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The 'two-bag' system, an adaptation of the euglycemic clamp technique, consists of simultaneous administration of 2 intravenous (IV) fluid bags of differing dextrose concentrations. Individualized therapy is dictated by adjustment of the infusion rate of each bag. We sought to assess the benefits of the two-bag system in the initial acute emergency department management of children in diabetic ketoacidosis (DKA). Thirty-three children presenting to an urban pediatric emergency department in DKA were randomized into 2 groups: patients managed with the two-bag system and patients managed with the traditional 'one-bag' system. Other aspects of the management were standardized. Outcome measures included rate of decline in serum glucose, rate of bicarbonate correction, time on IV insulin therapy, and response time for IV fluid changes. Study period was defined as time on IV insulin therapy. There were no differences between the 2 groups in demographic parameters, initial baseline metabolic parameters, or total time on IV insulin therapy. There were no differences between the groups in average rates of serum glucose decline: two-bag 33.1 mg/dL/hr (s.e. 5.57, 95% CI 22.2, 44), one-bag 30.2 mg/dL/hr (s.e. 5.72, 95% CI 19, 41.4); average rate of serum bicarbonate correction: two-bag 1.19 mEq/L/hr, one-bag 1.27 mEq/L/hr; or the average number of IV fluid bags used: two-bag 4.1 bags, one-bag 3.2 bags. However, there was a difference between the groups in regard to elapsed total time to make changes in the IV fluids: two-bag 1 minute, one-bag 42 minutes, (p <0.001). The 'two-bag' system enables a faster response time in making IV fluid therapy changes. This efficiency makes this system ideal for use in the emergency department. [ABSTRACT FROM AUTHOR]

1 case-controlled retrospective analysis compared the "two bag system," based on the euglycemic clamp technique, versus the traditional "one bag" method for intravenous diabetic ketoacidosis management. The two bag system can provide more cost-effective intravenous dextrose and fluid delivery and enhance quality of care by improving the efficiency, timeliness, and flexibility of overall control.

Insulin-like growth factor (IGF) binding protein-1 (IGFBP-1) gene transcription is known to be inhibited by insulin in vivo and in vitro. Levels of IGFBP-1 typically rise during fasting but also rise after acute hypoglycemia, including that induced by insulin, through an unknown mechanism that may involve counterregulatory hormones such as cortisol. To study the regulation of IGFBP-1 secretion during fasting, we measured IGFBP-1, insulin, cortisol, GH, and glucose during the course of standardized fasting studies in a total of 21 children. The fasting studies lasted 13-32 h and were terminated for a whole-blood glucose concentration of less than 50 mg/dL (2.8 mmol). Of the children studied, 9 children had no disorder, 8 had ketotic hypoglycemia, 2 had isolated GH deficiency, and 2 had fatty acid oxidation disorders. During fasting, IGFBP-1 rose above the mean baseline levels of 28+/-5 ng/mL to a mean level+/-SEM of 336+/-59 ng/mL at the time of hypoglycemia (P=0.001). IGFBP-1 was strongly associated with serum insulin and cortisol levels over the entire course of fasting (P < 0.0001)). The interaction of the 2 hormones across time was also strongly significant (P < 0.0001). There was no statistically significant association between IGFBP-1 and GH or glucose. At the time of hypoglycemia, insulin levels were suppressed to 1.7 microU/mL or less, and there was no correlation between IGFBP-1 levels at the end of fasting and final insulin level. In contrast, cortisol levels correlated with IGFBP-1 in the final hypoglycemic sample (r=0.56, P < 0.01). Partial correlation analysis revealed that the relationship between IGFBP-1 and cortisol was unchanged when the data was controlled for insulin levels. These data show that insulin and cortisol both regulate IGFBP-1 secretion during fasting; the effects of insulin and cortisol are strong during the course of fasting. Significant hypoglycemia stimulates a further rise in IGFBP-1, which seems to be regulated, in part, by cortisol. The cortisol-induced rise in IGFBP-1 during fasting and during hypoglycemia potentially serves to prevent the hypoglycemic effects of free IGFs.

We describe three families with hypoglycemia caused by familial hyperinsulinism (HI) in whom vertical transmission of the disorder occurred, suggesting autosomal dominant (AD) inheritance. We therefore examined the relationship between the apparent AD disorder and the more common autosomal recessive (AR) form of HI, which has recently been linked to the sulfonylurea receptor on chromosome 11p15.1. The clinical features of the 11 patients with AD HI were milder than those seen in 14 patients with AR HI. Hypoglycemia was readily controlled with either diet alone or with diazoxide in 10 of 11 patients with AD HI but in none of those with the AR form. In one large pedigree, analysis of genomic DNA with polymorphic simple sequence repeat markers excluded linkage of AD HI to the SUR locus in a dominant manner. The possibility of linkage to the SUR locus could not be absolutely excluded in the two smaller pedigrees. None of the published mutations of the SUR gene identified in patients with AR HI were detected in the patients with the AD form. We conclude that the AD form of hyperinsulinism is phenotypically different from the AR variant. The identification of more families with this form of HI may make it possible to locate the responsible gene by the use of linkage analysis.

