Quality of care in patients with diabetic kidney disease in Asia: The Joint Asia Diabetes Evaluation (JADE) Registry.

AIMS: Diabetic kidney disease independently predicts cardiovascular disease and premature death. We examined the burden of chronic kidney disease (CKD, defined as an estimated GFR < 60 ml/min/1.73 m(2) ) and quality of care in a cross-sectional survey of adults (age ≥ 18 years) with Type 2 diabetes across Asia. METHODS: The Joint Asia Diabetes Evaluation programme is a disease-management programme implemented using an electronic portal that systematically captures clinical characteristics of all patients enrolled. Between July 2007 and December 2012, data on 28 110 consecutively enrolled patients (China: 3415, Hong Kong: 15 196, India: 3714, Korea: 1651, Philippines: 3364, Vietnam: 692, Taiwan: 78) were analysed. RESULTS: In this survey, 15.9% of patients had CKD, 25.0% had microalbuminuria and 12.5% had macroalbuminuria. Patients with CKD were less likely to achieve HbA1c < 53 mmol/mol (7.0%) (36.0% vs. 42.3%) and blood pressure < 130/80 mmHg (20.8% vs. 35.3%), and were more likely to have retinopathy (26.2% vs. 8.7%), sensory neuropathy (29.0% vs. 7.7%), cardiovascular disease (26.6% vs. 8.7%) and self-reported hypoglycaemia (18.9% vs. 8.2%). Despite high frequencies of albuminuria (74.8%) and dyslipidaemia (93.0%) among CKD patients, only 49.0% were using renin-angiotensin system inhibitors and 53.6% were on statins. On logistic regression, old age, male gender, tobacco use, long disease duration, high HbA1c , blood pressure and BMI, and low LDL cholesterol were independently associated with CKD (all P < 0.05). CONCLUSIONS: The poor control of risk factors, suboptimal use of organ-protective drugs and high frequencies of hypoglycaemia highlight major treatment gaps in patients with diabetic kidney disease in Asia.

Impact of treatment with saxagliptin on glycaemic stability and ß-cell function in the SAVOR-TIMI 53 study.

AIMS: To study the effects of saxagliptin, a dipeptidyl peptidase-4 inhibitor, on glycaemic stability and ß-cell function in the SAVOR-TIMI 53 trial. METHODS: We randomized 16,492 patients with type 2 diabetes (T2D) to saxagliptin or placebo, added to current antidiabetic medications, and followed them for a median of 2.1 years. Glycaemic instability was defined by: (i) a glycated haemoglobin (HbA1c) increase of ≥ 0.5% post-randomization; (ii) the initiation of new antidiabetic medications for ≥ 3 months; or (iii) an increase in dose of oral antidiabetic medication or ≥ 25% increase in insulin dose for ≥ 3 months. ß-cell function was assessed according to fasting homeostatic model 2 assessment of ß-cell function (HOMA-2ß) values at baseline and at year 2 in patients not treated with insulin. RESULTS: Compared with placebo, participants treated with saxagliptin had a reduction in the development of glycaemic instability (hazard ratio 0.71; 95% confidence interval 0.68-0.74; p < 0.0001). In participants treated with saxagliptin compared with placebo, the occurrence of an HbA1c increase of ≥ 0.5% was reduced by 35.2%; initiation of insulin was decreased by 31.7% and the increases in doses of an oral antidiabetic drug or insulin were reduced by 19.5 and 23.5%, respectively (all p < 0.0001). At 2 years, HOMA-2ß values decreased by 4.9% in participants treated with placebo, compared with an increase of 1.1% in those treated with saxagliptin (p < 0.0001). CONCLUSIONS: Saxagliptin improved glycaemia and prevented the reduction in HOMA-2ß values. Saxagliptin may reduce the usual decline in ß-cell function in T2D, thereby slowing diabetes progression.

SURF - SUrvey of Risk Factor management: first report of an international audit.

