Hyperglycemia can cause hyperosmolarity, osmotic diuresis, and subsequent dehydration. Hyperglycemia is very common in ELBW and premature infants and is associated with an increase in mortality, white matter reduction on the magnetic resonance image (MRI) of the brain, intracranial hemorrhage, stage II/III NEC, risk of sepsis (if hyperglycemia occurs in the first few days after birth), retinopathy of prematurity (ROP) in ELBW infants, and developmental delay. Etiologies include excess administration or production, inadequate insulin secretion or insulin resistance, glucose intolerance, and defective glucoregulatory hormone control.
Factitious hyperglycemia
Blood drawn from an IV line containing glucose or a bolus was given when flushing a line.
False bedside hyperglycemia from a glucose meter. Some glucose meters will overestimate the serum glucose in an infant with galactosemia because of the lack of specificity of the enzyme used by the assay. Always confirm with a serum sample if glucose meter is high.
True hyperglycemia
Excess glucose administration has a major role in hyperglycemia. Giving infants more glucose than what they can handle needs to be evaluated first. Incorrect calculation of glucose levels or errors in the formulation of IV fluids may cause hyperglycemia.
Inability to metabolize glucose may occur with prematurity or secondary to sepsis or stress. Most commonly, a tiny infant on total parenteral nutrition becomes hyperglycemic because of glucose intolerance.
Impaired glucose homeostasis
Extremely low birthweight infants (<1000 g). These infants have greater fluid requirements because of their immature renal function and increased insensible water loss. This often leads to a high volume of fluid and administering too much glucose. They also may have insulin resistance, an immature insulin response, and are unable to stop gluconeogenesis when IV glucose is given.
Preterm infants/small for gestational age (SGA) infants. Preterm infants receiving a glucose challenge show variable increases in insulin levels consistent with insulin resistance. This resistance may be related to immaturity or downregulation of peripheral receptors. Transient hyperglycemia can also be seen in SGA infants from impaired glucose homeostasis.
Sepsis can cause hyperglycemia. Suspect sepsis in a neonate who had normal glucose levels with no change in the rate or amount of IV glucose. The etiologies can include the stress response, a reduction in the peripheral utilization of glucose, or a decrease in release of insulin. Hyperglycemia is more frequent in fungal than bacterial sepsis in the neonate. Hyperglycemia may be the first sign in neonatal sepsis; in Candida sepsis it can appear 2 to 3 days before other signs.
Hyperosmolar formula. Ask how the formula was made. An inappropriate dilution can lead to a hyperosmolar formula, which in turn can cause transient neonatal glucose intolerance. Severe dehydration from gastroenteritis can lead to hypernatremia and hyperglycemia.
Lipid infusion. Infants who receive lipid infusion even with low rates of glucose administration may develop hyperglycemia. Lipids are emulsified in a Dextran solution. The lipid component may also cause a glycemic response and a decrease in peripheral glucose utilization, and may inhibit insulin's effect. One study found that giving lipid infusion increased plasma glucose concentrations by 24% over baseline values.
Stress. Pain, painful procedures (venipuncture, vascular cutdowns, and others), surgical procedures (during surgery and postoperative), NEC, acute intracerebral bleeding, hypoxia, catecholamine infusions, respiratory distress, and others can all cause hyperglycemia secondary to increased cortisol.
Hypoxia can cause increased glucose production.
Medications such as maternal use of diazoxide can cause hyperglycemia in the infant. Drugs used in infants that have been associated with hyperglycemia include caffeine, theophylline (slight increase), steroids (common), vasoactive drugs, and phenytoin. Prostaglandin E1 has been associated with hyperglycemia in a case report.
Neonatal diabetes mellitus. It is a rare cause of diabetes and occurs when there is persistent hyperglycemia that lasts more than 2 weeks and requires insulin therapy. Neonatal diabetes occurs in infants <6 months old; it is not an autoimmune disease and is most commonly caused by genetic defects. Molecular analysis of chromosome 6 anomalies and the KCNJ11 and ABCC8 genes can provide a way of differentiating transient from permanent neonatal diabetes. Infants with neonatal diabetes mellitus can have metabolic acidosis, ketosis, and glycosuria. There are 2 types:
Transient neonatal diabetes mellitus (TNDM)(50–60% of cases). A developmental disorder of the production of insulin that resolves. It is primarily a genetic disorder (chromosome 6q24 anomalies and KATP channel defects). Most infants are SGA or have intrauterine growth restriction (IUGR); they present from 2 days to 6 weeks of age with hyperglycemia and require insulin therapy. It persists for more than 2 weeks and usually resolves by 3–4 months. Common findings are hyperglycemia, dehydration, glycosuria, polyuria, progressive wasting, hypoinsulinism, ketosis, metabolic acidosis and absent ketonuria, and normal or transiently low C-peptide levels in urine and serum. There is a positive family history in ∽33% of cases. About half of these cases go on to develop insulin-dependent diabetes in adolescence or in adulthood.
Permanent neonatal diabetes mellitus (PND or PNDM). (Less common than TNDM.) It develops in the neonatal period and does not go into remission. Genetic mutations are common (KCNJ11, ABCC8, and INS genes). It is not associated with IUGR.
Insulin-dependent (type 1) diabetes mellitus. An autoimmune disease that occurs in children and adolescents.
Idiopathic. No identifiable cause is found; a diagnosis of exclusion.