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Biomedical subjects

R M Cowett

Publications and source records attributed to R M Cowett.

At least 37 records · Page 2Linked to original sources
PubMed1988

Alpha-adrenergic agonists stimulate neonatal glucose production less than beta-adrenergic agonists in the lamb.

Epinephrine, a catecholamine with both alpha (alpha)- and beta (beta)-adrenergic agonist effects, may produce clinical hyperglycemia in the adult by increasing glucose production and decreasing glucose clearance. However, the relative contribution of alpha v beta adrenergic agonists in control of neonatal glucose kinetics has not been defined. Twenty-three term lambs (weighing 4.4 +/- 0.2 kg, mean +/- SEM, and aged 3.8 +/- 0.4 days) were infused with 0.9% NaCl at 0.6 mL.kg-1 min-1 + 100 microCi/kg D[6-3H]-glucose by prime plus constant infusion for 210 minutes. Ra (rate of production) was measured during infusion of variable doses of epinephrine with or without variable doses of propranolol, a competitive beta-adrenergic antagonist to isolate the alpha-adrenergic agonist effects. All basal kinetic data were comparable. Under conditions of epinephrine infusion, the plasma glucose concentration increased from 95 +/- 10 mg/dL to 129 +/- 18 mg/dL (50 ng.kg-1 min-1 epinephrine; P less than .0001) and from 85 +/- 6 mg/dL to 253 +/- 8 mg/dL (500 ng.kg-1 min-1 epinephrine; P less than .00001) compared with controls (96 +/- 7 mg/dL to 95 +/- 8 mg/dL). When epinephrine and propranolol were infused simultaneously, plasma glucose concentration increased from 95 +/- 10 mg/dL to 122 +/- 12 mg/dL (50 ng.kg-1 min-1 epinephrine + 1.1 micrograms.kg-1 min-1; P less than .0001) and from 78 +/- 9 mg/dL to 134 +/- 12 mg/dL (500 ng.kg-1 min-1 epinephrine + 11 micrograms.kg-1 min-1; P less than .0001) compared with controls (no epinephrine, no propranolol).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMed1988

Ontogeny of glucose homeostasis in low birth weight infants.

Suppression of the endogenous glucose production rate (Ra) is the adult response to glucose infusion. Persistent Ra (greater than or equal to 1 mg.kg-1min-1 or less than 80% decrease in basal Ra) in response to glucose infusion is evidence of a transitional homeostatic state in the neonate during the first days after birth. To determine whether postnatal development produces an adultlike response, Ra was measured in 11 infants (birth weight 1716 +/- 48 g, gestational age 33 +/- 0.3 weeks) at 2 to 5 weeks of age. In these paired studies, 4 micrograms.kg-1min-1 D-(U-13C)glucose tracer was infused by prime constant infusion to determine Ra, during infusion of either saline solution or glucose, the latter at a rate of 5.3 +/- 0.2 mg.kg-1min-1 (mean +/- SEM). When the results of the saline infusion turnover period were compared with those of the glucose infusion turnover period, plasma glucose concentration increased significantly, from 88 +/- 3 mg/dL to 101 +/- 4 mg/dL (P less than 0.001). Plasma insulin concentration remained unchanged (12 +/- 5 microU/mL vs 8 +/- 3 microU/mL). Ra was heterogenous during glucose infusion, and persistent Ra was present in six of 11 infants. Of the five infants who had decreased Ra during glucose infusion, three received glucose at a rate exceeding basal Ra. Of the remaining six infants who evidenced persistent Ra during glucose infusion, three received glucose at a rate equal to or in excess of basal Ra. We conclude that glucose homeostasis in low birth weight infants is transitional throughout the neonatal period.

Age Factors↗
PubMed1987

Hepatic response to insulin in control of glucose kinetics in the neonatal lamb.

