Antiplatelet agents aspirin and dipyridamole, and the risk of different carcinoma in patients with type 2 diabetes mellitus: A Taiwan retrospective cohort study.

Studies have shown aspirin decreases the risk of some cancers. However, the evidence reported the association between aspirin and cancer risk in the diabetic population. In this study, we investigate whether aspirin and dipyridamole decrease the risk of cancer in patients with type 2 diabetes. A total of 5308 patients with type 2 diabetes were identified by the National Health Insurance from 1998 to 2000 and followed up until 2013. The demographic characteristics among nondipyridamole nor aspirin, aspirin, and dipyridamole users were analyzed by using the χ(2) test. Cox proportional hazard regression models were used to determine the independent effects of no aspirin nor dipyridamole, aspirin, and dipyridamole users on the risk of different cancer. After adjustment with multiple covariates, both low and high doses of aspirin and dipyridamole decrease liver cancer with risk ratios of 0.56 (95% CI, 0.37-0.83), 0.14 (95% CI, 0.05-0.39), 0.61 (95% CI, 0.38-0.99), and 0.28 (95% CI, 0.12-0.66), respectively. Both low and high doses of aspirin decrease any types of cancer with risk ratios of 0.79 (95% CI, 0.64-0.98) and 0.49 (95% CI, 0.34-0.70), respectively. Therefore, we conclude aspirin may decrease any types of cancer and liver cancer, and dipyridamole may decrease the risk of liver cancer in patients with type 2 diabetes.

Association of depression and parasympathetic activation with glycemic control in type 2 diabetes mellitus.

AIM: Patients with type 2 diabetes mellitus exhibited autonomic nervous system (ANS) dysfunction and comorbidities with depressive or anxiety symptoms were related to poor glycemic control. Heart rate variability (HRV) converted from electrocardiogram (ECG) has been used as the ANS index. The study aimed to explore the associations between depression, anxiety, HRV, and glycemic control in patients with type 2 diabetes mellitus. METHODS: The Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) questionnaires were used to assess depressive and anxiety symptoms in 647 patients with type 2 diabetes mellitus (mean age was 63 ± 10 years, 56 % males). The ECG raw signals were collected from a 5-min sitting and resting baseline and then transformed to HRV indices referring ANS activation. Blood glucose and lipid profiles including glycated hemoglobin (HbA1c), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglyceride were obtained from the electronic medical records. RESULTS: Ninety-nine (15 %) participants had depressive symptoms and 59 (9 %) had anxiety symptoms. Depression and HbA1c were negatively correlated with parasympathetic activation. Depression and anxiety were positively correlated with sympathetic activation. After controlling for demographic data and lipid profiles, depression was a significant positive predictor for HbA1c levels; and HRV indices (lnLF and lnHF) were the significant negative predictors for HbA1c levels. Mediation effect analysis showed that depression was a mediator between parasympathetic activation and glycemic control. CONCLUSIONS: Lower parasympathetic activation and higher depressive symptoms may affect glycemic control in patients with type 2 diabetes mellitus. Intervention programs targeting to increase parasympathetic activities and reducing depression could be further tested for their effects on glycemic outcomes for potential clinical use.

Dipeptidyl Peptidase 4 Inhibitors Decrease the Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis C Infection and Type 2 Diabetes Mellitus: A Nationwide Study in Taiwan.

