ORIGINAL ARTICLE

Evaluation of safety of insulin degludec onundergoing total colonoscopy using continuous
glucose monitoring
Soichi Takeishi, Akihiro Mori*, Nobutoshi Fushimi, Hiroki Hachiya, Takayuki Yumura, Shun Ito, Takashi Shibuya,
Noritsugu Ohashi, Hiromi Kawai
Department of Endocrinology and Diabetes, Ichinomiyanishi Hospital, Aichi, Japan

Keywords
Continuous glucose monitoring,
Insulin degludec, Total colonoscopy*Correspondence
Akihiro Mori
Tel.: +81-586-48-0077
Fax: +81-586-48-0038
E-mail address: a-mori@anzu.or.jp
J Diabetes Investig 2015
doi: 10.1111/jdi.12409
Clinical Trial Registry
University Medical Information
Network
UMIN000012265

ABSTRACT
Aims/Introduction: There is little information regarding how to use insulin degludec(D) when diabetic patients are preparing for total colonoscopy (TCS).
Materials and Methods: A total of 12 patients with type 2 diabetes treated withinsulin D and scheduled to undergo TCS were enrolled in the present study. A continuous glucose monitoring device was attached to each patient for 4 days, from two evenings before TCS to the morning after the procedure. The patients fasted for 24 h,starting after 18.00 h the day before TCS. Insulin D was only discontinued the morning of
the day TCS was carried out.
Results: No patients experienced hypoglycemia during the daytime fasting period(08.00–18.00 h the day of TCS); the hypoglycemic index, mean glucose level, and standard
deviation were 0, 141.3 – 31.5 mg/dL and 15.6 – 6.5 mg/dL. The mean glucose level andstandard deviation during the daytime fasting period were significantly lower than during
the daytime control period (08.00–18.00 h the day before TCS; P = 0.003, P = 0.001,
respectively). The mean fasting glucose and fasting plasma glucose levels were significantly correlated (r = 0.78, P = 0.002), as were both the mean glucose level and standard
deviation during the daytime control period, and the change in the mean glucose level(fasting period minus control period; r = -0.79, P = 0.002, and r = -0.69, P = 0.01, respectively).
Conclusions: Patients can safely undergo TCS when insulin D is discontinued only
once on the day of the procedure.

INTRODUCTION
A signiﬁcant correlation between diabetes and the risk of coloncancer has been reported1. Therefore, screening for colon cancer
with total colonoscopy (TCS) in patients with type 2 diabetes isimportant. Although the gold standard for diagnosis of coloncancer is TCS2, bowel preparation for this procedure is sometimes cumbersome for patients with diabetes. Because mostpatients undergoing TCS are required to fast for a long period
except for intake of bowel lavage solution, which does not haveany calories, use of agents with hypoglycemic action should be
reduced or discontinued during preparation for TCS. In this scenario, glucose variability in patients with diabetes taking theseantidiabetic agents might be poorer. Furthermore, in patientstaking agents with a long-acting proﬁle, hypoglycemia could
consistently occur even with discontinuation of these agents.
Insulin degludec (D), which is an ultralong-acting insulin analog, has been available clinically in Japan since March 2013.
Insulin D can achieve both less glucose variability and a lower
frequency of hypoglycemia even in unstable patients with diabetes, because it provides a stable insulin concentration for morethan 42 h3. Recently, we reported that the action proﬁle ofinsulin D is beneﬁcial for glycemic control at night-time, when
patients are fasting4. When preparing to undergo TCS, mostpatients are required to fast both the night before and the day ofthe procedure. Theoretically, when the dose of insulin D isappropriate as basal insulin, even if patients treated withinsulin D are fasting, hypoglycemia is not supposed to occur
because of its pharmacological characteristics5. However, there

Received 11 February 2015; revised 23 July 2015; accepted 28 July 2015ª 2015 The Authors. Journal of Diabetes Investigation published by Asian Association of the Study of Diabetes (AASD) and Wiley Publishing Asia Pty Ltd
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution
in any medium, provided the original work is properly cited, the use is non-commercial and no modiﬁcations or adaptations are made.

