Glucose Homeostasis In Children Research Articles

Effect of concurrent resistance-aerobic training on inflammatory factors and growth hormones in children with type 1 diabetes: a randomized controlled clinical trial

BackgroundExercise training is a major factor in controlling type 1 diabetes mellitus (T1DM) in children. The present study aimed to assess the effect of concurrent resistance-aerobic training on selected inflammatory factors and hormones related to blood glucose homeostasis in children with T1DM.MethodsIn this randomized controlled clinical trial, 40 children (with the mean age of 11.11 ± 2.29 years) were randomly assigned to an experimental (N = 20) or control group (N = 20). They underwent a 16-week training program, composed of concurrent resistance-aerobic training performed intermittently for 60 min three times a week. Before and after training, blood samples were analyzed for glucose homeostasis, selected inflammatory factors, and growth factors. Data were analyzed by paired t-test and analysis of covariance (ANCOVA) in IBM SPSS version 22.ResultsThe exercise training intervention reduced fasting blood sugar index (P = 0.002) and glycosylated hemoglobin significantly (P = 0.003). The growth hormone levels were increased significantly only in the experimental group (P = 0.037), whereas no significant difference was noted in the insulin-like growth factor-1 (P = 0.712). It was also found that interleukin-1β and high-sensitivity C-reactive protein did not change in the experimental or control group as compared to the pretest (P > 0.05).ConclusionAs it was shown, it seems that concurrent resistance-aerobic training may improve blood glucose homeostasis and growth hormone. Therefore, these findings may suggest the benefit from exercise training of moderate intensity in children with T1DM. Besides, we recommend undertaking further clinical trials to determine if the exercise training was effective.Trial registrationThis study was registered in the Iranian Registry of Clinical Trials under the code IRCT20150531022498N30: https://en.irct.ir/trial/41031. Registered on July 26, 2019. All experiments on the participants were following the Declaration of Helsinki.

Glycaemic profile of children undergoing anaesthesia (GLYCANA) at Mercy James Centre in Malawi: an observational study

BackgroundHypoglycaemia and hyperglycaemia may develop during anaesthesia and surgery in children and can lead to severe adverse clinical outcomes. No study, as far as we know, has investigated glucose homeostasis in children undergoing surgery in Malawi. The aim of this study was to assess perioperative glucose levels of the children undergoing anaesthesia at Mercy James Centre (MJC) for Paediatric Surgery, Blantyre, Malawi.MethodologyThis was an observational cross-sectional study. We looked at 100 children aged 1 day to 15 years anaesthetised at MJC. Data were analysed using SPSS 28. Student t test and Analysis of the variance (ANOVA) were used to compare means. The level of significance was 5%.ResultsMale children represented 68%. The median age was 2.2 years. Sixten percents of patient were underweight. Fasting times were prolonged for 87%. Maintenance IV fluid with 2.5% dextrose was given to 14%. Overall, there was a significant increase of glycaemia from induction of anaesthesia to the end of the procedure. Hypoglycaemia was rare. The mean fasting glycaemia was 99.04 mg/dL ± 1.8, 116.95 mg/dL ± 34.2 at 30 min into the procedure and 127.62 mg/dL ± 46.8 at the end of the procedure. The differences in means were statistically significant (p < 0.001). Prolonged fasting times was associated with lower blood glucose means whereas nutrition status, type of the procedure, addition of dextrose in the fluid, and duration of procedure were associated with higher glycaemia means.ConclusionGlycaemia increases under anaesthesia and surgery. Recommended fasting times, optimising nutritional status, when possible, no dextrose or lower than 2.5% dextrose in IV maintenance fluid are possible strategies to maintain blood sugar homeostasis during paediatric surgery and anaesthesia.