Introduction: Dipeptidyl peptidase 4 inhibitors (DPP-4 inhibitors) are incretin-based oral antidiabetic drugs. Previous studies have shown an association between increased plasma activity of DPP-4 and chronic hepatitis C virus (HCV) infection. Dipeptidyl peptidase 4 inhibitors may be associated with preventing the development of chronic HCV infection. The aim of this study was to investigate whether the use of DPP-4 inhibitors is associated with a decreased risk of hepatocellular carcinoma (HCC) in patients with diabetes mellitus (DM) and chronic HCV infection. Methods: In this retrospective cohort study, we enrolled patients with type 2 diabetes and chronic HCV infection from the National Health Insurance Research Database (NHIRD) in Taiwan. The patients were divided into two groups (DPP-4 inhibitor cohort and non-DPP-4 inhibitor cohort) according to whether or not they received DPP-4 inhibitor treatment. Results: Multivariate Cox proportional hazard regression analysis showed a significantly lower risk of HCC in the patients who took DPP-4 inhibitors compared to those who did not. Kaplan-Meier survival analysis demonstrated a significantly higher HCC-free rate in the DPP-4 inhibitor cohort than in the non-DPP-4 inhibitor cohort. Conclusion: The use of DPP-4 inhibitors was associated with a lower risk of HCC in patients with type 2 DM and chronic HCV infection.

Obesity-related indices are associated with albuminuria and advanced kidney disease in type 2 diabetes mellitus.

Obesity is an important risk factor for the development of diseases including diabetes, hypertension, and cardiovascular disease. However, few reports have investigated the relationships between these obesity-related indices and diabetic nephropathy. The aim of this study was to evaluate associations between obesity-related markers with albuminuria and advanced kidney disease in patients with type 2 diabetes mellitus (DM). Obesity-related indices including body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), body roundness index (BRI), conicity index (CI), lipid accumulation product (LAP), visceral adiposity index (VAI), body adiposity index (BAI), abdominal volume index (AVI), body shape index (BSI), and triglyceride glucose (TyG) index were measured. Albuminuria was defined as a urine albumin/creatinine ratio of ≥30 mg/g. Advanced kidney disease was defined as an estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m2. A total of 1872 patients with type 2 DM (mean age 64.0 ± 11.3 years, 809 males and 1063 females) were enrolled. In multivariable analysis, 11 high obesity-related indices (BMI, WHR, WHtR, LAP, BRI, CI, VAI, BAI, AVI, ABSI, and TyG index) were significantly associated with albuminuria. In addition, high BMI, WHR, WHtR, LAP, BRI, CI, VAI, and AVI were significantly associated with eGFR <30 ml/min/1.73 m2. The results of this study showed that various obesity-related indices were significantly associated with albuminuria and advanced kidney disease in patients with type 2 DM. Screening may be considered in public health programs to recognize and take appropriate steps to prevent subsequent complications.

Common Risk Factors in Relatives and Spouses of Patients with Type 2 Diabetes in Developing Prediabetes.

Prediabetes should be viewed as an increased risk for diabetes and cardiovascular disease. In this study, we investigated its prevalence among the relatives and spouses of patients with type 2 diabetes or risk factors for prediabetes, insulin resistance, and ß-cell function. A total of 175 individuals were included and stratified into three groups: controls, and relatives and spouses of type 2 diabetic patients. We compared clinical characteristics consisting of a homeostatic model assessment for insulin resistance (HOMA-IR) and beta cell function (HOMA-ß), a quantitative insulin sensitivity check index (QUICKI), and triglyceride glucose (TyG) index. After a multivariable linear regression analysis, the relative group was independently correlated with high fasting glucose, a high TyG index, and low ß-cell function; the relatives and spouses were independently associated with a low QUICKI. The relatives and spouses equally had a higher prevalence of prediabetes. These study also indicated that the relatives had multiple factors predicting the development of diabetes mellitus, and that the spouses may share a number of common environmental factors associated with low insulin sensitivity.

Investigating states of gas in water encapsulated between graphene layers.

Conventionally, only two states are assumed to exist in water: well-dispersed gas monomers and gas bubbles. Rarely is this paradigm explored experimentally. To close this gap, here we used transmission electron microscopy (TEM) to study degassed water, deionized water, and gas-supersaturated water encapsulated in graphene liquid cells. While neither degassed water nor deionized water yielded specific features, two major microscopic structures were evident in gas-supersaturated water: (1) polycrystalline nanoparticles formed of gas molecules and (2) a high density of tiny cells. Dark-field TEM imaging revealed that water molecules surrounding each cell form crystalline structures-a surprising discovery of a clathrate state in gas-supersaturated water that may help resolve several long-standing puzzles. Overall, this study suggests that water may form a matrix that actively interacts with gas molecules in complex and subtle ways.

