Diabetes Research and Clinical Practice - Volume 120 - Supplement 1

Aims:

The coexistence of excessive accumulation of body fat

and loss of skeletal muscle increase the risk of physical

disability, morbidity, and mortality. The early detection

and prevention of sarcopenia are important in the manage-

ment of overweight/obese patients with type 2 diabetes,

because the combination may be particularly harmful to

diabetic patients. Thus, we analyzed the clinical character-

istics and risk factors of sarcopenia in overweight diabetic

patients.

Materials and methods:

The subjects of this study were 570

patients (325 men and 245 women) with type 2 diabetes aged

40 years or older, consisting of 299 lean (BMI < 25 kg/m

), 178

overweight (25

–

30 kg/m

, obese class I by Japanese criteria),

and 93 obese (

≥

30 kg/m

) individuals. Patients with malignant

disease, massive proteinuria, severe liver disease and chronic

pancreatitis were excluded. Body composition was measured

with a multi-frequency bioelectrical impedance analyzer.

Sarcopenia was defined as a skeletal muscle index (total

appendicular muscle mass/height2) <7.0 kg/m

in men and

<5.7 kg/m

in women.

Results:

The prevalence of sarcopenia was 31.6%. Although

sarcopenic subjects had a lower BMI than non-sarcopenic

subjects (21.4 ± 2.8 vs. 27.4 ± 4.9 kg/m

, p < 0.0001), 18 sarcope-

nic subjects were overweight. Sarcopenic overweight patients

were older than non-sarcopenic overweight patients

(69.5 ± 11.2 vs. 62.7 ± 10.9 years, p = 0.002). There was no

significant difference in HbA1c, FPG, IRI, CPR, HOMA-IR, FT3,

FT4, or TSH levels. Sarcopenic overweight subjects had more

fat mass in spite of a slightly lower BMI. Tuning fork vibration

time at the medial malleolus was significantly shorter in

sarcopenic subjects (9.7 ± 4.5 vs. 13.0 ± 4.2 sec, p = 0.003). The

difference remained significant after the adjustment of age.

Furthermore, the vibration time was correlated with the

skeletal muscle index (p < 0.0001). A multiple regression

analysis showed that, in addition to age and gender, vibration

time was an independent contributor to the skeletal muscle

index. A fecal fat test was positive in 69% of sarcopenic

overweight subjects and in 38% of non-sarcopenic overweight

subjects (p = 0.029). There was no significant difference in the

rate of having exercise habits.

Conclusion:

Here we showed that sarcopenia is a common

complication of type 2 diabetes even in overweight patients.

Diabetic neuropathy may accelerate sarcopenia directly or

indirectly through the reduction of exercise. Furthermore,

subclinical malabsorption may be involved in the develop-

ment of sarcopenia in diabetic patients. The appropriate

management of peripheral neuropathy and the improvement

of digestive function may be beneficial in prevention and

treatment of sarcopenia in diabetic patients.