BACKGROUND: Despite the fact that subjects with established coronary heart disease (CHD) are at high risk of further events and deserve meticulous secondary prevention, current audits such as EUROASPIRE show poor control of major risk factors. Ongoing monitoring is required. We present a new risk factor audit system, SURF (Survey of Risk Factor management), that can be conducted much more quickly and easily than existing audit systems and has the potential to allow hospitals of all sizes to participate in a unified international audit system that will complement EUROASPIRE. Initial experience indicates that SURF is truly simple to undertake in an international setting, and this is illustrated with the results of a substantive pilot project conducted in Europe and Asia. METHODS: The data collection system was designed to allow rapid and easy data collection as part of routine clinic work. Consecutive patients (aged 18 and over) with established CHD attending outpatient cardiology clinics were included. Information on demographics, previous coronary medical history, smoking history, history of hypertension, dyslipidaemia or diabetes, physical activity, attendance at cardiac rehabilitation, cardiac medications, lipid and glucose levels (and HbA1c in diabetics) if available within the last year, blood pressure, heart rate, body mass index, and waist circumference were collected using a one-page data collection sheet. Years spent in full time education was added as an additional question during the pilot phase. RESULTS: Three European countries - Ireland (n = 251), Belgium (n = 122), and Croatia (n = 124) - and four Asian countries - Singapore (n = 142), Taiwan (n = 334), India (n = 97), and Korea (n = 45) - were included in the pilot study. The results of initial field testing were confirmed in that it proved possible to collect data within 60-90 seconds per subject. There was poor control of several risk factors including high levels of physical inactivity (41-45%), overweight and obesity (59-78%), and ongoing smoking (15%). There were lower levels of individuals attending cardiac rehabilitation in Asia. More Europeans than Asians reached the low-density lipoprotein cholesterol target of <2.5 mmol/l (66 vs. 59%) reflecting differences in medication usage. However, blood pressure control was superior in Asia, with 71% <140/90 compared with 66% of Europeans (NS). CONCLUSIONS: This phase of SURF has confirmed its ease of use which should allow wide participation and the collection of representative risk factor data in subjects with CHD as well as ongoing data collection to monitor secular trends in risk factor control. Notwithstanding that this is a pilot study, the results suggest that risk factor control, particularly for lifestyle-related measures, is poor in both Europe and Asia.

A young male adolescent with feminine appearance: diagnosis of 46, XX syndrome neglected for 4 years with gynaecomastia presentation.

Gynaecomastia is common in infancy and adolescent boys, but other inciting causes should be kept in mind and necessitate further evaluation should be conducted to determine any underlying conditions. A 22-year-old unmarried male adolescent visited our endocrinology clinic for feminine appearance despite operations for bilateral gynaecomastia 4 years ago. Physical examination showed inverted triangular distribution of pubic hair, sparse beard, small-sized testes, flaccid short penis and surgical scar of the chest wall. Serum hormones study revealed primary hypergonadotropic hypogonadism, and cytogenetic study disclosed female complement (46, XX). The authors recommend that sexual chromosome abnormality should be considered in patients with hypogonadism to avert androgen deficiency-related complications early and that long-term team care should be provided to improve the patient's health-related quality of life.

Acarbose improves glycemic control and reduces body weight: Subanalysis data of South Asia region.