J Diabetes Investig Vol.  No.   2015

1

ORIGINAL ARTICLE
Takeishi et al.

are some concerns that patients treated with insulin D mightdevelop hypoglycemia if the fasting period is extended during the
day of the procedure, because the effect of this insulin continues
for more than 42 h. In such a situation, we have only limited
experience in using insulin D, and there is little information
available regarding how to use insulin D. In the present study,
we evaluated safety in patients with type 2 diabetes treated withinsulin D and scheduled to undergo TCS by measuring glucose
variability with continuous glucose monitoring (CGM).

MATERIALS AND METHODSPatients with type 2 diabetes who were treated with the same
dose of insulin D for more than 3 months were encouraged toundergo TCS for screening of colon cancer from December
2013 to January 2014, and we consecutively and prospectively
enrolled patients who agreed to the procedure. On admission, a
CGM device (Medtronic ipro2; Medtronic MiniMed, Northridge, CA, USA) was attached to each patient for 4 days, fromtwo evenings before (the ﬁrst day) undergoing TCS to themorning after the procedure (the fourth day), and glucose variability was evaluated. On the day before the procedure (the second day), patients were treated with their usual dose of insulin,
and consumed test meals at 08.00, 12.00 and 18.00 h. Purgatives (Sennoside A&B calcium and sodium picosulfate hydrate)
were given at 22.00 h. On the day TCS was carried out (thethird day), the patients consumed polyethylene glycol electrolyte
solution (1 L) and water (500 mL) within a 2-h period startingat 10.00 h. TCS was carried out at 16.00 h to integrate procedure time, because the time required for the bowel cleaning
was routinely up to 6 h, and the patients consumed a test mealat 18.00 h. By following this protocol, the patients fasted for
24 h. Neither glucagon nor any anticholinergic agent was given
to the patients to suppress bowel movement before or duringcolonoscopy. Insulin D was injected at 08.00 h every morning
except the third day (the day TCS was carried out), andpatients discontinued treatment with all antidiabetic agents only
at breakfast and lunch on the third day (the day TCS was carried out). The patients were given three meals per day, eachwith 1,440, 1,600 or 1,840 kcal, determined according to their
physique6. Identical test meals were given to each patient basedon the recommendation of the Japan Diabetes Society. The
patients did not have any special meal, such as a low-residue
diet, on the day before colonoscopy. The physical activity at
admission to the study was 1.5 metabolic equivalents based on
the analysis of baseline data. Patients with severe renal dysfunction (serum creatinine level ≥2.0 mg/dL) or judged to beunsuitable for participation for medical reasons, were excluded
from this study.
The primary aim of the present study was to evaluate thesafety of insulin D by measuring the frequency of cases ofhypoglycemia (<70 mg/dL), the hypoglycemic index7, and themean glucose level and standard deviation (SD)8 during thedaytime fasting period (fasting between 08.00 and 18.00 h on
the day of TCS). These parameters were also compared2

J Diabetes Investig Vol.  No.   2015

http://onlinelibrary.wiley.com/journal/jdi

between the daytime fasting period and daytime control period(non-fasting between 08.00 and 18.00 h on the day before
TCS), and the relationships of the change in the mean glucose
level (daytime fasting period – daytime control period) withthe mean glucose level during the daytime control period andSD during the daytime control period were determined.
Data are shown as mean and SD. Statistical analysis was carried out with Welch’s t-test, v2-test, paired t-test and Pearson’s
correlation coefﬁcient test. A P-value of <0.05 was consideredsigniﬁcant. The study protocol was approved by the EthicalCommittee of Ichinomiyanishi Hospital (authorization no.
25017), and was registered in a clinical trial database with the
University
MedicalInformation
Network(no.
UMIN000012265).

