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Purpose: We previously reported that insulin resistance, low high-density lipoprotein (HDL) cholesterol, and glycaemic exposure Index are independently associated with peripheral neuropathy in Korean patients with type 2 diabetes mellitus. We followed the patients who participated in that study in 2006 for another 6 years to determine the relationship between insulin resistance and neuropathy. Materials and Methods: This study involved 48 of the original 86 Korean patients with type 2 diabetes mellitus who were referred to the Neurology clinic for the assessment of diabetic neuropathy from January 2006 to December 2006. These 48 patients received management for glycaemic control and prevention of diabetic complications in the outpatient clinic up to 2012. We reviewed blood test results and the nerve conduction study findings of these patients, taken over a 6-year period. Results: Low HDL cholesterol and high triglycerides significantly influenced the development of diabetic neuropathy. Kitt value (1/insulin resistance) in the previous study affected the occurrence of neuropathy, despite adequate glycaemic control with HbA1c <7%. Insulin resistance affected the development of diabetic neuropathy after 6 years: insulin resistance in 2006 showed a positive correlation with a change in sural sensory nerve action potential in 2012. Conclusion: Diabetic neuropathy can be affected by previous insulin resistance despite regular glycaemic control. Dyslipidaemia should be controlled in patients who show high insulin resistance because HDL cholesterol and triglycerides are strongly correlated with later development of diabetic neuropathy. [ABSTRACT FROM AUTHOR]

Background Although body mass index (BMI) is the most widely accepted parameter for defining obesity, recent studies have indicated a unique set of patients who exhibit normal BMI and excess body fat (BF), which is termed as normal weight obesity (NWO). Increased BF is an established risk factor for atherosclerosis. However, it is unclear whether NWO subjects already have a higher degree of vascular inflammation compared to normal weight lean (NWL) subjects; moreover, the association of BF with vascular inflammation in normal weight subjects is largely unknown. Methods NWO and NWL subjects (n=82 in each group) without any history of significant vascular disease were identified from a 3-year database of consecutively recruited patients undergoing 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDGPET/ CT) at a self-referred Healthcare Promotion Program. The degree of subclinical vascular inflammation was evaluated using the mean and maximum target-to-background ratios (TBRmean and TBRmax) of the carotid artery, which were measured by 18 F-FDG-PET/CT (a noninvasive tool for assessing vascular inflammation). Results We found that metabolically dysregulation was greater in NWO subjects than in NWL subjects, with a significantly higher blood pressure, higher fasting glucose level, and worse lipid profile. Moreover, NWO subjects exhibited higher TBR than NWL subjects (TBRmean: 1.33±0.16 versus 1.45±0.19, p<0.001; TBRmax: 1.52±0.23 versus 1.67±0.25, p<0.001). TBR was significantly associated with total BF (TBRmean: r=0.267, p=0.001; TBRmax: r=0.289, p<0.001), age (TBRmean: r=0.170, p=0.029; TBRmax: r=0.165, p=0.035), BMI (TBRmean: r=0.184, p=0.018; TBRmax: r=0.206, p=0.008), and fasting glucose level (TBRmean: r=0.157, p=0.044; TBRmax: r=0.182, p=0.020). In multiple linear regression analysis, BF was an independent determinant of TBRmean and TBRmax, after adjusting for age, BMI, and fasting glucose level (TBRmean: regression coefficient=0.020, p=0.008; TBRmax: regression coefficient=0.028, p=0.005). Compared to NWL, NWO was also independently associated with elevated TBRmax values, after adjusting for confounding factors (odds ratio=2.887, 95% confidence interval 1.206-6.914, p=0.017). Conclusions NWO is associated with a higher degree of subclinical vascular inflammation, of which BF is a major contributing factor. These results warrant investigations for subclinical atherosclerosis in NWO patients. [ABSTRACT FROM AUTHOR]

Pheochromocytoma is a rare neuroendocrine tumor that is usually derived from adrenal medulla or chromaffin cells along with sympathetic ganglia. In Western countries, the prevalence of pheochromocytoma is estimated to be between 1:6,500 and 1:2,500, compared with an incidence in the United States of 500 to 1,100 cases per year. Despite this low incidence, pheochromocytoma should always be considered for differential diagnoses because previous studies have shown that this condition can be cured in approximately 90% of cases. However, an untreated tumor is likely to be fatal due to catecholamine-induced malignant hypertension, heart failure, myocardial infarction, stroke, ventricular arrhythmias or metastatic disease. Symptoms that result primarily from excess circulating catecholamines and hypertension include severe headaches, generalized inappropriate sweating and palpitations (with tachycardia or occasionally bradycardia). Pheochromocytoma, however, has highly variable and heterogeneous clinical manifestations, including fever, general weakness and dyspepsia, and can be observed in patients who are suffering from infectious diseases. Several of such case reports have been presented, but most of these included infectious patients with high blood pressure and severe fluctuations. In this study, we presented the case of a 53-year-old male who showed normal blood pressure, but had a sustained fever. He was diagnosed with diabetic ketoacidosis, infective endocarditis and asymptomatic adrenal incidentaloma. Despite treatment with antibiotics and valve replacement, the fever persisted. After the patient underwent evaluation for the fever, adrenal incidentaloma was identified as pheochromocytoma. After removal of the abdominal mass, his fever improved. [ABSTRACT FROM AUTHOR]

Background: Studies on factors which may predict the risk of diabetes are scarce. This prospective cohort study was conducted to determine the association between adiponectin and type 2 diabetes among Korean men and women. Methods: A total of 42,845 participants who visited one of seven health examination centers located in Seoul and Gyeonggi province, Republic of Korea between 2004 and 2008 were included in this study. The incidence rates of diabetes were determined through December 2011. To evaluate the effects of adiponectin on type 2 diabetes, the Cox proportional hazard model was used. Results: Of the 40,005 participants, 959 developed type 2 diabetes during a 6-year follow-up. After the adjustment for age, body mass. index (BMI), and waist circumference, the risks for type 2 diabetes in participants with normoglycemia had a 1.70-fold (95% confidence interval [CI], 1.21 to 2.38) increase in men and a 1.83-fold (95% CI, 1.17 to 2.86) increase in women with the lowest tertile of adiponectin when compared to the highest tertile of adiponectin. For participants with impaired fasting glucose (IFG), the risk for type 2 diabetes had a 1.46-fold (95% CI, 1.17 to 1.83) increase in men and a 2.52-fold (95% CI, 1.57 to 4.06) increase in women with the lowest tertile of adiponectin. Except for female participants with normoglycemia, all the risks remained significant after the adjustment for fasting glucose and other confounding variables. Surprisingly, BMI and waist circumference were not predictors of type 2 diabetes in menor women with IFG after adjustment for fasting glucose and other confounders. Conclusion: A strong association between adiponectin and diabetes was observed. The use of adiponectin as a predictor of type 2 diabetes is considered to be useful. [ABSTRACT FROM AUTHOR]

