Cardiovascular safety of evogliptin dual and triple therapy in patients with type 2 diabetes: a nationwide cohort study.

OBJECTIVE: To investigate the risk of cardiovascular events associated with commonly used dual and triple therapies of evogliptin, a recently introduced dipeptidyl peptidase-4 inhibitor (DPP4i), for managing type 2 diabetes in routine clinical practice. DESIGN: A retrospective cohort study. SETTING: Korean Health Insurance Review and Assessment database. PARTICIPANTS: Patients who initiated metformin-based dual therapy and metformin+sulfonylurea-based triple therapy in South Korea from 2014 to 2018. INTERVENTIONS: Initiation of combination therapy with evogliptin. PRIMARY AND SECONDARY OUTCOME MEASURES: Hazards of cardiovascular events, a composite endpoint of myocardial infarction, heart failure and cerebrovascular events, and its individual components. Cox proportional hazards model with propensity score-based inverse probability of treatment weighting were used to estimate HRs and 95% CIs. RESULTS: From the dual and triple therapy cohorts, 5830 metformin+evogliptin users and 2198 metformin+sulfonylurea+evogliptin users were identified, respectively. Metformin+evogliptin users, as compared with metformin+non-DPP4i, had a 29% reduced risk of cardiovascular events (HR 0.71, 95% CI 0.62 to 0.82); HRs for individual outcomes were cerebrovascular events (0.71, 95% CI 0.53 to 0.95), heart failure (0.70, 95% CI 0.59 to 0.82), myocardial infarction (0.89, 95% CI 0.60 to 1.31). Metformin+sulfonylurea+evogliptin users, compared with metformin+sulfonylurea+non-DPP4i, had a 24% reduced risk of cardiovascular events (0.76, 95% CI 0.59 to 0.97); HRs for individual outcomes were myocardial infarction (0.57, 95% CI 0.27 to 1.19), heart failure (0.74, 95% CI 0.55 to 1.01), cerebrovascular events (0.96, 95% CI 0.61 to 1.51). CONCLUSIONS: These findings suggest that dual or triple therapies of evogliptin for the management of type 2 diabetes in routine clinical practice present no cardiovascular harms, but could alternatively offer cardiovascular benefits in this patient population.

A multicentre, double-blind, placebo-controlled, randomized, parallel comparison, phase 3 trial to evaluate the efficacy and safety of pioglitazone add-on therapy in type 2 diabetic patients treated with metformin and dapagliflozin.

AIM: To investigate the efficacy and safety of pioglitazone compared to placebo when added to metformin plus dapagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, for patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: In a multicentre study, with a randomized, double-blind, placebo-controlled design, 249 Korean patients with T2DM suboptimally managed on metformin and dapagliflozin were assigned to receive either pioglitazone (15 mg daily) or placebo for 24 weeks, followed by a 24-week pioglitazone extension. Primary outcomes included changes in glycated haemoglobin (HbA1c), with secondary outcomes assessing insulin resistance, adiponectin levels, lipid profiles, liver enzymes, body weight and waist circumference. RESULTS: Pioglitazone administration resulted in a significant reduction in HbA1c levels (from 7.80% ± 0.72% to 7.27% ± 0.82%) compared with placebo (from 7.79% ± 0.76% to 7.69% ± 0.86%, corrected mean difference: -0.42% ± 0.08%; p < 0.01) at 24 weeks. Additional benefits from pioglitazone treatment included enhanced insulin sensitivity, increased adiponectin levels, raised high-density lipoprotein cholesterol levels and reduced liver enzyme levels, resulting in improvement in nonalcoholic fatty liver disease liver fat score. Despite no serious adverse events in either group, pioglitazone therapy was modestly but significantly associated with weight gain and increased waist circumference. CONCLUSIONS: Adjunctive pioglitazone treatment in T2DM inadequately controlled with metformin and dapagliflozin demonstrates considerable glycaemic improvement, metabolic benefits, and a low risk of hypoglycaemia. These advantages must be weighed against the potential for weight gain and increased waist circumference.

Fatty Liver Change in Older Adults as an Important Risk Factor for Type 2 Diabetes: A Nationwide Cohort Study.

