Probucol in Albuminuric Type 2 Diabetes Mellitus Patients on Renin-Angiotensin System Blockade: A 16-Week, Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: To determine the effect of probucol on urine albumin excretion in type 2 diabetes mellitus patients with albuminuria using angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. APPROACH AND RESULTS: This was a 16-week, phase II, randomized, placebo-controlled, parallel-group study in type 2 diabetes mellitus patients with a urinary albumin/creatinine ratio of ≥300 mg/g using angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, conducted in 17 tertiary referral hospitals. Eligible patients were randomized to probucol 250 mg/d (n=44), probucol 500 mg/d (n=41), and placebo (n=41) groups in a ratio of 1:1:1 after block randomization procedures, keeping the treatment assignment blinded to the investigators, patients, and study assistants. The primary end point was change in the geometric mean of urinary albumin/creatinine ratio from baseline to week 16 (ClinicalTrials.gov identifier NCT01726816). The study was started on November 8, 2012, and completed on March 24, 2014. The least squares mean change±SE from baseline in urinary albumin/creatinine ratio at week 16 was -7.2±639.5 mg/g in the probucol 250 mg/d group (n=43; P=0.2077 versus placebo group), 9.3±587.4 mg/g in the probucol 500 mg/d group (n=40; P=0.1975 versus placebo group), and 259.0±969.1 mg/g in the placebo group (n=41). Although the majority of subjects were on statins, probucol treatment significantly lowered total cholesterol and low-density lipoprotein cholesterol levels. QT prolongation occurred in one and two subjects in control and probucol 250 mg/d groups, respectively. CONCLUSIONS: Four months of probucol up to 500 mg/d failed to reduce urinary albumin excretion.

Serum Chemerin Levels Are Associated with Abdominal Visceral Fat in Type 2 Diabetes.

Chemerin is a recently identified adipokine suggested to play a role in obesity and its metabolic complications. The relationship between visceral obesity and serum chemerin levels in type 2 diabetes (T2DM) is unknown and may differ from that of subjects without diabetes. Therefore, we evaluated whether serum chemerin was associated with visceral abdominal obesity in patients with T2DM. A total of 218 Korean patients with T2DM were enrolled and metabolic parameters, abdominal visceral and subcutaneous fat areas, and serum chemerin levels were measured. Serum chemerin level showed positive correlation with fasting insulin, HOMA-IR, serum triglyceride, serum creatinine, urine albumin/creatinine ratio, high-sensitivity C-reactive protein (hsCRP), fibrinogen, abdominal visceral fat area, visceral to subcutaneous fat area ratio, and negatively correlation with high density lipoprotein cholesterol and creatinine clearance (CCr) after adjusting for age, gender and body mass index. Multiple linear stepwise regression analysis showed that abdominal visceral fat area (ß = 0.001, P < 0.001), serum triglyceride (ß = 0.001, P < 0.001), CCr (ß = -0.003, P = 0.001), hsCRP (ß = 0.157, P = 0.001), fibrinogen (ß = 0.001, P < 0.001) and BMI (ß = 0.02, P = 0.008) independently affected log transformed serum chemerin levels. Higher serum chemerin level was associated with higher level of abdominal visceral fat area, serum triglyceride, hsCRP and fibrinogen and lower level of CCr in patients with T2DM. Serum chemerin may be used as a biomarker of visceral adiposity and chemerin may play a role in inflammation, decreased renal function, and increased cardiovascular risk in T2DM.

Antiangiogenic Activity of Acer tegmentosum Maxim Water Extract in Vitro and in Vivo.

