Acetylation of yeast AMPK controls intrinsic aging independently of caloric restriction.

Acetylation of histone and nonhistone proteins is an important posttranslational modification affecting many cellular processes. Here, we report that NuA4 acetylation of Sip2, a regulatory ß subunit of the Snf1 complex (yeast AMP-activated protein kinase), decreases as cells age. Sip2 acetylation, controlled by antagonizing NuA4 acetyltransferase and Rpd3 deacetylase, enhances interaction with Snf1, the catalytic subunit of Snf1 complex. Sip2-Snf1 interaction inhibits Snf1 activity, thus decreasing phosphorylation of a downstream target, Sch9 (homolog of Akt/S6K), and ultimately leading to slower growth but extended replicative life span. Sip2 acetylation mimetics are more resistant to oxidative stress. We further demonstrate that the anti-aging effect of Sip2 acetylation is independent of extrinsic nutrient availability and TORC1 activity. We propose a protein acetylation-phosphorylation cascade that regulates Sch9 activity, controls intrinsic aging, and extends replicative life span in yeast.

Accountability and utilization of diabetes care from 2005 to 2014 in Taiwan.

BACKGROUND/PURPOSE: Diabetes mellitus (DM) prevalence has been rapidly increasing in Taiwan and globally. Team care for DM has been provided through diabetes shared-care networks in Taiwan more than 20 years. METHODS: The study analyzed the National Health Insurance (NHI) claims data from 2005 to 2014 to better understand diabetes care accountability and utilization in Taiwan. RESULTS: The completion rate of annual check-ups for various metabolic measurements increased significantly, which indicates improvement in diabetes management quality. The average annual visits and drug cost for each patient increased enormously from 2005 to 2014. The annual number of outpatient department/inpatient department (OPD/IPD) patients with diabetes undergoing dialysis increased. The number of OPD visits in patients with diabetes was 1.9 times higher than that in all patients in general. IPD cost appeared to increase, whereas both drug cost and the average length of hospitalization per patient decreased. Endocrine and metabolic diseases were still the leading cause of OPD expenses. The leading cause of IPD expenses was respiratory diseases. An increasing trend was noted in the medical cost for patients with microvascular instead of macrovascular complications. OPD care for patients with diabetes was rather evenly distributed since 2009. Regarding IPD care, medical centers and regional hospitals each hospitalized 37% of the diabetic outpatients in 2014. CONCLUSION: Accountability of diabetes care in Taiwan improved significantly till 2014. The ongoing fight against DM and tracing, examining and learning from the overall outcomes in future decades is still required.

Effects of high-dose phytoestrogens on circulating cellular microparticles and coagulation function in postmenopausal women.

BACKGROUND/PURPOSE: Estrogen in hormone replacement therapy causes homeostatic changes. However, little is known regarding the safety of high-dose phytoestrogen on coagulation and hematological parameters in healthy postmenopausal women. This study evaluated the effects of high-dose soy isoflavone (300 mg/day) on blood pressure, hematological parameters, and coagulation functions including circulating microparticles in healthy postmenopausal women. METHODS: The original study is a 2-year prospective, double-blind, placebo-controlled study. In total, 431 postmenopausal women (from 3 medical centers) were randomly assigned to receive either high-dose isoflavone or placebo for 2 years. At baseline, 6 months, 1 year, and 2 years after treatment, blood pressure, body weight, liver function tests, hematological parameters, and lipid profiles were measured. The 1(st) year blood specimens of 85 cases of 144 eligible participants (from one of the three centers) were analyzed as D-dimer, von Willebrand factor antigen, factor VII, plasminogen activator inhibitor type 1, and circulating cellular microparticles, including the measurement of monocyte, platelet, and endothelial microparticles. RESULTS: In the isoflavone group, after 1 year, the changes in liver function tests, hematological parameters, and coagulation tests were not different from those of the control. Triglyceride levels were significantly lower after 6 months of isoflavone treatment than the placebo group, but the difference did not persist after 1 year. Endothelial microparticles increased steadily in both groups during the 1-year period but the trend was not affected by treatment. CONCLUSION: The results of the present study indicate that high-dose isoflavone treatment (300 mg/day) does not cause hematological abnormalities or activate coagulation factors.

Incidence and prevalence rates of diabetes mellitus in Taiwan: analysis of the 2000-2009 Nationwide Health Insurance database.

