Nephrolithiasis is associated with the severity of coronary artery calcification, but not with coronary artery stenosis.

PURPOSE: Emerging data have indicated that nephrolithiasis is possibly associated with subclinical coronary artery disease (CAD). Considering that a significant proportion of obstructive CAD in non-elderly individuals occurs in those without detectable calcium score (CACS), this study aimed to investigate whether nephrolithiasis is still associated with CAD as assessed by coronary computed tomography (CT)-derived luminal stenosis [using Gensini score (GS)]. METHODS: A total of 1170 asymptomatic adults without known CAD who underwent health examinations were recruited. Nephrolithiasis was assessed using abdominal ultrasonography (US). Individuals with a self-reported stone history, but no evidence of nephrolithiasis were excluded. The CACS and GS were measured using 256-slice coronary CT. RESULTS: Nearly half of these patients had a CACS > 0 (48.1%), and a higher prevalence of nephrolithiasis was observed than in those who had zero CACS (13.1% vs. 9.7%). However, no significant intergroup difference in GS was detected. A greater proportion of stone formers than non-stone formers had a higher risk category, whereas no significant difference was noted in Gensini category. Multiple linear regression analyses showed that the CACS independently predicted the presence of nephrolithiasis after adjustment. Importantly, we found that stone formers had a nearly threefold higher risk than non-stone formers of developing severe coronary calcification (CAC > 400). CONCLUSIONS: Nephrolithiasis was significantly associated with coronary artery calcification presence and severity, but not coronary luminal stenosis in patients without known CAD. Accordingly, the relationship between stone disease and CAD remains controversial, and additional studies are imperative to validate these findings.

Functional status associated with postural dizziness, but not postural hypotension, in older adults: a community-based study.

BACKGROUND: Functional status, postural dizziness (PD), and postural hypotension (PH) were important issues in older adults. Only one study on the relationship for the three of them in female was without adjusting some important associated factors. This study was intended to investigate the association of PD and PH with functional status in older people of both genders. METHODS: Based on a stratified randomized cluster sampling, 1361 subjects ≥ 65 years in the community were recruited from Tainan City, Taiwan, from 2000 to 2001. PH was defined as a decrease in systolic/diastolic blood pressure of ≥ 20/10 mm Hg after 1 or 2 min of standing. PD was defined by a positive response to dizziness-like symptoms after standing up from a supine position. Functional status included the activities of daily living (ADLs) and instrumental activities of daily living (IADLs). RESULTS: After adjusting other variables, ADL disability (OR: 1.84, 95% CI: 1.35-2.51) and IADL disability (OR: 1.62, 95% CI: 1.21-2.17) were associated with PD, but not PH. In male and female subgroups, ADL disability (male OR: 1.70, 95% CI: 1.08-2.67; female OR 1.96, 95% CI: 1.26-3.07) was associated with PD. In male, IADL disability was associated with PD (OR: 2.32, 95% CI: 1.36-3.95). CONCLUSIONS: Impaired functional status, shown using ADLs or IADLs, was positively associated with PD, but not PH in older adults ≥ 65 years. Clinically, it may be important to evaluate PD in older adults with ADL or IADL disability.

Disease-related disability burden: a comparison of seven chronic conditions in middle-aged and older adults.

BACKGROUND: Although previous studies have explored the effect of chronic conditions on physical disability, little is known about the levels and rates of change in physical disability after a chronic condition diagnosis in middle-aged and older adults in the Asian population. The aim of this study is to ascertain the average levels and rates of change in the development of disability after disease diagnosis, as well as to determine the influences of sociodemographic and health-related correlates in the development of disability. METHODS: This is a retrospective cohort study analyzing data of nationally representative participants aged 50 and over with a chronic condition or having developed one during follow-ups based on data from the 1996-2011 Taiwan Longitudinal Study on Aging (TLSA) (n = 5131). Seven chronic conditions were examined. Covariates included age at initial diagnosis, gender, education level, number of comorbidities, and depression status. Physical disability was measured by combining self-reported ADL, IADL, and strength and mobility activities with 17 total possible points, further analyzed with multilevel modeling. RESULTS: The results showed that (1) physical disability was highest for stroke, followed by cancer and diabetes at the time of the initial disease diagnosis. (2) The linear rate of change was highest for stroke, followed by lung disease and heart disease, indicating that these diseases led to higher steady increases in physical disability after the disease diagnosis. (3) The quadratic rate of change was highest in diabetes, followed by cancer and hypertension, indicating that these diseases had led to higher increments of physical disability in later stage disease. After controlling for sociodemographic and comorbidity, depression status accounted for 39.9-73.6% and 37.9-100% of the variances in the physical disability intercept and change over time, respectively. CONCLUSIONS: Despite the fact that a comparison across conditions was not statistically tested, an accelerated increase in physical disabilities was found as chronic conditions progressed. While stroke and cancer lead to disability immediately, conditions such as diabetes, cancer, and hypertension give rise to higher increments of physical disability in later stage disease. Mitigating depressive symptoms may be beneficial in terms of preventing disability development in this population.

