Inpatient Diabetes Mellitus (DM) Management With Continuous Glucose Monitoring Devices, a Pilot Study.
Phase: NA
Conditions: Diabetes Mellitus
Sponsor: University of Maryland, Baltimore

 
“Inpatient Diabetes Mellitus (DM) Management With Continuous Glucose Monitoring Devices, a 
Pilot Study.” 
 
NCT Number: NCT02904512 
 
Uploaded 10/25/2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A.  Background and Significance: 
 
Several observational studies have shown that uncontrolled hyperglycemia in 
hospitalized patients in the non-critical care, non-Intensive Care Unit (non-ICU) setting is 
associated with prolonged length of stay, increased mortality and an increased incidence of 
infections [1-6].  Randomized clinical trials in both the critical and the non-ICU settings have 
shown that by improving glucose control there is a decrease in the incidence of infections, 
length of stay and inpatient health care costs [7-10]. 
 
While hyperglycemia has known deleterious effects, profound hypoglycemia can cause 
neurological damage [11], as well as induce fatal arrhythmias, due to increased counter 
regulatory hormones, such as catecholamines, especially in patients with preexisting coronary 
artery disease [12, 13]. Hypoglycemia in the inpatient setting is more common than in the 
outpatient setting, with prevalence rates among medical and surgical patients ranging between 
3-30% [7, 14-17]. Hypoglycemic events in the hospital setting have been associated with 
increased mortality and prolonged length of stay [18].  
 
Almost all patients with DM (Diabetes Mellitus) monitor their glucose values with Point of 
Care (POC) blood glucose testing. The accuracy of most handled glucose meters is at the very 
least “not optimal” and the FDA allows a variance of 20% for meter measurements and 10% for 
central laboratory measurements as compared to the true blood glucose levels [19]. Continuous 
glucose monitoring (CGM) systems have evolved as useful devices providing excellent clinical 
care in patients with DM [19]. These systems detect glucose in subcutaneous interstitial fluid 
using a glucose sensor that transmits glucose measurements to a receiving device that reads 
out average glucose levels every 5 minutes. Using traditional glucose monitors, gaps occur 
during which time glucose excursions are undetected/ undocumented. CGM provides glucose 
measures during these time gaps. CGM devices have been shown to improve glycemic control 
and decrease duration of hypoglycemia in outpatients with DM. CGM are recommended in 
patients with DM (outpatient setting) with hypoglycemic unawareness, as a declining glucose 
trend can trigger hypoglycemia-threshold alarms to alert the patient prior to the onset of severe 
hypoglycemia [20].  
Several published studies have examined the use of CGMs in the inpatient setting [21-
30]. Most of the studies have been performed in the ICU setting [21-28], where CGM use may 
not be beneficial to the patients, as patients are monitored closely, with glucose values checked 
every 1 hour or even more frequently. In the non-ICU setting, where the majority of patients are 
hospitalized (General Wards), the data for using CGM are limited. In a single arm observational 
study Burt and colleagues showed that CGM was able to detect for hyperglycemia excursions 
and more hypoglycemia events than POC-FSBG [29]. In a study that examined the use of CGM 
in hospitalized patients with DM2 [30], CGM use was able to detect more hypoglycemic events 
(55 vs 12, p=0.0001) compared to the group that was managed with POC-FSBG. 26.3% of the 
hypoglycemic events were asymptomatic and the majority of these events were identified by 
CGM use (86.7%). CGM use was more likely to detect nocturnal and daytime hypoglycemic 
events (p=0.0399 and 0.0066 respectively). Notably participants in this clinical trial [30] were 
insulin naïve (not previously on insulin) DM2 subjects, a group of patients that may not be at 

high risk for hypoglycemia. Both of these studies [29, 30] showed that CGM use can detect 
more hypoglycemic events. However, as these studies were blinded for both investigators and 
patients, interventions to prevent hypoglycemia were not performed. The next reasonable step 
is to examine whether CGM use can prevent hypoglycemic events.  
In this pilot study we propose to examine the clinical use of CGM in hospitalized insulin 
treated patients with DM2, admitted in General Medicine Wards setting who are at higher risk 
for hypoglycemia. We anticipate that our intervention will decrease the number of hypoglycemic 
events, which represents a significant safety concern in the inpatient setting. We also anticipate 
that our intervention may decrease hyperglycemia (mild or severe) and therefore may improve 
clinical outcomes such as nosocomial complications and length of stay.  This pilot study may 
lead us to obtain preliminary data that will help us to design larger clinical studies 
B. Aims: 
In this randomized clinical trial, we will evaluate whether inpatient use of CGM devices 
are beneficial in subjects with DM2 in the non-critical care setting (general wards).  
Groups: 
Half of the hospitalized patients will be monitored with POC testing and non blinded 
CGM (for both the investigators and the subjects, Intervention Group). Management of this 
group of patients  will be based on glucose values obtained by CGM and POC testing. 
Half of the subjects will be monitored by POC testing only. CGM results will be blinded 
(for both the investigators and the subjects, Control Group). Management of this group of 
patients will be based on glucose values obtained by POC-FSBG only.  
Aim 1: To determine if we can prevent more hypoglycemic values/ events in the 
Intervention Group vs Control group.  
Hypothesis 1: CGM use (un-blinded) and POC-FSBG will prevent more hypoglycemic 
values/events compared to subjects that we will be managed by POC-FSBG only.  
Aim 2: To determine if subjects that are in the Intervention Group will have 
decreased hyperglycemia compared to control Group. 
 
