Enteral nutrient supply for preterm infants: commentary from the European Society of Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition.

The number of surviving children born prematurely has increased substantially during the last 2 decades. The major goal of enteral nutrient supply to these infants is to achieve growth similar to foetal growth coupled with satisfactory functional development. The accumulation of knowledge since the previous guideline on nutrition of preterm infants from the Committee on Nutrition of the European Society of Paediatric Gastroenterology and Nutrition in 1987 has made a new guideline necessary. Thus, an ad hoc expert panel was convened by the Committee on Nutrition of the European Society of Paediatric Gastroenterology, Hepatology, and Nutrition in 2007 to make appropriate recommendations. The present guideline, of which the major recommendations are summarised here (for the full report, see http://links.lww.com/A1480), is consistent with, but not identical to, recent guidelines from the Life Sciences Research Office of the American Society for Nutritional Sciences published in 2002 and recommendations from the handbook Nutrition of the Preterm Infant. Scientific Basis and Practical Guidelines, 2nd ed, edited by Tsang et al, and published in 2005. The preferred food for premature infants is fortified human milk from the infant's own mother, or, alternatively, formula designed for premature infants. This guideline aims to provide proposed advisable ranges for nutrient intakes for stable-growing preterm infants up to a weight of approximately 1800 g, because most data are available for these infants. These recommendations are based on a considered review of available scientific reports on the subject, and on expert consensus for which the available scientific data are considered inadequate.

Glucose production in pregnant women at term gestation. Sources of glucose for human fetus.

The effects of pregnancy and diabetes on systemic glucose production rates and the sources of glucose for the human fetus in utero were evaluated in five normal, four gestationally diabetic, and one insulin-dependent diabetic subject undergoing elective caesarean section at term gestation. Five normal nonpregnant women were studied for comparison. Systemic glucose production rates were measured with stable tracer [1-(13)C]glucose according to the prime-constant rate infusion technique. Even though the plasma glucose concentration during normal pregnancy had declined as compared with the nonpregnant subjects (P < 0.0005), the systemic glucose production rate was 16% greater, a rate sufficient to provide the glucose requirement of the fetus at term gestation. The decline in glucose concentration could be the result of an increase in apparent volume of distribution of glucose. Systemic glucose production rates in well-controlled, gestationally diabetic subjects were similar to those in normal pregnant subjects (2.07+/-0.53 vs. 2.42+/-0.51 mg/kg.min). The sources of glucose for the human fetus at term gestation were evaluated by comparing (a) natural variation in (13)C:(12)C ratio of plasma glucose and (b) enriched (13)C:(12)C ratio of plasma glucose during [1-(13)C]glucose infusion in maternal and fetal blood at delivery in both normal and diabetic subjects. These data showed that the fetal glucose pool was in equilibrium with the maternal glucose pool in both normal and diabetic subjects, indicating that a brief maternal fast did not initiate systemic glucose production in human fetus. A materno-fetal gradient was observed for betahydroxybutyrate.

Use of 2H2O for estimating rates of gluconeogenesis. Application to the fasted state.

A method is introduced for estimating the contribution of gluconeogenesis to glucose production. 2H2O is administered orally to achieve 0.5% deuterium enrichment in body water. Enrichments are determined in the hydrogens bound to carbons 2 and 6 of blood glucose and in urinary water. Enrichment at carbon 6 of glucose is assayed in hexamethylenetetramine, formed from formaldehyde produced by periodate oxidation of the glucose. Enrichment at carbon 2 is assayed in lactate formed by enzymatic transfer of the hydrogen from glucose via sorbitol to pyruvate. The fraction gluconeogenesis contributes to glucose production equals the ratio of the enrichment at carbon 6 to that at carbon 2 or in urinary water. Applying the method, the contribution of gluconeogenesis in healthy subjects was 23-42% after fasting 14 h, increasing to 59-84% after fasting 42 h. Enrichment at carbon 2 to that in urinary water was 1.12 +/- 0.13. Therefore, the assumption that hydrogen equilibrated during hexose-6-P isomerization was fulfilled. The 3H/14C ratio in glucose formed from [3-3H,3-14C]lactate given to healthy subjects was 0.1 to 0.2 of that in the lactate. Therefore equilibration during gluconeogenesis of the hydrogen bound to carbon 6 with that in body water was 80-90% complete, so that gluconeogenesis is underestimated by 10-20%. Glycerol's contribution to gluconeogenesis is not included in these estimates. The method is applicable to studies in humans of gluconeogenesis at safe doses of 2H2O.

