Depression, Diabetes Mellitus and Mortality in Older Adults: A National Cohort Study in Taiwan.

Purpose: Diabetes mellitus (DM) increases the risk of cardiovascular and all-cause mortality. The coexistence of depression and DM is associated with an increased risk of DM complications and functional morbidity. The independent effect of depression on mortality in patients with DM is unclear, and relevant Asian studies have provided inconsistent results. Accordingly, this study assessed the independent and additive effects of DM and depression on mortality in a nationally representative cohort of older adults in Taiwan over a 10-year observation period. Patients and Methods: A total of 5041 participants aged 50 years or older were observed between 1996 and 2007. We defined depression as a score of ≥8 on the 10-item Center for Epidemiologic Studies Depression (CES-D 10) scale. Additionally, we defined participants as having type 2 DM if they had received a diagnosis of type 2 DM from a health-care provider. Cox proportional hazard models were applied to analyze predictors of mortality in depression and DM comorbidity groups. Results: During the 10-year follow-up period, 1637 deaths were documented. After adjustment for potential confounders, the hazard ratios for mortality in participants with both depression and DM, DM only, and depression only were 2.47 (95% confidence interval [CI]: 2.02-3.03), 1.95 (95% CI: 1.63-2.32), and 1.23 (95% CI: 1.09-1.39), respectively. Conclusion: The co-occurrence of depression with DM in Asian adults increased overall mortality rates. Our results indicate that the increased mortality hazard in individuals with DM and depression was independent of sex.

Association between systemic sclerosis and peripheral arterial disease: a nationwide observation retrospective claim records cohort study in Taiwan.

OBJECTIVES: Recent studies have proposed associations between systemic sclerosis (SSc) and atherosclerosis and between SSc and cardiovascular disease. However, in Asia, no large-scale studies have focused on the association between peripheral arterial disease (PAD) and SSc. SETTING: A nationwide observation retrospective cohort study. PARTICIPANTS: The National Health Insurance Research Database was used for selecting patients diagnosed with SSc from 2000 to 2011. Patients diagnosed with PAD before the index date were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES: The SSc cohort comprised 1106 patients with SSc, and the non-SSc cohort comprised 4424 matched controls. The Cox proportional hazards regression model was used for analysing the adjusted risk of PAD between the case and control patients. RESULTS: The SSc cohort exhibited a significantly higher risk (HR=2.15, 95% CI=1.47 to 3.14) of PAD than did the non-SSc cohort. Patients with heart failure exhibited the highest risk of PAD (adjusted HR=2.10, 95% CI=1.20 to 3.70). Moreover, even without any comorbidities, the SSc cohort exhibited a significantly higher risk (adjusted HR=4.17 fold, 95% CI=1.98 to 8.77) of PAD than did the non-SSc cohort. CONCLUSION: SSc is associated with a significantly high risk of PAD. Further studies are required to reduce the PAD risk among patients with SSc.

Liu Wei Di Huang Wan and the Delay of Insulin Use in Patients with Type 2 Diabetes in Taiwan: A Nationwide Study.

INTRODUCTION: Patients with type 2 diabetes are widely prescribed metformin for controlling blood glucose levels to avoid related comorbidities. In Taiwan, traditional Chinese medicine (TCM) is also commonly used, especially Liu Wei Di Huang Wan (LWDHW), which has been reported to delay the occurrence of kidney failure. However, the effect of combinational therapy of TCM and oral antidiabetic drugs is still unclear. This study aims to estimate their efficacy in delaying insulin use. MATERIALS AND METHODS: This case-control study was conducted using one million randomized samples from the National Health Insurance Research Database in Taiwan. The effects of TCM and LWDHW were estimated using the Cox proportional hazards model. RESULTS: In this study, 70,036 diabetic patients were enrolled; of them, 17,451 (24.9%) used insulin, while the rest (52,585, 75.1%) did not. TCM users had a lower risk for insulin use (HR: 0.58, 95% CI: 0.56-0.60). LWDHW users had a lower risk compared with patients who used other TCM (HR: 0.86, 95% CI: 0.82-0.90) and presented a dose-dependent effect. CONCLUSION: The use of LWDHW and oral antidiabetic drugs is highly associated with the delay in the use of insulin. Clinical practitioners may take them into consideration when treating patients with type 2 diabetes.

