Glucose Disposal of Low Birth Weight Infants: Steady State Hyperglycemia Produced by Constant Intravenous Glucose Infusion

PEDIATRICS ◽  
1979 ◽  
Vol 63 (3) ◽  
pp. 389-396 ◽  
Author(s):  
Richard M. Cowett ◽  
William Oh ◽  
Arnold Pollak ◽  
Robert Schwartz ◽  
Barbara S. Stonestreet

Tolerance for glucose was studied in 35 well, appropriate for gestational age, low birth weight (LBW) infants (mean birth weight, 1,216 gm; mean gestational age, 30 weeks) between 3 and 38 days of age. Infants were given a graded dose of glucose at 8.1, 11.2, or 14.0 mg/kg/min for three hours by continuous peripheral intravenous infusion. Plasma glucose and insulin, and timed urine glucose and volume were measured. A steady state of plasma glucose concentration was noted by one hour at all infusion rates. In the nine infants receiving 8.1 mg/kg/min, plasma glucose and insulin were similar to the baseline values during the steady state, and none of these infants evidenced glucosuria. In the 16 infants receiving 11.2 mg/kg/min, the plasma glucose concentration significantly increased (140 to 166 mg/dl) during the steady state but the plasma insulin levels were not significantly different compared to baseline. Half of these infants developed hyperglycemia (plasma glucose 150 mg/dl) and glucosuria. Ten infants receiving 14.0 mg/kg/min developed a significantly higher plasma glucose and plasma insulin response in colmparison to those infants who received 8.1 and 11.2 mg/kg/min, and all evidenced hyperglycemia and glucosuria. Glucosuria did not exceed 6.4 mg/kg/hr (0.1 mg/kg/min) so that glucose disposal (retention) exceeded 99% of intake, and an osmotic diuresis was not noted in those infants who had glucosuria. Our data suggested that in well LBW infants, a three-hour infusion of glucose up to 14.0 mg/kg/min (approximately 80 kcal/kg/day) did not produce an osmotic diuresis, but in the highest infusion group (14 mg/kg/min), hyperglycemia did occur. The effect of hyperglycemia in the neonate is unknown and needs to be investigated.

1992 ◽  
Vol 263 (5) ◽  
pp. E844-E849 ◽  
Author(s):  
K. A. Yunis ◽  
W. Oh ◽  
S. Kalhan ◽  
R. M. Cowett

To evaluate the mechanism(s) of the observed increase in plasma glucose concentration following the administration of an intravenous fat emulsion to the neonate, we measured glucose kinetics in eight low-birth-weight neonates by the prime constant rate infusion technique with D-[6,6-2H2]glucose at a rate of 0.22 +/- 0.01 mumol.kg-1 x min-1 (39.4 +/- 1.3 micrograms.kg-1 x min-1) while the neonates received 32 +/- 5 mumol.kg-1 x min-1 glucose (6.3 +/- 1.1 mg.kg-1 x min-1) plus an amino acid mixture (parenteral alimentation) alone and in combination with an intravenous fat emulsion (Intralipid). Following the latter combination, there were significant increases in plasma glucose concentration [4.07 +/- 0.11 (73 +/- 2 mg/dl) to 5.00 +/- 0.22 mmol/l (90 +/- 4 mg/dl); P < 0.01] and in plasma insulin concentration [72 +/- 14 (10 +/- 2 microU/ml) to 172 +/- 36 pmol/l (24 +/- 5 microU/ml); P < 0.05]. The parenteral alimentation and intravenous fat effusion combination did not affect the glucose production rate: 0.15 +/- 0.05 mumol.kg-1 x min-1 (0.03 +/- 0.01 mg.kg-1 x min-1) during the parenteral alimentation alone and 0.16 +/- 0.05 mumol.kg-1 x min-1 (0.03 +/- 0.01 mg.kg-1 x min-1) when parenteral alimentation was combined with an intravenous fat emulsion. We conclude that the increased plasma glucose concentration seen in association with administration of parenteral alimentation combined with an intravenous fat emulsion to the premature neonate is not due to enhanced glucose production but could be the result of alterations in glucose utilization.