Angiogenesis, the formation of new blood vessels, is critical for tumor growth and metastasis. Notably, tumors themselves can lead to angiogenesis by inducing vascular endothelial growth factor (VEGF), which is one of the most potent angiogenic factors. Inhibition of angiogenesis is currently perceived as one of the most promising strategies for the blockage of tumor growth. In this study, we investigated the effects of Acer tegmentosum maxim water extract (ATME) on angiogenesis and its underlying signal mechanism. We studied the antiangiogenic activity of ATME by using human umbilical vein endothelial cells (HUVECs). ATME strongly inhibited VEGF-induced endothelial cell proliferation, migration, invasion, and tube formation, as well as vessel sprouting in a rat aortic ring sprouting assay. Moreover, we found that the p44/42 mitogen activated protein (MAP) kinase signaling pathway is involved in the inhibition of angiogenesis by ATME. Moreover, when we performed the in vivo matrigel plug assay, VEGF-induced angiogenesis was potently reduced when compared to that for the control group. Taken together, these results suggest that ATME exhibits potent antiangiogenic activity in vivo and in vitro and that these effects are regulated by the extracellular regulated kinase (ERK) pathway.

Effect of lifestyle modification on serum chemerin concentration and its association with insulin sensitivity in overweight and obese adults with type 2 diabetes.

OBJECTIVE: Chemerin, a recently identified adipokine, has been linked to adiposity, insulin resistance, metabolic syndrome risk factors and inflammation. Here, we evaluated whether a 12-week lifestyle intervention in overweight and obese adults with type 2 diabetes could significantly affect the average blood glucose and serum chemerin levels over time. DESIGN: Thirty-five overweight or obese subjects with type 2 diabetes were randomized to receive intensive lifestyle modification including supervised exercise sessions or usual care for 12 weeks. Anthropometric and clinical data were collected before the intervention and after 12 weeks. RESULTS: Lifestyle intervention induced a significant decrease in HbA1c (-1·0 ± 0·5 vs 0·1 ± 0·6%, P < 0·001), BMI, total body fat content, serum lipocalin-2 and chemerin levels (-8·1 ± 21·6 vs + 8·2 ± 15·9 ng/ml, P = 0·021) and a significant increase in VO2 max after 12 weeks compared to the usual care group. Baseline chemerin levels were positively correlated with the homoeostasis model of assessment of insulin resistance (HOMA-IR), fasting insulin and the high-sensitivity C-reactive protein (hsCRP) and negatively correlated with insulin sensitivity index (ISI). Changes in the chemerin concentration during 12 weeks were independently negatively correlated with changes in ISI and positively correlated with changes in fasting plasma glucose, total cholesterol and lipocalin-2 levels. CONCLUSIONS: A 12-week intensive lifestyle intervention significantly decreased serum chemerin level compared to usual care. Decrease in serum chemerin level was associated with improved insulin sensitivity, and this may be involved in the beneficial effects of lifestyle intervention in overweight and obese type 2 diabetic patients.

Measurement of diabetes-related emotional distress using the Problem Areas in Diabetes scale: psychometric evaluations show that the short form is better than the full form.

BACKGROUND: The Problem Areas in Diabetes (PAID) scale is widely used for measuring diabetes-related emotional distress. There has been debate over the last 2 decades about the underlying factorial-construct validity of the PAID, with one- to four-factor structures being reported. A short form of the PAID, which comprises five items (PAID-5), was recently developed using Western patients with type 2 diabetes. This study measured the psychometric properties of the full and short forms of the PAID in Korean patients with type 2 diabetes, with the aim of determining which form is preferable. METHODS: The PAID and PAID-5 were translated into Korean (K-PAID and K-PAID-5, respectively) using a forward-and-backward translation technique. The study participants were recruited from university hospitals. The factorial-construct, convergent, and known-groups validity, and internal-consistency and test-retest reliability of both the K-PAID and K-PAID-5 were evaluated. RESULTS: For the K-PAID, confirmatory factor analysis revealed a marginal fit to the one-, two-, three-, and four-factor models. The three- and four-factor models of the K-PAID partially satisfied the internal-consistency and test-retest reliability, and convergent and known-groups validity. For the K-PAID-5, confirmatory factor analysis demonstrated an excellent fit to the one-factor model, with a Cronbach's alpha of 0.87 and an intraclass correlation coefficient of 0.89. The K-PAID-5 satisfied the convergent validity, as evaluated using the Center for Epidemiologic Studies Depression Scale and hemoglobin A1c. Known-groups validity by gender was also satisfied. CONCLUSIONS: The K-PAID-5 demonstrated excellent psychometric properties as a one-factor scale. The brevity of the K-PAID-5 represents a major advantage in a practical context in that it may impose a minimum burden upon patients with diabetes.

