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ABSTRACT: BACKGROUND: Atherosclerosis is an age-related disease. Adiponectin and C1q form a protein complex in human blood, and that serum C1q and C1q-binding adiponectin (C1q-APN) concentrations can be measured. We investigated circulating C1q and C1q-APN levels in Japanese men including elderly men. FINDINGS: The study subjects were 509 Japanese men including elderly men. Serum levels of total adiponectin (Total-APN), high-molecular weight-adiponectin (HMW-APN), C1q-APN and C1q were measured by enzyme-linked immunosorbent assay. Total-APN, HMW-APN and C1q-APN, but not C1q, correlated significantly and positively with aging (r=0.26, r=0.24, r=0.17, p<0.01, respectively). The HMW-APN/Total-APN ratio correlated significantly and positively with aging (r=0.14, p<0.01). The C1q-APN/Total-APN ratio and C1q-APN/HMW-APN ratio correlated significantly and negatively with aging (r=-0.17, p<0.01, r=-0.12, p=0.01). C1q-APN/C1q correlated significantly and positively with aging (r=0.09, p=0.03). Multiple regression analysis identified age and body mass index as significant determinants of C1q-APN. CONCLUSIONS: The present study demonstrates that serum HMW-APN, C1q-APN, and Total-APN, but not C1q, correlated positively with aging. These preliminary results could form the basis for future research.Trial registration: Clinical Trial Registration Number: UMIN000004318.
Diabetology and Metabolic Syndrome 03/2013; 5(1):17. · 1.53 Impact Factor
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Masaya Yamaoka,
Norikazu Maeda,
Seiji Nakamura,
Takuya Mori,
Kana Inoue,
Keisuke Matsuda,
Ryohei Sekimoto,
Susumu Kashine,
Yasuhiko Nakagawa,
Yu Tsushima,
Yuya Fujishima,
Noriyuki Komura,
Ayumu Hirata,
Hitoshi Nishizawa,
Yuji Matsuzawa,
Ken-Ichi Matsubara, Tohru Funahashi,
Iichiro Shimomura
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ABSTRACT: OBJECTIVE: Visceral fat obesity is located upstream of metabolic syndrome and atherosclerotic diseases. Accumulating evidences indicate that several immunocytes including macrophages infiltrate into adipose tissue and induce chronic low-grade inflammation. We recently analyzed the association between visceral fat adiposity and the gene expression profile in peripheral blood cells in human subjects and demonstrated the close relationship of visceral fat adiposity and disturbance of circadian rhythm in peripheral blood cells. In a series of studies, we herein investigated the association of visceral fat adiposity and mRNA levels relating to inflammatory genes in peripheral blood cells. APPROACH AND RESULTS: Microarray analysis was performed in peripheral blood cells from 28 obese subjects. Reverse transcription-polymerase chain reaction (RT-PCR) was conducted by using blood cells from 57 obese subjects. Obesity was defined as body mass index (BMI) greater than 25 kg/m(2) according to the Japanese criteria. Gene expression profile analysis was carried out with Agilent whole human genome 4×44 K oligo-DNA microarray. Gene ontology (GO) analysis showed that 14 genes were significantly associated with visceral fat adiposity among 239 genes relating to inflammation. Among 14 genes, RT-PCR demonstrated that S100A8, S100A9, and S100A12 positively correlated with visceral fat adiposity in 57 subjects. Stepwise multiple regression analysis showed that S100A8 and S100A12 mRNA levels were closely associated with HOMA-IR and S100A9 mRNA was significantly related to adiponectin and CRP. CONCLUSIONS: Peripheral blood mRNA levels of S100 family were closely associated with insulin resistance and inflammation.
