Release of human growth hormone during sleep is significantly related to slow, synchronized stages of sleep and therefore would seem to be controlled by related neural mechanisms. When sleep-waking cycles are reversed by 12 hours, the release of growth hormone with sleep is reversed; thus release does not follow an inherent circadian rhythm independent of sleep.

ABSTRACT.Background. There is an increase in the incidence of type 2 diabetes in children and adolescents. Absence of known diabetes autoimmune markers is sometimes required to confirm the diagnosis.Objective. To identify clinical and autoimmune characteristics of type 2 diabetes in a pediatric population.Method. We report an analysis of 48 children and adolescents with type 2 diabetes, compared with 39 randomly selected children with type 1 diabetes, diagnosed and followed at the Loma Linda University Pediatric Diabetes Center. Ethnic, familial, seasonal, and autoimmune marker characteristics are outlined. To determine the reliability of antibody testing in confirming the type of diabetes at diagnosis, we studied the incidence of positive islet cell antibodies (ICAs), glutamic acid decarboxylase antibodies (GADs), and insulin autoantibodies (IAAs) at diagnosis in both groups. ICA512, GADs, and IAAs were measured by radioimmunoassay.Results. The cohort with type 2 diabetes had a similar gender distribution as the group with type 1 diabetes but a significantly higher age at diagnosis. Ethnic background was significantly different between the 2 groups, predominantly Hispanic in type 2 and white in type 1. Body mass index was significantly higher in type 2 diabetes (mean ‫؍‬ 31.24 kg/m 2 ). Among the patients with type 2 diabetes, 33% presented in diabetic ketoacidosis, random blood glucose at diagnosis ranged from 11.4 to 22.25 mmol/L (228 -445 mg/dL), fasting C-peptide levels ranged from 0.89 to 2.7 nmol/L (2.7-8.2 ng/mL; normal: <1.36 nmol/L), and hemoglobin A 1C was 10.8 ؎ 3.5% (normal: <6.6%). None of these parameters was significantly different from the type 1 diabetes group. Although the incidence of diabetes antibody markers was significantly lower in type 2 versus type 1 diabetes, 8.1% of patients with type 2 diabetes had positive ICAs, 30.3% had positive GADs, and 34.8% had positive IAAs without ever being treated with insulin. In the type 2 diabetes group, none of the Hispanic patients had ICAs. However, there was no significant correlation between any of the diabetes antibodies and obesity, presence of acanthosis nigricans, or family history of diabetes. The frequency of thyroid antibodies was not significantly different from the group with type 1 diabetes. Daily insulin requirements 1 year after diagnosis were significantly lower in type 2 diabetes, ranging from 0 to 1.2 U/kg with a mean of 0.33. Conclusion.Absence of diabetes autoimmune markers is not a prerequisite for the diagnosis of type 2 diabetes in children and adolescents. Pediatrics 2001;107(6). URL: http://www.pediatrics.org/cgi/content/full/107/6/ e102; type 2 diabetes, adolescents, autoimmunity, islet cell antibodies, glutamic acid decarboxylase antibodies.

More than half of transplanted b -cells undergo apoptotic cell death triggered by nonimmunological factors within a few days after transplantation. To investigate the dynamic hypoxic responses in early transplanted islets, syngeneic islets were transplanted under the kidney capsule of balb/c mice. Hypoxiainducible factor-1a (HIF-1a ) was strongly expressed at post-transplant day (POD) 1, increased on POD 3, and gradually diminished on POD 14. Insulin secretion decreased on POD 3 in association with a significant increase of HIF-1a -related b -cell death, which can be suppressed by short-term hyperbaric oxygen therapy. On POD 7, apoptosis was not further activated by continually produced HIF-1a . In contrast, improvement of nerve growth factor and duodenal homeobox factor-1 (PDx-1) production resulted in islet graft recovery and remodeling. In addition, significant activation of vascular endothelial growth factor in islet grafts on POD 7 correlated with development of massive newly formed microvessels, whose maturation is advanced on POD 14 with gradual diminution of HIF-1a . We conclude that (1) transplanted islets strongly express HIF-1a in association with b -cell death and decreased insulin production until adequate revascularization is established and (2) early suppression of HIF-1a results in less b -cell death thereby minimizing early graft failure.

Children diagnosed with type 1 diabetes before 5 years of age may have different diabetes-related autoimmune and genetic characteristics from those diagnosed at a later age.

Cumulative exposure to ozone and sulfate in ambient air may predispose to the development of type 1 diabetes in children. Early infant formula feeding and passive smoking in the household may precipitate or accelerate the onset of type 1 diabetes.

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To determine the effect of insulin glargine on glycemic control in pediatric type 1 and 2 diabetes, a retrospective repeated-measure analysis of variance was performed of hemoglobin A1C (HbA1C), frequency of hypoglycemia and hyperglycemia, mean blood glucose, body mass index (BMI), and daily weight-adjusted insulin dosage before and after institution of glargine therapy in 72 children and adolescents with diabetes. At glargine start, age range was 1.2-19.6 years, mean age was 12.5 +/- 4.6 years, BMI was 22.48 +/- 6.3 kg/m(2), and mean HbA1C was 9.7 +/- 1.9%. Mean duration of diabetes was 3.58 years, and mean baseline insulin dose was 0.93 U/kg/day. Gender breakdown was 60% female, and the majority (83%) had type 1 diabetes. Average HbA1C decreased from 9.5% pre-glargine to 8.6% post-glargine (p < 0.001). HbA1C decrease was significant in both types of diabetes without a concomitant increase in frequency of hypoglycemia, BMI, or weight-adjusted insulin dose. Hypoglycemia decreased significantly in type 1 diabetes. Thus, glargine therapy may decrease HbA1C and frequency of hypoglycemia in toddlers, children, and adolescents with diabetes, without an increase in BMI or insulin requirements.

Background There is a recent focus on embolization of the portal vein by transplanted islets as a major cause of early graft loss. The resultant ischemia causes necrosis and/or apoptosis of cells within the liver. Thus, non-invasive assessment of the liver receiving the islet transplant is important to evaluate the status islet grafts. Methods In this study, we utilized non-invasive magnetic resonance imaging (MRI) for assessment of the post-transplant ischemic liver. Syngeneic islets in streprozotocin-induced diabetic mice were utilized. MRI and morphological liver assessments were performed at 0, 2, and 28 days after transplantation. Histological assessment of insulin, hypoxia induced factor 1-α and apoptosis were undertaken at similar time-points. Results Ischemic/necrotic regions in the liver were detected with MRI at 2 but not at 28 days after transplantation and were confirmed histologically. Liver injury was quantified from high intensity areas on T2-weighted images. Insulin release showed a peak 2 days after transplantation. Conclusion Onset and reversal of liver ischemia due to intraportal islet transplantation are detectable using T2-weighted MRI. These changes coincide with periods of maximum insulin release likely due to partial islet destruction. We propose that MRI, as a noninvasive monitor of graft-related ischemia, may be useful in assessment of liver and islet engraftment after intraportal islet transplantation in a clinical setting.