Validation of genome-wide association study-identified single nucleotide polymorphisms in a case-control study of pancreatic cancer from Taiwan.

BACKGROUND: Due to differences in genetic background, it is unclear whether the genetic loci identified by the previous genome-wide association studies (GWAS) of pancreatic cancer also play significant roles in the development of pancreatic cancer among the Taiwanese population. METHODS: This study aimed to validate the 25 pancreatic cancer GWAS-identified single nucleotide polymorphisms (SNPs) in a case-control study (278 cases and 658 controls) of pancreatic cancer conducted in Taiwan. Statistical analyses were conducted to determine the associations between the GWAS-identified SNPs and pancreatic cancer risk. Gene-environment interaction analysis was conducted to evaluate the interactions between SNPs and environmental factors on pancreatic cancer risk. RESULTS: Among the 25 GWAS-identified SNPs, 7 (rs2816938 (~ 11 kb upstream of NR5A2), rs10094872 (~ 28 kb upstream of MYC), rs9581943 (200 bp upstream of PDX1) and 4 chromosome 13q22.1 SNPs: rs4885093, rs9573163, rs9543325, rs9573166) showed a statistically significant association with pancreatic cancer risk in the current study. Additional analyses showed two significant gene-environment interactions (between poor oral hygiene and NR5A2 rs2816938 and between obesity and PDX1 rs9581943) on the risk of pancreatic cancer. CONCLUSIONS: The current study confirmed the associations between 7 of the 25 GWAS-identified SNPs and pancreatic risk among the Taiwanese population. Furthermore, pancreatic cancer was jointly influenced by lifestyle and medical factors, genetic polymorphisms, and gene-environment interaction. Additional GWAS is needed to determine the genetic polymorphisms that are more relevant to the pancreatic cancer cases occurring in Taiwan.

Non-alcoholic fatty liver disease among patients with sleep disorders: a Nationwide study of Taiwan.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases. Studies have shown that sleep apnea is associated with NAFLD. However, studies on the association between sleep disorders in general and NAFLD are limited. We conducted a nationwide population-based longitudinal study to evaluate this potential association. METHODS: We identified patients diagnosed with sleep disorders in the years 2000 through 2005 in Taiwan using the National Health Insurance Research Database and selected an equal number of patients without sleep disorders from the same database as the comparison cohort. The patients were followed from the index date to the diagnosis of NAFLD or the end of 2013. We used Cox proportional hazards models to estimate the risk of NAFLD associated with sleep disorders. RESULTS: A total of 33,045 patients with sleep disorders were identified. The incidence of NAFLD was 14.0 per 10,000 person-year in patients with sleep disorders and 6.2 per 10,000 person-year in the comparison cohort. The adjusted hazard ratio (AHR) of NAFLD associated with sleep disorders was 1.78 (95% confidence interval [95%CI]: 1.46-2.16), and other independent risk factors included male sex (AHR = 1.31, 95%CI: 1.12-1.54), age 40-59 years (AHR = 1.49, 95%CI: 1.21-1.82), and dyslipidemia (AHR = 2.51, 95%CI: 2.08-3.04). In the subgroup analyses, both patients with (AHR = 2.24, 95%CI: 1.05-4.77) and without (AHR = 1.77, 95%CI: 1.46-2.15) sleep apnea had an increased risk of NAFLD. CONCLUSIONS: Sleep disorders are associated with NAFLD, even in patients without sleep apnea. Further studies are warranted to explore the mechanisms of the association.

Metabolic abnormalities, but not obesity per se, associated with chronic kidney disease in a Taiwanese population.