Hypothesis 2: Subjects that will be managed by CGM and POC-FSBG will have 
decreased hyperglycemia compared to subjects that will be managed by POC-FSBG only.  
Aim 3: To determine if subjects that are in the Intervention Group will have 
decreased severe hyperglycemia compared to control Group. 
Hypothesis 3: Subjects that will be managed by CGM and POC-FSBG  will have 
decreased severe hyperglycemia compared to subjects that will be managed by POC-FSBG 
only. 
C. Design and Methods:  

Human Subjects 
Inclusion criteria: ≥21 years of age; history of type 2 DM managed with insulin (either 
basal bolus, basal with per os DM medications) who also fulfill 1 or more of the following criteria, 
all known risk factors of hypoglycemia [31-34]: Insulin use of more than 0.6 u/kg, age ≥65, BMI 
≤ 27, renal failure, liver failure, active malignancy, congestive heart failure, CVA or sepsis. We 
will also include hospitalized individuals with type 2 DM treated with insulin that developed a 
significant hypoglycemic episode in a recent (<6 months) hospitalization. 
Exclusion criteria: Subjects that have a history of type 1 DM. History of type 2 DM that 
are being treated with diet or any combination of oral antidiabetic drugs only, as these patients 
are less likely to benefit from CGM use. We will also exclude subjects that have significant 
hyperglycemia or DKA that requires treatment with intravenous insulin infusion and any patients 
that need hospitalization in the critical care (ICU) setting. Pregnant patients, patients receiving 
glucorticoids in doses (equivalent) to ≥ 20 mg of hydrocortisone/day, or patients that are 
expected to require a hospital stay <3 days will also be excluded [35]. Finally, we will exclude 
any individual with a mental condition rendering the subject incapable of understanding the 
objectives and potential consequences of the study. 
The ethics committee of the University of Maryland and VABMC will approve the study 
protocol. Informed consent will be obtained from all enrolled subjects.  
Lab Values and Glucose Measurements: 
All participants will have an Hba1c, CBC and BMP at the time of enrollment in the study, 
lab values that represent standard of care in admitted subjects with DM.  
For DM subjects monitored with POC-FSBG and CGM (Intervention Group) or with 
POC-FSBG only (Control Group): In both groups, participants will have their glucose values 
monitored with POC-FSBG as follows: Pre-breakfast (fasting), pre-lunch, pre-dinner, at bedtime 
and at 3am) [6, 36]. For admitted veterans that are not eating or that receive continuous enteral 
nutrition, we will check POC-FSBG every 6 hours [15]. 
For DM subjects enrolled in the POC-FSBG and CGM (Intervention Group), in addition 
to POC-FSBG, glucose values will be monitored continuously, over 24 hours, by CGM.  
POC-FSBG will be measured any time the CGM alarms. In addition POC-FSBG will be 
measured any time a participant (in either group) develops symptoms that are suggestive of 
hypoglycemia. 
Insulin Treatment: 
Titration of insulin will be not made based on the CGM values. Titration adjustments of 
the insulin regimen will be made by the inpatient diabetes management service team, based on 
POC-FSBG values. Titration of basal insulin (glargine) will be made based on the fasting am 
glucose values, based on the following algorithm (Table 1).  

Table 1. Titration of basal insulin (glargine) [35] 
Fasting am BG values  
Basal dose (IGla) adjustments 
If BG< 60 mg/dl 
Decrease dose by 20% 
If BG 60-79 mg/dl 
Decrease dose by 10% 
If BG 80-139 mg/dl 
No change 
If BG 140-179 mg/dl 
Increase dose by 10% 
If BG 180-249 mg/dl 
Increase dose by 20% 
If BG >250 mg/dl 
Increase dose by 30% 
 