BACKGROUND/PURPOSE: Formerly, Taiwan's diabetic population has been estimated by surveys conducted at irregular intervals and using different sampling methods. To obtain nationwide data on the incidence and prevalence of diabetes mellitus (DM) in Taiwan, we performed an analysis of the 2000-2009 claim data from the National Health Insurance (NHI) database. METHODS: One-third of the claims in the NHI database from 2000 to 2009 were randomly sampled. DM was defined by three or more outpatient visits with diagnostic codes (ICD-9-CM: 250 or A code: A181) within 1 year or by one inpatient discharge diagnosis of DM. Confirmation of type 1 diabetes mellitus was based on the issue of a catastrophic illness certificate with the same diagnostic codes. Age and/or gender distribution for DM were determined. RESULTS: In accordance with the global trend for DM, with a near constant standardized incidence rate, there was a more than 70% increase in the total diabetic population, or a 35% increase in the standardized prevalence rate, in Taiwan from 2000 to 2009. The incidence of diabetes was higher in men, especially in the 20-59-year-old age group, and the total number of men with diabetes exceeded the number of women with diabetes in 2005. However, the prevalence and incidence rates in women over the age of 60 years were higher than those in men. Type 1 DM was present in less than 1% of the diabetic population in Taiwan. CONCLUSION: The incidence of diabetes, including type 1, remained stable over this 10-year period in Taiwan. However, the incidence rate in men aged 20-59 years was higher than that in age-matched women. With our nationwide database, subgroup analysis of DM incidence can be performed to refine our health policies for the prevention, screening, and treatment of diabetes mellitus.

Diabetes-related kidney, eye, and foot disease in Taiwan: an analysis of the nationwide data for 2000-2009.

BACKGROUND/PURPOSE: Diabetes is one of the leading causes of dialysis, blindness, and amputation worldwide. However, the prevalence of diabetes-related kidney, eye, and foot diseases has not been investigated in national surveys. METHODS: In this study, we reviewed data sets of the National Health Insurance claims for the years 2000-2009. In 2009, the total population of Taiwan was 23 million. We de-identified the data and then analyzed them on inpatients and outpatients with diabetes mellitus, kidney diseases, eye diseases, peripheral vascular diseases (PVDs), and diabetic foot according to the International Classification of Diseases, 9(th) Revision with Clinical Modification diagnosis codes. RESULTS: The prevalence of diabetic nephropathy increased from 13.32% in 2000 to 15.42% in 2009. The corresponding diabetes dialysis rate increased from 1.5% to 2.46% during the same period (p < 0.001). The prevalence rates of retinopathy and PVD also increased (from 6.17% to 8.91%; p = 0.002 and from 1.87 to 2.47; p < 0.001, respectively). More than 94% of the patients treated for diabetic foot in the hospital had an associated foot infection. The prevalence of in-hospital diabetic foot decreased from 1.68% to 1.02% during the years 2000-2009 (p < 0.001), while the rates of lower extremity amputation as the treatment outcome did not show improvement (mean amputation rate: 28.35%). CONCLUSION: During the years 2000-2009, patients with diabetes in Taiwan had an increased risk for kidney, eye, and PVDs. Multidisciplinary teams need to be set up for the treatment of complications related to diabetic foot, and preventions programs that are specifically designed to target these complications should now be made mandatory.

Prevalence of hypertension and dyslipidemia and their associations with micro- and macrovascular diseases in patients with diabetes in Taiwan: an analysis of nationwide data for 2000-2009.