Biochemical and Biophysical Research Communications 03/2013; · 2.48 Impact Factor
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ABSTRACT: BACKGROUND: Visceral fat accumulation is caused by over-nutrition and physical inactivity. Excess accumulation of visceral fat associates with atherosclerosis. Polyunsaturated fatty acids have an important role in human nutrition, but imbalance of dietary long-chain polyunsaturated fatty acids, especially low eicosapentaenoic acid (EPA) / arachidonic acid (AA) ratio, is associated with increased risk of cardiovascular disease. The present study investigated the correlation between EPA, docosahexaenoic acid (DHA), AA parameters and clinical features in male subjects. FINDINGS: The study subjects were 134 Japanese with diabetes, hypertension and/or dyslipidemia who underwent measurement of visceral fat area (eVFA) by the bioelectrical impedance method and serum levels of EPA, DHA and AA. EPA/AA ratio correlated positively with age, and negatively with waist circumference and eVFA. Stepwise regression analysis demonstrated that age and eVFA correlated significantly and independently with serum EPA/AA ratio. Serum EPA/AA ratio, but not serum DHA/AA and (EPA+DHA)/AA ratios, was significantly lower in subjects with eVFA >=100 cm2, compared to those with eVFA <100 cm2 (p=0.049). Subjects with eVFA >=100 cm2 were significantly more likely to have the metabolic syndrome and history of cardiovascular diseases, compared to those with eVFA <100 cm2 (p<0.001, p=0.028, respectively). CONCLUSIONS: Imbalance of dietary long-chain polyunsaturated fatty acids (low serum EPA/AA ratio) correlated with visceral fat accumulation in male subjects.Clinical trial registration number: UMIN 000002271 - https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000002777&language=E.
Nutrition & Metabolism 03/2013; 10(1):25. · 2.88 Impact Factor
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ABSTRACT: BACKGROUND: Patients on maintenance hemodialysis (HD) have much higher levels of adiponectin (Total-APN). Adiponectin and C1q form a protein complex in human blood, and serum C1q-binding adiponectin (C1q-APN) can be measured. We recently reported that C1q-APN/Total-APN ratio rather than Total-APN correlated with atherosclerosis in diabetics. However, the characteristics of C1q-APN in HD patients remain unclear. The preset study investigated the characteristics of the adiponectin parameters including C1q-APN and also to clarify the relationship between various serum adiponectin parameters and atherosclerotic cardiovascular diseases (ACVD) in HD patients. METHODS: The single cross-sectional study subjects were 117 Japanese patients (males/females = 61/56) on regular HD. Blood Total-APN, high molecular weight-adiponectin (HMW-APN), C1q-APN and C1q concentrations were measured by enzyme-linked immunosorbent assays. ACVD were defined as stroke, coronary and peripheral artery diseases, thoracic and abdominal aneurysms. RESULTS: Stepwise regression analysis identified high-density lipoprotein-cholesterol (HDL-C) as the only significant and independent determinant of C1q-APN in males, and duration of HD as the only significant and independent determinant of C1q-APN in females. Stepwise regression analysis identified uric acid, low-density lipoprotein-cholesterol and triglyceride as significant and independent determinants of C1q-APN/Total-APN ratio in males, and leukocyte count and HDL-C as significant and independent determinants of C1q-APN/Total-APN ratio in females. Multiple logistic regression analysis identified inorganic phosphorus and C1q-APN or C1q-APN/C1q ratio as significant determinants of ACVD. CONCLUSIONS: Low serum C1q-APN and C1q-APN/C1q ratio, but not C1q-APN/Total-APN ratio, correlated with ACVD in HD patients.Trial registration: ClinicalTrials.gov: UMIN 000004318https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000005173&language=E.
BMC Nephrology 02/2013; 14(1):50. · 2.18 Impact Factor
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ABSTRACT: Visceral fat accumulation is located upstream of metabolic syndrome. Recent progress in adipocyte biology has clarified the molecular mechanism for pathophysiology of metabolic syndrome and its related disorders. In this review we summarize adiponectin and AQP7 in the role of metabolic syndrome and cardiovascular diseases.
