To investigate whether diabetes and regular hemodialysis are associated with false elevation of ankle systolic blood pressure and ankle-brachial systolic pressure index (ABI) because of their arterial calcification in patients with critical limb ischemia (CLI).
RESEARCH DESIGN AND METHODS
We recruited 269 Japanese patients who underwent endovascular therapy for CLI. Ankle systolic blood pressure and ABI were assessed before endovascular therapy. Arterial stenosis and calcification were evaluated angiographically. We investigated the associations among clinical comorbidities, arterial calcification, and measurements of ankle systolic blood pressure and ABI.
Ankle systolic blood pressure was 85 ± 56 mmHg, and ABI was 0.59 ± 0.37. Arterial calcification was observed in 69% of the patients. The prevalence of diabetes and regular hemodialysis was 71 and 47%. Diabetes and regular hemodialysis were both significantly associated with the presence of arterial calcification; their adjusted odds ratios were 2.33 (P = 0.01) and 7.40 (P < 0.01), respectively. However, there was no significant difference in ankle systolic blood pressure or ABI level between those with and without these comorbidities. Furthermore, the presence of arterial calcification was not associated with ankle systolic blood pressure or ABI level, whereas arterial stenoses of all segments in the lower body had independent associations with reduced ankle systolic blood pressure and ABI level.
Diabetes and regular hemodialysis were significantly associated with arterial calcification, but not with elevated measurements of ankle systolic blood pressure or ABI, in CLI patients.
Ephrin-B1 (EfnB1) was selected among genes of unknown function in adipocytes or adipose tissue and subjected to thorough analysis to understand its role in the development of obesity.
Methods and Results
EfnB1 mRNA and protein levels were significantly decreased in adipose tissues of obese mice and such reduction was mainly observed in mature adipocytes. Exposure of 3T3-L1 adipocytes to tumor necrosis factor-α (TNF-α) and their culture with RAW264.7 cells reduced EFNB1 levels. Knockdown of adipose EFNB1 increased monocyte chemoattractant protein-1 (Mcp-1) mRNA level and augmented the TNF-α-mediated THP-1 monocyte adhesion to adipocytes. Adenovirus-mediated adipose EFNB1-overexpression significantly reduced the increase in Mcp-1 mRNA level induced by coculture of 3T3-L1 adipocytes with RAW264.7 cells. Monocyte adherent assay showed that adipose EfnB1-overexpression significantly decreased the increase of monocyte adhesion by coculture with RAW264.7 cells. TNF-α-induced activation of extracellular signal-regulated kinase 1/2 (ERK1/2) was reduced by EFNB1-overexpression.
EFNB1 contributes to the suppression of adipose inflammatory response. In obesity, reduction of adipose EFNB1 may accelerate the vicious cycle involved in adipose tissue inflammation.
Inflammation is closely associated with the development of atherosclerosis and metabolic syndrome. Adiponectin, an adipose-derived secretory protein, possesses an anti-atherosclerotic property. The present study was undertaken to elucidate the presence and significance of adiponectin in vasculature.
Methods and Results
Immunofluorescence staining was performed in aorta of wild-type (WT) mice and demonstrated that adiponectin was co-stained with CD31. Thoracic aorta was cut through and then aortic intima was carefully shaved from aorta. Western blotting showed the existence of adiponectin protein in aortic intima, while there was no adiponectin mRNA expression. Adiponectin knockout (Adipo-KO) and WT mice were administered with a low-dose and short-term lipopolysaccharide (LPS) (1 mg/kg of LPS for 4 hours). The endothelium vascular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were highly increased in Adipo-KO mice compared to WT mice after LPS administration.
Adiponectin protein exists in aortic endothelium under steady state and may protect vasculature from the initiation of atherosclerosis.
Although many Asian type 2 diabetic patients have been considered to be not obese and have low capacity of insulin secretion, the proportion of obese patients with visceral fat accumulation has increased in recent years. We found previously considerable number of Japanese non-obese subjects (body mass index (BMI) < 25 kg/m2) with visceral fat accumulation and multiple cardiovascular risk factors. The aim of the study was to investigate the difference in clinical features of type 2 diabetic patients with and without visceral fat accumulation, focusing on vascular complications and changes in BMI.
We enrolled 88 Japanese hospitalized type 2 diabetic patients. Abdominal obesity represented waist circumference (WC) of ≥85 cm for males and ≥90 cm for females (corresponding to visceral fat area of 100 cm2). Subjects were divided into two groups; with or without abdominal obesity.