Contributions of gluconeogenesis to glucose production in the fasted state.

Healthy subjects ingested 2H2O and after 14, 22, and 42 h of fasting the enrichments of deuterium in the hydrogens bound to carbons 2, 5, and 6 of blood glucose and in body water were determined. The hydrogens bound to the carbons were isolated in formaldehyde which was converted to hexamethylenetetramine for assay. Enrichment of the deuterium bound to carbon 5 of glucose to that in water or to carbon 2 directly equals the fraction of glucose formed by gluconeogenesis. The contribution of gluconeogenesis to glucose production was 47 +/- 49% after 14 h, 67 +/- 41% after 22 h, and 93 +/- 2% after 42 h of fasting. Glycerol's conversion to glucose is included in estimates using the enrichment at carbon 5, but not carbon 6. Equilibrations with water of the hydrogens bound to carbon 3 of pyruvate that become those bound to carbon 6 of glucose and of the hydrogen at carbon 2 of glucose produced via glycogenolysis are estimated from the enrichments to be approximately 80% complete. Thus, rates of gluconeogenesis can be determined without corrections required in other tracer methodologies. After an overnight fast gluconeogenesis accounts for approximately 50% and after 42 h of fasting for almost all of glucose production in healthy subjects.

Effect of multi-nutrient insufficiency on markers of one carbon metabolism in young women: response to a methionine load.

BACKGROUND/OBJECTIVES: Multi-nutrient insufficiencies as a consequence of nutritional and economic factors are common in India and other developing countries. We have examined the impact of multi-nutrient insufficiency on markers of one carbon (1C) metabolism in the blood, and response to a methionine load in clinically healthy young women. SUBJECTS/METHODS: Young women from Pune, India (n=10) and Cleveland, USA (n=13) were studied. Blood samples were obtained in the basal state and following an oral methionine load (50 mg/kg of body weight in orange juice). Plasma concentrations of vitamin B12, folate and B6 were measured in the basal state. The effect of methionine load on the levels of methionine, total homocysteine, cysteine, glutathione and amino acids was examined. RESULTS: Indian women were significantly shorter and lighter compared with the American women and had lower plasma concentration of vitamins B12, folate and B6, essential amino acids and glutathione, but higher concentration of total homocysteine. The homocysteine response to methionine load was higher in Indian women. The plasma concentrations of glycine and serine increased in the Indian women after methionine (in juice) load. A significant negative correlation between plasma B6 and homocysteine (r= -0.70), and plasma folate and glycine and serine levels were observed in the Indian group (P<0.05) but not in the American group. CONCLUSIONS: Multi-nutrient insufficiency in the Indian women caused unique changes in markers of whole body protein and 1C metabolism. These data would be useful in developing nutrient intervention strategies.

Correlations between fatty acid and glucose metabolism. Potential explanation of insulin resistance of puberty.

In vivo resistance to the action of insulin on glucose uptake has been documented during puberty. To test the hypothesis that the glucose-fatty acid cycle, as proposed by Randle et al. (Randle PJ, Garland PB, Hales CN, Newsholme EA: The glucose fatty-acid cycle: its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1:785-789, 1963), may be responsible for this phenomenon, we studied nine prepubertal (Tanner I), nine pubertal (Tanner II-IV), and five young adult healthy subjects. The rate of lipolysis was measured with [d-5]glycerol tracer during basal state and during a stepwise hyperinsulinemic (10 and 40 mU.m-2.min-1)-euglycemic clamp. The rates of insulin-stimulated glucose disposal (Rd) were measured during the clamp, whereas glucose and fat oxidation were measured by using indirect respiratory calorimetry. Basal glycerol rate of appearance (Ra; lipolysis) and fat oxidation were similar between prepubertal and pubertal subjects but higher than adults when the data were expressed per kilogram body weight or per kilogram fat-free mass (FFM; glycerol Ra: 2.5 +/- 0.2, 2.6 +/- 0.2 vs. 1.6 +/- 0.2 mumol.min-1.kg FFM-1, P < 0.05; fat oxidation: 4.4 +/- 0.6, 4.8 +/- 0.3 vs. 3.2 +/- 0.6 mumol.min-1.kg FFM-1, P < 0.05). However, when expressed for total body, glycerol Ra and fat oxidation were higher in pubertal versus prepubertal and adult subjects. Insulin-like growth factor I (IGF-I) levels correlated with total-body lipolysis (r = 0.52, P = 0.006) and with total lipid oxidation (r = 0.44, P = 0.016) at baseline.(ABSTRACT TRUNCATED AT 250 WORDS)

Gestational diabetes mellitus. Is further improvement necessary?