Endocrine Journal 01/2013; · 2.03 Impact Factor
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Yukari Fujita,
Tetsuhiro Kitamura,
Michio Otsuki,
Daisuke Tamada,
Yukiko Tabuchi,
Junji Kozawa,
Tetsuyuki Yasuda,
Kohei Okita,
Akihisa Imagawa,
Hideaki Kaneto, Tohru Funahashi,
Iichiro Shimomura
Diabetes care 01/2013; 36(1):e8. · 8.09 Impact Factor
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Kikuko Hotta,
Aya Kitamoto,
Takuya Kitamoto,
Seiho Mizusawa,
Hajime Teranishi,
Rina So,
Tomoaki Matsuo,
Yoshio Nakata,
Hideyuki Hyogo,
Hidenori Ochi, [......],
Kazuaki Chayama,
Kazuyuki Hamaguchi,
Kentaro Yamada,
Toshiaki Hanafusa,
Shinichi Oikawa,
Toshiie Sakata,
Kiyoji Tanaka,
Yuji Matsuzawa,
Kazuwa Nakao,
Akihiro Sekine
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ABSTRACT: Aim: Visceral fat accumulation plays an integral role in morbidity and mortality rates by increasing the risk of developing metabolic disorders such as type 2 diabetes, dyslipidemia, and hypertension. New genetic loci associated with fat distribution, measured by waist-hip ratios and computed tomography (CT), have recently been identified by genome-wide association studies in European-descent populations. This study used CT to investigate whether single nucleotide polymorphisms (SNPs) that confer susceptibility to fat distribution are associated with visceral fat area (VFA) and subcutaneous fat area (SFA) in the Japanese population.Methods: We measured the VFAs and SFAs of 1424 obese Japanese subjects (BMI≥25 kg/m(2), 635 men and 789 women) that were genotyped at 15 SNPs, namely, TBX15 rs984222, DNM3 rs1011731, LYPLAL1 rs4846567, GRB14 rs10195252, NISCH rs6784615, ADAMTS9 rs6795735, CPEB4 rs6861681, LY86 rs1294421, VEGFA rs6905288, RSPO3 rs9491696, NFE2L3 rs1055144, ITPR2 rs718314, HOXC13 rs1443512, ZNRF3 rs4823006 and THNSL2 rs1659258.Results: The G-allele of LYPLAL1 rs4846567 was borderline associated with an increased ratio of VFA to SFA (V/S ratio; p= 0.0020). LYPLAL1 rs4846567 had a stronger effect on the V/S ratio in women (p= 0.0078) than in men (p= 0.12); however, neither result was significant after Bonferroni correction for multiple comparisons. NISCH rs6784615 was nominally associated with increased VFA (p=0.040) and V/S ratio (p= 0.020). The other SNPs analyzed were not significantly associated with body mass index (BMI), VFA, or SFA.Conclusion: Our results suggest that LYPLAL1 rs4846567 and NISCH rs6784615 may influence fat distribution in the Japanese population.
Journal of atherosclerosis and thrombosis 12/2012; · 2.69 Impact Factor
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ABSTRACT: OBJECTIVE: Adiponectin, an adipocyte-derived protein, has potential antiatherogenic properties. Low levels of serum total-adiponectin (Total-APN) correlate with diabetes and coronary artery disease (CAD). Adiponectin and C1q form a protein complex in blood, and serum C1q-binding adiponectin (C1q-APN) can be measured. We investigated the correlation between C1q-APN and CAD in patients with type 2 diabetes mellitus (T2DM). METHODS: The study subjects were 107 outpatients with T2DM who underwent evaluation for CAD. Blood C1q, Total-APN, high-molecular weight-adiponectin (HMW-APN) and C1q-APN were measured by enzyme-linked immunosorbent assays. RESULTS: Serum levels of C1q-APN/Total-APN ratio were higher in patients diagnosed with CAD (10.47±0.59, mean±SEM, n=54) than those without CAD (8.88±0.60, n=53, p=0.0482). Age- and sex-adjusted logistic regression analysis identified serum C1q-APN/Total-APN ratio and hypertension as significant and independent determinants of CAD. A high serum C1q-APN/Total-APN ratio was associated with 3.965-fold increase in CAD prevalence. CONCLUSIONS: High serum C1q-APN/Total-APN ratio correlates with CAD in T2DM.
