Gender-associated cardiometabolic risk profiles and health behaviors in patients with type 2 diabetes: a cross-sectional analysis of the Joint Asia Diabetes Evaluation (JADE) program.

Background: In Asia, diabetes-associated death due to cardiorenal diseases were 2-3 times higher in women than men which might be due to gender disparity in quality of care and health habits. Methods: Adults with type 2 diabetes (T2D) from 11 Asian countries/areas were assessed using the same protocol (2007-2015). We compared treatment target attainment (HbA1c < 7%, blood pressure [BP] < 130/80 mmHg, risk-based LDL-cholesterol, lack of central obesity [waist circumference <90 cm in men or <80 cm in women), use of cardiorenal-protective drugs (renin-angiotensin system [RAS] inhibitors, statins), and self-reported health habits including self-monitoring blood glucose (SMBG) by gender. Analyses were stratified by countries/areas, age of natural menopause (<50 vs. ≥50 years), and comorbidities (atherosclerotic cardiovascular disease [ASCVD], heart failure, kidney impairment [eGFR < 60 mL/min/1.73 m2]). Findings: Among 106,376 patients (53.2% men; median (interquartile range) diabetes duration: 6.0 (2.0-12.0) years; mean ± SD HbA1c 8.0 ± 1.9%; 27% insulin-treated), women were older and less likely to receive college education than men (28.9% vs. 48.8%). Women were less likely to smoke/drink alcohol and were physically less active than men. Women had lower BP (<130/80 mmHg: 29.4% vs. 25.7%), less general obesity (54.8% vs. 57.8%) but more central obesity than men (77.5% vs. 57.3%). Women were less likely to have ASCVD (12.8% vs. 17.0%) or heart failure (1.3% vs. 2.3%), but more likely to have kidney impairment (22.3% vs. 17.6%) and any-site cancer than men (2.5% vs. 1.6%). In most countries/areas, more men attained HbA1c <7% and risk-based LDL-cholesterol level than women. After adjusting for potential confounders including countries and centres, men had 1.63 odds ratio (95% CI 1.51, 1.74) of attaining ≥3 treatment targets than women. Interpretation: Asian women with T2D had worse quality of care than men especially in middle-income countries/areas, calling for targeted implementation programs to close these care gaps. Sponsor: Asia Diabetes Foundation. Funding: Nil.

Combined associations of family history and self-management with age at diagnosis and cardiometabolic risk in 86,931 patients with type 2 diabetes: Joint Asia Diabetes Evaluation (JADE) Register from 11 countries.

BACKGROUND: Family history (FamH) of type 2 diabetes might indicate shared genotypes, environments, and/or behaviors. We hypothesize that FamH interacts with unhealthy behaviors to increase the risk of early onset of diabetes and poor cardiometabolic control. METHODS: In a cross-sectional analysis of the prospective Joint Asia Diabetes Evaluation Register including patients from 427 clinics in 11 Asian countries/regions in 2007-2021, we defined positive FamH as affected parents/siblings and self-management as (1) healthy lifestyles (balanced diet, non-use of alcohol and tobacco, regular physical activity) and (2) regular self-monitoring of blood glucose (SMBG). RESULTS: Among 86,931 patients with type 2 diabetes (mean±SD age: 56.6±11.6 years; age at diagnosis of diabetes: 49.8±10.5 years), the prevalence of FamH ranged from 39.1% to 85.3% in different areas with FamH affecting mother being most common (32.5%). The FamH group (n=51,705; 59.5%) was diagnosed 4.6 years earlier than the non-FamH group [mean (95% CI): 47.9 (47.8-48.0) vs. 52.5 (52.4-52.6), logrank p<0.001]. In the FamH group, patients with both parents affected had the earliest age at diagnosis [44.6 (44.5-44.8)], followed by affected single parent [47.7 (47.6-47.8)] and affected siblings only [51.5 (51.3-51.7), logrank p<0.001]. The FamH plus ≥2 healthy lifestyle group had similar age at diagnosis [48.2 (48.1-48.3)] as the non-FamH plus <2 healthy lifestyle group [50.1 (49.8-50.5)]. The FamH group with affected parents had higher odds of hyperglycemia, hypertension, and dyslipidemia than the FamH group with affected siblings, with the lowest odds in the non-FamH group. Self-management (healthy lifestyles plus SMBG) was associated with higher odds of attaining HbA1c<7%, blood pressure<130/80mmHg, and LDL-C<2.6 mmol/L especially in the FamH group (FamH×self-management, pinteraction=0.050-0.001). CONCLUSIONS: In Asia, FamH was common and associated with young age of diagnosis which might be delayed by healthy lifestyle while self management  was associated with better control of  cardiometabolic risk factors especially in those with FamH.