Measurement equivalence of touch-screen computerized and paper-based diabetes-specific quality-of-life questionnaires.

Current advances in technology have enabled the development of a computer-based questionnaire that provides advantages over the paper-based mode of administration, such as automatic data entry, storage and calculations. However, before implementing a computer-based questionnaire, its equivalence with the original paper-based questionnaire must first be demonstrated. The purpose of this study was to evaluate the measurement equivalence of the computerized Diabetes-Specific Quality-of-Life questionnaire (cD-QOL) with its original paper-based counterpart. A two-period crossover design was used in this study. The measurement equivalence was evaluated using quadratic weighted kappa coefficients, intraclass correlations and Cronbach's alpha comparisons. The cD-QOL was equivalent to its original paper-based counterpart. Participants preferred the cD-QOL over the paper-based questionnaire and reported that it was easy to use.

Combined genome-wide linkage and association analyses of fasting glucose level in healthy twins and families of Korea.

This study was undertaken to identify genetic polymorphisms that are associated with the risk of an elevated fasting glucose (FG) level using genome-wide analyses. We explored a quantitative trait locus (QTL) for FG level in a genome-wide study from a Korean twin-family cohort (the Healthy Twin Study) using a combined linkage and family-based association analysis approach. We investigated 1,754 individuals, which included 432 families and 219 pairs of monozygotic twins. Regions of chromosomes 2q23.3-2q31.1, 15q26.1-15q26.3, 16p12.1, and 20p13-20p12.2, were found to show evidence of linkage with FG level, and several markers in these regions were found to be significantly associated with FG level using family-based or general association tests. In particular, a single-nucleotide polymorphism (rs6138953) on the PTPRA gene in the 20p13 region (combined P = 1.8 × 10(-6)) was found to be associated with FG level, and the PRKCB1 gene (in 16p12.1) to be possibly associated with FG level. In conclusion, multiple regions of chromosomes 2q23.3-2q31.1, 15q26.1-15q26.3, 16p12.1, and 20p13-20p12.2 are associated with FG level in our Korean twin-family cohort. The combined approach of genome-wide linkage and family-based association analysis is useful to identify novel or known genetic regions concerning FG level in a family cohort study.

Direct medical costs for patients with type 2 diabetes and related complications: a prospective cohort study based on the Korean National Diabetes Program.

We analyzed the direct medical costs for Korean patients with type 2 diabetes according to the type of complications and the number of microvascular complications. We analyzed costs for type 2 diabetes and associated complications in 3,125 patients. These data were obtained from the Korean National Diabetes Program (KNDP), a large, ongoing, prospective cohort study that began in 2005. The cost data were prospectively collected, using an electronic database, for the KNDP cohort at six hospitals. The costs were analyzed according to complications for 1 yr from enrollment in the study. Among 3,125 patients, 918 patients had no vascular complications; 1,883 had microvascular complications only; 51 had macrovascular complications only; and 273 had both complications. The annual direct medical costs for a patient with only macrovascular, only microvascular, or both macrovascular and microvascular complications were 2.7, 1.5, and 2.0 times higher than the medical costs of patients without complications. Annual direct medical costs per patient increased with the number of microvascular complications in patients without macrovascular complications. The economic costs for type 2 diabetes are attributable largely to the management of microvascular and macrovascular complications. Proper management of diabetes and prevention of related complications are important for reducing medical costs.

Association between nutrient intake and obesity in type 2 diabetic patients from the Korean National Diabetes Program: a cross-sectional study.

