Hypoglycemia Flashcards by Stacy Zahanova

Draw and label a beta cell

How well did you know this?

Not at all

Perfectly

List 5 genetic causes of hyperinsulinism

KATP-HI: ABCC8 (SUR1 subunit) or KCNJ11 (KIR6.2 subunit)
Glutamate dehydrogenase-HI: GLUD1
Glucokinase-HI: GCK - 3-hydroxy-acylCoA dehydrogenase deficiency: HADH
Exercise-induced HI: SLC16A1 (transporter MCT1)
HNF4A
HNF1A
Mitochondrial uncoupling protein HI: UCP2
Mosaic Beckwith Weidemann

How well did you know this?

Not at all

Perfectly

List 3 acquired causes of hyperinsulinism

Infant of a diabetic mother
Peripartum stress HI
Insulinoma (sporadic or MEN1)

How well did you know this?

Not at all

Perfectly

What is baby’s size in GCK hyperinsulinism?

AGA if mother is affected

LGA if mother is unaffected

How well did you know this?

Not at all

Perfectly

What is the pathophysiology of GCK hyperinsulinism?

Lowering of beta cell “glucosensor”

How well did you know this?

Not at all

Perfectly

In exercise-induced hyperinsulinism, how quickly does hypoglycemia occur?

Within 30 minutes of strenuous exercise (ex swimming)

How well did you know this?

Not at all

Perfectly

Which HNF mutation has HI plus Fanconi tublulopathy?

HNF4A

How well did you know this?

Not at all

Perfectly

What is the inheritance of diffuse and focal KATP HI?

Diffuse: recessive (less commonly dominant)

Focal: inheritance of a paternal mutation (second hit is the loss of maternal allele)

In close proximity to KATP gene are 2 tumor suppressor genes (H19 and CDKN1c) and a paternally expressed growth factor gene (IGF2). Therefore growth advantage after loss of maternal allele

How well did you know this?

Not at all

Perfectly

Is focal HI visible on routine imaging (ultrasound, CT, MRI)?

No (unlike insulinoma)

How well did you know this?

Not at all

Perfectly

What proportion of kids with KATP-HI are responsive to diazoxide?

30% (Dominant inheritance may be more responsive)

How well did you know this?

Not at all

Perfectly

Name 2 types of genetic hyperinsulinism that cause protein-induced hypoglycemia

Glutamate dehydrogenase (GDH) aka HI-HA
HADH (3-hydroxyacyl-CoA dehydrogenase)

How well did you know this?

Not at all

Perfectly

What test can localize a lesion in focal KATP-HI?

Fluorine-18 labelled fluoro-L-DOPA PET scan Intraoperative biopsies and examination by pathology

How well did you know this?

Not at all

Perfectly

How long should kids be able to fast for, by age?

1 week to 1 year: 15-24 (or 18) hours
1-5 years: 24 hours
>5 years: 36 hours
Adults: 48-72 hours

How well did you know this?

Not at all

Perfectly

How does diazoxide work?

Maintains KATP channel in open position, suppressing insulin release

How well did you know this?

Not at all

Perfectly

What are the side effects of diazoxide?

Fluid retention
Leukopenia (rare)
Thrombocytopenia (rare)
Pulmonary hypertension (rare)
Long term: hypertrichosis, coarsening of face

How well did you know this?

Not at all

Perfectly

How does octreotide work?

Somatostatin analogue. Suppresses insulin downstream of voltage-gated calcium channel
Other facts about octreotide: Subcutaneous injection. Tachyphylaxis develops

Name 2 ways to diagnose GDH-HI (aka HI-HA)

Genetic testing of GLUD1 gene
Acute insulin response to leucine-loading test

When does GCH-HI (aka HI-HA) present?

Later in infancy, when higher-protein foods and longer periods of fasting are introduced. Usually 4-12 months of age.

List clinical features of Beckwith-Wiedemann Syndrome

Macroglossia
Omphalocele
Hemihypertrophy
Renal malformations
Hyperinsulinism (mechanism is not clear)
Predisposition to embryonal tumors (Wilms, hepatoblastoma)

What is the mechanism for hypoglycemia in an infant of a diabetic mother?

Hyperglycemia in mother
Infant appropriately upregulates insulin secretion (macrosomia develops)
Glucose supply is abruptly interrupted at birth, hypoglycemia develops
Counter-regulatory glucagon and epinephrine are diminished due to immaturity of these axes

Where are the four GLUT transporters found?

