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Hemoglobin glycation index (HGI) is used to describe the difference between estimated and measured glycated hemoglobin (HbAThis retrospective cohort study enrolled 780 patients with type 2 diabetes and a low CKD risk according to the criteria of kidney disease: improving global outcomes. Participants were divided into two subgroups according to the baseline HGI calculated by fasting blood glucose and HbAThe participants were followed for a median of 7.3 years. A high HGI predicted rapid renal function decline without or with a resultant eGFR 60 ml/min/1.73 mHGI independently predicted renal function deterioration in patients with type 2 diabetes and a low CKD risk. Further investigations are warranted to elucidate its potential clinical impact.

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.

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.

To describe the clinical characteristics and chronic diabetic complications in early (EOD) and late onset type 2 diabetes mellitus (LOD) in Asia.Retrospective collection of information (basic patient data, treatment received for diabetes, hypertension, dyslipidaemia, clinical measurements, complications, life-style management, etc.) on paper form and prospective collection of blood samples for HbA(1c) assessment were performed. Means, proportions and associated factors were analyzed using non-parametric and logistic regression.The frequency of EOD (30 years) varies in different Asian countries (0.4-5.3%). Overweight (BMIor=23 kg/m2) was common in both EOD (60%) and LOD (66%). EOD was characterized by significantly higher levels of HbA(1c) (median 8.9% versus 7.9%) and FPG (median 9.8 mmol/L versus 8.3 mmol/L) but hypertension was less common (43% versus 59%). Lipid profiles (cholesterol and triglycerides) were similar between both groups of patients. Cataract was more common in LOD and was associated with onset age and diabetes duration whereas an increase in frequency of advanced eye disease, retinopathy and history of photocoagulation was found in EOD cohort.In addition to diabetic control and duration of the disease, the onset age conferred risk to certain subsets of chronic complications in type 2 diabetes population.

Diabetes mellitus (DM) in adults is a global health problem, although its prevalence varies widely between different populations and the rate has generally increased worldwide. In Taiwan, the mortality rate from DM has almost doubled over the past 10 years. The prevalence of DM in Taiwan was established between 1985 and 1996 and the rates were between 4.9 and 9.2%. The prevalence of impaired glucose tolerance (IGT) was 15.5% (men 15% and women 15.9%). The prevalence of DM and IGT increased significantly with age for both genders. The significant factors associated with newly diagnosed DM were age, BMI, family history of DM, systolic blood pressure (hypertension), physical activity and serum triglyceride levels. The prevalence of large vessel disease (LVD) in DM and non-diabetic subjects were 20.0 and 12.9%, respectively. Among diabetics, 15.8% had ischemic heart disease (IHD), 1.7% leg vessel disease (leg VD), and 2.5% stroke. In non-diabetics, the prevalence of the aforementioned macroangiopathies were 11.5, 0.2 and 1.2%, respectively. The diabetics had a significantly higher prevalence of macrovascular disease than non-diabetic subjects. The most significantly associated with the LVD was serum cholesterol levels. Serum cholesterol and HbA1(c) were significantly associated with the development of IHD. Cigarette smoking and female gender were significantly associated with the leg VD. The prevalence of diabetic retinopathy (DR) was 35.0%. (background DR 30%, preproliferative DR 2.8% and proliferative DR 2.2%, respectively.) The prevalence of DR for previously and newly diagnosed diabetics were 45.2 and 28.3% (men 42.8 vs. 33.3% and women 47.5 vs. 24.8%), respectively. From multiple logistic regression analysis, duration of DM was the most important risk factor related to DR. Diabetic subjects treated with insulin had a higher risk of developing retinopathy than those treated with dietary control. The prevalence of nephropathy and neuropathy were 12.9 and 23.5%, respectively. For those patients with and those without nephropathy and neuropathy, the duration of DM, percentage of insulin treatment, percentage of hypertension, and fasting plasma glucose were significantly different. Diabetic duration, hypertension, insulin treatment and glycemic control consistently correlated with nephropathy and neuropathy. In conclusion, the prevalence of DM in Taiwan was between 4.9 and 9.2%, and the prevalence of IGT was 15.5%. The possible risk factors of newly diagnosed diabetes were age, family history of DM, BMI, SBP (hypertension), physical activity and triglyceride levels. Diabetes in Chinese subjects share many characteristics similar to other Asian populations. The burden imposed by the chronic complications of diabetes is massive. In Taiwan, the mortality rates from DM have increased greatly over the past 10 years. Reduction of the modificable risk factors such as BMI, hypertenion and dyslipidemia, and increase of physical activity and good glycemic control through public health efforts may help to reduce the risk of DM and its chronic complications.