BACKGROUND AND AIMS: It is inconclusive whether obesity itself or metabolic abnormalities are linked to chronic kidney disease (CKD). The aim of this study was to examine the association between different subtypes of obesity and metabolic abnormalities with CKD in adults. METHODS AND RESULTS: This study enrolled 14,983 eligible subjects stratified into metabolically healthy normal weight (MHNW), metabolically healthy overweight (MHOW), metabolically healthy obesity (MHO), metabolically unhealthy normal weight (MUNW), metabolically unhealthy overweight (MUOW), and metabolically unhealthy obesity (MUO) according to body mass index and metabolic syndrome status (ATP-III criteria). The metabolic healthy phenotype was defined as the absence of both metabolic syndrome and any known diabetes, coronary artery disease, stroke, hypertension or dyslipidemia. Early and advanced CKD were defined as eGFR<60, proteinuria, or structural abnormalities as detected by renal sonography. The prevalence of CKD was 2.5, 3.0, 4.0, 10.6, 9.5, and 10.5% in subjects with MHNW, MHOW, MHO, MUNW, MUOW, and MUO, respectively. In the multivariate analysis, the MUNW (OR:2.22, P < 0.001), MUOW (OR:2.22, P < 0.001), and MUO (OR:2.45, P < 0.001) groups were associated with early CKD. For advanced CKD, the OR was 2.56 (P < 0.001), 2.31 (P < 0.001), and 3.49 (P < 0.001) in the MUNW, MUOW, and MUO groups, respectively. The associated risks of early and advanced CKD were not significant in the MHOW and MHO group. MUOW and MUO were associated with higher risk of CKD compared with MHOW and MHO after adjusting other variables. CONCLUSIONS: Metabolic abnormalities, but neither overweight nor obesity, were associated with a higher risk of CKD in adults.

Urban-rural disparity in lower extremities amputation in patients with diabetes after nearly two decades of universal health Insurance in Taiwan.

BACKGROUND: To assess the prevalence of urban-rural disparity in lower extremities amputation (LEA) among patients with diabetes and to explore whether patient-related or physician-related factors might have contributed to such disparity. METHODS: This was a population-based study including patients with diabetes aged ≥55 years from 2009 to 2013. Among them, 9236 received LEA. Data were retrieved from Taiwan's National Health Insurance (NHI) claims. A multiple Poisson regression model was also employed to assess the urban-rural difference in LEA prevalence by simultaneously taking into account socio-demographic variables and density of practicing physicians. RESULTS: Between 2009 and 2013, the annual prevalence of LEA declined from 30.4 to 20.5 per 10,000 patients. Compared to patients from urban areas, those who lived in sub-urban and rural areas suffered from a significantly elevated prevalence of LEA, with a prevalence rate ratio (PRR) of 1.47 (95% CI, 1.39-1.55) and 1.68 (95% CI, 1.56-1.82), respectively. The density of physicians who presumably provided diabetes care can barely explain the urban-rural disparity in LEA prevalence. CONCLUSIONS: Although the universal health insurance has largely removed financial barriers to health care, the urban-rural disparity in LEA prevalence still exists in Taiwan after nearly two decades of the NHI program.

Increased amount and duration of tea consumption may be associated with decreased risk of renal stone disease.

PURPOSE: Previous studies have looked into the association between tea consumption and renal stone disease, but the impact of tea consumption over time has not yet been fully clarified. Our study aimed to examine the amount and duration of tea consumption concomitantly in relation to the risk of renal stone disease. METHODS: A total of 13,842 subjects who underwent health check-ups were recruited. Average tea consumption per day was defined as the amount of tea consumption per day multiplied by the frequency per week divided by seven. A "cup" was defined as 120 mL for each Chinese traditional teapot," and "cup-year" was calculated by multiplying the number of daily cups and the years of tea consumption to express the cumulative dose of tea consumption over time. The diagnosis of renal stone disease was established based on the results of abdominal sonography. RESULTS: The amount of daily tea consumption was 119.2 ± 306.8 and 131.7 ± 347.3 mL in groups with and without renal stone disease. After adjusting for other clinical variables, daily tea consumption ≥ 240 mL vs. none was related to lower risk of renal stone disease (OR = 0.84, CI 0.71-0.99, p = 0.037). In another model, the associated risk of renal stone disease decreased significantly with tea consumption ≥ 20 cup-year (OR = 0.79, CI 0.66-0.94, p = 0.008), but not < 20 cup-year (OR = 0.92, CI 0.78-1.09, p = 0.34). CONCLUSIONS: Daily tea consumption ≥ 240 mL (two cups) was associated with a lower risk of renal stone disease. Tea consumption ≥ 20 cup-year also had a decreased associated risk of renal stone disease.