The aim of the study was to assess the association between usual dietary nutrient intake and obesity in Korean type 2 diabetic patients. We examined 2,832 type 2 diabetic patients from the Korean National Diabetes Program cohort who completed dietary assessment and clinical evaluation in this cross-sectional study. In men, higher dietary fiber intake was associated with a lower odds of being obese (P(trend) = 0.003) and in women, higher protein intake was associated with a lower odds of being obese (P(trend) = 0.03) after adjustment for age, diabetes duration, HbA1c, alcohol drinking, income, education level, and calorie intake. In men, higher fiber intake was associated with lower odds of obesity after further adjustment for diastolic blood pressure, physical activity, and possible confounding nutritional intake and medication. The multivariable adjusted odds ratio for the highest quintile of fiber intake was 0.37 (P(trend) < 0.001). In women, protein intake was not associated with obesity after further adjustment. In conclusion, higher intake of dietary fiber is associated with lower odds of being obese in type 2 diabetic men, suggesting a role for dietary fiber in the management and prevention of obesity in type 2 diabetes (ClinicalTrials.gov: NCT 01212198).

Serum Levels of Adipocyte Fatty Acid-Binding Protein Are Associated with Rapid Renal Function Decline in Patients with Type 2 Diabetes Mellitus and Preserved Renal Function.

BACKGROUND: Recent studies have demonstrated that the levels of adipocyte fatty acid-binding protein (A-FABP) are closely associated with diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). This study aimed to examine the association between serum A-FABP level and rapid renal function decline in patients with T2DM and preserved renal function. METHODS: This was a prospective observational study of 452 patients with T2DM and preserved renal function who had serial measurements of estimated glomerular filtration rate (eGFR). Rapid renal function decline was defined as an eGFR decline of >4% per year. The association between baseline serum A-FABP level and rapid renal function decline was investigated. RESULTS: Over a median follow-up of 7 years, 82 participants (18.1%) experienced rapid renal function decline. Median A-FABP levels were significantly higher in patients with rapid renal function decline, compared to non-decliners (20.2 ng/mL vs. 17.2 ng/mL, P=0.005). A higher baseline level of A-FABP was associated with a greater risk of developing rapid renal function decline, independent of age, sex, duration of diabetes, body mass index, systolic blood pressure, history of cardiovascular disease, baseline eGFR, urine albumin creatinine ratio, total cholesterol, glycosylated hemoglobin, high-sensitivity C-reactive protein and use of thiazolidinedione, insulin, angiotensin-converting-enzyme inhibitors and angiotensin II-receptor blockers and statin (odds ratio, 3.10; 95% confidence interval, 1.53 to 6.29; P=0.002). CONCLUSION: A high level of serum A-FABP is associated with an increased risk of rapid renal function decline in patients with T2DM and preserved renal function. This suggests that A-FABP could play a role in the progression of DKD in the early stages.

The C609T variant of NQO1 is associated with carotid artery plaques in patients with type 2 diabetes.

OBJECTIVE: Atherosclerosis in patients with type 2 diabetes has been linked to oxidative stress. NADP[1]:quinone oxidoreductase 1 (NQO1) plays a key role in cellular antioxidant defense. Recent reports suggest that highly expressed and inducible endogenous NQO1 from cardiovascular cells may act as a potential superoxide scavenger. We examined the relationship between the risk of NQO1 C609T polymorphism and carotid artery atherosclerosis in patients with type 2 diabetes. METHODS: We recruited 601 (Seoul set) and 233 (Koyang set) unrelated patients with type 2 diabetes from independent groups. The C609T variant of NQO1 was genotyped by Taqman RT-PCR. Mean and maximum carotid intima-media thickness (IMT) and carotid artery plaques were measured by high-resolution ultrasonography. RESULTS: Patients with the T allele exhibited a higher prevalence of atherosclerotic plaques than non-T allele carriers in both sets (Seoul set vs. Koyang set, p=0.021, p=0.023, respectively). After adjusting for age, sex, duration of diabetes, systolic blood pressure, body mass index, current smoking, HDL-cholesterol, LDL-cholesterol and HbA1c, subjects with the T allele had a significantly higher risk of carotid artery plaques (Seoul set vs. Koyang set, OR=1.65, p=0.015; OR=2.00, p=0.037, respectively) than subjects with the CC genotype. CONCLUSION: These results suggest that the C609T polymorphism of NQO1 is associated with carotid artery plaques in type 2 diabetic patients.

Functional and morphologic characterizations of the diabetic mouse corpus cavernosum: comparison of a multiple low-dose and a single high-dose streptozotocin protocols.