GLUT1: blood-brain barrier
GLUT2: pancreatic islets, liver
GLUT3: brain and others
GLUT4: adipocytes, muscle

What are the 3 metabolic systems that regulate response to fasting?

Hepatic glycogenolysis (stimulated by glucagon and epinephrine)
Hepatic gluconeogenesis (using amino acids from muscle protein)
Hepatic ketogenesis (fatty acid oxidation; ketones used by brain and muscle)

What is Whipple’s triad?

Signs and symptoms of hypoglycemia
Low BG (<2.8)
Resolution of symptoms after BG increased

What are factors that can affect measurement of BG?

Whole blood vs plasma (plasma 10-15% higher)
Time to sample measurement (more time = lower BG due to glycolysis by RBC and WBC)
Glucometers (inadequate sample = false low)
Sampling from line without adequate flush

Name 5 neurogenic symptoms of hypoglycemia (around 3 mmol/L)

* Shakiness, trembling, jitteriness (infants) * Sweating * Tachycardia * Hunger * Anxiety/nervousness * Weakness * Nausea/vomiting * Pallor (infants) * Hypothermia (infants)

Name 5 neuroglycopenic symptoms of hypoglycemia (\<2.8 mmol/L)

* Lethargy * Irritability, restlessness * Confusion * Headache, visual disturbance * Seizures * Poor feeding (infants) * Tachypnea * Apnea, cyanosis * Weak/high-pitched cry (infants) * Low tone, floppiness * Eye rolling, lip smacking (infants) * Loss of consciousness, coma

Why are babies with congenital hyperinsulinism born LGA?

Growth promoting effects of insulin in utero

Diagnostic criteria for hyperinsulinism? (Lab-based)

* Elevated plasma insulin (\>2 micromol/mL) * Low free fatty acids (\<1.5 mmol/L) * Low ketones (BOHB \<2.0 mmol/L) * Glycemic response to 1mg IV glucagon (\>30 mg/dl or 1.7 mmol/L)

What are the three genetic types of KATP hyperinsulinism? Do they respond to diazoxide?

1. Recessive, diazoxide unresponsive (most common). Essentially a complete absence of channels. 2. Dominant, diazoxide responsive 3. Dominant, diazoxide unresponsive

What are the actions of insulin, glucagon, epinephrine, GH and cortisol on glycogneolysis, gluconeogenesis, lipolysis and ketogenesis?

What drugs can cause hypoglycemia?

* Oral hypoglycemics (sulfonylureas) * Beta blockers * Insulin * Ethanol * Salicylates * Quinine * Unripe ackee fruit

What are the components of a critical sample?

* Glucose * Insulin * Beta-hydroxybutyrate * Free fatty acids * Growth hormone * Cortisol * Acylcarnitine profile * Plasma amino acids * Uric acid, ammonia, lactate * Urine: organic acids, urinalysis

Critical sample in: Insulinoma vs Adrenal Insufficiency vs Glyburide vs Exogenous Insulin

List 4 causes of a high insulin:glucose ratio in hypoglycemia

1. Exogenous insulin 2. Sulfonyluria (ex. glyburide) 3. Insulinoma 4. Monogenic hyperinsulinism (ABCC8, KCNJ11, GCK, GLUD1) 5. Dumping syndrome 6. Autoimmune hypoglycemia

List 6 causes of low insulin:glucose ratio in hypolgycemia

1. Adrenal insufficiency 2. GH deficiency 3. Benign ketotic hypoglycemia 4. Fatty acid oxidation defect 5. Glycogen storage disease 6. Sepsis 7. Alcohol or other drugs (salicylate, beta blockers) 8. Liver dysfunction 9. Chronic renal insufficiency 10. Starvation/malnourishment

List 4 safety issues to counsel in a patient with hypoglycemia unawareness

1. Driving: must be \>5 to drive 2. Alcohol: preventive measures to avoid hypoglycemia 3. Exercise: adjust food or insulin for activity 4. High-risk situations: avoid swimming alone 5. Medic Alert bracelet 6. Educate friends and family 7. Always carry meter and source of rapid glucose/glucagon

Name 3 genetic syndrome that can present with hyperinsulinism

1. Beckwith-Wiedemann syndrome 2. Sotos syndrome 3. Kabuki syndrome 4. Simpson-Golabi-Behmel syndrome