Alpha-glucosidase inhibitors (AGIs) are widely used especially in Asian countries as a treatment option for type 2 diabetes patients with high postprandial glycaemia. However, data from South Asia region is very limited. In order to examine the effect of AGI in real-life setting, 10 PMS/NIS from all over the world from the launch of acarbose to date were pooled in one database and exploratory analysis was performed for glycemic parameters and weight. In total 62,905 patients were pooled from 21 countries and regions. Mean follow up (± SD) was 12.2 ± 4.8 weeks (range 0.1-108.9). From South Asia region (India and Pakistan), 8,738 Asian patients were enrolled. Mean PPG decreased from 240.0 and 261.1 mg/dl at baseline by 70.26 ± 65.10 and 82.96 ± 56.59 mg/dl at the last visit in total and South Asian populations, respectively (n = 53,883; n = 7,991, P < 0.0001 for both). Mean FPG decreased from 171.6 and 176.5 mg/dl at baseline by 38.48 ± 47.83 and 49.59 ± 41.41 mg/dl at the last visit in total and South Asian populations, respectively (n = 56,672; n = 7,837, P < 0.0001 for both). Mean HbA1c decreased from 8.4 and 8.4% at baseline by 1.11 ± 1.31% and 0.91 ± 0.93% at the last visit in total and South Asian populations, respectively (n = 38,843; n = 2,343, P < 0.0001 for both). Mean relative reduction of body weight (BW) was 1.40 ± 3.28% and 1.10 ± 3.39% at the last visit for mean baseline BW 73.6 and 74.2 kg in total and South Asian populations, respectively (n = 54,760; n = 7,718, P < 0.0001 for both). Consistent with RCT meta-analyses, post-hoc analysis of real-life data showed acarbose treatment improved glycaemic control and reduced the BW. Acarbose treatment in real life setting showed significant reductions in all glycemic parameters and BW in Asian patients from South Asia region.

Alpha-glucosidase inhibitor, acarbose, improves glycamic control and reduces body weight in type 2 diabetes: Findings on indian patients from the pooled data analysis.

Alpha-glucosidase inhibitors are widely used especially in Asian countries as a treatment option for type 2 diabetes patients with high postprandial glycemia (PPG). The higher carbohydrate in the Indian diets lead to greater prandial glycemic excursion, increased glucosidase, and incretin activity in the gut and may need special therapeutic strategies to tackle these glucose peaks. This is the subgroup analysis of Indian subjects who participated in the GlucoVIP study that investigated the effectiveness and tolerability of acarbose as add-on or monotherapy in a range of patients with type 2 diabetes mellitus. A total of 1996 Indian patients were included in the effectiveness analysis. After 12.5 weeks (mean), the mean change in 2-hour PPG from baseline was -74.4 mg/dl, mean HbA1c decreased by -1.0%, and mean fasting blood glucose decreased by -37.9 mg/dl. The efficacy of acarbose was rated "very good" or "good" in 91.1% of patients, and tolerability as "very good" or "good" in 88.0% of patients. The results of this observational study suggest that acarbose was effective and well tolerated in the Indian patients with T2DM.

Hypoglycaemic episodes and risk of dementia in diabetes mellitus: 7-year follow-up study.

OBJECTIVE: We investigated the risk of dementia in patients with type 2 diabetes with or without prior hypoglycaemic episodes. SUBJECTS AND SETTING: One million subjects randomly selected from the National Health Insurance Research Database, Taiwan. RESULTS: A total of 15 404 diabetic subjects without prior dementia and a mean age of 64.2 years were enrolled in the study. About 2% (n = 289) of participants had at least one episode of hypoglycaemia in a 3-year period; these subjects were older and more likely to be women and also had higher rates of insulin use and comorbidities compared to those without hypoglycaemia. During a total of 7 years of follow-up (mean and median follow-up, 3.8 and 4.8 years, respectively), 1106 patients with diabetes (7.2%) developed dementia. The incidence rate of dementia was higher in diabetic subjects with [29.9 per 1000 person-years (95% CI 22.1-39.2)] compared to those without [11.1 per 1000 person-years (95% CI 10.3-11.8)] hypoglycaemic episodes. The crude rate ratio (RR) and age- and gender-adjusted RR values for dementia were 2.76 (95% CI 2.06-3.70, P < 0.001) and 1.60 (95% CI 1.19-2.14, P = 0.002), respectively, in diabetic subjects with hypoglycaemia compared to those without hypoglycaemia. Results of Cox proportional hazards analysis revealed that hypoglycaemia, older age, female gender and insulin use were independent predictors of dementia. CONCLUSION: Adult diabetic patients with prior hypoglycaemia had a significantly increased risk of dementia. The influence of hypoglycaemic episodes on brain function warrants further investigation.