Analysis and comparison of the cost-effectiveness of statins according to the baseline low-density lipoprotein cholesterol level in Korea.

WHAT IS KNOWN AND OBJECTIVE: There are a few Korean studies on the economics of statins based on reduction in low-density lipoprotein cholesterol (LDL-C) data from other countries. This study aimed to analyse and compare the cost-effectiveness of statins according to the baseline LDL-C level in Korea. METHODS: Between January 2009 and December 2015, the data of patients who were prescribed statins for the first time were extracted from electronic medical records. We performed a cost-effectiveness analysis (CEA) based on the LDL-C reduction rate (CEA-RR) and target achievement rate. RESULTS AND DISCUSSION: Among high-intensity statins, the CEA-RR value of rosuvastatin (20 mg) was significantly lower than that of atorvastatin (40 mg) at all baseline LDL-C levels, except levels of 160-189 mg/dL. Additionally, at baseline LDL-C levels of 130-159 mg/dL, the CEA-RR value of rosuvastatin (20 mg) was three times lower than that of atorvastatin (40 mg) (9·1 ± 2·5 $/% vs. 31·7 ± 15·0 $/%, P < 0·001). Among moderate-to-low-intensity statins, rosuvastatin (5 mg) showed the lowest CEA-RR value (4·0 ± 0·6 $/%), and the value significantly increased for pitavastatin (2 mg) (8·0 ± 0·6 $/%), atorvastatin (10 mg) (9·5 ± 0·5 $/%), simvastatin (10·8 ± 1·1 $/%) and pravastatin (40 mg) (11·5 ± 0·9 $/%) in order (P < 0·0001). On changing from atorvastatin (10 mg) to atorvastatin (20 mg), the additional yearly cost was 16·0 and additional CEA-RR value was 2·74 $/%. On the other hand, on changing from atorvastatin (10 mg) to rosuvastatin (10 mg), the additional yearly cost was -16·3 and additional CEA-RR value was -1·8 $/%. WHAT IS NEW AND CONCLUSION: We successfully compared the cost-effectiveness of statins according to the baseline LDL-C level in Korea. It is expected that our findings will help clinical decision-making with regard to statin prescription, and this will help reduce national medical expenditure.

Effect of an obesity prevention program focused on motivating environments in childhood: a school-based prospective study.

BACKGROUND/OBJECTIVES: There has been an increasing global recognition of the need for effective strategies to prevent and control childhood obesity. In this study, we aimed to identify the effectiveness of an obesity prevention program focused on motivating environments in school. SUBJECTS/METHODS: In this school-based, prospective, quasi-experimental study, we enrolled three elementary (fourth graders) and two middle (seventh graders) schools located in Chungju, Korea. We assigned three of the schools to the intervention group and two schools to the control group. The intervention group received 1 year of environmental intervention. Diet- and exercise-related educational video content was provided by internet protocol television services during rest time, and various design materials were painted along the school staircase and hallway to encourage physical activities. Overweight and obese students were recommended to join the summer vacation obesity care program. RESULTS: The final number of total participants was 768 (control 350 and intervention 418). After 1 year of follow-up, there was no significant difference in the overweight/obesity incidence rates and remission rates between the two groups. However, the intervention group showed a greater decrease in the body mass index (BMI) z-score (-0.11 (95% confidence interval (CI) -0.16 to -0.06), P<0.001), increase in height (1.1 cm (95% CI 0.8 to 1.4), P<0.001), reduction of body fat, and increase in muscle mass compared with the control group. In addition, blood pressure (BP) was significantly reduced, and significant improvement in physical fitness followed. In subgroup analysis, students of normal weight, boys and younger participants showed the most beneficial results in weight-related outcomes. In addition, the BP reduction was more pronounced in the higher BMI group, boys and older children. CONCLUSIONS: A simple environmental intervention could effectively influence children. By adding to previously studied strategies, we can develop a more effective obesity prevention program for children.