Pyogenic Liver Abscess Risk in Patients With Newly Diagnosed Type 2 Diabetes Mellitus: A Nationwide, Population-Based Cohort Study.

Background: To date, no comprehensive epidemiological study exists on pyogenic liver abscess (PLA) risk in patients with newly diagnosed type 2 diabetes mellitus (T2DM) worldwide. Methods: We conducted a retrospective cohort study by using data from Taiwan National Health Insurance Research Database (NHIRD) to examine the association between newly diagnosed T2DM and PLA. The T2DM cohort included patients newly diagnosed as having T2DM (ICD-9-CM:250) from 2000 to 2009, with follow-up until December 31, 2011. The comparison cohort was then recruited through 1:4 random frequency matching with the T2DM cohort. Finally, the adjusted hazard ratios for PLA were compared between the T2DM and comparison cohorts, which included 44,728 patients with T2DM and 178,912 patients without DM respectively. Results: In T2DM cohort, 166 patients were diagnosed as having PLA (incidence rate = 5.87 per 10,000 person-years) and in comparison cohort, 238 patients were diagnosed as having PLA (incidence rate = 2.06 per 10,000 person-years). The T2DM cohort exhibited higher PLA risk than did the comparison cohort (hazard ratio = 2.83, 95% confidence interval = 2.32-3.46). Furthermore, the adjusted hazard ratio for PLA risk in T2DM cohort was the highest in those who were younger, man and with duration of DM <2 years. In the T2DM cohort, the most common PLA causative agent was Klebsiella pneumonia (KP). In addition, PLA risk was high in T2DM patients with gallstone and cholecystitis. Compared with comparison cohort, patients with T2DM prescribed acarbose has a lower PLA risk, however glyburide significantly increased PLA risk in T2DM cohort. Conclusion: In patients with newly diagnosed T2DM, PLA risk was high and acarbose might reduce PLA risk.

Pitavastatin and metformin synergistically activate apoptosis and autophagy in pancreatic cancer cells.

Pancreatic cancer is the seventh leading cause of cancer-related deaths globally. Metformin is the standard first-line of treatment for hyperglycemia in Type 2 diabetes, whereas pitavastatin is a cholesterol-lowering drug used to prevent cardiovascular diseases. Both these agents evidently exert anticancer effects on pancreatic cancer; however, it remains unclear whether cotreatment using them has additive or synergistic anticancer effects on pancreatic cancer. Thus, we herein used the ASPC-1 and PANC-1 cells and treated them with metformin and/or pitavastatin. We performed the cell viability assay, transwell migration assay, and cell cycle analysis using flow cytometry. Western blotting was used to determine protein levels. We found that cotreatment with metformin (30 mM) and pitavastatin (10 µM) significantly reduced cell viability; caused G0/G1 cell cycle arrest; upregulated the expression levels of Bax, PCNA, cleaved PARP-1, cleaved caspase-3, LC3 II, and p27 Kip1 /p21Cip1 ; and inhibited cell migration. The combination index value for cell viability indicated a synergistic interaction between metformin and pitavastatin. Moreover, cotreating the cells with metformin (30 mM) and pitavastatin (10 µM) could preserve mitochondrial function, activate AMPK, and inhibit PI3K/mTOR than treatment with metformin or pitavastatin alone. These findings clearly indicated that metformin plus pitavastatin had a synergistic anticancer effect on pancreatic cancer cells, potentially caused due to the activation of AMPK and inhibition of PI3K/mTOR signaling. Altogether, our results provide that use of metformin plus pitavastatin maybe serve as a chemotherapeutic agent for human pancreatic cancer in future.

The Association Between Pleural Empyema and Peripheral Arterial Disease in Younger Patients: A Retrospective National Population-Based Cohort Study.