OBJECTIVE: To examine the association between changes in fatty liver disease (FLD) over time and the risk of type 2 diabetes in elderly individuals with prediabetes. METHODS: A total of 156,984 elderly individuals with prediabetes who underwent national health screening in 2009 and 2011 were followed up through December 31, 2019. The FLD status was defined as a change in the fatty liver index. Prediabetes was defined as impaired fasting glucose levels at baseline. Multivariable Cox proportional hazards regression was used to calculate the hazard ratio and CIs for type 2 diabetes according to the changes in FLD. RESULTS: During a median of 8.35 years of follow-up, type 2 diabetes developed in 29,422 (18.7%) elderly individuals with prediabetes. Multivariable adjusted hazard ratio of type 2 diabetes according to FLD change was 2.22 (95% CI, 2.11 to 2.34) in individuals with persistent FLD compared with those who have never had FLD. Although overall weight loss of 5% or more was associated with a 7% lower risk of type 2 diabetes in total participants, fatty liver status was important. Even with weight loss, those with a history of fatty liver-resolved FLD, new FLD, or persistent FLD-had an increased risk of type 2 diabetes. The risk of type 2 diabetes did not increase in individuals with sustained FLD-free status, regardless of weight change. CONCLUSION: The presence and change of FLD are important factors for the development of type 2 diabetes in elderly individuals with prediabetes.

Efficacy and Safety of Evogliptin Add-on Therapy to Dapagliflozin/Metformin Combinations in Patients with Poorly Controlled Type 2 Diabetes Mellitus: A 24-Week Multicenter Randomized Placebo-Controlled Parallel-Design Phase-3 Trial with a 28-Week Extension.

BACKGRUOUND: This study investigates the long-term efficacy and safety of evogliptin add-on therapy in patients with inadequately controlled type 2 diabetes mellitus (T2DM) previously received dapagliflozin and metformin (DAPA/MET) combination. METHODS: In this multicenter randomized placebo-controlled phase 3 trial, patients with glycosylated hemoglobin (HbA1c) levels 7.0% to 10.5% (n=283) previously used DAPA 10 mg plus MET (≥1,000 mg) were randomly assigned to the evogliptin 5 mg once daily or placebo group (1:1). The primary endpoint was the difference in the HbA1c level from baseline at week 24, and exploratory endpoints included the efficacy and safety of evogliptin over 52 weeks (trial registration: ClinicalTrials.gov NCT04170998). RESULTS: Evogliptin add-on to DAPA/MET therapy was superior in HbA1c reduction compared to placebo at weeks 24 and 52 (least square [LS] mean difference, -0.65% and -0.55%; 95% confidence interval [CI], -0.79 to -0.51 and -0.71 to -0.39; P<0.0001). The proportion of patients achieving HbA1c <7% was higher in the triple combination group at week 52 (32.14% vs. 8.51% in placebo; odds ratio, 5.62; P<0.0001). Evogliptin significantly reduced the fasting glucose levels and mean daily glucose levels with improvement in homeostatic model assessment of ß-cell function (LS mean difference, 9.04; 95% CI, 1.86 to 16.21; P=0.0138). Adverse events were similar between the groups, and no serious adverse drug reactions were reported in the evogliptin group. CONCLUSION: Long-term triple combination with evogliptin added to DAPA/MET showed superior HbA1c reduction and glycemic control compared to placebo at 52 weeks and was well tolerated.

Association between Sleep Duration and Metabolic Disorders among Filipino Immigrant Women: The Filipino Women's Diet and Health Study (FiLWHEL).

Background: Sleep plays a complex role in metabolic regulation, and the underlying linkage has not been clearly defined. We investigated the association between sleep duration and metabolic disorders in Filipino immigrants in Korea. Methods: We analyzed 410 participants from the 2014 to 2016 baseline population of the Filipino Women's Diet and Health Study. Usual sleep duration was self-reported, and anthropometric parameters were measured directly. Blood glucose, lipid, and insulin levels were examined from fasting serum samples. We used general linear models to acquire least squares (LS) means and logistic regression models to calculate odds ratios to test the cross-sectional association between sleep duration and metabolic markers with 95% confidence intervals (CIs). Results: We found a statistically significant linear association between increased sleep duration and elevated triglycerides, total cholesterol, and low-density lipoprotein cholesterol (LDL-C). LS means (95% CI) of <5, 5-6, 7-8, and >8 hours of sleep were 81.74 (71.43 to 93.54), 85.15 (76.65 to 94.59), 86.33 (77.84 to 95.75), and 105.22 (88.07 to 125.71), respectively, for triglycerides (P trend=0.049) and 174.52 (165.02 to 184.57), 180.50 (172.79 to 188.55), 182.51 (174.83 to 190.53), and 190.16 (176.61 to 204.74), respectively, for total cholesterol (P trend= 0.042). For LDL-C, the LS means (95% CI) were 97.34 (88.80 to 106.71), 100.69 (93.73 to 108.18), 104.47 (97.35 to 112.10), and 109.43 (96.94 to 123.54), respectively (P trend=0.047). Statistical significance persisted after additional adjustment for body mass index. The association with triglycerides was limited to current alcohol drinkers (P interaction=0.048). Conclusion: Longer sleep duration was associated with increased triglyceride, total cholesterol, and LDL-C levels. The association with triglycerides was more pronounced among moderate alcohol drinkers.