Causes of in-hospital death in patients with type 2 diabetes with microvascular and macrovascular complications in Taiwan.

AIMS: Diabetes mellitus is a major cause of death worldwide, including Taiwan. The mortality data of the subsets of patients who suffered from microvascular or macrovascular complications is limited. The aim of this study was to investigate the causes of in-hospital death of patients with type 2 diabetes, especially the patients with microvascular, macrovascular and both micro-macrovascular complications. METHODS: A total of 12 159 patients with type 2 diabetes were identified from the Taiwan National Health Insurance Research Database (NHIRD) to analyse the causes of death. Type 2 diabetic subjects with microvascular, macrovascular and both micro-macrovascular complications were further classified and compared to patients without microvascular and macrovascular complications in the logistic regression analysis of the risk of death. RESULTS: Pneumonia increased risk of in-hospital death in patients with microvascular, macrovascular and both micro-macrovascular complications, with adjusted odds ratios (AORs) of 2.13 (95% confidence interval [CI] 1.09-4.18), 3.26 (1.71-6.24) and 3.96 (2.17-7.22), respectively. Septicaemia increased risk of in-hospital death in patients with macrovascular (AOR 2.57 [1.31-5.04]) and both micro-macrovascular complications (AOR 4.69 [2.58-8.50]). CONCLUSION: Pneumonia increased risk of in-hospital death among the type 2 diabetic patients with microvascular, macrovascular and both micro-macrovascular complications. Therefore, efforts aim at preventing pneumonia or decreasing its severity may increase survival.

Highly UV Resistant Inch-Scale Hybrid Perovskite Quantum Dot Papers.

Halide perovskite quantum dots (PQDs) are promising materials for diverse applications including displays, light-emitting diodes, and solar cells due to their intriguing properties such as tunable bandgap, high photoluminescence quantum yield, high absorbance, and narrow emission peaks. Despite the prosperous achievements over the past several years, PQDs face severe challenges in terms of stability under different circumstances. Currently, researchers have overcome part of the stability problem, making PQDs sustainable in water, oxygen, and polar solvents for long-term use. However, halide PQDs are easily degraded under continuous irradiation, which significantly limits their potential for conventional applications. In this study, an oleic acid/oleylamine (traditional surface ligands)-free method to fabricate perovskite quantum dot papers (PQDP) is developed by adding cellulose nanocrystals as long-chain binding ligands that stabilize the PQD structure. As a result, the relative photoluminescence intensity of PQDP remains over ≈90% under continuous ultraviolet (UV, 16 W) irradiation for 2 months, showing negligible photodegradation. This proposed method paves the way for the fabrication of ultrastable PQDs and the future development of related applications.

Association between Geriatric Nutrition Risk Index and Skeletal Muscle Mass Index with Bone Mineral Density in Post-Menopausal Women Who Have Undergone Total Thyroidectomy.