BACKGROUND/PURPOSE: Cardiovascular complication is the leading cause of mortality in patients with diabetes. Dyslipidemia and hypertension are the major risk factors contributing to cardiovascular disease (CVD). This study was carried out to investigate the prevalence of dyslipidemia and hypertension and their associations with microvascular and macrovascular complications in patients with type 2 diabetes in Taiwan. METHODS: Health-care data and diagnostic codes were retrieved from the Taiwan Bureau of National Health Insurance claims files for the years 2000-2009. Based on these data the annual prevalences of dyslipidemia and hypertension were calculated and patients were stratified by age, gender, and diabetic complications. RESULTS: In patients with diabetes, the prevalence of dyslipidemia increased with age, with the highest rate recorded in adults (inclusive of both genders) between 40 and 65 years of age (p for trend <0.001). The prevalence of hypertension also increased with age with the highest rate seen in adults (inclusive of both genders) >65 years of age (p for trend <0.001). The prevalence of stroke and CVD decreased gradually (p for trend 0.025 and <0.001, respectively), while the prevalence of peripheral vascular disease (PVD) increased in patients with diabetes during the study period (p for trend <0.001). The prevalence of dyslipidemia increased in diabetic patients with eye diseases and in men with nephropathies, but decreased in women with nephropathies during the study period. In contrast, the prevalence of dyslipidemia decreased in patients with macrovascular complications, including CVD and cerebrovascular disease (cerebrovascular accident), but increased in those patients with PVD (p for all trends <0.05). In diabetic patients with various macrovascular complications, except PVD, there was a decrease in the prevalence of hypertension in the past 10 years. The prevalence of hypertension increased in patients with microvascular complications including retinopathy, patients on dialysis (inclusive of both genders), and in men with nephropathy. The prevalence of hypertension along with dyslipidemia increased in patients with microvascular complications including retinopathy, patients on dialysis (inclusive of both genders), and in men with nephropathy; however, the rate decreased in all macrovascular complications except in PVD. CONCLUSION: Although progressively increased prevalence of dyslipidemia and hypertension was observed in patients with diabetes in Taiwan, there was a decrease in the prevalence of stroke and CVD in the past 10 years. Among those with macrovascular diseases, except PVD, there was a trend of decreased prevalence of hypertension and dyslipidemia during the study period. In patients with microvascular diseases, prevalence of hypertension and dyslipidemia in patients with eye diseases increased in the past 10 years. More aggressive management of different risk factors is warranted in diabetic patients with various vascular diseases.

A longitudinal analysis of serum adiponectin levels and bone mineral density in postmenopausal women in Taiwan.

Since bone and fat mass are derived from mesenchyme in early development, adipokines secreted by adipose tissue may have an effect on bone metabolism. The relationship between adiponectin and bone mineral density (BMD) has been inconsistent in previous reports, with results being dependent on age, gender, menopausal status and bone sites. We investigated the relationship between serum adiponectin levels and the BMD of proximal femur and vertebrae bones in a 96-week longitudinal study of post-menopausal women with repeated measures of both. Linear regression models were used to determine the relation between adiponectin and BMD at each time point cross-sectionally, and a generalized estimating equation (GEE) model was used to investigate the longitudinal trends. Among 431 subjects, 376 (87%) provided baseline adiponectin measurements and 373 provided more than two measurements for longitudinal analysis. The means of serum adiponectin and BMD decreased with time. In linear regression models, adiponectin at baseline, the 48th week and the 96th week appeared to be inversely associated with BMD of proximal femur bone, but not lumbar spine after adjusting for age and various confounders. However, they all turn insignificant with further adjustment of body mass index. The inverse association between adiponectin and BMD of proximal femur is substantiated by all generalized equation models. Before adding the BMI in the model, the increase of 1 mg/dL of adiponectin can accelerate the decrease of proximal femur BMD by 0.001 (SE = 0.0004, p = 0.008). With BMI in the model, the drop rate was 0.0008 (SE = 0.0004, p = 0.026) and remained similar with further adjustment of two bone turnover markers. In this longitudinal analysis with both adiponectin and BMD measured at three time points, we demonstrate that with the increase of adiponectin level, the decline of proximal femur BMD in postmenopausal women accelerated during a period of 96 weeks.

Investigation of urodynamic characteristics and bladder sensory function in the early stages of diabetic bladder dysfunction in women with type 2 diabetes.

PURPOSE: We studied urodynamic characteristics and bladder sensory function in the early stages of diabetic bladder dysfunction in diabetic women. MATERIALS AND METHODS: A total of 86 consecutive type 2 diabetic women with minimal confounders of voiding dysfunction followed at a diabetes clinic were prospectively enrolled and subjected to urodynamic studies. The sensory response of Adelta and C fibers of the bladder was measured by intravesical current perception threshold testing at frequencies of 250 and 5 Hz, respectively. RESULTS: Of these 86 women 30 (34.9%) were classified as having detrusor underactivity, 12 (14.0%) presented signs of detrusor overactivity, 11 (12.8%) were referred to as having bladder outlet obstruction and 33 (38.4%) showed normal detrusor function on urodynamics. The normal detrusor function group was the reference group. The detrusor underactivity group showed impaired emptying function and decreased sensation on cystometry and intravesical current perception threshold testing. The detrusor overactivity group showed impaired storage and emptying function but had no significant changes in intravesical current perception threshold values. When the normal detrusor function group and detrusor underactivity group were pooled to perform multivariate analysis, an increase in current perception threshold values was associated with a decrease in bladder voiding efficiency on 5 and 250 Hz current perception threshold testing. CONCLUSIONS: Our data provide the electrophysiological evidence that indicates an association between impaired Adelta as well as C fiber bladder afferent pathways and poor emptying function in diabetic women with detrusor underactivity. Diabetes can affect the bladder presumably via peripheral pathogenetic mechanisms to induce detrusor overactivity with impaired contractility.