RESULTS
Baseline characteristics of patients

A total of 12 patients (8 men and 4 women) were enrolled in
the present study. The baseline characteristics included age of
65.6 – 11.3 years, body mass index of 23.7 – 2.6 kg/m2, glycated hemoglobin of 7.2 – 0.8% (54.7 – 8.4 mmol/mol), duration of diabetes of 18.0 – 14.2 years, fasting plasma glucose(FPG) level of 135.6 – 44.8 mg/dL and C-peptide index (CPI;=fasting C-peptide immunoreactivity/FPG 9 100) of 0.9 – 0.6.
Six patients received basal–bolus treatment (basal–bolus), andsix patients received basal insulin only (basal). The basal insulin
dose was 0.19 – 0.08 U/kg/day, and the total insulin dose was
0.31 – 0.18 U/kg/day. The total insulin dose was signiﬁcantly
higher in the basal–bolus group than in the basal group. In
regard to oral antidiabetic agents, dipeptidyl peptidase-4 inhibitors were used in signiﬁcantly more patients in the basal groupcompared with the basal–bolus group. Signiﬁcantly more female
patients were in the basal–bolus group compared with the basalgroup. There were no other signiﬁcant differences in characteristics between the two groups. A colon adenoma (diameter of
20 mm) was detected in one of the 12 patients and resectedsuccessfully. The performance time of TCS was 20.8 – 9.5 min(Table 1).
Primary ﬁndings
Evaluation of the 12 Patients

No patients experienced hypoglycemia during the daytime fasting period; the hypoglycemic index, mean glucose level, and SD
were 0, 141.3 – 31.5 and 15.6 – 6.5 mg/dL, respectively (Figure 1a and Table 2). The mean glucose level during the daytime fasting period and the FPG level were signiﬁcantly
correlated (r = 0.78, P = 0.002; Figure 2). There were no significant differences between the mean glucose level during thedaytime fasting period and the FPG level (141.3 – 31.5 vs
135.6 – 44.8, P = 0.49).
Evaluation of Each Insulin Regimen

No patients in the basal–bolus group experienced hypoglycemia during the daytime fasting period; the hypoglycemicª 2015 The Authors. Journal of Diabetes Investigation published by AASD and Wiley Publishing Asia Pty Ltd

ORIGINAL ARTICLE
Safety of degludec on undergoing TCS

http://onlinelibrary.wiley.com/journal/jdi

Table 1 | Baseline characteristics of patients
Characteristic

Overall

Basal–bolus

Basal

P (b vs c)n (male/female)Age (years)
Duration of diabetes (years)
BMI (kg/m2)
HbA1c, NGSP (%)
HbA1c, IFCC (mmol/mol)
Basal insulin dose (U/kg/day)Total (basal and bolus) insulin dose (U/kg/day)
FPG (mg/dL)
CPI
Injection time of basal insulin
Sulfonylurea agent (n)Biguanide agent (n)Thiazolidine (n)a-Glucosidase inhibitor (n)DPP4 inhibitor (n)GLP-1 analog (n)Insulinotropic agent with rapid onset (n)12 (8/4)
65.6 – 11.3
18.0 – 14.2
23.7 – 2.6
7.2 – 0.8
54.7 – 8.4
0.19 – 0.08
0.31 – 0.18
135.6 – 44.8
0.9 – 0.6
08.00 h
0
6
0
2
8
0
0

6 (2/4)62.8 – 15.0
18.0 – 14.8
22.6 – 2.5
7.5 – 0.9
58.1 – 10.3
0.23 – 0.07
0.46 – 0.10
147.0 – 58.2
0.7 – 0.6

6 (6/0)68.3 – 6.2
18.0 – 15.1
24.8 – 2.3
6.9 – 0.4
51.4 – 4.7
0.15 – 0.07
0.15 – 0.07
124.2 – 26.9
1.1 – 0.4

P2 = 0.01
P1 = 0.43
P1 = 1P1 = 0.15
P1 = 0.19
P1 = 0.19
P1 = 0.09
P1 = 0.0002
P1 = 0.41
P1 = 0.17

0
2
0
2
2
0
0

0
4
0
0
6
0
0

P2 = 1P2 = 0.25
P2 = 1P2 = 0.12
P2 = 0.01
P2 = 1P2 = 1

Data are shown as mean – standard deviation. P, basal–bolus vs basal; P1, Welch’s t-test; P2, v2-test. Basal, basal insulin only; Basal–bolus, basal–bolus
treatment; BMI, body mass index; CPI, C-peptide index (=fasting C-peptide immunoreactivity/FPG 9 100); DPP, dipeptidyl-peptidase; FPG, fasting
plasma glucose; GLP, glucagon-like peptide; HbA1c, glycated hemoglobin; IFCC, International Federation of Clinical Chemistry; NGSP, National Glycohemoglobin Standardization Program; SD; standard deviation.