BACKGROUND: Osteoporosis is highly prevalent in postmenopausal women and may result in fractures and disabilities. Total thyroidectomy has also been associated with loss of bone mass. The aim of this cross-sectional study was to evaluate associations among nutritional status, skeletal muscle index and markers of bone turnover to bone mineral density in postmenopausal women who had undergone total thyroidectomy. METHODS: Fifty postmenopausal women who had undergone total thyroidectomy were included. Body composition was measured using dual-energy X-ray absorptiometry (DXA). The Geriatric Nutritional Risk Index (GNRI) was calculated using baseline body weight and serum albumin level. Skeletal muscle mass index was calculated as the appendicular skeletal muscle mass (ASM) divided by the height squared and assessed using DXA. RESULTS: Multivariate stepwise linear regression analysis showed that a low GNRI was significantly associated with low lumbar spine bone mineral density (BMD) and T-score, and that a low ASM/height2 was significantly associated with low femoral neck BMD and T-score. A low vitamin D level was significantly associated with low femoral neck BMD and T-score and low total hip BMD and T-score. A high bone alkaline phosphatase (ALP) level was significantly associated with low femoral neck T-score and low total hip BMD and T-score. A low insulin-like growth factor-1 (IGF-1) was significantly associated with low total hip BMD and T-score. CONCLUSION: In the postmenopausal women who had undergone total thyroidectomy in this study, BMD was positively associated with GNRI, skeletal muscle mass index, and levels of vitamin D and serum IGF-1, and inversely associated with bone ALP level. Nutritional status, skeletal muscle mass index and bone turnover biomarkers can be used to early identify patients with a high risk of osteoporosis in this high-risk group.

Associations between Triglyceride-Glucose Index and Micro- and Macro-angiopathies in Type 2 Diabetes Mellitus.

Keywords: triglyceride-glucose index; microangiopathy; macroangiopathy; type 2 diabetes mellitus.

Comparison of the Effects of Fasting Glucose, Hemoglobin A1c, and Triglyceride-Glucose Index on Cardiovascular Events in Type 2 Diabetes Mellitus.

The triglyceride-glucose (TyG) index has been correlated with insulin resistance. We aim to investigate the role of the TyG index on cardiovascular (CV) events in type 2 diabetes mellitus and compare the roles of fasting glucose, hemoglobin A1c, and the TyG index in predicting CV events. This retrospective study enrolled 3524 patients with type 2 diabetes from the Kaohsiung Medical University Research Database in 2009 in this longitudinal study and followed them until 2015. The TyG index was calculated as log (fasting triglyceride level (mg/dL) × fasting glucose level (mg/dL)/2). CV events included myocardial infarction, unstable angina, stroke, hospitalization for coronary artery disease, peripheral artery disease, and CV-related death. The association between variables and CV events was assessed using a multivariable stepwise Cox proportional hazard analysis. Two hundred and fifteen CV events (6.1%) were recorded during a follow-up period of 5.93 years. The multivariable stepwise analysis showed that high fasting glucose (HR, 1.007; p < 0.001) and a high TyG index (HR, 1.521; p = 0.004) but not hemoglobin A1c or triglycerides were associated with a higher rate of CV events. Adding fasting glucose and the TyG index to the basic model improved the predictive ability of progression to a CV event (p < 0.001 and p = 0.018, respectively), over that of hemoglobin A1c (p = 0.084) and triglyceride (p = 0.221). Fasting glucose and the TyG index are useful parameters and stronger predictive factors than hemoglobin A1c and triglyceride for CV events and may offer an additional prognostic benefit in patients with type 2 diabetes.

Liraglutide Inhibits Hepatitis C Virus Replication Through an AMP Activated Protein Kinase Dependent Mechanism.

Insulin resistance and diabetes are both associated with chronic hepatitis C virus (HCV) infection, and the glucagon-like peptide-1(GLP-1) receptor agonist, liraglutide, is a common therapy for diabetes. Our aim was to investigate whether liraglutide treatment can inhibit HCV replication. A cell culture-produced HCV infectious system was generated by transfection of in vitro-transcribed genomic JFH-1 ribonucleic acid (RNA) into Huh-7.5 cells. Total RNA samples were extracted to determine the efficiency of HCV replication. The Ava5 cells were treated with liraglutide and cell viability was calculated. A Western blot analysis of the protein expression was performed. The immunoreactive blot signals were also detected. Liraglutide activated GLP-1 receptors in the HCV infectious system, and inhibited subgenomic HCV RNA replication in the HuH-7.5 cells. The Western blot analysis revealed both HCV protein and replicon RNA were reduced after treatment with liraglutide in a dose-dependent manner. Liraglutide decreased the cell viability of HCV RNA at an optimum concentration of 120 µg/mL, activated the 5' adenosine monophosphate-activated protein kinase (AMPK) and the phosphorylated- transducer of regulated cyclic adenosine monophosphate (CAMP) response element-binding protein 2 (TORC2), thereby decreasing the cell viability of phosphoenolpyruvate carboxykinase (PEPCK) and G6pase RNA Therefore, we conclude that liraglutide can inhibit HCV replication via an AMPK/TORC2-dependent pathway.

