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Aims: Evidence showed that SGLT2 inhibitors have greater protective effects against retinal diseases compared to other hypoglycemic agents. Thus, we explore the association between SGLT2 inhibitor usage and macular degeneration (MD) in Taiwanese patients with diabetes., Methods: The National Health Insurance (NHI) program's claim data are released as the National Health Insurance Research Database (NHIRD). This database covers more than 99% of the residents in Taiwan. We included data on patients who were newly diagnosed with type 2 diabetes mellitus (ICD-9-CM: 250, exclude 250.1x; ICD-10-CM: E11), with an age at diagnosis of over 20 years as our study population. Patients who received (sodium-glucose cotransporter 2 inhibitor) SGLT2i (ATC code: A10BK) over 90 days in 2016-2019 were defined as the SGLT2i cohort. Conversely, patients who did never received SGLT2i were defined as the non-SGLT2i cohort. The exclusion criteria were having MD before the index date, receiving SGLT2i within 1-89 days, and missing data on sex, age, or days of SGLT2i usage. Two cohorts were matched by 1:1 propensity score matching, which was based on age, sex, payroll bracket grade, urbanization, comorbidities, and medications., Results: Compared to non-SGLT2i cohort, patients who received SGLT2i had a significantly lower risk of MD (adjusted hazard ratio = 0.70, 95%CI = 0.66-0.75)., Conclusions: We found that SGLT2is has a strong protective effect against MD in patients with diabetes. SGLT2is may have benefits beyond glycemic control in patients with DR. However, additional clinical and experimental studies are required., (© 2024. The Author(s).)

Background: Sodium-glucose cotransporter-2 (SGLT2) inhibitors have demonstrated reduction in heart failure outcomes in patients with type 2 diabetes mellitus, although the exact mechanism of benefit remains unclear. Alteration in left atrial (LA) function due to chronic pressure or volume overload is a hallmark of heart failure., Objective: To evaluate the effect of the SGLT2 inhibitor empagliflozin on LA volume and function., Methods: 90 patients with coronary artery disease and type 2 diabetes (T2DM) were randomized to empagliflozin (n = 44) or placebo (n = 46), and underwent cardiac magnetic resonance (CMR) imaging at baseline and after 6 months. The main outcome was change in LA volume; LA function, including active and passive components, was also measured by a blinded reader., Results: At baseline, there was no significant difference in LA volumes between the empagliflozin (indexed maximum LA volume 26.4 ± 8.4mL/m 2 , minimum LA volume 11.1 ± 5.7mL/m 2 ) and placebo (indexed maximum LA volume 28.7 ± 8.2mL/m 2 , minimum LA volume 12.6 ± 5.0mL/m 2 ) groups. After 6 months, changes in LA volumes did not differ with adjusted difference (empagliflozin minus placebo): 0.99 mL/m 2 (95% CI: -1.7 to 3.7 mL/m 2 ; p = 0.47) for indexed maximum LA volume, and 0.87 mL/m 2 (95% CI: -0.9 to 2.6 mL/m 2 ; p = 0.32) for indexed minimum LA volume. Changes in total LA emptying fraction were also similar, with between-group adjusted mean difference - 0.01 (95% CI: -0.05 to 0.03, p = 0.59)., Conclusion: SGLT2 inhibition with empagliflozin for 6 months did not have a significant impact on LA volume and function in patients with T2DM and coronary artery disease. (Effects of Empagliflozin on Cardiac Structure in Patients with Type 2 Diabetes [EMPA-HEART]; NCT02998970)., (© 2024. The Author(s).)

Context: Type 2 diabetes (T2D) is the major contributor to chronic kidney disease and end-stage kidney disease (ESKD). The influence of trimethylamine N-oxide (TMAO) on kidney outcomes in T2D remains unclear., Objective: To examine the association between fasting serum TMAO levels and adverse kidney outcomes in patients with T2D., Methods: Between October 2016 and June 2020, patients with T2D were recruited and monitored every 3 months until December 2021. Serum TMAO levels were assessed using liquid chromatography-mass spectrometry. The primary kidney outcomes were doubling of serum creatinine levels or progression to ESKD necessitating dialysis; the secondary kidney outcome was a rapid 30% decline in estimated glomerular filtration rate within 2 years. All-cause mortality was also evaluated., Results: Among the 440 enrolled patients with T2D, those in the highest serum TMAO tertile (≥0.88 μM) were older, had a longer diabetes duration, elevated blood urea nitrogen, and lower estimated glomerular filtration rate. Over a median follow-up period of 4 years, 26 patients (5.9%) had a doubling of serum creatinine level or progression to ESKD. After propensity score weighting, the patients in the highest serum TMAO tertile had a 6.45-fold increase in the risk of doubling of serum creatinine levels or progression to ESKD and 5.86-fold elevated risk of rapid decline in kidney function compared with those in the lowest tertile. Additionally, the stepwise increase in serum TMAO was associated with all-cause mortality., Conclusion: Patients with T2D with elevated circulating TMAO levels are at higher risk of doubling serum creatinine, progressing to ESKD, and mortality. TMAO is a potential biomarker for kidney function progression and mortality in patients with T2D., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: DEHP, a common plasticizer known for its hormone-disrupting properties, has been associated with asthma. However, a significant proportion of adult asthma cases are "non-atopic", lacking a clear etiology., Methods: In a case-control study conducted between 2011 and 2015, 365 individuals with current asthma and 235 healthy controls from Kaohsiung City were enrolled. The control group comprised individuals without asthma, Type 2 Diabetes Mellitus (T2DM), hypertension, or other respiratory/allergic conditions. The study leveraged asthma clusters (Clusters A to F) established in a prior investigation. Analysis involved the examination of urinary DEHP metabolites (MEHP and MEHHP), along with the assessment of oxidative stress, sphingolipid metabolites, and inflammatory biomarkers. Statistical analyses encompassed Spearman's rank correlation coefficients, multiple logistic regression, and multinomial logistic regression., Results: Asthma clusters (E, D, C, F, A) exhibited significantly higher ORs of MEHHP exposures compared to the control group. When considering asthma-related comorbidities (T2DM, hypertension, or both), patients without comorbidities demonstrated significantly higher ORs of the sum of primary and secondary metabolites (MEHP + MEHHP) and MEHHP compared to those with asthma comorbidities. A consistent positive correlation between urinary HEL and DEHP metabolites was observed, but a consistent negative correlation between DEHP metabolites and selected cytokines was identified., Conclusion: The current study reveals a heightened risk of MEHHP and MEHP + MEHHP exposure in specific asthma subgroups, emphasizing its complex relationship with asthma. The observed negative correlation with cytokines suggests a new avenue for research, warranting robust evidence from epidemiological and animal studies., (© 2024. The Author(s).)