Background: To investigate the relationship between pleural empyema (PE) and peripheral arterial disease (PAD). Methods: We conducted a retrospective cohort study using data from the National Health Institute Research Database. Univariable and multivariable Cox's proportional hazard regressions were performed to investigate the association between PE and the risk of PAD. Kaplan-Meier method and the differences were assessed using a log-rank test. Results: The overall incidence of PAD was higher in the PE cohort than in the non-PE cohort (2.76 vs. 1.72 per 1,000 person-years) with a crude hazard ratio (HR) of 1.61 [95% confidence interval (CI) = 1.41-1.83]. After adjustment for age, gender, and comorbidities, patients with PE were noted to be associated with an increased risk of PAD compared with those without PE [adjusted HR (aHR) = 1.18, 95% CI = 1.03-1.35]. Regarding the age-specific comparison between the PE and non-PE cohorts, PAD was noted to be significantly high in the ≤ 49 years age group (aHR = 5.34, 95% CI = 2.34-10.1). The incidence of PAD was higher in the first 2 years, with an aHR of 1.35 (95% CI = 1.09-1.68) for patients with PE compared with those without PE. Conclusion: The risk of PAD was higher if patients with PE were younger than 49 years and within the 2-year diagnosis of PE.

Teaching the Concept of Computational Thinking: A STEM-Based Program With Tangible Robots on Project-Based Learning Courses.

The twenty-first century is arguably the century of computing. In such a world saturated by computing, Computational Thinking is now recognized as a foundational competency for being an informed citizen and being successful in STEM work. Nevertheless, how to effectively import different types of teaching methods in university courses (lecture based learning, project based learning) is subjected to further evaluation. Currently, the arguments in favor of tangible robots including high interaction, great practicality, and specific operation results make themselves to be often used as a teaching medium and tool for teaching activities between teachers and students. Hence, in addition to cultivating students with computational thinking ability, this paper discussed how to integrate tangible robots into project-based learning courses of thinking skills training to improve the learning performance of the computational thinking ability. This study conducted in one semester on the 105 students from three classes. Experimental results show that the project-based learning method integrated with the teaching material of robotic visual programs approach had significantly better effectiveness in improving students' learning achievements than the traditional teaching method integrated with paper practice teaching materials approach. Analysis of the questionnaire results showed that the proposed learning approach did not increase the students' cognitive burden. In sum, the proposed approach helps students' learning achievement and cognitive load.

Time-sequential correlations between diabetic kidney disease and diabetic retinopathy in type 2 diabetes - an 8-year prospective cohort study.

PURPOSE: To investigate the time-sequential correlations between progression/remission of diabetic kidney disease (DKD) and development of diabetic retinopathy (DR) or diabetic macular oedema (DME) in type 2 diabetes (T2D). METHODS: This was an 8-year prospective cohort study in which 576 patients with T2D and microalbuminuria from one medical centre in Taiwan were recruited. Progression of microalbuminuria was defined as shift of urinary albumin/creatinine ratio (ACR) into 300 mg/g or more; remission of microalbuminuria was defined as having a urinary ACR less than 30 mg/g in at least two of three tests over a period of 6 months. Cox regression analysis was used to evaluate the hazard ratios (HRs) for progression or remission of microalbuminuria on development of any DR, proliferative DR (PDR) and DME. RESULTS: After adjusting for baseline characteristics , remission of microalbuminuria was a significant protecting factor for development of PDR (HR = 0.290, 95% CI: 0.102-0.826, p = 0.020) and DME (HR = 0.404, 95% CI: 0.188-0.864, p = 0.020). After further adjustment for the mean follow-up HbA1c and systolic blood pressure, remission of microalbuminuria was still a significant protecting factor for development of PDR (HR = 0.348, 95% CI: 0.122-0.992, p = 0.048). CONCLUSIONS: Remission of microalbuminuria was an independent protecting factor for development of PDR and DME. Aggressive treatment for DKD might help prevent the progression of DR.

Association of Hemorrhoids With Hashimoto's Thyroiditis and Associated Comorbidities: A Nationwide Population-Based Cohort Study.

