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Background: Serum vascular adhesion protein-1 (VAP-1) predicts cancer-related mortality in diabetic subjects. However, whether serum VAP-1 predicts cancer incidence or cancer progression remains unclear. We conducted a cohort study to investigate whether serum VAP-1 and related clinical variables predict incident cancers in type II diabetic subjects.Methods: From 1996 to 2003, we enrolled 568 type II diabetic subjects who were free of cancer at baseline. Serum VAP-1 at enrollment was measured by time-resolved immunofluorometric assay. Chronic kidney disease (CKD) was defined as estimated glomerular filtration rate 2. The subjects were followed until first occurrence of cancer or until December 31, 2011.Results: During a mean follow-up of 11.3 years, 71 subjects developed incident cancers. The HRs for incident cancers in subjects with highest tertile of serum VAP-1 and in subjects with CKD were 2.95 [95% confidence interval (CI), 1.31–6.63; P = 0.009] and 2.29 (95% CI, 1.18–4.44; P = 0.015), respectively, after multivariate adjustment. There was an interaction between serum VAP-1 and CKD on the risk of incident cancers (P = 0.01 for log-transformed VAP-1 × CKD). The relationship among serum VAP-1, CKD, and incident cancers was similar if death was considered in the competing risk models or if subjects with shorter follow-up period were excluded.Conclusions: Higher serum VAP-1 and CKD can independently predict future development of cancers in type II diabetic subjects.Impact: Physicians should be aware of the early signs of cancer in diabetic individuals with elevated VAP-1 or renal dysfunction. More aggressive treatment strategies might be considered. Cancer Epidemiol Biomarkers Prev; 23(7); 1366–73. ©2014 AACR.

PDF - 80K, Baseline characteristics stratified by the presence of CKD in people with type 2 diabetes.

PDF - 78K, Cumulative incidence function (CIF) of cancer among subgroups (A) stratified by tertile of serum VAP-1 (B) stratified by the presence of chronic kidney disease.

PDF - 64K, HRs (95% CI) for incident cancers excluding subjects with shorter follow-up time.

Context Angiopoietin-like protein 6 (ANGPTL6) is a hepatokine that improves insulin sensitivity in animals. However, serum ANGPTL6 concentration was found to be higher in human participants with diabetes or metabolic syndrome in cross-sectional studies, implying that ANGPTL6 may be induced to counteract hyperglycemia. Objective To investigate whether serum ANGPTL6 can predict incident diabetes and explore whether glucose or insulin can regulate ANGPTL6 expression and secretion. Design This cohort study included adults without diabetes at baseline who were followed every 2 years for incident diabetes. Serum ANGPTL6 concentrations were measured at baseline and during oral glucose tolerance tests (OGTTs). A hepatic cell line, HepG2, and diet-induced obesity mouse model were used to evaluate the response of ANGPTL6 expression and secretion to hyperglycemia and the metabolic syndrome. Results We recruited 1103 participants without diabetes at baseline. During the 4.22-year follow-up, 113 (10.2%) participants developed incident diabetes. Serum ANGPTL6 was negatively associated with the incidence of diabetes (adjusted hazard ratio, 0.77; P = 0.042). However, serum ANGPTL6 level was higher in participants with prediabetes (P = 0.018) and was elevated during OGTT. In HepG2 cells, treatment with glucose, but not insulin, induced ANGPTL6 expression. Hepatic ANGPTL6 expression and serum ANGPTL6 concentrations were significantly higher in mice fed with a high-fat diet than in those fed with a standard chow (both P < 0.05). Conclusion A high serum ANGPTL6 level is associated with a low incidence of diabetes in humans. ANGPTL6 is expressed and secreted in response to hyperglycemia to maintain glucose homeostasis.

Vascular adhesion protein-1 (VAP-1) can enhance tissue glucose uptake in cell studies and normalize hyperglycemia in animal studies. However, serum VAP-1 concentration (sVAP-1) is higher in subjects with diabetes in cross-sectional studies. In this cohort study, we test our hypothesis that sVAP-1 is increased in prediabetes to counteract hyperglycemia and is associated with incident diabetes negatively. From 2006 to 2012, 600 subjects without diabetes from Taiwan Lifestyle Study were included and followed regularly. Diabetes was diagnosed if FPG ≥ 126 mg/dL (7 mmol/L), 2-h plasma glucose (2hPG) during an oral glucose tolerance test (OGTT) ≥ 200 mg/dL (11.1 mmol/L), or hemoglobin A1c (HbA1c) ≥ 6.5%, or if the subject received anti-diabetic medications. Abdominal fat areas were measured by abdominal computed tomography and sVAP-1 was analyzed by ELISA. sVAP-1 was higher in subjects with prediabetes (p

Supplementary Tables for the manuscript "Serum Angiopoietin-like Protein 6, Risk of Type 2 Diabetes, and Response to Hyperglycemia: A Prospective Cohort Study".

Aims Insulin resistance (IR) changes over time during the development of type 2 diabetes. Some reports showed that obesity was associated with progression of IR. However, no study has explored if change of IR predicts incident diabetes, and no study has investigated other factors associated with the change. Methods In this study, 1184 subjects without diabetes at baseline were enrolled in 2006–2016 with a median follow-up period of 4.5 years. Diabetes was diagnosed by oral glucose tolerance test and hemoglobin A1c, or if anti-diabetic agents were used. HOMA2-IR and ISI0,120 were used to estimate IR. Results The annual changes of HOMA2-IR(ΔHOMA2-IR/year) and ISI0,120(ΔISI0,120/year) were associated with BMI, waist circumference(WC), glucose, HbA1c, triglyceride and HDL-cholesterol. Subjects with pre-diabetes or metabolic syndrome were associated with a more rapid increase of IR. ΔHOMA2-IR/year and ΔISI0,120/year were correlated with annual changes of BMI and WC. The hazard ratios for ΔHOMA2-IR/year and ΔISI0,120/year to predict incident diabetes were 1.39 (95% CI 1.22–1.59, p Conclusions Change of IR can be used as a surrogate marker of incident diabetes. The progression of IR is an important pathophysiologic link between risk factors and the incidence of diabetes.