Titration of correctional (sliding scale) insulin will be adjusted daily based on fasting and 
pre-meals capillary BG levels (Table 2) [35]. If subjects are placed NPO, capillary blood glucose 
values will be checked every 6 hours and insulin will be administered based on the same insulin 
algorithm (Table 2). Subjects will be treated initially with the “insulin sensitive” regimen, as this 
group of individuals has a high risk for hypoglycemia. If capillary BG is persistently above 140 
mg/dl throughout the day in the absence of hypoglycemia, we will increase the insulin scale 
regimen from the “insulin sensitive” to the usual or from the “usual” to the “insulin resistant” 
regimen [15, 35]. If a research subject has POC-FSBG <80 mg/dl, we will decrease accordingly 
the insulin scale regimen from “insulin resistant” to “usual” or from “usual” to “insulin sensitive” 
[15, 35].  
Table 2. Titration of Correctional (Sliding Scale) Insulin (Novolog) [35]. 
BG Values 
Insulin sensitive 
Usual 
Insulin resistant 
<80 mg/dl 
-1 
-1 
-2 
80-139 mg/dl 
0 
0 
0 
140-159 mg/dl 
0 
+1 
+1 
160-199 mg/dl 
+1 
+1 
+2 
200-249 mg/dl 
+2 
+3 
+4 
250-299 mg/dl 
+3 
+5 
+7 
300-349 mg/dl 
+4 
+7 
+10 
>350 mg/dl 
+5 
+8 
+12 
 

Titration of short acting prandial insulin will be based on pre-lunch, pre-dinner and 
bedtime BG, adjusting the previous administrated prandial insulin dose, targeting BG values 
140-180 mg/dl.  If BG is 181-250 mg/dl we will increase the prandial dose by 15%, if it is 251-
300 by 20% and if BG was greater than 300 mg/dl we will increase by 30%. 
GGM alarm settings and Prevention of Hypoglycemia:  
CGM alarms will be set to <85 mg/dl (for prevention for low blood glucose levels) and 
>400 mg/dl (for alarming for high blood glucose levels). If CGM alarms for low glucose values, a 
POC-FSBG will be obtained. If it is the POC-FSBG is between 70-85 mg/dl, at least 10 gr of 
carbohydrates will be given to the subject as a preventive measurement for hypoglycemia. An 
additional POC-FSBG will be obtained in 15 min in order to confirm that the BG are rising. 
Similarly, the group of patients that are managed by POC-FSBG only (Control Group), if a 
POC-FSBG will be found to be between 70-85 mg/dl, at least 10 gr of carbohydrates will be 
given to the subject as a preventive measurement for hypoglycemia. 
Treatment of Hypoglycemia 
Treatment of hypoglycemia will be similar in the 2 groups and will be based on standard 
hospital protocols. 
Outcome Measures 
Aim 1: Hypoglycemic values will be defined as POC-FSBG<70 mg/dl and will be 
classified as severe if it involved loss of consciousness and/or seizures [35]  We will evaluate if 
there is a difference in the total number of hypoglycemic events between the 2 groups, by 
evaluating POC BG values. Time spent during hypoglycemia will be also calculated in both 
groups, using data from GCM devises.  
Aim 2: We will compare time spent in hyperglycemia (>180 mg/dl) between the 2 groups. 
We will  compare glucose values obtained from the CGM devises from Interventional group (un-
blinded) and Control group (blinded).   
Aim 3: We will compare time spent in severe hyperglycemia (>300 mg/dl) between the 2 
groups. We will compare glucose values obtained from the CGM devises from Interventional 
group (un-blinded) and Control group (blinded).   
Statistical plan 
Descriptive statistics including means and SDs will be computed for continuous 
variables, and counts and proportions will be computed for categorical variables. Wilcoxon’s 
rank sum test will be applied to comparing continuous variables between the intervention group 
and the standard-of-care group. Fisher’s exact test will be used to compare categorical 
variables between the two groups. Data analysis will be carried out using SAS statistical 
program. 
 

Safety 
All subjects that participate in the proposed study will be patients with DM that will be 
admitted to the VABMC hospital for medical reasons. Glucose monitoring for Control group will 
be made with POC-FSBG testing that represents standard of care. Interventional group will be 
monitored as above, however additionally CGM will be utilized. To address any daytime or 
overnight problems the PI will be on call. The PI is well versed in trouble shooting problems with 
the CGM devices. Nurses and house staff will receive additional training for the CGM devices.  
There are some functional limitations with regard to using CGM in the non-critical care 
unit.  As it is recommended, CGM devices will be removed during MRI or CT scanning. 
Calibration of CGM devices will be performed every 12 hours, as recommended. As CGM 
receivers with be used with multiple patients, the devices will be disinfected as recommended 
with Cavicide before and after use with each patient to prevent transmission of infectious 
agents. We are familiar with disinfection of CGM receivers, as we frequently use CGM devices 
in the VABMC DM outpatient clinic, in different patients.    
 
 
 
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