Hypertension, dyslipidemia and cardiovascular diseases were significantly more in the patients with abdominal obesity. The prevalence of cardiovascular disease in the non-obese patients (BMI < 25 kg/m2) with abdominal obesity were similar in obese patients (BMI ≥25 kg/m2). The mean BMI of the patients with abdominal obesity was < 25 kg/m2 at 20 years of age, but reached maximum to more than 30 kg/m2 in the course. Furthermore, substantial portion of the type 2 diabetic patients (52% in males and 43% in females) were not obese at 20 year-old (BMI < 25 kg/m2), but developed abdominal obesity by the time of admission.
These results emphasize the need to control multiple risk factors and prevent atherosclerotic disease in patients with abdominal obesity. The significant weight gain after 20 years of age in patients with abdominal obesity stresses the importance of lifestyle modification in younger generation, to prevent potential development of type 2 diabetes and future atherosclerotic cardiovascular disease.
Abdominal obesity; Type 2 diabetes; Waist circumference; Visceral fat accumulation; Body mass index; Cardiovascular disease
We herein report the case of a 41-year-old Japanese female office worker who developed symptomatic hypocalcemia with severe vitamin D deficiency following treatment for Graves' disease with methimazole. The patient's hypocalcemia was mainly caused by vitamin D deficiency due to unbalanced diets and inadequate exposure to sunlight in addition to the resolution of hyperthyroidism. Vitamin D deficiency is increasing worldwide, and it has been more recently shown to relate to the pathogenesis of Graves' disease. However, vitamin D deficiency as a cause of hypocalcemia has received little attention. Taken together, this case suggests that we should take more care in calcium kinetics and vitamin D status during treatment for Graves' disease with antithyroid drugs.
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.
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.
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.
Clinical Trial Registration Number: UMIN000004318
Adiponectin; C1q; C1q-binding adiponectin; Aging
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.
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).
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
Arachidonic acid; Eicosapentaenoic acid; Docosahexaenoic acid; Visceral fat; Metabolic syndrome; Obesity
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.
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.
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.
Low serum C1q-APN and C1q-APN/C1q ratio, but not C1q-APN/Total-APN ratio, correlated with ACVD in HD patients.
Adiponectin; C1q; C1q-binding adiponectin, Hemodialysis
Adiponectin is exclusively expressed in adipose tissues and exhibits protective effects against cardiovascular and metabolic diseases. It enhances AMP-activated kinase (AMPK) and peroxisome proliferator-activated receptor α (PPARα) signaling in the liver and skeletal muscles, however, its signaling pathways in macrophages remain to be elucidated. Here, we show that adiponectin upregulated the expression of vascular endothelial growth factor (VEGF)-C, and induced phosphorylation of extracellular signal-regulated kinase (ERK) in macrophages. Inhibition of Syk abrogated adiponectin-induced VEGF-C expression and ERK phosphorylation. Furthermore, inhibition of ERK blocked the induction of VEGF-C gene. Inhibition of Syk, but not that of ERK, abrogated adiponectin-induced expression of cyclooxygenase (COX)-2, tissue inhibitor of metalloproteinase (TIMP)-1, and interleukin (IL)-6. These results indicate that adiponectin regulates VEGF-C expression via Syk-ERK pathway in macrophages.
We report a case of 42-year-old male patient with hypogonadotropic hypogonadism. He suffered from general fatigue and erectile dysfunction after the treatment with transdermal fentanyl for chronic pain by traffic injury. Endocrine examinations and hormone stimulating tests showed that he had hypogonadotropic hypogonadism. Brain magnetic resonance imaging (MRI) showed no abnormal findings, and he had no past history of accounting for acquired hypogonadotropic hypogonadism. Therefore, his hypogonadism was diagnosed to be caused by opioid treatment. Although opioid-induced endocrine dysfunctions are not widely recognized, this case suggests that we should consider the possibility of endocrine dysfunctions in patients with opioid treatment.
Telmisartan is a well-established angiotensin II type 1 receptor blocker that improves insulin sensitivity in animal models of obesity and insulin resistance, as well as in humans. Telmisartan has been reported to function as a partial agonist of the peroxisome proliferator-activated receptor (PPAR) γ, which is also targeted by the nicotinamide adenine dinucleotide (NAD)-dependent deacetylase (SIRT1). Here, we investigated the pathways through which telmisartan acts on skeletal muscle, in vitro as well as in vivo.
