Treatment of Prednisolone-Induced Hyperglycemia in Hospitalized Patients: Insights from a Randomized-Controlled Study

Presentation Number: SUN 629
Date of Presentation: April 2nd, 2017

Anjana Radhakutty1, Jessica L Stranks2, Brenda L Mangelsdorf3, Sophie M Drake3, Gregory W Roberts4, Anthony T Zimmermann2, Stephen N Stranks3, Campbell H Thompson1 and Morton G Burt*1
1Flinders University, Adelaide, Australia, 2Lyell McEwin Hospital, Adelaide, Australia, 3Repatriation General Hospital, Adelaide, Australia, 4Flinders Medical Centre, Adelaide, Australia

Abstract

Introduction: Current guidelines recommend treatment of inpatient glucocorticoid-induced hyperglycemia with subcutaneous basal-bolus insulin, but do not specify the insulin formulation in detail (1). However, a morning dose of prednisolone, as commonly prescribed, has little effect on overnight glucose concentration and predominantly causes hyperglycemia in the afternoon and evening (2). Consequently, glargine-based basal-bolus insulin regimens may under-treat day-time hyperglycaemia and cause nocturnal hypoglycaemia. We investigated whether an isophane-based insulin regimen that delivers more insulin between midday and midnight is safer and more effective than a glargine-based insulin regimen.

Methods: 50 inpatients prescribed ≥20 mg/day prednisolone for an acute medical condition, with one finger prick blood glucose level (BGL) ≥15 mmol/L or two BGLs ≥10 mmol/L within 24 hours, were randomized to either insulin isophane or glargine before breakfast and insulin aspart before meals. The initial daily insulin dose was 0.5 U/kg body weight or 130% of the current daily insulin dose in both groups with 50% of the daily dose as basal insulin. Glycemic control was assessed using a continuous glucose monitoring system. Insulin regimens were adjusted daily using a standardized protocol. The primary endpoint was the percentage of time glucose was outside a glucose target range of 4-10 mmol/L on Day 1 of insulin treatment.

Results: On Day 1, there were no significant differences in the percentage time outside the target glucose range of 4-10 mmol/L (41 ± 6 vs 50 ± 6 %, p = 0.28), glucose <4 mmol/L (2.2 ± 1.1 vs 2.0 ± 1.3 %, p = 0.92) or mean daily glucose (10.2 ± 0.7 vs 10.8 ± 0.8 mmol/L, p = 0.57) in patients randomized to the isophane and glargine insulin regimens. Despite a greater daily insulin dose (0.97 ± 0.18 vs 0.55 ± 0.01 units/Kg, p <0.001), subjects who were on insulin prior to study entry spent more time outside the glucose target range (68.3±7.2 vs 39.5±4.1 %, p = 0.002) and had a higher mean glucose concentration (13.0 ± 1.1 vs 9.8 ± 0.5 mmol/L, p = 0.004) on Day 1 than patients not previously taking insulin. In patients treated for 3 days, prednisolone dose reduced (p=0.02) and insulin dose increased (p=0.02) over time, but the percentage of time outside the target 4-10 mmol/L glucose target range did not change over time (p=0.45) or differ between the groups (p=0.24).

Conclusions: There were no differences in the efficacy and safety of isophane and glargine-based insulin regimens in the treatment of prednisolone-induced hyperglycemia in hospitalized patients. We recommend a starting daily insulin dose of 0.5 units/Kg in most prednisolone treated patients, a greater than 30% increase in daily insulin dose in patients already on insulin and larger insulin dose adjustments than used in this study.

 

Disclosure: ATZ: Speaker, Astra Zeneca, Speaker, Merck & Co., Speaker, Novo Nordisk. SNS: Investigator, Novo Nordisk, Advisory Group Member, Astra Zeneca, Advisory Group Member, Lilly USA, LLC. Nothing to Disclose: AR, JLS, BLM, SMD, GWR, CHT, MGB