Diva D. De León, MD, Paul S. Thornton, MD, BCh, MRCPI, Charles A. Stanley, MD and Mark A. Sperling, MD

Chapter outline

Introduction

One of the most important genetic and metabolic events to mark the transition from fetal to neonatal life is the adaptation from an environment that has a readily available and continuous source of glucose—maternal blood—to an environment in which glucose is provided in a limited and intermittent supply. The complex events involved in the maintenance of plasma glucose concentration must be coordinated to avoid hypoglycemia and resultant damage to the central nervous system. A newborn or infant with hypoglycemia presents an urgent diagnostic and therapeutic challenge. The clinical features must be rapidly assessed and a plan of action developed based on the infant’s age, maternal and parturition history, severity and persistence of hypoglycemic state, and all other relevant clinical clues. In this chapter we will review the normal physiology of glucose metabolism and the pathophysiology of the most common disorders resulting in hypoglycemia in the neonate (first 4 weeks of life) and infant (1 month to 1 year of life) with an emphasis on the approach to the diagnosis and management of these pathologies.

Principles of glucose metabolism

A systematic approach to hypoglycemia in the newborn, infant, or child requires an appreciation of the central role of glucose in the body’s fuel economy.¹ Glucose metabolism accounts for approximately half of basal daily energy needs and is the principal metabolic fuel of the human brain. Glucose can be stored for energy in the form of glycogen and fat, and its carbon can be used for synthesis of protein and for structural components (such as cell membranes). The aerobic oxidation of glucose yields high energy by producing 36 mols of adenosine triphosphate (ATP) for each mol of glucose.

All glucose extracted by the brain is oxidized, and thus cerebral glucose utilization parallels cerebral oxygen uptake. In 5-week-old infants, cerebral glucose utilization already represents 71% to 93% of the adult level in most brain regions (ranging from 13 to 25 μmol/100 g/min). At that age, the areas with highest metabolic rates for glucose are the sensorimotor cortex, thalamus, midbrain, brainstem, and cerebellar vermis. By 3 months, metabolic rates for glucose increase in the parietal, temporal, and occipital cortices, as well as in basal ganglia. By 8 months, subsequent increases occur in the frontal cortex and various associative regions, concordant with the appearance of higher cortical and cognitive functions. Adult levels of cerebral glucose utilization (19 to 33 μmol/100 g/min) are reached by the time one is 2 years of age, and they continue to increase until 3 to 4 years of age—when they reach values ranging from 49 to 65 μmol/100 g/min, which are maintained to approximately 9 years of age. They then begin to decline, reaching adult levels by the end of the second decade.²

Glucose uptake by the brain occurs by means of a carrier-mediated facilitated diffusion process that is glucose concentration dependent, as well as energy, Na⁺, and insulin independent.³ This process is mediated by facilitative glucose transporter (GLUT) proteins. The human genome contains 14 members of the GLUT family. Each of these isoforms is expressed in a distinct tissue distribution. In most cells, GLUTs mediate the import of glucose, because hexokinase activity maintains low intracellular glucose concentrations. Characterization of the different members has provided new insights into the regulation and significance of glucose transport and its disorders in various tissues^3,4,5 (Table 6-1). Several members of the GLUT family have been detected in the brain. GLUT1 is located at the blood-brain barrier,⁶ and although some neurons express GLUT2 and GLUT4, the majority use GLUT3 as their primary transporter.⁷ The main isoform present in insulin-responsive tissues is GLUT4.^8,9

Of major importance is the confirmation at a molecular level of biochemical evidence that glucose entry into brain cells and its subsequent metabolism are not dependent on insulin but rather are dependent on circulating arterial glucose concentration.¹⁰ Therefore, a decrease in arterial glucose concentration or a defect in the glucose transport mechanism of the brain will result in intracerebral glucopenia and low cerebrospinal fluid glucose concentration (hypoglycorrhachia)—with attendant symptoms and signs of cerebral glucopenia as subsequently described.^10–12

In normal humans, plasma glucose concentrations range from 3.9 to 7.1 mmol/L (70 to 128 mg/dL) and in the brain the range is from 0.8 to 2.3 mmol/L (14 to 41 mg/dL).¹³ Brain glucose consumption will outstrip glucose transport at plasma glucose concentration < 2 mmol/L (36 mg/dL) (brain glucose will approach 0 mmol/L).¹⁴ To prevent circulating arterial blood glucose from decreasing precipitously under normal physiologic conditions, and therefore to prevent impairment of vital function that depends on cerebral glucose metabolism, an elaborate defense mechanism has evolved.¹ This defense against hypoglycemia is integrated by the autonomic nervous system and by hormones that act synergistically to enhance glucose production through enzymatic modulation of glycogenolysis and gluconeogenesis while simultaneously limiting peripheral glucose use.^15,16 Thus, hypoglycemia is the result of a defect in one or several of the complex interactions that maintain a normal range of glucose concentration, preventing its fall to less than 3.9 mmol/L (70 mg/dL) during fasting and its rise to more than 7.8 mmol/L (140 mg/dL) during feeding.