2011 ◽  
Vol 106 (S1) ◽  
pp. S105-S109 ◽  
Author(s):  
Adrian K. Hewson-Hughes ◽  
Matthew S. Gilham ◽  
Sarah Upton ◽  
Alison Colyer ◽  
Richard Butterwick ◽  
...  

A charge made against feeding dry foods to cats is that the high carbohydrate (i.e. starch) content results in high blood glucose levels which over time may have detrimental health effects. The present study determined the post-meal concentrations of plasma glucose and insulin in adult cats (seven males and four females) and dogs (Labrador retrievers; four males and five females) fed dry diets with low-starch (LS), moderate-starch (MS) or high-starch (HS) levels. In a cross-over design with at least 7 d between the test meals, plasma glucose and insulin concentrations were measured following a single meal of a LS, MS and HS diet (209 kJ/kg bodyweight). Only the HS diet resulted in significant post-meal increases in plasma glucose concentration in cats and dogs although the time-course profiles were different between the species. In cats, plasma glucose concentration was significantly increased above the pre-meal concentration from 11 h until 19 h after the meal, while in dogs, a significant increase above baseline was seen only at the 7 h time point. Plasma insulin was significantly elevated in dogs 4–8 h following the MS diet and 2–8 h after the HS diet. In cats, plasma insulin was significantly greater than baseline from 3–7 and 11–17 h after the HS diet. The time lag (approximately 11 h) between eating the HS diet and the subsequent prolonged elevation of plasma glucose concentration seen in cats may reflect metabolic adaptations that result in a slower digestive and absorptive capacity for complex carbohydrate.


PEDIATRICS ◽  
1980 ◽  
Vol 66 (4) ◽  
pp. 561-567 ◽  
Author(s):  
Barbara S. Stonestreet ◽  
Loren Rubin ◽  
Arnold Pollak ◽  
Richard M. Cowett ◽  
William Oh

Hyperglycemia and glucosuria, which may lead to an osmotic diuresis, are often seen in low birth weight infants receiving glucose infusions during parenteral alimentation. This study was designed to examine the degree of glucose tolerance and the renal handling of glucose, solute, and water during intravenous glucose infusions in low birth weight infants. Twenty infants (mean birth weight, 1,170 gm; gestational age, 30 weeks) were studied between 1 and 20 days of age. At similar glucose infusion rates, 12 of 20 infants of lower gestational ages (29 ± 0.6 weeks, mean ± SEM) had higher plasma glucose concentrations and developed glucosuria while the remaining eight of 20 infants of higher gestations (31.4 ± 0.5 weeks, P &lt; .05) did not. In the glucosuric infants, there were significant increments in the filtered glucose load on the basis of increased plasma glucose concentrations and slightly higher glomerular filtration rates, although the changes of the latter were not statistically significant. The percentage of tubular reabsorption of glucose decreased and urinary excretion of glucose increased significantly with increased plasma glucose. Although urine flow remained unchanged, significant increments occurred in osmolar and sodium excretions. Exogenous glucose infusions in low birth weight infants resulted in a greater degree of hyperglycemia in the less mature infants and produced significant changes in the renal handling of glucose and sodium associated with significant, although slight, increments in solute excretion. In this series of six-hour glucose infusions, untoward effects of an osmotic diuresis (significant urine loss) were not observed.


