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Graves disease (GD) and type 2 diabetes mellitus (T2DM) both impair liver function; we therefore explored the possibility of a relationship among diabetic control, thyroid function, and liver function. This retrospective, cross-sectional study compared serum liver function biomarkers of primary GD patients in a single center between 2016 and 2020, derived from clinical databases, and clarified the correlation of liver function in GD patients with or without T2DM. Furthermore, the diabetes mellitus group was divided into glycated hemoglobin A1C (HbA1C)6.5% group and ≥6.5% group to further analyze the effect by disease control in patients. Statistical differences between groups were assessed using independent t tests to clarify the association of serum biomarkers between GD with T2DM. Pearson test was applied to assess within-group statistical correlation of serum biomarkers. The correlation of factors in each group was demonstrated by using the Kendall tau-b method and stepwise regression analysis. A total of 77 patients were included in the study. In the study population, glutamate pyruvate transaminase (GPT) was significantly correlated with thyroid-stimulating hormone, and HbA1C was significantly correlated with alkaline phosphatase (ALK-P), glutamate oxaloacetate transaminase (GOT), and GPT. An examination of GOT, GPT, free thyroxine (FT4), and HbA1C levels revealed a significant difference between the non-T2DM and T2DM groups. GPT also exhibited a significant correlation with triiodothyronine in the T2DM group. The T2DM group was further divided into groups: HbA1C6.5% and ≥6.5%. The results demonstrated that ALK-P, GOT, GPT, and FT4 levels were significantly different between the groups. A significant correlation between ALK-P and thyroid-stimulating hormone and between GOT and FT4 was also identified in the HbA1C6.5% group. Our single-center study revealed that diabetes affects liver function in patients with GD. For patients with T2DM, when liver function becomes impaired, thyroid function control deteriorates. GPT was correlated with triiodothyronine but not with FT4, which indicated the impairment of deiodination in the liver. This phenomenon was not observed in the non-T2DM population. The early detection of abnormal liver function in patients with GD and T2DM may help limit the development of comorbidities and improve disease management.

Almonds can decrease glycemic index of co-consumed foods and are a rich source for oleic acid and α-tocopherol. The aim of the randomized, crossover, controlled feeding trial was to examine whether as compared to NCEP step II diet as control (CON), ~60 g/d almonds (ALM) added to CON would improve glucoregulation and cardiovascular disease (CVD) risk factors in 33 Chinese T2DM patients. Forty T2DM patients were enrolled and randomly assigned to receive CON or ALM for 12 wks after a 2-wk. run-in period. Blood and urine samples were collected in the beginning and at the end of each dietary intervention phase for the assessment of biomarkers of glucoregulation, lipid profile, inflammation, and oxidative stress. While ALM had a better overall nutritional quality than CON, neither ALM nor CON improved the glycemic status as the primary study outcome and other CVD risk factors, except the circulating nitric oxide being decreased by ALM compared to CON. Among 27 of 33 patients with the baseline HbA1c ≤8, ALM decreased post-interventional fasting serum glucose and HbA1c by 5.9% and 3.0% as compared to that of CON, respectively (P = 0.01 and 0.04). Mean total and LDL-cholesterol concentrations were not changed by both diets. These results suggest almonds incorporated into healthful diets can improve glycemic status in diabetic patients with a better glycemic control. NCT01656850 , registered 13 January 2012.

Aim: Addition of 1-3 dose of bolus insulin is recommended by ADA/EASD guidelines when basal insulin (BI) therapy becomes insufficient for T2DM patients to achieve HbA1c target of Method: 328 T2DM patients completed 48 weeks of stepwise intensification of PI + BI therapy (Main group). The primary objective of the study was to determine the mean change in HbA1c. Secondary objectives included; evaluation of change in FPG, 2h-PPG, PI and BI dose and the rate of HbA1c Result: Mean HbA1c was 9.16% in Main group at baseline. At week 48, significant difference in mean HbA1c change (-0.59 ± 1.16% vs. -0.07 ± 1.06%; p Conclusion: This study demonstrated the introduction of stepwise intensification of prandial insulin leads to greater improvements in HbA1c levels than basal insulin monotherapy in T2DM patients in Taiwan and this effect can be maintained during the study period of 48 weeks. Disclosure Y. Hung: Advisory Panel; Self; Sanofi. Y. Huang: Research Support; Self; Sanofi. H. Chen: Research Support; Self; Sanofi. R. Liu: Research Support; Self; Sanofi. N.C. Yu: None. H. Lam: None. C. Huang: Research Support; Self; Sanofi. C. Chen: Research Support; Self; Sanofi. P. Hsiao: Advisory Panel; Self; Sanofi. H. Chen: None. M. Chien: Research Support; Self; Sanofi. T. Lee: None. C.Y. Yang: None. C. Chen: Advisory Panel; Self; Sanofi-Aventis. S. Tu: None. H. Chen: None. W. Sheu: Advisory Panel; Self; Sanofi.