Metabolism: clinical and experimental 11/2012; · 2.59 Impact Factor
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ABSTRACT: Homeostasis model assessment of insulin resistance (HOMA-IR) is a simple and useful method for evaluating insulin sensitivity. But it is difficult to apply to type2 diabetes patients treated with insulin. We have devised a method for measuring HOMA-IR and investigated the validity of HOMA-IR for evaluating insulin sensitivity in patients with type 2 diabetes on insulin therapy. In the first arm of the study, 19 poorly controlled diabetic subjects were treated with insulin and underwent euglycemic clamp study. Then the relationship between insulin resistance index assessed by the clamp test (clamp-IR) and HOMA-IR was investigated in these subjects. Log transformed HOMA-IR correlated with log transformed M/I values derived from the standard euglycemic clamp (r=0.753, p=0.002). In the second arm of the study, we investigated the relationship between HOMA-IR and various clinical parameters in 156 patients with poorly controlled diabetes after glycemic control. Log transformed HOMA-IR correlated negatively with age (r=-0.292, p=0.0002), HDL-C (r=-0.342, p<0.0001), log transformed serum adiponectin (r=-0.309, p=0.0006) and log transformed KITT (r=-0.264, p=0.0009), and positively with body mass index (r=0.499, p<0.0001), waist circumstance (r=0.461, p<0.0001), visceral fat area (r=0.401, p<0.0001), diastolic blood pressure (r=0.223, p=0.0054), log transformed triglyceride (r=0.497, p<0.0001), urinary CPR (r=0.216, p=0.0099), ΔCPR of glucagon stimulation test (r=0.496, p<0.0001) and log transformed insulinogenic index (r=0.325, p=0.0002). These results suggest that HOMA-IR is a useful test for the evaluation of insulin sensitivity even in patients with type 2 diabetes treated with insulin.
Endocrine Journal 11/2012; · 2.03 Impact Factor
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ABSTRACT: We measured circulating C1q-binding adiponectin (C1q-APN) levels before and after 3-month treatment with pioglitazone in people with type 2 diabetes. The results indicate 3-month treatment with pioglitazone reduces circulating levels of C1q-APN/total-adiponectin ratio without changes in body mass index.
Diabetes research and clinical practice 11/2012; · 2.16 Impact Factor
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ABSTRACT: OBJECTIVE: Atherosclerosis is a disease of blood vessels. Adiponectin is a biomarker of atherosclerosis. Adiponectin and C1q form a protein complex in human blood, and serum C1q-binding adiponectin (C1q-APN) can be measured. We investigated the relationship between various serum adiponectin parameters and polyvascular atherosclerosis score assessed by vascular ultrasonography, in subjects with type 2 diabetes mellitus (T2DM). METHODS: The study subjects were 108 outpatients with T2DM who underwent evaluation for atherosclerosis by vascular ultrasonography. Polyvascular atherosclerosis score represented the sum of atherosclerotic abnormalities in the aorta, carotid, renal and common iliac arteries. Blood C1q, total-adiponectin (Total-APN), high molecular weight-adiponectin (HMW-APN) and C1q-APN were measured by enzyme-linked immunosorbent assays. The estimated visceral fat area (eVFA) was measured by bioelectrical impedance. RESULTS: Polyvascular atherosclerosis score correlated only with the C1q-APN/Total-APN ratio (p=0.018 for trend). There were no significant relationships between various adiponectin parameters and carotid maximum intima-media thickness and ankle-brachial index. Age-, sex-, eVFA-adjusted multiple logistic regression analysis that included the above variables identified serum C1q-APN/Total-APN ratio as the only significant and independent determinant of polyvascular atherosclerosis score. CONCLUSIONS: Serum C1q-APN/Total-APN ratio correlates with atherosclerosis detected by polyvascular vascular ultrasonography, independent of gender and visceral adiposity, in T2DM.