Aims: Type 2 diabetes mellitus (T2DM) increases the risk of major cardiovascular events. In SAVOR-TIMI53 trial, the excess heart failure (HF) hospitalization among patients with T2DM in the saxagliptin group remains poorly understood. Our aim was to evaluate left ventricular (LV) diastolic function after 6 months of saxagliptin treatment using cardiac magnetic resonance imaging (CMR) in patients with T2DM., Methods: In this prospective study, 16 T2DM patients without HF were prescribed saxagliptin as part of routine guideline-directed management. CMR performed at baseline and 6 months after initiation of saxagliptin treatment were evaluated in a blinded fashion. We assessed LV diastolic function by measuring LV peak filling rate with correction for end-diastolic volume (PFR/LVEDV), time to peak filling rate with correction for cardiac cycle (TPF/RR), and early diastolic strain rate parameters [global longitudinal diastolic strain rate (GLSR-E), global circumferential diastolic strain rate (GCSR-E)] by feature tracking (FT-CMR)., Results: Among the 16 patients (mean age of 59.9, 69% males, mean hemoglobin A1c 8.3%, mean left ventricular ejection fraction 57%), mean PFR was 314 ± 108 ml/s at baseline and did not change over 6 months (- 2.7, 95% CI - 35.6, 30.2, p = 0.86). There were also no significant changes in other diastolic parameters including PFR/EDV, TPF, TPF/RR, and GLSR-E and GCSR-E (all p > 0.50)., Conclusion: In T2DM patients without HF receiving saxagliptin over 6 months, there were no significant subclinical changes in LV diastolic function as assessed by CMR., (© 2023. Springer-Verlag Italia S.r.l., part of Springer Nature.)

The rise in diabetes cases is a growing concern due to the aging of populations. This not only places a strain on healthcare systems but also creates serious public health problems. Traditional blood tests are currently used to check blood sugar levels, but they are invasive and can discourage patients from regularly monitoring their levels. We recently developed nano-sensing probes that integrate Au microelectrodes and conductivity meters, requiring only 50 μL of saliva for measurement. The usage of the co-planar design of coating-free Au electrodes makes the measurement more stable, precise, and easier. This study found a positive correlation between the participant's fasting blood sugar levels and salivary conductivity. We observed a diabetes prevalence of 11.6% among 395 adults under 65 years in this study, using the glycated hemoglobin > 6.5% definition. This study found significantly higher salivary conductivity in the diabetes group, and also a clear trend of increasing diabetes as conductivity levels rose. The prediction model, using salivary conductivity, age, and body mass index, performed well in diagnosing diabetes, with a ROC curve area of 0.75. The study participants were further divided into low and high groups based on salivary conductivity using the Youden index with a cutoff value of 5.987 ms/cm. Individuals with higher salivary conductivity had a 3.82 times greater risk of diabetes than those with lower levels, as determined by the odds ratio calculation. In conclusion, this portable sensing device for salivary conductivity has the potential to be a screening tool for detecting diabetes.

Background: Adult asthma is phenotypically heterogeneous with unclear aetiology. We aimed to evaluate the potential contribution of environmental exposure and its ensuing response to asthma and its heterogeneity., Methods: Environmental risk was evaluated by assessing the records of National Health Insurance Research Database (NHIRD) and residence-based air pollution (particulate matter with diameter less than 2.5 micrometers (PM 2.5 ) and PM 2.5 -bound polycyclic aromatic hydrocarbons (PAHs)), integrating biomonitoring analysis of environmental pollutants, inflammatory markers and sphingolipid metabolites in case-control populations with mass spectrometry and ELISA. Phenotypic clustering was evaluated by t-distributed stochastic neighbor embedding (t-SNE) integrating 18 clinical and demographic variables., Findings: In the NHIRD dataset, modest increase in the relative risk with time-lag effect for emergency (N=209 837) and outpatient visits (N=638 538) was observed with increasing levels of PM 2.5 and PAHs. Biomonitoring analysis revealed a panel of metals and organic pollutants, particularly metal Ni and PAH, posing a significant risk for current asthma (ORs=1.28-3.48) and its severity, correlating with the level of oxidative stress markers, notably Nε-(hexanoyl)-lysine (r=0.108-0.311, p<0.05), but not with the accumulated levels of PM 2.5 exposure. Further, levels of circulating sphingosine-1-phosphate and ceramide-1-phosphate were found to discriminate asthma (p<0.001 and p<0.05, respectively), correlating with the levels of PAH (r=0.196, p<0.01) and metal exposure (r=0.202-0.323, p<0.05), respectively, and both correlating with circulating inflammatory markers (r=0.186-0.427, p<0.01). Analysis of six phenotypic clusters and those cases with comorbid type 2 diabetes mellitus (T2DM) revealed cluster-selective environmental risks and biosignatures., Interpretation: These results suggest the potential contribution of environmental factors from multiple sources, their ensuing oxidative stress and sphingolipid remodeling to adult asthma and its phenotypic heterogeneity., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Glycosylated hemoglobin (HbA1c) targets for patients with chronic kidney disease (CKD) and type 2 diabetes remain controversial. To evaluate whether baseline HbA1c and HbA1c trajectories are associated with the risk of end-stage kidney disease (ESKD) and all-cause mortality, we recruited adult patients with CKD and type 2 diabetes from a "Pre-ESKD Program" at a medical center in Taiwan from 2003 to 2017. Group-based trajectory modeling was performed to identify distinct patient groups that contained patients with similar longitudinal HbA1c patterns. Cox proportional hazard models were used to estimate hazard ratios (HRs) of ESKD and mortality associated with baseline HbA1c levels and HbA1c trajectories. In the analysis related to baseline HbA1c (n = 4543), the adjusted HRs [95% confidence interval (CI)] of all-cause mortality were 1.06 (0.95-1.18) and 1.25 (95% CI, 1.07-1.46) in patients with an HbA1c level of 7%-9% (53-75 mmol/mol) and >9% (>75 mmol/mol), respectively, as compared with those with an HbA1c level < 7% (<53 mmol/mol). In the trajectory analysis (n = 2692), three distinct longitudinal HbA1c trajectories were identified: nearly optimal (55.9%), moderate to stable (34.2%), and poor control (9.9%). Compared with the "nearly optimal" HbA1c trajectory group, the "moderate-to-stable" group did not have significantly higher mortality, but the "poorly controlled" group had 35% higher risk of mortality (adjusted HR = 1.35, 95% CI = 1.06-1.71). Neither baseline levels of HbA1c nor trajectories were associated with ESKD risk. In conclusion, in patients with CKD and type 2 diabetes, poor glycemic control was associated with an elevated risk of mortality but not associated with a risk of progression to ESKD., Competing Interests: The authors have declared that no competing interests exist.