The negative correlation between plasma adiponectin and blood pressure depends on obesity: a family-based association study in SAPPHIRe.

BACKGROUND: The association between plasma adiponectin level and blood pressure remains inconclusive. Because obese subjects may have different mechanisms to regulate blood pressure, we hypothesized that obesity may be an important modifier. In order to minimize confounding effects from unidentified factors, a family-based design was employed to explore the relationship. METHODS: A total of 1,048 subjects from 478 Chinese or Japanese families with a mean age of 50.4 +/- 9.0 years were included (the SAPPHIRe (Stanford-Asian Pacific Program in Hypertension and Insulin Resistance) cohort). Blood pressure was recorded automatically and the average of the last two out of three consecutive readings was used in the analysis. A subject with "hypertension" was defined as one with a systolic blood pressure (SBP) > or =140 mm Hg, or a diastolic blood pressure (DBP) > or =90 mm Hg, or who was already on medication for hypertension. Obesity was defined as having a body mass index (BMI) > or =25 kg/m(2). The updated homeostasis model assessment was used for calculating the indices of insulin sensitivity (HOMA2 %S). Fasting plasma adiponectin was determined using radioimmunoassay. RESULTS: Subjects with hypertension had significantly lower plasma adiponectin levels than those without hypertension (5.99 +/- 3.64 microg/ml vs. 6.65 +/- 3.86 microg/ml, P < 0.01). Plasma adiponectin level correlated negatively with hypertension after adjusting for age, sex, and HOMA2%S (odds ratio (OR) 0.94, 95% confidence interval (CI) 0.90-0.98). In subjects without hypertension (n = 349), the plasma adiponectin level correlated negatively with SBP in those who were obese, after adjustment for age, sex, BMI, and HOMA2 %S (beta = -0.58, P = 0.03). The association was not significant in those without obesity. CONCLUSIONS: Plasma adiponectin level correlates negatively with hypertension. In subjects without hypertension, the relationship between plasma adiponectin level and SBP depends on the presence of obesity.

The association between urinary albumin excretion and ankle-brachial index in elderly Taiwanese patients with type 2 diabetes mellitus.

OBJECTIVE: this study examined the association between urinary albumin/creatinine ratio (ACR) and ankle-brachial index (ABI), or peripheral arterial disease (PAD), in elderly patients with type 2 diabetes mellitus (T2DM). METHODS: a total of 290 (108 men, 182 women) T2DM, aged > or =65 (71.6 +/- 4.9) years were recruited. PAD was diagnosed by ABI<0.9, and ACR was divided into normoalbuminuria (<30.0 microg/mg), microalbuminuria (30.0-299.9 microg/mg), and macroalbuminuria (> or = 300.0 microg/mg). RESULTS: patients with PAD (n = 45) had higher ln(ACR) than patients without: 4.48 +/- 1.48 versus 3.73 +/- 1.39 (P<0.01). For normoalbuminuria (n = 112), microalbuminuria (n = 152), and macroalbuminuria (n = 26), respective PAD prevalence was 8.0, 17.1 and 38.5% (P<0.001). The proportion of normoalbuminuria, microalbuminuria and macroalbuminuria in patients with PAD was 20.0, 57.8 and 22.2%, respectively; and 42.0, 51.4 and 6.5%, respectively, in patients without (P<0.001). Ln(ACR) was inversely correlated with ABI in all patients (gamma = -0.198, P<0.01) and in separate sexes (gamma = -0.211 for men and gamma = -0.181 for women). The multivariate-adjusted odds ratios for PAD for every 1 unit increment of ln(ACR) was 1.66 (1.17-2.34); and for microalbuminuria versus normoalbuminuria and macroalbuminuria versus normoalbuminuria were 2.54 (1.05-6.17) and 5.86 (1.76-19.52), respectively. CONCLUSIONS: urinary ACR is not only associated with PAD, it is also significantly correlated with ABI in an inverse pattern in elderly Taiwanese with T2DM.