There are many studies on the prevalence, clinical characteristics, and economic burden of diabetes across the past four decades in Korea. Nonetheless, there is a dearth of nationwide study regarding diabetes encompassing all age group. Eight years ago, the Committee on the Epidemiology of Diabetes Mellitus of Korean Diabetes Association collaborated with Health Insurance Review & Assessment Service to evaluate the status of diabetes care and characteristics in diabetic patients in Korea. In 2007, the collaborative task force team published a comprehensive survey titled "Diabetes in Korea 2007." In this review, we reappraise the diabetic epidemics from the joint report and suggest further studies that are needed to be investigated in the future. [ABSTRACT FROM AUTHOR]

Beyond statin therapy for reducing low density lipoprotein cholesterol (LDL-C), additional therapeutic strategies are required to achieve more optimal reduction in cardiovascular risk among diabetic patients with dyslipidemia. To evaluate the effects and the safety of combined treatment with omega-3 fatty acids and statin in dyslipidemic patients with type 2 diabetes, we conducted a randomized, open-label study in Korea. Patients with persistent hypertriglyceridemia (≥200 mg/dL) while taking statin for at least 6 weeks were eligible. Fifty-one patients were randomized to receive either omega-3 fatty acid 4, 2 g, or no drug for 8 weeks while continuing statin therapy. After 8 weeks of treatment, the mean percentage change of low density lipoprotein (LDL) particle size and triglyceride (TG) level was greater in patients who were prescribed 4 g of omega-3 fatty acid with statin than in patients receiving statin monotherapy (2.8%±3.1% vs. 2.3%±3.6%, P=0.024; -41.0%±24.1% vs. -24.2%±31.9%, P= 0.049). Coadministration of omega-3 fatty acids with statin increased LDL particle size and decreased TG level in dyslipidemic patients with type 2 diabetes. The therapy was well tolerated without significant adverse effects. [ABSTRACT FROM AUTHOR]

Background: The relationship between body composition parameters such as thigh and calf circumference and insulin resistance or atherosclerosis in type 2 diabetes is poorly understood. The aim of this study was to investigate the relationship between insulin resistance, atherosclerosis, and thigh and calf circumference in patients with type 2 diabetes. Methods: A total of 4,427 subjects with type 2 diabetes were enrolled in this study. Insulin sensitivity was assessed according the rate constant for plasma glucose disappearance (Kitt) determined via the short insulin tolerance test. Biochemical and anthropometric profiles were measured according to a standardized protocol. Visceral fat thickness and carotid intima media thickness (IMT) were measured by ultrasonography. Results: Insulin sensitivity index (Kitt) was significantly correlated with weight adjusted thigh and calf circumference. Thigh circumference was inversely associated with IMT in men and women and calf circumference was negatively correlated with IMT in women. Multiple stepwise regression analysis revealed that thigh circumference was independently correlated with insulin sensitivity index (Kitt) and IMT. Furthermore, in multivariate logistic regression analysis, thigh circumference was an independent determinant factor for carotid atherosclerosis in patients with type 2 diabetes even after adjusting for other cardiovascular risk factors. Conclusions: Thigh and calf circumference were correlated with insulin resistance and carotid atherosclerosis, and thigh circumference was independently associated with insulin resistance and carotid atherosclerosis in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

The inflammatory marker, C-reactive protein (CRP) is associated with long-term cardiovascular events. The aim of the study was to investigate the factors contributing to serum CRP, assess the relationship between CRP level and the parameters of visceral obesity, and examine the association between leptin and CRP level in type 2 diabetic patients. 150 patients with type 2 diabetes were enrolled. These patients were recently diagnosed (≤3 years) with type 2 diabetes and were drug naive or taking sulfonylureas only. BMI, WC, and serum concentration of CRP, glycosylated hemoglobin (HbA1c), glucose, lipids, plasminogen activator-1 (PAI-1) and leptin were measured. Insulin resistance was estimated by the insulin resistance index of homeostasis model assessment (HOMA-IR). We measured the carotid intima-media thickness (IMT). Fat mass assessed by dual-energy X-ray absorptionmetry and abdominal fat distribution was determined by CT scan. Serum concentration of CRP was significantly correlated with BMI ( γ = 0.257, P < 0.01), WC ( γ = 0.293, P < 0.01), fat mass ( γ = 0.213, P < 0.01), total adipose tissue ( γ = 0.263, P < 0.01), visceral adipose tissue ( γ = 0.296, P < 0.01), insulin ( γ = 0.189, P = 0.047), PAI-1 ( γ = 0.206, P < 0.01), leptin ( γ = 0.322, P < 0.01), mean IMT ( γ = 0.132, P = 0.042), and HOMA-IR ( γ = 0.172, P = 0.045). After adjustment for age and gender, multiple regression analysis showed that serum CRP was significantly associated with leptin ( β = 0.326, P = 0.01) and visceral adipose tissue ( β = 0.265, P = 0.035). In conclusion, serum CRP level is significantly associated with obesity, especially the visceral adipose tissue, and serum leptin is another important independent factor associated with CRP in Korean type 2 diabetic patients. [ABSTRACT FROM AUTHOR]

Objective Dyslipidaemia is a well-known manifestation of thyroid dysfunction. Recently, small low-density lipoprotein (LDL) particle size has been linked with development of cardiovascular disease. To better understand the effects of thyroid dysfunction on the development of cardiovascular disease, we examined LDL particle size and lipid profiles in subjects with different thyroid function. Methods Included were 46 patients with overt hypothyroidism, 57 patients with subclinical hypothyroidism, 46 patients with overt hyperthyroidism, 51 patients with subclinical hyperthyroidism, and 110 age- and sex-matched healthy control subjects. We measured LDL particle size and lipid profiles in these subjects. Results No significant differences were found in LDL particle size between the groups with different thyroid function. Serum total cholesterol and LDL-cholesterol levels were significantly higher in the cases of hypothyroidism than in the cases of hyperthyroidism and the healthy control subjects. Serum triglyceride levels were higher in subjects with overt hypothyroidism than in those with overt hyperthyroidism or healthy control subjects. Conclusions LDL particle size, the emerging risk factor for atherosclerosis, did not appear to be significantly affected by the degree of thyroid dysfunction. Increased risk of atherosclerosis in hypothyroidism does not appear to be associated with LDL particle size, the non-traditional cardiovascular risk factor. [ABSTRACT FROM AUTHOR]