Dietary intakes of branched-chain amino acids and plasma lipid profiles among filipino women in Korea: the Filipino Women's Diet and Health Study (FiLWHEL).

BACKGROUND: The potential role of dietary branched-chain amino acids (BCAA) in metabolic health, including cardiovascular disease and diabetes, is evolving, and it is yet to be understood if dietary BCAA intakes are associated with plasma lipid profiles or dyslipidaemia. This study tested the association of dietary BCAA intakes with plasma lipid profiles and dyslipidaemia among Filipino women in Korea. METHODS: Energy-adjusted dietary BCAA intakes (isoleucine, leucine, valine, and total BCAA) and fasting blood profiles of triglycerides (TG), total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), and low-density lipoprotein-cholesterol (LDL-C) were determined in a sample of 423 women enrolled in the Filipino Women's Diet and Health Study (FiLWHEL). The generalized linear model was applied to estimate least-square (LS) means and 95% confidence intervals (CIs) and compare plasma TG, TC, HDL-C, and LDL-C across tertile distribution of energy-adjusted dietary BCAA intakes at P < 0.05. RESULTS: Mean of energy-adjusted dietary total BCAA intake was 8.3 ± 3.9 g/d. Average plasma lipid profiles were 88.5 ± 47.4 mg/dl for TG, 179.7 ± 34.5 mg/dl for TC, 58.0 ± 13.7 mg/dl for HDL-C, and 104.0 ± 30.5 mg/dl for LDL-C. LS means, and 95% CIs across tertiles of energy-adjusted total BCAA intakes were 89.9 mg/dl, 88.8 mg/dl and 85.8 mg/dl (P-trend = 0.45) for TG, 179.1 mg/dl, 183.6 mg/dl and 176.5 mg/dl (P-trend = 0.48) for TC, 57.5 mg/dl, 59.6 mg/dl and 57.1 mg/dl (P-trend = 0.75) for HDL-C and 103.6 mg/dl, 106.2 mg/dl and 102.3 mg/dl (P-trend = 0.68) for LDL-C. Furthermore, the multivariable-adjusted prevalence ratios and 95% confidence intervals for dyslipidaemia across increasing tertile distribution of energy-adjusted total BCAA intake were; 1.00, 0.67 (0.40, 1.13) and 0.45 (0.16, 1.27; P-trend = 0.03) for the first, second and third tertile, respectively. CONCLUSIONS: Higher dietary intakes of BCAA presented a statistically significant inverse trend with the prevalence of dyslipidaemia among Filipino women in this study and testing these associations in longitudinal studies may be necessary to confirm these findings.

Higher Non-High-Density Lipoprotein Cholesterol Was Higher Associated With Cardiovascular Disease Comparing Higher LDL-C in Nine Years Follow Up: Cohort Study.

Objective: Non-high-density lipoprotein cholesterol (non-HDL-C) may be equivalent to or superior to low-density lipoprotein cholesterol (LDL-C) for the prediction of cardiovascular disease (CVD). However, studies comparing the predictive values of LDL-C and non-HDL-C levels for CVD have yielded conflicting results. In this study, we evaluated the relationship between non-HDL-C, LDL-C, and CVD using a large-scale population dataset from the National Health Information Database (NHID). Methods: We performed a retrospective observational cohort study of 3,866,366 individuals ≥ 20 years, from 2009 to 2018, using the NHID. The participants were divided into LDL-C and non-HDL-C quartiles. The outcome variables included stroke, myocardial infarction (MI), and both. All outcomes were analyzed using Cox proportional hazards regression analysis while controlling for baseline covariates (age, sex, smoking, drinking, regular exercise, body mass index, diabetes, hypertension, and statin use). Results: During 9.1 years of mean follow-up, stroke was diagnosed in 60,081 (1.55%), MI in 31,234 (0.81%), and both stroke and MI in 88,513 (2.29%) participants. Multivariate-adjusted hazard ratios (HRs) for patients in the highest non-HDL-C quartile demonstrated that these patients had a higher risk of stroke (HR, 1.254; 95% confidence interval [CI], 1.224-1.285), MI (HR, 1.918; 95% CI, 1.853-1.986), and both (HR, 1.456; 95% CI, 1.427-1.486) compared with participants in the lowest quartile. These were higher than the HRs for patients in the highest LDL-C quartile for stroke (HR, 1.134; 95% CI, 1.108-1.160), MI (HR, 1.601; 95% CI, 1.551-1.653), and both (HR, 1.281; 95% CI, 1.257-1.306). Conclusion: In our large population study, higher non-HDL-C levels were associated with CVD than LDL-C levels.