Aim To investigate the appropriate fasting plasma glucose threshold by which to define prediabetes in children and adolescents, based on its ability to predict incident paediatric diabetes. Methods In a nationwide survey of diabetes and renal disease conducted between 1992 and 2000 in all school-aged children in Taiwan, those with abnormal results in repeated urine tests received further physical examination and blood tests. Students who had blood tests for at least two time points were selected for the present study (N = 12 119). The incidence of paediatric diabetes, adjusted hazard ratio and predictive power of fasting plasma glucose were analysed. Results The incidence of paediatric diabetes increased with increasing fasting plasma glucose levels. Groups with fasting plasma glucose >5.6 mmol/l had a higher adjusted hazard ratio. The adjusted hazard ratio of incident diabetes for participants with higher fasting plasma glucose rose continuously when using a higher threshold for fasting plasma glucose. The area under the receiver-operating characteristic curve for fasting plasma glucose was 0.628 for predicting paediatric diabetes. The association between fasting plasma glucose and incident paediatric diabetes and the area under the receiver-operating characteristic curve were similar in boys and girls and were higher in the age group 12-18 years. According to receiver-operating characteristic curve analysis, the optimal thresholds, sensitivity and specificity were 4.75 mmol/l, 65% and 51%, respectively, for those aged 6-11 years and 5.19 mmol/l, 60% and 73%, respectively, for those aged 12-18 years. Conclusion Fasting plasma glucose is associated with the incidence of paediatric diabetes. The results of the present study can be used as reference data to suggest a cut-off value to define paediatric prediabetes.

Background: Serum vascular adhesion protein-1 (VAP-1) predicts cancer-related mortality in diabetic subjects. However, whether serum VAP-1 predicts cancer incidence or cancer progression remains unclear. We conducted a cohort study to investigate whether serum VAP-1 and related clinical variables predict incident cancers in type II diabetic subjects. Methods: From 1996 to 2003, we enrolled 568 type II diabetic subjects who were free of cancer at baseline. Serum VAP-1 at enrollment was measured by time-resolved immunofluorometric assay. Chronic kidney disease (CKD) was defined as estimated glomerular filtration rate Results: During a mean follow-up of 11.3 years, 71 subjects developed incident cancers. The HRs for incident cancers in subjects with highest tertile of serum VAP-1 and in subjects with CKD were 2.95 [95% confidence interval (CI), 1.31–6.63; P = 0.009] and 2.29 (95% CI, 1.18–4.44; P = 0.015), respectively, after multivariate adjustment. There was an interaction between serum VAP-1 and CKD on the risk of incident cancers (P = 0.01 for log-transformed VAP-1 × CKD). The relationship among serum VAP-1, CKD, and incident cancers was similar if death was considered in the competing risk models or if subjects with shorter follow-up period were excluded. Conclusions: Higher serum VAP-1 and CKD can independently predict future development of cancers in type II diabetic subjects. Impact: Physicians should be aware of the early signs of cancer in diabetic individuals with elevated VAP-1 or renal dysfunction. More aggressive treatment strategies might be considered. Cancer Epidemiol Biomarkers Prev; 23(7); 1366–73. ©2014 AACR.

BACKGROUND: Few studies have investigated the relationship between injury location, mechanism and their association with complex regional pain syndrome (CRPS). We conducted a nationwide database survey to explore this issue. METHODS: This was a population-based case-control study. Five hundred and eighty-nine patients with at least one ambulatory visit or admission with a principal diagnosis of CRPS from 2004 to 2009 were selected. For each CRPS patient, ten age- and sex-matched non-CRPS subjects were randomly selected. The odds ratios (PLoS One. 2013;8:e57205) and 95% confidence intervals (95% CIs) of risk factors for CRPS were derived from multivariate logistic regression models. RESULTS: Injury was a risk factor for CRPS (OR, 2.96; 95% CI, 2.18 to 4.02) independent of age and sex. In adjusted models, open wound on the upper limbs (OR 1.25, 95% CI 1.02 to 1.54) conferred higher CRPS risk. Injury mechanisms including nerve and spinal cord injury (OR 2.42, 95% CI 1.44 to 4.08), muscle and joint sprain and strain (OR 1.69, 95% CI 1.40 to 2.03), superficial injury (OR 1.23, 95% CI 1.00 to 1.51), and contusion (OR 1.44, 95% CI 1.20 to 1.74), but not fracture, increased the risk of CRPS. CONCLUSION: Injury in the extremities rather than the trunk is an important risk factor for CRPS. Certain injury mechanisms confer higher risk of CRPS. This nationwide study demonstrated that injury increased CRPS nearly threefold. Open wound, sprain and strain, superficial injury, contusion, and nerve and spinal cord injury are main injury mechanisms. Injury in the extremities confers a higher risk of CRPS. Language: en

Semicarbazide-sensitive amine oxidase (SSAO)/vascular adhesion protein-1 (VAP-1) is involved in the pathogenesis of both atherosclerosis and cancer. Because chemical components and metabolites of cigarettes are deaminated by SSAO, the relationship between smoking and serum SSAO/VAP-1 was studied in humans.A total of 451 non-diabetic and normoalbuminuric Han Chinese subjects were recruited to participate in this study. Smoking history was obtained by using a questionnaire and those who smoked more than 100 cigarettes during a 6-month period were considered smokers. Serum VAP-1 concentration was measured by time-resolved immunofluorometric assay. Age, gender, waist circumference and estimated glomerular filtration rate (GFR) were adjusted in different statistical models.Smokers were mainly male (85.7% versus 26.3%) and were more obese than non-smokers (p 0.05). Subjects with higher serum VAP-1 concentrations were older (p 0.001) and tended to have larger waist circumferences and lower estimated GFR. Serum VAP-1 concentration was higher in smokers than in non-smokers (p 0.05) after adjusting for age, gender, waist circumference, estimated GFR, liver biochemistry and lipid profile.Cigarette smoking is associated with elevated serum VAP-1 concentration. Whether VAP-1 and its SSAO activity link the relationship between cigarette smoking, atherosclerosis and cancer requires further investigation.