Objective The current consensus algorithm for management of type 2 diabetes is based on the fasting glucose concentration and glycated haemoglobin A1c (HbA1c) level. We applied a new therapeutic strategy by assessing insulin secretion and insulin resistance, in addition to glucose concentrations in individual patients. Design and patients We enrolled 193 patients with type 2 diabetes. The patients were assigned to one of six groups according to insulin secretion measured by the serum fasting C-peptide concentration and insulin resistance measured by an insulin tolerance test (ITT). The two groups were treated differently: 108 patients were treated using a new staged diabetes management (SDM) strategy and 85 patients continued with conventional therapy. Measurements We compared metabolic variables in the two groups at baseline and 12 months after enrolment. Results In patients treated with the SDM strategy, fasting glucose concentration decreased from 9·8 ± 2·1 to 8·2 ± 1·7 mmol/l ( P < 0·001). Postprandial 2-h glucose concentration decreased from 14·19 ± 3·34 to 12·27 ± 3·24 mmol/l ( P < 0·001). HbA1c level decreased from 8·37 ± 1·42% to 7·72 ± 1·39% ( P < 0·001). About 43% of the new SDM group achieved an HbA1c of < 7·0% compared with 25% of patients in the conventional treatment group. Conclusions The new SDM strategy, based on individual data on insulin resistance and insulin secretion, may provide valuable clinical benefits in non-obese Korean patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominantly inherited syndrome. MEN1 is characterized by the presence of functioning and nonfunctioning tumors or hyperplasia of the pituitary gland, parathyroid glands, and pancreatic islet cells. In addition, MEN1 carriers can have adrenal or thyroid tumors and non-endocrine tumors, such as lipomas, angiofibromas, and leiomyomas. Although leiomyoma is not a major component of MEN1, it is thought to occur more frequently than expected. However, there has been no report of a case of MEN1 with leiomyoma in Korea so far. This report describes a patient with multiple leiomyomas in MEN1. A 50-year-old woman was referred for further evaluation of elevated calcium levels and osteoporosis. Biochemical abnormalities included hypercalcemia with elevated parathyroid hormone. There was hyperprolactinemia with pituitary microadenoma in sella MRI. An abdominal MRI demonstrated adrenal nodules and leiomyomas in the bladder and uterus. Endoscopic ultrasonography demonstrated esophageal leiomyoma and pancreatic islet cell tumor. A subtotal parathyroidectomy with thymectomy was performed. Sequencing of the MEN1 gene in this patient revealed a novel missense mutation (D350V, exon 7). This is the first case of MEN1 accompanied with multiple leiomyomas, parathyroid adenoma, pituitary adenoma, pancreatic tumor, and adrenal tumor. [ABSTRACT FROM AUTHOR]

OBJECTIVE--Posttransplantation diabetes mellitus (PTDM) is a major metabolic complication in renal transplant recipients, and insulin secretory defects play an important role in the pathogenesis of PTDM. The R325W (rs13266634) nonsynonymous polymorphism in the islet-specific zinc transporter protein gene, SLC30A8, has been reported to be associated with type 2 diabetes and possibly with a defect in insulin secretion. This study investigated the association between genetic variations in the SLC30A8 gene and PTDM in renal allograft recipients. RESEARCH DESIGN AND METHODS--A total of 624 unrelated renal allograft recipients without previously diagnosed diabetes were enrolled. Rs13266634 was genotyped in the cohort, which consisted of 174 posttransplantation diabetic patients and 450 non-posttransplantation diabetic subjects. The genotyping of the SLC30A8 polymorphism was performed using real-time PCR. RESULTS--The prevalence of PTDM was 33.8% in patients carrying the R/R genotype, 26.8% in patients with the R/W genotype, and 19.8% in patients with the W/W genotype. There was a strong association between the number of W-alleles and PTDM risk reduction (P for trend = 0.007). Patients with at least one T-allele showed a decreased risk of PTDM compared with those with the R/R genotype (R/W, risk ratio [RR] 0.78, P = 0.126; W/W, RR 0.52, P = 0.007). The effect of the SLC30A8 genotype remained significant after adjustments for age, sex, body weight gain, and type of immunosuppressant (R/W, hazard ratio [HR] 0.77, P = 0.114; W/W, HR 0.58, P = 0.026). CONCLUSIONS--These data provide evidence that the SLC30A8 rs13266634 gene variation is associated with protection from the development of PTDM in renal allograft recipients. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- Posttransplantation diabetes mellitus (PTDM) is a major complication associated with kidney transplantation. Defects in insulin secretion play a pivotal role in the pathogenesis of PTDM. A polymorphism in the transcription factor 7-like 2 (TCF7L2) gene was reported to be associated with type 2 diabetes and possibly associated with an insulin secretion defect. The aim of this study was to investigate the association between genetic variations in TCF7L2 and PTDM in renal allograft recipients. RESEARCH DESIGN AND METHODS-- A total of 511 unrelated renal allograft recipients without previously known diabetes were enrolled. Six single nucleotide polymorphisms (rs11196205, rs4506565, rs12243326, rs7903146, rs12255372, and rs7901695) were genotyped in the cohort, which consisted of 119 PTDM patients and 392 non-PTDM subjects. The genotyping of TCF7L2 polyrnorphisms was performed using real-time PCR. RESULTS-- rs4506565, rs7901695, and rs7903146 were found to be in complete linkage disequilibrium. The rs7903146 genotype distribution was CC 94.3% and CT 5.7%. The incidence of PTDM was significantly higher in patients with the CT genotype than in patients with the CC genotype (41.4 vs. 22.2%) (odds ratio 2.474 [95% CI 1.146-5.341]; P = 0.024). The effect of this genotype remains significant after adjustment for age, sex, amount of body weight gain, and type of immunosuppressant (2.655 [1.168-6.038]; P = 0.020). CONCLUSIONS-- These data suggest that the TCF7L2 rs7903146 genetic variation is associated with an increased risk of PTDM in renal allograft recipients. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to observe the changes in bone and mineral metabolism and to confirm the regulation of fibroblast growth factor-23 (FGF-23) in untreated Graves’ disease. Patients and measurements The study comprised 39 patients, with or without Graves’ disease. The Graves’ disease group was made up of 21 newly diagnosed patients, enrolled before starting treatment. Their disease was determined by biochemical and radiological means. The control group was composed of 18 people who were proven to be euthyroid without any diseases affecting bone and mineral metabolism. FGF-23, calcium, phosphate, PTH, 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] levels and bone turnover markers were compared between these groups. Results Serum calcium and phosphate, plasma FGF-23 and free T4 were significantly higher in the Graves’ disease group than in the healthy control group ( P < 0·05). The bone turnover markers serum osteocalcin and C-terminal cross-linked telopeptide of type 1 collagen (s-CTx) were also significantly elevated in the Graves’ disease group, and had a positive correlation with free T4 levels. However, there was no significant decrease in PTH and 1,25(OH)2D in the Graves’ disease group. Plasma levels of FGF-23 exhibited a positive correlation with serum phosphate levels and with free T4 levels ( P < 0·05). Conclusions These findings suggest that FGF-23 is physiologically related to serum phosphate homeostasis, as indicated indirectly by the changes in bone and mineral metabolism, in untreated Graves’ disease. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- The aim of this study was to assess the incidence of posttransplantation diabetes mellitus (PTDM) in renal allograft recipients and to investigate factors contributing to the onset and progression of PTDM and its underlying pathogenic mechanism(s). RESEARCH DESIGN AND METHODS -- A total of 77 patients with normal glucose tolerance (NGT) were enrolled in this study. An oral glucose tolerance test was performed 1 week before transplantation and repeated at 1 and 7 years after transplantation. RESULTS -- The overall incidence of PTDM was 39% at 1 year and 35.1% at 7 years posttransplantation. The incidence for each category of PTDM was as follows: persistent PTDM (P-PTDM) (patients who developed diabetes mellitus within 1 year of transplantation and remained diabetic during 7 years), 23.4%; transient PTDM (T-PTDM) (patients who developed diabetes mellitus during the 1st year after transplantation but eventually recovered to have NGT), 15.6%; late PTDM (L-PTDM) (patients who developed diabetes mellitus later than 1 year after transplantation), 11.7%; and non-PTDM during 7 years (N-PTDM7) (patients who did not develop diabetes mellitus during 7 years), 49.3%. Older age (≥40 years) at transplantation was a higher risk factor for P-PTDM, whereas a high BMI (≥25 kg/m²) and impaired fasting glucose (IFG) at 1 year posttransplantation were higher risk factors for L-PTDM. Impaired insulin secretion rather than insulin resistance was significantly associated with the development of P-and L-PTDM. CONCLUSIONS -- Impaired insulin secretion may be the main mechanism for the development of PTDM. Older age at transplantation seems to be associated with P-PTDM, whereas a high BMI and IFG at 1 year after transplantation were associated with L-PTDM. [ABSTRACT FROM AUTHOR]