Utility of glycated haemoglobin in assessing abnormal glucose homeostasis in children and adolescents with obesity undergoing oral glucose tolerance test

Utility of glycated haemoglobin in assessing abnormal glucose homeostasis in children and adolescents with obesity undergoing oral glucose tolerance test

Asprosin serum levels and glucose homeostasis in children with obesity

PurposeAsprosin is a novel adipokine involved in glucose homeostasis, food intake regulation and energy homeostasis. However, the role of asprosin in glucose homeostasis regulation remains still controversial, especially in pediatrics. Aims of the study were to compare fasting serum asprosin levels between obese children and controls and to investigate the relationships of asprosin with body mass index (BMI) and biochemical markers of insulin resistance, insulin sensitivity, β-cell function and cardio-metabolic risk in obese non-diabetic children. MethodsThis cross-sectional, case-controlled, study included 43 obese children and 24 lean matched controls consecutively recruited. Children underwent clinical and biochemical assessments, including oral glucose tolerance test. Fasting asprosin serum levels were measured using an enzyme-linked immunosorbentassay (ELISA). Homeostasis model assessment of insulin resistance (HOMA-IR), homeostasis model assessment of β-cell function (HOMA-B), Matsuda-index, Insulinogenic-index, Areas Under the Curves for glucose and insulin were calculated. Successively, asprosin variable was dichotomized according to mean value in order to create two ordered classes of values. ResultsFasting asprosin concentration was significantly lower in obese children compared to controls (331.9 ± 120.5 vs 358.1 ± 74.1 pg/ml; p = 0.013). Asprosin was lower in boys than in girls (313.7 ± 59.5 vs 361.1 ± 127.2 pg/ml; p = 0.044), while BMI standard deviation score (SDS) was higher in boys compared to girls (p = 0.024). Asprosin was negatively correlated with BMI (p = 0.024), BMI SDS (p = 0.044) and male sex (p = 0.043) in the entire cohort. No significant differences in asprosin levels were demonstrated between insulin resistant and non-insulin resistant obese children. Logistic regression models documented a significant negative association between BMI SDS and dichotomized asprosin. In particular, higher BMI SDS values were associated to lower asprosin serum levels class. A receiver operating characteristic (ROC) analysis showed existence of the best cut-off for BMI SDS (+2.7 SDS) variable into discriminating patients belonging to two asprosin classes in our cohort. ConclusionsIn conclusion, asprosin serum levels were significantly lower in obese children compared to control.Fasting asprosin decreased with increasing BMI, but it was not significantly affected by IR.

Glycated haemoglobin as a screening test for abnormal glucose homeostasis in childhood obesity

To estimate the proportion of type 2 diabetes mellitus and abnormal glucose homeostasis in childhood obesity and assess the predictive role of HbA1c as a diagnostic marker compared with oral glucose tolerance testing (OGTT). A retrospective study in a tertiary paediatric hospital. Data were collected on all overweight or obese children who underwent routine OGTT between 2012 and 2016. Ethnicity, anthropometry, comorbidities and other risk factors associated with diabetes were recorded systematically. Fasting venous glucose, insulin and HbA1c values, along with 120-min venous glucose were recorded. Receiver operating characteristic (ROC) curve analysis was performed to derive optimum thresholds of HbA1c for detection of type 2 diabetes, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT). Predictive HbA1c thresholds forthe detection of abnormal glucose homeostasis in children with obesity were calculated. Of 156 children, 13 (8%, 10 female, 10 Asian) had type 2 diabetes, 95 (61%) had normal glucose tolerance, 18 (12%) had isolated IFG, 19 (12%) had isolated IGT, and another 11 (7%) had both IFG and IGT. The proportion of abnormal glucose homeostasis was 39%. ROC curve analysis demonstrated that HbA1c ≥42mmol/mol (6.0%) predicted type 2 diabetes (specificity 95%, sensitivity 85%) but performed moderately for IFG (specificity 46%, sensitivity 78%) and IGT (specificity 78%, sensitivity 55%). Despite HbA1c being a less-sensitive diagnostic tool compared with OGTT for children with IFG and IGT, it is reliable in detecting type 2 diabetes in asymptomatic children with obesity, instead of the labour- and cost-intensive OGTT.

Arachidonic acid status negatively associates with forearm bone outcomes and glucose homeostasis in children with an overweight condition or obesity.

