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Medicine, Yuan-Sheng Hospital and Changhua Christian Hospital,
Yuanlin Branch, Yuanlin,
3
Department of Internal Medicine, Chung
Shan Medical University Hospital,
4
School of Medicine, Chung Shan
Medical University,
5
Department of Medical Research, Chung Shan
Medical University Hospital,
6
Department of Obstetrics and
Gynecology, Chung Shan Medical University Hospital, Taichung,
Taiwan
Objectives:
The aim of the study was to evaluate impact of
diabetes and Intercellular adhesion molecule-1 (ICAM-1)
genetic polymorphism on coronary artery disease (CAD) in
patients received coronary angiography to assess the genetic
risks and conventional risks.
Background:
The prevention of CAD might be facilitated by
identifying genes that confer susceptibility, as defined by
conventional risk factors. The pathogenesis of CAD is athero-
sclerosis which is a chronic inflammatory disease on the
vessel walls. Genetic variants in ICAM-1 gene have been shown
to have association with a range of inflammatory diseases.
Therefore, we conducted a study to investigate the association
of the single nucleotide polymorphisms (SNPs) of ICAM-1with
CAD.
Methods:
The study population comprised 525 unrelated
Taiwanese individuals who received elective coronary angi-
ography in Chung Shan Medical University. Among all study
subjects, 207 had diabetes mellitus, 364 individuals had
hypertension, 183 had hypercholesterolemia, and 219 were
active smokers. The single nucleotide polymorphismsof
ICAM-1 were determined by real time-PCR and genotyping.
Results:
Diabetes and other conventional risks were signifi-
cantly associated with CAD. Our study showed that
rs281432 (C8823G) was the only ICAM-1 SNP which affect the
development of CAD. Multivariate analysis revealed that
ICAM-1 SNP rs281432 CC/CG [p = 0.016; odds ratio (OR): 2.56,
95% confidence interval (CI): 1.19
–
5.56], male gender (p = 0.018;
OR: 1.66, 95% CI: 1.09
–
2.51), aspirin use in the past 7 days
(p = 0.001; OR: 2.05, 95% CI: 1.33
–
3.14), hypertension (p < 0.001;
OR: 2.15, 95% CI: 1.42
–
3.25), serum cardiac troponin I elevation
(p < 0.001; OR: 2.14, 95% CI: 1.47
–
3.24) and severe angina in
recent 24 hours (p = 0.001; OR: 1.97, 95% CI: 1.31
–
2.95) increase
the risk of CAD.
Conclusions:
In conclusion, diabetes remains one of the
strongest risks of CAD. And ICAM-1 SNP rs281432 is an
independent factor to predict the development of CAD.
ICAM-1 SNP rs281432 homozygotic mutant GG can reduce
the susceptibility to the CAD in Taiwanese subjects.
Genotyping of polymorphisms may prove informative for
assessment of the risks of CAD.
PB-15
Gain of muscle strength inmitochondrial diabetes treatedwith
SGLT2 inhibitors
Yoshihiko SUZUKI
1
*, Junichiro IRIE
2
, Motoaki SANO
3
,
Toshihide KAWAI
4
, Shu MEGURO
2
, Nobuhiro IKEMURA
3
.
1
HDC
Atlas Cliniv,
2
Department of Internal Medicine, Keio University
School of Medicine,
3
Department of Cardiology, Keio University
School of Medicine,
4
Department of Internal Medicine, Saiseikai
Central Hospital, Tokyo, Japan
In 1996, we reported the first identified case of mitochondrial
diabetes caused by a T-to-C transition at position 3271. The
proband was a 58-year-old male. Heteroplasmy of the 3271
mutation, strongly maternal inheritance of diabetes and other
evidences associated with mitochondrial dysfunction sug-
gested this 3271 mutation to be pathogenic.
