Week 1: Acute Complications of Diabetes

Question 1

Diagnostic features of diabetic ketoacidosis

Answer 1

1. hyperglycemia
2. ketonemia: excess ketons (acetoacetate and b-hydroxybutyrate) in serum
3. metabolic acidosis: wide anion gap

Question 2

Pathophysiology of hyperglycemia

Answer 2

• severe insulin deficiency leads to reduced glucose utilization in muscle and fat and increased glucose production
• stress hormones (esp epinephrine) stimulate further glucose production and limit utilization
• dehydration limits glucose excretion in the urine. Renal disease may also limit glucose excretion. Kidneys are like a safety valve to get rid of excess glucose. If blood glucose>600, dehydrated or renal failure.
• correction of hyperglycemia requires hydration +insulin

Question 3

Normal regulation of ketone and fatty acid metabolism

Answer 3

• normal fasting: insulin falls, glucagon rises
• increased TG breakdown and FFA release due to low insulin
• epinephrine, glucagon, and growth hormone promote FFA to TG
• FFA goes to liver and can be converted to ketones or TGs
• high glucagon promotes production of ketones from FFA by lowering molonyl coA and preventing it from inhibiting carnation acyl transferase.
• FFA converted to ketones in low insulin: glucagon ratio
• stress hormones are low, small amounts of insulin limits magnitude of FFA release and keeps things in balance

Question 4

Ketoacidosis pathogenesis

Answer 4

-insulin is very low or absent
-stress hormones are high and induce FFA release
-large supply of FFA to convert to ketones in liver (low insulin:glucagon ratio)
-ketone production exceeds utilization, build up of ketones
-H+KB–>H+ and KB-
-H+ soaked up by bicarb
results in low HCO3- and low pCO2 to compensate

Question 5

Two clinical scenarios of DKA

Answer 5

1. didn’t take insulin
   - stress hormones cause FFA release, hepatic ketogenesis occurs, leads to DKA
   - Rx with insulin and fluids
2. Acute illness
   - stress hormones lead to FFA release
   - this requires aggressive dose of insulin to treat to counterbalance stress hormones

Question 6

Metabolic acidosis in DKA

Answer 6

• wide anion gap in severe DKA, and normal anion gap in mild DKA
• use anion gap to monitor response to therapy

Question 7

Electrolyte abnormalities: potassium

Answer 7

• K+ is loss in urine with hyperglycemia due to osmosis diuresis
• low pH shifts K out of cells, keeps serum K+ normal
• but there is depletion of total body K+
• with correction of pH, and K shifting back into cells, serum K+ drops rapidly

Question 8

Electrolyte abnormalities: phosphate and creatinine

Answer 8

1. phosphate
   - loss during osmotic diuresis
   - very low serum levels associated with low supply of high energy phosphate compounds
   - severe phosphate depletion impaires functions of cells (ATP)
   - insulin therapy shifts phosphate into cells, DKA patients might need phosphate therapy to avoid severe hypophosphatemia
2. Creatinine
   - false elevation due to acetoacetate cross reaction in assays
   - Cr should be assessed after correction of ketoacidosis

Question 9

Dehydration in DKA

Answer 9

• due to osmotic diuresis, reduced fluid intake, vomiting

- worsens DKA by reducing blood flow to kidneys, limiting excretion of glucose and ketoacids

Question 10

Principles of treating DKA

Answer 10

• ketoacidosis: treated with INSULIN, fluid, underlying illnesses, bicarb for very low pH
• hyperglycemia: treat with FLUIDS, insulin
• electrolytes: monitor/give K and phosphate
• anion gap is treated by giving insulin, if it doesn’t come down, think of other causes of anion gap acidosis

Question 11

Diagnostic features of nonketotic hyperosmolar state

Answer 11

• hyperglycemia >600mg/dl
• elevated serum osmolality >320mosm/kg
• altered mental status
• no ketoacidosis

Question 12

Pathophysiology of hyperosmolar non ketotic state

Answer 12

1. hyperglycemia
   - low insulin, elevated glucose production, reduced utilization, DEHYDRATION, impaired RENAL function
   - hyperosmolar state occurs in those who: can’t drink to keep up with osmotic diuresis, have renal disease, have residual insulin secretion to suppress ketogenesis
2. elevated serum osmolality
   - dehydration
3. mental status
   - due to dehydration shifting water out of cells

Question 13

Principles of Rx of nonketotic hyperosmolar state

Answer 13

• Hyperglycemia: FLUIDS, insulin, rx other illnesses
• Associated abnormalities: monitor/give K and phosphate
• give fluids slowly due to idiogenic osmoses produced by brain cells so don’t overshoot treatment and cerebral edema