The maternal antepartum, intrapartum, and neonatal characteristics of 158 patients with gestational diabetes mellitus (GDM) attending a large teaching hospital between 1979 and 1983 were described and compared with a matched nondiabetic control group. The primary cesarean section rate in patients with GDM (18%) was significantly greater than in the control group (11%, P less than 0.04). Neonatal macrosomia, as reflected in mean birthweight (P less than 0.04), the number of neonates weighing greater than 4 kg (P less than 0.05) and large-for-gestational-age infants (P less than 0.05), and the birthweight adjusted for gestational age (K-score, P less than 0.01) was significantly increased in the diabetic group. The characteristics of patients with GDM treated with diet alone and diet and insulin together were examined. The insulin-therapy group was characterized by more patients older than 25 yr (P less than 0.01) and a higher mean birthweight (3743 +/- 677 g) (P less than 0.02) than the diet-alone group. This may reflect an increased magnitude of glucose intolerance in the insulin-treated group. Obese patients with GDM delivered heavier neonates than the nonobese patients with GDM (P less than 0.01). Although there was no difference between the groups, perinatal mortality was present in this study. These data indicate that the major perinatal morbidity in GDM included increased cesarean section for fetal macrosomia. Early diagnosis with strict diagnostic criteria and rigid antenatal surveillance may result in further improvements in outcome.

Protein and nitrogen metabolism in gestational diabetes.

Metabolic perturbations associated with gestational diabetes mellitus (GDM) have been shown to result in significant clinical morbidity, both for the mother and the neonate. Although a number of studies have documented the changes in glucose metabolism in GDM, the data on nitrogen and protein metabolism remain scant. Recent data in GDM show that 1) the rate of irreversible nitrogen loss as measured by the rate of urea synthesis in GDM is similar to that in normal pregnancy and is less than that in nonpregnant women; and 2) possibly related to the magnitude of metabolic decompensation as assessed by the nature of therapeutic intervention (diet or diet plus insulin), the rate of protein turnover measured by leucine kinetics is increased in insulin-treated GDM. Whether the decompensation in protein turnover contributes to the persistent fetal macrosomia, even in rigorously managed GDM, remains speculative.

Diagnosis of gestational diabetes in early pregnancy.

OBJECTIVE: To determine whether glucose intolerance can be identified early in gestation in a high-risk population so that early intervention can be planned to prevent associated morbidity. RESEARCH DESIGN AND METHODS: After appropriate dietary preparation, patients with a high risk for gestational diabetes underwent a 50-g oral glucose screening test during fasting. Patients were tested on enrollment and every 10 wk until delivery. Those with a 1-h plasma glucose value of greater than or equal to 7.5 mM underwent a 100-g oral glucose tolerance test. Gestational diabetes was based on either a markedly abnormal 50-g screening test or abnormal 100-g oral glucose tolerance test. RESULTS: Ten of 15 (66%) patients who developed gestational diabetes were diagnosed during the first half of the pregnancy. Six were diagnosed in the first trimester. If the definition of an abnormal 1-h plasma glucose value was lowered from 7.5 to 7.2 mM, an additional 2 patients could have been identified in the first trimester with an improvement in sensitivity from 70 to 91% with only a slight drop in specificity (from 91 to 88%). Diagnosis of gestational diabetes was not enhanced by measuring plasma insulin concentrations or insulin-glucose molar ratios. CONCLUSIONS: The diagnosis of gestational diabetes in a high-risk population can be made in the first half of pregnancy. Early diagnosis should permit evaluation of intervention strategies, which may result in improved perinatal outcome.

Clinically useful estimates of insulin sensitivity during pregnancy: validation studies in women with normal glucose tolerance and gestational diabetes mellitus.