OBJECTIVE Waist circumference (WC) is used to define central obesity. This study aimed to compare the performance of two recommended locations of WC measurement. RESEARCH DESIGN AND METHODS A cohort of 1,898 subjects who were without diabetes from 2006 to 2012 were followed for a median of 31 months (Taiwan Lifestyle Study). The WC-IC, recommended by the National Cholesterol Education Program Third Adult Treatment Panel, was measured at the superior border of the iliac crest, and the WC-mid, recommended by World Health Organization and International Diabetes Federation, was measured midway between the lowest ribs and the iliac crest. The abdominal subcutaneous fat area (SFA) and visceral fat area (VFA) were assessed by computed tomography. RESULTS There was greater difference between WC-IC and WC-mid measurements in women than in men (P < 0.001). Both WC-IC and WC-mid correlated significantly with BMI, VFA, and SFA (all P < 0.001). WC-mid was better correlated to VFA than WC-IC, particularly in women, and it correlated more strongly to blood pressure, plasma glucose, hemoglobin A1c, triglyceride levels, HDL cholesterol, and C-reactive protein (all P < 0.05). The association of WC-mid with hypertension, diabetes, and metabolic syndrome was slightly better than that of WC-IC (area under the receiver operator curve 0.7 vs. 0.69, 0.71 vs. 0.68, and 0.75 vs. 0.7, respectively; all age-adjusted P < 0.05). With 90 cm (male)/80 cm (female) as criteria for central obesity, WC-mid, but not WC-IC, predicted the incidence of diabetes development (age-adjusted P = 0.003). CONCLUSIONS WC-mid is a better measurement to define central obesity than WC-IC, particularly in women.

Gastric atrophy results in lower plasma ghrelin, higher gastrin secretion, a change in gut microbiota, and altered dietary nutrient absorption, which may be associated with the incidence of diabetes. Helicobacter pylori (H. pylori) infection is a major cause of gastric atrophy and is associated with diabetes in some reports. Since there is no study which investigates the impact of gastric atrophy on diabetes, we conduct a prospective cohort study to examine the relationship between H. pylori infection, gastric atrophy, and incident diabetes. In this study, subjects with gastric atrophy had a lower risk of incident diabetes, compared to those without gastric atrophy. The extent of gastric atrophy, measured by serum pepsinogen (PG) I/II ratio, was correlated with age, H. pylori IgG titer, HOMA2-IR, and HOMA2%B. When gastric atrophy is more extensive, presented as a lower serum PG I/II ratio, the risk of incident diabetes is lower. On the other hand, there was no significant association between H. pylori infection and the incidence of diabetes. In conclusion, the presence and the extent of gastric atrophy, but not H. pylori infection, are associated with incident diabetes. Further studies are needed to investigate the detailed mechanisms and the potential applications of the findings to guide diabetes screening and treatment strategies.

Diabet. Med. 30, 318–325 (2013) Abstract Aims To evaluate whether homeostasis model assessment and high-sensitivity C-reactive protein improve the prediction of isolated post-load hyperglycaemia. Methods The subjects were 1458 adults without self-reported diabetes recruited between 2006 and 2010. Isolated post-load hyperglycaemia was defined as fasting plasma glucose

Objectives To investigate the relationship among obesity, cardiovascular disease risk factors (CVDRFs), and plasma complement C3 concentration in children and adolescents. Methods In a nationwide survey conducted between 1992 and 2000, all school children aged 6–18 yr with abnormal results in repeated urine samples, including hematuria, proteinuria, and glucosuria (n = 97 312; 36 557 boys and 60 755 girls), were investigated for their body mass index (BMI), blood pressure, fasting plasma glucose, total cholesterol, and plasma complement C3 concentrations. Results Children in the higher percentile groups for BMI or having more CVDRFs, namely, hypertension, diabetes, and hypercholesterolemia, had higher plasma C3 concentrations independently (p for both trends

Aims/Introduction: To evaluate if hemoglobin A1c (A1C) can replace the use of the oral glucose tolerance test (OGTT) to diagnose diabetes in Chinese patients. Materials and Methods: Subjects without pre-existing diabetes were included in this community-based study. Each participant received a 75-g OGTT and A1C tests. Results: A total of 1362 subjects, 512 men and 850 women, aged 18–88 years, were enrolled. The prevalence of diabetes was 7.4 and 7.3% by OGTT and by A1C ≥ 6.5% criteria, respectively. The optimal A1C cut-off for diabetes defined by OGTT was 6.1%. The performance of A1C ≥ 6.1% to find diabetes by OGTT was poor, with a kappa 0.50, sensitivity 80% and specificity 91%. Using current criteria of fasting plasma glucose (FPG)

Summary Background The association between haemoglobin A1c (HbA1c) levels and subclinical atherosclerosis in carotid arteries in Chinese populations is unknown. Aim, design and methods The objective of this study was to investigate this relationship and evaluate the ability of HbA1c levels to predict carotid atherosclerosis in a Chinese population. This was a cross-sectional study, which included 541 subjects without known diabetes (Taiwan Lifestyle Study). About 67 (9·2%) subjects were newly diagnosed with diabetes during the study. Carotid intima–media thickness (IMT) and the presence of carotid plaques were determined using ultrasonography. Results The HbA1c level in all subjects was positively correlated with carotid IMT (β = 0·018, P = 0·03) after being adjusted for age, gender, smoking, low-density lipoprotein cholesterol level, hypertension and body mass index. HbA1c level was higher in subjects with plaques in carotid arteries (P = 0·01). There was a positive and linear relationship between HbA1c levels and the probability of having plaques, thickened carotid IMT or both (P for all comparisons