Background In the general population, a higher Alternate Healthy Eating Index (AHEI)-2010 score is related to decreased cardiovascular disease (CVD) risk. Few studies have described the dietary patterns that reduce the risk of CVD or coronary heart disease (CHD) in type 2 diabetes mellitus (T2DM) patients. In the present study, the association between the American Diabetes Association (ADA)-recommended dietary pattern, AHEI-2010 , and CVD risk factors and the CVD incidence over 52 months in T2DM patients was evaluated. Methods The ADA score was developed from the ADA dietary recommendations. In this prospective study, the 24-h dietary recall of 124 adult T2DM patients without nephropathy or chronic kidney disease was collected. The CVD risk factors were collected at baseline and at 6-month follow-up. Results Compared with lower ADA and AHEI-2010 score participants, the higher score participants exhibited a significantly lower waist circumference, serum low-density lipoprotein cholesterol level and 10-year risk of CHD. Participants with higher ADA dietary scores had a significantly reduced risk of central obesity and systolic blood pressure >140 mmHg. Higher AHEI-2010 scores were significantly related to a reduced risk of serum low-density lipoprotein cholesterol > 100 mg dL-1. Seven participants had their first-ever CVD during the follow-up period, although neither ADA score, nor AHEI-2010 score could predict CVD incidence. Conclusions The ADA-recommended dietary pattern and a higher AHEI-2010 score might both exhibit reduced risk factors of CVD in T2DM patients.

Supplemental Digital Content is available in the text, The main objective of this study is to investigate the outcome between surgical procedures and the risk of development of hypoparathyroidism followed by surgical procedure in patients with thyroid disorders. We analyzed the data acquired from Taiwan's Bureau of National Health Insurance (BNHI) research database from 1998 to 2011 and found 9316 patients with thyroid surgery. Cox regression model was used to calculate the hazard ratio (HR). A count of 314 cases (3.4%) of hypoparathyroidism was identified. The 9 years cumulated incidence of hypoparathyroidism was the highest in patient undergone bilateral total thyroidectomy (13.5%) and the lowest in the patient with unilateral subtotal thyroidectomy (1.2%). However, in the patients who had undergone unilateral subtotal, the risk was the highest in bilateral total (HR: 11.86), followed by radical thyroidectomy with unilateral neck lymph node dissection (HR: 8.56), unilateral total (HR, 4.39), and one side total and another side subtotal (HR: 2.80). The extent of thyroid resection determined the risk of development of hypoparathyroidism. It is suggested that the association of these factors is investigated in future studies.

Summary Background Diabetic foot ulcers (DFUs) superimposed by infection and ischaemia may result in amputation without prompt and adequate management. We investigated whether the diabetic foot ulcer treatment programme (DFUTP) involving immediate debridement within 12 h, flap coverage and/or revascularisation improved the outcome of patients with infected DFUs. Method Between 2006 and 2009, we randomly enrolled 350 patients in the DFUTP group and compared them with control patients (the non-DFUTP group, n = 386) in Taiwan. Inclusion criteria consisted of infected diabetic foot ulcers with or without ischaemia. The risk factors, dynamics and outcome of amputation and re-amputation were analysed in terms of patient demographics, glycaemic control and infection. Result The results of logistic regression analyses indicated that risk factors of amputation in both groups were HbA1c (odds ratio (OR) = 1.63, 95% confidence interval (CI) 1.31–2.02) and C reactive protein (OR = 1.12, 95% CI 1.01–1.24). The DFUTP group showed a lower amputation rate than the non-DFUTP group ( p = 0.001). The association between the amputation and University of Texas (UT) classification was not statistically significant. The Kaplan–Meier estimate showed that the time to complete recovery of the sugar level in the DFUTP group was faster than in the non-DFUTP group ( p = 0.001). For patients at stage D, the hospital stay in the non-DFUTP group was longer than in the DFUTP group ( p = 0.014). Conclusion The DFUTP provides an effective treatment programme for decreasing the amputation rate with infected DFUs. Immediate debridement and flap reconstruction decrease the amputation and re-amputation rate respectively.