The association between glycated albumin, glycohemoglobin, and glycated albumin to glycohemoglobin ratio in diabetic retinopathy of prediabetes.

Prediabetes increased risk of diabetes and diabetes-related macrovascular and microvascular complication. Glycohemoglobin (HbA1c ) is clinically used as the gold standard for glycemic control of diabetes. Glycated albumin (GA) is an early Amadori-type glycation protein between glucose and serum albumin, which changes in a shorter period of time than HbA1c and is superior to HbA1c in reflecting fluctuations in blood glucose. In this study, we aim to assess the predictive value of GA and glycohemoglobin (HbA1c) on a progression of diabetic retinopathy (DR) in prediabetic patients in Taiwan. This study was conducted at the outpatient department of a regional hospital in Southern Taiwan, and recruited 291 patients with prediabetes from January 2016 to February 2017. Blood and urine samples were obtained from all patients after fasting for 12 hours within 1 month of enrollment. The mean age is 62.5 ± 13.0 years and there are 161 males and 130 females. A total of 24.1% of patients have DR. The average value of GA and HbA1c are 14.6% ± 2.8% and 6.0% ± 0.4%, respectively. Old age, male, high systolic blood pressure, high HbA1C , and low total cholesterol are significantly associated with DR in patients with pre-DM. Therefore, in the prediabetic populations, high HbA1C, but not GA nor GA/HbA1C ratio, is significantly associated with DR.

GREATER LOW-DENSITY LIPOPROTEIN CHOLESTEROL VARIABILITY INCREASES THE RISK OF CARDIOVASCULAR EVENTS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS.

Objective: Variability in lipid levels has been associated with poor cardiovascular outcomes in patients with coronary artery disease. The aim of this study was to investigate whether low-density lipoprotein cholesterol (LDLC) variability can be used to predict cardiovascular events in patients with type 2 diabetes mellitus (DM). Methods: A total of 5,354 patients with type 2 DM were enrolled in this study. Cardiovascular events including peripheral arterial disease, coronary artery disease, stroke, and cardiovascular death were defined as the study endpoints, and standard deviations of lipid levels were used to define intra-individual lipid variability. Results: Univariate Cox proportional hazards analysis showed that LDL-C standard deviation (hazard ratio [HR] = 1.016; 95% confidence interval [CI] = 1.006 to 1.022; P<.001) was associated with a higher risk of cardiovascular events. Multivariate Cox proportional hazards analysis showed that an increase in LDL-C standard deviation significantly increased the risk of cardiovascular events (HR = 1.063; 95% CI = 1.025 to 1.102; P = .01). Kaplan-Meier analysis of cardiovascular event-free survival showed that the patients in tertiles 2 and 3 of the standard deviation of LDL-C had worse cardiovascular event-free survival compared to those in tertile 1. Conclusion: Variability in LDL-C could predict cardiovascular events in the patients with type 2 DM in this study. Abbreviations: CAD = coronary artery disease; CI = confidence interval; CVD = cardiovascular disease; DM = diabetes mellitus; eGFR = estimated glomerular filtration rate; HbA1c = glycosylated hemoglobin; HDL-C = high-density lipoprotein cholesterol; HR = hazard ratio; KMUHRD = Kaohsiung Medical University Hospital Research Database; LDL-C = low-density lipoprotein cholesterol; SD = standard deviation; UACR = urine albumin to creatinine ratio.