Associations of Dietary Intakes of Total and Specific Types of Fat with Blood Lipid Levels in the Filipino Women's Diet and Health Study (FiLWHEL).

Background: Limited evidence exists on the association between dietary fat intake and lipid profiles in Southeast Asian populations. Objectives: We aimed to examine the cross-sectional associations of dietary intake of total and specific types of fat with dyslipidemia in Filipino immigrant women in Korea. Methods: We included 406 Filipino women married to Korean in the Filipino Women's Diet and Health Study (FiLWHEL). Dietary fat intake was assessed using 24-hour recalls. Impaired blood lipid profiles were defined as high total cholesterol (TC) (≥200 mg/dL), high triglyceride (TG) (≥150 mg/dL), high LDL Cholesterol (LDL-C) (≥ 130 mg/dL), or low HDL cholesterol (HDL-C) (<50 mg/dL). The genomic DNA samples were genotyped using DNA chip. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariate logistic regression. Results: Substituting carbohydrates with dietary saturated fat (SFA) intake was associated with increased prevalence of dyslipidemia; ORs (95% CIs) for subsequent tertiles compared to the first tertile were 2.28 (1.19-4.35), and 2.88 (1.29-6.39) (P for trend = 0.02). When we examined individual markers, ORs (95% CIs, P for trend) comparing the third to the first tertile were 3.62 (1.53-8.55, 0.01) for high TC, 1.46 (0.42-5.10, 0.72) for high TG, 4.00 (1.48-10.79, 0.02) for high LDL-C, and 0.69 (0.30-1.59, 0.36) for low HDL-C. When we examined the interaction by LDL-C-related polymorphisms, the association with dyslipidemia was more pronounced among participants with CC alleles than among those with T alleles of rs6102059 (P for interaction = 0.01). Conclusions: High dietary SFA intake was significantly associated with a high prevalence of dyslipidemia in Filipino women in Korea. Further prospective cohort studies are warranted to determine risk factors for CVD in Southeast Asian populations.

Comparison of cardiovascular disease risk factors among FiLWHEL (2014-2016), NNS (2013) and KNHANES (2013-2015) women.

OBJECTIVES: This study assessed the CVD risk factors among Filipino women (FW) in Korea and compared them with FW in the Philippines and women in Korea (KW). METHODS: A cohort of 504 women from the Filipino Women's Health and Diet Study (FiLWHEL) aged 20-57 years old were age-matched (1:1 ratio) with women from the 2013 National Nutrition Survey in the Philippines and the 2013-2015 Korean National Health and Nutrition Examination Survey. Anthropometric data, blood pressure (BP), lipid and glucose levels were compared across the four populations by calculating the odds ratio (OR)s and 95% confidence interval (CI)s using conditional logistic regression models. RESULTS: Compared to KW, FW in Korea and FW in the Philippines were more than 2 and 3 times higher odds of having obesity for BMI ≥ 30 kg/m2 and waist circumference ≥ 88 cm, respectively. However, FW in Korea had the highest odds (OR 5.51, 95% CI 3.18-9.56) of having hypertension compared to KW. FW in the Philippines had the highest odds of having dyslipidemia (compared to KW, total cholesterol ≥ 200 mg/dL: OR 8.83, 95% CI 5.30-14.71; LDL-C ≥ 130 mg/dL: OR 3.25, 95% CI 2.13-4.98; and triglyceride ≥ 150 mg/dL: OR 2.59, 95% CI 1.59-4.22), but FW in Korea and KW had similar prevalence of dyslipidemia. CONCLUSIONS: FW in Korea had higher prevalence of obesity and hypertension, with similar prevalence of dyslipidemia compared to KW in this sample. FW in the Philippines had higher prevalence of dyslipidemia compared to FW in Korea. Further prospective studies are warranted to examine the CVD risk factors among continental and native-born Filipino women.

Evaluation and Treatment of Obesity and Its Comorbidities: 2022 Update of Clinical Practice Guidelines for Obesity by the Korean Society for the Study of Obesity.