Effects on clinical outcomes of intensifying triple oral antidiabetic drug (OAD) therapy by initiating insulin versus enhancing OAD therapy in patients with type 2 diabetes: A nationwide population-based, propensity-score-matched cohort study.

AIMS: To compare the effects of initiating insulin as a fourth-line antidiabetic therapy with the effects of enhancing oral antidiabetic drug (OAD) therapy in patients with type 2 diabetes mellitus (T2DM) with triple OAD therapy failure. MATERIALS AND METHODS: We conducted a nationwide population-based, retrospective cohort study involving 1022 (without prevalent diabetes-related complications [PDRCs]) and 2077 (with/without PDRCs) propensity score-matched pairs of fourth-line insulin therapy users and enhanced OAD therapy users identified in the period 2004 to 2010. Clinical outcomes including a composite cardiovascular outcome (myocardial infarction, stroke, heart failure or ischaemic heart disease), peripheral vascular disease (PVD), hypoglycaemia and all-cause mortality were assessed up to 2013. Hypoglycaemia was adjusted in Cox models to consider its potential effect on study outcomes. RESULTS: In a T2DM cohort without PDRCs, fourth-line insulin therapy was not associated with greater risks of clinical outcomes, except hypoglycaemia (hazard ratio [HR] 1.45, 95% confidence interval [CI] 1.02-2.07), compared with enhanced OAD therapy. Among patients with T2DM with/without PDRCs, fourth-line insulin therapy was associated with greater risks of the composite cardiovascular outcome (HR 1.23, 95% CI 1.03-1.46), heart failure (HR 1.59, 95% CI 1.12-2.25), ischaemic heart disease (HR 1.37, 95% CI 1.09-1.73), PVD (HR 1.17, 95% CI 1.00-1.36), hypoglycaemia (HR 1.49, 95% CI 1.20-1.85) and all-cause mortality (HR 1.48, 95% CI 1.01-2.17), but adjustment for hypoglycaemia significantly attenuated the risk of heart failure (HR 1.34, 95% CI 0.92-1.94), PVD (HR 1.15, 95% CI 0.98-1.34) and all-cause mortality (HR 1.30, 95% CI 0.84-1.99). CONCLUSIONS: Initiation of fourth-line insulin therapy can be considered for patients with T2DM with triple OAD therapy failure, and the importance of awareness and prevention of hypoglycaemia among insulin-treated patients with T2DM cannot be overstated.

Gender differences in the relationship between walking activity and sleep disturbance among community-dwelling older adult with diabetes in Taiwan.

This study explored the gender differences in the relationship between walking activity and sleep disturbances. A cross-sectional study of 201 community-dwelling older adults with diabetes was conducted in southern Taiwan. Using the Taiwanese version of the International Physical Activity Questionnaire, self-administered short version (IPAQ-SS), information on physical activity and sleep disturbance conditions was collected. Among older female adults with diabetes, 54.2% reported sleep disturbance significantly higher than males (38.1%). Logistic regression analysis suggested that for women, in addition to the active group, older adults in the low-active, high-walking group exhibited a significantly lower rate of sleep disturbance than did those who walked less.

Gallbladder stones and gallbladder polyps associated with increased risk of colorectal adenoma in men.

BACKGROUND AND AIMS: Most cases of colorectal cancer develop via an adenoma to carcinoma sequence. Gallbladder polyps share some risk factors with colorectal polyps. Little is known about the relationship between gallbladder diseases and different status of colorectal polyps by gender. This study was to investigate the association of gallbladder stones and polyps with colorectal adenomas by gender in a Taiwanese population. METHODS: A total of 7066 eligible subjects who underwent a total colonoscopy as a part of health check-up between January 2001 and August 2009 were recruited. Colonoscopic findings were classified into polyp-free, non-neoplastic polyps and colorectal adenomas. Gallbladder stones and gallbladder polyps were diagnosed based on ultrasonographic findings. RESULTS: There was a significant difference in the status of colon polyps between subjects with and without gallbladder polyps. However, the status of colon polyps was not significantly different between subjects with or without gallbladder stones. After adjusting obesity, fasting plasma glucose, and other variables, there was a positive relationship between gallbladder polyps and colorectal adenomas (odds ratio [OR]: 1.396, 95% confidence interval [CI]: 1.115-1.747) but not non-neoplastic polyps in all subjects. In men, gallbladder polyps (OR: 1.560, 95% CI: 1.204-2.019) and gallbladder stones (OR: 1.465, 95% CI 1.081-1.984) were positively associated with colorectal adenomas. In women, neither gallbladder polyps nor gallbladder stones were significantly related to colon polyps. CONCLUSIONS: Both gallbladder polyps and gallbladder stones were associated with an increased risk of colorectal adenomas in men but not in women. Gender difference was significant for the association between gallbladder lesions and colorectal polyps.