These mechanisms are not fully developed at birth, when there is an abrupt transition from intrauterine life to extrauterine life. A neonate delivered prematurely whose enzymatic machinery mechanisms are not yet fully developed and expressed or one whose placental insufficiency resulted in intrauterine growth retardation with limited tissue nutrient deposits may be particularly vulnerable to hypoglycemia,¹⁷ often with consequences to subsequent cerebral development or function.^18,19

Physiology of perinatal glucose homeostasis

Hormonal and metabolic systems of fasting adaptation

Hypoglycemia in neonates, infants, and children is essentially always a problem with fasting adaptation. Postprandial hypoglycemia is exceedingly rare and is limited to a few unusual situations, such as postprandial hypoglycemia after Nissen fundoplication and gastric tube feedings, hereditary fructose intolerance, or the protein-induced hypoglycemia seen in some forms of congential hyperinsulinism. Therefore, a consideration of the major hormonal and metabolic pathways that maintain fuel homeostasis during fasting provides an important framework for understanding the causes, diagnosis, and treatment of different forms of hypoglycemia.

Three metabolic systems regulate the physiologic response to fasting: (1) hepatic glycogenolysis, (2) hepatic gluconeogenesis, and (3) hepatic ketogenesis. The key enzymatic steps in these pathways are shown in Figure 6-1. These metabolic systems are coordinated by the endocrine system, consisting of suppression of insulin (the most important endocrine response to fasting, as insulin suppresses all three metabolic systems) balanced by the secretion of glucagon, epinephrine, cortisol, and growth hormone. Table 6-2 summarizes the counter-balancing effects of these counter-regulatory hormones on key metabolic pathways. There is a hierarchic redundancy in the interaction of these counter-regulatory hormones that provides a margin of safety (“fail-safe mechanism”) if only one counter-regulatory hormone is impaired. Epinephrine and glucagon are quick acting, each signaling its effects by activation of cyclic AMP. Deficiencies of glucagon, as occurs in long-standing type 1 diabetes mellitus, can be largely compensated for by an intact autonomic nervous system with appropriate α- and β-adrenergic, and cholinergic effects. Conversely, autonomic failure can be largely compensated for if glucagon secretion remains intact.¹

Hepatic glycogenolysis is sufficient to meet energy requirements for only a few hours. Beyond that time, glucose must be produced by hepatic gluconeogenesis from precursors such as amino acids, glycerol, and lactate recycled from glycolysis. The major source of gluconeogenic precursors is muscle protein. Although the pool of muscle protein is large, it is required for body function and thus in contrast to stores of glycogen and fat there are no “reserves” of protein to draw on during fasting. To spare the use of essential protein during extended fasting, glucose consumption must be suppressed by switching on the mobilization and oxidation of fatty acids from adipose triglyceride stores, producing ketone bodies and glycerol. The ketone bodies inhibit phosphofructokinase, hexokinase, and inactivate pyruvate dehydrogenase, thus reducing glucose utilization in the liver and preserving glucose for those cells dependent of glucose alone.

The essential function of fasting adaptation is to maintain fuel supply to the brain. Glucose homeostasis is very limited in neonates and infants compared to adults, in part because of their smaller reserves of liver glycogen and muscle protein but also because of their relatively larger rates of glucose consumption due to their larger brain-to-body-mass ratio. For example, the fuel stores of a 10-kg infant are only 15% of those of an adult. However, the caloric needs are 60% of those of an adult and glucose turnover rates per kilogram are two- to threefold greater. As shown in Figure 6-2, early in fasting, glucose is the primary brain fuel and accounts for over 90% of total body oxygen consumption. Glucose is provided chiefly from hepatic glycogenolysis, supplemented by hepatic gluconeogenesis utilizing amino acids released by muscle protein turnover. After 8 to 12 hours in normal infants (24 to 36 hours in adults), glucose production declines, because the supply of liver glycogen is limited and the rate of gluconeogenesis from amino acids remains constant. At this time, a transition to fat as the major fuel for the body begins, with accelerated adipose tissue lipolysis and increased fatty acid oxidation in muscle and ketogenesis in liver. Lipolysis also generates glycerol, which is an important gluconeogenic substrate once fasting adaptation is fully active. The brain cannot utilize fatty acids directly, because they do not pass the blood-brain barrier. However, the brain can substitute glucose consumption with the ketones acetoacetate and β-hydroxybutyrate, which are released by the liver as the end product of hepatic fatty acid oxidation. In late stages of fasting adaptation, fatty acid oxidation and ketone utilization account for 90% of total oxygen consumption.