Objective Although rosiglitazone, an insulin sensitizer, is known to have beneficial effects on high density lipoprotein cholesterol (HDL-C) concentrations and low density lipoprotein (LDL) particle size, it has unwanted effects on total cholesterol (TC) and LDL cholesterol (LDL-C) concentrations and body weight in some short-term studies. The aim of this study was to evaluate the long-term effects of rosiglitazone on serum lipid levels and body weight. Design Open labelled clinical study. Patients and measurements We prospectively evaluated fasting serum glucose, haemoglobin A1c (HbA1c), lipid profiles and body weight at baseline and every 3 months after the use of rosiglitazone (4 mg/day) for 18 months in 202 type 2 diabetic patients. Results TC levels increased maximally at 3 months and decreased thereafter. However, overall, TC levels remained significantly higher at 18 months than those at baseline. LDL-C levels from the 3-month to the 12-month timepoint were significantly higher than those at baseline. However, after 15 months, LDL-C concentrations were not significantly different from basal LDL-C concentrations. HDL-C levels increased after the first 3 months and these levels were maintained. The increment of change in HDL-C was more prominent in patients with low basal HDL-C concentrations than in patients with high basal HDL-C concentrations. Body weight increased after the first 3 months and these levels were maintained. Conclusions HDL-C and body weight increased and remained elevated for the duration of the study. There was an initial increase in LDL-C but this attenuated and by the end of the study was not significantly elevated above baseline levels. [ABSTRACT FROM AUTHOR]

Genetic variations in the Calpain-10 gene, CAPN10, have been reported to be associated with the risk of type 2 diabetes mellitus (T2DM) in Mexican-Americans and Northern Europeans whereas these variations are not associated with T2DM in other populations. The aim of this study was to determine whether there is an association between specific CAPN10 diplotype (SNP-43, -19, and -63) and T2DM in the Korean population. Overall, 454 Korean patients with T2DM (male 230, female 224) and 236 non-diabetic controls (male 124, female 112) with no family history of diabetes were enrolled in this study. All the subjects were genotyped according to CAPN10 SNP-43, -19, and -63. The restriction fragment length polymorphism method was used for the three SNPs. There were eight estimated haplotype allelic variations. After adjusting for gender and age, the 111 haplotype was associated with a high risk of T2DM ( P <0.0001). The 111/121 diplotype was associated with a high risk of T2DM (odds ratio =2.580, 95% confidence interval =1.602–4.155, P =0.001). The high-risk haplotype (112/121) in Mexican-Americans was not significant in our study population. In conclusion, we found that a novel 111/121 diplotype in Calpain-10 gene is associated with T2DM in the Korean population. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- The aim of this study was to examine the effects of perilipin gene (PLIN) polymorphisms on weight gain with rosiglitazone treatment in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS -- A total of 160 type 2 diabetic patients were treated with rosiglitazone (4 mg/day) for 12 weeks in addition to their previous medications, which were unchanged. Four single nucleotide polymorphisms (SNPs) at the PLIN locus were genotyped: PLIN 6209T>C, PLIN 11482G>A, PLIN 13041A>G, and PLIN 14995A>T. RESULTS -- Although fasting plasma glucose and HbA1c levels decreased; mean body weight increased significantly after rosiglitazone treatment. Among the four SNPs tested, only the PLIN 11482G>A polymorphism was associated with weight gain from rosiglitazone treatment. In addition, there was a significant difference in the increase in the body weight among the genotypes. Patients with the 11482A/A genotype showed less increase in body weight than those with other genotypes. CONCLUSIONS -- These data suggest that genetic variations in the perilipin gene can affect weight gain associated with rosiglitazone treatment in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aims: To assess the efficacy of rosiglitazone in blocking ethanol-induced hangover in rats. Methods: Rats injected with ethanol (4 g/kg body weight) were subjected to social interaction tests. Levels of aldehyde dehydrogenase 2 (ALD2), involved in an anti-hangover mechanism, were measured by semi-quantitative RT-PCR and western blot analysis. Results: Rosiglitazone caused an upregulation of mitochondrial ALD2, thus significantly detoxifying acetaldehyde. Conclusions: Rosiglitazone alleviated the symptoms of ethanol-induced hangover by inducing ALD2 expression; this result was reconfirmed by eliminating the effect of rosiglitazone by injecting cyanamide, an ALD2 inhibitor. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- Despite the popularity of coronary stenting in coronary artery disease (CAD), restenosis remains a challenging clinical problem. This study evaluated the efficacy of rosiglitazone for preventing in-stent restenosis in type 2 diabetic patients. RESEARCH DESIGN AND METHODS -- We conducted a prospective, randomized, case-controlled trial involving 95 diabetic patients with CAD who were randomly assigned to either the control or rosigtitazone group (48 and 47 patients, respectively). Quantitative coronary angiography (QCA) was performed at study entry and again at 6-month follow-up. The primary end point was the restenosis rate, which was determined by QCA. RESULTS -- Eighty-three patients (45 patients with 55 lesions in the control group and 38 patients with 51 lesions in the rosiglitazone group) completed follow-up angiography. Rosiglitazone treatment for 6 months reduced fasting insulin concentration. The high-sensitivity C-reactive protein concentration was significantly reduced in the rosiglitazone group compared with that in the control group (from 2.92 ± 1.98 to 0.62 ± 0.44 mg/l, P < 0.001 vs. from 2.01 ± 1.33 to 1.79 ± 1.22 mg/l, P = NS). However, the baseline and follow-up glucose and lipid concentrations were not different between two groups. The rate of in-stent restenosis was significantly reduced in the rosiglitazone group compared with the control group (for stent lesions: 17.6 vs. 38.2%, P = 0.030). The rosiglitazone group had a significantly lower degree of diameter stenosis (23.0 ± 23.4% vs. 40.9 ± 31.9%, P = 0.004) compared with the control group. CONCLUSIONS -- We demonstrated that treatment with rosiglitazone significantly reduces in-stent restenosis in diabetic patients with CAD who underwent coronary stent implantation. [ABSTRACT FROM AUTHOR]