Background: Lower BMI cutoffs as compared to standard cut-offs have been recommended to reduce the risk of obesity-related co-morbidities in some ethnic populations (e.g. south Asian and Chinese populations). Recent attempts have also been made to establish ethnicity-specific BMI cutoffs to identify individuals affected with obesity in relation to type 2 diabetes risk in multi-ethnic populations based in the UK and North America. However, to date, there is yet to have any published work done to identify these cut-offs in Central Asia populations nor specify any difference for genders even though the fat distribution varies amongst the different ethnic groups as well as between the genders. To the best of the authors' knowledge, this is the first study exploring new BMI and WC cut-offs in this population., Methods: To address this gap, we used a database of secondary care electronic health records from the National Research Cardiac Surgery Center to identify BMI and waist circumference cutoffs for obesity based on the risk of developing diabetes and other cardiometabolic disorders among 297 adults in Kazakhstan. Bivariate and multivariable logistic regression analysis were utilized to investigate the relationships between risk factors and type 2 diabetes mellitus (T2DM). BMI and WC thresholds were predicted using the Youden index., Results: For an equivalent age-adjusted and sex-adjusted incidence of type 2 diabetes at a BMI of 30·0 kg/m 2 in White populations, we found higher BMI cutoffs for Kazakhstani women (30.5 kg/m 2 ) but lower cut-offs for men (28·9 kg/m 2 ). As for waist circumference, the cut-off points for females were 95cm and 104 cm for males., Conclusions: For Central Asia populations, the current recommended BMI and WC cutoffs may not be suitable and further work is needed to establish specific cut-offs for this population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kali, Gusmanov, Aripov and Chan.)