PI-31

Role of novel variants of PGC-1

in the pathogenesis of

obesity

Kazuhiro NOMURA

*, Tetsuya HOSOOKA

, Tsutomu SASAKI

Tadahiro KITAMURA

, Hiroshi SAKAUE

, Masato KASUGA

Wataru OGAWA

Division of Diabetes and Endocrinology, Kobe

University Graduate School of Medicine,

Metabolic Signal Research

Center, Gunma University,

Department of Nutrition and

Metabolism, University of Tokushima Graduate School,

Research Institute, National Center for Global Health and

Medicine, Japan

Peroxisome proliferator-activated receptor

coactivator-1

(PGC-1

) is a transcriptional coactivator that regulates vari-

ous metabolic processes, including mitochondrial biogenesis

and thermogenesis. Given that mitochondrial dysfunction and

impaired thermogenesis are often observed in individuals

with insulin resistance and obesity and that the abundance of

PGC-1

is reduced in skeletal muscle of such affected animals

and humans, PGC-1

has been implicated in the pathogenesis

of these health problems. We have recently identified variants

of PGC-1

(PGC-1

b/c) generated by transcription from an

alternative promoter. These variants are robustly induced in

skeletal muscle by acute exercise. Mice specifically lacking the

novel variants (PGC-1

b/cKO) developed age-dependent

obesity and insulin resistance. Abundance of total PGC-1

skeletal muscle was not altered in PGC-1

b/cKO mice, likely

because the canonical isoform is predominant under static

conditions. However, increases in total PGC-1

abundance and

energy expenditure in response to exercise were attenuated in

PGC1-

b/cKO mice, likely contributing to their obesity-prone

phenotype. Among various exercise-mimetic stimuli, a

agonist clenbuterol most specifically and potently up-regu-

lated PGC-1

b/c in skeletal muscle, and the exercise-induced

up-regulation of PGC-1

b/c in skeletal muscle was inhibited by

-adrenergic antagonist propranolol. Furthermore, clenbu-

terol-induced oxygen consumption was attenuated in PGC1-

b/cKO mice. These data indicate that the

2 adrenergic

signaling is largely responsible for exercise-induced induction

of PGC1-

b/c. The expression of PGC-1

b/c induced by

clenbuterol was impaired in skeletal muscle of obese model

mice including db/dbmice and high fat-fedmice. Furthermore,

the increase in energy expenditure in response to

2 adrener-

gic stimuli was impaired in such obese model mice. In skeletal

muscle of obese animals, the expression of

2 adrenergic

receptor (Adrb2) mRNA was decreased and the percentage of

methylated CpG sites in the Adrb2 promoter was increased as

compared to non-obese mice, suggesting that the epigenetic

regulation of Adrb2 likely contributes to the development of

adrenaline resistance via the downregulation of Adrb2 in

skeletal muscle. Our results thus indicate that exercise-

induced expression of PGC1-

b/c plays an important role in

the control of energy expenditure during exercise and that

impaired induction of PGC1-

b/c in skeletal muscle of obese

animals, which is at least partly induced by the downregula-

tion Adrb2, leads to the impaired energy expenditure during

exercise.

PI-32

Pioglitazone ameliorates hepatic steatosis via enhancing

cytosolic- and autophagy-related lipolysis dominantly

mediated by PPAR

Pi-Jung HSIAO

*, Kung-Kai KUO

, Wei-Wen HUNG

He-Jiun JIANG

, Pi-Chen LIN

, Tusty-Jiuan HSIEH

Shyi-Jang SHIN

Division of Endocrinology and Metabolism,

Department of Internal Medicine, Kaohsiung Medical University,

Kaohsiung Medical University Hospital,

Hepatobiliary Division,

Department of Surgery, Kaohsiung Medical University, Kaohsiung

Medical University Hospital,

Graduate Institute of Medical Genetics,

School of Medicine, College of Medicine, Kaohsiung Medical

University, Taiwan

Aims:

Impaired cytosolic- and autophagy-lipolysis evidently

contribute to the development of obesity and insulin resist-

ance. Pioglitazone has been shown to lessen hepatic steatosis

in human studies. However, the molecular mechanism is still

unclear. Enhancing hepatic lipolysis is supposed to elucidate

the intracellular lipid regulation by pioglitazone. The study

investigated the modulation of cytosolic- and autophagy-

related lipolysis by pioglitazone in a mouse model of high fat

diet and cell model treated by palmitic acid.

Methods:

Male C57BL/6micewere divided into (1) chowdiet, (2)

high fat diet and (3) high fat diet co-administered with

pioglitazone 100 mg/kg/day for 8 weeks. Hepatic steatosis

was measured by hepatic triglyceride content and Oil-red O

staining. Expression of the genes and proteins [(Atg 7, LC3,

lysosomal acid lipase (LAL), adipose triglyceride lipase (ATGL)

and hormone-sensitive lipase (HSL)] related to autophagy- and

cytosolic-lipolysis were compared among groups. The AML12

liver cell model was used to test the regulation by small

interfering RNA (siRNA) of PPAR

and PPAR

Results:

Our results showed that a high fat diet induced

prominent hepatic steatosis and diminished expression of

autophagy-related proteins 7 (Atg7) and LC3. These

Poster Presentations / Diabetes Research and Clinical Practice 120S1 (2016) S65

–

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S191