Background: Visceral obesity is closely associated with cardiovascular disease and the metabolic syndrome. Estimating the amount of visceral fat is important and requires a straightforward, reliable, and practical method. Objective: We investigated whether visceral fat thickness (VFT) measured by ultrasonography can adequately assess visceral fat accumulation and predict cardiovascular or metabolic diseases. Design: Diabetic patients (240 men and 106 women) underwent ultrasonography to estimate visceral fat accumulation. Results: The visceral adipose tissue area had the best correlation with VFT (r = 0.799, P < 0.001). VFT correlated with HDL cholesterol, triacylglycerol, and high-sensitivity C-reactive protein concentrations, the homeostasis model assessment for insulin resistance, and the intima-media thickness at the common carotid artery (r= -0.30, 0.39, 0.34, 0.31, and 0.33, respectively; P < 0.05) in men and with triacylglycerol and high-sensitivity C-reactive protein concentrations and the homeostasis model assessment for insulin resistance (r = 0.33, 0.44, and 0.30, respectively; P < 0.05) in women. Men in the middle and high VFT tertiles had a higher odds ratio (OR) of coronary artery disease [ORs: 4.48 (95% CI: 1.29, 5.51) and 2.04 (1.06, 3.94), respectively; P = 0.016], hypertriacylglycerolemia [ORs: 2.87 (1.41, 5.86) and 1.91 (1.24, 2.95), respectively; P < 0.003], and the metabolic syndrome [ORs: 3.38 (1.61, 7.10) and 1.95 (1.16, 3.27), respectively; P = 0.003] than did those in the low tertile, after adjustment for age, waist circumference, and body mass index. Conclusion: VFT might be a reliable index for assessing the amount of visceral fat and for identifying diabetic patients, particularly men, who are at high risk of cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background: Guidelines for switching to triple combination therapy directly after monotherapy failure are limited. This study investigated the efficacy, long-term sustainability, and safety of either mono or dual add-on therapy using alogliptin and pioglitazone for patients with type 2 diabetes mellitus (T2DM) who did not achieve their target glycemic range with metformin monotherapy. Methods: The Practical Evidence of Antidiabetic Combination Therapy in Korea (PEAK) was a multicenter, placebo-controlled, double-blind, randomized trial. A total of 214 participants were randomized to receive alogliptin+pioglitazone (Alo+Pio group, n=70), alogliptin (Alo group, n=75), or pioglitazone (Pio group, n=69). The primary outcome was the difference in glycosylated hemoglobin (HbA1c) levels between the three groups at baseline to 24 weeks. For durability, the achievement of HbA1c levels <7% and <6.5% was compared in each group. The number of adverse events was investigated for safety. Results: After 24 weeks of treatment, the change of HbA1c in the Alo+Pio, Alo, and Pio groups were --1.38%±0.08%, -1.03%±0.08%, and -0.84%±0.08%, respectively. The Alo+Pio group had significantly lower HbA1c levels than the other groups (P=0.0063, P< 0.0001) and had a higher proportion of patients with target HbA1c achievement. In addition, insulin sensitivity and β-cell function, lipid profiles, and other metabolic indicators were also improved. There were no significant safety issues in patients treated with triple combination therapy. Conclusion: Early combination triple therapy showed better efficacy and durability than the single add-on (dual) therapy. Therefore, combination therapy with metformin, alogliptin, and pioglitazone is a valuable early treatment option for T2DM poorly controlled with metformin monotherapy. [ABSTRACT FROM AUTHOR]

OBJECTIVE--This study was conducted to investigate the association of diabetic peripheral neuropathy (DPN) with both arterial stiffness and intima-media thickness (IMT). RESEARCH DESIGN AND METHODS--We conducted a cross-sectional analysis of 731 subjects with type 2 diabetes. DPN was diagnosed on the basis of neuropathic symptoms, insensitivity to a 10-g monofilament, abnormal pin-prick sensation, and abnormal current perception threshold. Arterial stiffness was assessed by cardio-ankle vascular index (CAVI), and IMT was assessed by B-mode ultrasonography. RESULTS--Patients with DPN had higher CAVI than those without DPN in multivariateadjusted models, whereas no differences in IMT were observed between patients with and without DPN after adjustment for age and sex. In the multivariate analysis, CAVI was a significant determinant of DPN (odds ratio 1.36 [95% CI 1.13-1.65], P = 0.001). CONCLUSIONS--DPN is significantly associated with arterial stiffness without carotid intimal changes in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Lipin1 protein is required for normal adipose tissue development and metabolism. Lipin1 is a product of LPIN1 gene (MIM605518) which has been mapped at chromosomes 2p21. Lipin1 deficiency results in the development of immature adipocytes in fatty liver dystrophy in mice and in lipodystrophy in human. Recently, pioglitazone is reported to increase adipocyte lipin1 expression in human. In this study, we evaluate the effects of LPIN polymorphisms on rosiglitazone response in patients with type 2 diabetes (T2DM). A total of 152 T2DM patients were treated with rosiglitazone (4 mg/day) for 12 weeks in addition to their previous medications, which were unchanged. Six single nucleotide polymorphisms (SNPs) at the LPIN1 locus were genotyped: SNP2 (rs11693809, T/C), SNP3 (rs10192566, C/G), SNP4 (rs2278513, T/C), SNP5 (rs2577262, G/A), SNP6 (rs2716610, C/T), and SNP7 (rs1050800, C/T). SNP2, SNP3, and SNP4 are in nearly complete linkage (D' >0.958, r²>0.882). Among the six SNPs tested, only the LPIN SNP3 C/G polymorphism was significantly associated with rosiglitazone treatment response. Patients with G allele in SNP3 showed larger degree of HbA1c decrease with rosiglitazone treatment than those without G allele (1.147 vs. 0.635, p=0.013). Haplotypes were constructed by these 6 SNPS. Haplotype frequencies were 79.234% for TCTXXX and 18.664% for CGCXXX. Patients with CGCXXX haplotype were associated with high amount of HbA1c decrease with rosiglitazone (p=0.014). These data suggest that genetic variations in the LPIN1 gene can affect rosiglitazone treatment response in patients with T2DM. [ABSTRACT FROM AUTHOR]