Triglycerides/glucose index is a useful surrogate marker of insulin resistance among adolescents.

OBJECTIVES: Our aim was to investigate the association between the triglycerides/glucose index (TyG index) and the homeostasis model assessment-estimated insulin resistance (HOMA-IR) in the prediction of insulin resistance (IR) among adolescents. METHODS: We conducted a cross-sectional study among 221 Korean adolescents (168 males and 53 females aged 9-13 years) from May to June 2014 in Chung-ju city. The TyG index was calculated as ln [triglycerides (mg dl-1) × fasting glucose (mg dl-1)/2]. IR was defined using HOMA-IR >95th percentile for age and sex. RESULTS: In the IR group, weight, body mass index (BMI), waist circumference, body fat, fasting insulin, fasting plasma glucose, triglyceride levels and triglycerides/high-density lipoprotein cholesterol (TG/HDL-C) were significantly higher than that in the non-IR group. The TG index was significantly different between the IR group (n=22) and non-IR group (n=199), at 8.43±0.45 and 8.05±0.41, respectively (P<0.001). The TyG index was well correlated with HOMA-IR (r=0.41; P<0.001) and showed a strong positive association with TG/HDL-C (r=0.84; P<0.001). The cut-off of the TyG index for diagnosis of insulin resistance was 8.18. CONCLUSIONS: The TyG index is a simple, cost-effective surrogate marker of insulin resistance among adolescents compared with HOMA-IR.

The prevalence of osteoporosis and the rate of bone loss in Korean adults: the Chungju metabolic disease cohort (CMC) study.

Because the rate of bone loss is an important risk factor for fracture, we studied longitudinal changes in bone mineral density (BMD). Although the BMD of the hip decreased over time, spine BMD remained largely stable or increased. Therefore, spine BMD may not be appropriate for assessing BMD change. INTRODUCTION: The rate of age-dependent bone loss has been shown to be an important risk factor for fracture. However, longitudinal rates of BMD loss in Korea have not yet been reported. The objective of this study was to evaluate longitudinal changes in BMD in Korea. METHODS: This cohort study was performed in a population of individuals 40 years of age or older living in the rural area of Chungju City, Korea. A second BMD examination was conducted approximately 4 years after a baseline examination. A total of 3755 of the 6007 subjects completed the follow-up visit, corresponding to a follow-up rate of 62.51%. RESULTS: The age-standardized osteoporosis prevalence was 12.81% in males and 44.35% in females. In males, the average annual BMD loss at the total hip increased from -0.25% per year in their 40s to -1.12% per year in their 80s. In females, the average annual BMD loss at the total hip increased from -0.69% per year in their 40s to -1.51% per year in their 80s. However, the average annual percentage change in spine BMD in females increased from -0.91% per year in their 40s to +1.39% per year in their 80s. CONCLUSIONS: A substantial number of subjects had osteoporosis, even though we standardized the prevalence of osteoporosis. In total hip, the mean BMD was decreased during the follow-up period; in addition, the annual percentage loss increased with age. However, spine BMD remained approximately stable or increased over time and therefore may not be appropriate for assessing BMD change.

Supplementary tibial fixation in anterior cruciate ligament reconstruction - Direct cortical fixation using spiked washer screw vs. post-tie using washer screw.

We compare clinical outcomes of two different supplementary tibial fixation in anterior cruciate ligament (ACL) reconstruction using free tendon Achilles allograft. Eighty subjects underwent ACL reconstruction using Endobutton CL for femoral fixation and Bio-interference screw for tibial fixation. Supplementary tibial fixation was performed as direct -cortical fixation using spiked washer screw (group I) or as post-tie using washer screw (group II). -Lachman test, pivot shift test, IKDC classification, Lysholm score, and side-to-side difference (SSD) were evaluated. Thirty six in group I and thirty five in group II could follow up for at least 2 years. At the last follow-up, 7 in group I and 1 in group II showed 2+ or 3+ in Lachman test (p = 0.027). Mean SSD was 2.4mm in group I and 1.4mm in group II (p = 0.048). Post-tie using washer screw was more effective than direct cortical fixation using spiked washer screw to restore stability. Level of evidence : Therapeutic Level I ; Randomized controlled clinical trial.