Comparative cardiovascular risks of dipeptidyl peptidase 4 inhibitors with other second- and third-line antidiabetic drugs in patients with type 2 diabetes.

AIMS: Dipeptidyl peptidase 4 inhibitors (DPP4is) are suggested as a second- and third-line antidiabetic treatment for type 2 diabetes. Previous studies assessed only the cardiovascular effects of DPP4is as a second-line treatment, included sulphonylurea as the only comparator, and yielded inconclusive results on the risk of heart failure. The present study therefore evaluated the comparative cardiovascular risks of DPP4is with other second- and third-line antidiabetic drugs. METHODS: Based on a large nationwide diabetic cohort, 113 051 patients with type 2 diabetes newly on metformin-based dual or triple therapy were identified in 2009-2011 and followed until 2013, or death if this occurred sooner. Primary interest targeted hospitalizations for ischaemic stroke, myocardial infarction and heart failure. Secondary outcomes were hypoglycaemia and all-cause mortality. Cox proportional hazards models were performed to assess time-to-event hazard ratio between propensity score-matched antidiabetic treatment groups. RESULTS: DPP4is as a second-line add-on to metformin had a significantly lower stroke risk [hazard ratio (HR) 0.817 (95% confidence interval 0.687, 0.971)] and all-cause mortality [HR 0.825 (0.687, 0.992)] than those for sulphonylurea. DPP4is as a third-line add-on to metformin and sulphonylurea combined dual therapy had a significantly lower risk for stroke [HR 0.826 (0.740, 0.923)] and all-cause mortality [HR 0.784 (0.701, 0.878)] than those for acarbose, and significantly lower risks for stroke [HR 0.653 (0.542, 0.786)], heart failure [HR 0.721 (0.568, 0.917)] and all-cause mortality [HR 0.689 (0.594, 0.703)] than those for meglitinide. CONCLUSIONS: DPP4is as a second- or third-line add-on treatment provided cardiovascular benefits and posed no increased risks for heart failure, hypoglycaemia or death.

Development of diabetes-specific quality of life module to be in conjunction with the World Health Organization quality of life scale brief version (WHOQOL-BREF).

BACKGROUND: Although numerous health-related quality of life (HRQoL) instruments are available for patients with diabetes, the length of these measures may limit their feasibility to routine practice. Also, these measures do not distinguish items for generic and diabetes-specific HRQoL. This study was aimed to develop a diabetes-specific quality of life questionnaire module (DMQoL) to be in conjunction with the World Health Organization Quality of Life scale brief version (WHOQOL-BREF). METHODS: One hundred seventeen patients with diabetes were enrolled from a medical center in Taiwan. The item content of DMQoL was constructed based on an extensive review of existing HRQoL instruments for diabetes, expert discussions and patient interviews. A series of psychometric tests were conducted to ensure the reliability and validity of DMQoL. The WHOQOL-BREF served as an existing HRQoL measure for construct validity testing. The response scale of DMQoL was adopted from the 5-point Likert scale of WHOQOL-BREF. RESULTS: A total of 10 items without ceiling or floor effects were selected from 20 items. Exploratory factor analysis (EFA) with parallel analysis and Rasch analysis concluded that the 10 items were embedded in the same underlying concept. The corrected item-total correlations and factor loadings from EFA were all above 0.4. The internal consistency of the 10 items was satisfactory (Cronbach's α = 0.84). The DMQoL total score was moderately correlated with that of WHOQOL-BREF (r = 0.48, p < 0.001). The known-group validity showed that patients with HbA1c ≤ 7% had significantly higher mean scores of DMQoL than did those with HbA1c > 8% (3.66 ± 0.47 vs. 3.41 ± 0.53; p = 0.037). CONCLUSIONS: The DMQoL with only 10 items is developed and it is sensitive to the change of diabetes progression in early phases (e.g., glycemic changes). The combination of WHOQOL-BREF and DMQoL provides a comprehensive picture of overall HRQoL in patients with diabetes and enhance the instrument's ability to detect clinically meaningful changes in diabetes.