A measure of insulin resistance is routinely evaluated as the rate constant for plasma glucose disappearance. The purpose of this study was to develop a mixed effect model approach to estimate insulin resistance that can be applied to sparsely-sampled plasma glucose data. Data were taken from 1516 subjects who took an insulin tolerance test. Blood samples were collected at 3, 6, 9, 12, 15 min after intravenous injection of insulin with a dose of 0.1U/kg. Plasma glucose concentrations were analyzed by the glucose oxidase method. A one-compartment pharmacokinetic model consisting of the plasma glucose disappearance rate constant (K) and the baseline plasma glucose concentration (CO) was used incorporating clinical covariates to describe the time course of glucose, within the context of mixed effect model framework. Validity of the model was tested by internal validation. Based on the model so derived, a set of sparse sample times that best describes the original glucose kinetics was determined from the combinations of the 5 sample times. Estimated population means for K and C0 were 0.0362min[sup -1] and 4.8769mmol/L with interindividual variability of 41.71% and 4.83% in CV, respectively. Important covariates found were age, sex and clinical status for K, while C0 dependent only on clinical status. The weighted residuals (WRES) obtained from NONMEM lied approximately within -3 and 3 with a mean of about zero, indicating no bias for the model. For a sparse sample design, a set of samples at 3, 6, and 15 min allowed best prediction of plasma glucose concentration, with no noticeable deviation in the estimate of K. This work suggests the feasibility of applying a sparse-sample design approach to assessing insulin resistance. The classical approach such as the glucose clamp test may be necessary to further validate the accuracy of the model suggested. [ABSTRACT FROM AUTHOR]

Rosiglitazone, a peroxisome proliferator activated receptor (PPAR)-γagonist and originally developed as an anti-diabetic agent, have been known to have a protective effect against alcoholic toxicity in patients with non-alcoholic fatty liver. To investigate the underlying mechanisms of this protective effects of rosiglitazone, several in vitro experiments including the measurement of cell viability, mitochondrial aldehyde dehydrogenase (ALD2) expression, antioxidant enzymes activities, the mitochondrial apoptotic cascades and in vivo experiments including histopathologic examinations of liver by hematoxylin & eosin and TUNEL staining and blood chemistry were performed. We found that ALD2 and anti-oxidant enzymes expressions were inhibited by 72 and 40% compared with control in HepG2 cells under hyperlipidemic condition, and rosiglitazone reversed the expression of these genes. Sole acetaldehyde and acetaldehyde-free fatty acids (FFAs) impaired both ALD2 (81 and 51% compared with control) and anti-oxidant enzymes (50 and 30% compared with control) expressions. However, these conditions were reversed by rosiglitazone treatment indicating that rosiglitazone may regulate ALD2 and anti-oxidant enzymes in HepG2 cells. It also prevented apoptotic cascades including Bax and Bcl-2 ratio, cytochrome c release, and caspase-3 activation. In in vivo experiment, we found that high fat diet and alcohol-induced aspartate aminotransferase, alanine aminotransferase, triglycerides, free fatty acids, and total bilirubin were significantly decreased and hepatic apoptosis was prevented by rosiglitazone treatment. Finally, we propose that rosiglitazone treatment may provide therapeutic strategy for the prevention of alcohol toxicity in non-alcoholic fatty liver via recovery of ALD2 and anti-oxidant enzymes. [ABSTRACT FROM AUTHOR]

For decades, exercise has been considered a cornerstone of diabetes managements, along with diet and medication. Many studies have shown that regular physical activity improves quality of life, reduces the risk of mortality from all causes, and is particularly advantageous in subjects with impaired glucose tolerance or type 2 diabetes mellitus. However, high-quality evidence and basic data on the importance of exercise and physical fitness in Korean diabetic patients were lacking until recent years. This study included 240 diabetic patients (122 men, 118 women) recruited from 6 diabetic centers in Korea. To measure step length and walking velocity at normal walking speed, we made the patient walk 12 meter at normal speed. The patients wore the pedometer for 7 days and we got the equation between the walking steps per day and calorie expenditure for 7 days. From the equation, we calculated appropriate steps, distance and duration of Walking in type 2 diabetic patients as exercise program. The step length was determined by height, age, and gender. In men, the walking velocity was 4.4 ± 0.6 km/h and step length was 67.6 ± 7.3 cm at normal walking speed. In women, the walking velocity was 4.0 ± 0.6 km/h and step length was 58.4 ± 5.5 cm at normal walking speed. The equation between kcal per week and steps per day was that kcal/week = (steps/day) x 0.263 + 9.775 (R²=0.865, p<0.01) in men and kcal/week in women = (steps/day) x 0.263 + 9.775 (R²=0.865, p<0.01). The walking steps/day, distance and duration which correspond to 700 kcal/week was 2373 steps/day, 21.9 min and 1604 meter in men, and 2887 steps/day, 25.3 min and 1690 meter in women at normal walking speed. To exert at least 700 kcal/week with exercise, it is recommended that type 2 diabetic patients walk at least 25 min/day or 1700 meter/day or 2500 steps/day in men and 30 min/day or 1800 meter/day or 3000 steps/day in women at normal walking speed. [ABSTRACT FROM AUTHOR]

Sex hormone-binding globulin (SHBG) are down-regulated by insulin and could serve as potential indicators of the metabolic syndrome and hyperinsulinemia-related cardiovascular risk. The purpose of this study was to investigate the relationship between serum SHBG and vascular endothelial dysfunction in type 2 diabetic patients. The study subjects included 31 newly diagnosed type 2 diabetic patients (age 29-70, mean age 50±10.0, 61.3% male). There was no patient taking any drugs that could affect glucose metabolism and endothelial function. Serum SHBG concentration was measured by radioimmunoassay. The Flow-mediated dilatation (FMD) of brachial artery was performed to examine endothelial dysfunction. The median and mean values of SHBG were 46 and 54±27.8 nmol/L, respectively (range 12-106 nmol/L). Log[sub 10] (SHBG) was positively correlated with age (r =0.498, P <0.05) and FMD (r = 0.417, P <0.05), but negatively correlated with HOMA[sub IR] (r= - 0.516, P <0.05) and monocyte count (r = -0.369, P <0.05). In multiple regression analysis after an adjustment for age, monocyte count and HOMA[sub IR], log[sub 10](SHBG) showed significant correlation with FMD (β = 0.485, P = 0.007). This study shows that serum SHBG levels are significantly associated with endothelial function. SHBG might be a surrogate marker of both insulin resistance and endothelial dysfunction in type 2 diabetes. [ABSTRACT FROM AUTHOR]

