Steroid-Induced Diabetes Mellitus

Steroid induced diabetes mellitus is hyperglycaemia, or new diabetes, caused by glucocorticoid therapy, in people with or without pre-existing diabetes. Once daily morning oral prednisolone typically raises glucose in the afternoon and evening while fasting glucose stays near normal.

Risk is dose and duration dependent and begins within days. Risk factors are age over 60, obesity, prediabetes, previous gestational diabetes, family history of diabetes, high dose, chronic kidney disease and hepatitis C.

Causative agents are prednisolone, methylprednisolone and dexamethasone, by oral, intravenous, intra-articular, inhaled (high dose) or topical (extensive) routes. Dexamethasone and divided doses give hyperglycaemia across 24 hours.

Pathophysiology.

Glucocorticoids induce insulin resistance in muscle, liver and fat, increase hepatic gluconeogenesis and impair beta cell insulin secretion and the incretin effect.

Unlike fasting hyperglycaemia, the post-prandial rise is prominent, so fasting glucose and HbA1c underestimate the problem in short courses.

• Polyuria, thirst, blurred vision and weight change, usually from days after starting treatment.
• Often silent, found only on monitoring.

Red flags.

• Glucose over 30 mmol/L with drowsiness, marked dehydration or osmolality over 320 mmol/kg suggests hyperosmolar hyperglycaemia.
• Ketones 3.0 mmol/L or more suggest ketoacidosis in insulin deficient patients.

• Check capillary glucose before the evening meal (or 1 to 2 hours after lunch) for the first 48 hours in high risk patients and weekly after that during therapy; fasting values miss most cases.
• Treatment threshold: glucose above 12 mmol/L on two readings in 24 hours. Aim for 6 to 10 mmol/L before meals.
• Diabetes by usual criteria: random glucose 11.1 mmol/L or more with symptoms. HbA1c is unreliable in courses under 3 months.
• Repeat HbA1c or fasting glucose 3 months after stopping steroids to detect persistent diabetes.

Differential diagnosis.

• Previously undiagnosed type 2 diabetes unmasked by steroids.
• Stress hyperglycaemia from acute illness or sepsis.
• Pancreatitis or pancreatogenic diabetes, and enteral or parenteral feeding.
• Drug causes other than steroids (thiazides, calcineurin inhibitors, immune checkpoint inhibitors).

• Pre-existing diabetes on insulin: raise doses by 20 to 40% for prednisolone doses of 20 mg or more and monitor glucose before each meal and at bedtime.
• Morning prednisolone: gliclazide 40 mg with breakfast, titrated to 160 mg daily (maximum 320 mg daily), or metformin if eGFR is 30 or more (maximum 1000 mg daily at eGFR 30 to 44; stop under 30).
• Isophane insulin given with the morning steroid: 0.1 units/kg for each 10 mg of prednisolone, up to 0.4 units/kg daily at 40 mg or more. Increase by 10 to 20% daily to target.
• Dexamethasone or divided steroid doses: basal insulin (glargine or detemir) once daily, or twice daily isophane insulin, plus correction doses.
• Reduce insulin or stop gliclazide in step with each steroid reduction. Hypoglycaemia occurs when steroids are cut quickly.
• Hyperosmolar hyperglycaemia: intravenous 0.9% sodium chloride, fixed rate insulin 0.05 units/kg/h once glucose stops falling with fluids alone, thromboprophylaxis, and critical care review.

Special groups. Pregnancy: antenatal betamethasone for foetal lung maturation raises insulin needs for several days, so monitor glucose before and 1 hour after meals and titrate insulin.

Monitoring. Pre-evening-meal glucose daily during therapy, HbA1c at 3 months after stopping steroids.

Referral and escalation. Diabetes team if glucose is persistently over 20 mmol/L, insulin is needed in a patient without prior diabetes, or hyperosmolar features appear.