Long-chain polyunsaturated fatty acids are implicated in musculoskeletal health in adults. This study examined whether fatty acid status relates to bone health outcomes in children with overweight condition or obesity (body mass index z score, 3.1 ± 0.1; age, 9.0 ± 0.2 years; n = 108). Nondominant forearm bone density (distal one-third), geometry (4% site), and soft tissue composition (66%) were assessed using dual-energy X-ray absorptiometry and peripheral quantitative computed tomography. Red blood cell (RBC) fatty acid profile and indices of glucose homeostasis were measured. Differences in outcomes among RBC arachidonic acid (AA, C20:4n-6) tertiles were tested using mixed-model ANOVA. Ultra-, mid-, and total-distal forearm bone mineral content, adjusted for sex, age, percentage body fat, race, and forearm length, were 10% to 13% greater in children in the first AA tertile relative to the third. Children in the second tertile had the highest bone cross-sectional area and estimated strength at the 66% radius. Muscle cross-sectional area was 15% lower in the third tertile compared with the first, along with higher fasting insulin concentrations (27%) and homeostasis model of assessment estimate of insulin resistance (31%). Higher RBC AA status aligns with deficits in forearm bone mass, geometry, and muscle mass in children with excess adiposity and early signs of insulin resistance. Novelty Higher arachidonic acid status is associated with lower forearm bone mass in children with overweight condition or obesity. Children with higher arachidonic acid status had increased fasting insulin concentrations and indices of insulin resistance.

Insulin function in obese children within the low and high ranges of impaired fasting glycemia.

Impaired fasting glycemia (IFG) reflects an intermediate hyperglycemia in the fasting state. Which fasting glucose level that actually is associated with impaired insulin-glucose homeostasis in children and adolescents with obesity is unknown. The aim of this study was to investigate how insulin and glucose homeostasis in children and adolescents with obesity in Sweden varies within different fasting glucose levels in the non-diabetic range. The subjects, n = 333, were divided into three groups based on their fasting glucose level. Normoglycemic range: up to 5.5 mmol/L (n = 268); the exclusive range the American Diabetes Association (ADA) has for IFG diagnosis: 5.6-6.0 mmol/L (n = 44); and IFG according to World Health Organization: 6.1-6.9 mmol/L (n = 21). The three groups were of similar age, degree of obesity, fasting insulin levels, sex, and migrant background distribution. We used an insulin-modified frequent sample intravenous glucose tolerance test to study acute insulin response (AIR), insulin sensitivity (SI), and disposition index (DI) in children and adolescents with obesity. The main outcome measures were AIR, SI, and DI in three groups based on fasting glucose level. Fasting glucose levels ranging from 5.6 to 6.0 mmol/L were not associated with a lower AIR, SI, or DI compared with the normoglycemic range. However, glucose levels ranging from 6.1 to 6.9 mmol/L were associated with lower AIR and lower DI, but no statistical differences in SI were present. IFG in the exclusive ADA range was not associated with disturbed glucose metabolism. This suggests that IFG contributes to adverse metabolic profile in children differently to what has been described previously in adult obese populations.

Glucose Homeostasis and Energy Balance in Children With Pseudohypoparathyroidism.

Pseudohypoparathyroidism (PHP) is a rare genetic disorder characterized by early-onset obesity and multihormone resistance. To treat abnormal weight gain and prevent complications such as diabetes, we must understand energy balance and glucose homeostasis in PHP types 1A and 1B. The aim of this study was to evaluate food intake, energy expenditure, and glucose homeostasis in children with PHP. Assessments included resting energy expenditure (REE), physical activity, food intake, sucrose preference, questionnaires, endocrine status, and auxological status. All patients underwent an oral glucose tolerance test (OGTT). Vanderbilt University Medical Center. We assessed 16 children with PHP1A, three with PHP1B, and 15 healthy controls. Food intake during an ad lib buffet meal and glucose at five time points during OGTT. PHP1A and control groups were well matched. Participants with PHP1A had significantly lower REE without concomitant change in food intake or physical activity. At baseline, participants with PHP1A had significantly lower fasting glucose and insulin resistance. During OGTT, participants with PHP1A had significantly delayed peak glucose and a slower rate of glucose decline despite similar oral glucose insulin sensitivity. Participants with PHP1A had 0.46% lower HbA1c levels than controls from a clinic database after adjustment for OGTT 2-hour glucose. The PHP1B group was similar to the PHP1A group. In contrast to other monogenic obesity syndromes, our results support reduced energy expenditure, not severe hyperphagia, as the primary cause of abnormal weight gain in PHP. Patients with PHP are at high risk for dysglycemia without reduced insulin sensitivity.