The operation of the metabolic and endocrine systems of fasting adaptation is evidenced by the changes in circulating levels of metabolic fuels and hormones during a fast. As shown in Figure 6-3, in young infants a 24-hour fast is accompanied by a gradual fall in plasma glucose levels as hepatic glycogen stores are depleted, a progressive fall in concentrations of gluconeogenic substrate (e.g., lactate, alanine) as they are used for hepatic gluconeogenesis, a brisk rise in free fatty acids as lipolysis is activated, and a dramatic rise in β-hydroxybutyrate (the major ketone) as hepatic ketogenesis is turned on.^1,42

By the time that plasma glucose concentration has fallen to < 2.8 mmol/L (50 mg/dL), all the metabolic systems and the hormonal responses described earlier will have fully engaged. A “critical sample” drawn at this time will therefore enable an evaluation of these systems and detect abnormalities of fasting adaptation. As an example, when insulin concentration is above the lower limit of detection according to the assay at the time when plasma glucose concentration is 2.8 mmol/L (50 mg/dL) or less, there is a hyperinsulinemic state reflecting failure of the mechanisms that normally result in suppression of insulin secretion during fasting or hypoglycemia.43–45 Thus, a snapshot of the integrity of the metabolic and endocrine fasting systems can easily be obtained by measuring the plasma levels of the major fuels and hormones at the end of a fast, when the blood glucose approaches hypoglycemic levels (“critical samples”) (Table 6-3; also see also Box 6-2, presented later in the chapter). The use of these critical samples in diagnosing the cause of hypoglycemia is discussed later.

Definition of hypoglycemia in neonates and infants

The classic definition of symptomatic hypoglycemia is “Whipple’s triad”—symptoms, signs or both consistent with hypoglycemia, a low plasma glucose concentration, and resolution of symptoms/signs after the plasma glucose concentration is raised. These three criteria were originally used for diagnosing insulinomas in adults. However, in neonates and infants, who cannot dependably communicate their symptoms and in whom clinical signs of hypoglycemia are not specific, it may not be possible to satisfy Whipple’s triad. In these cases, recognition of hypoglycemia may require confirmation by repeated measurements of plasma glucose concentrations on multiple occasions or by formal provocative testing.

Beyond the first 48 hours of life, normal plasma glucose concentration in neonates and infants are not different than in older children and adults. Thus, plasma glucose concentrations in the postabsorptive state range between 3.9 and 5.6 mmol/L (70 and 100 mg/dL), with a mean of 4.4 to 4.7 mmol/L (80 to 85 mg/dL). A plasma glucose level of 2.8 mmol/L (50 mg/dL) is conventionally used as an end point for provocative diagnostic tests for hypoglycemia. This value is low enough to strongly stimulate the endocrine and metabolic defenses against hypoglycemia for identifying the mechanism responsible for hypoglycemia. Falling glucose levels elicit a typical sequence of responses: plasma insulin levels begin to decrease when plasma glucose falls to the range of 4.4 to 4.7 mmol/L (80 to 85 mg/dL) and insulin secretion is generally “switched off” at glucose concentrations below 2.5 to 3 mmol/L (45 to 54 mg/dL); glucagon secretion increases when plasma glucose levels are in the range of 3.6 to 3.9 mmol/L (65 to 70 mg/dL); epinephrine, cortisol, and growth hormone responses are activated in the range of 3.6 to 3.9 mmol/L (65 to 70 mg/dL). As the plasma glucose falls below 3.3 mmol/L (59 mg/dL), auditory and visual reaction time is prolonged and cognitive function begins to decline as the plasma glucose concentration declines below 2.5 to 3.5 mmol/L (45 to 63 mg/dL), with some of this variability dependent of the testing employed.^13,46

In some disorders, such as defects in ketogenesis, signs and symptoms may begin to appear during fasting at plasma glucose levels of 3.3 mmol/L (60 mg/dL). On the other hand, some patients (those with glucose 6-phosphatase deficiency) may have few symptoms of neuroglycopenia at plasma glucose levels as low as 1.1 to 1.7 mmol/L (20 to 30 mg/dL) because their high plasma levels of lactate provide an alternative substrate for the brain. Plasma glucose levels between 2.8 and 3.9 mmol/L (50 and 70 mg/dL) should be regarded as suboptimal and below the goal for therapy for hypoglycemia.