Background: To evaluate the relationship between hemorrhoids and Hashimoto's thyroiditis (HT). Methods: Using Taiwan's Longitudinal Health Insurance Database, we compared the incident risk of HT between the study cohort (comprising patients with hemorrhoids) and the comparison cohort (comprising patients without hemorrhoids). Both cohorts were followed from index date until the date of HT diagnosis, withdrawal from the National Health Insurance program, or the end of 2015. Results: The study cohort and comparison cohort comprised 6,486 patients with hemorrhoids and 25,944 patients without, respectively. The mean follow-up time was ~3 years. The incidence rate of HT in the study cohort was 5.37 per 1,000 person-years, which was higher than that of the control cohort (2.46 per 1,000 person-years). The risk of developing HT in the study cohort was 2.06 times (95% confidence interval [CI] = 1.02, 4.19) higher than that in the comparison cohort. Conclusion: In our study, patients with hemorrhoids could be at increased risk of HT compared with patients with other comorbidities of HT, such as cardiovascular disease.

Effects of dipeptidyl peptidase-4 inhibitor treatment doses on tuberculosis in patients with diabetes: a long-term nationwide population-based cohort study.

BACKGROUND: To investigate the association of dipeptidyl peptidase-4 inhibitors (DPP4is) treatment doses and tuberculosis (TB) in patients with diabetes. METHODS: We allocated participants into DPP4i users and non-users from the Longitudinal Health Insurance Database. A chi-square test and Wilcoxon's rank-sum test were used to analyze the baseline discrete variables and continuous variable, respectively. The incidence rate was calculated in 1,000 personyears. The hazard ratios (HRs) were adjusted using a multivariate Cox regression model. The effect of DDP4i dosage on TB was analyzed. The Kaplan-Meier method was used to assess the cumulative incidence curves with a log-rank test. RESULTS: We identified 6,399 DPP4i users and 6,399 non-users. The incidence rate of TB in DPP4i users and non-users was 22.2 and 16.2 per 1,000 person-years, respectively. The HR of TB for DPP4i users relative to non-users was 1.04 (P=0.89). Most of the analysis of factors such as the incidence rate, gender and diabetic comorbidities in our study were non-significant. The risk of developing TB in patients with over 20 average defined daily doses (DDDs) per year was increased by 2.19 times (P=0.048). CONCLUSIONS: In our long-term nationwide population-based cohort study, higher doses of DPP4i (20 average DDDs) could increase TB infection risk in patients with diabetes. To pay more attention to this kind of diabetic patients with DPP4i treatment will be more important for the public health issue of TB prevention.

Hashimoto's thyroiditis might increase polycystic ovary syndrome and associated comorbidities risks in Asia.

BACKGROUND: To investigate whether increased the comorbidities such as coronary artery disease (CAD) and risks between Hashimoto's thyroiditis (HT) and polycystic ovary syndrome (PCOS) in Taiwanese women. METHODS: Patients newly diagnosed as having HT during 2000-2012 were assigned to the case group. Cases and controls were matched for age and comorbidities at a 1:2 ratio using propensity score matching. Incidence was calculated in the unit of 1000 person-year. Univariate and multivariate Cox proportional hazard regression, multivariate Cox, logistic regression, and Kaplan-Meier analyses were performed. RESULTS: Among 3,996 participants, 2,664 constituted the control group and 1,332 constituted the case group. The PCOS risk in patients with HT increased by 2.37 times [95% confidence interval (CI): 1.22-4.62] compared with the controls. Hypertension (HTN) [adjusted odds ratio (OR): 1.31, 95% CI: 1.03-1.66] and hyperlipidemia (adjusted OR: 1.55, 95% CI: 1.2-1.9) were more common in HT patients without PCOS than in other patients. The adjusted OR for CAD in patients with HT was 1.51 (95% CI: 1.11-2.06), whereas that in patients with HT and PCOS was 5.92 (95% CI: 1.32-26.53). CONCLUSIONS: In our study, the PCOS risk in patients with HT increased by 2.37 times, which is lower than the increase in HT risk in Asian patients with PCOS (4.56 times). The proportion of CAD increased significantly by 5.92 times in patients with HT and PCOS compared with patients with HT only.

Dipeptidyl peptidase-4 inhibitor treatment could decrease Klebsiella pneumoniae pneumonia in patients with type 2 diabetes.