OBJECTIVE Vascular adhesion protein-1 (VAP-1) participates in inflammation and catalyzes the breakdown of amines to produce aldehyde, hydrogen peroxide, and ammonia. Serum VAP-1 correlates positively with both acute hyperglycemia and diabetes. We conducted a cohort study to evaluate whether serum VAP-1 predicts 10-year survival in type 2 diabetic patients. RESEARCH DESIGN AND METHODS Between July 1996 and June 2003, we enrolled 661 type 2 diabetic subjects at National Taiwan University Hospital. Serum VAP-1 in the samples obtained at enrollment was measured by time-resolved immunofluorometric assay. The vital status of all subjects was ascertained by linking their data with computerized death certificates in Taiwan. RESULTS The medium follow-up period was 10.4 years. Subjects with serum VAP-1 in the highest tertile had a hazard ratio (HR) of 2.19 (95% CI 1.17–4.11) for all-cause mortality adjusted for age, sex, smoking, history of cardiovascular disease, obesity, hypertension, hemoglobin A1c, diabetes duration, total cholesterol, use of statins, abnormal ankle-brachial index, estimated glomerular filtration rate (eGFR), and proteinuria. The adjusted HRs for logarithmically transformed serum VAP-1 were 5.83 (95% CI 1.17–28.97) for cardiovascular mortality, 6.32 (95% CI 1.25–32.00) for mortality from cardiovascular and diabetic causes, and 17.24 (95% CI 4.57–65.07) for cancer mortality. There were four variables, including age, serum VAP-1, proteinuria, and eGFR, which could enhance mortality prediction significantly. CONCLUSIONS Serum VAP-1 can predict 10-year all-cause mortality, cardiovascular mortality, and cancer mortality independently in type 2 diabetic subjects. Serum VAP-1 is a novel biomarker that improves risk prediction over and above established risk factors.

The aim of this study is to develop strategies to screen diabetic subjects with isolated postload hyperglycemia (IPH) in Chinese population. We included 1175 adult subjects who did not report diabetes were included. Diabetes was diagnosed by oral glucose tolerance tests. IPH was defined as fasting plasma glucose (FPG)7 mmol/l and 2-hour post-load plasma glucose (2hPG) greater than 11.1 mmol/l. Using FPG criteria, only 59.8% of diabetic subjects were not identified, showing a poor agreement between FPG and 2hPG criteria (kappa 0.294). Age, FPG, total cholesterol, triglycerides, blood pressure, body mass index, HbA1c and medication for hypertension were associated factors for IPH. Four scores were constructed using all these factors, age and blood test results, age and HbA1c, and data from non-invasive examinations, respectively. The area under the ROC curve were 0.9296(95%CI 0.8948-0.9643), 0.9111(95%CI 0.8713-0.9508), 0.8902(95%CI 0.8341-0.9646), 0.8924(95%CI 0.7835-0.8753), and 0.8654(95%CI 0.7963-0.9345) for score 1, 2, 3, 4, and HbA1c, respectively. The sensitivity of all four risk scores to detect IPH was better than that of impaired fasting glucose (IFG). The sensitivity and specificity of HbA1c at cutoff 6.2% for detecting IPH was also better than that of IFG. In conclusion, the risk scores and HbA1c are useful to identify subjects with undiagnosed IPH, with better performance than IFG.

Wei J-N, Li H-Y, Wang Y-C, Chuang L-M, Lin M-S, Lin C-H, Sung F-C. Detailed family history of diabetes identified children at risk of type 2 diabetes: a population-based case-control study. Objectives: Recently, the incidence of type 2 diabetes (T2D) in children has increased dramatically. Mass screening is suffering and costly. It remains unknown if a detailed family diabetes mellitus history (FDMH) can identify children with different risks of T2D. This study investigated how FDMH was associated with childhood T2D. Methods: From 1992 to 1997, a nationwide survey conducted in Taiwan for all 3 000 000 school children aged between 6 and 18 yr identified 1966 children with diabetes. For comparison, 1780 children were randomly selected as the control group from all students with normal fasting glycemia (NFG). Telephonic Interviews were conducted using questionnaire for detailed FDMH. In the present analysis, 505 children with T2D and 619 children with NFG were enrolled. Results: Children with more family members having diabetes were more likely to have T2D. Children with the parental FDMH had a higher risk for T2D than children with the grandparental FDMH; the odds ratios (ORs) were 2.61 (95% confidence interval (CI) 1.25–5.48, p < 0.05) for boys and 6.47 (95% CI 2.69–15.6, p < 0.05) for girls, adjusting for age, birth weight, gestational age and body mass index (BMI) z-score. Children with maternal FDMH had a higher risk for T2D than children with paternal FDMH, and much greater in boys (OR = 29.5, 95% CI 3.67–237, p < 0.05) than in girls (OR = 7.63, 95% CI 2.05–28.4, p < 0.05), adjusted for age, birth weight, gestational age, BMI z-score, and FDMH in grandparents. Conclusions: Children with parental FDMH, especially the maternal FDMH, have an elevated risk for T2D. Detailed FDMH is a convenient alternative to identify children with different risks of T2D.