Comparative analysis of the efficacy of omega-3 fatty acids for hypertriglyceridaemia management in Korea.

WHAT IS KNOWN AND OBJECTIVE: This study aimed to compare the ability of statin monotherapy (ST group), omega-3 fatty acid monotherapy (OM_A group) and combination therapy with omega-3 fatty acids and a statin (OM_S group), to reduce triglyceride (TG) levels in patients with hypertriglyceridaemia. METHODS: In this retrospective cohort study, we extracted data from the electronic medical records of patients initially prescribed either a statin or omega-3 fatty acids between January, 2009 and December, 2013. We performed a comparative analysis of the change in cholesterol levels between baseline and an average of 3 months later. RESULTS AND DISCUSSION: Data were extracted for 2071 patients. The average daily eicosapentaenoic acid (EPA) ethyl ester and docosahexaenoic acid (DHA) ethyl ester intake was 1689 mg, and 79-86% of the OM_A and OM_S groups were prescribed two omega-3 fatty acid capsules. At a baseline TG level of between 200 and 500 mg/dL, TG levels were reduced by 16 ± 2·8% in the ST group, 28 ± 2·8% in the OM_A group and 29 ± 2·3% in the OM_S group (P = 0·001 for ST group vs. OM_A and OM_S groups), with no difference between the OM_A and OM_S groups. At a baseline TG level ≥500 mg/dL, there was no difference in TG level reduction between the three groups (54 ± 7·3%, 55·8 ± 3·5% and 51·8 ± 6·8%, respectively, P = 0·851). WHAT IS NEW AND CONCLUSION: Although omega-3 fatty acids are not considered the primary medication for hypertriglyceridaemia, the prescription of omega-3 fatty acids is justifiable if reduction in TG levels is judged to be necessary.

Statin-related aminotransferase elevation according to baseline aminotransferases level in real practice in Korea.

WHAT IS KNOWN AND OBJECTIVE: Higher rate of statin-related hepatotoxicity has been reported for Koreans than for Westerners. Moreover, statin-related aminotransferase elevation for those who show borderline levels of aspartate transaminase (AST) and alanine transaminase (ALT) (≤×3 of UNL) at baseline has not been fully investigated. METHODS: Post-statin changes AST/ALT levels during the first year for 21 233 Korean outpatients at two large academic teaching hospitals from January 2009 to December 2013 were analysed using electronic health record data. The date of the first statin prescription was set as baseline. We also performed a comparative analysis of statin-related AST/ALT elevations according to the type of statin, followed by an analysis of clinical risk factors. RESULTS AND DISCUSSION: The progression rate to abnormal AST/ALT values [>×3 the upper normal limit (UNL)] was significantly higher (2·4-16% vs. 0·3-1·7%, P < 0·001) in subjects with borderline (>×1, but ≤×3 of UNL) compared with normal AST/ALT values at baseline. Those with normal baseline AST/ALT did not show significantly different progression rate between different statin medications (P = 0·801). However, patients taking pitavastatin (HR = 0·76, P = 0·657) were least likely to develop abnormal AST/ALT, whereas those taking fluvastatin (HR = 2·96, P = 0·029) were the most likely to develop abnormal AST/ALT compared with atorvastatin for patients who were with baseline borderline AST/ALT. However, given the small sample sizes and the observational nature of our study, these need further study. WHAT IS NEW AND CONCLUSION: It is advisable to regularly monitor AST/ALT levels even in patients with AST/ALT increases >×1. Future studies should aim to determine the possible risk factors for each specific statin type by analysing various confounding variables.

Analysis and comparison of statin prescription patterns and outcomes according to clinical department.

