Deborah V. Edidin

A controlled trial of insulin infusion and parenteral nutrition in extremely low birth weight infants with glucose intolerance

To determine whether a continuous insulin infusion improves glucose tolerance in extremely low birth weight infants, we conducted a prospective, randomized trial in 24 neonates 4 to 14 days old (mean birth weight 772.9 +/- 128 gm; mean gestational age 26.3 +/- 1.6 weeks). Infants who had glucose intolerance were randomly assigned to receive either intravenous glucose and total parenteral nutrition with insulin through a microliter-sensitive pump or standard intravenous therapy alone. One infant assigned to receive insulin never required it. The groups were similar in birth weight, gestational age, race, gender, medical condition, and energy intake before the study. The mean duration of therapy was 14.6 days (range 7 to 21 days). During the study, the 11 insulin-treated infants tolerated higher glucose infusion rates (20.1 +/- 2.5 vs 13.2 +/- 3.2 mg/kg/min (1.1 +/- 0.1 vs 0.7 +/- 0.2 mmol/L); p less than 0.01), had greater nonprotein energy intake (124.7 +/- 18 vs 86.0 +/- 6 kcal/kg/day; p less than 0.01), and had better weight gain (20.1 +/- 12.1 vs 7.8 +/- 5.1 gm/kg/day; p less than 0.01) than the 12 control infants. The incidence of hypoglycemia, electrolyte imbalance, chronic lung disease, and death did not differ between groups. We conclude that a controlled insulin infusion improves and sustains glucose tolerance, facilitates provision of calories, and enhances weight gain in glucose-intolerant premature infants.

Echocardiographic evidence for impaired myocardial performance in children with type I diabetes mellitus

Thirty-three children with type I diabetes mellitus and 51 normal children underwent M-mode echocardiography. Abnormalities of myocardial performance were present in many of the diabetic children. The mean end-systolic volume of the left ventricle was greater in diabetics compared to control subjects. Mean ejection fraction, minor axis shortening, and velocity of circumferential fiber shortening were decreased in the diabetics. There was no evidence of increased myocardial mass in these diabetic children. There was no correlation between myocardial dysfunction, clinical assessment of control, or glycohemoglobin in the diabetic children.

Intractable early childhood obesity as the initial sign of insulin resistant hyperinsulinism and precursor of polycystic ovary syndrome.

OBJECTIVE We report that intractable early childhood obesity may be associated with severe insulin resistance syndromes (pseudo-Cushings syndrome and pseudo-acromegaly) and precede polycystic ovary syndrome (PCOS). STUDY DESIGN/RESULTS Patient 1 had prepubertal obesity followed by early puberty and was diagnosed with pseudo-Cushings syndrome and insulin resistance at 10.3 years. Oligomenorrhea, androgen excess, and type 2 diabetes mellitus (DM2) emerged at 13.5 years. Patient 2 developed intractable prepubertal obesity followed by atypical true sexual precocity and pseudo-Cushings syndrome in early childhood. By 11.3 years, oligomenorrhea, androgen excess, and DM2 had appeared. Patient 3 had prepubertal overgrowth in weight and height and was diagnosed with pseudo-acromegaly, menstrual irregularity, androgen excess, and impaired glucose tolerance at 14.3 years of age. Patient 4 had prepubertal overgrowth that evolved into pseudo-acromegaly, insulin resistance, secondary amenorrhea, and androgen excess at 15.6 years. CONCLUSIONS Intractable prepubertal obesity was recognized to culminate in early childhood pseudo-Cushings syndrome or pseudo-acromegaly, which are manifestations of insulin-resistant hyperinsulinism, and to herald adolescent PCOS.

The Effect of Dexamethasone and Surgically Induced Intrauterine Growth Retardation on Renal and Hepatic Levels of Phosphoenolpyruvate Carboxykinase in the Rat

Renal and hepatic levels of the rate-limiting gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK) were determined in control and intrauterine growth-retarded rate neonates and dams. Dexamethasone and surgically induced intrauterine growth retardation (IUGR) resulted in an elevation of neonatal renal PEPCK activity, but did not affect hepatic PEPCK levels. In the dam, glucocorticoid administration resulted in an increase in renal PEPCK, but did not affect the hepatic enzyme. We have demonstrated that, unlike the hepatic enzyme, renal PEPCK could potentially contribute to gluconeogenesis in utero, since dexamethasone administration significantly increased renal PEPCK at birth. This study confirms the hypothesis that hepatic and renal PEPCK activities are regulated independently in both the adult and neonatal animal.