Nine-week-old male db/db mice were fed a 60% high-fat diet, with orally administrated either vehicle (carboxymethyl-cellulose, CMC), 5 mg/kg telmisartan, or 5 mg/kg telmisartan and 1 mg/kg GW9662, a selective irreversible antagonist of PPARγ, for 5 weeks. Effects of telmisartan on Sirt1 mRNA, AMPK phosphorylation, and NAD+/NADH ratio were determined in C2C12 cultured myocytes.
Results and discussion
Telmisartan treatment improved insulin sensitivity in obese db/db mice fed a high-fat diet and led to reduction in the size of hypertrophic pancreatic islets in these mice. Moreover, in vitro treatment with telmisartan led to increased expression of Sirt1 mRNA in C2C12 skeletal muscle cells; the increase in Sirt1 mRNA in telmisartan-treated C2C12 myoblasts occurred concomitantly with an increase in AMPK phosphorylation, an increase in NAD+/NADH ratio, and increases in the mRNA levels of PGC1α, FATP1, ACO, and GLUT4.
Our results indicate that telmisartan acts through a PPARγ-independent pathway, but at least partially exerts its effects by acting directly on skeletal muscle AMPK/SIRT1 pathways.
Adiponectin; AMP-activated protein kinase; Obesity; Peroxisome proliferator-activated receptor-γ; SIRT1
Evidence suggests that visceral fat accumulation plays a central role in the development of metabolic syndrome. Excess visceral fat causes local chronic low-grade inflammation and dysregulation of adipocytokines, which contribute in the pathogenesis of the metabolic syndrome. These changes may affect the gene expression in peripheral blood cells. This study for the first time examined the association between visceral fat adiposity and gene expression profile in peripheral blood cells. The gene expression profile was analyzed in peripheral blood cells from 28 obese subjects by microarray analysis. Reverse transcription-polymerase chain reaction (RT-PCR) was performed using peripheral blood cells from 57 obese subjects. Obesity was defined as body mass index (BMI) greater than 25 kg/m2 according to the Japanese criteria, and the estimated visceral fat area (eVFA) was measured by abdominal bioelectrical impedance. Analysis of gene expression profile was carried out with Agilent whole human genome 4×44 K oligo-DNA microarray. The expression of several genes related to circadian rhythm, inflammation, and oxidative stress correlated significantly with visceral fat accumulation. Period homolog 1 (PER1) mRNA level in blood cells correlated negatively with visceral fat adiposity. Stepwise multiple regression analysis identified eVFA as a significant determinant of PER1 expression. In conclusion, visceral fat adiposity correlated with the expression of genes related to circadian rhythm and inflammation in peripheral blood cells.
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.
Liraglutide; Glucagon-like peptide-1 (GLP-1); Obesity; Eating behavior; Diabetes; Incretin
To investigate the basal insulin requirement in total daily insulin dose in Japanese type 1 diabetic patients who use the insulin pump.
RESEARCH DESIGN AND METHODS
The basal insulin requirement in 35 type 1 diabetic patients without detectable C-peptide using the insulin pump (Paradigm 712) was investigated during 2–3 weeks of hospitalization. The patients were served diabetic diets of 25–30 kcal/kg ideal body weight. Each meal omission was done to confirm stable blood glucose levels within 30 mg/dL variance until the next meal. Target blood glucose level was set at 100 mg/dL before each meal and 150 mg/dL at 2 h after each meal.
Total daily insulin dose was 31.6 ± 8.5 units, and total basal insulin requirement was 8.7 ± 2.9 units, which was 27.7 ± 6.9% of the total daily dose.
Basal insulin requirement is ∼30% of the total daily dose in Japanese type 1 diabetic patients who use the insulin pump.
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.
B-type natriuretic peptide; Hyperinsulinemia; Visceral fat
Sleep-disordered breathing (SDB), especially obstructive sleep apnea (OSA), has frequent complications include hypertension, dyslipidemia and insulin resistance based on abdominal obesity or excess visceral fat (called Syndrome Z). OSA is a potential risk factor for cardiovascular diseases. The clinical characteristics of Japanese OSA subjects with OSA remain unclear. The present study investigated prevalence and predictive factors of intracoronary stenosis detected by multislice computed tomography (MSCT) in Japanese male subjects with SDB/OSA.
The study (O-VFStudy) subjects were 39 Japanese men with SDB/OSA who underwent all-night cardiorespiratory monitoring with fully attended polysomnography, and moreover both fat computed tomography (CT) scan and 64-row MSCT coronary angiography. The prevalence of coronary stenosis in this selected population with SDB/OSA was 15%. Logistic regression analysis showed a significant relationship between age-adjusted CAD and metabolic syndrome (p < 0.05), but not serum adiponectin levels and nocturnal fall in adiponectin. Subjects with the metabolic syndrome had significantly higher prevalence of CAD (31.3 versus 4.3%, p = 0.033), and lower levels of serum adiponectin (4.5 ± 0.6 versus 6.4 ± 0.6 μg/mL, p = 0.014), compared with groups without the metabolic syndrome.
