Hyperglycemic Emergencies Flashcards
Hamnvic’s diagram of insulin release
Cellular response to insulin
Hamnvic diagam of incretin physiology and pharmacology
Hamnvic renal glucose handling
Hamnvic Insulin Pharmacology diagram
Glucagon and the fasting metabolic profile
Diabetic ketoacidosis (DKA) is a condition caused by ___
Diabetic ketoacidosis (DKA) is a condition caused by absolute insulin deficiency
Most common diabetic emergency in type II diabetes
Hyperglycemic hyperosmolar state
Characterized by very high blood glucose levels and plasma osmolality.
Differentiating DKA and HHS
Triggers of DKA
- Omission of insulin doses
- Increased insulin requirements from concurrent illness: Infections, cardiovascular disease (especially myocardial infarction), stroke
Major mediators of catabolic mobilization of glucose in insulin deficiency
- The glucose stress hormones!
- Corticosteroids, growth hormone, epinephrine, glucagon
In DKA, the high glucose level in the blood leads to . . .
. . . osmotic diuresis
Thereby causing intravascular volume depletion. The glycosuria is accompanied by elevated urinary potassium, leading to a total body deficit in potassium (hypokalemia).
Don’t forget about this effect when thinking of DKA! It is not just the ketones causing problems.
Clinical presentation of DKA
- Sudden onset, never more than a few days
- Nausea, vomiting, fatigue
- Polyuria, polydipsia
- Mental status change (drowsiness, sometimes coma)
- Tachycardia, orthostatic hypotension, hypotension (all from hypovolemia)
- Acetone breath
- By definition, elevated plasma glucose, positive urine and plasma ketones, and acidosis / reduced bicarbonate
- Often hyperosmolar hyponatremia
- Sometimes hypokalemia
Treating DKA
- Restore plasma volume
-
Lower blood glucose and osmolality
- Insulin
- Replenishment of electrolyte loss (specifically potassium)
- Identify and treat precipitating cause
- Transfer to ICU
Why is giving bicarbonate contraindicated in childhood DKA?
It increases the risk of cerebral edema, a deadly complication of DKA for children.
Pathogenesis of HHS
- Severe hyperglycemia, hyperosmolarity, and dehydration, but no significant ketosis
- Lead to mental status changes, coma, death
- Occurs in type II DM
- Risks include renal insufficiency and CHF
- Precipitated by pneumonia, stroke, MI, peri-operative state, drugs
- Initiating factor is a relative insulin deficiency, leading to increased glucose output
- Glycosuria and an osmotic diuresis
- Once volume contraction reaches a certain point, renal insufficiency develops due to pre-renal hypoperfusion
Presentation of HHS
- Insidious presentation over weeks to months
- Polyuria, polydipsia, weakness
- Milder symptoms than DKA
- Signs of hypovolemia on exam
- Severe hyperglycemia and elevated serum osmolality
- Renal impairment, elevated BUN and creatinine
Treatment of HHS
- Very similar to treating DKA
- Fluids
- Insulin
- Electrolyte replacement
-
Outcomes in HHS are often worse compared to DKA
- largely due to comorbidities of the type II DM population
- More advanced metabolic changes at time of presentation
- Venous thrombosis more common in this group
Transient, non-pathologic hypoglycemic states
- Prolonged fasting: Glucose levels may go as low as 55 mg/dL in men, 30 mg/dL in women. Ketones here are adaptive.
- Intense exercise: May cause glucose levels to go as low as 45 mg/dL.
- Normal pregnancies: Glucose may progressively drop due to fetal glucose demand, but this is a normal part of pregnancy and not pathologic
- Falsely low glucose lab results: Seen due to glucose consumption in the blood collection tube by blood cell elements, especially when the white blood cell is very high such as in leukemia or leukemoid reactions. Prevented by adding fluoride.