The goal of the 8th edition of the Clinical Practice Guidelines for Obesity is to help primary care physician provide safe, effective care to patients with obesity by offering evidence-based recommendations to improve the quality of treatment. The Committee for Clinical Practice Guidelines comprised individuals with multidisciplinary expertise in obesity management. A steering board of seven experts oversaw the entire project. Recommendations were developed as the answers to key questions formulated in patient/problem, intervention, comparison, outcomes (PICO) format. Guidelines underwent multi-level review and cross-checking and received endorsement from relevant scientific societies. This edition of the guidelines includes criteria for diagnosing obesity, abdominal obesity, and metabolic syndrome; evaluation of obesity and its complications; weight loss goals; and treatment options such as diet, exercise, behavioral therapy, pharmacotherapy, and bariatric and metabolic surgery for Korean people with obesity. Compared to the previous edition of the guidelines, the current edition includes five new topics to keep up with the constantly evolving field of obesity: diagnosis of obesity, obesity in women, obesity in patients with mental illness, weight maintenance after weight loss, and the use of information and communication technology-based interventions for obesity treatment. This edition of the guidelines features has improved organization, more clearly linking key questions in PICO format to recommendations and key references. We are confident that these new Clinical Practice Guidelines for Obesity will be a valuable resource for all healthcare professionals as they describe the most current and evidence-based treatment options for obesity in a well-organized format.

The Gangwon Obesity and Metabolic Syndrome Study: Methods and Initial Baseline Data.

Background: The prevalence of obesity has been continuously increasing, especially in rural areas of South Korea. Therefore, it is important to examine various genetic, behavioral, and environmental factors associated with obesity in these rural areas. The Korean Society for the Study of Obesity commenced a community-based prospective cohort study of the Gangwon area called the Gangwon Obesity and Metabolic Syndrome (GOMS) study to investigate longitudinal changes in the status of obesity and its related factors. Methods: A total of 317 adults 40-69 years of age were recruited from Hongcheon and Inje districts, Gangwon province, as part of the first wave of this cohort study. Information on participants' demographic, behavioral, psychological, dietary, and environmental factors and past medical histories were collected by self-administered questionnaires and interviewer-administered questionnaires. Anthropometric measurements, blood tests, and a hand grip strength test were performed, and skin keratin and stool samples were collected. Among the 317 enrolled subjects, two participants who did not have anthropometric data were excluded from the data analyses, resulting in an inclusion of a total of 315 participants. Results: The mean age of the 315 participants in the GOMS initial baseline survey was 58.5 years old, 87 of them were men, and the mean body mass index was 24.7±3.7 kg/m2. Among all participants, 48.9% had hypertension, 21.4% had diabetes mellitus (DM), 55.6% had dyslipidemia, and 46.0% had metabolic syndrome (MS). Both the prevalence rates of DM and MS were significantly higher in men. Conclusion: The first baseline survey of the GOMS study was initiated, and a more detailed analysis of respondents' data is expected to be continued. Further follow-up and additional recruitment will allow the investigation of risk factors and the etiology of obesity and its comorbidities in rural areas of Gangwon province.

Dietary branched-chain amino acids and odds of obesity among immigrant Filipino women: the Filipino women's diet and health study (FiLWHEL).

BACKGROUND: The dietary environment promoting adiposity keeps evolving and of interest is the significance of dietary branched-chain amino acids (BCAA). This study assessed the association between dietary BCAA intakes and odds of obesity among immigrant Filipino women in Korea. METHOD: We included 423 immigrant Filipino women enrolled in the Filipino Women's diet and health study in the Republic of Korea. Dietary BCAA intakes were estimated from 24 hour recalls and adjusted for energy intake using the residual method. General obesity was derived from direct anthropometric measurements (height, weight and waist circumference - WC) and defined as body mass index (BMI) ≥25 kg/m2 and abdominal obesity as WC ≥80 cm. Odds ratios (OR) and 95% confidence intervals (CI) by tertile distribution of energy-adjusted BCAA intakes were estimated using multivariable logistic regression with a two-sided P < 0.05. RESULTS: Median (interquartile range) for BCAA intakes in g/day were; 7.9 (5.8, 10.3) g/day for total BCAA; 2.0 (1.5, 2.6) g/day for isoleucine, 3.5(2.5, 4.6) g/day for leucine and 2.4 (1.8, 3.1) g/day for valine. Mean BMI and WC were 23.6 ± 3.8 kg/m2 and 79.8 ± 9.3 cm, respectively. Also, 30.2% (128) had BMI ≥25 kg/m2 and 42.0% (178) had WC ≥80 cm. ORs (95%CIs) of general obesity across tertile distribution of energy-adjusted total BCAA intakes were 1.00, 0.81 (0.47, 1.37) and 0.62 (0.36, 1.07; P for trend = 0.08). A similar trend was observed across tertile distribution of energy-adjusted isoleucine, leucine and valine intakes. However, there was a statistically significant inverse association between total BCAA intake and odds of general obesity in a subset of non-smokers; 1.00, 0.68 (0.39, 1.20) and 0.55 (0.31, 0.98; P for trend = 0.04). CONCLUSION: We found a suggestive inverse association between higher dietary BCAA intake and odds of obesity in this sample of immigrant Filipino women, particularly among non-smokers. Prospective cohort studies among the immigrant population will be necessary to verity these findings.