Type 2 diabetes prevalence and incidence among adults in Taiwan during 1999-2004: a national health insurance data set study.

AIM: To evaluate annual prevalence and incidence of Type 2 diabetes and to examine possible trends among adults in Taiwan. METHODS: A retrospective nationwide longitudinal study using the Taiwan National Health Insurance Research Database collected during 1999-2004. Adult patients aged > or = 20 years old with prevalent and incident Type 2 diabetes were identified using ICD-9-CM diagnostic codes. Age-specific and age-direct-standardized annual incidence and prevalence were calculated to describe their trends in different gender and age group and compared using Poisson regression. RESULTS: During the study years, the age-standardized prevalence of Type 2 diabetes increased from 4.7 to 6.5% for men and from 5.3 to 6.6% for women. The increasing trends in prevalence were significant and higher among people aged < 40 and > or = 80 years. The age-standardized incidence rates of Type 2 diabetes per 1000 person-years were approximately 7.6 and remain stable for men, but decreasing from 7.7 to 6.9 for women. However, the incidence increased significantly in younger adults aged < 40 years whose relative incidence (RI with 95% confidence interval) was 1.31 (1.20-1.42) for men and 1.04 (1.01-1.08) for women. The incidence trends for people aged > or = 40 years were decreased for men and women. The differences in incidence trends between age groups and between genders were all statistically significant (all P < 0.001). CONCLUSIONS: This study demonstrated a substantial increasing trend in Type 2 diabetes prevalence during 1999-2004 among adults in Taiwan. Despite the incidence decreased in older people, young men aged 20-40 years were most susceptible to higher incidence of Type 2 diabetes.

Use of therapeutic responses to glucose replacement to predict glucose patterns in diabetic patients presenting with severe hypoglycaemia.

OBJECTIVE: The purpose of this study was to determine whether initial serum glucose levels, therapeutic responses to intravenous glucose replacement and changes in serum glucose levels over time could predict serum glucose patterns. METHODS: The patients enrolled in this retrospective chart review had been previously diagnosed with diabetes mellitus and were later hospitalised for severe hypoglycaemia (SH). They were all admitted to the emergency department (ED) during a 4-year period between January 2003 and December 2006. Comparison of the therapeutic responses to glucose replacement according to the serum glucose patterns [categorised into recurrent hypoglycaemia (RH), overshoot hyperglycaemia (OH) and favourable groups] during the first 48 h was performed. RESULTS: Compared with the favourable group, therapeutic responses to glucose replacement were significantly lower in the RH group and higher in the OH group; the changes in serum glucose levels over time were also significantly lower in the RH group and higher in the OH group. CONCLUSION: Therapeutic responses to glucose replacement and changes in serum glucose levels over time can differentiate diabetic patients with RH and OH from those with favourable glucose patterns during the first 48 h after presentation in the ED with SH. We believe that a 'response-to-treatment' based strategy is useful in determining the ED disposition of diabetic patients presenting with SH.

Visfatin-induced expression of inflammatory mediators in human endothelial cells through the NF-kappaB pathway.

BACKGROUND: Visfatin is an adipokine that is highly expressed in visceral fat. Plasma levels of visfatin have been reported to be higher in subjects with obesity and/or type 2 diabetes mellitus. However, the role of visfatin in endothelial dysfunction has been largely unexplored. OBJECTIVES: We investigated the possible pathogenic role of visfatin in endothelial dysfunction, particularly focusing on its effect on inflammatory mediators. DESIGN: Primary human umbilical vein endothelial cells (HUVECs) pretreated with visfatin (1, 10 and 50 ng ml(-1)) were used to study the relationship between visfatin and endothelium dysfunction. Expressions of adhesion molecules (ICAM-1, VCAM-1 and E-selectin) and cytokines (interleukin (IL)-6 and IL-8) affected by visfatin were investigated by enzyme-linked immunosorbent assay, flow cytometry and real-time PCR. Activity of nuclear factor (NF)-kappaB was examined by electrophoretic mobility shift assay. RESULTS: At a visfatin concentration of 50 ng ml(-1), significant increases in IL-6, IL-8, ICAM-1, VCAM-1 and E-selectin gene expression along with increased IL-6, IL-8 and sE-selectin protein levels in the conditioned medium were detected. Flow cytometry showed that the addition of visfatin significantly increased ICAM-1 expression and VCAM-1 expression (10 and 50 ng ml(-1), respectively). Electrophoretic mobility shift assay confirmed that visfatin increased the DNA-binding activity of NF-kappaB. In addition, pretreatment with visfatin (10 and 50 ng ml(-1)) increased human monocyte cell line THP-1 adhesion to HUVECs. CONCLUSIONS: Our findings suggest that visfatin causes endothelial dysfunction by increasing inflammatory and adhesion molecule expression at least partly through the upregulation of NF-kappaB activity.