Physiologic cutoffs in low plasma glucose level
Effects of catecholamines on metabolism
Causes of hypoglycemia (for reference, short list)
Triggers for hypoglycemia in diabetic patients
- Reduced food intake
- Inappropriate timing of insulin administration
- Increased physical activity
- Increase in insulin dosage
Signs of moderate hypoglycemia in diabetic patients
- Stem from catecholamine activation
- Sweating
- Hunger
- Tachycardia/palpitations
- Nausea
- Restlessness
Signs of moderate-on-severe hypoglycemia
- Stem from the beginnings of cerebral glucose shortage
- Irritability
- Confusion
- Blurred vision
- Tiredness
- Headache
- Difficulty speaking
Signs of severe hypoglycemia
- Stem from total insufficiency of glucose supply to brain
- Syncopy
- Coma
- Seizure
- Death
In patients who experience frequent hypoglycemic episodes, ___ can develop as a complicating factor.
In patients who experience frequent hypoglycemic episodes, hypoglycemia unawareness can develop as a complicating factor.
The patient does not experience typical sympathetic and parasympathetic symptoms until the glucose level is much lower! This means that neuroglycopenic symptoms may be the first warning of hypoglycemia.
This is part of why it is so important for patients to regularly check their blood sugar.
Defective counterregulatory responses to glucose in type I diabetes mellitus
Treatment of hypoglycemia in diabetic patients
- Depends on the patient’s mental status
- If patient can take food orally, they should be given 15g of oral glucose
- Therefore, insulin-treated patients with diabetes should carry a portable source of sugar
- If the patient is unable to take glucose by mouth, then glucagon can be administered parenterally (usually intramuscularly).
- Glucagon injection kits are provided to the patient and family members for emergency use.
- Intravenous glucose (e.g., dextrose) can also be given once trained medical personnel arrives.
Other drugs which may cause hypoglycemia
- Stated elsewhere, but sulfonylureas and other ATP-dependent K channel antagonists are major contributors
- Quinolone antibiotics
- ACE inhibitors
- Alcohol
Insulinomas
- Associated with MEN-1 (remember PPP)
- Malignant in 10% of cases
- Recurrent hypoglycemia, often with mostly neuroglycopenic symptoms (fatigue, blurred vision, car accidents). Adrenergic symptoms are often blunted due to hypoglycemia unawareness
- Whipple’s triad: symptoms of hypoglycemia, confirmed low blood sugar while experiencing symptoms, resolve with treatment of the hypoglycemia
Diagnosing insulinomas
- Measuring high or inappropriately normal insulin levels in the setting of hypoglycemia
-
C-peptide and proinsulin are useful markers
- If they are low, exogenous insulin should be suspected
- In certain cases, for proper diagnosis, hypoglycemia may need to be triggered by a supervised fast (no more than 72 hrs, in hospital setting)
- Glucagon tolerance test (will antagonize insulin-mediated hypoglycemia, but not other causes of hypoglycemia)
Treating insulinomas
- Localization is often very difficult, as tumors are very small
- If CT/MRI are unsuccessful, endoscopic ultrasound may help
- In some cases, selective calcium-stimulated angiography is needed
- Once found, surgically resected
-
Diazoxide may be given prior to surgery
- Agonizes the ATP-dependent K+ channel, preventing depolarization and insulin release
- Octreotide (somatostatin mimetic) used with variable success
- Streptozotocin (alkylating agent) used for malignant insulomas
Diazoxide
- Used to treat insulinomas
- Binds the SUR1 subunit of K+/ATP channels in pancreatic β-cells and stabilizes the ATP-bound (open) state of the channel so that the β-cells remain hyperpolarized and less insulin is released.
- Its main side effects are edema and hyperkalemia.
Autoimmune hypoglycemia
- Antibodies to insulin or the insulin receptor
- Type II hypersensitivity
- These conditions are rare
- Most are reported in Japan, which is thought to be due to a much higher incidence of a predisposing HLA allele in the Japanese population.
Reactive hypoglycemia
- Postprandial hypoglycemia
- Caused by rapid absorption of carbohydrates from the meal
- May occur following Roux-en-Y gastric bypass or other gastric surgeries
- The initial high glucose absorption is accompanied by excess levels of insulin, leading to the subsequent hypoglycemia.
- Diagnosis is done with a mixed meal test, where hypoglycemia is confirmed
- Treatment usually consists of frequent small meals with limited simple carbohydrates.
- Acarbose may be used
Acarbose
- α-glucosidase inhibitor
- Slows down absorption of complex carbohydrates
