The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2018

Introduction: In a patient with type 1 diabetes, who is insulinopenic, the hyperosmolar hyperglycaemic state with suppressed ketones is a rare presentation. In the insulinopenic state counter-regulatory hormones at high concentrations (glucagon, adrenaline and cortisol) increase the action of hormone sensitive lipase, releasing free fatty acids from adipose tissue predisposing to diabetic ketoacidosis (DKA) through beta-oxidation and conversion to ketone bodies. We report a patient who in the setting of intermittent insulin adherence with methamphetamine use and acute on chronic renal impairment presented with Hyperosmolar Hyperglycaemic State (HHS) instead of DKA.

Case: A 36-year-old Caucasian male with type 1 diabetes and established micro and macrovascular complications including nephrotic range proteinuria, was brought into the Emergency Department obtunded. He presented febrile (38^oC), tachycardic (112 beats per minute), hypertensive (BP 240/110 mmHg) and dehydrated. Laboratory investigation results revealed a pH: 7.3 a normal anion gap 16 mmol/L, venous glucose 82 mmol/L and ketones 0.66 mmol/L. Increased serum osmolarity of 345 mOsmol/L. Creatinine 504 umol/L baseline Creatinine 280 umol/L and hyperkalaemia (K: 6.3mmol/L).

He was diagnosed to have a hyperosmolar hyperglycaemic state (HHS) complicated by acute on chronic kidney disease (CKD) in the setting of methamphetamine use.

We propose the following mechanism for this:

1. Renal impairment reduces insulin clearance and subsequently increases its half-life. Ketosis suppression requires 1/10 of insulin required for hyperglycaemia suppression1.
2. Suppression of glucagon a hormone secreted by alpha cells of the pancreas and enteroendocrine cells in the gut by cocaine and amphetamine regulated transcript (CART). CART is a pancreatic peptide released in response to methamphetamine suppresses glucagon release.

Conclusion: In the setting of acute on chronic renal failure with methamphetamine use the counter regulatory hormone suppression is the proposed link in supressing ketoses and predisposing to hyperosmolar hyperglycaemia state in susceptible patients with Type 1 Diabetes.