cytoplasm. The contractile property of cells was evaluated using a three-dimensional cell culture model. Our results show that wound fibroblasts contract collagen gels during the first days more strongly than dermal fibroblasts. These results show that, in vitro, wound fibroblasts have greater contractile capacity than dermal cells. The significant proportion of wound fibroblasts containing alpha-smooth muscle actin suggests that alpha-smooth muscle actin ratio may be related to wound contraction.

Should we still use the Harris and Benedict equations?

Resting metabolic rate (RMR) is commonly predicted using the Harris-Benedict (HB) equations, but an overestimation of 10% to 15% is normally found. More recent studies have proposed equations with a better predictive value. In this study, we explore the relationship between measured RMR and HB in 67 healthy volunteers and in a data set from the literature and compared measured RMR with six more recent equations. Mean differences between RMR and HB were 21%, 12%, 10%, and 4% for the lowest to the highest RMR quartile, respectively, and 20%, 8%, 6%, and -4% for Owen's subjects. Among the six recent equations, only the World Health Organization (WHO) equations predicted RMR within 10% in 100% of the cases. Our results suggest that overestimation of RMR by HB is not a homogenous finding but is inversely related to RMR. This may have important implications for predicting RMR in women and in patients with diminished lean body mass. In addition, the WHO equations appear more precise than the HB equations.

Length of care in patients with severe burns with or without early enteral nutritional support. A retrospective study.

The possible influence of early enteral nutritional support on the length of care was explored retrospectively in 25 patients with burns greater than 20% total body surface area (TBSA). Patients were divided into two groups according to the time of their admission: group 1, from July 1986 to February 1987 (n = 12) and group 2, from July 1987 to January 1988 (n = 13). The only difference in treatment between the two groups was the start of early enteral nutritional support in group 2. Age, percent TBSA burned, surfaces of skin grafts, associated respiratory injury, and medical condition were identical in both groups. The following parameters were compared: lag time between hospital admission and the beginning of nutritional support, energy intake, nitrogen intake during the 4-week postadmission period, and length of care. A regression analysis including all patients was also performed to identify the factors associated with length of care. Lag time was shorter in group 2 than in group 1: 3 +/- 2 days versus 7 +/- 2 days (p less than 0.01). Group 2 received more energy than group 1 during the first 2 weeks after admission: 120 +/- 54 kj/kg/day versus 73 +/- 34 kj/kg/day (p less than 0.05) and 175 +/- 36 kj/kg/day versus 137 +/- 41 kj/kg/day (p less than 0.05) for the first and the second week, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Corticosteroid-binding globulin during inflammation and burn injury: nutritional modulation and clinical implications.

Corticosteroid-binding globulin (CBG) is the main carrier of glucocorticoids in mammals. Serum CBG shows little physiological variation with the exception of pregnancy. Experimental inflammation and burn injury decrease serum CBG in rats and while the mechanism of this effect is unknown, in vitro experiments suggest that interleukin-6 may be involved. In severely burned patients, we have found that CBG was markedly decreased within a few hours postinjury. This decrease lasted about 2 weeks and was accompanied by an increase in the free fraction of serum cortisol. In addition, serum CBG responded to dietary manipulation in these patients, with low fat feeding resulting in higher serum CBG concentrations and lower serum-free cortisol values. This feeding suggests that during severe stress, CBG may be important in regulating the amount of cortisol reaching target tissues such as the immune system and wounds.

Role of the autonomic nervous system in the thermogenic response to food in lean individuals.

The aim of this study was to determine the role of the autonomic nervous system (ANS) in obligatory and facultative components of the thermogenic response to food (TRF). Nineteen lean, healthy subjects participated in this study, which comprised two protocols, each exploring one component of the ANS. In the first experimental group, propranolol (prime: 80 micrograms/kg; continuous: 1 microgram.kg-1.min-1) was infused intravenously to inhibit sympathetic nervous activity (SNA), whereas in the second group atropine (prime: 5 micrograms/kg; continuous: 5 micrograms.kg-1.min-1) was used to inhibit parasympathetic nervous activity (PNA). The TRF was measured on four occasions: 1) after oral ingestion of a breakfast, during 0.9% NaCl perfusion, 2) after oral ingestion of the same breakfast, during the perfusion of one of the drugs, 3) after intragastric injection of a pureed form of the same meal as in part 1, during 0.9% NaCl perfusion, and 4) after intragastric feeding, during the administration of one of the drugs. Energy expenditure was measured by indirect calorimetry for 30 min before and 6 h after ingestion of the meal. Facultative TRF was defined as the difference between oral and intragastric TRF. Intragastric feeding significantly reduced TRF in both studies: 6.6 +/- 1.0 vs. 8.7 +/- 0.8% of the ingested energy in the SNA study and 5.5 +/- 1.6 vs. 7.4 +/- 3.1% in the PNA study. During propranolol infusion, TRF was significantly lower than it was during saline infusion after oral feeding (6.9 +/- 1.0% vs. 8.7 +/- 0.8% of ingested energy) but not after intragastric feeding. During atropine administration, TRF was reduced after both oral and intragastric feeding, although statistical significance was not reached in the latter. Atropine administration decreased gastric emptying (measured with an isotopic method) 2 h postingestion by 50%. These results show that the SNA is necessary for the facultative component of TRF to occur in humans. The role of the PNA appears to be related to its action on gastric emptying.

Decreased thermogenic response to food with intragastric vs. oral feeding.

To examine the effects of sensory stimulations associated with eating on postprandial energy expenditure, thermogenic response to food (TRF) was measured in nine subjects after ingestion of a test meal and after intragastric injection of the same pureed meal through a nasogastric tube. A third measure was made after ingestion of water and a fourth after chewing the meal without deglutition. Each measurement lasted 6 h. Intragastric injection of the meal elicited a lower TRF than oral ingestion in every subject, and this difference was seen whether TRF was calculated from the pretest energy expenditure (PTEE) or from energy expenditure measured after water ingestion (EEW) (175 +/- 57 vs. 83 +/- 32 and 209 +/- 68 vs. 106 +/- 45 kJ for PTEE and EEW, respectively; P less than 0.05 for each test). In both tests, changes in respiratory quotient, plasma glucose, and insulin were similar. Sensory stimulation by the meal without deglutition did not induce a significant change in energy expenditure. These results suggest that TRF has two components in humans, one of which is dependent on preabsorptive sensory stimulations. Lack of change in substrate oxidations between oral and intragastric feeding suggests that TRF related to preabsorptive stimulations does not depend on the preferential use of fatty acids or glucose as a source of fuel.

Effect of sustained hyperglycemia on GHRH induced GH secretion in man.

Effect of sustained and severe hyperglycemia (greater than 200 mg/dl) on GHRH induced GH secretion was studied in 9 healthy volunteers who received GHRH (1 microgram/kg/BW, iv) during either saline or dextrose infusions which were started 2 hours before testing. During the latter, plasma glucose concentration plateaued at 303 mg/dl +/- 82 (mean +/- SD, range 200-450 mg/dl). Hyperglycemia resulted in a 57% decrease of peak plasma GH concentration: 9.3 +/- 4 vs 21.8 +/- 12 ng/ml (P less than 0.05). Two subjects had no change in GHRH induced plasma GH rise during hyperglycemia. No correlation was found between plasma glucose or insulin concentrations and percentage change in GHRH induced GH secretion. These data suggest that: 1) inhibition by hyperglycemia of GHRH induced GH secretion in non-diabetic subjects is neigter complete nor constant; 2) plasma glucose levels cannot predict the magnitude of the inhibition.