ERM2 - Hypoglycemia

• -plasma glucose concentration low enough to cause sx
• -~ 55mg/dL

• 1. Increase glucose transport into cells
• 2. Increase glucose utilization and ATP generation
• 3. Increase production of glycogen in LV and SKM
• 4. Increase AA absorption and protein synthesis
• 5. Increase TG synthesis

• 1. Increase breakdown of glycogen (glycogenolysis)
• 2. Increase breakdown of fats to FAs
• 3. Increase hepatic glucose synthesis

• 1. hypoglycemic sx
• 2. low plasma glucose
• 3. reversal of sx with food or glucose

• 1. Autonomic
•      -diaphoresis
•      -hunger
•      -paresthesias
•      -tremulousness
•      -palpitations
•      -anxiety

• 2. Neuroglycopenic
•      -cognitive impairement
•      -visual changes
•      -behavioural changes
•      -weakness
•      -lethargy
•      -dizziness
•      -seizures
•      -coma

• -decreased insulin
• -increased glucagon
• -increased Epi (accentuates insulin and glucagon responses)

• -increased growth hormone (increased lipolysis, antagonize insulin)
• -increased cortisol (increase lipolysis, prot catabolism and liver gluconeogenesis)

• 1. Insulin Mediated
• -endogenous hyperinsulinism
• -exogenous hyperinsulinism

• 2. Non-Insuling Mediated
• -drugs, alcohol
• -critical illnesses
• -non-islet tumor

-failure to suppress insulin levels as glucose falls

• Pro-insulin: increased
• C peptide: increased
• insulin: increased

• BHB levels < 2.7 mM/L (insulin inhibits ketogenesis)
• Increase glucose >25 mg/dL in response to glucagon

• 1. Insulinoma
• 2. Non-insulinoma Pancreatogenous Hypoglycemia Syndrome
• 3. Autoimmune Hyperinsulinism (anti-insulin Ab)

• -neuroendocrine tumor of islet cells
• -typically have fasting hypoglycemia
• -can be part of MEN1
• -less than 10% become malignant

• -nesidioblastosis: diffuse islet hypertrophy/hyperplasia
• -typically post prandial hypoglycemia
• -very rare: can develop months after gastric bypass

1. Medication-Induced

• -Sulfoylureas: stimulate insulin secretion
• -Meglitinides: stimulate insulin secretion

• Pro-Insulin: increased
• C-peptide: increased
• Insulin: increased

*distinguish from endogenous hyperinsulinism with SFU panel

• 1. Non-islet cell tumor hypoglycemia
• 2. Autoimmune hypoglycemia
• 3. Alcohol-related hypoglycemia

• -seen in a small number of patients with non-islet cell tumors
• -usually large tumors

MOA: secrete a form of IGF-II that has insulin-like activity (incompletely processed, has less affinity for IGFBP than WT --> increased free IGF-II)

• Pro-insulin: suppressed
• C-peptide: suppressed
• Insulin: suppressed

• 1. Abs to endogenous insulin
• -unregulated binding/dissociation of the Ab to insulin leads to hyperinsulinism

• 2. Abs to insulin R
• -activation of the R in the absence of insulin

-during fasting in normal ppl gluconeogenesis in the liver is responsible for the majority of glucose production

-Alcohol metabolism produces excess NADH, shunting precursors away from the gluconeogenesis pathway

--> inhibits gluconeogenesis

-also tend to be malnourished and have poor hepatic glycogen stores

• -tx underlying disorder
• -dietary modification (frequent small meals)
• -surgery
• -medical therapy to control sx in unresectable disease

• 1. diazoxide: decreases insulin secretion
• 2. Octreotide: inhibits insulin secretion
• 3. Verapamil/Phenytoin: may decrease insulin secretion
• 4. Glucocorticoids: increase insulin resistance
• 5. Everolimus: inhibits mTOR