ASSOCIATIONS BETWEEN TRIGLYCERIDE/HIGH-DENSITY LIPOPROTEIN CHOLESTEROL RATIO AND MICRO- AND MACROANGIOPATHIES IN TYPE 2 DIABETES MELLITUS.

OBJECTIVE: The triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio has been reported to be a marker of insulin resistance. The aim of this study was to investigate associations between the TG/HDL-C ratio and micro- and macroangiopathies in patients with type 2 diabetes mellitus (DM). METHODS: A total of 1,981 (851 male and 1,130 female) patients with type 2 DM were enrolled from our outpatient clinic. These patients were stratified into 4 groups according to TG/HDL-C ratio quartiles. RESULTS: There were significant trends for stepwise increases in albuminuria ≥30 mg/g ( P<.001), coronary artery disease (CAD, P = .040), cerebrovascular disease (CVA, P = .002) and ankle-brachial index (ABI) <0.9 ( P = .001) corresponding to TG/HDL-C ratio quartiles, but not diabetic retinopathy ( P = .105). Furthermore, quartile 4 of the TG/HDL-C ratio was significantly associated with albuminuria, CAD, CVA, and ABI <0.9 after multivariate analysis compared to quartile 1. CONCLUSION: A high TG/HDL-C ratio was significantly associated with albuminuria, CAD, CVA, and peripheral artery occlusive disease (PAOD) in patients with DM, which translated into an increased risk of cardiovascular disease. ABBREVIATIONS: ABI = ankle-brachial index; ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin II receptor blocker; BMI = body mass index; CAD = coronary artery disease; CI = confidence interval; CVA = cerebrovascular disease; DM = diabetes mellitus, DR = diabetic retinopathy; eGFR = estimated glomerular filtration rate; HbA1c = glycated hemoglobin A1c; HDL-C = high-density lipoprotein cholesterol; OR = odds ratio; PAOD = peripheral artery occlusive disease; TGs = triglycerides.

Association Between Metabolic Syndrome and Microvascular and Macrovascular Disease in Type 2 Diabetic Mellitus.

BACKGROUND: The prevalence of metabolic syndrome (MetS) in patients with type 2 diabetes mellitus is high. The aim of this study was to investigate the association between MetS and micro- and macrovascular disease in patients with diabetes and the associated risk factors. METHODS: The study enrolled 1,986 (854 men and 1,132 women) patients with type 2 diabetes mellitus from outpatient clinics. MetS was defined according to the Adult Treatment Panel III for Asians. RESULTS: Of the enrolled patients, 1,363 had MetS and 623 did not. The patients with MetS had significantly higher rates of albuminuria (40.8% vs. 21.8%, P < 0.001), retinopathy (37.9% vs. 28.6%, P < 0.001), coronary artery disease (19.4% vs. 11.6%, P < 0.001), cerebrovascular disease (5.8% vs. 3.2%, P = 0.014), and an ankle-brachial index < 0.9 or ≥ 1.3 (6.1% vs. 3.0%, P = 0.015). Moreover, there were significant trends for stepwise increases in albuminuria, retinopathy, coronary artery disease, cerebrovascular disease and peripheral artery disease corresponding to the number of MetS components (all P for trend < 0.05). Risk factors including MetS, old age, sex, wide pulse pressure, increased hemoglobin A1c, dyslipidemia and decline renal function were associated with micro- and macrovascular disease. CONCLUSIONS: MetS and the number of its components were significantly associated with micro- and macrovascular disease in the study patients with diabetes and this resulted in a higher risk of cardiovascular disease. Screening programs to allow for early detection and interventions should be established to lower the risk of cardiovascular disease.

Effect of metformin on kidney function in patients with type 2 diabetes mellitus and moderate chronic kidney disease.