Factors Associated with Body Weight Gain among Korean Adults during the COVID-19 Pandemic.

Background: Obesity is of grave concern as a comorbidity of coronavirus disease 2019 (COVID-19). We examined the factors associated with weight gain among Korean adults during the COVID-19 pandemic. Methods: We conducted an online survey of 1,000 adults (515 men and 485 women aged 20-59 years) in March 2021. Multivariable logistic regression analysis was performed to evaluate the factors associated with weight gain. The analysis was adjusted for sex, age, region, depressive mood, anxiety, eating out, late-night meals, alcohol consumption, exercise, sleep disturbance, meal pattern, subjective body image, comorbidities, marital status, living alone, and income. Results: After adjusting for confounding variables, the odds for weight gain increased in the group aged 20-34 years compared with the group aged 50-59 years (1.82; 95% confidence interval [CI], 1.01-3.32). Women were more associated with the risk of weight gain compared with men. The odds for weight gain increased in the lack of exercise group compared with the exercise group (4.89; 95% CI, 3.09-7.88). The odds for weight gain increased in the eating-out and late-night meal groups compared with that in the groups not eating out and not having late-night meals. Individuals watching a screen for 3-6 hr/day were more associated with the risk of weight gain compared with those who rarely watched a screen. The odds for weight gain increased in participants who considered themselves obese compared with those who did not consider themselves obese. Conclusion: A healthy diet and regular physical activity tend to be the best approach to reduce obesity, a risk factor for COVID-19.

Association Between Obesity and Cardiovascular Disease in Elderly Patients With Diabetes: A Retrospective Cohort Study.

CONTEXT: Some studies have suggested that patients with type 2 diabetes mellitus (T2DM) concomitant with obesity have better clinical outcomes than normal-weight patients with T2DM. OBJECTIVE: We evaluated associations among obesity, cardiovascular disease (CVD) events, and mortality in elderly patients with T2DM without CVD. METHODS: This retrospective observational study from 2009 to 2017, with a mean follow-up of 7.26 years, included 249 903 elderly (≥ 65 years) patients with T2DM and no preexisting CVD from the Korean National Health Information Database. We categorized subjects according to body mass index (BMI) and waist circumference (WC) and analyzed a composite of stroke, myocardial infarction, and all-cause death using Cox proportional hazards regression analysis, adjusting for baseline covariates. RESULTS: The incidence rate of composite primary outcomes was 30.95/1000 person-years. The primary outcome risk had an L-shaped and a U-shaped association with BMI and WC, respectively. In the multivariable Cox proportional hazard models, the risk of primary composite outcomes in the highest BMI group (≥ 30 kg/m2; hazard ratio [HR] = 0.824; 95% CI, 0.794-0.855) was lower than in the normal BMI group (≥ 18.5 and < 23 kg/m2). Conversely, that in the highest WC group (≥ 100 cm/≥ 95 cm; men/women; HR = 1.434; 95% CI, 1.384-1.486) was higher than in the normal WC group (< 90 cm/< 85 cm; men/women). CONCLUSION: Our study with elderly patients with diabetes results suggest that while BMI is an inadequate risk indicator for outcomes related to obesity, WC is a suitable alternative.

Blood Pressure and Cardiovascular Disease in Older Patients With Diabetes: Retrospective Cohort Study.

Background Blood pressure (BP) targets in elderly patients with diabetes remain unclear. We evaluated the association between BP and cardiovascular disease in elderly patients with diabetes without cardiovascular disease or heart failure. Methods and Results We performed a retrospective cohort study of 225 563 elderly (aged ≥65 years) patients with diabetes without cardiovascular disease or heart failure from 2009 to 2017 using the National Health Information Database. We divided the participants by systolic BP (SBP) and diastolic BP. Primary composite outcomes were stroke, myocardial infarction, heart failure, and all-cause death analyzed by Cox proportional hazards regression analysis adjusted for baseline covariates. During a median follow-up of 7.76 years, the incidence rate of primary composite outcomes was 26.62 per 1000 person-years. In multivariable Cox proportional hazard modeling, the risk of the primary outcome had a U-curved association with SBP/diastolic blood pressure with a nadir between 120 and 129 mm Hg/65 and 69 mm Hg, respectively. Hypertension medication was associated with lower risk of primary composite outcomes in SBP ≥140 mm Hg (P for interaction for SBP <0.001) and diastolic blood pressure ≥90 mm Hg (P for interaction for diastolic blood pressure=0.018). In participants aged ≥80 years, SBP ≥160 mm Hg was only a marginally higher risk for primary composite outcomes (hazard ratio=1.11; 95% CI, 0.98-1.24). Conclusions In this large sample of older Korean patients with diabetes, cardiovascular events were more common in people with resting SBP or diastolic BP ≥140 or 95 mm Hg, respectively, and also more common in people with resting SBP or diastolic BP <120 or 65 mm Hg, respectively.