INTRODUCTION: With the advent of genetically modified mice, it seems particularly advantageous to develop a mouse model of diabetic erectile dysfunction. AIM: To establish a mouse model of type I diabetes by implementation of either multiple low-dose streptozotocin (STZ) protocol or single high-dose STZ protocol and to evaluate morphologic alterations in the cavernous tissue and subsequent derangements in penile hemodynamics in vivo. METHODS: Eight-week-old C57BL/6J mice were divided into three groups: a control group, a group administered the multiple low-dose STZ protocol (50 mg/kg x 5 days), and a group administered the single high-dose STZ protocol (200 mg/kg). MAIN OUTCOME MEASURES: After 8 weeks, erectile function was measured by electrical stimulation of the cavernous nerve. The penis was then harvested and stained with hydroethidine (in situ analysis of superoxide anion), TUNEL, or antibodies to nitrotyrosine (marker of peroxynitrite formation), PECAM-1, smooth muscle alpha-actin, and phospho-eNOS. Penis specimens from a separate group of animals were used for phospho-eNOS and eNOS western blot or cGMP determination. RESULTS: Erectile function was significantly less in diabetic groups than in control group. The generation of superoxide anion and nitrotyrosine and the number of apoptotic cells in both cavernous endothelial and smooth muscle cells were significantly higher in diabetic groups than in control group. Cavernous tissue phospho-eNOS and cGMP expression and the number of endothelial and smooth muscle cells were lower in diabetic groups than in control group. Both diabetic models resulted in similar structural and functional derangements in the corpus cavernosum; however, the mortality rate was higher in mice receiving single high-dose of STZ than in those receiving multiple low-doses. CONCLUSION: The mouse model of type I diabetes is useful and technically feasible for the study of the pathophysiologic mechanisms involved in diabetic erectile dysfunction.

Development and validation of a highly sensitive LC-MS/MS method for in vitro measurement of histamine concentration.

The basophil histamine release test (HRT) is an important in vitro diagnostic assay to evaluate immunoglobin E (IgE)-mediated allergic responses. In this study, a bioanalytical LC-MS/MS method was developed and validated to quantify histamine in the leukocyte suspension from human peripheral blood. The method used pre-column derivatization with phenylisothiocyanate (PITC) and the resulting phenylthiocarbamyl (PTC) histamine was analyzed by positive-ion electrospray ionization using the multiple reaction monitoring mode. Chromatographic separation was achieved using an Imtakt-HT C18 column (2.1 mm × 50 mm, 3.0 µm), with a flow rate of 0.35 mL/min, 2 µL injection, and gradient elution with a mixture of acetonitrile-2 mM ammonium acetate buffer (both containing 0.1% formic acid). The total runtime of the method was 3.0 min including equilibration time. The method had a lower limit of detection of 0.1 ng/mL, and the quantifiable range was 0.1-100 ng/mL in the leukocyte suspension. The intra-day and inter-day precision and accuracy results were within the acceptable limits. It was established that histamine quantification should be performed within 2 h of preparing the leukocyte suspension, and freezing and thawing should be avoided. This method was successfully applied to the diagnosis and evaluation of the pathophysiologic mechanism of respiratory or cutaneous allergic diseases.

A Randomized, Double-Blind Trial Comparing the Pharmacokinetics of CT-P16, a Candidate Bevacizumab Biosimilar, with its Reference Product in Healthy Adult Males.