Effect of cranberry extracts on lipid profiles in subjects with Type 2 diabetes.

AIM: To examine the effect of cranberry ingestion on lipid profiles in Type 2 diabetic patients taking oral glucose-lowering drugs. METHODS: Thirty Type 2 diabetic subjects (16 males and 14 females; mean age 65 +/- 1 years) who were taking oral glucose-lowering medication regularly were enrolled in this randomized, placebo-controlled, double-blind study. Changes in lipid profiles, oxidized low-density lipoprotein (ox-LDL), glycaemic control, components of the metabolic syndrome, C-reactive protein (CRP) and urinary albumin excretion (UAE) were assessed after cranberry or placebo treatment for 12 weeks. RESULTS: Low-density lipoprotein (LDL) cholesterol decreased significantly in the cranberry group (from 3.3 +/- 0.2 to 2.9 +/- 0.2 mmol/l, P = 0.005) and the decrease was significantly greater than that in the placebo group (-0.4 +/- 0.1 vs. 0.2 +/- 0.1 mmol/l, P < 0.001). Total cholesterol and total : high-density lipoprotein (HDL) cholesterol ratio also decreased significantly (P = 0.020 and 0.044, respectively) in the cranberry group and the reductions were significantly different from those in the placebo group (P < 0.001 and P = 0.032, respectively). However, ox-LDL levels did not change significantly in response to cranberry consumption. Neither fasting glucose nor glycated haemoglobin improved in either group. Changes in components of the metabolic syndrome, UAE and CRP were not significantly different between groups. CONCLUSIONS: Cranberry supplements are effective in reducing atherosclerotic cholesterol profiles, including LDL cholesterol and total cholesterol levels, as well as total : HDL cholesterol ratio, and have a neutral effect on glycaemic control in Type 2 diabetic subjects taking oral glucose-lowering agents.

Serum testosterone level and related metabolic factors in men over 70 years old.

BACKGROUND: Sex hormone decline remarkably decreases metabolic function in elderly men. Many degenerative diseases may relate to testosterone deficiency. OBJECTIVE: To evaluate the serum testosterone concentration in elderly men, its related metabolic and inflammatory factors, and the relationship of metabolic syndrome to testosterone levels. METHODS: 381 elderly men (78.8+/-4.1 yr old) residing in a veterans' nursing home were enrolled. We measured body height and weight, waist and hip circumferences, body fat, blood pressure, blood glucose and insulin, glycosylated hemoglobin (HbA1c), lipid profile, complete blood count, high sensitivity C-reactive protein (hsCRP), total testosterone, and SHBG. Free testosterone was calculated by Nanjee-Wheeler's method. RESULTS: Serum total testosterone levels were 0.20-15.74 ng/ml (free testosterone 11.78-478.31 pmol/l). Total testosterone correlated negatively with body mass index (BMI), waist-hip ratio, body fat, blood glucose, blood insulin, HbA1c, serum triglyceride, white blood cell (WBC) count and hsCRP; but positively with HDL-cholesterol (HDL-C) and hemoglobin. Multiple regression stepwise forward analysis revealed that BMI values, fasting blood glucose, WBC count, fasting hsCRP and hemoglobin were independent factors related to total testosterone. Furthermore, total testosterone is lower in elderly men with metabolic syndrome, according to National Cholesterol Education Program criteria with a modification of waist circumference. However, free testosterone plays a small role in association with metabolic factors in this elderly men's population. CONCLUSION: Total testosterone level is significantly related to metabolic and inflammatory factors in elderly men. Low total testosterone may be a significant indicator for development of metabolic syndrome in elderly men.