A retrospective cohort study was conducted using claims data from Taiwan's National Health Insurance program to assess the effect of diabetic pay-for-performance (P4P) program on major adverse limb events (MALE) and major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus (T2DM). This study included patients with T2DM who had completed or not completed a 1-year P4P program from 2002 to 2013. Propensity-score matching was used to balance the baseline characteristics between groups. The Cox proportional-hazard model and Fine and Gray subdistribution hazard model were used to examine the association between P4P and the risks of MALE, MACE, systemic thromboembolism (ST), heart failure (HF) hospitalization, and all-cause mortality. Patients who underwent the P4P program had a significantly decreased incidence of MALE (2.0% vs. 2.6%, subdistribution hazard ratio [SHR] 0.73, 95% CI 0.71-0.76). Regarding the individual components, the P4P group demonstrated lower risks for foot ulcer (1.1% vs 1.3%, SHR 0.80, 95% CI 0.77-0.84), gangrene (0.57% vs 0.93%, SHR 0.59, 95% CI 0.56-0.63), percutaneous transluminal angioplasty (0.61% vs 0.79%, SHR 0.72, 95% CI 0.68-0.77), and amputation (0.46% vs 0.75%, SHR 0.58, 95% CI 0.55-0.62). In addition, the risks of MACE, ST, HF hospitalization, and all-cause mortality were remarkably lower in the P4P group. The P4P program might significantly reduce critical events of MALE, MACE, ST, HF, and mortality in the diabetic population., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Aims: Increased serum uric acid (SUA) is common in type 2 diabetes mellitus (T2DM) and is associated with left ventricular (LV) myocardial dysfunction. Nonetheless the association of SUA with right ventricular (RV) function in T2DM has not been studied. This study aimed to investigate the association of SUA with biventricular myocardial function in patients with T2DM., Methods and Results: A total of 560 patients with T2DM were enrolled and divided into four groups according to sex-specific quartiles of SUA. Transthoracic echocardiography was performed and two-dimensional speckle tracking was used to measure biventricular myocardial strain, including LV global longitudinal strain (GLS), circumferential strain (CS), radial strain (RS), and RV free wall longitudinal strain (RV-FWLS). The absolute value of all biventricular strain parameters showed a stepwise decrease across SUA quartiles (all P < 0.01). In particular, LV assessment by GLS, CS and RS demonstrated that those in the 4th quartile were impaired compared with the other quartiles (all P < 0.05). Similarly, RV-FWLS of the 4th quartile was significantly impaired compared with the 1st and 2nd quartiles (all P < 0.05). The same reduction in biventricular strain across SUA quartiles was observed in patients with estimated glomerular filtration rate < or ≥60 ml/min/1.73 m 2 , and glycated hemoglobin < or ≥7.0% (all P < 0.05). Multivariable linear regression analysis demonstrated that higher quartile of SUA was independently associated with impaired biventricular myocardial strain (all P < 0.05)., Conclusions: SUA was independently associated with biventricular myocardial dysfunction in asymptomatic T2DM patients, regardless of renal function or diabetic control., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Aims: Few prospective studies have evaluated sex-specific pattern, natural progression of left ventricular (LV) remodelling, and diastolic dysfunction in patients with type 2 diabetes (T2DM). The aim of this study was to study the sex-specific prevalence, longitudinal changes of LV remodelling, and diastolic dysfunction in patients with T2DM. Further, the prognostic value of diastolic function in women and men was also evaluated., Methods and Results: A total of 350 patients with T2DM (mean age 61 ± 11 years; women, 48.3%) was recruited. Detailed echocardiography was performed at baseline and after 25 months. A major adverse cardiovascular event (MACE) was defined as cardiovascular death, heart failure hospitalization, or myocardial infarction. Despite a similar age, prevalence of hypertension and body mass index, women had a higher prevalence of LV hypertrophy and diastolic dysfunction at baseline and follow-up compared with men. A total of 21 patients developed MACE (5 cardiovascular death, 9 hospitalization for heart failure, and 7 myocardial infarction) during a median follow-up of 56 months. Women with diastolic dysfunction had a higher incidence of MACE than those with normal diastolic function but this association was neutral in men. Multivariable Cox-regression analysis indicated that diastolic dysfunction was associated with MACE in women [hazard ratio = 6.30; 95% confidence interval (CI) = 1.06-37.54; P < 0.05] but not men (hazard ratio = 2.29, 95% CI = 0.67-7.89; P = 0.19)., Conclusion: LV hypertrophy and diastolic dysfunction, both at baseline and follow-up, were more common in women than men. Pre-clinical diastolic dysfunction was independently associated with MACE only in women with T2DM but was neutral in men., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Little is known about the association between deep vein thrombosis (DVT) and arterial complications in patients with type 2 diabetes (T2DM). The aim of this retrospective cohort study was to assess the influence of prior DVT on major adverse limb events (MALEs) and major adverse cardiovascular events (MACEs) in T2DM. A total of 1,628,675 patients with T2DM with or without a history of DVT from 2001 to 2013 were identified in the National Health Insurance Research Database of Taiwan. Before matching, the patients in the DVT group (n = 2020) were older than the control group (66.3 vs. 58.3 years). Patients in the DVT group were more likely to be female than the control group (54.3% vs. 47.5%). Before matching, the DVT group had higher prevalence of most comorbidities, more prescription of antiplatelet, antihypertensive agents and insulins, but less prescription of metformin and sulfonylurea. During a mean follow-up of 5.2 years (standard deviation: 3.9 years), the matched DVT group (n = 2017) have a significantly increased risk of MALE (8.4% vs. 5.2%; subdistribution hazard ratio [SHR] 1.60, 95% CI 1.34-1.90), foot ulcer (5.2% vs. 2.6%, SHR 1.96, 95% CI 1.57-2.45), gangrene (3.4% vs. 2.3%, SHR 1.44, 95% CI 1.10-1.90) and amputation (2.5% vs. 1.7%; SHR 1.42, 95% CI 1.03-1.95) than the 10,085 matched controls without DVT. They also tended to have a greater risk of all-cause mortality (38.1% vs. 33.1%; hazard ratio [HR] 1.18, 95% CI 1.09-1.27) and systemic thromboembolism (4.2% vs. 2.6%; SHR 1.56, 95% CI 1.22-1.99), respectively. We showed the presence of DVT may be associated with an increased risk of MALEs, major amputation, and thromboembolism, contributing to a higher mortality rate in T2DM.

Background: Diabetes mellitus is a known risk factor for infection. Pay for Performance (P4P) program is designed to enhance the comprehensive patient care. The aim of this study is to evaluate the effect of the P4P program on infection incidence in type 2 diabetic patients., Methods: This is a retrospective longitudinal cohort study using data from the National Health Insurance Research Database in Taiwan. Diabetic patients between 1 January 2002 and 31 December 2013 were included. Primary outcomes analyzed were patient emergency room (ER) infection events and deaths., Results: After propensity score matching, there were 337,184 patients in both the P4P and non-P4P cohort. The results showed that patients' completing one-year P4P program was associated with a decreased risk of any ER infection event (27.2% vs. 29%; subdistribution hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.86-0.88). While the number needed to treat was 58 for the non-P4P group, it dropped to 28 in the P4P group. The risk of infection-related death was significantly lower in the P4P group than in the non-P4P group (4.1% vs. 7.6%; HR 0.46, 95% CI 0.45-0.47). The effect of P4P on ER infection incidence and infection-related death was more apparent in the subgroups of patients who were female, had diabetes duration ≥5 years, chronic kidney disease, higher Charlson's Comorbidity Index scores and infection-related hospitalization in the previous 3 years., Conclusions: The P4P program might reduce risk of ER infection events and infection-related deaths in type 2 diabetic patients.