A number of potential artifacts can interfere with measuring glucose levels in neonates and infants (Box 6-1). Whole-blood glucose concentrations are 10% to 15% lower than plasma glucose levels because erythrocytes have a higher concentration of protein (hemoglobin) versus plasma with its higher water content, and hence higher dissolved glucose concentrations. The difference may be greater in neonates with higher hematocrits. Blood samples that are not processed promptly can have erroneously low glucose levels, owing to glycolysis by red and white blood cells. At room temperature, the decline of whole-blood glucose can be 5 to 7 mg/dL/hr. The use of inhibitors, such as fluoride, in collection tubes avoids this problem.

Hospital bedside glucose meters and similar home glucose meters are less precise than clinical laboratory methods and can be expected to have an error range of 10% to 15%. These methods are also prone to errors, such as outdated strips or inadequate sampling—most of which result in falsely low glucose values. For this reason, bedside monitors can be used for screening purposes—but any glucose value below 3.3 mmol/L (60 mg/dL) should be verified in the clinical laboratory. Falsely low (or high) glucose values may occur with samples drawn from indwelling lines without adequate flushing of the saline (or glucose) infusate.

For infants beyond the transitional period, treatment should be initiated promptly for plasma glucose values below 2.8 mmol/L (50 mg/dL). Plasma glucose values below 3.3 mmol/L (60 mg/dL) should be rechecked, and treatment considered if values are confirmed to be below 3.3 mmol/L (60 mg/dL). Symptomatic infants and neonates should be treated with intravenous dextrose (0.2 g/kg bolus, followed by infusion at 5 to 10 mg/kg/min). These rates approximate the normal hepatic glucose production rates in neonates and young infants (Figure 6-4). Asymptomatic neonates with plasma glucose levels below 2.8 mmol/L (50 mg/dL) may be treated with oral glucose, but only if there is good reason to believe the problem is a transient one that will not recur. This essentially only applies to otherwise normal neonates during the first 12 to 24 hours after birth who have delayed feedings, such as with initiation of breastfeeding. Beyond the first day of life, all neonates with verified plasma glucose concentration less than 2.8 mmol/L (50 mg/dL) should be suspected of having a hypoglycemic disorder.

Clinical symptoms and signs associated with hypoglycemia

The clinical features of hypoglycemia in infants may be associated with both neurogenic and neuroglycopenic components (Table 6-4). Symptoms are often subtle and not specific, therefore a high index of clinical suspicion must be maintained. Any alteration in clinical status in a newborn that suggests a change in neurologic behavior, fall in temperature, change in feeding pattern, or presence of tremors must be considered a possible initial presentation of a hypoglycemic episode. A seizure must always be considered a possible manifestation of hypoglycemia.

Diagnostic approach

Treatment of hypoglycemia in neonates and infants requires making a specific diagnosis of the underlying cause. The diagnosis should be based on the combination of data obtained from the history, physical examination, laboratory findings, and, especially, the hormonal and fuel responses at the time of fasting hypoglycemia. A logical approach to diagnosis and treatment must be to analyze a hypoglycemic event as a maladaptation to fasting, and thus the most important information required for diagnosis comes from tests on the blood and urine specimens obtained at a time of hypoglycemia (also known as the critical samples).

Important facts from the history include the duration of fasting that provoked hypoglycemia. Onset within a few hours of a meal would be consistent with hyperinsulinism or glucose 6-phosphatase deficiency, whereas onset after 10 to 12 hours would be consistent with a defect in fatty acid oxidation. Pituitary deficiency with growth hormone or adrenocorticotropic hormone (ACTH)-cortisol deficiency might be suspected by the presence of midline facial malformations, microphthalmia, or microphallus (follicle-stimulating hormone [FSH]/luteinizing hormone [LH] deficiency in utero). Growth failure is also a prominent feature of glucose 6-phosphatase deficiency or debrancher deficiency glycogen storage disease after the first 3 months of life. Both of these disorders are associated with massive hepatomegaly. Abnormal results of liver function tests (transaminases) and hyperammonemia, with or without elevated creatine kinase level, would suggest a possible fatty acid oxidation disorder (see Table 6-3).