BACKGROUND: CT-P16 is a candidate biosimilar of bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor that is used in the treatment of a range of advanced solid cancers. OBJECTIVE: The objective of this study was to demonstrate the pharmacokinetic equivalence of CT-P16 and European Union (EU)-approved bevacizumab (EU-bevacizumab) and US-licensed bevacizumab (US-bevacizumab) reference products. METHODS: In this double-blind, parallel-group phase I trial (ClinicalTrials.gov identifier NCT03247673), healthy adult males were randomized (1:1:1) to receive a single dose of CT-P16 5 mg/kg, EU-bevacizumab 5 mg/kg, or US-bevacizumab 5 mg/kg. Primary study endpoints were area under the concentration-time curve (AUC) from time zero to infinity (AUC∞), AUC from time zero to the last quantifiable concentration (AUClast), and maximum serum concentration (Cmax). Pharmacokinetic equivalence was shown if the 90% confidence intervals (CIs) of the geometric mean (GM) ratios of the AUC∞, AUClast, and Cmax were within the predefined bioequivalence margin of 80-125%. Safety and immunogenicity were also evaluated. RESULTS: A total of 144 subjects were randomized: 47 to CT-P16, 49 to EU-bevacizumab, and 48 to US-bevacizumab. The 90% CIs for the GM ratios of AUC∞, AUClast, and Cmax for CT-P16/EU-bevacizumab, CT-P16/US-bevacizumab, and EU-bevacizumab/US-bevacizumab comparisons were all within the bioequivalence margin. Mean serum concentration-time profiles, secondary pharmacokinetic parameters, and safety and immunogenicity profiles were comparable across all three treatment groups. CONCLUSION: CT-P16 demonstrated pharmacokinetic equivalence to EU-bevacizumab and US-bevacizumab. Safety and immunogenicity profiles were similar for CT-P16, EU-bevacizumab, and US-bevacizumab. These data support the further clinical evaluation of CT-P16 as a bevacizumab biosimilar. CLINICAL TRIALS REGISTRATION: NCT03247673.

Presence of Carotid Plaque Is Associated with Rapid Renal Function Decline in Patients with Type 2 Diabetes Mellitus and Normal Renal Function.

BACKGROUND: Recent evidences indicate that early rapid renal function decline is closely associated with the development and progression of diabetic kidney disease. We have investigated the association between carotid atherosclerosis and rapid renal function decline in patients with type 2 diabetes mellitus and preserved renal function. METHODS: In a prospective, multicenter cohort, a total of 967 patients with type 2 diabetes mellitus and preserved renal function were followed for 6 years with serial estimated glomerular filtration rate (eGFR) measurements. Common carotid intima-media thickness (CIMT) and presence of carotid plaque were assessed at baseline. Rapid renal function decline was defined as an eGFR decline >3.3% per year. RESULTS: Over a median follow-up of 6 years, 158 participants (16.3%) developed rapid renal function decline. While there was no difference in CIMT, the presence of carotid plaque in rapid decliners was significantly higher than in non-decliners (23.2% vs. 12.2%, P<0.001). In multivariable logistic regression analysis, presence of carotid plaque was an independent predictor of rapid renal function decline (odds ratio, 2.33; 95% confidence interval, 1.48 to 3.68; P<0.0001) after adjustment for established risk factors. The model including the carotid plaque had better performance for discrimination of rapid renal function decline than the model without carotid plaque (area under the receiver operating characteristic curve 0.772 vs. 0.744, P=0.016). CONCLUSION: Close monitoring of renal function and early intensive management may be beneficial in patients with type 2 diabetes mellitus and carotid plaques.

The effect of lowering the threshold for diagnosis of impaired fasting glucose.

PURPOSE: The aim of this study was to evaluate the effect of lowering the fasting plasma glucose (FPG) criteria for impaired fasting glucose (IFG) on the prevalence of IFG and the risk for the development of diabetes associated with IFG in Koreans. MATERIALS AND METHODS: A total of 7,211 subjects who had normal glucose tolerance (NGT) or IFG were recruited. Subjects were evaluated at baseline and after two years follow up. Clinical data including total cholesterol, FPG and blood pressure were examined. RESULTS: Lowering the criteria for IFG from 6.1 mmol/L (110 mg/dL) to 5.6 mmol/L (100 mg/dL) increased the prevalence of IFG from 6.6% (494 subjects) to 24.4% (1829 subjects). After the 2 years follow up period, 91 subjects (1.3%) developed diabetes. Twenty one (0.3%) subjects developed diabetes among 5,382 NGT subjects and 70 (3.8%) subjects developed diabetes among 1,829 IFG (5.6-7.0 mmol/L) subjects. Lowering the IFG threshold from 6.1 mmol/L to 5.6 mmol/L resulted in a 18.4% decrease in specificity and 23.9% increase in sensitivity for predicting diabetes. The baseline FPG for predicting the development of diabetes after 2 years at a point on the receiver operating characteristic curve that was closest to the ideal 100% sensitivity and 100% specificity was 5.7 mmol/L (103 mg/dL). CONCLUSION: Lowering the FPG criterion of IFG should have benefits in predicting new onset type 2 diabetes mellitus in Koreans. The economic and health benefits of applying the new IFG criteria should be evaluated in future studies.