Background: Stress cardiovascular magnetic resonance (CMR) to screen for silent myocardial ischaemia in asymptomatic high risk patients with type 2 diabetes mellitus (DM) has never been performed, and its effectiveness is unknown. Our aim was to determine the feasibility of a screening programme using stress CMR by obtaining preliminary data on the prevalence of silent ischaemia caused by obstructive coronary artery disease (CAD) and quantify myocardial perfusion in asymptomatic high risk patients with type 2 diabetes., Methods: In this prospective cohort study, we recruited 63 asymptomatic DM patients (mean age 66 years ± 4.4 years; 77.8% male); with Framingham risk score ≥ 20% from 3 sites from June 2017 to August 2018. Normal volunteers were recruited to determine normal global myocardial perfusion reserve index (MPRI). Adenosine stress CMR and global MPRI was performed and measured in all subjects. Positive stress CMR cases were referred for catheter coronary angiography (CCA) with/without fractional flow reserve (FFR) measurements. Positive CCA was defined as an FFR ≤ 0.8 or coronary narrowing ≥ 70%. Patients were followed up for major adverse cardiovascular events. Prevalence is presented as patient numbers and percentage. Mann-Whitney U test was used to compare global MPRI between patients and normal volunteers., Results: 13 patients had positive stress CMR with positive CCA (20.6% of patient population), while 9 patients with positive stress CMR examinations had a negative CCA. 5 patients (7.9%) had infarcts detected of which 2 patients had no stress perfusion defects. 12 patients had coronary artery stents inserted, whilst 1 patient declined stent placement. DM patients had lower global MPRI than normal volunteers (n = 7) (1.43 ± 0.27 vs 1.83 ± 0.31 respectively; p < 0.01). After a median follow-up of 653 days, there was no death, heart failure, acute coronary syndrome hospitalisation or stroke., Conclusion: 20.6% of asymptomatic DM patients (with Framingham risk ≥ 20%) had silent obstructive CAD. Furthermore, asymptomatic patients have reduced global MPRI than normal volunteers., Trial Registration: ClinicalTrials.gov Registration Number: NCT03263728 on 28th August 2017; https://clinicaltrials.gov/ct2/show/NCT03263728.

Aim: This study investigated the effect of severe hyperglycemia episodes on survival and associated factors related to risk of mortality in type 2 diabetes mellitus (DM) patients with dementia., Methods: We enrolled all type 2 DM patients newly diagnosed as having dementia in Taiwan from 1998 to 2005. These patients were categorized into those who had hyperglycemia episodes and those who did not based on whether or not they had been hospitalized for hyperglycemia after dementia diagnosis. Factors independently associated with mortality were evaluated., Results: Of 5314 patients identified, 303 (5.7%) had at least one hyperglycemia hospitalization. Patients with at least one hyperglycemia hospitalization had a 30% greater risk of mortality than those who had no such admissions (adjusted hazard ratio: 1.30, 95% confidence interval: 1.09-1.55). Other variables, including age, sex, geographical region, insurance amount, patient with congestive heart failure, cerebrovascular disease, renal disease, use of anti-hypertensive drugs, use of anti-lipid drugs, and use of insulin were independently associated with risk of mortality., Conclusion: Severe hyperglycemia is common in type 2 DM patients with dementia and it substantially shortens their life. The findings of this study suggest a great need to improve care in DM patients with dementia., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Incidence of dementia is growing rapidly and affects many people worldwide. Type 2 diabetes mellitus (DM) might link cognitive decline and dementia, but the reasons for this association remain unclear. Our study explored the factors associated with type 2 DM in patients with dementia., Methods: Patients (n = 40,404) with vascular dementia were identified in Taiwan's 1997 to 2008 National Health Insurance Research Database and divided into a DM group and non-DM group. Eleven comorbidities were identified and categorized into four groups: cardiovascular and cerebrovascular diseases, digestive system diseases, renal and metabolic system diseases, and cancer. The associations of these factors with type 2 DM were explored through multivaraible logistic regression., Results: Of the patients with dementia, 22.5% had DM. Associated with a higher likelihood of DM in this population were female sex (adjusted odds ratio [OR]: 1.44, 95% confidence interval [CI]: 1.36-1.52), young age (range of adjusted OR: 0.55-1.13), low income (range of adjusted OR: 1.09-1.18), and renal and metabolic system diseases (OR: 2.81, 95% CI: 2.64-2.98)., Conclusions: The findings of this study suggest that clinicians should encourage patients with dementia to receive regular glucose impairment screening if they are female, have low socioeconomic status, or have renal or metabolic diseases.

Background: Type 2 diabetes is a huge burden both for individuals and society as a whole. Although depression has been negatively associated with ideal glycemic control, little is known about the prevalence of depression or its associated factors among rural Taiwanese adults with Type 2 diabetes mellitus (type2 DM)., Purpose: The purposes of this study were to investigate the prevalence of depression in rural-dwelling sufferers of type2 DM and to highlight the relationships between their depression status and health promoting behaviors such as physical activity, keeping active in life, sleep sufficiency, and adopting a diabetic diet., Methods: A cross-sectional, correlational design was used to recruit 696 participants from local healthcare centers in rural areas of Chiayi County, Taiwan. Data were collected from March 30, 2010, to August 30, 2012. The Chinese version of the Geriatric Depression Scale and its associated physiological biomarkers were used as screening tools. Logistic regression was used to identify the factors that were associated with depression status., Results: The prevalence of depression in this study was 16.8%. Factors found to be associated with depression included being female, having a low level of education, receiving reduced family support, having little physical activity, failing to follow a diabetic diet, frequent inactivity, and having insufficient sleep. There were no significant differences in the physiological indicators between the depressive and nondepressive groups. After controlling for confounding factors, a logistic regression model showed that depression status was associated with a lack of sleep (OR = 2.85, p < .001), less frequent exercise (OR = 2.67, p < .001), and frequent inactivity (OR = 2.35, p = .001)., Conclusions/implications for Practice: This study showed that the prevalence of depression among adults with type2 DM living in rural areas is relatively high. From the perspective of health promotion, future research should focus on how to improve quality of sleep by enhancing daily physical activity and on investigating the effect of promoting a more active lifestyle among those at risk on depression.