BACKGROUND: Impaired renal function can lead to the accumulation of metformin, and elevated concentrations of metformin have been associated with lactic acidosis. The aim of this study was to evaluate the effect of continuous metformin treatment in patients with type 2 diabetes mellitus (DM) and moderate chronic kidney disease (CKD) (estimated glomerular filtration rate (eGFR) 30-0 ml/min/1.73 m2) on renal function. METHODS: A total of the 616 patients were enrolled from the research database of Kaohsiung Medical University Hospital from January 1 to 2009 and December 31, 2013. The patients were divided into two groups: those who continued metformin treatment (continuation group; n = 484), and those who discontinued metformin treatment for at least 100 days (interruption group; n = 132). RESULTS: The slope of eGFR in the metformin interruption group was statistically lower than that in the metformin continuation group (0.75 ± 0.76 vs. -1.32 ± 0.24 mL/min/1.73 m2/year, p = 0.0007). After adjusting for baseline covariates in the multivariate linear regression analysis, the continuation of metformin (unstandardized coefficient ß, -2.072; 95% confidence interval, -3.268- -0.876) was a risk factor for the patients with DM and moderate CKD. CONCLUSIONS: Metformin may have an adverse effect on renal function in patients with type 2 DM and moderate CKD.

Abnormally Low or High Ankle-Brachial Index Is Associated With the Development of Diabetic Retinopathy in Type 2 Diabetes Mellitus.

Although some studies have reported an association between peripheral artery disease (PAD) and diabetic retinopathy (DR) in patients with diabetes, whether or not a causal relationship exists is unknown. The aim of this study was to investigate whether PAD, as indicated by an abnormally low or high ankle-brachial index (ABI), is associated with the development of DR in patients with type 2 diabetes mellitus (DM) without DR. We enrolled 414 (221 men and 193 women) patients with type 2 DM who underwent ABI measurements at our outpatient clinic. PAD was defined as an abnormally low (<0.9) or high (≥1.3) ABI in either leg, and DR was defined as being non-proliferative or proliferative. Of the enrolled patients, 69 (16.7%) had an ABI <0.9 or ≥1.3. The median follow-up period was 23 (15-40) months, during which 74 (17.9%) patients developed DR. In multivariate analysis, an ABI <0.9 or ≥1.3 was independently associated with the development of DR (vs. ABI ≥0.9 to <1.3; hazard ratio, 2.186; 95% confidence interval, 1.261 to 3.789; p = 0.005). An abnormal ABI was associated with the development of DR in our patients with type 2 DM without DR.

Greater HbA1c variability is associated with increased cardiovascular events in type 2 diabetes patients with preserved renal function, but not in moderate to advanced chronic kidney disease.

Emerging evidence suggests that glycemic variability may be a more reliable measure of glycemic control than mean HbA1c in type 2 diabetes mellitus. This study aimed to determine if HbA1c variability is associated with cardiovascular events in type 2 diabetic patients and if different renal functions affect such association. This longitudinal study enrolled 8259 diabetic patients from the Kaohsiung Medical University Research Database in 2009 and were followed-up until 2015. Intra-individual HbA1C variability was defined as the standard deviation (SD) of HbA1c and cardiovascular events were defined as hospitalization for coronary artery disease, unstable angina, myocardial infarction, stroke, peripheral artery disease, and cardiovascular death. The patients were grouped into two based on their estimated glomerular filtration rate (eGFR) ≥ 60 or < 60 min/ml/1.73m2. In a mean follow-up period of 6.3 years, cardiovascular events were recorded in 8.9% of the patients. In an adjusted Cox model, high HbA1c SD (hazard ratio, 1.290; 95% confidence interval, 1.008-1.650; p = 0.043), but not mean HbA1c, was associated with significantly increased risk of cardiovascular events in patients with eGFR ≥ 60 min/ml/1.73m2. This association was not seen in patients with eGFR < 60 min/ml/1.73m2. In this study, greater HbA1c variability is associated with increased risk of cardiovascular among patients with preserved renal function, but not in those with moderate to advanced chronic kidney disease.