Clinical Background
Hypoglycemia may constitute a medical emergency because it may result in permanent neurologic defects.
Epidemiology
- Incidence of hypoglycemia
- Newborns - 1-3/1,000 live births
- Familial forms - 1/50,000 in sporadic populations (high in Ashkenazi Jews)
- Diabetic patients
- Type 1 - 10-30%/yr
- Type 2 - 1-2%/yr
Risk Factors
- Infants or Newborns
- Newborn hyperinsulinemic hypoglycemia
- Genetic
- Defects in genes ABCC8 or KCNJ11
- Gain-of-function mutations in glucokinase and glutamate dehydrogenase
- Loss-of-function mutations in short-chain acyl-CoA dehydrogenase
- Beckwith-Wiedemann syndrome
- Intrauterine growth retardation
- Maternal diabetes mellitus
- Children
- Diabetes mellitus
- Higher risk in patients receiving insulin
- Medication abuse
- Insulin
- Oral hypoglycemic agents
- Adults
- Diabetes mellitus
- Higher risk in patients receiving insulin
- Medication abuse
- Insulin
- Oral hypoglycemic agents
- Insulinoma
- Insulin autoantibodies
- Autoimmune diseases
- Post bariatric surgery patients (gastric bypass procedures)
Pathophysiology
- Dysregulated insulin secretion with defects in glucose counter-regulatory hormones
- Insulin drives glucose into sensitive tissues (liver, adipose, skeletal muscle) which can cause profound hypoglycemia
- Nesidioblastosis (abnormally enlarged islets, hypertrophic beta cells and periductal cells in the pancreas) is likely explanation for pathology in gastric bypass patients
Clinical Presentation
- Adults and children
- Lethargy, confusion, anxiety, sweating
- Nausea
- Focal neurologic defects
- Seizures
- Post gastric bypass patients may experience symptoms 1-2 years after procedure and 1-3 hours postprandially
- Infants and newborns
- Lethargy, confusion, sweating
- Poor feeding
- Recurrent hypoglycemia can cause neurologic damage
- Beckwith-Wiedemann syndrome - omphalocele, gigantism, macroglossia, microcephaly, visceromegaly
- 50% of infants have hyperinsulinemic hypoglycemia
- Hypoglycemias associated with all but genetic defects tend to be transient and resolve spontaneously after several months
Treatment
- Prevent hypoglycemia when possible
- Treat hypoglycemia with intravenous glucose
See Also
Diagnosis
Diagnosis
- Indications for testing - suspicious history
- Laboratory testing
- Glucose - decreased
- May need to do a fasting level to see blood glucose drop
- Insulin - increased
- Based on clinical scenario, other tests to consider include:
- C-peptide - elevated (decreased with exogenous insulin use)
- Elevated insulin and C-peptide may also be seen with insulinoma and surreptitious use of sulfonylureas
- Beta hydroxybutyrate - low
- Free fatty acids - low (if high, consider fatty acid oxidation disorders)
- Rule out sulfonylurea hypoglycemics surreptitious use of oral hypoglycemic agents
- Insulin antibodies
- Proinsulin
Tests generally appear in the order most useful for common clinical situations
| Test name: Glucose, Plasma or Serum
|
| ARUP #: 0020024 |
| Methodology: Enzymatic
|
| Use: Screen for hyperinsulinemic hypoglycemia in neonates |
| Test name: Insulin, Random
|
| ARUP #: 0070107 |
| Methodology: Chemiluminescent Immunoassay
|
| Use: Differential diagnosis of hypoglycemia |
| Test name: Fatty Acids, Free
|
| ARUP #: 0080120 |
| Methodology: Spectrophotometry
|
| Use: Screen for hyperinsulinemic hypoglycemia in neonates |
| Limitations: |
| Follow-up:
|
| Test name: C-Peptide, Serum or Plasma
|
| ARUP #: 0070103 |
| Methodology: Chemiluminescent Immunoassay
|
| Use: Differential diagnosis of hypoglycemia |
| Test name: Insulin Antibody
|
| ARUP #: 0099228 |
| Methodology: Radioimmunoassay
|
| Use: Differential diagnosis of hypoglycemia |
| Test name: Beta-Hydroxybutyric Acid
|
| ARUP #: 0080045 |
| Methodology: Enzymatic
|
| Use: Differential diagnosis of hypoglycemia |
| Test name: Proinsulin
|
| ARUP #: 0070112 |
| Methodology: Two-Site Enzyme Immunoassay
|
| Use: Screen for insulin |
| Test name: Sulfonylurea Hypoglycemics, Serum or Plasma
|
| ARUP #: 0090944 |
| Methodology: High Performance Liquid Chromatography/High Performance Liquid Chromatography
|
| Use: Differential diagnosis of hypoglycemia |
| Test name: Sulfonylurea Hypoglycemics, Urine
|
| ARUP #: 0091100 |
| Methodology: High Performance Liquid Chromatography/High Performance Liquid Chromatography
|
| Use: Differential diagnosis of hypoglycemia |
References
General References
Blaak EE. Fatty acid metabolism in obesity and type 2 diabetes mellitus. Proc Nutr Soc.