Metabolism: clinical and experimental 10/2012; · 2.59 Impact Factor
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Yuya Fujishima,
Norikazu Maeda,
Kana Inoue,
Susumu Kashine,
Hitoshi Nishizawa,
Ayumu Hirata,
Junji Kozawa,
Tetsuyuki Yasuda,
Kohei Okita,
Akihisa Imagawa, Tohru Funahashi,
Iichiro Shimomura
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ABSTRACT: We recently reported that short-term treatment with liraglutide (20.0 ± 6.4 days) reduced body weight and improved some scales of eating behavior in Japanese type 2 diabetes inpatients. However, it remained uncertain whether such liraglutide-induced improvement is maintained after discharge from the hospital. The aim of the present study was to determine the long-term effects of liraglutide on body weight, glycemic control, and eating behavior in Japanese obese type 2 diabetics.
Patients with obesity (body mass index (BMI) >25 kg/m2) and type 2 diabetes were hospitalized at Osaka University Hospital between November 2010 and December 2011. BMI and glycated hemoglobin (HbA1c) were examined on admission, at discharge and at 1, 3, and 6 months after discharge. For the liraglutide group (BMI; 31.3 ± 5.3 kg/m2, n = 29), patients were introduced to liraglutide after correction of hyperglycemic by insulin or oral glucose-lowering drugs and maintained on liraglutide after discharge. Eating behavior was assessed in patients treated with liraglutide using The Guideline For Obesity questionnaire issued by the Japan Society for the Study of Obesity, at admission, discharge, 3 and 6 months after discharge. For the insulin group (BMI; 29.1 ± 3.0 kg/m2, n = 28), each patient was treated with insulin during hospitalization and glycemic control maintained by insulin after discharge.
Liraglutide induced significant and persistent weight loss from admission up to 6 months after discharge, while no change in body weight after discharge was noted in the insulin group. Liraglutide produced significant improvements in all major scores of eating behavior questionnaire items and such effect was maintained at 6 months after discharge. Weight loss correlated significantly with the decrease in scores for recognition of weight and constitution, sense of hunger, and eating style.
Liraglutide produced meaningful long-term weight loss and significantly improved eating behavior in obese Japanese patients with type 2 diabetes.
Cardiovascular Diabetology 09/2012; 11:107. · 3.35 Impact Factor
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Mitsuyoshi Takahara,
Naoto Katakami,
Ken Kishida,
Hideaki Kaneto, Tohru Funahashi,
Iichiro Shimomura,
Sai Matsunaga,
Satoko Kubo,
Hideaki Fukamizu,
Akihito Otsuka,
Kikuo Ichihara,
Tadashi Nakamura
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ABSTRACT: Aim: The aim of the current study was to investigate circulating adiponectin levels and their associated factors in young lean healthy Japanese women.Methods: We recruited 82 healthy Japanese women in their twenties and thirties with their body mass index <25 kg/m(2), and performed anthropometric, sphygmomanometric, and laboratory examinations. Laboratory examinations included adiponectin levels, as well as lipid profiles, glucose, hemoglobin A1c, transaminase, and creatinine levels, from which the glomerular filtration rate was estimated (eGFR).Results: The median and interquartile range of circulating adiponectin levels were 8.1 (6.2-10.0) µg/ mL. HDL cholesterol levels and eGFR, but not the other examined clinical parameters, were significantly correlated with log-transformed adiponectin levels; their correlation coefficients were 0.323 (p<0.01) and .0.311 (p<0.01), respectively. Statistical significance was still observed even after adjustment for each other (both p= 0.02). In adjusted models, subjects with HDL cholesterol levels ≥80 mg/dL had 1.3 times higher adiponectin levels than those with 40-60 mg/dL, whereas eGFR ≥110 mL/min/1.73m(2) and 60-90 mL/min/1.73m(2) showed a 1.5-fold difference in adiponectin levels.Conclusions: Adiponectin levels of young lean healthy Japanese women had significant associations with HDL cholesterol levels and eGFR, even though their HDL cholesterol levels and eGFR were distributed within normal ranges. It seems important to take into account these two variables in evaluating adiponectin levels of these subjects, even if the two variables are within normal ranges.