Adiponectin SNP276 is associated with obesity, the metabolic syndrome, and diabetes in the elderly.

BACKGROUND: Genetic variations of the human adiponectin gene are associated with metabolic phenotypes, including obesity, insulin sensitivity, and diabetes. However, these associations have not been examined in an elderly population. OBJECTIVE: The objective of the study was to investigate whether the genetic variants of adiponectin are associated with any metabolic phenotype in the elderly. DESIGN: In a population-based, case-control genetic association study, a total of 1438 subjects >65 y old were recruited from the community. The phenotypes of the metabolic syndrome (MetS) were measured. Four single-nucleotide polymorphisms (SNP) were genotyped by mass spectrometry. RESULTS: The G allele of SNP276 in intron 2 was associated with a reduced risk of obesity, MetS, and diabetes mellitus. The GT genotype relative to the GG genotype had an age- and sex-adjusted odds ratio of 1.32 for obesity [body mass index (BMI; in kg/m(2)) >or= 25; P = 0.014] and of 1.33 (P = 0.011) and 1.47 (P = 0.001) for MetS according to modified National Cholesterol Education Program and International Diabetes Federation criteria, respectively. The age-, sex-, and BMI-adjusted odds ratio of diabetes mellitus for the GT and TT genotypes relative to the GG genotype were 1.28 (P = 0.042) and 1.72 (P = 0.013), respectively, and there was an obvious dosage effect (P for trend = 0.004). In linear regression after adjustment for age, sex, and BMI, the GT and TT genotypes were associated with fasting plasma glucose concentrations 5.2 and 11.1 mg/dL higher, respectively, than those of the GG genotype. CONCLUSIONS: Genetic variation of the adiponectin gene is associated with obesity, MetS, and diabetes mellitus in the elderly. The genetic effect on diabetes mellitus is partially independent of BMI.

Relationship of homocysteine levels to quadriceps strength, gait speed, and late-life disability in older adults.

BACKGROUND: Elevated homocysteine, causing tissue injury by such mechanisms as oxidative stress, endothelial damage, and protein homocysteinylation, is associated with multiple age-related problems including cardiovascular diseases, dementia, and osteoporotic fracture. Disability is one of the most common features in older adults. However, little is known about the role of homocysteine in physical disability among older adults. METHODS: Participants (>60 years, N = 1677) were from the National Health and Nutrition Examination Survey (NHANES) 1999-2002. Nineteen questionnaires in five major domains were administered to assess the level of difficulty in performing various tasks: activities of daily living (ADL), instrumental ADL (IADL), leisure and social activities (LSA), lower extremity mobility (LEM), and general physical activities (GPA). Peak quadriceps strength was obtained by using an isokinetic dynamometer. Habitual gait speed was obtained from a 20-foot timed walk. Homocysteine levels were measured by the Abbott homocysteine assay, an automated fluorescence polarization immunoassay (FPIA). RESULTS: Elevated homocysteine was associated with disability in ADL, IADL, LSA, and GPA after multivariate adjustment. The odds ratios (ORs) for disability in these domains comparing participants in the highest quartile of homocysteine to those in the lowest were 2.18 (95% confidence interval [CI], 1.32-3.59) for ADL; 1.62 (95% CI, 1.02-2.57) for IADL; 2.00 (95% CI, 1.14-3.51) for LSA; and 1.52 (95% CI, 1.05-2.21) for GPA. The strength of associations weakened somewhat after additional adjustment of quadriceps strength and/or gait speed, suggesting a mediating role of quadriceps strength and gait speed in the association between homocysteine and disability. Homocysteine had an inverse relationship to quadriceps strength and gait speed. Likewise, quadriceps strength seemed to mediate the inverse association between homocysteine and gait speed. CONCLUSIONS: Elevated homocysteine is associated with multiple domains of disability mediated in part by muscle strength and gait speed. The results suggest that homocysteine levels may be important indicators of performance status in older adults.

Multi-country study on the prevalence and clinical features of peripheral arterial disease in Asian type 2 diabetes patients at high risk of atherosclerosis.

