Steroid Induced Diabetes

Steroid induced diabetes is hyperglycaemia caused by systemic glucocorticoids in a person who may or may not have had diabetes before. Glucocorticoids raise glucose by increasing hepatic gluconeogenesis, causing insulin resistance in muscle and fat, and impairing insulin secretion, so the typical pattern is normal fasting glucose with marked hyperglycaemia from the afternoon to the late evening after a morning dose of prednisolone.

• Risk rises with dose and duration: prednisolone 10 mg daily or more (or equivalent) for 1 week or longer, and with each additional risk factor: age over 60, obesity, family history of type 2 diabetes, prediabetes, previous gestational diabetes, South Asian, African or Caribbean ancestry, chronic kidney disease, and concurrent drugs (thiazides, tacrolimus, ciclosporin, antipsychotics).
• Prednisolone 5 mg is equivalent to hydrocortisone 20 mg, methylprednisolone 4 mg and dexamethasone 0.75 mg. Dexamethasone and long acting preparations cause sustained hyperglycaemia including fasting values. Inhaled, intra articular and epidural steroids can also raise glucose for days.
• Frequency: about 20 to 50 percent of people on high dose treatment develop hyperglycaemia, and about 2 percent develop persistent diabetes.
• Complications include hyperosmolar hyperglycaemic state (more often than ketoacidosis), infections, poor wound healing, and hypoglycaemia when steroid doses fall while glucose lowering treatment is left unchanged.

• Thirst, polyuria, nocturia, fatigue, blurred vision, weight loss and recurrent thrush or urinary infection, often starting 1 to 2 days after treatment begins and worst in the afternoon and evening.
• Often asymptomatic, found on routine testing in patients on steroid courses.
• Red flags for hyperosmolar state: confusion, severe dehydration, drowsiness, glucose above 30 mmol/L (540 mg/dL), tachycardia, hypotension.
• Examination: weight, blood pressure, hydration, cushingoid features, skin infection, feet.

• Check capillary glucose before the evening meal (4 to 6 hours after a morning steroid dose) because fasting glucose often misses the problem. Check twice daily (before lunch and before the evening meal) in the first week of high dose treatment in people with risk factors.
• Diagnostic thresholds: random or post-lunch venous glucose 11.1 mmol/L (200 mg/dL) or more with symptoms, or on two readings; fasting 7.0 mmol/L or more; HbA1c 48 mmol/mol (6.5 percent) or more, but HbA1c reflects the previous 3 months and is unreliable in short courses, anaemia and recent transfusion.
• Urea, electrolytes, creatinine, osmolality and ketones (urine or blood) when glucose is above 20 mmol/L or the patient is unwell.
• After stopping steroids, test fasting glucose or HbA1c at 3 months to find persistent diabetes or pre-existing diabetes unmasked.
• Differentials: type 1 or type 2 diabetes first presenting during illness, stress hyperglycaemia from the underlying disease, pancreatitis, Cushing syndrome.

General

• Use the lowest effective steroid dose for the shortest time, give a single morning dose of prednisolone (or divide hydrocortisone) and consider inhaled or topical routes when clinically suitable.
• Dietary advice: reduce refined carbohydrate and sugary drinks, regular meals, no fasting; maintain hydration.
• Teach glucose monitoring and symptoms of hyperglycaemia and hypoglycaemia, and sick day rules.

Treatment of known diabetes starting steroids

• Increase monitoring to twice or four times daily. Raise doses early: expect to increase insulin by 20 to 50 percent, and reduce again as steroid dose falls.
• People on metformin alone: increase to 1 g twice daily (eGFR above 45) and add gliclazide 40 mg with breakfast, titrated every 2 to 3 days to 160 mg daily.
• People on insulin: add isophane (NPH) insulin in the morning with the steroid dose, or increase pre-meal doses, by about 10 to 20 percent for each 10 mg of prednisolone.

New steroid induced hyperglycaemia (glucose above 12 mmol/L on two readings)

• Gliclazide 40 mg with breakfast, increased every 2 to 3 days by 40 mg to 160 mg daily (maximum 320 mg in divided doses, specialist). Hypoglycaemia risk rises in older adults, chronic kidney disease and when steroids are reduced. Avoid in pregnancy.
• Or isophane (NPH) insulin given in the morning at the same time as prednisolone: start 0.1 units/kg per 10 mg of prednisolone (maximum 0.4 units/kg at 40 mg or more), adjusting every 1 to 2 days to target pre-evening meal glucose 6 to 10 mmol/L. Reduce the insulin by the same ratio as each steroid dose reduction, and stop when steroids stop.
• Metformin 500 mg daily, increased to 1 g twice daily, is useful in mild cases (avoid if eGFR below 30, acute illness, dehydration).
• Pioglitazone 15 to 30 mg daily or a DPP-4 inhibitor (sitagliptin 100 mg daily) are alternatives, but weight gain and fluid retention occur with pioglitazone and the effect of gliptins is modest.
• Sodium glucose cotransporter 2 inhibitors are not suitable during acute illness because of ketoacidosis risk.

Hyperosmolar hyperglycaemic state or ketoacidosis

• Emergency admission for intravenous fluids and insulin.

Special groups

• Pregnancy: use insulin; avoid gliclazide.
• Older adults: aim for glucose 8 to 12 mmol/L, avoiding hypoglycaemia.
• Children: refer to paediatric endocrinology.
• Long term steroid users (more than 3 months): give full diabetes care, with HbA1c monitoring every 3 to 6 months, foot and eye checks and cardiovascular risk management.

Follow up

• Review within 1 week of starting treatment, with each steroid dose change, and 3 months after stopping steroids.