LETTER TO THE EDITOR

Pilot Study of Using Neutral Protamine Hagedorn Insulin

to Counteract the Effect of Methylprednisolone in Hospitalized
Patients With Diabetes
Stacey A. Seggelke, RN, MS, CDE Division of Endocrinology, Metabolism, and Diabetes, Department of Medicine, University of Colorado
Joanna Gibbs, PA-C Denver, School of Medicine, Denver, Colorado.
Boris Draznin, MD, PhD

Administration of steroids has a detrimental effect on glyce- and after methylprednisolone and went up by approxi-
mic control in patients with diabetes,1,2 which presents a mately 40% in the course of the follow-up. This increase
significant challenge during both outpatient and inpatient was accounted for by NPH insulin in Group 1 and by
management. increasing doses of glargine and lispro in Group 2.
Methylprednisolone raised prelunch and predinner glyce-
Patients and Methods mia in patients treated with glargine and lispro. In contrast,
We conducted a pilot study in 20 patients with cystic fibro- administration of NPH insulin concomitant with methyl-
sis–related diabetes (CFRD), after bone marrow or solid prednisolone significantly prevented increases in hypergly-
organ (liver, kidney, or lung) transplantation, who received cemia (Table 1) relative to the glargine/lispro group. Fasting
methylprednisolone intravenously (10-60 mg) during admis- glycemia rose only slightly and nonsignificantly in all
sions to the University of Colorado Hospital, Denver, Colo- patients on methylprednisolone. There were no episodes of
rado. All patients received basal glargine and premeal lispro hypoglycemia in either group during the study period.
insulins. A total of 10 patients (randomized 1:1) received
neutral protamine Hagedorn (NPH) insulin at the time of
administration of methylprednisolone between 8 and 11 am
Conclusions
This pilot study demonstrates potential clinical effectiveness
(Group 1). The dose of NPH insulin was selected as follows:
of NPH insulin to counteract hyperglycemic influence of
1 unit (U) for 1 mg methylprednisolone for the first 20 mg
methylprednisolone in hospitalized patients with diabetes.
of steroid; 0.5 U of insulin for 1 mg of methylprednisolone
Even though NPH insulin is traditionally given twice daily,
for the next 20 mg of steroid; and 0.25 U of insulin for each
we used it on a once-daily basis concomitantly with admin-
subsequent milligram of steroid. The average dose of NPH
istration of methylprednisolone. Previously, Bevier et al.2
was 23 6 5 U. In the remaining 10 patients, the doses of
used continuous glucose monitoring to estimate insulin
glargine and lispro were increased according to the Univer-
requirement in patients with type 1 diabetes during a short
sity of Colorado Hospital’s standard protocols for use of
course of prednisone administration (60 mg daily, given
subcutaneous insulin to achieve the best possible control
orally for 3 days). Prednisone was administered
(Group 2). Point-of-contact glycemia immediately prior to
initiation of steroids and for the 3 days of methylpredniso-
lone administration was compared. Results are expressed as TABLE 1. Glycemia (mg/dL) in Hospitalized Diabetic
mean 6 standard deviation and compared using the Student Patients on Methylprednisolone Treated for 3 Days With
t test with P value < 0.05 considered significant. Glargine, Lispro, and NPH Insulins (Group 1) or Glargine
and Lispro (Group 2)
Results Days 1, 2, 3 Group 1 Group 2 P Value
Preadmission glycemic control (as assessed by the hemoglo-
bin A1C on admission: 7.8 6 2.1% vs. 7.5 6 2.6%) and ca- Day 1: fasting* 131 6 34 125 6 31 NS
loric intake (regular diet) during the 3 days of follow-up Prelunch 193 6 36 257 6 57 < 0.01
were equally variable in both groups (data not shown). Predinner 197 6 33 300 6 60 < 0.001
Day 2: fasting 137 6 28 140 6 21 NS
Doses of glargine and lispro insulins 1 day before initia- Prelunch 189 6 25 279 6 35 < 0.001
tion of methylprednisolone therapy were 30 6 16 and 35 6 Predinner 193 6 24 302 6 45 < 0.001
12 U, respectively, in Group1 (mean total daily insulin Day 3: fasting 154 6 27 159 6 23 NS
[TDI], 65 U); and 32 6 18 and 31 6 8 U in Group 2 (mean Prelunch 194 6 25 292 6 23 < 0.001
Predinner 193 6 22 319 6 32 < 0.001
TDI, 63 U). On the third day of methylprednisolone admin-
istration, the doses of glargine, lispro, and NPH were 30 6 Results are expressed as mean 6 standard deviation of 10 values per each time point per group. *Fast-
16, 37 6 7, and 23 6 U in Group 1 (mean TDI, 90 U); and ing levels on day 1 were obtained before methylprednisolone was started. Abbreviation: NS, not
46 6 10 U of glargine and 44 6 12 U of lispro in Group 2 significant.
(mean TDI, 90 U). TDI was similar in both groups before

2011 Society of Hospital Medicine DOI 10.1002/jhm.874

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Journal of Hospital Medicine Vol 6 No 3 March 2011 175

experimentally, because none of these patients required ste-
roids for medical reasons. All patients were on insulin
pumps, and their basal rates and boluses were adjusted to
control steroid-induced hyperglycemia. The investigators
found that increases in insulin doses, both basal and
boluses, were evident by 6 hours of the first dose of predni-
sone. Even though in that study the TDI increased by 30 to
100%, patients did not achieve normoglycemia. Our study,
although in a different patient population, concurs with
their findings as we observe an increase in TDI of approxi-
mately 40%. We were somewhat reluctant to be more
aggressive with glargine and lispro for the fear of potential
hypoglycemia that might be detrimental to hospitalized
patients.3,4
Limitations of the study include a small number of
patients, very specific patient population (patients with
CFRD, after bone marrow or solid organ transplantation), as
well as inclusion only of patients on 1 daily intravenous ste-
roid administration. Further studies are needed to evaluate
2011 Society of Hospital Medicine DOI 10.1002/jhm.874
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176 Journal of Hospital Medicine Vol 6 No 3 March 2011
effectiveness of NPH insulin for patients on multiple steroid
injections and for patients on oral steroids.
We conclude that in this small pilot study, NPH insulin
in doses described above appears to be safe and effective in
achieving reasonable glycemic control in hospitalized dia-
betic patients receiving methylprednisolone.
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