Figure 6-5 outlines an algorithm for diagnosis of different forms of hypoglycemia based on readily available laboratory tests on the “critical” blood and urine samples. The first discriminant is a measure of acidemia at the time of hypoglycemia using the serum bicarbonate. If the acidemia is caused by elevations of the ketoacids (β-hydroxybutyrate and acetoacetate), possibilities include a normal child fasted for too long (ketotic hypoglycemia), a defect in glycogenolysis (glycogen storage disease type 3), or counter-regulatory hormone deficiency (hypopituitarism). If the acidemia is caused by an elevation of lactic acid, a block of gluconeogenesis should be suspected (glucose 6-phosphatase or fructose 1,6-diphosphatase deficiency or ethanol ingestion).

If there is no acidemia (i.e., absence of the normal elevation of ketones) but free fatty acid levels are high, a defect in fatty acid oxidation and ketogenesis should be suspected (MCAD deficiency). If ketones are not appropriately increased but the free fatty acid concentrations are also suppressed, hyperinsulinism should be suspected. In the neonatal period, the features of hyperinsulinism can be mimicked by congenital pituitary deficiency. Further tests can then be planned using the initial critical specimens to confirm the suspected diagnosis. These may include physiologic tests (such as the glucagon stimulation test at a time of hypoglycemia to confirm hyperinsulinism) or specialized laboratory tests (such as a plasma acyl-carnitine profile) to identify a defect in mitochondrial β-oxidation.

In some cases, a formal fasting test may be necessary to diagnose the cause of hypoglycemia. The goal of this test is to reproduce the setting in which hypoglycemia occurs in order to identify the underlying cause. The fasting test should be considered a method of testing a hypothesis that has already been developed, based on available clinical and laboratory data about the cause of the hypoglycemia. Thus, the test can be modified with additions or deletions to the basic protocol. This is important, because challenging an infant with fasting is not without risk—particularly if a genetic defect in fatty acid oxidation or adrenal insufficiency is present. Therefore, fasting or other diagnostic challenges should be done only in the hospital under carefully controlled settings with an experienced physician and nursing staff readily available.

Infants younger than 1 year are usually fasted for up to 24 hours, whereas in older children the maximum fast may be up to 36 hours. The fast is terminated when the plasma glucose falls below 2.8 mmol/L (50 mg/dL), but it may be ended sooner if plasma β-hydroxybutyrate rises to greater than 2.5 mmol/L or if there are any adverse signs or symptoms. Periodic blood samples are obtained for analysis of major fuels and hormones and for appropriate ancillary tests (e.g., serum total carnitine, acyl-carnitine profile, liver transaminases, creatine phosphokinase, or urinary organic acids). If hyperinsulinism is suspected, the fasting test may be ended with glucagon (1 mg given intravenously) to evaluate the glycemic response.

Special note should be made that the most frequent cause of hypoglycemia in neonates, infants, and children (hyperinsulinism) often cannot be diagnosed based solely on the plasma insulin concentration. With very sensitive assays, serum insulin concentrations will be less than 1 to 2 μU/mL at times of hypoglycemia (i.e., below the sensitivity of most insulin assays). Therefore, the diagnosis must often be made based on evidence of inappropriate insulin effects: hypoketonemia, hypo-free fatty acidemia, and a positive glycemic response to glucagon.

Classification of causes of persistent hypoglycemia in the neonate and infant (box 6-2)

Hyperinsulinemic hypoglycemia

Transient hyperinsulinism resulting from maternal factors

Transient hyperinsulinism is a well-recognized complication in neonates after a pregnancy complicated by gestational diabetes. At birth, infants born to these mothers may be large and plethoric—and their body stores of glycogen, protein, and fat are replete. The classic clinical description of the effect of hyperinsulinism relates to the infant of the diabetic mother⁴⁷:

These infants are remarkable not only because like fetal versions of Shadrack, Meshack, and Abednego, they emerge at least alive from within the fiery metabolic furnace of diabetes mellitus, but because they resemble one another so closely they might well be related. They are plump, sleek, liberally coated with vernix caseosa, full-faced, and plethoric. The umbilical cord and placenta share in the gigantism. During their first 24 or more extrauterine hours, they lie on their backs, bloated and flushed, their legs flexed and abducted, their lightly closed hands on either side of the head, the abdomen prominent and their respiration sighing. They convey a distinct impression of having had such a surfeit of both food and fluid pressed upon them by an insistent hostess that they desire only peace so that they may recover from their excesses. On the second day their resentment of the slightest noise improves the analogy when their trembling anxiety seems to speak of intrauterine indiscretions of which we know nothing.