2003;
62(
3):
753-760.
Cohen MM Jr. Persistent hyperinsulinemic hypoglycemia of infancy. Am J Med Genet A.
2003;
122(
4):
351-353.
de Lonlay P, Giurgea I, Robert JJ, Fournet JC, Touati G, Nihoul-Fekete C, Brunelle F, Jaubert F, Rahier J, Sempoux C, Junien C, Saudubray JM, Dunne M, Otonkoski T, Ribeiro M, Bellane-Chantelot C. Hyperinsulinemic hypoglycemia in children. Ann Endocrinol (Paris).
2004;
65(
1):
96-98.
Dekelbab BH, Sperling MA. Recent advances in hyperinsulinemic hypoglycemia of infancy. Acta Paediatr.
2006;
95(
10):
1157-1164.
Delonlay P, Simon A, Galmiche-Rolland L, Giurgea I, Verkarre V, Aigrain Y, Santiago-Ribeiro MJ, Polak M, Robert JJ, Bellanne-Chantelot C, Brunelle F, Nihoul-Fekete C, Jaubert F. Neonatal hyperinsulinism: clinicopathologic correlation. Hum Pathol.
2007;
38(
3):
387-399.
Hussain K, Cosgrove KE, Shepherd RM, Luharia A, Smith VV, Kassem S, Gregory JW, Sivaprasadarao A, Christesen HT, Jacobsen BB, Brusgaard K, Glaser B, Maher EA, Lindley KJ, Hindmarsh P, Dattani M, Dunne MJ. Hyperinsulinemic hypoglycemia in Beckwith-Wiedemann syndrome due to defects in the function of pancreatic beta-cell adenosine triphosphate-sensitive potassium channels. J Clin Endocrinol Metab.
2005;
90(
7):
4376-4382.
Ismail D, Werther G. Persistent hyperinsulinaemic hypoglycaemia of infancy: 15 years' experience at the Royal Children's Hospital (RCH), Melbourne. J Pediatr Endocrinol Metab.
2005;
18(
11):
1103-1109.
Jabri AL, Bayard C. Nesidioblastosis associated with hyperinsulinemic hypoglycemia in adults: review of the literature. Eur J Intern Med.
2004;
15(
7):
407-410.
Kraegen EW, Cooney GJ, Ye J, Thompson AL. Triglycerides, fatty acids and insulin resistance--hyperinsulinemia. Exp Clin Endocrinol Diabetes.
2001;
109(
4):
S516-S526.
Pucci E, Chiovato L, Pinchera A. Thyroid and lipid metabolism. Int J Obes Relat Metab Disord.
2000;
24 Suppl 2:
S109-S112.
Service GJ, Thompson GB, Service FJ, Andrews JC, Collazo-Clavell ML, Lloyd RV. Hyperinsulinemic hypoglycemia with nesidioblastosis after gastric-bypass surgery. N Engl J Med.
2005;
353(
3):
249-254.
Sperling MA, Menon RK. Differential diagnosis and management of neonatal hypoglycemia. Pediatr Clin North Am.
2004;
51(
3):
703-23, x.
Medical Reviewers
Grenache, David G., Ph.D. Medical Director, Special Chemistry at ARUP Laboratories; Assistant Professor, Clinical Pathology, University of Utah
Meikle, A. Wayne, M.D. Medical Director, RIA and Endocrinology at ARUP Laboratories; Professor of Internal Medicine and Pathology, University of Utah
Comprehensive Review: March 2008
Last Update: May 2008