Glucose level (mg/dL)(a) 400

Discontinue

D

D

300
200
100
0
8 pm

TCS
8 am

6 pm

8 am

6 pm

Glucose level (mg/dL)(b) 400

D

300
200
100
0
8 pm

(c) 400
Glucose level (mg/dL)

Discontinue

D

8 am
Meal

TCS
8 am

6 pm

8 am

6 pm

Discontinue

D

8 am
Meal
D

300
200
100
0
8 pm

TCS
8 am

6 pm

8 am

6 pm

8 am
Meal

Figure 1 | Glucose variability on continuous glucose monitoring in patients during treatment with insulin degludec. Values represent median (thicklines) and interdecile ranges (fine lines). (a) Overall (n = 12). (b) Basal–bolus treatment (n = 6). (c) Basal (basal insulin only; n = 6). (d) Insulin
degludec. TCS, total colonoscopy.

index, mean glucose level, and SD were 0, 146.0 – 39.0
and 17.2 – 6.0 mg/dL, respectively. In addition, no patientsin the basal group experienced hypoglycemia; the hypo-ª 2015 The Authors. Journal of Diabetes Investigation published by AASD and Wiley Publishing Asia Pty Ltd

glycemic index, mean glucose level, and SD were 0,
136.6 – 24.5 and 14.1 – 7.1 mg/dL, respectively (Figure 1b,cand Table 2).

J Diabetes Investig Vol.  No.   2015

3

ORIGINAL ARTICLE
Takeishi et al.

4

0141.3 – 31.5
15.6 – 6.5
0
191.0 – 50.8
43.0 – 20.1
Hypoglycemic index
Mean glucose level (mg/dL)
SD (mg/dL)

Daytimefasting period
Daytime control
periodJ Diabetes Investig Vol.  No.   2015

Data are shown as mean – standard deviation (SD). P, paired t-test. Daytime control period, daytime non-fasting control period (non-fasting between 08.00 and 18.00 h on the day
before total colonoscopy); Daytime fasting period, daytime fasting period (fasting between 08.00 and 18.00 h on the day before total colonoscopy).

0
136.6 – 24.5
14.1 – 7.1
0
187.7 – 52.4
38.9 – 21.8
1
0.003
0.001

0
194.4 – 53.9
47.1 – 19.4

Daytimefasting period
Daytimecontrol period0146.0 – 39.0
17.2 – 6.0

1
0.09
0.02

Daytimefasting period
Daytimecontrol period

Basal
P
Basal–bolus
P
Overall

Table 2 | Parameters of glucose variability in patients treated with insulin degludec during the daytime control period and daytime fasting period

P

1
0.02
0.06

http://onlinelibrary.wiley.com/journal/jdi

Secondary ﬁndings
Comparison of Parameters Between the Daytime Fasting Period
and Daytime Control Period
Evaluation of the 12 patients

No patients experienced hypoglycemia during the daytime control period, and the hypoglycemic index was 0. There were no
signiﬁcant differences in the hypoglycemic index between thedaytime fasting period and daytime control period. The mean
glucose level and SD during the daytime fasting period weresigniﬁcantly lower than those during the daytime control period(P = 0.003 and P = 0.001, respectively; Figure 1a and Table 2).
Evaluation of each insulin regimen

No patients in the basal–bolus group experienced hypoglycemia
during the daytime control period, and the hypoglycemic index
was 0. There were no signiﬁcant differences in the hypoglycemic index between the daytime fasting period and daytime
control period. The mean glucose level during the daytime fasting period tended to be lower than that during the daytime
control period (P = 0.09). The SD during the daytime fasting
period was signiﬁcantly lower than that during the daytime
control period (P = 0.02; Figure 1b and Table 2).
Similarly, no patients in the basal group experienced hypoglycemia during the daytime control period, and the hypoglycemic index was 0. There were no signiﬁcant differences in
the hypoglycemic index between the daytime fasting period anddaytime control period. The mean glucose level during the daytime fasting period was signiﬁcantly lower than that during thedaytime control period (P = 0.02). The SD during the daytime
fasting period tended to be lower than that during the daytime
control period (P = 0.06; Figure 1c and Table 2).
Estimation of the relationship between the mean glucose level
during the daytime control period and the change in the mean
glucose level

The mean glucose level during the daytime control period andthe change in the mean glucose level were signiﬁcantly correlated (r = -0.79, P = 0.002; Figure 3a), although the mean glucose level during the daytime control period was not
signiﬁcantly correlated with the total insulin dose or CPI (Figure 3b,c).
Estimation of the relationship between the SD during thedaytime control period and the change in the mean glucose
level

The SD during the daytime control period and the change inthe mean glucose level were signiﬁcantly correlated (r = -0.69,
P = 0.01; Figure 4a), although the SD during the daytime control period was not signiﬁcantly correlated with the total insulin
dose or CPI (Figure 4b,c).