Objectives: To explore the prevalence, discomfort, and self-relief behaviours of painful diabetic neuropathy (PDN) among rural community residents with type 2 diabetes., Design: A community-based, cross-sectional study., Setting: This study was part of a longitudinal cohort study of a nurse-led health promotion programme for preventing foot ulceration in Chiayi County, Taiwan., Participants: Six hundred and twenty-eight community adults with type 2 diabetes participated in this study., Outcome Measures: Parameters assessed included peripheral neuropathy, peripheral vasculopathy, glycaemic control and metabolic biomarkers. Statistical analyses included descriptive statistics and a multivariate logistic regression model., Results: About 30.6% of participants (192/628) had PDN. Factors associated with PDN included an abnormal ankle brachial index (ABI; OR=3.4; 95% CI 1.9 to 6.2; p<0.001), Michigan neuropathy screening index (OR=1.69; 95% CI 1.0 to 2.6; p=0.021), triglyceride level (OR=1.61; 95% CI 1.0 to 2.4; p=0.036) and being female (OR=1.68; 95% CI 1.1 to 2.4; p=0.022). PDN was characterised by uncomfortable feelings of prickling, stinging or burning pain and inexplicable dullness around the base or dorsal areas of the feet, but received little attention or treatment from primary healthcare providers., Conclusions: A high prevalence of PDN was found in rural community residents with type 2 diabetes and the healthcare workers provided little attention to, or treatment of, discomfort. It is important to identify high-risk groups with PDN early in order to prevent foot ulceration and reduce the incidence of amputation of the extremities. It is also urgent to develop appropriate treatment and self-relief behaviours to halt or reverse the progression of PDN for this population living in rural areas., Competing Interests: Conflicts of Interest: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

This retrospective cohort study investigated the progression risk of sequential complication in Asian type 2 diabetes (T2D) patients using the Taiwan Pay-for-Performance Diabetes Registry and claim data from November 2003 to February 2009. 226,310 adult T2D patients without complication were followed from diagnosis to complications, including myocardial infarction (MI), other ischemic heart disease (IHD), congestive heart failure (CHF), stroke, chronic kidney disease (CKD), retinopathy, amputation, death or to the end of study. Cumulative incidences (CIs) of first and second complications were analyzed in 30 and 4 years using the cumulative incidence competing risk method. IHD (29.8%), CKD (24.5%) and stroke (16.0%) are the most common first complications. The further development of T2D complications depends on a patient's existing complication profiles. Patients who initially developed cardiovascular complications had a higher risk (9.2% to 24.4%) of developing IHD or CKD, respectively. All-cause mortality was the most likely consequence for patients with a prior MI (12.0%), so as stroke in patients with a prior MI (10.8%) or IHD (8.9%). Patients with CKD had higher risk of developing IHD (16.3%), stroke (8.9%) and all-cause mortality (8.7%) than end-stage renal disease (4.0%). Following an amputation, patients had a considerable risk of all-cause mortality (42.1%).

Background: Peripheral arterial disease (PAD) is one of the major manifestations of systemic atherosclerosis and plays an important role in low-extremity amputation in type 2 diabetic patients. The aim of this study was to explore the prevalence and risk factors for asymptomatic PAD in type 2 diabetic community residents., Methods: This cross-sectional study enrolled 552 type 2 diabetic adults (232 men and 320 women) without subjective symptoms of intermittent claudication. We defined the PAD group as an ankle-brachial index (ABI) ≤ 0.90, and the normal group as an ABI 0.91-1.30. Their clinical characteristics, Michigan Neuropathy Screening Instrument (MNSI) scores and blood pressure were compared., Results: We discovered that 51 patients have asymptomatic PAD. Univariate logistic regression analysis revealed that age, history of stroke, longer duration of diabetes (> 10 years), unemployment or retirement, pulse pressure, systolic blood pressure, and high MNSI score (> 2) were risk factors for PAD. By multivariate logistic regression analysis, pulse pressure, high MNSI score, age, and history of stroke were independent risk factors with odds ratios (95% confidence intervals, CI) of 1.032 (1.012-1.053), 2.359 (1.274-4.370), 1.050 (1.010-1.091), and 5.152 (1.985-13.368), respectively. Furthermore, the prevalence of PAD increased significantly with increment in the pulse pressure and MNSI., Conclusions: In summary, the overall prevalence of asymptomatic PAD in the type 2 diabetic adults was 9.2%. Age, history of stroke, pulse pressure and MNSI score may provide important clinical information. Primary care physicians should be aware of asymptomatic patients with high pulse pressure and MNSI scores.

Aims and Objectives: To explore the factors associated with the numbers of remaining teeth among type 2 diabetes community residents., Background: Promoting oral health is an important nursing role for patients with diabetes, especially in disadvantaged areas. However, limited research has been carried out on the relationship between numbers of remaining teeth, diabetes-related biomarkers and personal oral hygiene among diabetic rural residents., Design: A cross-sectional, descriptive design with a simple random sample was used., Methods: This study was part of a longitudinal cohort study of health promotion for preventing diabetic foot among rural community diabetic residents. It was carried out in 18 western coastal and inland districts of Chiayi County in central Taiwan. In total, 703 participants were enrolled in this study., Results: The findings indicated that a high percentage of the participants (26%) had no remaining natural teeth. Nearly three quarters (74%) had fewer than 20 natural teeth. After controlling for the potential confounding factors, multivariate analysis demonstrated that the factors determining numbers of remaining teeth were age (p < 0.001), education (p < 0.001), using dental floss (p = 0.003), ankle brachial pressure index (p = 0.028), waist circumference (p = 0.024) and HbA1C (p = 0.033)., Conclusions: Except for some unmodifiable factors, the factors most significantly associated with numbers of remaining teeth were less tooth-brushing with dental floss, abnormal ankle brachial pressure and poor glycemic control., Relevance to Clinical Practice: This study highlights the importance of nursing intervention in oral hygiene for patients with type 2 diabetes. It is necessary to initiate oral health promotion activities when diabetes is first diagnosed, especially for older diabetic residents of rural or coastal areas who are poorly educated., (© 2013 John Wiley & Sons Ltd.)