2000 ◽  
Vol 164 (1) ◽  
pp. 1-6 ◽  
Author(s):  
CT Musabayane ◽  
O Munjeri ◽  
P Bwititi ◽  
EE Osim

We report successful oral administration of insulin entrapped in amidated pectin hydrogel beads in streptozotocin (STZ)-diabetic rats, with a concomitant reduction in plasma glucose concentration. The pectin-insulin (PI) beads were prepared by the gelation of humilin-pectin solutions in the presence of calcium. Separate groups of STZ-diabetic rats were orally administered two PI beads (30 micrograms insulin) once or twice daily or three beads (46 micrograms) once daily for 2 weeks. Control non-diabetic and STZ-diabetic rats were orally administered pectin hydrogel drug-free beads. By comparison with control non-diabetic rats, untreated STZ-diabetic rats exhibited significantly low plasma insulin concentration (0.32+/-0. 03 ng/ml, n=6, compared with 2.60+/-0.44 ng/ml in controls, n=6) and increased plasma glucose concentrations (25.84+/-1.44 mmol/l compared with 10.72+/- 0.52 mmol/l in controls). Administration of two PI beads twice daily (60 micrograms active insulin) or three beads (46 micrograms) once a day to STZ-diabetic rats increased plasma insulin concentrations (0.89+/-0.09 ng/ml and 1.85+/- 0.26 ng/ml, respectively), with a concomitant reduction in plasma glucose concentration (15.45+/-1.63 mmol/l and 10.56+/-0.26 mmol/l, respectively). However, a single dose of PI beads (30 micrograms) did not affect plasma insulin concentrations, although plasma glucose concentrations (17.82+/-2.98 mmol/l) were significantly reduced compared with those in untreated STZ-diabetic rats. Pharmacokinetic parameters in STZ-diabetic rats show that the orally administered PI beads (30 micrograms insulin) were more effective in sustaining plasma insulin concentrations than was s.c. insulin (30 micrograms). The data from this study suggest that this insulin-loaded amidated pectin hydrogel bead formulation not only produces sustained release of insulin, but may also reduce plasma glucose concentration in diabetes mellitus.


2011 ◽  
Vol 106 (S1) ◽  
pp. S101-S104 ◽  
Author(s):  
Adrian K. Hewson-Hughes ◽  
Matthew S. Gilham ◽  
Sarah Upton ◽  
Alison Colyer ◽  
Richard Butterwick ◽  
...  

Data from intravenous (i.v.) glucose tolerance tests suggest that glucose clearance from the blood is slower in cats than in dogs. Since different physiological pathways are activated following oral administration compared with i.v. administration, we investigated the profiles of plasma glucose and insulin in cats and dogs following ingestion of a test meal with or without glucose. Adult male and female cats and dogs were fed either a high-protein (HP) test meal (15 g/kg body weight; ten cats and eleven dogs) or a HP+glucose test meal (13 g/kg body-weight HP diet+2 g/kg body-weight d-glucose; seven cats and thirteen dogs) following a 24 h fast. Marked differences in plasma glucose and insulin profiles were observed in cats and dogs following ingestion of the glucose-loaded meal. In cats, mean plasma glucose concentration reached a peak at 120 min (10·2, 95 % CI 9·7, 10·8 mmol/l) and returned to baseline by 240 min, but no statistically significant change in plasma insulin concentration was observed. In dogs, mean plasma glucose concentration reached a peak at 60 min (6·3, 95 % CI 5·9, 6·7 mmol/l) and returned to baseline by 90 min, while plasma insulin concentration was significantly higher than pre-meal values from 30 to 120 min following the glucose-loaded meal. These results indicate that cats are not as efficient as dogs at rapidly decreasing high blood glucose levels and are consistent with a known metabolic adaptation of cats, namely a lack of glucokinase, which is important for both insulin secretion and glucose uptake from the blood.


1967 ◽  
Vol 45 (1) ◽  
pp. 29-38 ◽  
Author(s):  
Shafeek S. Sanbar ◽  
John R. Evans ◽  
Boniface Lin ◽  
Geza Hetenyi Jr.