DISCUSSION
Patients undergoing TCS are often required to fast for nearly
20 h, and occasionally for a full 24 h because both breakfastª 2015 The Authors. Journal of Diabetes Investigation published by AASD and Wiley Publishing Asia Pty Ltd

ORIGINAL ARTICLE
Safety of degludec on undergoing TCS

http://onlinelibrary.wiley.com/journal/jdi

250

FPG level (mg/dL)

200

150

100
r = 0.78, P = 0.002

50
50

100
150
200
Mean glucose level during the daytime fasting period (mg/dL)

250

Figure 2 | Figure showing a significant correlation between the mean glucose level during the daytime fasting period and the fasting plasma
glucose (FPG) level (r = 0.78, P = 0.002, Pearson’s correlation coefficient test [n = 12, r = 0.58]). Daytime fasting period, daytime fasting period(fasting between 08.00 and 18.00 h on the day of total colonoscopy).

0

50

100

150

200

Change in mean glucose level (mg/dL)

–20

–40

–60

250

300

(c)

–80

–100
r = –0.79, P = 0.002
–120

–140
Mean glucose level during the daytime
control period (mg/dL)

Mean glucose level during the daytime
control period (mg/dL)0(b)
Mean glucose level during the daytime
control period (mg/dL)(a) 20

300
250
200
150
100
ns

50
0

0

20
30
10
Total insulin dose (U/kg/day)

40

0.5

2

300
250
200
150
100
ns

50
0

0

1
CPI

1.5

Figure 3 | (a) A significant correlation between the mean glucose level during the daytime control period and the change in the mean glucose
level (daytime fasting period – daytime control period; r = -0.79, P = 0.002, Pearson’s correlation coefficient test [n = 12, r = 0.58]). Daytime control
period, daytime non-fasting control period (non-fasting between 08.00 and 18.00 h on the day before total colonoscopy). (b) The lack of any
significant correlation between the total insulin dose and the mean glucose level during the daytime control period. (c) The lack of any significant
correlation between the C-peptide index (CPI; =fasting C-peptide immunoreactivity/FPG 9 100) and the mean glucose level during the daytime
control period.

ª 2015 The Authors. Journal of Diabetes Investigation published by AASD and Wiley Publishing Asia Pty Ltd

J Diabetes Investig Vol.  No.   2015

5

ORIGINAL ARTICLE
Takeishi et al.

http://onlinelibrary.wiley.com/journal/jdi(a) 20

0
10

20

30

40

50

60

70

80

Change in mean glucose level (mg/dL)

–20

–40

–60

90

(c)

–80

–100
r = –0.69, P = 0.01
–120

–140
SD during the daytime control period (mg/dL)

SD during the daytime control period(mg/dL)0

SD during the daytime control period(mg/dL)

(b)

80
70
60
50
40
30
20

ns

10
0

0

10
20
30
Total insulin dose (U/kg/day)

40

0.5

2

80
70
60
50
40
30
20

ns

10
0

0

1
CPI

1.5

Figure 4 | (a) A significant correlation between the standard deviation (SD) during the daytime control period and the change in the mean
glucose level (r = -0.69, P = 0.01, Pearson’s correlation coefficient test [n = 12, r ≥ 0.58]). (b) The lack of any significant correlation between the
total insulin dose and the SD during the daytime control period. (c) The lack of any significant correlation between the C-peptide index (CPI) andthe SD during the daytime control period.