Imprecise control of neonatal glucose homeostasis may be partially due to decreased hepatic response to insulin. In prior kinetic studies the effect of that response could not be determined because the hormonal effects of insulin could not be separated from those of glucagon. Somatostatin (SRIF) suppresses secretion of both and has been used to differentiate the hormonal effects. Eighteen term lambs (age 4.2 +/- 0.3 days and birth weight 4.0 +/- 0.2 kg (M +/- SEM] were infused with 0.9% NaCl at 0.06 mL.kg-1 min-1 plus 100 microCi/kg D[6-3H] glucose by prime plus constant infusion. Ra (production) and Rd (utilization) were measured during infusion of SRIF or SRIF plus replacement insulin (0.2 mU.kg-1 min-1). There was a rise in pl. glucose (98 +/- 10 to 119 +/- 10 mg/dL (P less than .0001)); a fall (46.2%) in pl insulin [13 +/- 2 to 7 +/- 1 microU/mL (P less than .0004); a rise in Ra (7.8 +/- 1.5 to 13.2 +/- 4.1 mg.kg-1 min-1 P less than .047); and a rise in Rd (7.7 +/- 1.4 to 11.3 +/- 3.0 mg.kg-1 min-1 (P less than .047)) in SRIF treated animals compared to nontreated controls. There was no change in plasma glucagon (454 +/- 182 to 255 +/- 141 pg/mL) in SRIF treated animals compared to nontreated controls. All perturbations were eliminated when SRIF plus replacement insulin produced control insulin levels. Insulin suppression in the neonatal period resulted in glucagon being unopposed which produced an elevated rate of glucose production and elevated plasma glucose concentration.

Animals↗
PubMed1986

Effects of maternal transport on admission patterns at a tertiary care center.

Major changes have occurred in the delivery of perinatal care during the last two decades. Documentation of perinatal regionalization statistics at Women and Infants Hospital of Rhode Island in Providence support the increasing proportion of low birth weight infants in the region being born at the tertiary care center, the decreasing number of neonatal transports in concert with an increasing number of maternal transports, and the increasing proportion of neonatal transports with birth weights greater than or equal to 2500 gm. Patterns of modern perinatal care are materially changing the delivery of health care at tertiary care facilities.

Birth Weight↗
PubMed1985

Hepatic and peripheral responsiveness to a glucose infusion in pregnancy.

To enhance glucose transfer to the fetus, the pregnant woman may evidence hyperglycemia after feeding. In order to evaluate whether hepatic responsiveness, in contrast to peripheral uptake, contributes to this response, the glucose production rate was measured in 15 pregnant nondiabetic patients, in 12 pregnant insulin-dependent diabetic patients, and in 12 nonpregnant nondiabetic patients (controls). Seventeen of the women were infused with 3.2 mg X kg-1 min-1 of glucose. All glucose-infused groups had an elevated plasma glucose concentration compared to their saline solution-infused counterparts. The glucose production rate was suppressed in the nondiabetic glucose-infused groups. The glucose production rate of the pregnant nondiabetic patients was similar to that of the pregnant insulin-dependent diabetic patients, but the glucose production rate of the latter group was more variable than that of nonpregnant nondiabetic controls (p less than 0.05). We conclude that in third trimester, pregnant nondiabetic and insulin-dependent diabetic subjects have parallel hepatic and peripheral responsiveness to glucose and insulin compared to their nonpregnant counterparts. Although the pregnant patient may exhibit relative insulin insensitivity, hepatic or peripheral responsiveness to insulin would not explain the persistence of the relative hyperglycemia noted clinically.

Adult↗
PubMed1985

Pathophysiology, diagnosis, and management of glucose homeostasis in the neonate.

The neonate appears to be in a transitional stage of glucose homeostasis. Maturation of neonatal glucose homeostasis requires coordination of opposing hormonal, neural, and enzymatic controls. The vulnerability of the neonate to carbohydrate disequilibrium has been described by tracing the maturation of carbohydrate homeostasis physiologically. The many examples of neonatal hypoglycemia and hyperglycemia have been enumerated. Much information in recent years has increased our understanding of the mechanism of these conditions in the newborn. Continued research of the biochemical and physiologic bases for alterations of carbohydrate metabolism should further enhance our ability to diagnose and treat the neonate effectively.

Adult↗
PubMed1985

Mechanisms of beta sympathomimetic action on neonatal glucose homeostasis in the lamb.