The relationship between serum vascular adhesion protein-1 (VAP-1) and plasma glucose in normal and drug-naïve type 2 diabetes subjects is unclear. We examined if serum VAP-1 changed acutely to oral glucose loading and analyzed the relationship between serum VAP-1, fasting plasma glucose (FPG), hemoglobin A1c, and type 2 diabetes.Adults without history of diabetes were included. Subjects taking anti-diabetic drugs were excluded. Serum VAP-1 was analyzed by time-resolved immunofluorometric assay.We recruited 333 subjects (186 females and 147 males), aged 56.1 +/- 11.6 y. After glucose challenge, serum VAP-1 rose significantly at 30 min (p0.0001) and lasted until 2 h (p0.0001). The change of serum VAP-1 between fasting and 30-min postload correlated inversely to the change of plasma insulin (r = -0.21, p = 0.049). Fasting serum VAP-1 was associated with FPG in those with FPGor = 5.55 mmol/l (p = 0.025) but not in those with FPG5.55 mmol/l (p = NS). Fasting serum VAP-1 were higher in diabetic subjects (p = 0.04) and correlated positively to hemoglobin A1c (r = 0.18, p = 0.002) after adjusting for age, gender, and waist circumference.Serum VAP-1 is increased in both acute and chronic hyperglycemia. Whether serum VAP-1 is a good biomarker for hyperglycemia-associated complications merits further investigation.

We investigated if serum vascular adhesion protein-1 (SSAO/VAP-1) changed acutely following oral glucose loading and whether such changes are correlated with surrogate markers of atherosclerosis.A total of 115 non-diabetics subjects were enrolled for an oral glucose tolerance test (OGTT). Carotid intima-medial thickness (IMT) was measured by ultrasonography. Serum SSAO/VAP-1 was analyzed by time-resolved immunofluorometric assay. Serum thiobarbituric acid reactive substances (TBARS) and advanced glycated end products (AGEs) were measured by fluorometric assays.Serum SSAO/VAP-1 increased significantly at 30 min after oral glucose loading and lasted to 2 h (p=0.0005 and p0.0001, for 30 min and 2 h respectively). The area under curve of serum SSAO/VAP-1 during OGTT (AUC-VAP-1) correlated significantly with carotid IMT, independent of age, gender, low-density lipoprotein cholesterol, systolic blood pressure, hemoglobin A1c, serum TBARS, AGEs, and high-sensitivity C-reactive protein. Subjects with a positive AUC-VAP-1 had significantly higher serum TBARS and AGEs than subjects with a negative AUC-VAP-1 adjusted for age and gender.Serum SSAO/VAP-1 changed acutely following oral glucose loading in non-diabetic subjects. Change of serum SSAO/VAP-1 correlated independently to serum TBARS, AGEs, and carotid IMT. Our findings suggest that acute change of serum SSAO/VAP-1 is a novel marker for hyperglycemia-induced atherosclerosis.

An increased level of serum vascular adhesion protein-1 (VAP-1) has been found in patients with diabetes mellitus and vascular disorders. This study examined whether serum VAP-1 levels are associated with chronic kidney disease (CKD).We included 262 subjects aged 30 and above with fasting plasma glucose level7 mmol/L checked within 1 year. First morning urine specimens were collected. Microalbuminuria was defined if urinary albumin-to-creatinine ratioor =30 microg/mg creatinine. The glomerular filtration rate (GFR) was estimated. CKD stages were defined according to the suggestions of the National Kidney Foundation. Serum VAP-1 levels were analyzed by immunofluorometric assay.Serum VAP-1 levels were positively associated with the urinary albumin-to-creatinine ratio (r=0.29, p0.0001) and negatively associated with estimated GFR (r=-0.24, p=0.0001). Subjects with CKD stage 2 (N=51) and stage 3 (N=91) had significantly higher levels of serum VAP-1 than those without CKD (p=0.0003 and p=0.035, adjusted for age and gender, respectively). A high serum VAP-1 level was associated with the presence of CKD (OR 1.63 for 1 SD increase of VAP-1, p=0.018), adjusting for age, sex, and smoking. Ordered logit models revealed that high serum VAP-1 levels correlated with advanced stages of CKD.Serum levels of VAP-1 are associated with the severity of kidney damage or stages of kidney disease. The true mechanism which links the serum VAP-1 and CKD remains to be elucidated in further studies.

In the diagnosis of diabetes mellitus, hemoglobin A1c (HbA1c) is sometimes measured to determine the need of an oral glucose tolerance test (OGTT). However, HbA1c does not accurately reflect glycemic status in certain conditions. This study was performed to test the possibility that measurement of serum glycated albumin (GA) better assesses the need for OGTT. From 2006 to 2012, 1559 subjects not known to have diabetes or to use anti-diabetic medications were enrolled. Serum GA was measured, and a 75-g OGTT was then performed to diagnose diabetes. Serum GA correlated significantly to age (r = 0.27, p

Background Diabetes is the leading cause of end-stage renal disease (ESRD) worldwide. Vascular adhesion protein-1 (VAP-1) participates in inflammation and catalyzes the deamination of primary amines into aldehydes, hydrogen peroxide, and ammonia, both of which are involved in the pathogenesis of diabetic complications. We have shown that serum VAP-1 is higher in patients with diabetes and in patients with chronic kidney disease (CKD), and can predict cardiovascular mortality in subjects with diabetes. In this study, we investigated if serum VAP-1 can predict ESRD in diabetic subjects. Methods In this prospective cohort study, a total of 604 type 2 diabetic subjects were enrolled between 1996 to 2003 at National Taiwan University Hospital, Taiwan, and were followed for a median of 12.36 years. The development of ESRD was ascertained by linking our database with the nationally comprehensive Taiwan Society Nephrology registry. Serum VAP-1 concentrations at enrollment were measured by time-resolved immunofluorometric assay. Results Subjects with serum VAP-1 in the highest tertile had the highest incidence of ESRD (p