OBJECTIVES: To investigate the effect of dipeptidyl peptidase-4 inhibitor (DPP4i) for Klebsiella pneumoniae (KP) pneumonia in patients with diabetes. PATIENTS AND METHODS: Patients newly diagnosed with type 2 diabetes from 2009 to 2012 were recruited for this population-based and observational study. Diabetes complications severity index (DCSI) score and defined daily dose (DDD) were used for analysis. The multivariable Cox proportional hazards models were used to estimate the risk of KP pneumonia by DPP4i use, with adjustments for propensity score. The Kaplan-Meier method with the log-rank test was used to estimate the risk of KP pneumonia for DPP4i users. RESULTS: 34774 patients were included. The incidence rate of KP pneumonia in DDP4i users was 1.51 per 1000 person-years and that for the comparison was 2.25 per 1000 person-years. DDP4i users also had a significantly lower cumulative incidence of KP pneumonia (log-rank test p-value = 0.03). DDP4i users had a significantly lower risk of developing KP pneumonia compared with nonusers (adjusted HR = 0.67, 95% CI = 0.48-0.95). CONCLUSIONS: For public health issue with type2 diabetes and infection, DPP4i use decreased KP pneumonia. Male gender, patients with co-morbidities, patients with higher DSCI score and higher DDD of DPP4i were observed to decrease KP pneumonia infection in our analysis. The possible role of DPP4i causing immunological disturbances should be considered.

Synergistic Anticancer Effects of Gemcitabine with Pitavastatin on Pancreatic Cancer Cell Line MIA PaCa-2 in vitro and in vivo.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with an overall 5-year survival rate of 9.3%, and this malignancy is expected to become the second leading cause of cancer-related death by 2030. Gemcitabine resistance develops within weeks of PDAC patient's chemotherapeutic initiation. Statins, including pitavastatin, have been indicated to have anticancer effects in numerous human cancer cell lines. Thus, in this study, we hypothesized that a combination of gemcitabine and pitavastatin may have a greater anticancer effect than gemcitabine alone on the human pancreatic carcinoma cell line MIA PaCa-2. METHODS: The anticancer effects of gemcitabine with pitavastatin were evaluated using human MIA PaCa-2 cell line in vitro and in vivo Balb/c murine xenograft tumor model. Cell viability was assessed with CCK-8, and cell migration was stained by crystal violet. Cell cycle distribution, apoptosis and mitochondrial membrane potential were examined by flow cytometry. Activation of drug transporters (hENTs, hCNTs), intracellular drug activating (dCK) and inhibition of inactivating enzymes (RRMs) pathways were assessed by Western blotting analysis. Molecular mechanisms and signaling pathways of apoptosis, necrosis and autophagy also were assessed by Western blotting. RESULTS: We observed that gemcitabine and pitavastatin synergistically suppressed the proliferation of MIA PaCa-2 cells through causing sub-G1 and S phase cell cycle arrest. Activation of apoptosis/necrosis was confirmed by annexin V/propidium iodide double staining, which showed increasing levels of active caspase 3, cleaved poly(ADP-ribose) polymerase and the RIP1-RIP3-MLKL complex. Moreover, gemcitabine-pitavastatin-mediated S phase arrest downregulated cyclin A2/CDK2 and upregulated p21/p27 in MIA PaCa-2 cells. Furthermore, this combination improved drug cellular metabolism pathway, mitochondria function and activated autophagy as part of the cell death mechanism. In vivo, gemcitabine-pitavastatin effectively inhibited tumor growth in a nude mouse mode of Mia PaCa-2 xenografts without observed adverse effect. CONCLUSION: Combined gemcitabine-pitavastatin may be an effective novel treatment option for pancreatic cancer.

Increased the risk of heart failure and comorbidities in patients with gout treatment: a population-based cohort study.