A novel hepatokine, HFREP1, plays a crucial role in the development of insulin resistance and type 2 diabetes.

AIMS/HYPOTHESIS: Type 2 diabetes is highly correlated with nonalcoholic fatty liver disease (NAFLD). Hepatocyte-derived fibrinogen-related protein 1 (HFREP1) is a hepatokine that mediates NAFLD development; however, the role of HFREP1 in the development of insulin resistance and diabetes remains obscure. METHODS: A total of 193 age- and sex-matched participants with normal glucose tolerance, impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and newly diagnosed diabetes (NDD) were recruited for a cross-sectional study. Plasma HFREP1 levels were measured and multivariate linear regression analysis was used to evaluate the relationship between HFREP1, IFG, IGT and NDD. The causal relationship between HFREP1 and insulin resistance was then investigated in animal and cell models. Glucose and insulin tolerance tests, and euglycaemic-hyperinsulinaemic clamp, were used to evaluate insulin sensitivity in animals with Hfrep1 overexpression or knockdown in liver by lentiviral vectors. HepG2 cells were used to clarify the possible mechanism of HFREP1-induced insulin resistance. RESULTS: Plasma HFREP1 concentrations were significantly increased in participants with IFG, IGT and NDD. HFREP1 concentrations were independently associated with fasting plasma glucose levels, insulin resistance, IFG, IGT and NDD. Injection of recombinant HFREP1 or Hfrep1 overexpression induced insulin resistance in mice, and HFREP1 disrupted insulin signalling to induce insulin resistance through an extracellular signal-regulated kinase (ERK)1/2-dependent pathway. Moreover, hepatic knockdown of HFREP1 improved insulin resistance in both mice fed a high-fat diet and ob/ob mice. CONCLUSIONS/INTERPRETATION: These findings highlight the crucial role of HFREP1 in insulin resistance and diabetes, and provide a potential strategy and biomarker for developing therapeutic approaches to combat these diseases.

Risks of cardiovascular diseases associated with dipeptidyl peptidase-4 inhibitors and other antidiabetic drugs in patients with type 2 diabetes: a nation-wide longitudinal study.

BACKGROUND: Several antidiabetic drugs (i.e., sulfonylureas; SU, rosiglitazone) have been reported to be associated with increased risks of cardiovascular diseases (CVD) in patients with type 2 diabetes mellitus (T2DM). Dipeptidyl peptidase-4 inhibitors (DPP4i) are newly available antidiabetic drugs. Most studies only compared DPP4i with a placebo or SU, or targeted a specific CVD event of interest (i.e., heart failure; HF). Comparative research of CVD risks of DPP4i with other antidiabetic drugs (i.e., metformin, thiazolidinediones, meglitinides, acarbose, and insulin) remains scarce. This study was aimed to assess comparative risks of CVD, including ischemic stroke, myocardial infarction (MI) and HF, and hypoglycemia of DPP4i with other antidiabetic drugs. METHODS: We utilized Taiwan's National Health Insurance Research Database. A total of 123,050 T2DM patients newly prescribed oral antidiabetic treatments were identified in 2009-2010 and followed until 2013. Outcome endpoints included a composite of CVD events: hospitalizations for ischemic stroke, MI and HF, and hypoglycemia. Time-varying Cox proportional hazards regression was applied to assess the time to event hazards of various antidiabetic drugs, adjusted for patients' demographics, comorbidity, diabetic complications, and co-medications. Additional analyses were performed for the patients with and without CVD history, respectively. RESULTS: DPP4i users had significantly lower CVD risks as compared to that of non-DPP4i users (adjusted hazard ratio [aHR]: 0.83, 95 % confidence interval [CI]: 0.76-0.91). Compared to DPP4i users, meglitinides (aHR 1.3, 95 % CI 1.20-1.43) and insulin users (aHR 3.73, 95 % CI 3.35, 4.14) had significantly higher risks for composite CVD, as well as those for stroke, MI, HF, and hypoglycemia. Additionally, metformin users had significantly lower risks for composite CVD risk (aHR 0.87, 95 % CI 0.79-0.94), as well as those for MI, HF, and hypoglycemia, as compared to those of DPP4i users. Although there was a trend toward low CVD risks in pioglitazone users, the role of potential confounding by indication cannot be excluded. CONCLUSIONS: DPP4i-treated T2DM patients had lower risks for CVD as compared to those for non-DPP4i users, except metformin users.