The inflammatory marker, C-reactive protein (CRP) is associated with long-term cardiovascular events. The aim of the study was to investigate the factors contributing of serum CRP and the relationship between parameters of visceral obesity measured by CT and the CRP levels and examined the association between leptin and CRP levels in type 2 diabetic patients. One hundred and fifty patients with type 2 diabetes were enrolled. These patients were recently diagnosed (≤3 years) with type 2 diabetes and were drug naive or taking sulfonylureas only. BMI, WC, and serum concentration of CRP, glycosylated hemoglobin (HbA1c), glucose, lipids (triglycerides, HDL cholesterol, and total cholesterol), plasminogen activator-1 (PAI-1) and leptin were measured. Insulin resistance was estimated by the insulin resistance index of homeostasis model assessment (HOMA-IR). Fat mass assessed by dual-energy X-ray absorptionmetry and abdominal fat distribution was determined by computerized tomography scan. Serum concentration of CRP was significantly correlated with BMI γ=0.257, P<0.01) WC(γ=0.293, P<0.01) fat mass (gamma;=0.213, P<0.01), total adipose tissue (γ=0.263, P<0.01), visceral adipose tissue (γ=0.296, P<0.01), insulin (γ0.189, P=0.047), PAI-1 (γ=0.306, P<0.01), leptin (γ=0.322, P<0.01), HOMA-IR (γ=0.172, P=0.045). After adjustment for age and sex, multple regression analysis showed that serum CRP was significantly associated with leptin (β=0.326, P=0.01) and visceral adipose tissue (β=0.265, P=0.035). In conclusion, it can be concluded that serum CRP level is significantly associated with obesity, especially visceral adipose tissue and serum leptin are another important independent factors associated with CRP in Korean type 2 diabetic patients. [ABSTRACT FROM AUTHOR]

Background: Carotid intima-media thickness (cIMT) is a strong predictor of macrovascular disease. Pioglitazone has been reported to have antiatherogenic effect and anti-inflammatory effect. But the dose of pioglitazone in previous clinical trial was 30mg or 45 mg daily. This study was performed to assess the effect of pioglitazone 15mg, which has been commercially used dose in Korea, to carotid intima-media thickness. Method: A12 weeks, open-label, prospective, controlled clinical study was done. Patients were randomized to pioglitazone 15mg administerd group or control group. Biochemical and clinical markers was assessed including cIMT, fasting glucose, insulin, lipids, high sensitivity C-reactive protein (hsCRP), fibrinogen, and HbA1c. Result: The study was completed by 88 patients (48 pioglitazone group, 40 control group). There were no difference baseline characteristics between two groups. The average and maximal cIMT were reduced only in the pioglitazone group after 12 weeks (-0.043±0.109 vs 0.006±0.105 mm, - 0.052±0.127 vs -0.002±0.127mm; p<0.05). And fasting serum insulin, HOMA-IR, hsCRP, and triglyceride levels were improved only in pioglitazone group. Conclusions: There were a regression of cIMT, a decrease of hsCRP and an improvement of HOMA-IR after pioglitazone 15mg therapy. This result implies pioglitazone 15mg has an anti-inflammatory effect and an antiatherogenic effect too. [ABSTRACT FROM AUTHOR]

Background: This study investigated the overall status of diabetes control and screening for diabetic microvascular complications in patients with type 2 diabetes mellitus attending primary care clinics in Korea. Methods: In this cross-sectional observational study, 191 primary care clinics were randomly selected across Korea from 2015 to 2016. In total, 3,227 subjects were enrolled in the study. Results: The patients followed at the primary care clinics were relatively young, with a mean age of 61.4±11.7 years, and had a relatively short duration of diabetes (mean duration, 7.6±6.5 years). Approximately 14% of subjects had diabetic microvascular complications. However, the patients treated at the primary care clinics had suboptimal control of hemoglobin A1c levels, blood pressure, and serum lipid levels, along with a metabolic target achievement rate of 5.9% according to the Korean Diabetes Association guidelines. The screening rates for diabetic nephropathy, retinopathy, and neuropathy within the past 12 months were 28.4%, 23.3%, and 13.3%, respectively. Conclusion: The overall status of diabetes management, including the frequency of screening for microvascular complications, was suboptimal in the primary care clinics. More efforts should be made and more resources need to be allocated for primary care physicians to promote adequate healthcare delivery, which would result in stricter diabetes control and improved management of diabetic complications. [ABSTRACT FROM AUTHOR]

Background: Recently, the triglyceride glucose (TyG) index has been considered a surrogate marker of insulin resistance which is a well-known pathogenic factor in nonalcoholic fatty liver disease (NAFLD). However, few studies have investigated the relationship between the TyG index and NAFLD. Thus, we investigated the relationship between the TyG index and NAFLD and the effectiveness of the TyG index compared with the homeostasis model assessment of insulin resistance (HOMA-IR) in identifying NAFLD in Korean adults. Methods: Participants of 4,986 who underwent ultrasonography in a health promotion center were enrolled. The TyG index was calculated as ln [fasting triglycerides (mg/dL)×fasting glucose (mg/dL)/2], and HOMA-IR was estimated. NAFLD was diagnosed by ultrasonography. Results: Significant differences were observed in metabolic parameters among the quartiles of the TyG index. The prevalence of NAFLD significantly increased with increment in the TyG index. After adjusting for multiple risk factors, a logistic regression analysis was performed. When the highest and lowest quartiles of the TyG index and HOMA-IR were compared, the odds ratios for the prevalence of NAFLD were 2.94 and 1.93 (95% confidence interval, 2.32 to 3.72 and 1.43 to 2.61; both P for trend <0.01), respectively. According to the receiver operating characteristic analysis, the TyG index was superior to HOMA-IR in predicting NAFLD. Conclusion: The TyG index and prevalence of NAFLD were significantly related and the TyG index was superior to HOMA-IR in predicting NAFLD in Korean adults. [ABSTRACT FROM AUTHOR]

Islets are highly vascularized for prompt insulin secretion. Although angiopoietin-1 (Ang1) is a well-known angiogenic factor, its role in glucose homeostasis remains largely unknown. The objective of this study was to investigate whether and how Ang1 contributes to glucose homeostasis in response to metabolic challenge. We used inducible systemic Ang1 knockout (Ang1sys-/-) and β-cell-specific Ang1 knockout (Ang1β-cell-/-) mice fed a high-fat diet for 24 weeks. Although the degree of insulin sensitivity did not differ between Ang1sys-/- and Ang1sys+/+ mice, serum insulin levels were lower in Ang1sys-/- mice, resulting in significant glucose intolerance. Similar results were observed in Ang1β-cell-/- mice, suggesting a critical role of β-cell-derived Ang1 in glucose homeostasis. There were no differences in β-cell area or vasculature density, but glucose-stimulated insulin secretion was significantly decreased, and PDX-1 expression and GLUT2 localization were altered in Ang1β-cell-/- compared with Ang1β-cell+/+ mice. These effects were associated with less pericyte coverage, disorganized endothelial cell ultrastructure, and enhanced infiltration of inflammatory cells and upregulation of adhesion molecules in the islets of Ang1β-cell-/- mice. In conclusion, β-cell-derived Ang1 regulates insulin secretion and glucose homeostasis by stabilizing the blood vessels in the islet and may be a novel therapeutic target for diabetes treatment in the future. [ABSTRACT FROM AUTHOR]