OBJECTIVE: PAD-SEARCH was the first international study to investigate the prevalence of peripheral arterial disease (PAD) in Asian type 2 diabetic patients and to demonstrate the relationships between putative risk factors and PAD. SUBJECTS AND METHODS: In total 6625 type 2 diabetic patients aged 50 and older were enrolled and determined ankle-brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV) in Korea, China, Taiwan, Hong Kong, Indonesia, Thailand and the Philippines. RESULTS: Mean patient age was 63.7+/-8.2 years and mean duration of diabetes was 10.3+/-8.0 years. One thousand one hundred and seventy-two (17.7%) subjects were diagnosed as PAD by ABI (< or =0.9). PAD subjects had a significantly longer duration of diabetes, hypertension, higher HbA1c, and a significantly lower mean BMI than non-PAD subjects. In terms of lipid profiles, triglyceride was the only significant variable. Notably, mean ABI and baPWV in females were significantly poorer than age matched males in subjects with a normal ABI. However, mean ABI and baPWV in males were significantly poorer than in age matched females in subjects with PAD. CONCLUSIONS: These findings suggest that PAD is a common complication in Asian type 2 diabetic patients. Therefore, PAD screening and treatment should be emphasized for Asian diabetic patients with high risk factors.

Clinical and laboratory predictors of all-cause mortality in older population.

Although some clinical and laboratory tests have been studied on their individual relationship with total mortality or cause-specific mortality such as cardiovascular mortality, the overall effect of these indicators on mortality has rarely been evaluated. The purposes of this study were to assess the relationship of clinical and laboratory measures and all-cause mortality and to evaluate their potential clinical importance in mortality prediction in older adults. A sample of 2086 persons aged 65 and older participating the population-based health examination in 1995 and 1996 in Kaohsiung City, Taiwan was followed until the end of 2003. All participants completed medical history and underwent clinical assessment and laboratory tests. Measures selected for analysis were pulse rate, blood pressure, height, weight, serum level of cholesterol, triglyceride, creatinine, and uric acid, fasting blood glucose (FBG), hemoglobin (HG) and red (RBC) and white blood cell (WBC) counts. Cox regression was used to select measures significant to total mortality. All participants were further classified into risk groups, based on disease history and values of measures identified from analyses, to evaluate mortality risk. A total of 409 deaths occurred during an average of 8.2 years of follow-up time. Among all 14 measures assessed individually, five (systolic blood pressure=SBP, creatinine, uric acid, FBG, and HG) were statistically related to total mortality. SBP (hazard ratio (HR)=1.22; 95% confidence interval (CI)=1.09-1.36), FBG (HR=1.18; CI=1.08-1.29), and HG (HR=0.81; CI=0.73-0.91) were further identified to have independent effect on total mortality in the multivariate analysis. Age- and sex-adjusted total mortality HRs for disease risk (with disease history but with normal biomedical values), biomedical risk (without disease history but with abnormal biomedical values), and combined risk groups (with disease history and with abnormal biomedical values) were 1.94 (CI=1.22-3.10), 2.08 (CI=1.57-2.76), and 2.45 (CI=1.83-3.27) compared with low risk group (without diseases history and with normal biomedical values). Results from this study reveal the importance of incorporating clinical and laboratory measures on the assessment of mortality in older adults. Establishing mortality risk profile based on both diseases conditions and inexpensive biomedical measures (for example, SBP, FBG and HG identified in the study) may help physicians in evaluating older persons' prognosis.

Independent association between triglycerides and coronary artery disease in Taiwanese type 2 diabetic patients.

BACKGROUND: This study evaluated the association between triglycerides (TG) and coronary artery disease (CAD) in Taiwanese adults with type 2 diabetes mellitus (T2DM). METHODS: A total of 1150 patients (542 men and 608 women) aged 62.5+/-11.6 years were studied. CAD was diagnosed by history or an abnormal electrocardiogram (coronary probable or possible by Minnesota codes). Age, body mass index (BMI), smoking, use of insulin, anti-hypertensive agents and lipid-lowering agents, fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), systolic blood pressure (SBP), diastolic blood pressure (DBP), serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c) were considered as potential confounders. RESULTS: Patients with CAD were older, had higher prevalences of use of anti-hypertensive and lipid-lowering agents, and had higher BMI, SBP, DBP and TG. CAD increased significantly with increasing quartiles of TG (P-trend < 0.001). Ln(TG) was significantly correlated with BMI, FPG, HbA1c, DBP, TC, HDL-c (inversely) and LDL-c. Ln(TG) was associated with CAD with an unadjusted odds ratio of 1.411 (1.145-1.740). The odds ratio after adjustment for all confounders was slightly attenuated but still statistically significant: 1.380 (1.043-1.826). None of the other lipid parameters of TC, HDL-c and LDL-c were significantly associated with CAD in logistic models when they were entered for adjustment either separately or simultaneously. Sensitivity analyses by using history alone or history and coronary probable as diagnostic criteria for CAD did not change the association between TG and CAD. CONCLUSIONS: TG is an independent risk factor for CAD in Taiwanese T2DM, independent of TC, HDL-c, LDL-c or other confounders.