The present study describes that the prevalence of greater than 50% intracoronary stenotic lesions detected by MSCT was 15% and the metabolic syndrome was correlated with intracoronary stenosis detected by MSCT in Japanese SDB/OSA subjects.
Coronary Stenosis; Sleep apnea-hypopnea; Visceral fat; Adiponectin
We examined the relationship between the presence and extent of coronary stenosis and carotid intima-media thickness (CIMT) in type 2 diabetic patients without history of coronary artery disease (CAD) but with carotid atherosclerosis.
RESEARCH DESIGN AND METHODS
A total of 91 type 2 diabetic patients underwent multi-slice computed tomography coronary angiography.
Max-IMT in the ≥50% stenosis group by multi-slice computed tomography coronary angiography estimation was significantly greater than the 0–25 and 25–50% stenosis group (2.68 ± 0.77 vs. 1.61 ± 0.49 mm, P < 0.0005, and 2.14 ± 0.81 mm, P < 0.05, respectively), and max-IMT in the 25–50% stenosis group was significantly greater than the 0–25% stenosis group (P < 0.05) after adjustment for age, sex, duration of type 2 diabetes, hypertension, and dyslipidemia. In the analysis for trend through the categories of max-IMT, as max-IMT increased, the percentage of ≥50% stenosis increased and the percentage of 0–25% stenosis decreased.
Our data suggest that max-IMT might be closely associated with the extent of coronary stenosis in type 2 diabetic patients without history of CAD but with carotid atherosclerosis.
The prevalence of gastroesophageal reflux disease (GERD) has been increasing worldwide. Abdominal obesity or visceral fat accumulation rather than simple obesity is associated with GERD. Previous reports demonstrated the association between GERD and type 2 diabetes mellitus (T2DM). Signification of visceral fat accumulation and adiponectin in T2DM patients with GERD remains unclear. The present study investigated the relationships between GERD symptoms, visceral fat accumulation and adiponectin in subjects with T2DM.
The study (ADMIT study) subjects were 66 Japanese T2DM outpatients, who answered the questionnaire regarding GERD symptoms in Frequency Scale for the Symptoms of GERD (FSSG), and were measured visceral fat area by bioelectrical impedance analysis. Patients with FSSG scores of more than 8 were considered as positive. The prevalence of FSSG score ≥ 8 and average FSSG score in T2DM subjects with the metabolic syndrome (Mets) were significantly higher compared to those without Mets. The prevalence of FSSG score ≥ 8 and average FSSG score in T2DM subjects with low levels of serum adiponectin were significantly higher compared to those with high levels of serum adiponectin. Moreover, the combination of Mets and hypoadiponectinemia had a multiplicative effect on GERD symptom score (p = 0.047).
Our study showed that the coexistence of MetS and low levels of serum adiponectin was associated with the higher prevalence of FSSG score ≥ 8 and the higher scores of GERD symptom in subjects with T2DM.
gastroesophageal reflux symptom; metabolic syndrome; visceral fat; adiponectin
To reveal the influence of preoperative factors on the prognosis of patients undergoing percutaneous transluminal angioplasty (PTA) for critical limb ischemia (CLI).
RESEACH DESIGN AND METHODS
We recruited 278 Japanese patients who underwent PTA for CLI between 2003 and 2009. The outcome measures were mortality and major amputation. Cox proportional hazards regression analyses were performed.
The prevalence of diabetes was 71%, and A1C was 7.0 ± 1.4%. The follow-up period was 90 ± 72 weeks, and 48 patients underwent major amputations and 89 died. The presence of diabetes in the whole population and A1C level in the diabetic population had no influence on morality; rather, mortality was associated with age (P = 0.007), impaired activities of daily living (P < 0.001), hemodialysis (P < 0.001), and albumin level (P = 0.010). In contrast, the presence of diabetes and A1C level had significant association with major amputation (P = 0.012 and P = 0.007, respectively). The quartile analysis showed that diabetic subjects with an A1C ≥6.8%, but not <6.8%, had a significantly higher risk of major amputation than nondiabetic subjects. The adjusted hazard ratio of diabetes with A1C ≥6.8% was 2.907 (95% CI 1.606–5.264) (P < 0.001).