Aims: To determine the effect of an oral dose of sitagliptin on the secretion of ghrelin and gastrin hormones. Methods: Ten healthy volunteers were recruited in this study. A baseline blood sample was drawn before oral dosing with a 100-mg tablet of sitagliptin. Two blood samples were obtained 0.5 and 1 h after dosing. Three additional postprandial blood samples were drawn at 0.5, 1, and 2 h. Radioimmunoassay was used for determining hormonal levels. A Student’s t test, Pearson correlation analysis, and multivariate approach to repeated-measures analysis of variance were used for statistics. Results: After sitagliptin dosing, but before the meal, there was no significant change in circulating ghrelin, gastrin, insulin, and glucose levels. Only after meal loading was there a progressive and persistent decline in ghrelin levels until the end of the study, while a rapid and temporary rise in gastrin, insulin, and glucose levels at 0.5 h was observed. The levels of gastrin, insulin, and glucose then declined progressively. Conclusions: Preprandial oral dose of sitagliptin does not affect circulating ghrelin, gastrin, insulin, and glucose concentrations in normal subjects. Decreased ghrelin and increased gastrin and insulin levels occurred only after meal loading. These results support the theory that sitagliptin might not cause appetite-enhanced body weight gain and insulin-induced hypoglycemia.

Myocardial ATP-sensitive potassium (KATP) channels have been implicated in attenuating cardiac hypertrophy by modulating endothelin-1 concentrations. Sulfonylureas differ in their affinity for cardiac KATPchannels and therefore may vary in their effects on left ventricular (LV) mass. We sought to determine the differential effects of sulfonylureas on LV mass in type 2 diabetic patients. All patients had been taking glibenclamide for more than 3 mo before being randomized to either switch to an equipotent dose of gliclazide or continue glibenclamide. A total of consecutive 240 diabetic patients were randomized into glibenclamide, gliclazide, a combination of glibenclamide and nicorandil, or gliclazide and nicorandil for 6 mo. In the gliclazide-treated group, the LV mass index was significantly decreased compared with that in the glibenclamide-treated groups. Nicorandil administration significantly reduced LV mass in glibenclamide-treated patients compared with patients treated with glibenclamide alone. Measurements of endothelin-1 concentrations mirrored the functional status of KATPchannel. Multivariate analysis revealed that regression of LV mass was significantly correlated only with the changes in endothelin-1 ( P < 0.0001). Our results show that KATPchannels may play a pathogenetic role, probably through an endothelin-1-dependent pathway, in diabetes mellitus-related ventricular hypertrophy. Patients treated with gliclazide may have a beneficial effect in attenuating ventricular mass.

Diabetes is a state of increased oxidant stress and there is evidence that oxidation may play a role in the genesis of higher left ventricular mass. Gliclazide has been shown to possess free radical scavenging properties. We assessed whether gliclazide may have a beneficial effect on left ventricular mass via reducing 8-iso-prostaglandin F(2alpha) concentrations, a reliable marker of oxidant injury. A total of 41 patients were randomized into two groups. All patients had been taking glibenclamide for more than 3 months before being randomized to switch either an equipotent dose of gliclazide (n=21) or to continue on glibenclamide (n=20). Baseline characteristics were similar in both groups. At 6 months, gliclazide-treated patients showed a significant regression in left ventricular mass index compared with the glibenclamide-treated group (-16% versus 3%, P=0.003). Gliclazide patients had significantly lower plasma 8-iso-prostaglandin F(2alpha) compared with baseline (299+/-101 pg/ml versus 400+/-112 pg/ml, P=0.001) and the glibenclamide-treated patients (299+/-101 pg/ml versus 388+/-114 pg/ml, P=0.01) after 6-month therapy. The magnitude of left ventricular mass index regression correlated univariately with the magnitude of inhibition of 8-iso-prostaglandin F(2alpha) formation (r=0.74, P