BACKGROUND: To investigate the association between gout treatment and heart failure (HF). METHODS: Patients with gout between 2000 and 2010 constituted the gout cohort. The main outcome was a new diagnosis of HF. Multivariable Cox proportional hazard regression models were used to measure the effect of gout on the risk of developing HF. The Kaplan-Meier method was used to estimate the cumulative HF incidence curve for the gout and nongout cohorts. RESULTS: The cohort study included 50,166 patients with gout. The incidence of HF was 1.96 times higher in the gout cohort than the non-gout cohort (7.11 vs. 3.63 per 10,000 person-years). The adjusted HR of developing HF was a 1.06-fold increase (95% CI: 1.06-1.07) with age and a 1.08-fold increase for women compared with men (95% CI: 1.02-1.14). HF incidence was higher in patients with receiving any two or more types of anti-gout drug treatment. CONCLUSIONS: Our study revealed that gout could increase the risk of HF. Gout treatment in Taiwan cannot improve HF and actually increase the risk for HF after combination therapy for gout. The public health burden of gout should be resolved in the future.

Graves' disease could increase polycystic ovary syndrome and comorbidities in Taiwan.

Background: To investigate the association between Graves' disease (GD) and polycystic ovary syndrome (PCOS) and its comorbidities.Methods: Logistic regression was performed to determine the association between the two conditions. Cumulative incidence curves were obtained using the Kaplan-Meier method and log-rank test. Hazard ratios were determined using the Cox proportional hazards regression model.Results: We included 5399 patients with GD as the study group and 10,798 patients without GD as the control group. The cumulative incidence curve of PCOS in patients with GD was significantly higher than that in patients without GD (p = .02). The adjusted hazard ratio for PCOS in patients with GD compared with patients without GD was 1.47 (95%CI = 1.09-1.98). The adjusted odds ratio of hyperlipidemia in patients with GD and PCOS was 2.18 (95%CI = 1.14-4.17) higher than that in patients with GD only.Conclusion: Our study demonstrated that women with GD could be at risk of developing PCOS; additionally, a higher incidence of comorbidities, including hyperlipidemia, was noted in women with GD and PCOS.

Gout can increase the risk of periodontal disease in Taiwan.

Objectives: To evaluate the risk of periodontal disease (PD) in gout patients. Methods: This retrospective cohort study was conducted using data from the Longitudinal Health Insurance Database 2000. The gout cohort included 31,759 patients newly diagnosed with gout from 2000 to 2012, and the comparison (nongout) cohort included 63,517 patients. Univariate and multivariable adjusted hazard ratios (aHRs), with corresponding 95% confidence intervals (CIs), were estimated using the Cox proportional hazard model for determining the occurrence of PD in both cohorts. We also measured the cumulative incidence of PD in these two cohorts using the Kaplan-Meier method and assessed the curve difference using the log-rank test. Results: The mean follow-up time was more than 6 years for both cohorts. The overall incidence rate of PD was significantly higher in the gout cohort than in the comparison cohort (5.04 vs 4.16 per 10,000 person-years; aHR = 1.13, 95% CI = 1.10-1.16). Only patients using colchicine had a significantly lower risk of PD (aHR = 0.85, 95% CI = 0.79-0.91). Conclusion: In our study, patients with gout showed an increased risk of PD, and treatment with colchicine could decrease the risk. Abbreviations: PD: periodontal disease; LHID: Longitudinal Health Insurance Research Database; NHIRD, National Health Insurance Research Database; ICD-9-CM: International Classification of Diseases, Ninth Revision, Clinical Modification; CI: confidence interval; HR: hazard ratio.

Increased Risk of Polycystic Ovary Syndrome and It's Comorbidities in Women with Autoimmune Thyroid Disease.

OBJECTIVE: To investigate the prevalence of polycystic ovary syndrome (PCOS) and its comorbidities in patients with autoimmune thyroid disease (AITD). POPULATION: In this cohort study, patients newly diagnosed as having Hashimoto thyroiditis (HT) or Grave disease (GD) were recruited into the AITD group. METHOD: The logistic regression model was used to investigate the association between exposure, endpoint, later diseases and treatment. MAIN OUTCOME MEASURES: We assessed the cumulative incidence using the Kaplan-Meier method and verified the difference by the log-rank test. RESULTS: The AITD group included 3599 GD patients and 1332 HT patients. PCOS risk in patients with AITD was higher than that in the control group (adjusted hazard ratio = 1.39; 95% confidence interval = 1.07-1.71). In patients with both AITD and PCOS, the odds ratios of diabetes, hyperlipidemia and coronary artery disease were 2.48, 2.05 and 2.63, respectively. CONCLUSIONS: The risks of PCOS and its comorbidities such as diabetes, dyslipidemia and cardiac artery disease are high in patients with AITD in Taiwan.