WHAT IS KNOWN AND OBJECTIVE: There is a disparity between the Korean treatment guidelines and actual clinical prescription habits. This study was designed to evaluate the department-specific disparities and achievement rates for low-density lipoprotein cholesterol (LDL-C) targets, based on each department's specific statin prescription patterns. METHODS: We retrospectively evaluated data from 31 718 patients who had been prescribed a statin at least once between January 2008 and June 2013 at our institution. Patients were classified into the high-risk (target LDL-C < 100 mg/dL) or moderate-risk (target LDL-C < 130 mg/dL) groups, according to the National Cholesterol Education Programme-Adult Treatment Panel III guidelines. RESULTS AND DISCUSSION: Statins were most commonly prescribed in the cardiology (32·0%) and endocrinology (26·6%) departments. For the high-risk group, 70% of patients in the cardiology, endocrinology and cardiac surgery departments achieved their target LDL-C levels (<100 mg/dL). However, the target achievement rates in most other departments were <70%. For the moderate-risk group, 79·2% of patients achieved their target levels. Departments that prescribed a greater number of high- or intermediate-potency statins were more likely to achieve their target LDL-C levels. The group that achieved their target LDL-C levels (<100 mg/dL) exhibited a significant positive relationship (Spearman's correlation coefficient = 0·8571, P = 0·0065), from low to high potency. WHAT IS NEW AND CONCLUSION: Some departments tend to undertreat when prescribing statins. However, to reach to the target LDL-C levels, physicians must overcome their tendency to undertreat with statins. We believe that the target achievement rate will increase if doctors are more actively aware of a patient's individual status and related risk factors before prescribing statins.

Quality of care in patients with diabetic kidney disease in Asia: The Joint Asia Diabetes Evaluation (JADE) Registry.

AIMS: Diabetic kidney disease independently predicts cardiovascular disease and premature death. We examined the burden of chronic kidney disease (CKD, defined as an estimated GFR < 60 ml/min/1.73 m(2) ) and quality of care in a cross-sectional survey of adults (age ≥ 18 years) with Type 2 diabetes across Asia. METHODS: The Joint Asia Diabetes Evaluation programme is a disease-management programme implemented using an electronic portal that systematically captures clinical characteristics of all patients enrolled. Between July 2007 and December 2012, data on 28 110 consecutively enrolled patients (China: 3415, Hong Kong: 15 196, India: 3714, Korea: 1651, Philippines: 3364, Vietnam: 692, Taiwan: 78) were analysed. RESULTS: In this survey, 15.9% of patients had CKD, 25.0% had microalbuminuria and 12.5% had macroalbuminuria. Patients with CKD were less likely to achieve HbA1c < 53 mmol/mol (7.0%) (36.0% vs. 42.3%) and blood pressure < 130/80 mmHg (20.8% vs. 35.3%), and were more likely to have retinopathy (26.2% vs. 8.7%), sensory neuropathy (29.0% vs. 7.7%), cardiovascular disease (26.6% vs. 8.7%) and self-reported hypoglycaemia (18.9% vs. 8.2%). Despite high frequencies of albuminuria (74.8%) and dyslipidaemia (93.0%) among CKD patients, only 49.0% were using renin-angiotensin system inhibitors and 53.6% were on statins. On logistic regression, old age, male gender, tobacco use, long disease duration, high HbA1c , blood pressure and BMI, and low LDL cholesterol were independently associated with CKD (all P < 0.05). CONCLUSIONS: The poor control of risk factors, suboptimal use of organ-protective drugs and high frequencies of hypoglycaemia highlight major treatment gaps in patients with diabetic kidney disease in Asia.

Different effect of alcohol consumption on hypertension according to metabolic health status.

We aimed to investigate whether the effect of problematic alcohol drinking on hypertension differed according to metabolic health statuses. Male participants from the fifth Korea National Health and Nutrition Examination Survey were recruited. Problematic alcohol drinkers were designated as subjects with heavy drinking (⩾30 g per day), binge drinking (⩾7 glasses per day) or a high alcohol use disorders identification test score (⩾20). Metabolically obese status was defined as having ⩾1 or ⩾2 components of the diagnostic criteria for metabolic syndrome, excluding the blood pressure component. Because the prevalence of problematic alcohol drinking and the prevalence of hypertension largely differed by age groups, separate analyses were performed for the two age groups (<50 and ⩾50 years). Among a total of 6329 subjects, 37.04% had hypertension. In the younger age group, subjects with problematic alcohol drinking demonstrated a higher prevalence of hypertension in both nonobese and obese individuals compared with subjects who were nonobese and who were not problematic alcohol drinkers. Of note, problematic alcohol drinking increased the risk of having hypertension ∼3 times in young nonobese individuals who demonstrated a metabolically obese phenotype compared with those who were metabolically healthy. However, metabolic health status did not have a significant impact on the risk for having hypertension in obese participants, regardless of their age groups. For the prevention of hypertension, avoidance of problematic alcohol drinking should be emphasized, especially in young subjects who show poor metabolic health status despite being nonobese.