Background: The discovery of asynchronous or synchronous double or multiple malignancies in patients is not uncommon. The co-occurrence of second primary malignancy (SPM) could be randomly occurring or association with risk factors such as environmental, genetic predisposition and therapy-related. Materials and methods: We retrieved ∼782 million claim records consisting of 10.8 million males and 10.6 million females from Taiwan’s National Health Insurance, which were collected for a period of 3 years (January 2000–December 2002). All the patient records were stratified by gender and ages at a 20-year interval with SPMs and specific groups. Interestingness or Q -value was used to measure strength of the disease–disease associations. Results: A total of 9423 thyroid cancer (female: 7483, male: 1940), 276 184 SPM (female: 141 023, male: 135 161) and 861 co-occurrence cases (female: 583, male: 278) were recorded. The co-occurrence incidence rate of head and neck, breast, digestive system and lung was 1.93%, 1.59%, 1.44% and 1.18%, respectively. Malignancy of salivary glands, laryngx, sarcoma, lymphoid tissue, mouth, central nervous system and lungs found Q -value >10. Malignancies with intermediate Q -values (5.0–9.9) were observed in nasopharynx, kidney and ureter, breast, stomach and skin. Prostate, leukemia, urinary bladder, ovary, colon, liver and uterine cervix cancer have lower Q -values (1.0–4.9). Conclusion: Co-occurrence ratio of thyroid cancer and SPM was high, occurred in all organ systems. We postulated that the aggressive use of modern diagnostic modalities, aggressive radioiodine treatment, pre-existing molecular oncogen mutations, and thyroid hormone for simultaneously supple-mentary and suppressive therapies were responsible.

PURPOSE: The previous studies of extrapulmonary tuberculosis (EPTB) have not focused on the impacts of diabetes mellitus. We conducted a retrospective study to explore the difference between EPTB patients with and without diabetes. METHODS: The EPTB patients receiving initial treatments from Taipei Medical University Hospital between January 2003 and March 2008 were recruited. They were divided into with-diabetes (WD) group or non-diabetes (ND) group according to coexistence of diabetes mellitus or not, respectively. All characteristics of these two groups were compared. RESULTS: Seventy-five patients were enrolled into our study. Fifteen patients and 60 patients were recruited into WD and ND groups, respectively. The basic characteristics and tuberculosis sites of the two groups were compared. The prevalence of hypertension (66.7% vs. 38.3%, p=0.048) and chronic liver diseases (33.3% vs. 3.3%, p=0.003) in WD group were higher than in ND group. The incidence of tuberculous peritonitis in WD group was higher than in ND group (26.7% vs. 6.7%, p=0.046). The odds ratio of tuberculous peritonitis for WD group was 5 091 (95% CI 1.103-23.493, p=0.037). The random glucose level (10.9+/-5.8 vs. 6.8+/-1.6 mmol/L, p=0.025), the fasting glucose level (8.6+/-4.4 vs. 5.6+/-0.9 mmol/L, p=0.038), and the hemoglobin A1c level (7.4+/-1.1 vs. 5.6+/-0.4%, p=0.037) were higher in WD group than in ND group. The total bilirubin level was higher in WD group than in ND group (18.4+/-6.2 vs. 13+/-7.2 micromol/L, p=0.042). Presenting symptoms and other laboratory data were not different statistically between these two groups. CONCLUSIONS: This is the first study about the impacts of diabetes on EPTB. The prevalence of hypertension and chronic liver diseases, the incidence of tuberculous peritonitis, and the total bilirubin level were higher in EPTB patients with diabetes than those without diabetes.

COPD estimates the third leading cause of death by 2020. To reduce its complications becomes an important issue. The purpose of this study is to investigate the influenza vaccine effect for IHD occurrence with secondary to COPD. We used 11 years Taiwan National Health Insurance cohort research database and analyzed the relationships between vaccination and incident of IHD for COPD patients stratified by age. Total 29,178 COPD patients, 703 patients got vaccination out of 1464 who have developed IHD and 6010 patients vaccinated out of 27,714 that did not developed IHD. Major findings we observed: vaccination was associated with a reduced risk of IHD (OR, 0.746; 95% CI, 0.595-0.937) in elderly COPD patients. Influenza vaccination was associated with a reduced risk for IHD only in elderly COPD patients. Moreover, COPD patients with IHD had higher vaccination rate than without IHD.

BACKGROUND: Medication errors are common, life threatening, costly but preventable. Information technology and automated systems are highly efficient for preventing medication errors and therefore widely employed in hospital settings. The aim of this study was to construct a probabilistic model that can reduce medication errors by identifying uncommon or rare associations between medications and diseases. METHODS AND FINDINGS: Association rules of mining techniques are utilized for 103.5 million prescriptions from Taiwan's National Health Insurance database. The dataset included 204.5 million diagnoses with ICD9-CM codes and 347.7 million medications by using ATC codes. Disease-Medication (DM) and Medication-Medication (MM) associations were computed by their co-occurrence and associations' strength were measured by the interestingness or lift values which were being referred as Q values. The DMQs and MMQs were used to develop the AOP model to predict the appropriateness of a given prescription. Validation of this model was done by comparing the results of evaluation performed by the AOP model and verified by human experts. The results showed 96% accuracy for appropriate and 45% accuracy for inappropriate prescriptions, with a sensitivity and specificity of 75.9% and 89.5%, respectively. CONCLUSIONS: We successfully developed the AOP model as an efficient tool for automatic identification of uncommon or rare associations between disease-medication and medication-medication in prescriptions. The AOP model helps to reduce medication errors by alerting physicians, improving the patients' safety and the overall quality of care.