OBJECTIVE: We examined whether selected indexes of insulin sensitivity derived from an oral glucose tolerance test (IS(OGTT)) or fasting glucose/insulin levels (IS(QUICKI) and IS(HOMA)) can be used to predict insulin sensitivity in women before and during pregnancy. RESEARCH DESIGN AND METHODS: A 2-h euglycemic-hyperinsulinemic clamp (5 mmol/l glucose, 40 mU. m(-2). min(-1) insulin) and a 120-min oral glucose tolerance test (75 g load pregravid, 100 g pregnant) were repeated on 15 women (10 with normal glucose tolerance [NGT] and 5 with gestational diabetes mellitus [GDM]) pregravid and during both early (12-14 weeks) and late (34-36 weeks) pregnancy. An index of insulin sensitivity derived from the clamp (IS(CLAMP)) was obtained from glucose infusion rates adjusted for change in fat-free mass and endogenous glucose production measured using [6,6(-2)H(2)]glucose. RESULTS: Univariate analysis using combined groups and periods of pregnancy resulted in significant correlations between IS(CLAMP) and IS(OGTT) (r(2) = 0.74, P < 0.0001), IS(QUICKI) (r(2) = 0.64, P < 0.0001), and IS(HOMA) (r(2) = 0.53, P < 0.0001). The IS(OGTT) provided a significantly better correlation (P < 0.0001) than either IS(QUICKI) or IS(HOMA.) Multivariate analysis showed a significant group effect (P < 0.0003) on the prediction model, and separate equations were developed for the NGT (r(2) = 0.64, P < 0.0001) and GDM (r(2) = 0.85, P < 0.0001) groups. When subdivided by period of pregnancy, the correlation between IS(CLAMP) and IS(OGTT) pregravid was r(2) = 0.63 (P = 0.0002), during early pregnancy was r(2) = 0.80 (P < 0.0001), and during late pregnancy was r(2) = 0.64 (P = 0.0002). CONCLUSIONS: Estimates of insulin sensitivity from the IS(OGTT) during pregnancy were significantly better than from fasting glucose and insulin values. However, separate prediction equations are necessary for pregnant women with NGT and women with GDM.

Inhibitory effect of prednisone on insulin secretion in man: model for duplication of blood glucose concentration.

Treatment with oral prednisone (15 mg every 6 h) for 1 day plus a 4-h glucose infusion at 2.8 mg/min kg body weight to 5 normal, healthy individuals raised their blood glucose to 137 +/- 4.5 mg per 100 ml (mean +/- SEM). In order to evaluate the effects of steroid-induced hyperglycemia on insulin responses, a model for the duplication of blood glucose concentration in serial studies was developed. During glucose infusion at 5.7 mg/min kg body weight, the fractional uptake of glucose at the end of infusion (KG) was 2.08 +/- 0.2%/min and the apparent volume of distribution (V) was 285 +/- 10.5 ml/kg. Further increase in the rate of glucose infusion did not affect KG and V. Based on these parameters, KG and V, the stable blood glucose achieved during the prednisone study (C) was duplicated both after short (4 h) and prolonged (28 h) glucose infusions (138 +/- 4.5 and 146 +/- 4.5 mg/100 ml, respectively) at rates calculated as the product of KG.C.V. The effects of prednisone treatment on insulin secretion were examined (1) during fasting, (2) at identical glucose concentrations during glucose infusions at constant rates, and (3) in response to glucose pulse (0.1 g/kg) during the infusions. During fasting, there was a significant elevation of mean blood glucose with prednisone (99 +/- 1.8 mg/100 ml) compared with that in the control study (88 +/- 1.7 mg/100 ml). The plasma IRI, however, remained unchanged (10 +/- 2.3 vs 10 +/- 1.6 muU/ml). During glucose infusions in the presence of similar blood glucose levels, the IRI was lower after prednisone treatment (18 +/- 1.5 muU/ml) than during the short and prolonged glucose infusions (42 +/- 5.1 and 63 +/- 7.0 muU/ml). The insulin response to the glucose pulse also was significantly lower during steroid treatment. Thus, prednisone apparently has an early inhibitory effect on the insulin response to glucose.

Measurement of glucose turnover in the human newborn with glucose-1-13C.

Systemic glucose production rates were measured in 6 normal newborn infants by dilution of glucose-1-13C tracer according to the prime constant-rate infusion technique. Glucose production rates were 4.4 +/- 0.39 mg/kg. min. (Mean +/- S.D.) in 4 infants at 2 hours of age, and were 3.83 and 3.86 mg/kg. min. in 2 infants at 1 day of age. Systemic glucose production accounts for 50% of the substrate utilized for oxidative metabolism in newborn infants.