Serum preadipocyte factor 1 concentrations and risk of developing diabetes: a nested case-control study.

AIM: To determine whether preadipocyte factor 1 could be a predictive marker for the development of diabetes in people without diabetes at baseline. METHODS: We conducted a population-based, nested case-control study of individuals who progressed to diabetes (n = 43) or prediabetes (n = 345) and control participants matched on age, sex and fasting plasma glucose concentration, who maintained normal glucose tolerance (n = 389) during a 4-year follow-up using data from the Chungju Metabolic disease Cohort Study. Circulating levels of preadipocyte factor 1 were measured using an enzyme-linked immunosorbent assay. RESULTS: Baseline serum preadipocyte factor 1 levels showed a stepwise decrease across the glucose tolerance status groups at follow-up (normal glucose tolerance: 10.02 ± 3.02 ng/ml; prediabetes: 9.48 ± 3.35 ng/ml; diabetes: 8.66 ± 3.29 ng/ml; P for trend, 0.0151). Individuals whose fasting plasma glucose level had increased or whose homeostasis model assessment of ß-cell function had decreased at follow-up showed significantly lower levels of preadipocyte factor 1 compared with their control group counterparts. After adjusting for age, BMI, fasting plasma glucose, serum insulin levels, systolic blood pressure and triglycerides, the incidence of diabetes was nearly threefold higher in the lowest vs. the upper three quartiles of circulating preadipocyte factor 1 (relative risk 2.794; 95% CI 1.188-6.571; P = 0.0185). Notably, these findings were significant in women but not in men. CONCLUSIONS: Levels of circulating preadipocyte factor 1 may be a useful biomarker for identifying women at high risk of developing diabetes.

Lower serum zinc levels are associated with unhealthy metabolic status in normal-weight adults: The 2010 Korea National Health and Nutrition Examination Survey.

AIM: This study investigated whether serum zinc concentration is associated with glucose tolerance, insulin resistance and metabolic health status in Korean adults. METHODS: Subjects with available serum zinc levels were recruited from the fifth Korea National Health and Nutrition Examination Survey (KNHANESV) cohort. Those in the highest quartile on homoeostasis model assessment for insulin resistance (HOMA-IR) and with a body mass index (BMI) of 18.5-25kg/m(2) were classified as metabolically obese and normal weight (MONW). RESULTS: A total of 1813 subjects with a mean age of 45.2±0.5 years and a mean BMI of 24.01±0.11kg/m(2) were enrolled. Those in the lower serum zinc quartiles exhibited higher levels of fasting blood glucose and insulin resistance indices compared with those in the higher quartiles. However, these associations were positive only in normal-weight subjects. Those categorized as MONW exhibited significantly lower serum zinc levels than the metabolically healthy and normal weight (MHNW) subjects (131.6±3.0µg/dL vs 141.7±2.8µg/dL, respectively; P=0.0026), whereas serum zinc levels did not differ according to metabolic health in obese subjects. The odds ratio for being categorized as MONW was 4.12 (95% CI: 1.75, 9.72) among those in the lowest serum zinc quartile compared with those in the highest quartile even after adjusting for possible confounding factors. CONCLUSION: Lower serum zinc levels were associated with unhealthy metabolic status in normal-weight adults. Further prospective studies are required to define the role of zinc in metabolic health.

A novel criterion for identifying metabolically obese but normal weight individuals using the product of triglycerides and glucose.