Background: Preventing diabetic foot problems (DFP) and their associated consequences is a critical in rural regions. The objective is to present an association of non-invasive DFP assessment tools and physiological indicators for early detection among rural cases of diabetes in Taiwan., Methods: Secondary data analysis of 387 participants previously diagnosed with type 2 diabetes was used. The Michigan Neuropathy Screening Instrument (MNSI), Ankle Brachial Index (ABI), optimal scaling combination (OSC) of MNSI, and age were used to examine peripheral neurovascular function. The King's College classification (KC) and Texas risk classification (TRC) were used to understand diabetic foot complications., Results: The findings indicated that MNSI was negatively correlated with ABI, but positively with diabetes duration, age, KC, TRC, fasting blood glucose, low density of lipoprotein cholesterol, body mass index and waist circumference. The area under the receiver operating characteristic curves for assessing the risk of ABI based on OSC was larger than for MNSI, KC, and TRC., Conclusion: It is shown that using OSC, MNSI, and ABI as community screening tools is useful in detecting early neurovasculopathy. In addition, where an ABI machine is unavailable, primary healthcare providers that perform MNSI or OSC may be cost-effective. The study was approved by the institutional review board of the ethical committee (No 98-2224-B).

Aims: To evaluate the self-perception of diabetes control associated with physical indicators and with practicing exercise and a healthy diet, among rural residents., Background: It remains unclear whether a subject's self-perception of diabetes control increases its deleterious effects., Design: Cross-sectional, correlational., Methods: We recruited 715 participants from 18 primary healthcare centres in the rural regions of Chiayi County, Taiwan. Data were collected between 1 January 2009-30 June 2010. Logistic regression was conducted to identify the determinant factors associated with perceptions of diabetes control., Results: A high percentage of participants overestimated their fasting blood glucose and HbA1 C status. Total cholesterol, triglyceride, low density lipoprotein cholesterol, blood pressure, and waist circumference exceeded the medical standard in the 'feel good' group, and many did not adopt a healthy diet and undertake physical activity. The final logistic regression model demonstrated that residents with diabetes who exercised frequently had normal fasting glucose, and normal HbA1 C tended to perceive 'feel good' control., Conclusion: Misperception and unawareness of diabetes control were prevalent among rural residents. Addressing misperceptions among rural residents with diabetes and increasing their knowledge of professional advice could be important steps in improving diabetes control in an elder population., (© 2012 Blackwell Publishing Ltd.)

Objectives: Improving diabetes control is a critical issue world-wide, because mortality rates and costs are increasing dramatically. Maintaining a healthy lifestyle is positively associated with diabetes control. However, the availability of practical screening tools suitable for determining and modifying healthy or unhealthy lifestyle choices is limited. The main aim of this study was to determine the appropriateness of the type 2 diabetes and health promotion scale (T2DHPS) for use in patients with type 2 diabetes., Methods: This study examined the Cronbach's alpha, content validity, construct and concurrent validity of the Chinese language version of the T2DHPS for assessing lifestyle and disease control among patients with type 2 diabetes. The dimensions of the T2DHPS were generated from the Chinese version of adult health promotion and interviews with experts, and were corroborated by the literature. A total of 323 patients previously diagnosed with type 2 diabetes were recruited. A cross-sectional, descriptive design questionnaire was developed and tested at diabetes outpatient departments in three teaching hospitals between August 2010 and June 2011. Construct validity was established using factor analysis. The total and subscale scores of the T2DHPS were correlated with biomarkers of diabetes control for concurrent validity., Results: Kaiser-Meyer-Olkin (KMO) and Bartlett's sphericity tests showed that the sample met the criteria required for factor analysis. A 28-item Likert-type scale of the T2DHPS was established, and explained 56.7% of the total variance. The simplified version of the T2DHPS was made up of six dimensions of behavior: physical activity, risk reduction, stress-management, enjoy life, health responsibility and a healthy diet. The reliability coefficient for the total scale was 0.89, and alpha coefficients for the subscales ranged from 0.63 to 0.86. Concurrent validity indicated that the T2DHPS is significantly positively associated with diabetes control., Conclusions: T2DHPS was shown to be a reliable and valid tool for assessing patients with type 2 diabetes, and can possibly predict diabetic control. This scale appears to be a useful screening tool for type 2 diabetic people in primary health care settings, to promote health status through modification of an unhealthy lifestyle., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Aims: This paper is a report of a study examining the diabetes control and foot self-care capability in farmers and fishermen following introduction of a multi-stage, multi-disciplinary team and community-based small group health promotion programme., Background: Improving the control of diabetes is a critical issue in Taiwan because mortality rates are increasing dramatically, particularly in rural populations., Methods: A quasi-experimental research design was deployed from January to December 2009. A total of 387 participants living in nine rural districts with previous diagnoses of type-2 diabetes were randomly selected. Three hundred and twenty-three completed the 3-stage programme, including health assessment, health promotion education and individually tailored telephone counselling and evaluation over a 1-year period., Results: Most of the participants were fishermen or farmers who had <6 years of education (79%) and were elders (68·9 ± 9·5 years). Most of the physiological variables and foot self-care capabilities showed statistically significant improvement after the programme. Furthermore, 37 participants with severe high risk of diabetic foot accepted additional referral treatments, and their peripheral nerve and vascular functions improved., Conclusion: The research outcomes support the value of community-based health promotion programmes in rural areas, incorporating a multidisciplinary health team and culturally competent materials to help the elder rural inhabitants with diabetes enjoy better health and quality of life., (© 2011 Blackwell Publishing Ltd.)

