Hyperosmolar Hyperglycaemic State (HHS)

Question 1

List DDx for a presentation of elevated BMI, 42 yo male, dehydrated, fluctuating LOC, hx polyuria and polydipsia?

Answer 1

PDx. hyperosmolar hyperglycaemic state (secondary to T2DM)

DDx.

• DKA (T1DM complication, younger onset, thinner, ketonuria)
• Diabetes insipidus
• Ketoacidosis: alcoholic, starvation
• Acidosis: lactic (exercise), uraemic (CKD)
• Drug-induced: paracetamol. salicylate
• Toxins: ETOH, methanol, ethylene glycol

Question 2

Describe the pathophysiology of HHS?

Answer 2

Causes: infection, CVA, MI, surgery, poor compliance to insulin or hyperglycaemic agents, newly Dx DM

Path:

• > insulin deficiency or resistance (T2DM, sometimes T1DM)
• > lack of regulated glucose absorption into adipose tissue and striated muscle (GLUT-4 insulin transporter) AND high hepatic gluconeogenesis
• > hyperglycaemia
• > increased glucose in blood (osmotically active, hyperosmolar) -> causes water to be drawn from cells
• > glucose excreted in kidney tubules but cannot be resorbed
• > increased osmotic pressure
• > increased water retention in lumen
• > osmotic diuresis -> dehydration

Question 3

Differentiate between HHS and DKA?

Answer 3

HHS

• older pt (60s), high BMI
• mostly T2DM
• glucose >33.3mmol/L
• serum osmolality >320mmol/L
• pH >7.3
• NO ketonuria
• mental changes more common
• mortality 10-20%

DKA

• younger pt (20s), normal BMI
• mostly T1DM
• glucose not as high (>13.9)
• serum osmolality varies
• ketoacidosis (pH <7.3), large anion gap
• ketonuria
• abdo pain more common
• mortality 1-4%

Ketones: in T2DM relative insulin deficiency means the small amount of insulin enough to minimise ketone development but not enough to control hyperglycaemia

Question 4

How do you calculate effective serum osmolality?

Answer 4

Effective serum osmolality

= (2 x Na) + (glucose/ 18)

Question 5

Describe the emergency management of HHS?

Answer 5

• Fluid resuscitation w isotonic saline (0.9% saline) infusion
• Insulin: give once BSL plateaus after fluid replacement and K >3.5mmol/L
• > once BSL <15mmol/L, give IV glucose 5% until pt able to eat -> subcut insulin
• Potassium: give if serum K <3.5mmol/L (stop >4.5)

Question 6

Describe Metformin therapy?

Answer 6

Biguanides e.g. Metformin
▪ MOA: reduces hepatic gluconeogenesis, increases insulin action (in muscle and fat) -> increased uptake and utilization of glucose
▪ SE: nausea and vomiting, diarrhoea, rash, rarely – lactic acidosis

Question 7

Describe Sulfonylureas therapy?

Answer 7

Sulfonylureas e.g. Glibenclamide
▪ MOA: stimulates insulin secretion from pancreas by blocking ATP sensitive K+ channels on beta cells -> Ca2+ influx, depolarisation and insulin release
▪ SE: hypoglycaemia, GIT effects, weight gain
▪ CI: breastfeeding