Hypoglycemia in the preterm neonate: etiopathogenesis, diagnosis, management and long-term outcomes.

Glucose, like oxygen, is of fundamental importance for any living being and it is the major energy source for the fetus and the neonate during gestation. The placenta ensures a steady supply of glucose to the fetus, while birth marks a sudden change in substrate delivery and a major change in metabolism. Hypoglycemia is one of the most common pathologies encountered in the neonatal intensive care unit and affects a wide range of neonates. Preterm, small for gestational age (GA) and intra-uterine growth restricted neonates are especially vulnerable due to their lack of metabolic reserves and associated co-morbidities. Nearly 30-60% of these high-risk infants are hypoglycemic and require immediate intervention. Preterm neonates are uniquely predisposed to developing hypoglycemia and its associated complications due to their limited glycogen and fat stores, inability to generate new glucose using gluconeogenesis pathways, have higher metabolic demands due to a relatively larger brain size, and are unable to mount a counter-regulatory response to hypoglycemia. In this review we will discuss the epidemiology; pathophysiology; clinical presentation; management and neurodevelopmental outcomes in affected infants and summarize evidence to develop a rational and scientific approach to this common problem.

Transient hypothyroidism in the newborn: to treat or not to treat.

Transient congenital hypothyroidism (CH) refers to a temporary deficiency of thyroid hormone identified after birth, with low thyroxine (T4) and elevated thyrotropin (TSH), which later recovers to improved thyroxine production, typically in first few months of infancy. Approximately 17% to 40% of children diagnosed with CH by newborn screening (NBS) programs were later determined to have transient hypothyroidism. Causes of transient CH are prematurity, iodine deficiency, maternal thyrotropin receptor blocking antibodies, maternal intake of anti-thyroid drugs, maternal or neonatal iodine exposure, loss of function mutations and hepatic hemangiomas. The classic clinical symptoms and signs of CH are usually absent immediately after birth in vast majority of infants due to temporary protection from maternal thyroxine. NBS has been largely successful in preventing intellectual disability by early detection of CH by performing thyroid function tests in infants with abnormal screening results. In this review we present the evidence for decision making regarding treatment vs. withholding treatment in infants with transient CH and present a rational approach to identifying transient CH based on American Academy of Pediatrics (AAP) recommendation.

Sulfonylurea treatment before genetic testing in neonatal diabetes: pros and cons.

CONTEXT: Diabetes in neonates nearly always has a monogenic etiology. Earlier sulfonylurea therapy can improve glycemic control and potential neurodevelopmental outcomes in children with KCNJ11 or ABCC8 mutations, the most common gene causes. OBJECTIVE: Assess the risks and benefits of initiating sulfonylurea therapy before genetic testing results become available. DESIGN, SETTING, AND PATIENTS: Observational retrospective study of subjects with neonatal diabetes within the University of Chicago Monogenic Diabetes Registry. MAIN OUTCOME MEASURES: Response to sulfonylurea (determined by whether insulin could be discontinued) and treatment side effects in those treated empirically. RESULTS: A total of 154 subjects were diagnosed with diabetes before 6 months of age. A genetic diagnosis had been determined in 118 (77%), with 73 (47%) having a mutation in KCNJ11 or ABCC8. The median time from clinical diagnosis to genetic diagnosis was 10.4 weeks (range, 1.6 to 58.2 wk). In nine probands, an empiric sulfonylurea trial was initiated within 28 days of diabetes diagnosis. A genetic cause was subsequently found in eight cases, and insulin was discontinued within 14 days of sulfonylurea initiation in all of these cases. CONCLUSIONS: Sulfonylurea therapy appears to be safe and often successful in neonatal diabetes patients before genetic testing results are available; however, larger numbers of cases must be studied. Given the potential beneficial effect on neurodevelopmental outcome, glycemic control, and the current barriers to expeditious acquisition of genetic testing, an empiric inpatient trial of sulfonylurea can be considered. However, obtaining a genetic diagnosis remains imperative to inform long-term management and prognosis.

Thiazolidinediones enhance insulin-mediated suppression of fatty acid flux in type 2 diabetes mellitus.

Type 2 diabetes mellitus is characterized by insulin-resistant glucose and lipid metabolism. Thiazolidinediones (TZDs) enhance insulin-mediated glucose disposal, but their effects on lipid kinetics are unknown. We evaluated the effect of the TZD troglitazone on insulin-mediated suppression of fatty acid and glycerol kinetics. Eight obese men and women (body mass index [BMI], 34.1 +/- 2.3 kg/m(2)) with insulin-requiring type 2 diabetes were studied before and after 12 weeks of troglitazone therapy (400 mg/d). Whole-body and abdominal fat masses were determined by dual-energy x-ray absorptiometry and magnetic resonance imaging, respectively. Palmitate and glycerol rates of appearance (R(a)) into plasma were evaluated during a 3-stage hyperinsulinemic euglycemic clamp, which spanned the physiologic range of plasma insulin concentrations that regulate lipolysis. Troglitazone therapy did not alter body composition. Palmitate and glycerol R(a) decreased progressively during each stage of hyperinsulinemia (P <.001). Suppression of palmitate R(a) by insulin was greater after than before troglitazone therapy (P <.001), whereas glycerol R(a) was unchanged. These results demonstrate that TZDs increase insulin-mediated suppression of fatty acid release into plasma in obese subjects with type 2 diabetes mellitus, which may contribute to their metabolic benefits. However, TZD therapy did not affect whole-body glycerol R(a), possibly because of upregulation of lipoprotein lipase action on plasma triglycerides.