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.

To evaluate the efficacy of exenatide in Asian patients with type 2 diabetes (T2D) inadequately controlled with oral agents.Patients taking metformin (MET) alone or with a sulphonylurea (SU) were randomly assigned to exenatide 5 microg then 10 microg twice-daily for 4 and 12 weeks, respectively, or placebo. The primary endpoint was baseline to endpoint HbA(1c) change.466 patients (age 54+/-9 years, weight 68.7+/-11.2 kg, BMI 26.3+/-3.3 kg/m(2), and HbA(1c) 8.3+/-1.1%; mean+/-S.D.) were enrolled in the full analysis set. Endpoint HbA(1c) reduction (mean [95% CI]) with exenatide was superior to placebo (-1.2 [-1.3, -1.1]% vs. -0.4 [-0.5, -0.2]%, p0.001). More exenatide- than placebo-treated patients achieved HbA(1c)or=7% (48% vs. 17%, p0.001). At endpoint, weight reduction was greater with exenatide (-1.2 [-1.5, -0.9]kg) than placebo (-0.1 [-0.3, 0.2]kg), p0.001. Nausea, generally mild-to-moderate, was the most common adverse event with exenatide (25% vs. 1% with placebo). The incidence of symptomatic hypoglycaemia with exenatide and placebo were 36% and 9%, respectively (p0.001). Hypoglycaemia rates (events/patient-year) for patients taking exenatide with MET or MET and SU were 1.8 (0.9, 3.7) and 4.7 (3.5, 6.5), respectively.Exenatide treatment improved glycaemic control in Asian patients with T2D and had a similar safety profile as in non-Asian patients.

Objective: To describe the gender differences in cases and characteristics of diabetes mellitus (DM) that can be identified from a mass urine screen program for school children in Taiwan. Method: Screening for the childhood asymptomatic proteinuria and glucosuria began in 1992 for school children. Students were instructed to collect mid-stream samples of the first morning urine for glucosuria and proteinuria tests using urine strip devices. Students with positive results for glucose and/or protein and/or occult blood in the first examination received a second urine test. The third screening test was performed for urine and fasting blood sample for 11-item examinations if the second test was positive. The 1997 criteria of American Diabetes Association were used for defining DM. Results: Approximately 2 615 000–2 932 000 students received the preliminary screening each semester. The overall average rates of newly identified diabetes from 1993 to 1999 were 8.3 per 100 000 among boys, and 12.0 per 100 000 among girls. The average rate of new cases increased significantly from sixth grade for boys and fourth grade for girls, with peak rates of 14.7 per 100 000 in eighth grade for boys and 19.0 per 100 000 in sixth grade for girls. Similar prevalence trends by sex and grade were observed, higher in girls than in boys. Conclusions: This mass screening data suggest that childhood diabetes of all types in Taiwan is elevated in the age of puberty and higher in girls than in boys.

Some environmental and genetic factors play important roles in etiopathogenesis of type 1 or insulin-dependent diabetes mellitus (IDDM). HLA genes, the IDDM1 locus located the human chromosome 6, were found to be associated with insulin-dependent diabetes mellitus. However, the incidence of IDDM varied greatly among various populations. To evaluate the pathogenetic factors contributing to the development of IDDM in Taiwan, HLA typing was performed in a group of IDDM unrelated individuals and IDDM pedigrees along with the normal controls from the northern Taiwan. DNA genotypes of class II HLA were done by polymerase-chain-reaction based oligotyping techniques. We confirmed that class II HLA genes were significantly associated with IDDM in Taiwan. To study detailed molecular structure of class II HLA molecules and disease association, we examined several amino acid residues on DQα and DQβ chains and the molecular mechanisms to explain the heterozygotic effect of the DR3/DR4 and DR3/DR9 in the Chinese population. Linkage analysis in our pedigrees confirmed the association between HLA and IDDM in population association studies. Among the several class II alleles, a closer segregation of HLA-DQB1*0401 to the affected persons might suggest that HLA-DQB1*0401 itself or an allele closely linked to the DQB1 locus was the IDDM-predisposing allele in Taiwanese. For IDDM2 ( INS ) region, association with IDDM was not found due to that more than 90% of the population carried class I alleles. In our collection of IDDM, we found few cases (2.4%) carried mitochondrial DNA mutation. Our studies in Taiwanese confirm a multigenetic nature for IDDM.