The diagnosis of hypoglycemia caused by hyperinsulinism may be difficult because insulin levels are not uniformly elevated at the time of hypoglycemia. Insulin-like growth factor binding protein-1 (IGFBP-1) is a 28 kd protein whose secretion is acutely inhibited by insulin. We hypothesized that serum levels of IGFBP-1 would be a useful marker of hyperinsulinism. We measured IGFBP-1 levels during the course of standardized fasting studies in hospitalized children; 36 patients became hypoglycemic during the fasting studies, and samples obtained at the point of hypoglycemia were analyzed. On the basis of the currently used diagnostic criteria, 13 children had hyperinsulinism, 16 had ketotic hypoglycemia or no disorder, 3 had hypopituitarism or isolated growth hormone deficiency, 2 had glycogen storage disease type 1 and 2 had fatty acid oxidation disorders. In control subjects (children with ketotic hypoglycemia or no disorder), IGFBP-1 levels rose during fasting to a mean of 343.8 +/- 71.3 ng/ml in the sample drawn at the time of hypoglycemia. Mean IGFBP-1 levels at hypoglycemia for the entire group with hyperinsulinism were 52.4 +/- 11.5 ng/ml, significantly different from levels seen in control subjects (p < 0.0001). In children with moderately controlled hyperinsulinism (fasting tolerance > 4 hours), mean IGFBP-1 levels at the time of hypoglycemia were 71.5 +/- 16.9 ng/ml. IGFBP-1 levels in the children with poorly controlled hyperinsulinism (fasting tolerance < 4 hours) failed to rise during fasting, with a mean of 30.1 +/- 10.4 ng/ml in the final sample. IGFBP-1 levels were inversely correlated with serum insulin and C-peptide levels (r = -0.71 and -0.72, respectively; p < 0.0001). Patients with other endocrinologic or metabolic diseases that result in fasting hypoglycemia demonstrated a rise in IGFBP-1 levels similar to that seen in ketotic hypoglycemia. Low serum levels of IGFBP-1 at the time of hypoglycemia provide an additional marker of insulin action that might help to differentiate hyperinsulinism from other hypoglycemic disorders.

Objective: We have evaluated the frequency of endocrine abnormalities in a large group of patients with hypothalamic/chiasmatic glioma (H/CG) and its correlation with the different forms of therapy., Design: Descriptive retrospective study using case note review analysis., Patients: The records of 68 children who survived H/CG were analysed. One third had neurofibromatosis. The mean age at tumour presentation was 5 years. The median time of follow-up was 3.6 years. Thirty-eight children received cranial radiation, of whom 17 also had surgery. Surgery was performed in a total of 24 patients. Fifteen patients received only chemotherapy. Eight children, all with neurofibromatosis, received no specific tumour treatment., Measurements: Endocrine dysfunction was determined by clinical manifestations and biochemical evaluation of hypothalamic-pituitary function., Results: Endocrine dysfunction occurred in 42% of the children. The most common disorder was GH deficiency (GHD). Of 50 children evaluated, 15 of the 19 with GHD received cranial irradiation (P < 0.05). HOwever, 15 children treated with more than 15 Gy grew normally. Precocious puberty was diagnosed in 11 patients. Nine patients, all treated with cranial irradiation, developed hypogonadotrophic hypogonadism. Of the 14 patients with hypothyroidism, 10 had surgery (P < 0.005). Hypoadrenalism and diabetes insipidus each occurred in eight patients, and were associated with multiple endocrine deficiencies and surgery. Endocrine deficiencies occurred in children with neurofibromatosis as frequently as children without neurofibromatosis but only when comparing those treated with cranial irradiation or surgery., Conclusions: Nearly all studies assessing the patients with different tumour therapy evaluate patients wit different tumour types. This study investigates a specific and large population of patients with H/CG and correlates the different form of treatment with the endocrine outcome. Precocious puberty, in children with this tumour, is probably due to tumour location rather than oncological therapy. Conversely, although endocrine deficiencies can be a result of tumour location, the major causes of endocrine abnormalities were field irradiation and tumour surgery. A notable finding not previously reported is that endocrine dysfunction occurs less often in neurofibromatosis patients treated conservatively. Furthermore, this study documents that a significant number of young children grew normally despite receiving brain irradiation of greater than 45 Gy.