and lunch are skipped to allow for preparation for TCS. This isa cumbersome issue for diabetic patients who are treated withagents with hypoglycemic action, especially long-acting
insulin D. In the present study, we investigated safety inpatients with type 2 diabetes treated with insulin D and scheduled to undergo TCS by measuring glucose variability with
CGM. Although there was concern that hypoglycemia would
occur during the daytime fasting period (24–34 h after the last
injection of insulin D), none of the patients in the present
study experienced hypoglycemia during this time, even though
they were fasting and skipped only one dose of insulin D on
the day TCS was carried out. Furthermore, we conﬁrmed that
glucose variability was minor, and the mean glucose level during the daytime fasting period was stable and at nearly thesame level as the FPG. Similarly, on evaluation of glucose variability in the basal–bolus and basal groups, we found no difference between the insulin regimens. This suggested that theeffect of insulin D persisted for more than 24 h, and remained
stable and safe until at least 34 h after the last injection. This isbecause insulin D is present as a dihexamer in pharmaceuticalpreparations; after subcutaneous injection, insulin D lodges inthe subcutaneous tissue temporarily as a multihexamer. Subsequently, insulin D converts into the monomer gradually, and isabsorbed into the bloodstream slowly and continuously. We
believe that this mechanism enables a stable blood insulin concentration of insulin D, and achieves stable and safe blood glucose regulation9.
However, the ‘carryover effect’ of insulin D means that theeffect beyond 24 h can vary, depending on the level of glycemic
6

J Diabetes Investig Vol.  No.   2015

control of each patient on the previous day. As a result, inpatients with comparatively low glucose control on the previous
day, the carryover effect of insulin D could cause hypoglycemia
during the daytime fasting period. Conversely, in patients whoare in hyperglycemia, the effect of insulin D might be insufﬁcient.
Therefore, we evaluated the relationship between the mean glucose level during the daytime control period and the change inthe mean glucose level (daytime fasting period – daytime control
period). Our ﬁndings showed that the mean glucose level and SD
during the daytime control period were both signiﬁcantly correlated with the change in the mean glucose level. In patients withhigher glucose levels or wider glycemic variability, the mean glucose level during the daytime fasting period might be subject togreater decreases or wider ﬂuctuation. In view of the correlation
between the mean glucose level during the daytime fasting period
and the FPG level, which was observed in the present study, themean glucose level during the daytime control period might
decrease to the FPG level in most patients, independent of themean glucose level or SD. Although the present study was notdesigned to evaluate the causes of the observed association, it islikely that the pharmacokinetic properties of insulin D contributed to this observed effect, as the mean glucose level or SD
during the daytime control period did not depend on the exogenous insulin dose or CPI, which is indicative of an endogenous
insulin secretory capacity10.
Insulin D has the following pharmacological characteristics5.
First, there is a carryover effect, which continues from 24 to
42 h, overlaps for a couple of days and reaches steady state. Second, in steady state, there is little difference between peak andª 2015 The Authors. Journal of Diabetes Investigation published by AASD and Wiley Publishing Asia Pty Ltdhttp://onlinelibrary.wiley.com/journal/jdi

trough concentrations. Third, once the concentration becomessteady state, the effect would maintain appropriate glycemic control if the daily insulin dose were comparable with daily insulin
consumption; if not, glycemic control would be unstable. For
these reasons, in the present study, stable and appropriate glycemic control seems to have been achieved during the daytime fasting period, because almost all patients were in steady state of
insulin D concentration and had a good FPG level; furthermore,
one dose of insulin was equivalent to the daily intake of insulin
in each patient. Thus, we consider that insulin D can maintainstable and appropriate glycemic control during the daytime fasting period as long as two meals (breakfast and lunch) and one
dose of insulin are simultaneously discontinued.
Recent reports have shown increasingly stronger links
between diabetes and several types of gastroenterological cancers, such as colon cancer1, hepatoma11,12 and pancreatic cancer13,14, so it is desirable for more diabetic patients to undergo
routine screening for these cancers. Gastrointestinal endoscopy,
abdominal ultrasonography, contrast-enhanced computed
tomography and other imaging methods are often used widelyfor screening. Unfortunately, if malignant lesions are found,patients need to undergo surgical procedures or chemotherapy.
Because patients are often required to fast for these examinations or treatments, even if they are treated with long-acting
insulin, such as insulin D, a reduction or discontinuation of adose of insulin might be unavoidable. Therefore, treatment ofmalignant disease in patients with diabetes is cumbersome,because frequent modiﬁcation of doses of insulin aggravates
glycemic control15. In the present study, we showed that
insulin D can maintain appropriate glycemic control during
fasting without additional regulation of insulin as long as
insulin D is only discontinued once in patients with stable glycemic control. This ﬁnding could provide beneﬁcial information
for the treatment of patients with diabetes. However, hypoglycemia can occur occasionally in patients with long-acting
basal insulin during a long fast period, in cases of overdose
compared with insulin practical requirement. We should be
careful about hypoglycemia whenever diabetic patients are
exposed to a long fast period.
However, some limitations to the present study, such as theobservational study design and small sample size, preempt thedrawing of any deﬁnitive conclusions regarding the safety of
insulin D. Based on this pilot study, a prospective clinical study
is planned to elucidate this pharmaceutical effect comparedwith that of insulin glargine.