A multi-center prospective study was conducted to assess the function and impact of diabetic education programs on diabetic control. A total of 208 subjects with type 2 diabetes were recruited. Diabetes self-care, assessed by questionnaire, was evaluated before, and 4 months after attending a diabetes education course. A total of 121 subjects who received advanced diabetes education courses were designated as the experimental group. A second group of 87 cases receiving a basic course served as controls. In addition to basic knowledge, the advanced education programs included dietary control, blood glucose monitoring, management of hypoglycemia, medication compliance, foot care and exercise. Diabetes self-care techniques were significantly improved in the experimental group. The overall score for diabetes self-care techniques improved in both groups at the 4th month over baseline values. The change was significant with the controls' (P < 0.001). Multiple regression analysis confirmed the intensity of diabetic education was the only significant variable correlated with the decrease of fasting blood glucose and systolic blood pressure. In conclusion, integrated and intensive diabetes education program in diabetes education centers provides an effective method for improving diabetes self-care techniques and metabolic outcome.

Mutation of the glucokinase gene has recently been identified as a cause of maturity-onset diabetes of the young (MODY), a subset of non-insulin-dependent diabetes mellitus (NIDDM). However, its role in the wide variety of NIDDM remains controversial due to conflicting reports of association studies, negative results of linkage studies and low prevalence of glucokinase mutations in the common variety of NIDDM. In this study, two (CA)n-microsatellite polymorphisms flanking both ends of the glucokinase gene, termed GCK1 and GCK2, were used to evaluate the role of glucokinase on NIDDM susceptibility of Taiwanese. For GCK1, three alleles (Z,Z+2 and Z+4 with a polymorphic information content index (PIC) of 0.53) and six genotypes were evident in 119 Taiwanese. When compared with control subjects, the NIDDM group had a much less frequency of the Z+2 allele (14.0% vs. 23.9%). In addition, the Z+2 allele was noted to have a marginal protective effect for NIDDM in Taiwanese with the odds ratio of 0.52 (95% confidence interval (C.I.) 0.26-1.03, P = 0.058). For GCK2, four alleles (0, 2, 4 and 6 with a PIC of 0.48) and seven genotypes were identified. There was no significant difference in allele frequency between NIDDM and control groups in the locus of GCK2. Our data were in agreement with reports from American Blacks, Mauritian Creoles, Asian Indians, Japanese and Finnish--that there is a positive association of GCK1 and a negative association of GCK2 with NIDDM. Furthermore, the Z+2 allele was a protective factor for NIDDM in Taiwanese.

A total of 26 non-insulin-dependent diabetic patients were enrolled for a clinical study of the effect of buflomedil on microalbuminuria. None of the subjects had hypertension or macroproteinuria. Sixteen cases without previously known urinary albumin excretion rate (AER) were enrolled as experimental group. Buflomedil (Loftyl) was administered orally 600 mg daily in two divided doses in the experimental group while AER was determined 3 times with 3 weeks apart in all of the subjects. Ten cases with known microalbuminuria (greater than 8.55 micrograms/min) were enrolled as control group to check the extent of fluctuation in AER from collection to collection in the absence of urinary tract infection. Six of the experimental group showed AER of microalbuminuric level at the time before buflomedil administration and the remaining 10 patients were normoalbuminuric. The effects of buflomedil were compared between the microalbuminuric and normoalbuminuric subjects in the experimental group. The microalbuminuric group showed a significant decrease of AER from a baseline of 30.4 micrograms/min to 19.8 and 16.8 micrograms/min, respectively, after 3 and 6 weeks of treatment (P less than 0.05, Friedman two-way ANOVA). However, the respective values in the normoalbuminuric group were 5.3, 5.6 and 5.0 micrograms/min (P greater than 0.05, Friedman two-way ANOVA). The AER in the control group remained stationary during the study period (14.0, 12.1 and 11.4, respectively, Friedman two-way ANOVA, P greater than 0.05). These results suggest that buflomedil might be beneficial for the patients with microalbuminuria.

Urinary albumin excretion rate (AER) was monitored for periods of up to 3 years and 8 months with an ELISA method in 63 non-insulin-dependent diabetic Chinese subjects and was compared with 50 normal subjects. AER was 3.15 +/- 0.25 micrograms/min (M +/- SE) with a range of 0.27-8.40 micrograms/min for the normal subjects and 7.11 +/- 0.50 (2.11-19.45) micrograms/min for the diabetic subjects. The latter had significantly higher AER (P less than 0.0005). Age, sex, duration of diabetes, HbA1c and BMI did not correlate with AER in the diabetics. The presence of hypertension was found to be accompanied by an accelerated elevation of AER (5.96 +/- 1.58 vs 10.16 +/- 2.17 micrograms/min, at the beginning and at the end of the observation, respectively). Once hypertension became evident, control of blood pressure to a level comparable to that of the non-hypertensive group was not sufficient to halt the deterioration of urinary albumin excretion.