Efficacy and Safety of Switching to Teneligliptin in Patients with Type 2 Diabetes Inadequately Controlled with Dipeptidyl Peptidase-4 Inhibitors: 52-Week Results from a Prospective Observational Study.

INTRODUCTION: The aim of this study was to assess the efficacy and safety of switching to teneligliptin from other dipeptidyl peptidase-4 (DPP-4) inhibitors in patients with type 2 diabetes mellitus (T2DM) inadequately controlled despite treatment with a stable dose of other DPP-4 inhibitors. METHODS: Patients with glycosylated hemoglobin (HbA1c) ≥ 7% despite taking DPP-4 inhibitors other than teneligliptin, with or without other antidiabetic agents, for at least 3 months were enrolled in this study. Patients on DPP-4 inhibitors administered prior to participation in this study were switched to 20 mg teneligliptin once daily and the dose was maintained for the 52-week study period. The primary endpoint was the change in HbA1c at week 12. Fasting plasma glucose (FPG) and the blood lipid profile were also evaluated. Adverse events were monitored for safety assessment. RESULTS: At weeks 12, 24, and 52, the HbA1c values significantly decreased by - 0.39, - 0.44, and - 0.52%, respectively, compared to the baseline value (p < 0.0001); in addition, 56.3, 60.3, and 62.3% of patients, respectively, achieved decreases in HbA1c of at least 0.3%, and 40.1, 46.5, and 52.4% of patients, respectively, achieved decreases in HbA1c of at least 0.5%. The proportion of the patient population achieving HbA1c < 7.0% increased throughout the study period, reaching 30.4, 35.4, and 36.9% at weeks 12, 24, and 52, respectively; at these same time points, the percentage of patients achieving HbA1c < 6.5% increased to 9.5, 11.9, and 13.2% of the total study population. FPG levels and lipid parameters were also significantly decreased after teneligliptin treatment. There were no significant safety concerns. CONCLUSION: Our results suggest the significant glucose-lowering effect of teneligliptin after switching from other DPP-4 inhibitors in patients with T2DM. The improvement in glycemic control was maintained for up to 52 weeks without safety concerns.

Association Between Diet Quality and Prevalence of Obesity, Dyslipidemia, and Insulin Resistance Among Filipino Immigrant Women in Korea: The Filipino Women's Diet and Health Study.

Objectives: Diet quality may be a key modifiable factor for the prevention of non-communicable disease. We aimed to investigate the association between diet quality and prevalence of obesity, dyslipidemia, and insulin resistance among Filipino immigrant women in Korea. Methods: A total of 413 participants from the 2014-2016 baseline population of the Filipino Women's Diet and Health Study (FiLWHEL) were examined. Individual dietary intakes were evaluated through 24-h recalls and then converted into two dietary quality assessments: Minimum Dietary Diversity for Women (MDD-W) developed by the Food and Agriculture Organization (FAO) and the Data Derived Inflammation Index (DDII) originally developed by our group. Fasting blood levels of triglycerides, high-density lipoprotein cholesterols, glucose, and insulin were measured. We used logistic regression models for odds ratios (ORs) with 95% confidence intervals (CIs). Results: We found a statistically significant association between MDD-W scores and decreased prevalence of abdominal obesity; ORs (95% CIs) of the 3rd vs. 1st tertiles were 0.58 (0.36-0.94; p for trend = 0.029). Increased DDII was associated with elevated prevalence of dyslipidemia and insulin resistance; ORs (95% CIs) of the 5th vs. 1-3rd quintiles were 6.44 (2.56-16.20) for triglycerides (TG), 3.90 (1.92-7.90) for low-density lipoprotein (LDL) cholesterol, 3.36 (1.81-6.24) for total cholesterol (TC), 6.25 (2.53-15.41) for abnormal TG/HDL ratios, 3.59 (1.96-6.59) for HbA1c, 2.61 (1.11-6.17) for fasting blood glucose levels, 9.67 (4.16-22.48) for insulin levels, and 9.73 (4.46-21.25) for homeostasis model assessment of insulin resistance (HOMA-IR) (p for trend <0.001 for all, except 0.033 for fasting blood glucose). Conclusions: Greater dietary diversity was inversely associated with the prevalence of abdominal obesity in Filipino immigrant women. Proinflammatory scores based on diet and lifestyle factors were associated with an increased prevalence of dyslipidemia and insulin resistance. Further, epidemiological studies on the relationship between dietary acculturation and chronic disease are warranted.