Roles of insulin resistance and beta-cell dysfunction in the pathogenesis of glucose intolerance in cystic fibrosis.

The roles of insulin deficiency and insulin resistance in the pathogenesis of glucose intolerance in cystic fibrosis (CF) were evaluated in eight patients (aged 16.5 +/- 1.9 yr), four with normal glucose tolerance (NGT) and four with impaired glucose tolerance (IGT), and in seven healthy control (CN) subjects. First and second phase insulin secretions were evaluated during a hyperglycemic clamp. Hepatic glucose production (HGP) and insulin-stimulated glucose disposal were measured using [6,6-2H2]glucose and a stepwise hyperinsulinemic-euglycemic clamp. First and second phase insulin levels were significantly lower in both groups of CF patients compared with control values. There was an inverse relationship between glycohemoglobin level and first phase insulin (r = -0.81; P = 0.015) and second phase insulin (r = -0.97; P < 0.001). During the hyperglycemic clamp, the insulin sensitivity index was lower in CF-IGT, but not CF-NGT, compared with control values (6.66 +/- 1.79, 12.82 +/- 1.61, and 13.02 +/- 1.78 mumol/kg.min/pmol.L, respectively; P < 0.05). Basal HGP and fasting plasma glucose were higher in CF vs. CN [24.8 +/- 2.9 vs. 16.9 +/- 1.4 mumol/kg.min (P = 0.036) and 5.8 +/- 0.2 vs. 5.4 +/- 0.1 mmol/L (P = 0.035), respectively]. During the hyperinsulinemic euglycemic clamp, insulin-stimulated glucose disposal was significantly lower in CF-IGT (45.68 +/- 4.87 mumol/kg.min) vs. CF-NGT (78.99 +/- 1.34 mumol/kg.min) and CN (71.74 +/- 6.88 mumol/kg.min). Insulin sensitivity was lower in CF-IGT vs. CF-NGT (7.04 +/- 0.86 and 14.38 +/- 0.84 mumol/kg.min/pmol.L; P < 0.05). We conclude that 1) glycohemoglobin is a strong correlate of insulin deficiency in CF; and 2) glucose intolerance in this group of CF patients occurred as a consequence of concomitant insulin deficiency and insulin resistance.

Estimation of glucose turnover and 13C recycling in the human newborn by simultaneous [1-13C]glucose and [6,6-1H2]glucose tracers.

To compare two methods of estimating systemic glucose production rates and to quantify carbon tracer recycling, six newborn infants, aged 2 h to 3 days, were infused simultaneously with [1-13C]glucose and [6,6-2H2]glucose tracers. The older infants were studied 6 h after a meal. [1-13C]Glucose was infused at 6 microgram/kg.min. Systemic glucose production rates were calculated from tracer dilution, assuming steady state kinetics. Although 13C was expected to randomize away from the C-1 of glucose, recycling occurred and was estimated from the difference in the rate of systemic glucose production quantified by the dilution of the two tracers. Systemic glucose production rates ranged from 4.2--5.4 mg/kg.min. Recycling on the glucose C-1 was 3--20% of the systemic glucose production rate and did not change with the age of the infant. Because recycling of glucose carbon signifies gluconeogenesis from lactate or pyruvate, it is concluded that the human newborn is able to initiate gluconeogenesis soon after birth.

Protein metabolism in pregnancy.

Adaptation to pregnancy involves major changes in maternal metabolism to provide for the growing demands of the conceptus. Although changes in glucose metabolism, and possibly in fatty acid metabolism, occur in parallel with the increasing energy demands of the mother and the fetus, adaptation of protein metabolism appears to be in anticipation of maternal and fetal needs. During pregnancy, there is an excess of maternal nitrogen in the form of lean body mass over that deposited in the fetus and the products of conception; there is also a pregnancy-induced hypoaminoacidemia and a diminished amino acid response to protein intake, suggesting an increased uptake of amino acids in the splanchnic compartment. With the use of stable-isotope-labeled tracers, it was shown that there is a decreased rate of urea synthesis during pregnancy that is evident early in gestation. Kinetic studies of leucine metabolism showed no significant change in leucine carbon turnover but a significantly lower rate of leucine nitrogen turnover, suggesting a lower rate of leucine transamination. These data suggest an integral regulation of whole-body protein and nitrogen metabolism starting early in gestation and aimed at conservation and accretion of nitrogen by the mother and the fetus.