OBJECTIVES: Metabolically obese but normal weight (MONW) individuals constitute a subgroup of normal weight individuals that display impaired insulin sensitivity with a higher risk of developing diabetes, cardiovascular disease and mortality. We aimed to propose a novel criterion for defining MONW by examining the usefulness and the cutoff value of the TyG index, a product of the levels of triglycerides and glucose, in identifying MONW individuals. In addition, the performance of this criterion in predicting the future incidence of diabetes was assessed. SUBJECTS/METHODS: A total of 7541 non-diabetic, normal weight (body mass index ⩾18.5 and <25 kg m(-)(2)) subjects were selected from the Korea National Health and Nutrition Examination Survey conducted in 2009-2010. Another 3185 participants with follow-up studies were selected from a prospective community-based cohort study. The TyG index was calculated as ln(fasting triglycerides (mg dl(-1)) × fasting glucose (mg dl(-1))/2). RESULTS: The levels of the TyG index paralleled the prevalence of metabolic syndrome and its components. The cutoff value of the TyG index that reflected MONW based on the receiver operating characteristics analysis was 8.82 for men and 8.73 for women, with the area under the curve values being 0.855 and 0.868, respectively. The sensitivity and the specificity were 84.2 and 77.6% in men and 69.1 and 89.4% in women, respectively. Individuals designated as MONW, who have a normal weight and TyG levels higher than cutoff, displayed a metabolically unhealthy phenotype and an approximately twofold higher risk of developing diabetes compared with metabolically healthy normal weight subjects. CONCLUSIONS: We propose a simple diagnostic criterion of MONW, which might be used to discriminate subjects with a higher risk of metabolic diseases.

Reduction of radiation exposure by lead curtain shielding in dedicated extremity cone beam CT.

OBJECTIVE: A dedicated extremity cone beam CT (CBCT) was introduced recently, and is rapidly becoming an attractive modality for extremity imaging. This study aimed to evaluate the effectiveness of a curtain-shaped lead shielding in reducing the exposure of patients to scattered radiation in dedicated extremity CBCT. METHODS: A dedicated extremity CBCT scanner was used. The lead shielding curtain was 42 × 60 cm with 0.5-mm lead equivalent. Scattered radiation dose from CBCT was measured using thermoluminescence dosimetry chips at 20 points, at different distances and directions from the CT gantry. Two sets of scattered radiation dose measurements were performed before and after installation of curtain-shaped lead shield, and the percentage reduction in dose in air was calculated. RESULTS: Mean radiation exposure dose at measured points was 34.46 ± 48.40 µGy without curtains and 9.67 ± 4.53 µGy with curtains, exhibiting 71.94% reduction (p = 0.000). The use of lead shielding curtains significantly reduced scattered radiation at 0.5, 1.0 and 1.5 m from the CT gantry, with percent reductions of 84.8%, 58.0% and 35.5%, respectively (p = 0.000, 0.000 and 0.002). The percent reduction in the diagonal (+45°, -45°) and vertical forward (0°) directions were 86.3%, 83.1% and 77.7%, respectively, and were statistically significant (p = 0.029, 0.020 and 0.041). CONCLUSION: Shielding with lead curtains suggests an easy and effective method for reducing patient exposure to radiation in extremity CBCT imaging. ADVANCES IN KNOWLEDGE: Lead shielding curtains are an effective technique to reduce scattered radiation dose in dedicated extremity CBCT, with higher dose reduction closer to the gantry opening.

Liraglutide pharmacokinetics and dose-exposure response in Asian subjects with Type 2 diabetes from China, India and South Korea.

AIMS: To investigate the population pharmacokinetics and exposure-response relationship of liraglutide, a human glucagon-like peptide-1 (GLP-1) analogue, in Asian subjects with Type 2 diabetes mellitus. METHODS: Data were derived from a published 16-week, randomized, double-blind, double-dummy, active-controlled, parallel-group trial of liraglutide in China, India and South Korea. The analysis utilized 2061 pharmacokinetic (PK) samples from 605 subjects exposed to liraglutide 0.6, 1.2 or 1.8 mg once daily. Demographic factors (body weight, age, gender, country) of importance for liraglutide clearance were evaluated. An exploratory exposure-response analysis was conducted to investigate effects on glycated haemoglobin (HbA1c) and body weight. RESULTS: Estimated liraglutide exposure (area under the curve; AUC) appeared to increase proportionally with increasing liraglutide dose (0.6-1.8 mg). The covariate analysis confirmed previous findings in a global clinical trial. Body weight was a predictor of liraglutide exposure; compared to a reference subject of 67 kg, exposure was 32% lower for maximum (115 kg) and 54% higher for minimum (37 kg) observed body weights. Gender, age and country had no relevant effect on exposure. Exposure-response analysis supported the use of 1.2mg as maintenance dose with the option of individual dose escalation to 1.8 mg to optimize treatment outcomes. CONCLUSIONS: Exposure appeared to increase proportionally with increasing liraglutide dose in Asian subjects with Type 2 diabetes mellitus. The only PK relevant predictor of exposure was body weight. The exposure-response relationships for HbA1c and body weight in Asian subjects were similar to observations in global populations.