Increased risk of glomerular hyperfiltration in subjects with impaired glucose tolerance and newly diagnosed diabetes.

BACKGROUND: Glomerular hyperfiltration is closely related to diabetes and may lead to subsequent nephropathy, but the association between glomerular hyperfiltration and prediabetic state is unclear. We examined the relationship of different glycemic statuses, including normal glucose tolerance (NGT), isolated impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and newly diagnosed diabetes (NDD), with glomerular hyperfiltration. METHODS: This study included 12 833 subjects ≥20 years of age without a history of renal disease, cancer, moderate/severe anemia or diabetes and taking medications for hypertension, diabetes, hyperlipidemia or cardiovascular disease from National Cheng Kung University Hospital between January 2000 and August 2009. Hyperfiltration was defined as an estimated GFR (eGFR) above the age- and gender-specific 95th percentile for apparently healthy subjects, while hypofiltration was defined as an eGFR below the 5th percentile. eGFR was assessed using the Chronic Kidney Disease Epidemiology Collaboration equation. RESULTS: After further excluding hypofiltration and adjusting for available confounders, fasting plasma glucose (FPG), 2-hour postload glucose (2hPG), 2hPG-FPG (fluctuating blood glucose), HbA1c (average blood glucose), NDD and IGT but not isolated IFG were significantly associated with increased eGFR and a higher risk of hyperfiltration {NDD: odds ratio [OR] 1.97 [95% confidence interval (CI), 1.48-2.64], P < 0.001; IGT: OR 1.34 (95% CI 1.07-1.66), P = 0.009}. CONCLUSIONS: High glucose states increase hyperfiltration risk. In addition to newly diagnosed diabetes, excessively high GFR also deserves attention in subjects with IGT.

Life Expectancy and Lifetime Health Care Expenditures for Type 1 Diabetes: A Nationwide Longitudinal Cohort of Incident Cases Followed for 14 Years.

OBJECTIVES: To assess additional life expectancy (LE), expected years of life lost , and lifetime health care expenditures after type 1 diabetes diagnosis, stratified by sex and age of first diagnosis (early: 0-12 years; late: 13-40 years). METHODS: A longitudinal cohort of patients with diabetes was constructed from Taiwan's National Health Insurance Research Database of 1999 to 2012. The survival functions for diabetic patients and age- and sex-matched general population were estimated by using a semiparametric extrapolation method with annual life tables. The average monthly health care expenditures were multiplied by the corresponding monthly survival rates and summed to calculate the lifetime health care expenditures. Cox proportional hazard models were constructed to corroborate the effects of sex and age, after being adjusted for comorbidities, complications, and calendar years. RESULTS: A total of 2386 cases (45% early diagnosis, 49% males) were identified. An additional LE after diabetes diagnosis was 45.12 years, with an estimated 17.63 years of life lost. The predicted total and diabetes-related lifetime costs were $56,939 and $102,140, respectively. Early diagnosed patients had a longer LE and lower health care spending compared with those of late-diagnosed patients. Male patients had a shorter LE and a higher expected years of life lost than the female patients, which corresponded to lower lifetime costs for the former. The Cox model results for overall mortality corroborated these trends. CONCLUSIONS: Early detection of type 1 diabetes and sex-specific strategies would probably improve long-term health outcomes and save on the cost of diabetes care.

Nonalcoholic fatty liver disease vs. obesity on the risk of erosive oesophagitis.

