Diabetes Research and Clinical Practice - Volume 106 - Supplement 1 - November 2014 - page 10

Oral presentation abstracts / Diabetes Research and Clinical Practice 106S1 (2014) S1–S41
S3
as fasting plasma glucose (FPG), lipid profile. Summary of
Diabetes Self-Care Activities (SDSCA) was checked before and
after study.
Result:
Total 29 subjects with mean age of 53.7±1.6 years
completed the study. Initial HbA1c, FPG and body mass index
(BMI) were 7.7±0.1%, 140.9±7.3mg/dL, and 25.0±2.8 kg/m
2
.
After 12 weeks, HbA1c (7.1±0.1%, p = 0.0002) and FPG
(120.1±5.7mg/dL, p = 0.0051) were significantly reduced. There
was positive correlation between initial HbA1c and the
amount of change in HbA1c (r = −0.61, p = 0.0004). Interestingly,
the subjects who input glucose more showed the more
reduced HbA1c (r = 0.53, p = 0.0029). So we performed subgroup
analysis with the groups of glucose input 80% (good users,
n = 20) and
<
80% (no-good users, n = 9). In good users, HbA1c
changed from 7.8±0.2% to 7.0±0.1% (p = 0.0002). However,
in no-good users, HbA1c was not significantly changed
(7.4±0.3% to 7.3±0.3%, p = 0.57). As for SDSCA, scores of ‘blood
glucose testing’ (p
<
0.0001), ‘general diet’ (p = 0.0001), and
‘exercise’ (p = 0.0019) were dramatically improved, and this
improvement was more remarkable in good users.
Conclusion:
Using PDSS for 12 weeks in patients with type 2
diabetes presented remarkable reduction in HbA1c, and the
amount of reduction showed good correlation with number
of entered glucose level. This system was recognized to be
helpful for the patients to control diet, check daily glucose
level, and exercise more. Based on this pilot study with
favorable results, multicenter, randomized-controlled study
is under preparation.
OP5
THE IMPACT OF NOCTURNAL HYPOGLYCAEMIA ON SLEEP
IN SUBJECTS WITH TYPE 2 DIABETES
S. Madsbad
1
, N. Rye Jørgensen
2
, R. Rabøl
3
, P.-L. Chu
4
,
K. Stender-Petersen
3
, P.J. Jennum
5
.
1
Department of
Endocrinology, Hvidovre Hospital, Hvidovre,
2
Department of
Diagnostics, Copenhagen University Hospital Glostrup, Glostrup,
3
Novo Nordisk A/S, Søborg, Denmark ;
4
Novo Nordisk Inc.,
Plainsboro, United States;
5
Danish Center for Sleep Medicine,
Copenhagen University Hospital Glostrup, Glostrup, Denmark
Background:
Nocturnal hypoglycaemia is a major barrier
in achieving optimal glycaemic control in patients with
diabetes. Knowledge about the consequences of nocturnal
hypoglycaemia on sleep is limited. The aim of the present trial
was to investigate the impact of nocturnal hypoglycaemia on
sleep pattern.
Method:
In this randomised, single-blinded, two-period,
cross-over trial, 26 subjects with type 2 diabetes attended
two experimental night visits (one normoglycaemic and one
hypoglycaemic) in randomised order to assess the impact of
nocturnal hypoglycaemia on sleep (using polysomnography)
and on hormonal responses. Plasma glucose levels were
controlled on the experimental nights by hyperinsulinaemic
glucose clamping. On the hypoglycaemic night, hypogly-
caemia was induced when subjects had reached sleep
stage N2 or deeper by turning off the glucose infusion
(plasma glucose target: 2.7–2.8mmol/L) for approximately
15 minutes, after which subjects were brought back to
normoglycaemia. On the normoglycaemic night, plasma
glucose was maintained at 5–7mmol/L throughout the night.
Result:
There was no difference between the hypoglycaemic
night and the normoglycaemic night, in either the number
of electroencephalogram-identified arousals or awakenings
in the first 4 hours of sleep (0–4 hours after reaching sleep
stage N2). During the last 4 hours (4–8 hours) and during
the entire night (0–8 hours), the number of awakenings was
significantly lower (p
<
0.05) on the hypoglycaemic night than
on the normoglycaemic night (observed geometric means 4–8
hours: 10 versus 14 awakenings and 0–8 hours: 25 versus
30 awakenings). Total sleep time tended to be longer on
the hypoglycaemic night (observed means: 366 versus 349
minutes, p = NS). Statistically significantly higher hormonal
counter-regulatory responses (adrenaline, growth hormone
and cortisol) to hypoglycaemia were observed as compared
with normoglycaemic night.