A new comprehensive diabetes health literacy scale: Development and psychometric evaluation.

BACKGROUND: The prevalence of diabetes is close to reaching an epidemic level, and health literacy has recently emerged as a concept that can influence the health outcomes of patients with diabetes. Health literacy was once defined from the perspective of basic reading and understanding skills, but this has now become more comprehensive to include the abilities and skills to assess, understand, appraise, communicate, and use health information. Nevertheless, there is no instrument reflecting the comprehensive health literacy relevant to diabetes. OBJECTIVES: The aims of this study were to develop a comprehensive Diabetes Health Literacy Scale and to evaluate its psychometric properties. DESIGN: An instrument-development study was applied that comprised three steps: conceptualization, item generation and content validity, and field testing of the psychometric properties. SETTINGS: A convenience sample of 462 participants was recruited from December 2016 to September of 2017 at outpatient clinics in 2 Korean university hospitals. PARTICIPANTS: The inclusion criteria for participants were being aged at least 19 years, articulate in the Korean language, and diagnosed with diabetes, while the presence of gestational diabetes was applied as an exclusion criterion. Approximately half of the participants were female (51.1%). The participants were aged 54.5 (SD, 11.0) years, 67.1% of them were taking an oral hypoglycemic agent, and 21.9% of them had well-controlled blood-glucose levels. METHODS: The content validity, factorial structure validity, convergent validity, criterion validity, internal consistent reliability, and test-retest reliability of the Diabetes Health Literacy Scale were evaluated. Data were analyzed using exploratory and confirmatory factor analyses, Pearson's correlation, Cronbach's alpha, and the intraclass correlation coefficient. RESULTS: The content validity was assessed by five experts. Exploratory and confirmatory factor analyses yielded a three-factor solution. Convergent validity was demonstrated using measures of diabetes knowledge and self-efficacy. Criterion validity was demonstrated with generic health-literacy questions. Internal consistency reliability and test-retest reliability were found to be acceptable, as indicated by a Cronbach's alpha of 0.91 and an intraclass correlation coefficient of 0.89, respectively. CONCLUSIONS: The Diabetes Health Literacy Scale is a new instrument that measures comprehensive aspects of informational, numeracy, and communicative health literacy. It is a short instrument, comprising only 14 items scored on a 5-point Likert scale. The instrument exhibits good psychometric properties for four validity metrics (content, structural, convergent, and criterion validity) and two reliability metrics (internal consistency and test-retest reliability). These findings indicate that the instrument can be applied in both research and clinical practice.

Metformin reduces the risk of cancer in patients with type 2 diabetes: An analysis based on the Korean National Diabetes Program Cohort.

The epidemiological literature suggests that insulin resistance, hyperinsulinemia, and increased levels of insulin-like growth factors place patients with type 2 diabetes mellitus (T2DM) at greater risk of cancer. The association between cancer incidence and the use of antidiabetic medications in patients with T2DM has been recently examined. There have been conflicting reports regarding an association between metformin and cancer risk. The aim of this study was to investigate the relationship between metformin use and the incidence of cancer in Koreans with T2DM.Data from The Korean National Diabetes Program (KNDP, 2006-2014), a nationwide, large-scale, prospective, multicenter cohort study in Korea, were used to study patients with T2DM. Patients ≥30 years old whose complete medical records were available were included in this study. Patients with a history of any cancer on KNDP registration or those who had been diagnosed with any type of cancer within 1 year of metformin use were excluded. Survival curves with respect to the incidence of cancer were plotted using the Kaplan-Meier method. Hazard ratios and 95% confidence intervals for cancer were estimated in a Cox proportional hazards regression analysis.During a mean 5.8 years of follow-up, 164 of the 1918 study patients (335 metformin nonusers and 1583 metformin users) developed cancer. The incidence per 1000 person-years was 21.8 in metformin nonusers and 13.2 in metformin users. Metformin users had a reduced risk of cancer, even after adjustment for demographic characteristics, metabolic parameters, diabetic complications, and other antidiabetic medications (hazard ratio 0.513, 95% confidence interval 0.318-0.826, P = .0060). Subgroup analysis of metformin users showed a reduced risk of cancer in males, patients < 65 years of age, patients with a T2DM duration < 5 years, nonobese patients, nonsmokers, and good glycemic control group.This large-scale, prospective, multicenter cohort study demonstrated an association between metformin use and reduced cancer risk in patients with T2DM.