DISCLOSURE
The authors declare no conﬂict of interest.
REFERENCES
1. Larsson SC, Orsini N, Wolk A. Diabetes mellitus and risk ofcolorectal cancer: a meta-analysis. J Natl Cancer Inst 2005;
97: 1679–1687.

ª 2015 The Authors. Journal of Diabetes Investigation published by AASD and Wiley Publishing Asia Pty Ltd

ORIGINAL ARTICLE
Safety of degludec on undergoing TCS

2. Atkin W, Dadswell E, Wooldrage K, et al. Computed
tomographic colonography versus colonoscopy forinvestigation of patients with symptoms suggestive ofcolorectal cancer (SIGGAR): a multicentre randomised trial.
Lancet 2013; 381: 1194–1202.
3. Heise T, Hermanski L, Nosek L, et al. Insulin degludec: fourtimes lower pharmacodynamic variability than insulin
glargine under steady-state conditions in type 1 diabetes.
Diabetes Obes Metab 2005; 14: 859–864.
4. Soichi T, Nobutoshi F, Takashi S, et al. Comparison of insulin
degludec vs. insulin glargine using continuous glucose
monitoring (CGM): Crossover study (in Japanese withEnglish abstact). J Jpn Diab Soc 2014; 57: 321–328.
5. Heise T, Nosek L, Coester HV, et al. Steady state is reachedwithin two to three days of once-daily administration ofultra- long-acting insulin degludec. Diabetes 2012; 61(Suppl
1): A259.
6. Nishimura R, Tsujino D, Taki K, et al. Continuous glucose
monitoring with Humalog Mix 25 versus Humalog Mix 50,
twice daily: a comparative pilot study -Results from the
Jikei-EValuation of insulin Lispro mixture on
pharmacodynamics and glycemic VariancE (J-EVOLVE) study.
Cardiovasc Diabetol 2010; 9: 16: 1–5.
7. Rodbard D. New and improved methods to characterize
glycemic variability using continuous glucose monitoring.
Diabetes Technol Ther 2009; 11: 551–565.
8. Juvenile Diabetes Research Foundation Continuous Glucose
Monitoring Study Group. Effectiveness of continuous
glucose monitoring in a clinical care environment: evidence
from the Juvenile Diabetes Research Foundation continuous
glucose monitoring (JDRF-CGM) trial. Diabetes Care 2010; 33:
17–22.
9. Jonassen I, Havelund S, Hoeg-Jensen T, et al. Design of thenovel protraction mechanism of insulin degludec, an ultralong-acting basal insulin. Pharm Res 2012; 29: 2104–2114.
10. Peacock I, Tattersall RB. The difficult choice of treatment forpoorly controlled maturity onset diabetes tablets or insulin?
Br Med J (Clin Res Ed) 1984; 288(6435): 1956–1959.
11. El-Serag HB, Tran T, Everhart JE. Diabetes increases the riskof chronic liver disease and hepatocellular carcinoma.
Gastroenterology 2004; 126: 460–468.
12. Matsuo M. Association between diabetes mellitus andhepatocellular carcinoma: results of a hospital-andcommunity-based case-control study. Kurume Med J 2003;
50: 91–98.
13. Latchford A, Greemhalf W, Vitone LJ, et al. Peutz-Jeghers
syndrome and screening for pancreatic cancer. Br J Surg
2006; 93: 1446–1455.
14. Inoue M, Iwasaki M, Otani T, et al. Diabetes mellitus andthe risk of cancer. Arch Intern Med 2006; 166: 1871–1877.
15. Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic
crises in adult patients with diabetes. Diabetes Care 2009;
32: 1335–1343.

J Diabetes Investig Vol.  No.   20157