The International Diabetes Federation (IDF) proposed a new definition for metabolic syndrome (MS) in 2005. We conducted this study to compare the association of MS by IDF and ATP III definition to various metabolic variables. In 2005, we enrolled 654 Chinese people in a screening program in Taiwan. Anthropometric and biochemical profiles, including high-sensitivity C-reactive protein (hsCRP), were measured. Serum hsCRP levels were higher in those with MS by IDF definition (2.4+/-1.9mg/l versus 1.3+/-1.4mg/l, p0.0001). Serum hsCRP levels increase with the number of components of MS they met (p for trend0.001). Serum LDL levels were higher in those with MS by IDF definition (131+/-39 versus 125+/-32, p0.05) but not in those with MS by ATP III definition (p=0.2). Serum hsCRP levels correlate significantly to MS by ATP III definition, after adjusting for age, sex, smoking, body mass index, serum apolipoprotein A1 and LDL levels. Adding MS status by IDF definition in this model significantly increased model fitness in men (MS by IDF definition, partial r=0.18, p0.05, MS by ATP III definition, partial r=0.12, p=0.071). In conclusion, IDF definition of MS has a stronger relationship with serum hsCRP than ATP III definition in men.

To explore the relationship between birth weight and type 1 diabetes, data from national birth registry and national surveillance of diabetes in Taiwanese schoolchildren were analyzed. From 1992 to 1997, all schoolchildren aged 6-18 years were screened for diabetes by a mass urine survey program in Taiwan Province. This cohort consisted of 1966 children with diabetes and 1780 of randomly selected subjects with normal fasting glycemia. Questionnaires were designed for telephone interviews with students' parents or physicians to classify subjects' types of diabetes. The birth history of each participant was obtained from the Taiwan's Birth Registry. After merging the data, there were 835 subjects, including 277 of type 1 diabetes and 533 of normal fasting glycemia available for the present analyses. The odds ratio (95% CI) for type 1 diabetes, after adjusting age, sex, socioeconomic status, family history of diabetes, birth order, breast-feeding, BMI, and gestational diabetes mellitus was 2.24 (1.11-4.50) for children with low birth weight (5th percentile, i.e.,or =2600 g) when compared with the referent group of a birth weight of 3000-3542 g (equivalent to the 25-75th percentile). In conclusion, low birth weight was associated with increased risk of type 1 diabetes in Taiwanese schoolchildren.

We validated infant birth weight by interview with mothers.Infant birth weights obtained from maternal interview were compared with the data documented in birth certificates. Study subjects were mothers of 1,432 schoolchildren who participated in a diabetes mass screening program in 1992-1997, Taiwan. Data of infant birth weight obtained from telephone interview with mothers were compared with those from birth certificates to evaluate the accuracy of maternal report in eight categorized groups:2,000, 2,000-2,499, 2,500-2,999, 3,000-3,499, 3,500-3,999, 4,000-4,499, 4,500-4,999, andor=5,000 g.The exact agreement was as low as 15.9% but increased substantially to 67.7% if maternal reports of weight one category higher than birth registry weight were considered to be indicative of agreement. Lower orders of birth weight were significantly associated with reports of higher category. But teen mothers and/or low-income mothers were associated with lower risks of overreport.Our data suggested that birth weight-associated studies in Taiwan should "round number" to an upper category rather than a lower category to avoid serious misclassification in birth weight.

OBJECTIVE—To study the effect of body composition and adiponectin on insulin resistance and β-cell function in schoolchildren during puberty. RESEARCH DESIGN AND METHODS—Plasma adiponectin level and its relationships with insulin sensitivity and β-cell function were analyzed in 500 randomly recruited nondiabetic Taiwanese schoolchildren (245 boys and 255 girls) aged 6–18 years in a national survey program for diabetes in 1999. Insulin resistance and β-cell function were evaluated by homeostasis model assessment (HOMA). Plasma adiponectin concentrations were determined with radioimmunoassay. RESULTS—Plasma glucose levels remained stable, whereas insulin resistance increased with a compensatory rise in β-cell function during this period. A transient drop of adiponectin level with a trough at 10–12 years was found in boys but not in girls. This pubertal drop of adiponectin levels in boys coincides with the sharp rise in testosterone concentration. A negative correlation between testosterone levels and adiponectin concentration was also noted in boys (r = −0.142, P = 0.032). Plasma adiponectin levels correlated inversely with relative body weight, fasting insulin concentrations, and insulin resistance index by HOMA in boys aged 15–18 years and in girls aged 11–14 years. No association was observed between adiponectin levels and β-cell function by HOMA. CONCLUSIONS—There is a transient drop in the level of adiponectin during male puberty, correlated with the increase in testosterone level in boys. Plasma adiponectin levels were inversely correlated with obesity and insulin resistance in boys and girls during the pubertal period.

OBJECTIVE—To study the effect of birth weight on risk of type 2 diabetes in the schoolchildren in Taiwan. RESEARCH DESIGN AND METHODS—From 1992 to 1997, all schoolchildren aged 6–18 years were screened for diabetes in Taiwan Province. This cohort consisted of 1,966 patients with diabetes and 1,780 randomly selected subjects with normal fasting glycemia (NFG). Questionnaire interviewing was designed to classify diabetes. The birth weight was obtained from the Taiwan’s Birth Registry. After merging the data, there were 978 subjects, including 429 with type 2 diabetes and 549 with of NFG enrolled in the present analyses. RESULTS—The odds ratios (95% CI) for type 2 diabetes, after adjusting age, sex, BMI, family history of diabetes, and socioeconomic status, were 2.91 (1.25–6.76) for children with low birth weight ( CONCLUSIONS—A U-shaped relationship between birth weight and risk of type 2 diabetes was found in the schoolchildren aged 6–18 years in Taiwan. Schoolchildren with type 2 diabetes who were born with low birth weight had different metabolic phenotypes compared with those born with high birth weight.

