182. Hypoglycemia & Islet Issues

Question 1

When does hypoglycemia occur?

Define the following:

• Severe hypoglycemia
• Documented Sx Hypoglycemia
• Asx hypoglycemia
• Probable Sx Hypoglycemia
• Pseudo-hypoglycemia
• WHIPPLE’S TRIAD

Answer 1

Occurs when BG < 70 mg/dL

Severe Hypo: requiring assistance of others for carbs/glucagon/action, neuro recovery following return of BG to normal (sufficient evidence, no BG level needed)
Documented Sx Hypo: typical hypo sx and BG < 70
Asx Hypo: no sx of hypo and BG < 70
Probably Sx Hypo: sx of hypo w/o definite BG
Pseudo-Hypo: sx of hypo and BG > 70 (but downtrending/approaching 70)

whipples triad

1. Sx consistent with hypo (trembling, sweating, hunger, reduced consciousness)
2. Low BG measured precisely (plasma, not glu monitor)
3. Relief of sx after BG level raised

Question 2

What is the physiologic response to lowering blood glucose?

How is BG regulated? How is it maintained?

Answer 2

BG 80-85: Suppress insulin
BG 65-70: Secrete glucagon, secrete epi, secrete cortisol/GH
BG 50-55: Sx, increase feeding
BG <50: reduced cognition (compromises behavioral defense)

BG regulated by insulin!
BG maintained by: endogenous glu production, hepatic glycogenolysis, hepatic/renal gluconeogenesis

Question 3

What are the signs/sx of hypoglycemia?

List causes of hypoglycemia (what hormone abnormalities?)

Answer 3

Sx: diaphoresis, pallor, high BP/HR, confusion, fatigue, seizure, LoC, death, adrenergic (palpitations, tremor, anxiety), cholinergic (sweating, hunger, paresthesias)

Causes: Drugs (ins, ins analogs, alcohol), critical illness (hepatic, renal, cardiac, sepsis, starvation), hormone DEFICIENCY (low cortisol, low glucagon, low epi), endogenous hyperinsulinism, insulin receptor autoimmunity, accidental/surreptitious/malignant ins use

Question 4

What are the risk factors of hypoglycemia in DM?

What is hypoglycemia-associated autonomic failure?

Answer 4

RF: relative or absolute ins excess
Ins excess: ins doses excessive, ill-timed, wrong type, decreased influx of exogenous meals (skipped meals, overnight fast), high ins-independent glu utilization (exercise)
High ins sensitivity: improved glycemic control, due to increased fitness/weight loss
Decreased endogenous glu production: due to alcohol ingestion (liver focuses on metabolizing alcohol, blocking gluconeogenesis)
Decreased insulin clearance: renal failure (exo ins RENAL, endo ins LIVER)

HAAT: REVERSIBLE disorder

• occurs in beta cell failure (ins levels high due to pharm replacement, glucagon levels do not rise)
• EPI secretions blunted as hypoglycemic events occur = loss of adrenergic + cholinergic sx during hypoglycemia (unaware of hypoglycemia)
• reversible with avoidance of hypoglycemia

Question 5

How do the following cause hypoglycemia?

• renal failure
• hepatic failure
• cardiac failure
• sepsis
• starvation
• Addison’s disease
• Cortisol Deficiency
• GH Deficiency

Answer 5

Renal: decreased exo ins clearance, lower mobilization of gluconeogenesis precursors
Hepatic: fasting hypoglycemia, less glycogen stores
Cardiac: unclear
Sepsis: increased glu utilization by cytokines in macrophage-rich tissues, decreased glu production
Starvation: decreased body fat stores, loss of gluconeogenesis precursors, increased glu utilizations
Addison’s Disease - glycogen depletion
Cortisol deficiency - blocks gluconeogenesis, low levels of gluconeogenic precursors
GH deficiency - assoc with hypoglycemia in children (hypoglycemia = less growth)

Question 6

Hypoglycemia from Non-Beta-Cell Tumors

• pt type
• pathophys
• dx
• tx

Answer 6

Pt’s with large mesenchymal/epithelial tumors (hepatoma, adrenocortical ca, carcinoids)
Ins secretion appropriately suppressed
PPhys: hypoglycemia due to overproduction of IGF2 - interacts with ins receptors (IGF2 does not complex with circulating proteins and faster access to target tissues)
Dx: see tumor on CT, labs - high IGF2:IGF1 ratio, high free and pro-IGF2 levels
Tx: surgical resection (cure rare), reduce tumor bulk to improve hypoglycemia (less IGF2), meds: steroids +/- GH

Question 7

Insulinoma

• what is it
• pt type
• pathophys
• dx
• tx

Answer 7

uncommon, >90% benign, treatable cause of potentially fatal hypoglycemia, sporadic or genetic (MEN1)
Pt: median age 50 in sporadic, 30 in genetic
PPhys: tumoral production of ins - 99% in pancreas, usually small (<2cm), dx from hypoglycemic sx
Dx: biochemical (high endogenous production of ins, c-peptide, pro-insulin DURING hypoglycemia - low BG), sx of hypoglycemia with no resolution by glucagon (normally suppresses ins production), imaging US/CT/MRI for masses, octreotide scan for detection
Selective pancreatic arterial Ca injection: increase in hepatic venous insulin levels based on artery tested help localize tumor

Tx: surgical resection (curative)
meds: diazoxide (inhibits ins secretion)
octreotide (SS analog, tx for hypoglycemia if tumor unresectable)
everolimus (mTOR inhibitor for advanced insulinomas)

Question 8

Post-Gastric Bypass Hypoglycemia

• what is it
• mechanism
• dx
• tx (what don’t you do?)

Answer 8

Post-prandial (not fasting) hypoglycemia due to endogenous hyperinsulinism
mech: exaggerated GLP-1 response to meals in intestine (due to less digestion in stomach) = hyperins and hypoGlu
Dx: post-prandial hypoglycemia esp after high glycemic index meal, imaging does not show tumor
Tx: DO NOT GIVE GLU (will further increase GLP and worsen sx)
- diet modification (high protein, low glycemic index foods)
- meds: Acarbose (blocks glu absorption in intestine), octreotide
- surgery: partial pancreatectomy

Question 9

Accidental, Surreptitious, Malicious Hypoglycemia

• causes
• dx (differentiate from type of med used)

Why might glucose measurements be inaccurate? How do you prevent this?

Answer 9

Cause:

• accidental ingestion of ins secretagogue (pharmacy/medical error) or insulin
• surreptitious/malicious administration of ins mimics insulinoma
• most common in health care workers, pts/relatives with DM, pts with history of factitious illness

Dx: HIGH C-PEPTIDE (hyperinsulinism or SU use)
LOW C-PEPTIDE (high exogenous ins administration suppresses endogenous ins production)

Low BG levels may be artifacts due to continued glu metabolism by cells in blood sample in tube, enhanced by states of increased cell numbers (leukocytosis (infection), erythrocytosis, thrombocytosis)
Prevent by using GREY TOP TUBE (separates blood from cells!)