Fasting glucose-to-HbA1c ratio is a good indicator of G6PD deficiency, but not thalassemia, in patients with type 2 diabetes mellitus.

AIMS: Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency or thalassemia have a shorter red blood cell lifespan; therefore, HbA1c is underestimated in these patients. To address these issues, we sought an early indicator for G6PD deficiency or thalassemia in DM patients. METHODS: A total of 4908 patients with DM and 1848 subjects without DM were included in this study. Fasting glucose (FG) levels, HbA1c levels, hemogram profiles and G6PD activities were measured. Genotypic analyses of G6PD deficiency and thalassemia were performed. RESULTS: DM patients with G6PD deficiency had significantly higher FG/HbA1c ratios than did those without G6PD deficiency (26.54 vs. 18.36; p < 0.0001). We divided the FG level into four categories: ≤150, 151-250, 251-350, and ≥351 mg/dL. Among all groups, only patients with DM and G6PD deficiency had higher FG/HbA1c ratios than those of patients with DM alone or DM with thalassemia. To evaluate the reliability of the FG/HbA1c ratio, receiver operating characteristic analyses were performed. The areas under the curve for detecting FG ≤ 150, 151-250, 251-350, and ≥351 mg/dL with G6PD deficiency based on the FG/HbA1c ratio were 0.839 (p < 0.001), 0.888 (p < 0.001), 0.891 (p < 0.001), and 0.640 (p = 0.3954), respectively. G6PD deficiency was confirmed by genetic analysis. We found common mutations that influenced G6PD activity and HbA1c levels. CONCLUSIONS: The FG/HbA1c ratio is a good indicator of DM with G6PD deficiency. If this ratio is determined to be high in a clinical setting, then the clinician must consider whether the patient has a G6PD deficiency, and HbA1c reference values must be adjusted to avoid misdiagnosis and incorrect treatment decisions.

Fasting plasma glucose variability is an independent risk factor for diabetic retinopathy and diabetic macular oedema in type 2 diabetes: An 8-year prospective cohort study.

IMPORTANCE: Long-term stability in plasma glucose may affect the development of diabetic retinopathy (DR) and diabetic macular oedema (DMO). BACKGROUND: To investigate the associations between glycaemic variability and the development of DR and DMO in type 2 diabetes (T2D). DESIGN: An 8-year prospective cohort study. PARTICIPANTS: 2005 patients with T2D. METHODS: DR and DMO were detected with non-mydriatic fundus photography. MAIN OUTCOME MEASURES: The visit-to-visit variability of fasting glucose or HbA1c was calculated as the standard deviation (SD) or coefficient of variation (CV = SD/mean) of all records during the follow-up periods or before the onset of the targeted event. Cox regression analysis was used to evaluate the hazard ratios (HRs) for new-onset DR, proliferative diabetic retinopathy (PDR), and DMO. RESULTS: After adjusting for the baseline and mean follow-up values, the SD and CV of fasting glucose during the follow-up periods were both correlated with the development of PDR (SD: HR = 1.011, P = .005; CV: HR = 6.858, P < .001), and DMO (SD: HR = 1.008, P = .038; CV: HR = 4.027, P = .017). As for HbA1c, neither the SD nor CV was correlated with the development of DR, PDR, or DMO (P > .05 for all). CONCLUSIONS AND RELEVANCE: High visit-to-visit fasting glucose variability was associated with new-onset PDR and DMO, independent of baseline and mean follow-up fasting glucose and HbA1c in T2D. Long-term stability in plasma glucose is important for reducing the risk of the development and progression for DR and DMO.

Author Correction: The beneficial effects of Lactobacillus reuteri ADR-1 or ADR-3 consumption on type 2 diabetes mellitus: a randomized, double-blinded, placebo-controlled trial.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.