Beta sympathomimetic drugs are used clinically to inhibit premature labor. Significant alterations in glucose homeostasis have been documented in both mother and offspring. To determine the mechanism(s) of beta sympathomimetic drugs on neonatal glucose homeostasis, ritodrine hydrochloride was infused in a newborn term lamb model of glucose kinetics by a crossover design. There was a progressive rise in plasma glucose concentration and plasma insulin concentration during ritodrine hydrochloride infusion compared with the control (saline) infusion. The rise in plasma glucose concentration was associated with a progressive rise in Ra (rate of appearance, production) and Rd (rate of disappearance, utilization). The ritodrine hydrochloride-infused animals had a progressive rise in [insulin/glucose] compared with our prior studies in the newborn lamb, suggesting direct stimulation of pancreatic beta cell secretion. In the neonatal lamb, beta sympathomimetic drugs directly stimulate both hepatic glucose production and pancreatic beta cell secretion. These effects explain, in part, why infants of mothers infused with ritodrine hydrochloride may evidence alterations in neonatal glucose homeostasis.

Adrenergic beta-Agonists↗
PubMed1985

The effects of arterial glucose infusion above the celiac axis in the neonatal lamb.

Refractory hypoglycemia has been reported in an infant receiving glucose infusion via an umbilical artery catheter (UAC) above the celiac axis. To prove the hypothesis that hypoglycemia resulted from direct glucose infusion to the pancreas, 15 term spontaneously delivered lambs were infused with 5.3 +/- 0.1 mg X kg-1 min-1 of glucose via an arterial catheter. In 9 glucose was infused below the celiac, and the glucose production rate (GPR) was derived. After a recovery period, the study was repeated with glucose infused above the celiac. During glucose infusion above the celiac, the plasma glucose concentration was lower than when the infusion was given below the celiac (140 +/- 6 vs. 175 +/- 11 mg/dl, p less than 0.01). There was also a fall in the average GPR (3.7 +/- 0.5 vs. 5.5 +/- 0.8 mg X kg-1 min-1, p less than 0.05). In 6 lambs the study was performed in the reverse sequence (high then low infusion) and no differences were noted in the parameters measured. However, there was a marked heterogeneity in the paired GPR in these lambs. We conclude that direct glucose infusion above the celiac increases glucose delivery to the pancreas. This produces increased insulin delivery to the portal system resulting in suppressed GPR and reduction in plasma glucose concentration. These changes may account for refractory hypoglycemia in infants clinically when glucose is infused above the celiac through a UAC.

Animals↗
PubMed1985

Neonatal morbidities in infants of mothers with glucose intolerance in pregnancy.

Of 1839 pregnant women screened prospectively, 52 were identified to have glucose intolerance. Ten additional pregnant women identified as having glucose intolerance before the universal screening were also included in the study cohort. These 62 patients were followed in a perinatal high-risk clinic with weekly plasma glucose determinations. The patients were treated with diet and, in addition, 21 of 62 were treated with insulin therapeutically. By observational cohort design, the infants and a comparable number of matched controls were evaluated for evidence of neonatal morbidities and classified into percentile for birth weight. Compared with the control group, the operative mode of delivery, the mean birth weight, the birth-weight percentile, the male/female ratio, the frequency of low Apgar score (less than or equal to 6 at 1 min), and the number of infants with congenital anomalies were significantly higher in the infants born to the glucose-intolerant mothers. Although the mean maternal blood sugar was maintained within a reasonably euglycemic range, the usual neonatal morbidities were not eliminated entirely. Further understanding and management of glucose intolerance in pregnancy is necessary to further diminish or eliminate neonatal morbidities.

Apgar Score↗
PubMed1984

Glucose kinetics in glucose-infused small for gestational age infants.

To evaluate the maturation of glucose homeostasis in the small for gestational age (SGA) neonate, glucose kinetics were measured with 78% enriched D-[U-13C]glucose by the prime plus constant infusion technique in nine SGA infants and compared with the rate obtained in seven term appropriate for gestational age infants and 13 preterm appropriate for gestational age infants. All of the infants had received glucose intravenously from birth and continued to receive the glucose infusion throughout the study. Fasting plasma glucose and plasma insulin concentrations and plasma [13/12C]ratios were measured during the steady state turnover period. From this data, the glucose production rate was derived. During the turnover period, the SGA and both groups of appropriate for gestational age infants had similar average plasma glucose, plasma insulin, plasma glucagon concentrations, and similar persistent rates of glucose production during glucose infusion. We conclude that under stimulation of glucose infusion, the SGA infant and his AGA counterpart have similar hormonal regulatory responses as well as functional integrity in handling glucose during the second day after birth.