Treatment of type 2 diabetes mellitus in a primary care setting in Taiwan: comparison with secondary/tertiary care.

BACKGROUND: This study investigated the status of diabetes control and management in patients treated in a primary healthcare setting and compared the results with data previously obtained for secondary/tertiary care patients in Taiwan. METHODS: This study was conducted at 51 primary healthcare stations randomly selected island-wide in Taiwan in 2001. A total of 1302 type 2 diabetes patients who had been followed-up for more than 1 year were included. Blood was collected for centralized HbA1c assay. The remaining data and information were collected by review of medical records and patient interview. RESULTS: Compared with the results of a previous study on patients treated in a secondary/tertiary care setting, a significantly smaller percentage of primary care patients were receiving insulin therapy. Primary care patients also had a shorter duration of diabetes, a higher HbA1c level, better blood pressure control and a lower prevalence of complications. The proportion of patients achieving optimal control of glycemia and blood pressure was low. Patients aged < 65 years had a significantly shorter duration of diabetes, poorer diabetes control and better blood pressure control than elderly patients aged > or = 65 years. Primary care patients aged > or = 65 years had a significantly higher frequency of stroke than those aged < 65 years. The elderly group of secondary/tertiary care patients had a significantly higher frequency of coronary heart disease and stroke. Duration of diabetes and hypertension were the leading risk factors for complications in diabetes patients treated in both primary and secondary/tertiary care settings. CONCLUSION: Diabetes control was poorer in primary care than in secondary/tertiary care patients, but control of blood pressure was better in primary care patients. The shorter duration of diabetes and better control of blood pressure in primary care patients and in patients aged < 65 years compared with their elderly counterparts might be related to a lower prevalence of complications.

Associations between lower urinary tract dysfunction and glycemic control in women with type 2 diabetes: A cross-sectional study.

AIMS: Patients with diabetes are predisposed to develop a variety of complications, including lower urinary tract (LUT) dysfunction. We aimed to examine the associations between glycemic control and LUT dysfunction in women with type 2 diabetes (T2D). METHODS: We included 400 women with T2D (age range, 48-75 years) in this cross-sectional analysis. The participants were divided into tertiles according to glycosylated hemoglobin (HbA1c) measurements. The mean HbA1c levels for tertiles 1, 2, and 3 were 6.2% (N=132), 7.1% (N=132), and 8.4% (N=136), respectively. We evaluated LUT dysfunction with the American Urological Association Symptom Index (AUA-SI) questionnaire, uroflowmetry (UFM), and post-void residual (PVR). RESULTS: No significant differences were found among HbA1c tertiles regarding storage, voiding and total AUA-SI scores, and prevalence of LUT symptoms. However, women in tertile 3 had higher prevalences of severe LUT symptoms (AUA-SI≥20) and clinically significant PVR (≥100mL) compared to women in the other tertiles. Multivariate analysis revealed that diabetic neuropathy, but not HbA1c, significantly predicted LUT symptoms in women with T2D after adjustment for age, body mass index (BMI) and hypertension. However, HbA1c was associated with an increased risk of developing clinically significant PVR. CONCLUSIONS: Our findings do not support significant associations between glycemic control and LUT symptoms in women with T2D. However, women with poor glycemic control are more likely to develop urinary retention than women with proper glycemic control. Clinicians should, therefore, be aware of and educate patients about the association between urinary retention and glycemic control.

Retinoic acid blocks pro-inflammatory cytokine-induced matrix metalloproteinase production by down-regulating JNK-AP-1 signaling in human chondrocytes.