Background: The standardized mortality rate of type 2 diabetes is higher in Taiwan than that in other developed countries. In Taiwan, the diabetes mortality rate in Chiayi County is the highest nationwide., Purpose: This study was designed to explore the health status (to measure six physiological indicators), the health-related behaviors, and the associated factors among type 2 diabetes sufferers living in rural communities., Methods: Researchers used a cross-sectional, correlation design and conducted the study at nine local health districts in Chiayi County, Taiwan. A total of 387 participants previously diagnosed with type 2 diabetes were randomly selected and invited to join in the program., Results: Fifty-nine percent of participants were women; their mean age was 68.7 years, and their mean duration with diabetes was 7.9 years. Most were treated at local health centers and took oral medications (90.7%). More than 40% did not exercise regularly and 33.9% did not practice diet control. Results found a higher percentage of abnormal health indicators in terms of participant body mass index, waist circumference, HbA1C, and peripheral neurovascular function. After controlling for potential confounding factors, researchers found smaller waist circumference, participating in community support groups, better foot self-care capability, and frequent exercise to be associated with better health indicators. Diabetes duration, lower education, and being of male gender were found to be negatively associated with health status., Conclusions/implications for Practice: This study found that rural residents with diabetes do not adequately control their diabetes and exhibit inadequate health-related behavior. Joining community support groups, increasing exercise frequencies, and improving foot self-care capabilities should be employed in nursing strategies and health policies for diabetes control--especially for those who have less formal education or are male.

Aims: The SLC2A9 gene encodes the glucose transporter 9, with the abilities of transporting both glucose and uric acid and is involved in the pancreatic glucose-stimulated insulin secretion. The single nucleotide polymorphisms (SNPs) of SLC2A9 accounted for 5% variance of serum uric acid (UA). UA was identified as a risk factor for type 2 diabetes mellitus (DM). We investigated whether the SLC2A9 gene variations are associated with type 2 DM in Han Chinese., Methods: Three common SNPs of the SLC2A9, rs1014290, rs2280205, and rs3733591, were genotyped in 1003 Han Chinese randomly selected from Kaohsiung, Taiwan., Results: The variant SNP rs1014290 is associated with decreased 0.12-fold risk of type 2 DM (P = .002). Per-copy increase in the minor C-allele results in 0.13 mmol/L (P = .037) and 10.03 μmol/L (P = .016) decrease in serum glucose and UA, respectively., Conclusions: The SNP rs1014290 within the SLC2A9 gene is associated with type 2 DM in Han Chinese.

Objectives: There is growing evidence suggesting the mutual link between type 2 diabetes mellitus (T2DM) and hepatitis C virus (HCV) infection. However, the impact of HCV infection on the suite of glucose abnormalities has rarely been investigated. The study aimed to determine the difference regarding the prevalence and the characteristics of glucose abnormalities between chronic hepatitis C (CHC) patients and community-based controls. It also aimed to investigate the related clinical, virological, and histological features of glucose abnormalities in HCV infection., Methods: Six hundred eighty-three CHC patients and 515 sex-/age-matched controls were included. Oral glucose tolerance test (OGTT) was performed in 522 CHC patients and 447 controls without known T2DM. Clinical data were assessed upon the different stages of glucose abnormalities based on OGTT results., Results: The prevalence of normoglycemia, IGT, and T2DM in 683 CHC patients was 27.7%, 34.6%, and 37.8%, respectively. There was a significant linear trend from normoglycemia to T2DM in terms of age, family history of T2DM, and advanced liver fibrosis in CHC patients. For those CHC patients without fibrosis, the prevalence of glucose abnormalities reached 67.9% high. All CHC patients carried a significantly higher prevalence than controls regarding those aged <65 yr. For those without known DM, there was a 3.5-fold increase in the prevalence of glucose abnormalities in CHC (65.8%) patients in comparison with controls (35.3%) (OR 3.51, 95% CI 2.70-4.56, P < 0.001)., Conclusions: CHC patients carried a high prevalence of glucose abnormalities. Determination of glucose abnormalities by OGTT may be suggested.

Objectives: There is growing evidence with regard to the association between hepatitis C virus (HCV) infection and type 2 diabetes mellitus (T2DM). However, the mutual link and related virological implication have not been fully clarified. The impact of hepatitis B virus (HBV) infection on the epidemiological link remains unclear. This study aimed to elucidate the link between T2DM and viral hepatitis infections, especially HCV infection. It also aimed to analyze the associated virological characteristics and implication., Methods: Cross-sectional analysis of a computer-sampling survey among 10,975 participants (aged 40-65 yr) was performed in an area endemic for HBV and HCV infections in Taiwan. Outcome measures included prevalence of T2DM among different groups of viral hepatitis infection, and comparison of related biochemical and virological profiles., Results: Of 10,975 participants studied, 9,932 eligible participants were analyzed. The prevalence of T2DM, seropositivity for HBV surface antigen (HBsAg) and HCV antibodies (anti-HCV), and HCV viremia was 12.5%, 13.1%, 6.5%, and 4.8%, respectively. Prevalence of HCV viremia showed significant difference between T2DM and non-T2DM subjects (6.9% vs 4.5%, P<0.001), whereas anti-HCV seropositivity showed borderline significance (7.8% vs 6.3%, P=0.047). There was no HCV genotype-specific difference between HCV genotype 1 and 2 in the association with T2DM. On the other side, the prevalence of HBsAg (+) did not differ between T2DM and non-T2DM subjects (12.5% vs 13.9%, P=0.19). The prevalence of T2DM among HCV viremic subjects (18.0%, 86/478) was significantly higher than HBsAg (+) subjects (11.4%, 155/1,363, P=0.001) and those negative for both viral hepatitis markers (12.5%, 997/8,004, P=0.001). Multivariate logistic regression analyses showed that HCV viremia was the leading significant factor associated with T2DM, followed by male gender, hypertension, body mass index, and age., Conclusions: HBV infection did not increase the association with T2DM. A significant mutual link between T2DM and HCV viremia existed in this HBV/HCV endemic area. There was no HCV genotype-specific difference between HCV genotype 1 and 2 in the association with T2DM.