Changes of brachial flow-mediated vasodilation in different ischemic stroke subtypes.

The relationship between endothelial dysfunction and stroke subtypes is unclear. We prospectively measured brachial flow-mediated vasodilation (FMD) in 143 patients with acute ischemic stroke and 40 controls. The overall stroke patients had impaired FMD, but only lacunar infarction had significantly impaired FMD vs the controls. Impaired FMD was an independent predictor for lacunar infarction. Ischemic stroke is associated with endothelial dysfunction, which is more conspicuous in lacunar infarction.

The relationships between insulin resistance and components of metabolic syndrome in Taiwanese Asians.

Metabolic syndrome (MetS) is a complicated clinicopathological entity with clustering of cardiovascular and metabolic risk factors, which includes central obesity, hypertension, dyslipidemia and glucose intolerance. There were many studies investigating a wide variety of clinical and pathophysiological aspects of this syndrome. However, the cutoffs of the components of MetS are not yet being evaluated by measured the insulin resistance (IR) directly. In this study, we enrolled 564 (male/female: 250/314) middle-aged healthy subjects. Each of the male and the female group was further divided into four subgroups (group 1 to group 4). Group 4 had the top 25 percentile of most severe IR determined by insulin suppression test. We then obtain the mean values of each component of the MetS in group 4 and compared them with the definitions of World Health Organization, National Cholesterol Education Program Adult Treatment Panel III, European Study Group of Insulin Resistance and International Diabetes Federation. The means of the blood pressure (BP) (male, 125/81; female, 125/80 mmHg) and the triglyceride (TG) (male, 1.6; female, 1.4 mmol/l) in group 4 were lower, and the fasting plasma glucose (6.2 mmol/l) was higher than the cutoffs of the other four sets of the criteria. The means of the high-density lipoprotein cholesterol (male, 0.9; female, 1.03 mmol/l) and the body mass index (male, 26.9; female 26.1 kg/m(2)) in group 4 were consistent with the cutoffs of other four groups and also the Taiwan Health Department criteria. In conclusion, we suggest to lower the cutoffs of the BP from 140/90 to 125/80 mmHg, TG from 1.7 to 1.6 mmol/l for males and 1.4 mmol/l for females for MetS definition, at least in Taiwan. This may help to early detect subjects under high risk of future coronary heart disease and diabetes. Still, these newly proposed cutoffs need larger-scale epidemiological studies to confirm.

Sibutramine improves insulin sensitivity without alteration of serum adiponectin in obese subjects with Type 2 diabetes.