Aims/Introduction: To evaluate if hemoglobin A1c (A1C) can replace the use of the oral glucose tolerance test (OGTT) to diagnose diabetes in Chinese patients. Materials and Methods: Subjects without pre‐existing diabetes were included in this community‐based study. Each participant received a 75‐g OGTT and A1C tests. Results: A total of 1362 subjects, 512 men and 850 women, aged 18–88 years, were enrolled. The prevalence of diabetes was 7.4 and 7.3% by OGTT and by A1C ≥ 6.5% criteria, respectively. The optimal A1C cut‐off for diabetes defined by OGTT was 6.1%. The performance of A1C ≥ 6.1% to find diabetes by OGTT was poor, with a kappa 0.50, sensitivity 80% and specificity 91%. Using current criteria of fasting plasma glucose (FPG)

Apelin regulates insulin sensitivity and secretion in animals. However, whether plasma apelin predicts incident diabetes in humans remains unknown.We studied a cohort including 447 subjects (148 men, 299 women) without diabetes and followed for an average of 3y. Diabetes was diagnosed by an oral glucose tolerance test, plasma hemoglobin A1c, and if the subject was taking medications for diabetes. Plasma apelin-12 at baseline was measured with a commercial kit.Plasma apelin concentrations were higher in women than in men at baseline (p=0.007). During follow-up, 43 subjects developed type 2 diabetes. Higher plasma apelin concentrations were associated with a higher risk of diabetes in men (p=0.049) but not in women. Plasma apelin predicted incident type 2 diabetes in men (hazard ratio, 2.13, 95% CI 1.29-3.51, p0.05), but not in women, adjusted for age, family history of diabetes, hemoglobin A1c, body mass index, hypertension, and HOMA2-IR. Apelin could improve the prediction ability beyond traditional risk factors in men, and the sensitivity and specificity of plasma apelin at 0.9ng/ml for this prediction were 63.2% and 58.9%, respectively. In men at risk for diabetes (HbA1c 5.7-6.4%, FPG 100-125mg/dl, or OGTT-2h-PG 140-199mg/dl), the risk for developing diabetes was higher in those with higher plasma apelin concentration than in those with lower plasma apelin concentrations (10.6%/year vs. 5.1%/year, p0.001).Plasma apelin is a novel biomarker for predicting type 2 diabetes in men.

Vascular adhesion protein-1 (VAP-1) participates in inflammation and catalyzes the breakdown of amines to produce aldehyde, hydrogen peroxide, and ammonia. Serum VAP-1 can predict cancer mortality, including colorectal cancer (CRC) mortality, in type 2 diabetic subjects. However, it remains unknown if serum VAP-1 can predict mortality in CRC patients. This prospective cohort study investigates if serum VAP-1 is a novel biomarker for mortality prediction in CRC.We enrolled 300 CRC patients. Preoperative serum VAP-1 was measured by time-resolved immunofluorometric assay. They were followed until September 2009 or death, which was ascertained by the National Death Registration System.The median follow-up period was 4.7 years. Compared with normal counterpart, VAP-1 immunoactivity was upregulated in CRC tissues, especially at the invasion front. Serum VAP-1 can independently predict all-cause mortality (HR: 1.0026, 95% CI: 1.0003-1.0050, P0.05) and cancer-related mortality (HR: 1.0026, 95% CI: 1.0001-1.0050, P0.05). A risk score composed of age, gender, carcinoembryonic antigen (CEA)5 ng/ml, tumor grading, tumor staging, and serum VAP-1 could stratify CRC patients into low-, intermediate-, and high-risk subgroups, with a 5-year mortality rate of 10%, 34%, and 78%, respectively.Serum VAP-1 predicts mortality independently and improves risk stratification in CRC subjects.

Background We conducted a cohort study to determine if proteinuria predicts cancer-related mortality in type 2 diabetic subjects. Methods Between July 1996 and June 2003, we enrolled 646 type 2 diabetic subjects. Participants were followed-up until December 31, 2008. The vital status was ascertained by linking records with computerized death certificates in Taiwan. Results During a median follow-up of 10.4years, 158 subjects had died, including 59 from cancers. Subjects with proteinuria had a hazard ratio (HR) of 2.77 (95% CI 1.82–4.21) for all-cause mortality and 1.99 (95% CI 1.00–3.94) for cancer-related mortality after adjustment for demographic factors and medical conditions. Specifically, proteinuria showed a trend of increased colon cancer death. The presence of proteinuria significantly improved the predictive ability of cancer-related mortality (increase in concordance statistics or area under the ROC curve=0.03). Patients with both proteinuria and estimated glomerular filtration rate 2 showed higher HR for all-cause mortality than patients with proteinuria only (adjusted HRs (95% CI), 4.01 (2.42–6.67) vs. 2.69 (1.51–4.79), both p Conclusions Proteinuria can predict 10-year all-cause and cancer-related mortalities independently in type 2 diabetic subjects, over and above the established risk factors associated with type 2 diabetes.

Background To evaluate the relationship between hemoglobin A1c variability and all-cause mortality in type 2 diabetic patients. Methods This was a retrospective cohort study in type 2 diabetic patients followed for at least 2years between 2003 and 2009. A1C variability was determined from the standard deviation or coefficient of variation of serial A1C values (A1C SD or A1C CV ). Subjects were categorized into either the high or low A1C variability group according to their A1C CV median. Hazard ratios (HRs) of various factors for all-cause mortality were determined from Cox's proportional hazard models. Results A total of 881 subjects (422 men, 459 women) were included and 73 (8.3%) died during follow-up. The follow-up period was 4.7±2.3years. All-cause mortality was higher in subjects with high A1C CV (11.0% vs. 5.4%, p=0.002). In the Kaplan–Meier failure curve, subjects with higher A1C CV demonstrated a trend of higher mortality (p=0.1). In multivariate Cox's proportional hazards models, A1C SD and A1C CV significantly predicted all-cause mortality with an HR of 1.987 (p=0.02) and 1.062 (p=0.013), respectively, after adjusting for age, gender, body mass index, duration of diabetes, mean systolic blood pressure, use of antihypertensives and statins, mean LDL-cholesterol, smoking status, chronic kidney disease, and mean A1C values (A1C MEAN ). The ability of A1C SD and A1C CV to predict all-cause mortality was more evident in subjects with relatively low A1C MEAN. Conclusions A1C variability is an important risk factor for all-cause mortality in type 2 diabetic patients.

