Management of Glucocorticoid-Induced Hyperglycemia

Figures & data

Table 1 Common Indications for Use of Glucocorticoid Therapy

Physiological replacement	● Adrenal insufficiency ● Congenital adrenal hyperplasia
Anti-inflammatory and immunosuppressive effects (supraphysiological doses)
Organ system
Respiratory	● Bronchial asthma ● Acute exacerbation of COPD ● Interstitial lung disease ● Hypersensitivity pneumonitis ● COVID-19 ● ARDS ● Cytokine storm ● Anaphylaxis ● Sarcoidosis ● Cystic fibrosis
Rheumatologic	● Rheumatoid arthritis ● SLE ● Ankylosing spondylitis ● Polymyositis/dermatomyositis ● Polyarteritis ● Vasculitis
Dermatological	● Acute severe dermatitis ● Urticaria/angioedema ● Pemphigus vulgaris
Ophthalmological	● Uveitis ● Keratoconjunctivitis ● Optic neuritis
Hematological	● Lymphoma/leukemia ● Hemolytic anemia ● Idiopathic thrombocytopenic purpura
Endocrine	● Subacute thyroiditis ● Lymphocytic hypophysitis
Gastrointestinal	● Ulcerative colitis ● Crohn’s disease ● Autoimmune hepatitis
Renal	● Nephrotic syndrome
Organ transplantation	● Heart, kidney, liver ● Cornea
Neurological	● Multiple sclerosis ● GBS ● AIDP or CIDP ● Cerebral edema

Box 1 Standard definitions for hyperglycemia

● Diabetes: FPG ≥126 mg/dL (7.0 mmol/L). Fasting is defined as no caloric intake for at least 8 h.* OR 2-h PG ≥200 mg/dL (11.1 mmol/L) during OGTT. The test should be performed as described by WHO, using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water.* OR A1C ≥6.5% (48 mmol/mol). The test should be performed in a laboratory using a method that is NGSP certified and standardized to the DCCT assay.* OR In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose ≥200 mg/dL (11.1 mmol/L). ● Prediabetes: FPG 100 mg/dL (5.6 mmol/L) to 125 mg/dL (6.9 mmol/L) (IFG) OR 2-h PG during 75-g OGTT 140 mg/dL (7.8 mmol/L) to 199 mg/dL (11.0 mmol/L) (IGT) OR A1C 5.7–6.4% (39–47 mmol/mol). (* For all three tests, risk is continuous, extending below the lower limit of the range and becoming disproportionately greater at the higher end of the range. * In the absence of unequivocal hyperglycemia, diagnosis requires two abnormal test results from the same sample or in two separate test samples) ● In-hospital/inpatient hyperglycemia: any glucose value >140 mg/dL (7.8 mmol/L) in hospitalized patients. Bedside capillary glucose values are acceptable in this setting. ● Stress-induced hyperglycemia: elevation of fasting glucose ≥ 126 mg/dL (≥7 mmol/L), or 2-hour postprandial glucose > 200 mg/dL (≥11 mmol/L) measured at any time, in a patient without evidence of previous diabetes and who spontaneously returns to normal range post discharge. ● Glucocorticoid-induced hyperglycemia: A general term for increase in blood glucose levels due to steroid treatment, including persons with pre-existing diabetes who have a glycemic control deterioration. ● Glucocorticoid-induced diabetes: Individuals who develop diabetes in relation to steroid therapy without previously having had a diagnosis of diabetes.

Table 2 Glucocorticoids in Clinical Use: Preparations and Equivalent Potency

	Type of Glucocorticoid	Duration of Action (Hours)	Equivalent Potency	Relative Glucocorticoid Activity	Relative Mineralocorticoid Activity	Peak of Action (h)
Short acting	Hydrocortisone	8–12	20 mg	1	1	1
	Cortisone	8–12	25 mg	0.8	0.8	–
Intermediate acting	Prednisone	12–36	5 mg	4	0.8	1–3
	Prednisolone	12–36	5 mg	4	0.8	–
	Methylprednisolone	12–36	4 mg	5	Minimal	–
	Triamcinolone	12–36	4 mg	5	0	–
	Deflazacort	12–24	6 mg	4		1.3
Long acting	Dexamethasone	36–72	0.75 mg	30	Minimal	1.6–2
	Betamethasone	36–72	0.6 mg	30	Negligible	–
	Fludrocortisone	12–36	Not used for glucocorticoid activity due to very high mineralocorticoid activity	10–15	125–150	–

Notes: Data from: Liu et al, 2013;¹² Pickup, 1979;¹³ Möllmann et al, 1995;¹⁴ Derendorf et al, 1991;¹⁵ and Leow et al, 1986.⁴⁶

Box 2 Glycemic Targets (AACE)

● Targets for patients on glucocorticoids in domiciliary care and ward areas: <140 pre-meal and <180 post-meal. ● Target for ICU patients: 140–180 mg/dL (7.8–10.0 mmol/L). ● Hypoglycemia should be avoided.

Table 3 Dose Treatment Regimens and Duration

Dose Effects	Prednisolone/day Equivalent Dose (mg)
Low dose	<7.5 mg per day (physiological replacement)
Moderate dose	7.5–30 mg per day
High dose	30 mg per day
Very high dose	100 mg per day
Pulse therapy	250 mg per day for one or few days
Duration
Short-term duration (oral corticosteroids)	<21 days

Note: Data adapted from Buttgereit et al, 2002.¹⁷

Table 4 Management of Glucocorticoid-Induced Hyperglycemia

Patient Clinical Status	Management
Patients with pre-existing DM who are stable with no metabolic or medical compromise	● Monitor regularly ● Continue existing therapy ● Increase insulin dose by 20% ● Increase dose/add sulfonylurea for post prandial control ● Meglitinides for post-lunch control ● Sulfonylurea and meglitinides should not be used together ● Alpha glucose inhibitors for post prandial control ● Metformin, pioglitazone, DPP-4 inhibitors and SGLT2 inhibitors as well as GLP1Ra can be continued as such unless there is clinical deterioration or patient is not eating well
Patients in Non-ICU/Ward	● Begin basal bolus with correction regimen ● If not feasible, begin premix with an oral (metformin, +/- short acting sulfonylureas/meglitinides/DPP-4 inhibitors) at lunch
Patients in ICU	● Intravenous insulin ● If not feasible, basal-supported correction bolus dose

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