Diabetes with poor glycemic control is associated with major amputation, but not mortality, in CLI patients undergoing PTA. Prognostic indicators seem somewhat different between survival and limb salvage in the population.
To examine the effects of liraglutide, a glucagon-like peptide-1 (GLP-1) analogue, on visceral fat adiposity, appetite, food preference, and biomarkers of cardiovascular system in Japanese patients with type 2 diabetes.
The study subjects were 20 inpatients with type 2 diabetes treated with liraglutide [age; 61.2 ± 14.0 years, duration of diabetes; 16.9 ± 6.6 years, glycated hemoglobin (HbA1c); 9.1 ± 1.2%, body mass index (BMI); 28.3 ± 5.2 kg/m2, mean ± SD]. After improvement in glycemic control by insulin or oral glucose-lowering agents, patients were switched to liraglutide. We assessed the estimated visceral fat area (eVFA) by abdominal bioelectrical impedance analysis, glycemic control by the 75-g oral glucose tolerance test (OGTT) and eating behavior by the Japan Society for the Study of Obesity questionnaire.
Treatment with liraglutide (dose range: 0.3 to 0.9 mg/day) for 20.0 ± 6.4 days significantly reduced waist circumference, waist/hip ratio, eVFA. It also significantly improved the scores of eating behavior, food preference and the urge for fat intake and tended to reduce scores for sense of hunger. Liraglutide increased serum C-peptide immunoreactivity and disposition index.
Short-term treatment with liraglutide improved visceral fat adiposity, appetite, food preference and the urge for fat intake in obese Japanese patients with type 2 diabetes.
liraglutide; glucagon-like peptide-1; obesity; eating behavior
Circulating thiobarbituric acid-reacting substance (TBARS) levels, a marker of systemic oxidative stress, are predictive of cardiovascular events. However, they has not been evaluated in Japanese, especially with regard to the factors that contribute to the changes in circulating TBARS levels. We investigated the cross-sectional and longitudinal relationships between circulating TBARS levels and various clinicobiochemical parameters in middle-aged men.
In this population-based study (The Amagasaki Visceral Fat Study), 1,178 Japanese male urban workers who had undergone health check-ups in 2006, 2007 and 2008 and were not on medications for metabolic disorders during the follow-up period, were enrolled. Serum TBARS levels were measured by the method of Yagi. The estimated visceral fat area (eVFA) by bioelectrical impedance was measured annually. After health check-ups, subjects received health education with lifestyle modification by medical personnel.
The number of cardiovascular risk factors (hypertension, hyperglycemia, low HDL-C, hypertriglyceridemia, hyperuricemia, hyper-LDL-C and impaired renal function) augmented with the increases in log-eVFA (p < 0.0001) and log-TBARS (p < 0.0001). The combination of TBARS and eVFA had a multiplicative effect on risk factor accumulation (F value = 79.1, p = 0.0065). Stepwise multiple regression analysis identified log-eVFA, as well as age, log-body mass index (BMI), LDL-C, log-adiponectin, γ-glutamyl transpeptidase (γ-GTP) and uric acid as significant determinants of log-TBARS. Stepwise multiple regression analysis identified one-year changes in eVFA as well as BMI, γ-GTP and estimated glomerular filtration rate (eGFR) as significant determinants of one-year change in TBARS, and biennial changes in eVFA as well as BMI and γ-GTP, eGFR as significant determinants of biennial change in TBARS.
The present study showed a significant cross-sectional and longitudinal correlation between TBARS and eVFA, as well as BMI and γ- GTP, eGFR. Visceral fat reduction may independently associate with the improvement in systemic ROS in middle-aged Japanese men.
The Amagasaki Visceral Fat Study UMIN000002391.
visceral fat accumulation; systemic reactive oxidative stress; visceral fat reduction
The metabolic syndrome has received worldwide recognition and is useful clinical aid in early-preventing atherosclerosis. Visceral adiposity is the main component of the metabolic syndrome in Japan, based on ethnic and racial difference in the pattern of adiposity. In the Amagasaki Visceral Fat Study, subjects had undergone annual health check-ups and then received health education by medical personnel. Visceral fat reduction improved hypoadiponectinemia and the number of obesity-related cardiovascular risk factors, and effectively prevented cardiovascular events. The health education that includes voluntary lifestyle modification aimed at reducing visceral fat could be useful in preventing cardiovascular events in the metabolic syndrome.
Visceral fat syndrome; adipocyte dysfunction; health education; Hokenshido; metabolic syndrome