Glucose homeostasis in GHD children during long-term replacement therapy: a case-control study.

To evaluate glucose homeostasis in children with growth hormone (GH) deficiency (GHD) receiving long-term replacement therapy. We evaluated glucose, insulin, HOmeostasis Model Assessment (HOMA-IR), and HbA1c in 100 GHD children at diagnosis and during 5 years of therapy. One hundred healthy children comparable to patients were evaluated at baseline and after 1 and 5 years. No difference was detected at baseline between GHD patients and controls in glucose (79.58 ± 9.96 vs. 77.18 ± 8.20 mg/dl), insulin (4.50 ± 3.24 vs. 4.30 ± 2.60 µU/ml), HbA1c (5.20 ± 0.31 vs. 5.25 ± 0.33%) levels, and HOMA-IR (0.93 ± 0.72 vs. 0.86 ± 0.61). One year of GH was associated with a significant increase in insulin (7.21 ± 4.84, p < 0.001) and HOMA-IR (1.32 ± 0.98, p < 0.001) in GHD children, which became different from controls (p < 0.001 and p = 0.004). These parameters did not change further during the following years of treatment in GHD subjects. In contrast, controls did not show significant changes in insulin (4.40 ± 2.60) and HOMA-IR (0.82 ± 0.60) during the first year; however, at the fifth year of the study a significant increase in insulin (6.50 ± 3.50, p = 0.004) and HOMA-IR (1.29 ± 0.54, p < 0.001) was documented, making these parameters comparable between patients and controls. Our results suggest that growth hormone (GH) treatment is not associated with significant impairment of insulin sensitivity in GHD children. The slight impairment observed in GHD adolescents after long-term GH is comparable to that physiologically occurring in healthy pubertal subjects.

Blood glucose monitoring in pediatric patients on cardio-pulmonary bypass

Background: Meticulous blood glucose control during cardio-pulmonary bypass has received a lot of attention recently. Children are more vulnerable to adverse effects of cardio-pulmonary bypass (CPB) on glucose homeostasis. Objectives of the study were to find out changes in blood glucose due to cardio-pulmonary bypass and the Insulin requirements intra - operatively. Methods: A single centre, prospective trial in 130 children undergoing cardiac surgery for congenital cyanotic/ acyanotic heart disease, requiring cardio-pulmonary bypass. We administered dextrose IV 0.5g/kg/hr in pre bypass period to avoid hypoglycemia. Blood glucose levels were measured at various point of time [baseline, after 10 min and then every half hourly during bypass, 30 minutes after bypass and next during the immediate post-operative using a Hemo-cue glucometer]. To control blood glucose on cardio-pulmonary bypass pump, we used inj. Insulin as per study protocol. The statistical analysis was done using paired and unpaired t test & chi square test. Results: We had examined 130 pediatric patients going on CPB for cardiac surgery. Blood glucose was monitored in patients who did not required inj. Insulin (Group II) on bypass for hyperglycemia (n=33) while 97 patients required insulin (Group I) on bypass because of hyperglycemia. 74% of patient required insulin on pump shows that cardio-pulmonary bypass significantly affects glucose homeostasis in children; most of the children (43%) required insulin 30 min after starting cardio-pulmonary bypass. Conclusions: Blood glucose rise in children of congenital cardiac disease was significant after induction of anesthesia; on hypothermic CPB children of congenital cardiac disease may had rising blood glucose trend and the pre-operative blood glucose significantly affects the trend of blood glucose on CPB. The duration of CPB might not significantly affect insulin requirement of pediatric patients. CPB significantly affected glucose homeostasis in children. Hence it seems prudent to administer small amount of IV dextrose in prebypass period to avoid hypoglycemia but rate and dose of insulin should be adjusted as it may affect blood glucose level on CPB.