Journal of atherosclerosis and thrombosis 09/2012; · 2.69 Impact Factor
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Yukio Arita,
Shinji Kihara,
Noriyuki Ouchi,
Masahiko Takahashi,
Kazuhisa Maeda,
Jun-ichiro Miyagawa,
Kikuko Hotta,
Iichiro Shimomura,
Tadashi Nakamura,
Koji Miyaoka,
Hiroshi Kuriyama,
Makoto Nishida,
Shizuya Yamashita,
Kosaku Okubo,
Kenji Matsubara,
Masahiro Muraguchi,
Yasuichi Ohmoto, Tohru Funahashi,
Yuji Matsuzawa
Biochemical and Biophysical Research Communications 08/2012; 425(3):560-4. · 2.48 Impact Factor
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ABSTRACT: OBJECTIVE: Adiponectin and C1q have similar sequences, exist abundantly in blood, and are produced by adipose tissues. The aim of this study was to examine whether adiponectin and C1q form protein-complex in blood and to know the clinical significance of the C1q-adiponectin (C1q-APN) complex in serum. METHODS: The direct interaction between adiponectin and C1q was investigated by far western blotting and co-immunoprecipitation. The relationship between serum C1q-APN and various clinical features was analyzed in 329 Japanese men who underwent health check-up, including measurements of visceral (VFA) and subcutaneous fat area (SFA) by computed tomography (Victor-J study). RESULTS: Adiponectin bound to C1q in vitro and C1q-APN complex existed in human blood. C1q-APN complexes were identified in high- and middle-molecular weight forms of adiponectin in human serum by gel-filtration chromatography. Stepwise multiple regression analysis identified body mass index, VFA and SFA as significant determinants of serum C1q-APN level. Serum C1q-APN/Total-APN ratio correlated positively with cardiovascular risk factor accumulation in subjects with VFA ≥100 cm(2). CONCLUSIONS: These results indicate that high- and middle-molecular forms of adiponectin partly consist of adiponectin-complex with other proteins including C1q and that the blood C1q-APN/Total-APN ratio may serve as a biomarker of the metabolic syndrome in general male subjects.
Metabolism: clinical and experimental 07/2012; · 2.59 Impact Factor
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Aki Hiuge-Shimizu,
Ken Kishida, Tohru Funahashi,
Yuko Ishizaka,
Rie Oka,
Minoru Okada,
Shizu Suzuki,
Norihide Takaya,
Tohru Nakagawa,
Toshiki Fukui,
Hiroshi Fukuda,
Naoya Watanabe,
Tohru Yoshizumi,
Tetsuya Ohira,
Tadashi Nakamura,
Yuji Matsuzawa,
Minoru Yamakado,
Iichiro Shimomura
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ABSTRACT: Aim: Visceral fat accumulation is associated with obesity-related cardiovascular risk factor accumulation and atherosclerosis. The present study investigated whether one-year reduction of the visceral fat area (VFA) correlates with a decrease in the number of such factors in Japanese with or without visceral fat accumulation.Methods: The study subjects comprised 5,347 Japanese, who underwent health check-ups in 2007 and 2008, including measurements of VFA and subcutaneous fat area (SFA) by computed tomography at 9 centers in Japan. Subjects with one or more such factor(s) were categorized into tertiles based on the one-year change in VFA. We investigated the multivariate age, sex, and one-year change in SFA-adjusted odds ratios (ORs) and 95% confidence intervals (CI) for reductions in the number of risk factors in each of the three categories based on the one-year change in VFA, in subjects with one or more such factors (n= 3,648).Results: In the entire group (n=3,648), the OR and 95%CI for reductions in the number of risk factors in the first tertile were 0.804 (0.673-0.962, p=0.0172), compared with the second tertile set at 1.0. Subjects with VFA <100cm(2) showed no reduction in the number of risk factors. In subjects with VFA .100 cm(2), OR in the first tertile was 0.788 (0.639-0.972, p=0.0257) relative to the second tertile set at 1.0.Conclusions: In subjects with multiple cardiovascular risk factors, visceral fat reduction correlated with a decrease in the number of such factors in subjects with VFA≥100cm(2), but not in those with VFA<100cm(2).