Failure of monotherapy in clinical practice in patients with type 2 diabetes: The Korean National Diabetes Program.

AIMS/INTRODUCTION: We investigated the failure of monotherapy in patients with type 2 diabetes mellitus in real practice settings. MATERIALS AND METHODS: The Korean National Diabetes Program was a prospective, multicenter observational cohort study of type 2 diabetes mellitus patients in Korea. Of the 3,950 patients enrolled in the study, we studied 998 who were continuously maintained on monotherapy for at least 90 days at six participating centers. To balance the baseline characteristics of patients in each group, we used propensity matching at a 1:1 ratio (metformin vs sulfonylureas) and 4:1 ratio (metformin vs meglitinides and metformin vs alpha-glucosidase inhibitors [aGIs]). The hazard ratios (HRs) of treatments (compared with metformin) were determined by Cox's proportional hazards regression modeling. RESULTS: The median follow-up time was 56 months, and monotherapy failed in 45% of all patients. The annual incidences of failure were 15.6%, 21.3%, 27% and 9.6% in the metformin, sulfonylurea, meglitinide and aGI groups. Compared with metformin, sulfonylureas and meglitinides were associated with higher risks of monotherapy failure (HR 1.39, 95% confidence interval [CI] 1.08-1.80; HR 1.92, 95% CI 1.13-3.27), and aGIs with risks similar to that of metformin (HR 0.80, 95% CI 0.44-1.45). When analyzed by failure type, sulfonylureas, meglitinides and aGIs were associated with a higher risk of a switch to other agents (HR 4.43, 95% CI 2.14-9.17; HR 18.80, 95% CI 6.21-56.93; HR 4.25, 95% CI 1.49-12.13), and aGIs with a lower risk of prescription of add-on second agents (HR 0.16, 95% CI 0.04-0.64). CONCLUSIONS: Metformin was associated with a lower failure risk than were sulfonylureas and meglitinides, but a comparable aGI failure rate.

Beneficial Effects of Aerobic Exercise Training Combined with Rosiglitazone on Glucose Metabolism in Otsuka Long Evans Tokushima Fatty Rats.

BACKGROUND: Regular aerobic exercise is essential for the prevention and management of type 2 diabetes mellitus and may be particularly beneficial for those treated with thiazolidinediones, since it may prevent associated weight gain. This study aimed to evaluate the effect of combined exercise and rosiglitazone treatment on body composition and glucose metabolism in obese diabetes-prone animals. METHODS: We analyzed metabolic parameters, body composition, and islet profiles in Otsuka Long Evans Tokushima Fatty rats after 28 weeks of aerobic exercise, rosiglitazone treatment, and combined exercise and rosiglitazone treatment. RESULTS: Combined exercise with rosiglitazone showed significantly less increase in weight and epididymal fat compared to rosiglitazone treatment. Aerobic exercise alone and combined rosiglitazone and exercise treatment led to similar retention of lean body mass. All experimental groups showed a decrease in fasting glucose. However, the combined exercise and rosiglitazone therapy group showed prominent improvement in glucose tolerance compared to the other groups. Rescue of islet destruction was observed in all experimental groups, but was most prominent in the combined therapy group. CONCLUSION: Regular aerobic exercise combined with rosiglitazone treatment can compensate for the adverse effect of rosiglitazone treatment and has benefit for islet preservation.