Nesidioblastosis is Not a Histopathologic Diagnosis. 380

Nesidioblastosis is a condition characterized clinically by intractable hyperinsulinemic hypoglycemia. Since serum insulin levels are rarely extremely elevated, diagnostic confirmation has historically relied upon characteristic histopathologic changes in the pancreatic tissue removed as a therapeutic modality of this condition. Although the finding of abundant nests of endocrine tissue budding off of ductal elements is considered to be confirmatory, there have been reports in the adult and pathology literature that such findings may be present in normal individuals. We present here the case of an infant which demonstrates that nesidioblastosis is not a histopathologic diagnosis.

29 DECREASE IN CYTOCHROME P-450 DEPENDENT 3-N-DEMETHYLATION OF CAFFEINE MEASURED BY THE CAFFEINE 13 CO 2 BREATH TEST (CET) FOLLOWING GROWTH HORMONE THERAPY IN GROWTH HORMONE (GH) DEFICIENT CHILDREN

Significant changes in hepatic drug clearance occur in the transition from childhood to adulthood. These changes probably parallel the functional capacity of the hepatic cytochrome P-450 dependent mixed function oxidase (MFO) system. GH decreases hepatic MFO activity in animals and may act similarly in humans. Caffeine labelled with stable 13C has been shown to be a substrate for the MFO system. Five GH deficient children underwent CBT, with collections of expired air for 13CO2 enrichment analysis following ingestion of 13C-caffeine (3 mg/Kg) before, and 4-5 weeks following GH 0.1 u/Kg S.C. t.i.w. All children showed a decrease in % 13CO2 dose exhaled over 2 hours following GH administration:Pre 9.1±1.5, Post 7.3±2.9 (p < .05, paired t-test) The CBT is a safe effective technique for the measurement of the hepatic MFO system. N-demethylation of caffeine is decreased by GH therapy in GH deficient children. The capacity for N-demethylation is highest in prepubertal children. This may partially correlate with changing patterns of GH release.

Prepubertal Gynecomastia and Scalp Inunction-Reply

In Reply .—We thank Dr Harris for bringing attention to this interesting report of scalp inunction, resulting in isosexual precocity in a 5-year-old girl. We believe that our report is singular in that heterosexual precocity resulted, a condition that is more likely to be pernicious and pursued by invasive diagnostic procedures.

239 THE EFFECT OF INTRAUTERINE GROWTH RETARDATION (IUGR) UPON HEPATIC AND RENAL PHOSPHOENOL PYRUVATE CARBOXY- KINASE (PEPCK) ACTIVITY IN THE NEONATAL RAT

The contribution of renal gluconeogenesis to glucose homeostasis in the newborn has been neglected despite its well-established role in fasting glucose homeostasis. We have studied the activity of the key gluconeogenic enzyme PEPCK (forward spectro-photometric reaction) in normal and IUGR rat neonates (uterine vessel ligation) fasted for 4 hours postpartum (34°C).Neonatal PEPCK activity was lower than maternal hepatic (1.14±.11 μmol/min/g) and renal (0.99±0.10 μmol/min/g) activity. Hepatic PEPCK activity was diminished in IUGR animals, but this was not significant. In contrast, renal PEPCK activity was significantly increased in IUGR neonates. This suggests independent regulation of neonatal renal and hepatic gluconeogenesis. The compensatory increase in renal PEPCK activity in growth-retarded newborns may contribute significantly to gluconeogenic capacity since PEPCK is the rate-limiting enzyme in the system.

1121 ECHOCARDIOGRAPHIC EVIDENCE FOR IMPAIRED MYOCARDIAL PERFORMANCE IN CHILDREN WITH TYPE I DIABETES MELLITUS

Myocardial performance was assessed by M-mode echocardiography in 33 children (6 8/12-19 3/12 yr) with Type I diabetes mellitus and in 51 normal children (6 2/12-18 8/12). Left ventricular end systolic dimension (LVESD), and left ventricular end systolic volume/M2 (LVESV/M2) were greater in diabetics than controls. Left ventricular ejection fraction (LVEF), minor axis shortening (MAS), and velocity of circumferential fiber shortening (VCF) were less in diabetics than controls.Hgb A1 levels in children with diabetes (15.5±0.6%, range 10.1-22.2%, normal 5.9-8.7%) correlated with clinical assessment of control (p<.01). Age, Hgb A1, duration of diabetes, and clinical assessment did not predict myocardial function. We conclude that there is impaired myocardial contractility in some children with insulin-dependent diabetes not correlated with duration of diabetes, age, clinical assessment of control, or Hgb A1. The long-term significance of this finding and the effect of improved control remain to be assessed.