Journal of atherosclerosis and thrombosis 07/2012; · 2.69 Impact Factor
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ABSTRACT: The incidence of type 2 diabetes mellitus (T2DM) has been increasing in recent years. Sleep loss and circadian rhythm abnormalities are thought to be one of the underlying causes of adverse metabolic health. However, little is known about sleep-wake cycle irregularities in T2DM. The present study compared the bedtime, waking time, and estimated sleep duration between T2DM and non-T2DM subjects.
The study subjects were 106 consecutive outpatients with lifestyle-related diseases (males/females = 56/50), who answered a questionnaire on sleep status. Subjects were divided into two groups; non-T2DM (n = 32) and T2DM (n = 74) subjects.
T2DM subjects retired to bed on weekdays and holidays significantly later than non-T2DM subjects (23:43 versus 22:52, p = 0.0032; 23:45 versus 22:53, p = 0.0038, respectively), and woke up significantly later on weekdays and holidays, compared with non-T2DM subjects (06:39 versus 06:08, p = 0.0325; 06:58 versus 06:24, p = 0.0450, respectively). There was no significant difference in the estimated sleep duration between the two groups. Daytime sleepiness was reported significantly more commonly by T2DM subjects than non-T2DM subjects (p = 0.0195).
Sleep-wake cycle irregularities are more common in T2DM subjects than non-T2DM. Confirmation that such irregularity plays a role in the metabolic abnormalities of T2DM requires further investigation in the future.
UMIN 000002998.
Diabetology and Metabolic Syndrome 05/2012; 4(1):18. · 1.53 Impact Factor
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ABSTRACT: Aim: Visceral adiposity is linked with sleep-disordered breathing (SDB) (called Syndrome Z), and both correlate with coronary artery disease (CAD). The aim of the present study was to determine the significance of excess visceral fat, SDB and circulating levels of biomarkers in CAD in Japanese men.Methods: SDB, visceral fat area (VFA), and circulating levels of biomarkers were assessed in 60 Japanese male patients who underwent coronary angiography and overnight cardiorespiratory monitoring.Results: Age-adjusted logistic analysis showed a significant relationship between CAD and diabetes, hypertension, dyslipidemia, SDB (AHI ≥5 events/hour), visceral fat accumulation (VFA ≥100 cm(2)), the combination of visceral fat accumulation and hypertension or dyslipidemia, as well as the combination of visceral fat accumulation and SDB. Patients with VFA ≥100 cm(2) and SDB had significantly lower serum adiponectin levels and higher serum soluble CD40 ligand levels than those with VFA<100 cm(2) and SDB. The prevalence of CAD was significantly higher in patients with VFA ≥100 cm(2) and SDB than in patients with VFA <100 cm(2) and AHI <5 events/hour, patients with VFA<100 cm(2) and AHI ≥5 events/hour or patients with VFA ≥100 cm(2) and AHI <5 events/hour (93% versus 14%, p <0.001, 53%, p <0.01 or 63%, p <0.01, respectively).Conclusions: The present study indicates that patients with both visceral fat accumulation and SDB develop CAD in association with hypoadiponectinemia and inflammatory activity.