Lobeglitazone and pioglitazone as add-ons to metformin for patients with type 2 diabetes: a 24-week, multicentre, randomized, double-blind, parallel-group, active-controlled, phase III clinical trial with a 28-week extension.

We aimed to compare the efficacy and safety of lobeglitazone and pioglitazone as add-ons to metformin in patients with type 2 diabetes. Patients who were inadequately controlled by metformin were randomized and treated once daily with either lobeglitazone (0.5 mg, n = 128) or pioglitazone (15 mg, n = 125) for 24 weeks, with a 28-week extension trial of lobeglitazone treatment in patients who consented. The primary endpoint was the change in glycated haemoglobin (HbA1c) concentration from baseline to week 24. At week 24, the mean change from baseline in HbA1c was -0.74% for the lobeglitazone group and -0.74% for the pioglitazone group, with a mean difference of 0.01% [95% confidence interval (CI) of difference, -0.16 to 0.18]. The effects of lobeglitazone on lipid variables and the adverse events associated with lobeglitazone were similar to those observed with pioglitazone. Lobeglitazone was not inferior to pioglitazone as an add-on to metformin in terms of their efficacy and safety.

Anagliptin and sitagliptin as add-ons to metformin for patients with type 2 diabetes: a 24-week, multicentre, randomized, double-blind, active-controlled, phase III clinical trial with a 28-week extension.

We conducted a 24-week, multicentre, double-blind, randomized study with a 28-week extension to compare the efficacy and safety of anagliptin and sitagliptin as an add-on to metformin in patients with type 2 diabetes. Patients inadequately controlled on metformin were randomized to either anagliptin (100 mg twice daily, n = 92) or sitagliptin (100 mg once daily, n = 88). The primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline to week 24. The mean changes in HbA1c were -0.85 ± 0.70% (p < 0.0001) for anagliptin and -0.83 ± 0.61% (p < 0.0001) for sitagliptin, with a mean difference of -0.02% (95% confidence interval of difference, -0.22 to 0.18%). In both groups, the fasting proinsulin : insulin ratio significantly decreased from baseline, with improved insulin secretion. Safety profiles were similar in each group. In conclusion, the non-inferiority of the efficacy of anagliptin to sitagliptin as an add-on therapy was established with regard to efficacy and safety.

The optimal morning:evening ratio in total dose of twice-daily biphasic insulin analogue in poorly controlled Type 2 diabetes: a 24-week multi-centre prospective, randomized controlled, open-labelled clinical study.

AIMS: Biphasic insulin analogues are widely used in patients with Type 2 diabetes mellitus suboptimally controlled on oral anti-diabetic drugs. Several topics in this area remain controversial, including how to divide the daily dose of biphasic insulin analogue. We aimed to determine the optimal dosing ratio of twice-daily biphasic insulin analogue and to compare the glycaemic efficacy among groups of patients using different initial dosing ratios of biphasic insulin analogue. METHODS: A total of 100 poorly controlled insulin-naive subjects with Type 2 diabetes [HbA1c ≥ 58 mmol/mol, (7.5%)] on oral anti-diabetic drugs were randomized into three groups according to initial morning:evening dosing ratio (group I, 50:50; group II, 55:45; group III, 60:40) of twice-daily biphasic insulin analogue (biphasic insulin aspart 70/30, biphasic insulin aspart 30). The primary outcome measure was the difference in pre-breakfast to pre-dinner dose ratio at the end of the study. RESULTS: Twice-daily biphasic insulin analogue showed a significant improvement in glycaemic control [HbA1c from 70 mmol/mol (8.6%) to 60 mmol/mol (7.6%)] after 24 weeks regardless of the initial dose ratio given. Despite the similar efficacy and safety profiles among three groups, morning dose was significantly increased (from 50:50 to 55:45-60:40) in group I after 24 weeks. However, there was no significant change in splitting ratio in groups II and III (with higher morning dose) over the 24-week treatment period. CONCLUSIONS: These results indicate that initiating twice-daily biphasic insulin analogue on regimens with a higher dose before breakfast than before dinner (i.e. ratio approximately 55:45 to 60:40) might be more appropriate in Korean subjects with Type 2 diabetes.