Thiazide-Induced Hyperglycemia in a 6 Years Old Girl: A Case Report and Review of the Literature

Various factors may affect glucose homeostasis in children resulting in rare clinical scenarios. Alterations in glucose regulation and hyperglycemia may result from pharmacologic interventions and the introduction of new medications. Although used most commonly to control fluid balance, an uncommon adverse effect of the thiazide diuretics is hyperglycemia. We present a 6-year-old girl with congenital heart disease who developed clinically significant hyperglycemia when a thiazide diuretic was added to her medication regimen. Previous reports of similar responses are reviewed, physiologic mechanisms are postulated, and treatment strategies are proposed. J Med Cases. 2016;7(2):49-51 doi: http://dx.doi.org/10.14740/jmc2403w

A preliminary trial of the effect of recombinant human growth hormone on short-term linear growth and glucose homeostasis in children with Crohn’s disease

It is unclear whether recombinant human growth hormone (rhGH) improves linear growth in children with Crohn's disease (CD). To investigate the effects of rhGH on height velocity (HV) and glucose homeostasis over a 6-month period. Randomized controlled trial in two tertiary children's hospitals in 22 children with inflammatory bowel disease amongst whom 21 had CD. Duration of disease from diagnosis and number of acute relapses requiring either exclusive enteral nutrition or therapeutic dose of oral prednisolone were similar in the treatment and control groups. Either rhGH (0·067 mg/kg per day) as daily subcutaneous injections (rhGH group; n, 11) or no rhGH, (Ctrl; n, 11) for 6 months. Percentage change in HV after 6 months in the two groups. Auxology, puberty, skeletal age, disease factors, treatment and glucose homeostasis were also assessed. Median HV increased from 4·5 (range, 0·6, 8·9) at baseline to 10·8 (6·1, 15·0) cm/year at 6 month (P = 0·003) in the rhGH group, whereas in the Ctrl group, it was 3·8 (1·4, 6·7) and 3·5 cm/year (2·0, 9·6), respectively (P = 0·58). Median percentage increase in HV after 6 months in the rhGH group was 140% (16·7, 916·7) compared with 17·4% (-42·1%, 97·7%) in the Ctrl group (P < 0·001). There were no significant differences in disease activity and proinflammatory cytokines at baseline and 6 months in both groups and change in bone age for chronological age was also similar in the two groups. In the rhGH group, fasting insulin increased from 4·0 (2·0, 11·0) to 7·0 mU/l (2·0, 16·0) (P = 0·02), whereas in the Ctrl group, it was 3·0 (1·2, 12·7) and 3·8 mU/l (2·1, 7·0) (P = 0·72), respectively. Although this pilot trial shows that rhGH can improve short-term linear growth in children with CD, the clinical efficacy of this therapy needs to be further studied in longer-term studies of growth, glucose homeostasis and disease status.

PPAR-γ2 Pro12Ala polymorphism is associated with post-challenge abnormalities of glucose homeostasis in children and adolescents with obesity