Conclusion:
Nocturnal hypoglycaemia in patients with type 2
diabetes caused a decrease in awakening response following
the event. These findings underscore the risks associated with
nocturnal hypoglycaemia since these events potentially affect
the subject’s ability to wake up and respond adequately to
hypoglycaemia.
ClinicalTrials.gov: A Trial to Investigate the Impact of
Nocturnal Hypoglycaemia on Sleep in Subjects With Type 2
Diabetes; clinical trial number NCT01780272, supported by
Novo Nordisk.
Disclosure of Interest:
S. Madsbad Receiving support from:
Novo Nordisk, Consultant with: Novartis Pharma, Novo
Nordisk, Merck Sharp & Dome, Sanofi-Aventis, AstraZeneca,
Johnson & Johnson, Astra-Zeneca, Boehringer-Ingelheim,
Lilly, Intarcia Therapeutics, Bristol-Meyer Squibb, Member of:
speaker bureau for Novo Nordisk, Merck, Sharp & Dome,
Astra-Zeneca, Sanofi-Aventis, Novartis Pharma, E Lilly, Bristol-
Meyer Squibb, N. R. Jørgensen: None Declared, R. Rabøl
Employee with: Novo Nordisk, P.-L. Chu Employee with: Novo
Nordisk, K. Stender-Petersen Employee with: Novo Nordisk, P.
Jørgen Jennum: None Declared
Therapeutics
oral and novel agents
OP6
CNX-013-B2, A SELECTIVE REXINOID, PROVIDES ROBUST
CONTROL OF HYPERGLYCEMIA, IMPROVES INSULIN
SENSITIVITY AND HAS A POTENTIAL TO CONTROL
CARDIAC HYPERTROPHY
B.P. Somesh
1
, Y. Moolemath
1
, M. Omkaramurthy
1
,
C. Harish
1
, O. Patil
1
, M.N. Lakshmi
1
, K. Harsha
1
, T.M. Anil
1
,
A.M. Oommen
1
, M.K. Govind
1
, M.V. Venkataranganna
1
,
M.R. Jagannath
1
.
1
Connexios Life Sciences PVT LTD, Bangalore,
India
Background:
Retinoid X Receptors regulate multiple phys-
iological and metabolic pathways in various organs that
have shown reduced glucose and lipid (cholesterol) levels,
improved insulin sensitivity and anti-obesity effects. Retinoid
X receptors are also known to play a major role in
many cellular processes including cell differentiation, cell
proliferation apart from metabolic syndrome. It functions
as a permissive heterodimer partner for RXR: PPARs, RXR:
LXRs, RXR: BAR/FXR, and RXR: NGFI-B (nerve growth factor
induced gene B) (1) and non-permissive heterodimer partners
for RXR:RAR, RXR:TR. Selective rexinoids are considered as
potential therapeutics for treating metabolic syndrome. We
report the anti-hyperglycemic effects of CNX-013-B2, an orally
bioavailable small molecule agonist of RXR from both
in vitro
cell system and in disease animal model.
Method:
Female ZDF rats were fed with chow diet (10% fat
diet) or high fat diet (HFD) (48% fat diet) for 8 weeks. HFD
fed animals were assigned to either vehicle or CNX-013-B2
(10mg/kg, p.o., o.d.) treatment groups (n = 8) for 14 weeks.
H9C2 cells were differentiated and used to profile effect of
CNX-013-B2 on cardiac hypertrophy.
Result:
CNX-013-B2 was identified in a screening system
where compounds capable of specifically activating only a
chosen sub-set of heterodimer partners of RXR. CNX-013-
B2 is a highly potent and selective small molecule rexinoid
with an EC50 of 48 nM towards human RXRa. This selective
rexinoid activates all the 3 PPAR isoforms and does not
activate human isoforms of LXRa, AhR and RAR. Treatment
of fZDF with CNX-013-B2 resulted in a reduction of ~30% in
fasting plasma glucose, 25–30% in fed plasma glucose, ~14% in
1,2,3,4,5,6,7,8,9 11,12,13,14,15,16,17,18,19,20,...288