AIM: To evaluate the effect of sibutramine on weight loss, insulin sensitivity and serum adiponectin levels in obese patients with Type 2 diabetes. METHODS: This study is a randomized, double-blind, placebo-controlled parallel comparison study of sibutramine 15 mg/day and placebo. Forty-eight eligible obese patients with Type 2 diabetes (age between 30 and 75 years with body mass index > or = 27 kg/m(2)) were randomly assigned to receive either placebo (n = 24) or sibutramine (15 mg/day) (n = 24) for 6 months. Fifteen subjects in each group underwent meal tests and modified insulin suppression tests before and after 6 months' treatment. RESULTS: After 6 months of sibutramine treatment statistically significant changes from baseline were observed for body weight (85.4 +/- 2.5 vs. 82.9 +/- 2.4 kg, P < 0.005) and body mass index (32.0 +/- 0.7 vs. 31.4 +/- 0.6 kg/m(2), P < 0.05) without a significant alteration of waist-hip ratio (W/H), blood pressure, heart rate, glycaemic parameters or lipid profiles. The steady-state plasma glucose (SSPG) level during the modified insulin suppression test was significantly reduced in the sibutramine group (17.33 +/- 2.92 vs. 14.29 +/- 4.19 mmol/l, P < 0.05) despite similar steady-state plasma insulin (SSPI) concentrations. In addition, serum adiponectin and C-reactive protein (CRP) levels remained unchanged, although modest weight reduction was achieved after sibutramine treatment. There were also no significant correlations between changes in serum adiponectin and reduction of SSPG or body weight. Daily ambient plasma insulin and glucose concentrations in response to a test meal were not significantly different in subjects receiving sibutramine treatment. CONCLUSIONS: We conclude that treatment with sibutramine 15 mg once daily effectively reduces weight and enhances insulin sensitivity without alteration of serum adiponectin levels in obese patients with Type 2 diabetes.

Biethnic comparisons of autosomal genomic scan for loci linked to plasma adiponectin in populations of Chinese and Japanese origin.

Adiponectin is secreted by adipocytes and is thought to have insulin-sensitizing and antiatherogenic effects. Two previous genome scans for plasma adiponectin have identified different regions for European and Pima Indian populations. We here present multipoint linkage analysis of adiponectin levels using a variance-components model for 1007 siblings (from 360 nuclear families) of Chinese origin and 352 siblings (from 147 nuclear families) of Japanese origin. We found heritability for adiponectin concentrations was 0.70 for Chinese and 0.48 for Japanese. Autosomal genome scan was performed using microsatellite markers span at an interval of approximately 10 cM. Suggestive linkage of adiponectin, after adjusting for age and sex, was found on chromosome 15 at 39 cM (maximal LOD score = 3.19, P = 6.3 x 10(-5)) for Chinese; and on chromosome 18 at 28 cM (maximal LOD score = 2.40, P = 4.4 x 10(-4)) for Japanese. There were tentative loci of weak linkage on chromosomes 3, 18, and 20 in Japanese. We provide novel loci on chromosomes 15, 18, and 20 and confirm a region on chromosome 3 as reported in Pima Indians, which may influence differentially on circulating adiponectin concentrations in Chinese and Japanese populations. Further fine mapping of these regions will help to identify the gene(s) that might affect adiponectin levels.

Increased serum soluble tumor necrosis factor receptor levels are associated with insulin resistance in liver cirrhosis.

Insulin resistance is present in nearly all patients with liver cirrhosis, but its etiology remains unclear. Recent studies have shown that tumor necrosis factor-alpha (TNF-alpha) system is involved in the insulin resistance of human obesity. Serum concentrations of TNF-alpha, and 2 soluble TNF receptors (sTNF-RI and sTNF-RII) are increased in cirrhotic patients. This study explored whether TNF-alpha system activity was associated with insulin resistance in liver cirrhosis. A total of 26 male nondiabetic patients with liver cirrhosis (mean age, 59 +/- 3 years; body mass index, 23.7 +/- 0.4 kg/m2) and 25 male control subjects (age, 65 +/- 2 years; body mass index, 24.4 +/- 0.5 kg/m2) were studied. Serum insulin, c-peptide, TNF-alpha, sTNF-RI, and sTNF-RII concentrations were determined by immunoassay. The insulin resistance was estimated by homeostasis assessment model (HOMA IR). In cirrhotic patients, serum levels of TNF-alpha, sTNF-RI, and sTNF-RII were all higher than those in the controls, and correlated with disease severity. Also, the serum c-peptide, insulin concentrations, and the HOMA IR were higher in liver cirrhosis with comparable blood glucose to control subjects, indicating a degree of insulin insensitivity. In the whole population, there was a moderate, but statistically significant, correlation between serum sTNF-RI or sTNF-RII, and HOMA IR. Also, body mass index was associated with HOMA IR, but not related to serum TNF-alpha, and sTNF-Rs levels. In multiple regression analysis, both sTNF-RII and body mass index jointly contributed to 30% variance of HOMA IR. Our study demonstrated that elevated sTNF-RII levels were associated with insulin resistance in liver cirrhosis. The data indicated that TNF-alpha system might play a role in modulating insulin action in patients with liver cirrhosis.