The aim of the study was to investigate the association between PPAR-gamma2 Pro12Ala polymorphism and laboratory characteristics of carbohydrate metabolism in children and adolescents with obesity. In addition, serum levels of tumor necrosis factor (TNF)-alpha, and soluble form of its receptors (sTNFR1 and sTNFR2) were assessed. In a cross-sectional study, 79 obese children and adolescents of Caucasian origin were investigated. PPAR-gamma2 Pro12Ala polymorphism was determined using polymerase chain reaction--restriction fragment length polymorphism technique. Serum levels of TNF-alpha, sTNFR1 and sTNFR2 were measured by enzyme amplified sensitivity immunoassay. The minor Ala allele frequency was found to be 14.56% in our cohort. No significant differences in age, BMI, waist circumference, blood pressure, serum lipid, uric acid, TNF-alpha, sTNFR1 and sTNFR2 values were found between carriers of the Ala allele (Pro/Ala and Ala/Ala; n=21) vs. homozygous carriers of the Pro allele (Pro/Pro; n=58). However, post-challenge (120 min) plasma glucose and insulin values were significantly lower in Ala allele carriers vs. homozygous Pro allele carriers (6.56 +/- 0.26 vs. 7.36 +/- 0.25 mmol/L and 65.9 +/- 13.8 vs. 111.8 +/- 20.7 microU/mL, respectively; p < 0.05); while no significant differences were found at fasting state. The association between PPAR-gamma2 Prol2Ala polymorphism and glucose metabolism is already present in children and adolescents with obesity who might be at the very beginning of the natural course of type 2 diabetes. At this stage, higher insulin sensitivity can be detected in Ala allele carriers compared to homozygous Pro subjects at post-challenge but not in fasting state; however, the TNF-system seems not to be involved in the alteration of glucose homeostasis due to PPAR-gamma2 Pro12Ala polymorphism.

Does Dietary Carbohydrate Content Affect Glucose Homeostasis in Children?

Does Dietary Carbohydrate Content Affect Glucose Homeostasis in Children?

Effect of minimizing preoperative fasting on perioperative blood glucose homeostasis in children

SummaryTwo hundred healthy, unpremedicated children, ages 1–10 years, scheduled for elective outpatient surgery were studied in order to examine the effect of minimizing preoperative fasting on perioperative blood glucose concentrations in paediatric patients. None of the patients ingested solids after midnight. On the day of surgery, the children were assigned to one of two groups. Group A children (n= 113) were not allowed any liquids for at least 6 h prior to surgery (NPO). Children in Group B (n= 87) ingested 10 ml·kg−1 of apple juice 2–4 h prior to the induction of anaesthesia. All patients received lactated Ringer's solution intraoperatively, unless BG at induction was &lt; 50 mg·dl−1 (2.8 m·mol·l−1) in which case dextrose 2.5% in lactated Ringer's solution was administered. None of the patients who received apple juice was hypoglycaemic during induction of anaesthesia. However, two children in the NPO group had blood glucose values ± 50 mg·dl−1 (2.8 m·mol·l−1) at the time of induction of anaesthesia. Thirteen (11%) patients in Group A and 6 (7%) patients in Group B showed either no change or a further decrease in their postoperative BG concentration as compared with their induction values. Two of 43 patients in Group A and 2 of 41 patients in Group B had gastric fluid volumes &gt; 0.4 ml/kg. All patients in both groups had gastric pH &lt; 2.5. This study shows that gastric fluid volume and pH following a 2–4 h fast are not different from the values measured in children who were subjected to a traditional fasting period of 6 h or longer. Moreover, apple juice consumed 2–4 h prior to surgery neither buffers gastric pH nor does it modify intraoperative glucose homeostasis in children.