Estimation of total body water in very-low-birth-weight infants by using anthropometry with and without bioelectrical impedance and H2[(18)O].

The usefulness of bioelectrical impedance (BI) with anthropometry to measure total body water (TBW) was evaluated in very-low-birth-weight (VLBW) infants. A specific regression equation to measure TBW in a VLBW population was developed by simultaneously using the H2[(18)O] dilution method and BI in 12 infants with a gestational age of 24-30 wk and weighing <1200 g at birth. After an oral dose of H2[(18)O], the tracer dilution was measured in expired carbon dioxide. BI measurements were made with a model BIA-101 apparatus (RJL Systems, Detroit). Electrodes were placed in the standard position as well as proximally on the leg and the forearm. The best correlation was observed between body weight and TBW (r = 0.989). For BI, the best correlation was obtained when gestational age was used as a covariable along with body weight and crown-heel length (r = 0.985). The correlation was comparable with proximal electrode placement (r = 0.985). The new correlation was evaluated in 6 infants weighing < 1008 g. A significant correlation between BI and H2[(18)O]-measured TBW was observed (r = 0.988). Published regression equations for infants consistently gave higher estimates of TBW in another group of 14 infants weighing <1200 g than did the new correlations. TBW represented 84-95% of body weight in these VLBW infants. TBW could be computed simply from body weight alone. Use of BI and length as covariables did not add significantly to the estimate of TBW in VLBW infants.

Leucine kinetics and fuel utilization during a brief fast in human pregnancy.

To examine proteolysis, protein and leucine oxidation, and fuel utilization during a brief fast (approximately 17 hours) in human pregnancy, we determined leucine kinetics, urea nitrogen excretion, and respiratory quotient (RQ) in 11 pregnant subjects during the second half of gestation, and in 11 normal nonpregnant controls. The total rate of appearance (Ra) of leucine was similar in the pregnant and control groups (pregnant 4.99 +/- 0.60 v control 5.25 +/- 1.60 mmol/h [mean +/- SD]). However, leucine Ra per kilogram was significantly lower in pregnant subjects (pregnant 68 +/- 7 v control 82 +/- 13 mumol/kg/h, P less than .01). In addition, urinary urea nitrogen excretion was also significantly less in pregnant subjects (pregnant 3.74 +/- 1.09 v control 5.58 +/- 1.6 mg/kg/h, P less than .01). The RQ measured in the pregnant group was significantly higher than controls (0.82 +/- 0.05 v 0.76 +/- 0.04, P = .01), resulting in higher calculated carbohydrate oxidation rates during fasting in pregnancy. These data suggest that total rates of proteolysis (reflected by leucine flux) are similar in pregnant and nonpregnant subjects after an overnight fast. When normalized to body weight, proteolysis is lower in pregnant subjects. Urea excretion rates are also lower in pregnancy. These findings support the hypothesis that there is a pregnancy-induced adaptation to conserve maternal protein stores during a brief fast. The higher rate of carbohydrate oxidation during fasting in pregnancy may be a reflection of the fetal-placental unit's use of glucose as its predominant oxidative substrate.

Hepatic insulin action in adolescents with insulin-dependent diabetes mellitus: relationship with long-term glycemic control.

The relationship between hepatic insulin action and long-term glycemic control was assessed in 20 adolescents with insulin-dependent diabetes mellitus (IDDM) and five healthy matched controls using a two-step (0.8 and 1.6 mU/kg/min) hyperinsulinemic-euglycemic clamp and [6,6-2H2]glucose. The night before the study, diabetic patients received variable-rate intravenous insulin in an attempt to normalize fasting plasma glucose concentrations. In the postabsorptive state, hepatic glucose production (HGP) was similar in IDDM patients and controls (593 +/- 40 v 518 +/- 27 mumol/m2/min); however, plasma glucose and free insulin concentrations were higher in IDDM patients than in controls (6.5 +/- 0.4 v 5.4 +/- 0.1 mmol/L [P = .01], and 207 +/- 21 v 104 +/- 10 pmol/L [P < .001], respectively). There was a positive correlation (r = .62 P = .002) between basal HGP and glycohemoglobin level (HbA1). Separation of the patients at the median HbA1 (group no. 1 < and group no. 2. > 11.4% HbA1) revealed two distinct patient populations with regard to hepatic and peripheral insulin action and plasma free fatty acid (FFA) suppression. During hyperinsulinemia, the percent suppression of HGP was lower in group no. 2 compared with group no. 1 (65.7% +/- 9.8% v 94.4% +/- 3.8%; P = .018). Rates of glucose disposal were lower in group no. 2 compared with controls and with group no. 1. Postabsorptive FFA levels were similar between group no. 2 and group no. 1 (0.45 +/- 0.03 and 0.43 +/- 0.04 mmol/L) despite higher free-insulin concentrations in group no. 2 (260 +/- 30 v 171 +/- 25 pmol/L; P = .04).(ABSTRACT TRUNCATED AT 250 WORDS)