To investigate the relationship among obesity, cardiovascular disease risk factors (CVDRFs), and plasma complement C3 concentration in children and adolescents.In a nationwide survey conducted between 1992 and 2000, all school children aged 6-18 yr with abnormal results in repeated urine samples, including hematuria, proteinuria, and glucosuria (n = 97 312; 36 557 boys and 60 755 girls), were investigated for their body mass index (BMI), blood pressure, fasting plasma glucose, total cholesterol, and plasma complement C3 concentrations.Children in the higher percentile groups for BMI or having more CVDRFs, namely, hypertension, diabetes, and hypercholesterolemia, had higher plasma C3 concentrations independently (p for both trends0.05, adjusted for age and gender). The odds ratios (ORs) for having one, two, or three CVDRFs in obese children were 4.74 [95% confidence interval (CI) = 4.47-5.03], 19.8 (95% CI = 17.8-22.0), and 139 (95% CI = 96.6-200), respectively, adjusted for age, gender, and family history of diabetes, which were substantially reduced after adjustment for plasma C3 concentrations. The ORs for children with plasma C3 concentrations in the highest quartile to have one, two, or three CVDRFs were 2.32 (95% CI = 2.21-2.44), 5.68 (95% CI = 4.83-6.67), and 58.6 (95% CI = 19.7-174), respectively, adjusted for age, gender, family history of diabetes, and BMI.Obesity is associated with clustering of CVDRFs in children and adolescents. Obesity and clustering of CVDRFs are associated with elevated plasma complement C3. Children and adolescents with higher plasma C3 concentrations have higher risk of clustering of CVDRFs independent of obesity.

Li H-Y, Wei J-N, Ma W-Y, Sung F-C, Lin M-S, Lin C-H, Chiang C-C, Chuang L-M. Hypertension and hypercholesterolemia aggregate in nondiabetic children and adolescents with higher fasting plasma glucose levels. Objective: To investigate how hypertension and hypercholesterolemia aggregate at different fasting plasma glucose (FPG) levels in children aged 6–16 yr. Research design and methods: In a nationwide survey conducted between 1992 and 2000, all schoolchildren aged 6–18 yr with abnormal results in repeated urine samples were included. In this study, we recruited 27 535 students aged 6- to 16-yr whose FPG levels were 90–125 mg/dL. Another 17 907 children were randomly selected as control from schoolchildren with FPG

Aims We conducted this study to compare the relationships between subclinical atherosclerosis and metabolic syndrome (MS) defined by four definitions in Chinese subjects. Methods In 2006–2007, we enrolled 140 Chinese subjects without reported diabetes in this study. Anthropometric, biochemical profile, and carotid intima-media thickness (IMT) were measured. MS was defined by International Diabetes Federation (IDF), American Heart Association and the National Heart, Lung, and Blood Institute (AHA/NHLBI), National Cholesterol Education Program Adult Treatment Panal III (NCEP-ATP III), and World Health Organization (WHO) criteria. Results Subjects with MS defined by IDF and AHA/NHLBI criteria had significantly higher carotid IMT, controlling for age, gender, smoking, and serum LDL-C (MS by IDF, partial r = 0.225, p = 0.008; AHA/NHLBI, partial r = 0.176, p = 0.04). The association between carotid IMT and MS defined by NCEP-ATP III or WHO criteria was not significant. Subjects with more components of MS defined by IDF, AHA/NHLBI, or NCEP-ATP III criteria correlated to higher carotid IMT in adjusted models (p-values for trend, MS by IDF, 0.011; AHA/NHLBI, 0.011; NCEP-ATPIII, 0.01; WHO, 0.113). Conclusion MS definitions by IDF and AHA/NHLBI criteria are the best among four definitions in detecting subclinical atherosclerosis in non-diabetic Chinese subjects; whereas MS defined by WHO criteria is the worst.

Glucometers are used to quickly obtain glucose concentrations in the hospital and at home. For quality assurance, the American Diabetes Association recommends periodically comparing the results from glucometers with those from referenced laboratories (1). Usually, measurement using glucometers is done one-by-one by technicians, which is costly regarding manpower. In contrast, measurement using blood analyzers in laboratories saves manpower by analyzing after sufficient samples are collected. Tubes containing glycolytic inhibitors such as sodium fluoride are used to keep the glucose level constant (2). If analyses by glucometers could be …

Global prevalence of type 2 diabetes mellitus in children is rising recently, likely due to an increasing rate of childhood obesity. In Taiwan, an annual program of mass screen for diabetes with two-staged design, i.e. diagnosis by fasting plasma glucose when glycosuria was positive in two consecutive urine samples, has been conducted since 1992 for all schoolchildren aged 6 to 18. A recent survey showed that the incidence of type 2 diabetes is 6-fold higher than those of type 1 diabetes. The prevalence of diabetes is elevated during puberty and is higher in girls than in boys. Obesity is the most important risk factor of type 2 diabetes in childhood and adolescence. Besides, genetics, family history, polycystic ovarian syndrome, ethnicity, and puberty are also risk factors of pediatric diabetes. We also briefly discuss the current state of management of obesity and type 2 diabetes, with special emphasis on behavioral and lifestyle modification, the need to create adequate and safe environment, and the psychological as well as family support in children and adolescents. Limited experience of the pharmacological agents in terms of their long-term effect and safety is also discussed.