Blood Glucose↗
PubMed1983

Glucose kinetics in nondiabetic and diabetic women during the third trimester of pregnancy.

Glucose kinetics were measured with 78% enriched D-[U-13C] glucose by the prime constant infusion technique during the third trimester of pregnancy in nine nondiabetic women, nine insulin-dependent diabetic women, six gestational diabetic women, and five control women (nonpregnant, nondiabetic) after an overnight fast. The patients not dependent on insulin were diagnosed as diabetic by oral glucose tolerance tests with the use of O'Sullivan and Mahan's criteria as modified by Carpenter and Coustan during the third trimester. The turnover studies were repeated post partum (6 weeks to 5 months after delivery) in 14 of the 24 pregnant subjects. All pregnant groups had a progressive fall in plasma glucose concentration during the study, but there was a steady state of plasma glucose concentration during the turnover period. In comparison to the control subjects, both the pregnant nondiabetic and pregnant insulin-dependent diabetic women had significantly higher plasma insulin concentrations throughout the study (p less than 0.05). There were no differences in the glucose turnover rate between any of the pregnant groups (1.7 +/- 0.2 mg . kg-1 min-1 in pregnant nondiabetic women; 1.5 +/- 0.2 mg . kg-1 min-1 in pregnant insulin-dependent diabetic women; and 2.1 +/- 0.4 mg . kg-1 min-1 in gestational diabetic women) and the control group of women (1.8 +/- 0.2 mg . kg-1 min-1) (mean +/- SEM). When the pregnant patients were studied post partum, the glucose turnover rate was similar when referenced to body weight; however, because of a 9.6% to 14.5% fall in weight post partum, the absolute values were higher in the pregnant women. We conclude that, in the basal state after an overnight fast, (1) both nondiabetic and diabetic patients accelerated their glucose turnover rate during pregnancy to provide for increased maternal and fetoplacental metabolic requirements, and (2) in the diabetic subjects the nearly normal plasma glucose and insulin concentrations and other metabolic parameters, as well as the glucose turnover rate, suggested good metabolic control during pregnancy in most of the insulin-dependent and in all of the gestational diabetic patients.

Adult↗
PubMed1983

Glucose kinetics in infants of diabetic mothers.

Glucose kinetic studies were performed to define the glucose turnover rate with 78% enriched D-[U-13C] glucose by the prime constant infusion technique at less than or equal to 6 hours of age in nine infants of diabetic mothers (four insulin-dependent and five chemical diabetic patients) at term. Five normal infants were studied as control subjects. All infants received 0.9% saline intravenously during the study with the tracer. Fasting plasma glucose, insulin, and glucose13/12C ratios were measured during the steady state, and the glucose turnover rate was derived. The average plasma glucose concentration was similar during the steady state in the infants of the diabetic mothers and in the control infants, and the glucose turnover rate was not significantly different among the groups: 2.3 +/- 0.6 mg . kg-1 min-1 in infants of insulin-dependent diabetic patients; 2.4 +/- 0.4 mg . kg-1 min-1 in infants of chemical diabetic patients; and 3.2 +/- 0.3 mg . kg-1 min-1 in the control subjects. Good control of maternal diabetes evidenced by the normal maternal hemoglobin A1c and plasma glucose concentration at delivery and cord plasma glucose concentration resulted in glucose kinetic values in the infants of diabetic mothers that were indistinguishable from those of control subjects. The data further support the importance of good control of the diabetic state in the pregnant woman to minimize or prevent neonatal hypoglycemia.

Blood Glucose↗
PubMed1983

Persistent glucose production during glucose infusion in the neonate.