Background: Genetic variations in calpain-10 and adiponectin gene are known to influence insulin secretion and resistance in type 2 diabetes mellitus. Recently, several single nucleotide polymorphisms (SNPs) in calpain-10 and adiponectin gene have been reported to be associated with type 2 diabetes and various metabolic derangements. We investigated the associations between specific calpain- 10 and adiponectin gene polymorphisms and Korean type 2 diabetes patients. Methods: Overall, 249 type 2 diabetes patients and 131 non-diabetic control subjects were enrolled in this study. All the subjects were genotyped for SNP-43 and -63 of calpain-10 gene and G276T and T45G frequencies of the adiponectin gene. The clinical characteristics and measure of glucose metabolism were compared within these genotypes. Results: Among calpain-10 polymorphisms, SNP-63 T/T were more frequent in diabetes patients, and single SNP-63 increases the susceptibility to type 2 diabetes. However, SNP-43 in calpain-10 and T45G and intron G276T in adiponectin gene were not significantly associated with diabetes, insulin resistance, nor insulin secretion. Conclusion: Variations in calpain-10, SNP-63 seems to increase the susceptibility to type 2 diabetes in Koreans while SNP-43 and adiponectin SNP-45, -276 are not associated with impaired glucose metabolism. [ABSTRACT FROM AUTHOR]

Over the past three decades, human pancreatic islet isolation and transplantation techniques have developed as a routine clinical procedure for selected patients with type 1 diabetes mellitus. However, due to the donor shortage and required chronic systemic immunosuppression, the widespread application of islet transplantation is limited. To overcome these limitations, providing a physical barrier to transplanted islet cells with encapsulating biomaterial has emerged as a promising approach to enhance engraftment and promote islet survival post-transplantation. Alginate has been considered to be a reliable biomaterial, as it enhances islet survival and does not hamper hormone secretion. Alginate-catechol (Al-CA) hydrogel was reported to provide high mechanical strength and chemical stability without deformation over a wide range of pH values. In this study, we, demonstrated, for the first time in the literature, that encapsulation of murine pancreatic islet cells with Al-CA hydrogel does not induce cytotoxicity ex vivo for an extended period; however, it does markedly abate glucose-stimulated insulin secretion. Catechol should not be considered as a constituent for alginate gelation for encapsulating islet cells in the application of islet transplantation. [ABSTRACT FROM AUTHOR]

In『 Yingshu(􃖃樞)』『, Sumun(素問)』and『 Najing(難經)』, there are differences in viewing FiveSu-point(五輸穴) and its practical application in treatment. The following conclusions are induced from these different point of views. 1. Fundamental features of FiveSu-point are shown in『Yingshu(􃖃樞)』 2. In『 Internal classic(內經)』and『 Najing(難經)』, it seems attachment that FiveSu-point is identical to the Five Elements, but there are differences in using the Five Elements sangsyang-sangguk in treatment. 3. There are clear differences between『 Internal classic(內經)』and『 Najing(難經)』in attachment of FiveSu-point and Four-seasons. Differences are shown in each chapter of『 Yingshu(􃖃樞)』. 4. Different application of FiveSu-point's various cases is shown in『 Yingshu(􃖃樞)』『, Sumun(素問)』and『 Najing(難經)』. 5. Different application of FiveSu-point in『 Yingshu(􃖃樞)』『, Sumun(素問)』and『 Najing(難經)』is due to different historical background.

Background: Pentoxifylline is a methylxanthine derivative with significant anti-inflammatory, anti-fibrotic, and anti-proliferative properties. Studies have shown that pentoxifylline may have renoprotective effects in patients with diabetic nephropathy. However, most of these studies were limited by small sample sizes. Therefore, we investigated whether pentoxifylline could reduce proteinuria in patients with diabetic nephropathy and residual proteinuria who received an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin II receptor blocker (ARB). We also studied the effects of pentoxifylline on glycemic control, insulin resistance, and inflammatory parameters. Methods: This was a prospective, randomized double-blind, placebo-controlled, multi-center study. A total of 174 patients with type 2 diabetes and albuminuria (>30 mg/g of creatinine) who were taking the recommended dosage of ACEI or ARB for > 6 months and receiving conventional therapy for diabetes were randomly assigned to receive pentoxifylline (1200 mg, daily; n = 87) or a placebo (n = 87) for 6 months. The endpoints were the effects of pentoxifylline on proteinuria, renal function, glucose control, and inflammatory parameters. Results: The percentage changes in proteinuria from baseline in the pentoxifylline and placebo groups were a decrease of 23 % and 4 %, respectively (p = 0.012). In addition, significant reductions in fasting plasma glucose, glycated hemoglobin, and insulin resistance according to the homeostasis model assessment were observed in the pentoxifylline group compared to those in the placebo group. However there was no significant difference in serum tumor necrosis factor (TNF)-α between the groups. Conclusions: Pentoxifylline therapy reduced proteinuria and improved glucose control and insulin resistance without significant change of serum TNF-α in patients with type 2 diabetic nephropathy. Therefore, pentoxifylline is a potential therapeutic alternative for treating diabetes and diabetic nephropathy. Trial registration: NCT01382303 [ABSTRACT FROM AUTHOR]

Background: We evaluated the effects of two dipeptidyl peptidase-4 (DPP-4) inhibitors, sitagliptin and vildagliptin, on metabolic parameters in patients with type 2 diabetes mellitus. Methods: A total of 170 type 2 diabetes patients treated with sitagliptin or vildagliptin for more than 24 weeks were selected The patients were separated into two groups, sitagliptin (100 mg once daily, n = 93) and vildagliptin (50 mg twice daily, n=77) We compared the effect of each DPP-4 inhibitor on metabolic parameters, including the fasting plasma glucose (FPG), postprandial glucose (PPG), glycated hemoglobin (HbAlc), and glycated albumin (GA) levels, and lipid parameters at baseline and after 24 weeks of treatment. Results: The HbAlc, FPG, and GA levels were similar between the two groups at baseline, but the sitagliptin group displayed a higher PPG level (P=0.03). After 24 weeks of treatment, all of the glucose-related parameters were significantly decreased in both groups (P=0.001). The levels of total cholesterol and triglycerides were only reduced in the vildagliptin group (P=0 001) although the sitagliptin group received a larger quantity of statins than the vildagliptin group (P=0.002).The mean change in the glucose- and lipid-related parameters after 24 weeks of treatment were not significantly different between the two groups (P=not significant). Neither sitagliptin nor vildagliptin treatment was associated with a reduction in the high sensitive C-reactive protein level (P=0.714). Conclusion: Vildagliptin and sitagliptin exert a similar effect on metabolic parameters, but vildagliptin exerts a more potent beneficial effect on lipid parameters. [ABSTRACT FROM AUTHOR]