The development of osteoarthritis (OA) has recently been implicated as a result of immune-mediated damage of chondrocytes and their supporting matrixes. Pro-inflammatory cytokines like interleukin (IL)-1 and tumor necrosis factor alpha (TNF-alpha) play pivotal roles in immunopathogenesis of OA. Because vitamins preserving anti-oxidative effects are suggested to provide protection in OA patients from joint damage, in the present study, we examined the effects and mechanisms of all-trans retinoic acid (t-RA) in suppressing pro-inflammatory cytokine-induced matrix metalloproteinases (MMPs) production in human chondrocytes. Chondrocytes were prepared from cartilage specimens of OA patients receiving total hip or total knee replacement. The protein concentration was measured by ELISA, the mRNA expression by reverse transcriptase-polymerase chain reaction, the protein expression by Western blotting, the transcription factor DNA-binding activity by electrophoretic mobility shift assay and the protein kinase activity by kinase assay. We showed that both MMP-1 and MMP-13 mRNA expression, protein production and enzyme activity induced by either IL-1 or TNF-alpha were suppressed by t-RA or different retinoid derivatives. The molecular investigation revealed that the t-RA-mediated suppression was likely through blocking p38 kinase and c-Jun N-terminal kinase-activator protein-1 signaling pathways. In contrast, t-RA had no effect on extracellular signal-regulated kinase activity, nuclear factor (kappa)B (NF-(kappa)B) DNA-binding activity and I(kappa)B(alpha) degradation. Furthermore, we showed that t-RA could reduce IL-1-induced TNF-alpha production in chondrocytes. Our results suggest that vitamin A may protect OA patients from pro-inflammatory cytokine-mediated damage of chondrocytes and their supporting matrixes.

Arsenic ingestion and increased microvascular disease risk: observations from the south-western arseniasis-endemic area in Taiwan.

BACKGROUND: We established the association between arsenic ingestion and increased risk of vascular diseases associated with diabetes. However, the specific microvascular diseases in relation to arsenic exposure level have not been well reported. METHODS: The study population was obtained through national health database linkage. A total of 28 499 subjects living in the study area were successfully linked with their medical records from the National Health Insurance database in 1999-2000. The arsenic concentrations of artesian well water in the villages of the study area were utilized as indices of previous ingestion level. Both stratified analysis and unconditional logistic regression were used to examine mainly neurological and renal disease in relation to the arsenic exposure taking into account diabetes status. RESULTS: The age-adjusted and gender-adjusted prevalence of microvascular diseases was 7.51% [95% confidence interval (CI) 7.50-7.51] for arsenic level of <0.1 mg/litre, and then increased from 6.59% (6.59-6.60) for the arsenic concentrations of 0.1-0.29 mg/litre to 8.02% (8.02-8.03) and 11.82% (11.81-11.83) for those of 0.3-0.59 mg/litre and > or =0.6 mg/litre in non-diabetic subjects. For diabetic patients, the prevalence was 16.41% (95% CI 16.37-16.45), 15.85% (15.8-15.9), 21.69% (21.6-21.8), and 28.31% (28.2-28.4) for arsenic levels <0.1, 0.1-0.29, 0.3-0.59, and > or =0.6 mg/litre, respectively. The prevalence of microvascular diseases increased significantly with arsenic exposure, especially at higher levels, and the relationship is stronger in diabetics than in non-diabetic subjects. The results for neurological disease are very similar, and the patterns are the same for renal disease. CONCLUSIONS: The increased prevalence of microvascular diseases, including neurological and renal disorders, is associated with arsenic ingestion. This excess risk was further elevated in diabetic subjects. Further studies are necessary to verify the hypotheses of threshold or dose-response relationships.

Allele-specific differential expression of a common adiponectin gene polymorphism related to obesity.

Adiponectin gene polymorphisms have recently been reported to be associated with obesity, insulin sensitivity, and the risk of type 2 diabetes. We examined a T94G polymorphism of the adiponectin gene in 245 ostensibly normal nondiabetic subjects. The G allele frequency was lower among subjects with higher BMI (> or =27) than in those with lower BMI. BMI was inversely correlated with the dose of G allele. Multivariate linear regression analyses showed that the adiponectin genotypes were significantly related to BMI after adjusting for age and gender. The dose of the G allele was associated with a reduction of approximately 1.12 kg/m(2) in BMI. We further found that the relative mRNA levels of G allele were consistently higher than those of T allele in the omental adipose tissue from 21 heterozygous subjects. Finally, we observed that the expression levels of adiponectin affected insulin-stimulated glucose uptake in differentiated 3T3-L1 adipocytes. In conclusion, the allele-specific differential expression of this common polymorphism could be responsible for its biological effects observed in this and the other studies.