BACKGROUND: Erosive oesophagitis (EE) may be complicated by oesophageal ulcers, peptic stricture, Barrett's oesophagus and oesophageal adenocarcinoma. There have been few studies examining the influence of nonalcoholic fatty liver disease (NAFLD) on EE, and even fewer exploring the simultaneous effects of NAFLD, general and central obesity on EE. We thus aim to clarify the relationship between NAFLD and EE when general and/or central obesity are considered simultaneously. MATERIALS AND METHODS: In this cross-sectional study, we enrolled 12 090 subjects who underwent a health check-up at the Health Examination Center of a university hospital between January 2000 and August 2009 for analysis. NAFLD was diagnosed using liver ultrasound and EE was defined according to the Los Angeles classification by oesophagogastroduodenoscopy. RESULTS: Subjects with EE (1922; 15·9%) had a higher proportion of NAFLD, general and central obesity. With adjustment for age, gender, hypertension, diabetes mellitus, hiatal hernia, hypertriglyceridemia, high-density lipoprotein cholesterol, alcohol consumption, tea drinking, smoking and habitual exercise, the results of the multivariate analyses showed that general obesity, central obesity and NAFLD were all significantly associated with EE in their separate models. When considering general obesity, central obesity and NAFLD simultaneously, NAFLD, but neither general nor central obesity, remained positively correlated to EE. In addition, male gender, hiatal hernia and hypertriglyceridemia were all significantly associated with EE. CONCLUSION: In addition to general and central obesity, NAFLD is independently associated with increased risk of EE, and the detrimental effect of NAFLD on EE might be greater than those of general and central obesity.

Moderate to severe, but not mild, nonalcoholic fatty liver disease associated with increased risk of gallstone disease.

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) and gallstone disease (GSD) share some of the same risk factors. The association between NAFLD and GSD was inconsistent. Moreover, there are no studies on the association between GSD and the severity of NAFLD in the literature. The aim of this study was to determine the relationship between the severity of NAFLD and GSD in a Taiwanese population. MATERIALS AND METHODS: A total of 12,033 subjects were enrolled. The diagnoses of GSD and NAFLD were based on the finding of abdominal ultrasonography. The severity of NAFLD was divided into mild, moderate, and severe. RESULTS: Compared with the non-GSD group, the GSD one was older and had a higher BMI, blood pressure, fasting plasma glucose, cholesterol, triglyceride, and higher prevalence of diabetes and hypertension, but they had a lower eGFR and HDL-C level and less prevalence of current smoking and alcohol drinking. There was a significant difference in the severity of NAFLD between subjects with and without GSD. Based on logistic regression, age ≥65 versus <40 years, 40-64.9 versus <40 years, female, current alcohol drinking, diabetes, hypertension, HDL-C level and moderate to severe NAFLD, but not mild NAFLD, were the independently associated risk factors of GSD. CONCLUSION: Moderate to severe, but not mild, NAFLD was associated with an increased risk of GSD, independent of the traditional cardio-metabolic risk factor. Age, female, diabetes, and hypertension were also related to a higher risk of GSD, but HDL-C level and moderate alcohol drinking showed a lower risk.

Gastric Helicobacter pylori infection associated with risk of diabetes mellitus, but not prediabetes.

BACKGROUNDS AND AIM: The association between Helicobacter pylori infection and diabetes was inconsistent in previous studies. Moreover, there are no studies on the relationship between H. pylori infection and prediabetes in the literature. The aim of this study is thus to assess the association of Helicobacter infection, diagnosed by pathology from gastric biopsy, with diabetes and prediabetes. METHODS: This cross-sectional study included 1285 subjects aged 19-85 who underwent esophagogastroduodenoscopy and gastric biopsy during health examinations at National Cheng Kung University Hospital from 2000 to 2009. Subjects were divided into three groups, including normal glucose tolerance, prediabetes, and diabetes. Diabetes and prediabetes were assessed according to the American Diabetes Association diagnostic criteria. Gastric Helicobacter infection was an independent variable. Chi-square tests, analysis of variance, and multinomial logistic regression models were used to analyze the effects of Helicobacter infection on the risk of diabetes and prediabetes while controlling for age, lifestyle, pathological conditions, and laboratory variables. RESULTS: There were significant differences in the prevalence of gastric Helicobacter infection among the three groups. The results of multivariate analysis showed that age, obesity, family history of diabetes, hypertension, and hypertriglyceridemia were significantly related to both prediabetes and diabetes. Helicobacter pylori infection was positively associated with diabetes (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.01-2.01), but not prediabetes (OR 1.02, 95% CI 0.77-1.36), in addition to male gender, education level (≤ 9 vs > 12 years), pre-hypertension, and low high-density lipoprotein cholesterol. CONCLUSIONS: Gastric H. pylori infection is associated with diabetes, but not prediabetes.