Cardiovascular safety of evogliptin in patients with type 2 diabetes: A nationwide cohort study.

AIM: To assess whether the use of evogliptin, a novel dipeptidyl peptidase-4 inhibitor (DPP-4i), was associated with an increased risk of cardiovascular events compared with glimepiride in patients with type 2 diabetes (T2D). METHODS: We conducted a population-based cohort study using South Korea's nationwide healthcare database from 1 January 2014 to 31 December 2018. We identified a base cohort of patients with T2D who newly initiated metformin monotherapy, from which we identified a study cohort of patients who either added or switched to glimepiride or DPP-4is (including evogliptin). Patients were followed up from initiation of DPP-4is or glimepiride until the earliest of either outcome occurrence or 31 December 2018. Our primary outcome was hospitalization or an emergency visit for cardiovascular events, a composite endpoint comprised of cerebrovascular events, heart failure, myocardial infarction, transient ischaemic attack, angina pectoris and revascularization procedures; secondary outcomes were the individual components of the primary outcome. A multivariable Cox proportional hazards model was used to estimate adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) for the risk of study outcomes associated with evogliptin compared with glimepiride. RESULTS: Our base and study cohorts had 317,307 and 128,788 patients, respectively, of which 100,038 were DPP-4i users (2946 were evogliptin users) and 28,750 were glimepiride users within the study cohort. The median follow-up was 195 days for evogliptin and 113 days for glimepiride users. Compared with glimepiride, evogliptin was associated with a reduced risk of the primary outcome (aHR 0.67, 95% CI 0.48-0.95) and cerebrovascular events (aHR 0.41, 95% CI 0.22-0.78) but showed non-significant associations for myocardial infarction (aHR 0.63, 95% CI 0.27-1.46), heart failure (aHR 0.35, 95% CI 0.09-1.47), transient ischaemic attack (aHR 0.23, 95% CI 0.03-1.72) and angina pectoris (aHR 1.35, 95% CI 0.82-2.21). CONCLUSIONS: Findings from this population-based cohort study provide novel real-world evidence that the use of evogliptin, compared with glimepiride, did not increase the risk of cardiovascular events, including cerebrovascular events, myocardial infarction, heart failure, transient ischaemic attack and angina pectoris.

Effects of bisphenol A on cardiovascular disease: An epidemiological study using National Health and Nutrition Examination Survey 2003-2016 and meta-analysis.

As the most widely consumed endocrine-disrupting chemical, bisphenol A (BPA) has been linked to reproductive dysfunction, diabetes mellitus, and obesity. However, the evidence for an association between BPA and cardiovascular disease (CVD) remains insufficient. In the present study, we aimed to identify the association between BPA and CVD, using data from the 2003-2016 National Health and Nutrition Examination Surveys (NHANES). We estimated urine BPA concentration after adjustments for creatinine (ng/mg) and normalized the asymmetrical distribution using natural logarithmic transformation (ln-BPA/Cr). A multivariate logistic regression was performed to evaluate the odds ratio (OR) and 95% confidence interval (CI) for CVD, with ln-BPA/Cr concentration as predictor. We then performed a Mantel-Haenszel meta-analysis with five eligible studies and NHANES 2003-2016 data. Our subjects were 11,857 adults from the NHANES data. After adjusting for age, sex, race/ethnicity, body mass index (BMI), cigarette smoking, diabetes status, hypertension, and dyslipidemia, OR between ln-BPA/Cr and CVD was 1.13 (95% CI: 1.02-1.24). After propensity-score-matching with age, sex, race/ethnicity, BMI, cigarette smoking, diabetes, hypertension, and dyslipidemia, OR continued to be significant for the association between ln-BPA/Cr and CVD (OR: 1.18, 95% CI: 1.04-1.33). A restricted cubic spline plot of this relationship revealed a dose-dependent increase in OR. However, untransformed BPA had a linear relationship with CVD only at low concentrations, whereas the OR of BPA plateaued at high concentrations. In a meta-analysis with 22,878 subjects, after adjusting for age, sex, and various cardiometabolic risk factors, OR was 1.13 (95% CI, 1.03-1.23). In conclusion, our study provides additional epidemiological evidence supporting an association between BPA and CVD.