Background/Aim: While it has been demonstrated that rice bran might lower the cholesterol level in hypercholesterolemic individuals, its effects on the levels of adiponectin and glycated hemoglobin (HbA1c) in patients with type 2 diabetes mellitus remain unknown. Methods: Twenty-eight volunteers with type 2 diabetes were randomly divided into 2 groups, one of which received a dietary supplement of 20 g of stabilized rice bran and the other placebo once daily for 12 weeks. Parameters such as the level of HbA1c, glucose, insulin, homeostasis model assessment for estimation of relative insulin resistance, high-density and low-density lipoprotein (LDL) cholesterol and adiponectin were evaluated. Results: At the end of the study period, postprandial glucose and the area under the glucose curve of the rice bran group were significantly lower than baseline levels by 14.4 and 15.7%, respectively. Compared to baseline, the HbA1c values in the rice bran group were also significantly lower. Serum total cholesterol and LDL cholesterol concentrations in the rice bran group were 9.2 and 13.7% lower, respectively, than in the placebo group. The plasma free fatty acid and adiponectin concentrations were 20% lower and 40% higher in the rice bran group compared to the placebo group. Conclusions: This study demonstrated that stabilized rice bran can lower the level of HbA1c and blood lipids and increase blood adiponectin concentrations in type 2 diabetic subjects. In light of this, we conclude that stabilized rice bran may represent an important functional nutrient to ameliorate lipid and glycemic anomalies in type 2 diabetic subjects.

To determine the effects of chromium (Cr) supplementations on oxidative stress of type 2 diabetes and euglycemic (EU) subjects, adult having HbA(1C) values of6.0% (EU), 6.8-8.5% (mildly hyperglycemic, MH), and8.5% (severely hyperglycemic, SH) were supplemented for 6 months with 1000 microg/day of Cr (as Cr yeast) or with a placebo. In the beginning, the levels of the plasma Cr in the MH and SH groups were 25-30% lower than those of the EU subjects. The values of thiobarbituric acid reactive substances (TBARS) and total antioxidative status (TAS) of the MH and SH groups were significantly higher than those of the EU ones. Following supplementations, the levels of plasma TBARS in the Cr groups of MH and SH groups were significantly decreased (the inverse was found in the EU) and showed no significant changes in the placebo group. The levels of plasma TAS in the Cr groups of EU and MH were significantly decreased (the inverse was found in the SH) and showed no significant changes in the placebo group. No significant difference was found in the antioxidant enzyme (superoxide dismutase, glutathione peroxidase, catalase) activities during supplementations. These data suggest that Cr supplementation was an effective treatment strategy to minimize increased oxidative stress in type 2 diabetes mellitus patients whose HbA(1C) level was8.5%, and the Cr in EU groups might act as a prooxidant.

ObjectiveThe early identification of subjects at high risk for diabetes is essential, thus, random rather than fasting plasma glucose is more useful. We aim to evaluate the time interval between pre-diabetes to diabetes with anti-diabetic drugs by using HbA1C as a diagnostic tool, and predicting it using a mathematic model.MethodsWe used the Taipei Medical University Affiliated Hospital Patient Profile Database (AHPPD) from January-2007 to June-2011. The patients who progressed and were prescribed anti-diabetic drugs were selected from AHPPD. The mathematical model used to predict the time interval of HbA1C value ranged from 5.7% to 6.5% for diabetes progression.ResultsWe predicted an average overall time interval for all participants in between 5.7% to 6.5% during a total of 907 days (standard error, 103 days). For each group found among 5.7% to 6.5% we determined 1169.3 days for the low risk group (i.e. 3.2 years), 1080.5 days (i.e. 2.96 years) for the increased risk group and 729.4 days (i.e. 1.99 years) for the diabetes group. This indicates the patients will take an average of 2.49 years to reach 6.5%.ConclusionThis prediction model is very useful to help prioritize the diagnosis at an early stage for targeting individuals with risk of diabetes. Using patients' HbA1C before anti-diabetes drugs are used we predicted the time interval from pre-diabetes progression to diabetes is 2.49 years without any influence of age and gender. Additional studies are needed to support this model for a long term prediction.