The hypoglycemia in infants of diabetic mothers is related chiefly to hyperinsulinemia and in part to diminished glucagon secretion. Hypertrophy and hyperplasia of their islets have been documented, as has their brisk, biphasic, and typically adult insulin response to glucose. This insulin response is absent in normal infants. Infants born to diabetic mothers also have a subnormal surge in plasma glucagon immediately after birth, subnormal glucagon secretion in response to stimuli, and (initially) excessive sympathetic activity that may lead to adrenomedullary exhaustion because urinary excretion of epinephrine is diminished. Thus, despite their abundance of tissue stores of available substrate, the normal plasma hormonal pattern of low insulin, high glucagon, and catecholamines is reversed. Their endogenous glucose production is inhibited and glucose utilization is increased compared with that in normal infants, thus predisposing them to hypoglycemia.

Mothers whose diabetes has been well controlled during pregnancy in general have near-normal-sized infants who are less likely to develop neonatal hypoglycemia and other complications formerly considered typical of maternal diabetes. Nevertheless, treatment of infants born to mothers with diabetes commonly requires provision of intravenous glucose for a few days until the hyperinsulinemia abates. For these infants, glucose should be provided at a rate of 5 to 10 mg/kg/min. However, the appropriate dosage for each patient should be individually adjusted.

During labor and delivery, maternal hyperglycemia should be avoided because it may result in fetal hyperglycemia—which predisposes to rebound hypoglycemia when the glucose supply is interrupted at birth. Other maternal factors that can result in transient neonatal hyperinsulinism include oral hypoglycemics (such as sulfonylureas) or other medications (terbutaline or propranolol).

By definition, transient hyperinsulinism as a cause of neonatal hypoglycemia in an infant of a diabetic mother should abate in 1 or 2 days. If the condition persists, prolonged or congenital hyperinsulinism must become a prominent consideration, and the index of suspicion must remain high until it is ruled out.

Prolonged neonatal hyperinsulinism: Perinatal stress-induced hyperinsulinism

As shown in Figure 6-6, the risk of postnatal hypoglycemia is increased in neonates who are small for gestational age. There is increasing evidence that prolonged hypoglycemia in some neonates exposed to perinatal stress such as birth asphyxia, maternal toxemia, prematurity, or intrauterine growth retardation or other peripartum stress is due to hyperinsulinism.^48–50 The estimated incidence of prolonged neonatal hyperinsulinism is 1:12,000 live births.⁵⁰

FIGURE 6-6  ​Incidence of plasma glucose level being less than 30 mg/dL before first feeding at 3 to 6 hours of age in newborns, classified by birth weight and gestational age. (From Lubchenko LO, Bard H [1971]. Incidence of hypoglycemia in newborn infants by birth weight and gestational age. Pediatrics 47:831.)

The clinical presentation of perinatal stress-induced hyperinsulinism is characterized by high glucose utilization, and the response to fasting hypoglycemia shows an elevated plasma insulin level (although it may be normal), low β-hydroxybutyrate and free fatty acid levels, and inappropriate glycemic response to glucagon at the time of hypoglycemia. Unlike the transient hyperinsulinism seen in the infant of the diabetic mother, perinatal stress-induced hyperinsulinism may persist for several days to several weeks. In a series of neonates with perinatal stress-induced hyperinsulinism, the median age of resolution was 6 months.⁵⁰ The mechanism responsible for the dysregulated insulin secretion is not known. Acute insulin responses (AIRs) show that in general the patterns of insulin response to secretagogues (calcium, tolbutamide, glucose, and leucine) in infants with prolonged neonatal hyperinsulinism resembled those of normal controls.⁵⁰

Only gold members can continue reading. Log In or Register to continue

Share this:

• Click to share on Twitter (Opens in new window)
• Click to share on Facebook (Opens in new window)

Related

Related posts:

Overview and principles of pediatric endocrinology Neonatal diabetes mellitus Lipid disorders in children and adolescents Laboratory methods in pediatric endocrinology Receptor transduction pathways mediating hormone action Adrenal cortex and its disorders

Stay updated, free articles. Join our Telegram channel

Join