C-reactive protein and risk factors for peripheral vascular disease in subjects with Type 2 diabetes mellitus.

AIMS: To compare the importance of different inflammatory markers and traditional risk factors in predicting peripheral vascular disease (PVD) in patients with Type 2 diabetes mellitus. METHODS: A cross-sectional analysis of 30 Type 2 diabetic patients with PVD defined by ankle-brachial index (ABI) < 0.9, and 60 Type 2 diabetic patients without PVD (ABI > 1.0). Overnight blood was drawn and sent for study. RESULTS: Longer diabetic duration (15 +/- 8 vs. 10 +/- 7 years, P = 0.007), higher serum creatinine level (0.11 +/- 0.04 vs. 0.09 +/- 0.03 mmol/l, P = 0.001), higher total cholesterol/high-density lipoprotein-cholesterol (TC/HDL-C) ratio (5.2 +/- 1.6 vs. 4.3 +/- 1.1, P = 0.004) and increased hypertension status (70% vs. 52%, P = 0.014) and cerebral infarction (CI) history (23% vs. 3%, P = 0.009) were noted in Type 2 diabetes with PVD. Those with PVD also showed significantly higher serum levels of C-reactive protein (CRP) (median 0.282 vs. 0.102 mg/dl, P < 0.001) and interleukin (IL)-6 (10.6 +/- 1.81 vs 1.6 +/- 4.6 pg/ml, P = 0.001). Multivariate regression analysis showed that higher serum levels of C-reactive protein (CRP), longer diabetic duration, and use of angiotensin converting enzyme inhibitor (ACEI) were independently associated with PVD in Type 2 diabetes mellitus. CONCLUSIONS: Type 2 diabetic patients with PVD had longer diabetic duration, higher serum creatinine levels, higher TC/HDL-C ratio, higher hypertension and CI history and higher CRP and IL-6 levels. Only serum CRP level, diabetic duration, and use of ACEI were independently associated with PVD in Type 2 diabetes mellitus.

Sagittal abdominal diameter is associated with insulin sensitivity in Chinese hypertensive patients and their siblings.

The purpose of the study is to observe the relation between anthropometric measurements, focusing on sagittal abdominal diameter (SAD), and insulin sensitivity indices in Chinese hypertensive patients and their siblings. In total, 907 participants, 537 hypertensive and 370 nonhypertensive, from 311 Taiwanese families were drawn from the Stanford Asia and Pacific Program for Hypertension and Insulin Resistance for the study. The participants received anthropometric measurements and 75-g oral glucose tolerance tests after an overnight fast. Fasting insulin, homeostasis model assessment for insulin resistance (HOMA-IR), and the insulin sensitivity index ISI(0,120) were chosen as surrogate measures of insulin sensitivity. In addition to Pearson and partial correlations, we used generalized estimating equations (GEEs) to examine the association between anthropometric measurements and insulin sensitivity indices. A small deviance in the GEEs indicates the goodness of model fit, irrespective of the independence among variables. The hypertensive patients were older in age, wider in waist circumference (WC), larger in body mass index (BMI) and SAD, and more insulin resistant than the nonhypertensive counterparts. The logarithmic transformation of fasting insulin, HOMA-IR, and ISI(0,120) significantly correlated with SAD, WC, and BMI before and after adjustments for age and sex. The deviances of SAD in the GEEs were similar to those of WC in all subjects, while BMI had smaller deviances than SAD and WC in the hypertensive patients. Our results suggest that the performance of SAD in predicting insulin sensitivity is comparable with WC in Chinese hypertensive patients and their siblings. BMI, however, seems to have better association with insulin sensitivity than SAD and WC in the patients with hypertension.