During a 20 year follow-up, in 2014, he received SGLT2 inhibitor
(Sodium glucose transporter 2 inhibitor: SGLT2i), first ipragli-
flozin 50 mg/day for 6 weeks, subsequently luseogliflozin
2.5 mg/day for 4 weeks, dapagliflozin 10 mg/day for 4 weeks,
tofogliflozin 20 mg/day for 2 weeks, and again dapagliflozin
10 mg/day for 4 weeks. The four different products of SGLT2i
seemingly had similar effect on weight loss and the decrease
of HbA1c. Then, he lost weight and attained improvement of
glycemic control with HbA1c from 6.5% to 6.3%. Concurrently,
the dose of glimepiride was adjusted to decrease from 6 mg to
1mg daily. Body weight decreased from 64.7 to 58.7 kg within
three months (height 174 cm. BMI: from 21.4 to 19.4). These
phenomena suggested that he relieved insulin resistance.
The patients with sarcopenia have been believed to suffer from
loss of muscle power and frailty. Therefore, it is noteworthy
that, in this patient, his grip strength (GS) and back strength
(BS) got stronger despite robust weight loss. Before SGLT2i
treatment, GS was 37.6 kg in right hand and 30.5 kg in left
hand, respectively. BS was 82 kg. After three months of SGLT2i,
GS of right hand grew stronger to 39.4 kg (+1.8 kg) and left hand
to 32.2 kg (+1.7 kg). BS also grew stronger to 105 kg (+23 kg).
Thus the case provides a novel information in diabetes
treatment and the role of mitochondria. Caloric restriction
that reduces oxidative damage improves mitochondrial func-
tion. In our previous study, defective insulin secretion as well
as insulin resistance is a salient feature of mitochondria
diabetes. Reduced glucose flux in muscles with SGLT2i
treatment possibly mitigates insulin resistance via decreased
oxidative stress. Insulin resistance is one of risk factors of
sarcopenia. Hence, the recovery of muscle strength after
SGLT2i treatment in our patient is attributed to regained
energy from restored mitochondria.
Conclusion:
SGLT2i upon the patient of mitochondrial diabetes
could induce remarkable weight loss within short time and
decrease of insulin resistance, which seemingly compensated
genetic deficit of mitochondrial DNA. This supports our
previous published study.
PB-16
Mitochondrial diabetes and subjective hypoglycemia
unawareness
Yoshihiko SUZUKI
1
*, Junichiro IRIE
2
, Motoaki SANO
3
,
Toshihide KAWAI
4
, Shu MEGURO
2
, Nobuhiro IKEMURA
3
.
1
HDC
Atlas Clinic,
2
Department of Internal Medicine, Keio University School
of Medicine,
3
Department of Cardiology, Keio University School of
Medicine, Tokyo,
4
Department of Internal Medicine, Saiseikai Central
Hospital, Tokyo, Japan
Mitochondrial diabetes (MtDM) usually lacks endocrinal
insulin secretion from pancreas. Therefore, most patients are
on insulin injection therapy. Hence, among MtDM, rare
patients are free of insulin injection. We experienced two
MtDM patients without insulin therapy, both of whom had
never noticed subjective hypoglycemia.
Case 1: 26 y/o. women (at 2006). She was diagnosed as having
diabetes at age 12 y/o. During 14 years observation, she never
noticed hypoglycemia under sulfonylurea treatment. As
examination, we injected rapid insulin to induce absolute
hypoglycemia. In result, she never noticed symptoms even
when the plasma glucose level became lower than 30 mg/dL.
She was afterward diagnosed to have mitochondrial DNA
(mitDNA) mutation at position 3243. Her detailed profile are
described already (Diabetologia 47:592
–
3, 2004).
Case 2: 59 y/o. men (at 2018). He was diagnosed as having
MtDM diabetes at age 33 y/o. During 26 years observation, he
never noticed hypoglycemia. Though he was under glimepir-
ide 6 mg daily treatment, he had never experience of
hypoglycemia. His detailed profile are already described
(Diabetes Care 19: 1304
–
1305, 1996).
Discussion:
Some cases of Kearns-Sayre syndrome (KSS),
resulting from a mitochondrial DNA deletion, associated
with diabetes that presented with hyperosmolar hyperglyce-
mia with minimal ketosis were reported. Some cases of MtDM
and MELAS were reported with ketoacidosis in literature.
Ketone bodies are produced in liver, mainly from the oxidation
of fatty acids, and exported to peripheral tissues for use as an
energy source. They are particularly important for the brain,
which has no other substantial non-glucose-derived energy
Poster Presentations / Diabetes Research and Clinical Practice 120S1 (2016) S65
–
S211
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