In adults, glucose infusion results in a decreased glucose production rate (GPR) as a mechanism for maintaining euglycemia. To document the development of glucose homeostasis, we derived the GPR in 23 preterm appropriate for gestational age infants, 14 term appropriate for gestational age infants, and in 6 adults. After a 3-h fast, the average plasma glucose and insulin concentration was measured and the GPR was derived. During glucose infusion (5.6 +/- 0.3 mg X kg-1 min-1), compared with saline controls, the preterms had a rise in plasma glucose and plasma insulin, and the GPR was 1.4 mg X kg-1 min-1 (range, 0-4.4) vs. 3.0 mg X kg-1 min-1 (range, 1.8-4.1) (saline controls). In the term infants, only the plasma insulin concentration was elevated when the glucose infused (5.7 +/- 0.3 mg X kg-1 min-1) infants were compared with the saline controls and GPR was 0.4 X kg-1 min-1 (range, 0-2.6) vs. 3.4 mg X kg-1 min-1 (range, 2.8-5.7) (saline controls). In comparison to saline infused adults, glucose infusion (3.2 +/- 0.1 mg X kg-1 min-1) resulted in a significant rise in plasma glucose and in plasma insulin; and the GPR was reduced to 0.1 mg X kg-1 min-1 (range, 0-0.3) from 2.0 mg X kg-1 min-1 (range, 1.5-2.4). 5 of 13 preterms and 2 of 7 term infants had persistent GPR during glucose infusion; in contrast, the GPR in all adults was unmeasurable. There was no correlation between the plasma glucose concentration and the GPR in the newborn or in the adult. Both newborns and adults did have a correlation between plasma insulin concentration and the GPR; however, there was considerable variability in the neonate. We conclude that there are significant developmental differences in neonatal glucose homeostasis and that insulin is important in neonatal hormonal control of glucose production.

Adult↗
PubMed1983

Post-hepatic insulin secretion in the fetal lamb.

Post-hepatic insulin secretion was measured in six chronically catheterized fetal lambs (fetal weight 2.8 +/- 0.3 kg, mean +/- S.E.M.) and the results were compared with those obtained in nine prematurely delivered newborn lambs (birth weight 3.1 +/- 0.3 kg and postnatal age 1.3 +/- 0.2 days). The fetal and neonatal lambs received either a 0.45% saline or a glucose infusion respectively, which resulted in a 2-fold increase in the plasma glucose concentration. [131I]insulin was infused for 110 min to determine the rate of insulin secretion during a steady state of plasma glucose concentration. Post-hepatic insulin secretion and the metabolic clearance rate were calculated. With the 2-fold rise in plasma glucose concentration, the post-hepatic insulin secretion rate increased significantly in the newborn lamb and in three out of four fetuses. The plasma insulin concentration increased significantly in the fetus (11 +/- 4.0 to 35 +/- 8 microU/ml, P less than 0.05) during glucose stimulation as a result of decreased metabolic clearance rate of insulin (10.6 +/- 1.9 to 6.3 +/- 1.8 ml . kg-1 . min-1) and an increase in post-hepatic insulin secretion rate. In spite of an increase in post-hepatic insulin secretion rate, the increase in plasma insulin concentration in the newborn lamb was not significant because of large variation in the values obtained. The data suggest that pancreatic beta-cells in the newborn and in the fetal lamb are equally responsive to a 2-fold increase in plasma glucose concentration.

Animals↗
PubMed1982

Glycemic response to lipid infusion in the premature neonate.

The effect of lipid infusion on glucose homeostasis in the preterm newborn infant was evaluated. Seven infants were given a test dose of 0.25 gm/kg/hour of lipid emulsion. Their response was characterized by :(1) a two fold increase in serum free fatty acid concentrations, (2) a small, transient rise in insulin values, and (3) a sustained increase in serum glucose concentration (mean increment in serum glucose was 24% over baseline). Nine infants received a test dose of 0.5 gm/kg/hr of lipid. Their response was similar to that in the lower infusion group, but of a greater magnitude: an eightfold increase in free fatty acids, sustained increase in serum insulin concentration, and a mean increment in serum glucose values of 65% over baseline. Increased lipid availability in the low-birth-weight newborn infant plays a significant role in promoting an increase in serum glucose concentrations.

Blood Glucose↗