Studies were carried out in anesthetized dogs to elucidate the mechanism of action of octanoate on glucose metabolism.Octanoate infusion in intact healthy dogs significantly decreased plasma glucose concentration, and in four out of seven dogs it raised plasma insulin concentration in peripheral blood. In contrast, intravenous administration of octanoate in four totally pancreatectomized dogs produced only small changes in plasma glucose concentration. These data suggest that the hypoglycemic action of octanoate may be mediated by increased secretion of insulin.The mean k value ([Formula: see text] of plasma glucose concentration) of intravenous glucose tolerance tests was significantly higher (2.38/minute) in healthy dogs that received an infusion of octanoate than in dogs that did not (1.2/minute). Octanoate also produced in healthy dogs greater increases in plasma insulin concentrations of peripheral blood during the tolerance tests. Furthermore, when delivered during a continuous intravenous administration of glucose (about 8 mg/kg per minute), octanoate infusion had no effect on either plasma glucose concentration or the rate of disappearance of glucose-U-14C from plasma to tissues. These findings indicate that octanoate does not impair glucose utilization in healthy dogs but actually improves tolerance of an intravenous glucose load, probably by stimulating greater release of insulin. These findings in vivo are discussed in the light of opposite effects of octanoate in vitro, to be described elsewhere, on glucose metabolism in the isolated heart and fat pad of rats.


1992 ◽  
Vol 12 (3) ◽  
pp. 448-455 ◽  
Author(s):  
Graeme F. Mason ◽  
Kevin L. Behar ◽  
Douglas L. Rothman ◽  
Robert G. Shulman

The concentration of intracerebral glucose as a function of plasma glucose concentration was measured in rats by 13C NMR spectroscopy. Measurements were made in 20–60 min periods during the infusion of [1-13C]d-glucose, when intracerebral and plasma glucose levels were at steady state. Intracerebral glucose was found to vary from 0.7 to 19 μmol g−1 wet weight as the steady-state plasma glucose concentration was varied from 3 to 62 m M. A symmetric Michaelis–Menten model was fit to the brain and plasma glucose data with and without an unsaturable component, yielding the transport parameters Km, Vmax, and Kd. If it is assumed that all transport is saturable ( Kd = 0), then Km = 13.9 ± 2.7 m M and Vmax/ Vgly = 5.8 ± 0.8, where Vgly is the rate of brain glucose consumption. If an unsaturable component of transport is included, the transport parameters are Km = 9.2 ± 4.7 m M, Vmax/ Vgly = 5.3 ± 1.5, and Kd/ Vgly = 0.0088 ± 0.0075 ml μmol−1. It was not possible to distinguish between the cases of Kd = 0 and Kd > 0, because the goodness of fit was similar for both. However, the results in both cases indicate that the unidirectional rate of glucose influx exceeds the glycolytic rate in the basal state by 2.4-fold and as a result should not be rate limiting for normal glucose utilization.


PEDIATRICS ◽  
1978 ◽  
Vol 61 (4) ◽  
pp. 546-549 ◽  
Author(s):  
Arnold Pollak ◽  
Richard M. Cowett ◽  
Robert Schwartz ◽  
William Oh

The effects of exogenous insulin administration on glucose disposal during steady-state hyperglycemia were evaluated in eight well, low-birth-weight (LBW) infants (mean birth weight 1,090 gm; mean gestation 29 weeks) at age 5 to 14 days. The study was performed on two consecutive days. On the first day, at midpoint during a four-hour constant glucose infusion (14 mg/kg/min), a placebo was given. The following day, insulin (10 mU/kg/min) replaced the placebo. Serum insulin level increased significantly during steady-state hyperglycemia on both days. In contrast to placebo, the administration of exogenous insulin resulted in normoglycemia. It is speculated that the hyperglycemia during glucose infusion in well LBW infants is the result of persistent endogenous hepatic glucose production and/or decreased peripheral glucose utilization, both of which could be due to ineffective mediation of insulin on the liver or other insulin-sensitive peripheral tissues. The prompt reduction in serum glucose level which occurs as a result of the administration of exogenous insulin further suggests that in LBW infants a higher insulin level is necessary to achieve the appropriate control of glucose homeostasis. During this study, no osmotic diuresis was observed since the quantity of urinary glucose did not constitute an osmolar load.


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