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Glycemic Control For Patients Receiving Corticosteroids

Oct 26, 2019
Editor: Steve Freed, R.PH., CDE

Author: Hira Gohar, Florida A&M University, College of Pharmacy, PharmD Candidate

Data from Randomized Clinical Trial on treating corticosteroid-induced hyperglycemia with the use of NPH insulin protocol therapy.

This randomized controlled trial was conducted and sponsored by the Hennepin Healthcare Research Institute. The study was targeted toward inpatients with diabetes that were receiving corticosteroids and how those corticosteroids affected their blood sugar levels. The use of corticosteroids in patients with or without diabetes can result in the patient developing severe hyperglycemia. 


How do corticosteroids induce hyperglycemia? Many ask this question because most people don’t understand the correlation. Corticosteroids are medications that have been used for many years, for patients with acute and chronic illnesses. They are medications that are mainly prescribed for their anti-inflammatory and immunosuppressive qualities. Although they have great benefits, they come with equally drastic disadvantages, such as the biggest one: corticosteroid-induced hyperglycemia. The pathophysiology behind how corticosteroids cause this effect is that they oppose the action of insulin and stimulate the act of gluconeogenesis, which is basically a metabolic pathway in the body that allows it to store energy in order to increase glucose production. This entire process leads to increased glucose output by the liver. There are people whose bodies can combat this process by producing more insulin to make up for this outcome and manage normal glucose levels, but then there are many people whose bodies cannot make up for this effect, thus resulting in the patient developing diabetes if they didn’t have it before, or becoming hyperglycemic if they were already diagnosed with diabetes prior to being hospitalized.

The focus of this study was directed towards using an NPH (neutral protamine Hagedorn) insulin protocol in order to help better control patients’ glucose levels. The use of this NPH insulin protocol was suggested to try in these hospitalized patients who were at risk for developing hyperglycemia. NPH insulin is properly timed in that on average it will begin to decrease blood glucose within 1 to 2 hours after injecting. NPH insulin also has a longer duration of action; it continues to work even after 12 hours have gone by. Researchers proposed the use of this insulin protocol in order to neutralize the corticosteroid-induced hyperglycemia. This insulin was given to patients alongside their regular insulin procedure and timed to correlate with the dose of corticosteroids that the patient was also taking. This protocol was intended to place patients in independent and control group settings, thereby timely monitoring their glucose levels during their hospital stay.

It was a randomized, prospective, non-blinded study that involved patients with diabetes who were inpatients at the hospital and were concurrently receiving more than or equal to 10 mg of prednisone per day or equivalent. The high dose corticosteroid group included patients who were receiving more than 40 mg of prednisone or equivalent. The patients on the high dose of corticosteroids received a 0.3 unit/kg dose of NPH insulin between 6:00 AM through 8:00 PM if they were eating. If they were not eating, they received a dose of 0.2 unit/kg of NPH insulin between the hours of 8:00 PM and 6:00 AM. The patients on the low dose of corticosteroids were those receiving prednisone 10-40 mg per day; these patients received 0.15 units/kg between 6:00 AM and 8:00 PM if they were eating. If they were not eating, they received 0.1 units/kg between the hours of 8:00 PM and 6:00 AM.

Primary outcome measures included the point of care glucose levels between both the independent and the control groups. These values are the umbrella of the mean point of care blood glucose. The independent group that received NPH insulin with each corticosteroid dose had an overall mean of 225 mg/dl. The control group that received their normal insulin without the NPH insulin had an overall mean of 266 mg/dl. This clearly indicated that the control group patients had an increased measurement of glucose as compared to the independent group. A key secondary outcome that was measured included episodes of hypoglycemia between the NPH group and the control group. Through this measure, the researchers observed that six patients in the independent NPH group underwent hypoglycemic episodes as compared to zero patients in the control group. This is a significant discovery in moving forward with this study because as readers we can clearly piece together the effects of the NPH insulin protocol and how it drastically influenced these patients’ glycemic levels. Another significant secondary outcome was the incidence of hyperglycemia shown as glucose levels above 400 mg/dL. In the independent NPH group, the percentage of total measurements was 5.9 percent as compared to the control group, which was 8.5 percent. This key difference in percent again confirmed that there was a major effect on glycemic levels in those patients’ receiving NPH insulin while on corticosteroids versus those who were not.

In summary, patients with diabetes who are hospitalized do have the opportunity to counteract the risk of becoming hyperglycemic if they are also taking a corticosteroid. This study proves that an NPH insulin protocol will help in achieving and maintaining proper glycemic control and thus overall better quality of life.

Practice Pearls:

  • Hospitalized patients who have diabetes are at a higher risk of developing hyperglycemia if they are concurrently given a corticosteroid.
  • An NPH insulin protocol helped in achieving proper glycemic control and maintaining patients’ standard of living in this specific patient population.
  • It is important to further assess and understand studies in which patients with diabetes have increased risks of developing hyperglycemia.

Khowaja, Ameer, et al. “Glycemic Control in Hospitalized Patients with Diabetes Receiving Corticosteroids Using a Neutral Protamine Hagedorn Insulin Protocol: A Randomized Clinical Trial.” Diabetes Therapy : Research, Treatment, and Education of Diabetes and Related Disorders, Springer Healthcare, Aug. 2018, https://www.ncbi.nlm.nih.gov/pubmed/29961246?dopt=Abstract.

“Corticosteroid-Induced Hyperglycemia : Nursing2019.” LWW, https://journals.lww.com/nursing/Fulltext/2012/11000/Corticosteroid_induced_hyperglycemia.21.aspx.

Inpatient Diabetes on Corticosteroids – Study Results.” Study Results – ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/results/NCT01970241?recrs=e&cond=diabetes&draw=2&rank=26&view=results.

 Hira Gohar, Florida A&M University, College of Pharmacy, PharmD Candidate