Glucose homeostasis in children with severe cyanotic congenital heart disease

Six children with severe forms of cyanotic congenital heart disease underwent a series of challenge studies in an attempt to clarify the pathophysiology of the hypoglycemia observed in these disorders. The glycemic response to intravenous glucagon positively correlated with the fasting glucose concentration (P<0.01). Following a 26-to 30-hour fast, two of six CCHD children developed hypoglycemia in the absence of significant differences in ketone body, alanine, or insulin concentrations when compared with controls. Blood lactate (P<0.05), pyruvate (P<0.02), plasma glucagon (P<0.05), and cortisol (P<0.01) values were increased at the end of the fast when compared to those in normal fasting children. Intravenous alanine challenge at the end of the fast demonstrated normal glycemic responses in all subjects, regardless of initial plasma glucose or lactate concentrations. One subject had an abnormal rise in lactate and β-hydroxybutyrate following alanine administration. Glucose and alanine turnover studies utilizing stable isotopes revealed normal glucose kinetics but lower alanine flux (8.4±1.1 μmol/kg·min vs 12.3±1.15 μmol/kg/min, P<0.05) and metabolic clearance rates (28.0±3.5 vs 51.0±7.4 ml/kg·min) in the CCHD subjects when compared to normal children. We conclude that hepatic glycogenolytic and glyconeogenic enzyme mechanisms are intact in patients with CCHD. The hypoglycemia is associated with glycogen depletion but not with abnormal secretion of glycoregulatory hormones. The decreased alanine metabolic clearance rate and the increased fasting lactate and pyruvate concentrations may reflect decreased hepatic uptake of these potential gluconeogenic substrates, leading to a functional defect in hepatic gluconeogenesis. These abnormalities may be secondary to decreased hepatic perfusion, but other mechanisms cannot be directly excluded. Six children with severe forms of cyanotic congenital heart disease underwent a series of challenge studies in an attempt to clarify the pathophysiology of the hypoglycemia observed in these disorders. The glycemic response to intravenous glucagon positively correlated with the fasting glucose concentration (P<0.01). Following a 26-to 30-hour fast, two of six CCHD children developed hypoglycemia in the absence of significant differences in ketone body, alanine, or insulin concentrations when compared with controls. Blood lactate (P<0.05), pyruvate (P<0.02), plasma glucagon (P<0.05), and cortisol (P<0.01) values were increased at the end of the fast when compared to those in normal fasting children. Intravenous alanine challenge at the end of the fast demonstrated normal glycemic responses in all subjects, regardless of initial plasma glucose or lactate concentrations. One subject had an abnormal rise in lactate and β-hydroxybutyrate following alanine administration. Glucose and alanine turnover studies utilizing stable isotopes revealed normal glucose kinetics but lower alanine flux (8.4±1.1 μmol/kg·min vs 12.3±1.15 μmol/kg/min, P<0.05) and metabolic clearance rates (28.0±3.5 vs 51.0±7.4 ml/kg·min) in the CCHD subjects when compared to normal children. We conclude that hepatic glycogenolytic and glyconeogenic enzyme mechanisms are intact in patients with CCHD. The hypoglycemia is associated with glycogen depletion but not with abnormal secretion of glycoregulatory hormones. The decreased alanine metabolic clearance rate and the increased fasting lactate and pyruvate concentrations may reflect decreased hepatic uptake of these potential gluconeogenic substrates, leading to a functional defect in hepatic gluconeogenesis. These abnormalities may be secondary to decreased hepatic perfusion, but other mechanisms cannot be directly excluded.

METABOLIC RESPONSE TO I.V. GLUCAGON IN CHILDREN WITH CHRONIC LIVER DISEASE

Studies were performed to evaluate glucose homeostasis in children with intrahepatic biliary hypoplasia (IBH) with chronic cholestatic syndrome and growth retardation. Eight I.V. glucagon tolerance tests (30 μg/kg) on five IBH patients (4-12 yrs of age) were compared to 8 controls. Fasting (14-16 hr) glucose was lower in IBH (67 ± 4 mg% vs 80.8 ± 3.67; p < 0.025), and peak rise was significantly less (107 ± 10.6 vs 147 ± 7.9; p < 0.01). Baseline urinary cyclic AMP levels in IBH vs controls (5.8 ± 2 M ± S.E.M. nmoles/mg creatinine vs 4.5 ± 0.4) and 2 hour excretion response to glucagon (31.1 ± 3 vs 28.6 ± 5.2) were not significantly different. Insulin response to glucagon were similar in IBH vs control. Glucagon has previously been shown to lower plasma gluconeogenic amino acids as a indication of hepatic uptake and gluconeogenesis. Fasting plasma alanine was not significantly different in IBH vs control (210 ± 38 umoles/L vs 245 ± 40). Controls had a significant delta decline at 30 minutes post - glucagon of 100 umoles/L for alanine, 66 for glycine and 39 for glutamine plus asparagine. IBH patients failed to elicit a consistent reduction in gluconeogenic amino acids. These studies suggest that hepatic gluconeogenesis and glycogen storage are impaired in chronic liver disease. The noted cyclic AMP response may reflect adequate adenyl cyclase activity in spite of hepatocellular damage.