Journal of atherosclerosis and thrombosis 04/2012; 19(8):728-35. · 2.69 Impact Factor
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Aki Hiuge-Shimizu,
Ken Kishida, Tohru Funahashi,
Masaaki Okutsu,
Ryosuke Kametani,
Hiroshi Kobayashi,
Yoichi Nozaki,
Akihiro Nomura,
Hiroyoshi Yokoi,
Tohru Yoshizumi,
Tetsuya Ohira,
Tadashi Nakamura,
Yuji Matsuzawa,
Satoru Sumitsuji,
Iichiro Shimomura
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ABSTRACT: Multiple risk factor syndrome is a target for the prevention of coronary artery disease (CAD). A cluster of multiple risk factors, such as hypertension, glucose intolerance, and/or dyslipidemia, is encountered in Japanese without and with excess visceral fat. The present study investigated the relationship between multiple risk factor accumulation and CAD in Japanese without and with visceral fat accumulation.
The study subjects comprised 257 Japanese with suspected CAD (males/females= 153/ 104), who underwent 64-row multislice computed tomography (CT) coronary angiography and visceral fat area (VFA) measurement by CT. Based on the Japanese criteria for visceral fat accumulation, they were divided into those with VFA <100 and ≥10 cm(2).
In subjects with VFA <100 cm(2), the age- and sex-adjusted odds ratios (ORs) for 2 and 3 risk factors were 5.33 (95% confidence intervals; 1.04-27.38, p=0.0449) and 4.07 (0.72-23.15, p=0.1138), respectively, compared with VFA <100 cm(2) and 0 risk factor set at 1.0 (p=0.0569 for trend). In contrast, the respective ORs for subjects with VFA ≥100 cm(2) were much higher [6.46 (1.25-33.44, p=0.0261) and 20.42 (3.60-115.73, p=0.0007)] (p<0.0001 for trend). The multivariate adjusted model demonstrated a significant relative excess CAD risk of 1.08 (p=0.0484) and 5.01 (p<0.0001) for the interactions of 2 risk factors and VFA ≥100 cm(2), and 3 risk factors and VFA ≥100 cm(2), whereas multiple risk factor accumulation was not related with the increase of CAD risk in subjects with VFA <100 cm(2).
Coexistence of visceral fat and risk factor accumulations is strongly associated with CAD in Japanese.
Journal of atherosclerosis and thrombosis 04/2012; 19(7):657-63. · 2.69 Impact Factor
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ABSTRACT: B-type natriuretic peptide (BNP), a member of the natriuretic peptide family, is a cardiac-derived secretory hormone with natriuretic, diuretic, and vasorelaxant activities. Intraabdominal fat accumulation is associated with atherosclerotic cardiovascular diseases and cardiac dysfunction. Circulating BNP levels are relatively low (within the normal limits) in obesity and the metabolic syndrome. However, the relationship between plasma BNP levels and visceral fat accumulation in general population has not been reported. The present study analyzed the relationships between plasma BNP levels and various clinical variables, including insulin, visceral and subcutaneous fat area (VFA and SFA, respectively), in normal Japanese men.
The study (Victor-J study) subjects were consecutive 500 Japanese male workers, who underwent a health checkup and were measured VFA and SFA by computed tomography.
Age-adjusted simple linear regression analysis showed that log-BNP correlated positively with HDL-cholesterol, and negatively with VFA, log-immunoreactive insulin (IRI), log-triglyceride, and LDL-cholesterol, but not body mass index or SFA. Stepwise multiple regression analysis identified log-IRI and HDL-cholesterol as significant determinants of log-BNP. Subjects with IRI ≥5.5 μIU/mL had lower plasma BNP levels than those with IRI < 5.5 μIU/mL, irrespective of obesity (body mass index, cutoff value 25 kg/m2), visceral fat accumulation (VFA, cutoff value 100 cm2) and subcutaneous fat accumulation (SFA, cutoff value 128 cm2).
Our study showed that hyperinsulinemia correlated with low levels of plasma BNP in general men, irrespective of fat distribution.
UMIN 000004318.
Cardiovascular Diabetology 03/2012; 11:22. · 3.35 Impact Factor