Glucose-alanine relationship in normal human pregnancy.

In order to quantify the glucose-alanine relationship in normal human pregnancy, the turnover rates of alanine and the incorporation of alanine carbon into glucose were quantified in 15 pregnant women during the last 4 weeks of gestation following a ten-hour fast. Eight nonpregnant women of similar age group were studied as controls. L-[2,3-13C2]Alanine and D[6,6-2H2]glucose were infused as tracers. The 13C enrichment of alanine, lactate, and glucose and the deuterium enrichment of glucose were measured by gas chromatography-mass spectrometry. In five pregnant and five nonpregnant women, the contribution of alanine carbon to expired CO2 directly and via glucose was estimated by combining indirect respiratory calorimetry with the tracer infusions. The alanine turnover rates in the pregnant and nonpregnant women were similar (pregnant, 4.43 +/- 0.82 mumol/kg x min; nonpregnant, 4.11 +/- 1.08 mumol/kg x min, mean +/- SD). However, the fraction of alanine incorporated into glucose was significantly lower during pregnancy (23.5 +/- 8.3% v 30.8 +/- 8.2%, P less than .04). In pregnant women, 20% of lactate pool was derived from alanine as compared with 28% in nonpregnant subjects (P less than .02). Twenty-four percent of alanine turnover was converted to CO2 in both pregnant and nonpregnant women. The plasma insulin concentration was increased significantly during pregnancy (P less than .05). These data suggest that gluconeogenesis from alanine is attenuated during pregnancy. This decrease in gluconeogenesis is not the result of decreased alanine flux, but due to intrinsic intrahepatic mechanism such as decreased deamination of alanine mediated by the predominant insulin effect or a decreased hepatic uptake of alanine.(ABSTRACT TRUNCATED AT 250 WORDS)

Urea synthesis, nitrogen balance, and glucose turnover in growth-hormone-deficient children before and after growth hormone administration.

We measured the effect of human growth hormone (hGH) on urea synthesis, nitrogen retention, and glucose turnover in ten euthyroid growth hormone (GH)-deficient children before and after seven daily injections of 0.1 U/kg hGH. The patients were fed a weight-maintaining diet with 9% of energy derived from protein. Following an overnight fast, urea synthesis and glucose turnover were determined using a primed constant infusion of [15N2] urea and a constant infusion of [6,6-2H2] glucose. Human growth hormone produced a decrease in urea nitrogen synthesis from 6.8 +/- 0.5 to 4.2 +/- 0.4 mg/kg.h; (P less than .01), while plasma urea nitrogen decreased from 13.1 +/- 0.8 to 7.4 +/- 0.8 mg/dL; (P less than .01). The decrease in urea synthesis was reflected in a corresponding decrease in urine urea nitrogen excretion (-2.8 mg/kg.h). There was a significant correlation between plasma urea nitrogen and urea synthesis rate both before (r = 0.85, P less than .01) and after (r = 0.79, P less than .01) hGH treatment. In response to hGH, there was a rise in both plasma glucose (81.4 +/- 2.2 v 89.8 +/- 2.3 mg/dL; P less than .05) and insulin (5.7 +/- 0.8 v 13.1 +/- 3.0 microU/mL; P less than .05), however, glucose turnover remained unchanged (4.7 +/- 0.3 v 4.6 +/- 0.6 mg/kg.min). After seven days of growth hormone treatment, the patients were placed on 0.1 U/kg of hGH three times a week for 6 months, and their growth rate was calculated.(ABSTRACT TRUNCATED AT 250 WORDS)