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In October 2022, the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) updated the previous consensus report for management of hyperglycemia in type 2 diabetes (T2DM). In January 2023, ADA Standards of Care in Diabetes with pharmacologic approaches to achieve a glycemic target were published to align with the consensus report by ADA and EASD. This recent consensus report and ADA Standards of Care in Diabetes emphasized weight management as an important aspect of the holistic approach to management of T2DM. In addition, it included numerous results of cardiorenal trials involving glucagon-like peptide 1 (GLP-1) receptor agonist and sodium glucose cotransporter 2 (SGLT2) inhibitor in type 2 diabetes. This information was added to address broader recommendations for cardiorenal risk reduction, in particular for organ (heart and kidney)-specific protection. This review summarizes the 2022 ADA-EASD consensus report and 2023 ADA standards of care for diabetes regarding management of hyperglycemia in T2DM.

Background: Previous studies have reported that abnormal glucose metabolism is associated with poor cancer outcomes. Glycated hemoglobin A1c (HbA1c) is an important indicator of glucose metabolism. This study aimed to investigate the relationship between nondiabetic HbA1c levels and cancer-related mortality. Methods: This was a retrospective cohort study of Koreans who attended an annual or biennial health checkup program. The study group was categorized based on the quintile of HbA1c level (Q1, 3.0–5.1%; Q2, 5.2–5.3%; Q3, 5.4%; Q4, 5.5–5.6%, Q5, 5.7–6.4%). Cancer-related mortality was determined using the mortality data from the Korea National Statistical Office. Participants with an established diagnosis of diabetes or cancer were excluded. Cancer-related mortality was assessed depending on each HbA1c level with adjustment for factors that could influence mortality. Results: A total of 589,457 participants were included in this study. During a median follow-up duration of 6.99 years, 1712 cancer-related deaths were reported. The risk of cancer-related mortality was significantly higher in the Q5 group (hazard ratio (HR) 1.23, range 1.02–1.47 in model 1; HR 1.25, range 1.04–1.50 in model 2). HbA1c levels were linearly associated with cancer-related deaths (Ptrend = 0.021 in model 1; 0.013 in model 2). HbA1c level and colorectal, stomach, and lung cancer mortality exhibited a positive relationship, whereas liver cancer-related mortality showed an inverse relationship with HbA1c level (Ptrend = 0.001). Conclusions: Our study showed that abnormal glucose metabolism is significantly associated with cancer-related mortality, and its relationship varies with each type of cancer.

Background: This study aimed to evaluate the dose-dependent effects of smoking on risk of diabetes among those quitting smoking.Methods: We analyzed clinical data from a total of 5,198,792 individuals age 20 years or older who received health care check-up arranged by the national insurance program of Korea between 2009 and 2016 using the Korean National Health Insurance Service database. Cumulative smoking was estimated by pack-years. Smokers were classified into four categories according to the amount of smoking: light smokers (0.025 to 5 smoking pack-years), medium smokers (5 to 14 smoking pack-years), heavy smokers (14 to 26 smoking pack-years), and extreme smokers (more than 26 smoking pack-years).Results: During the study period, 164,335 individuals (3.2% of the total population) developed diabetes. Compared to sustained smokers, the risk of diabetes was significantly reduced in both quitters (hazard ratio [HR], 0.858; 95% confidence interval [CI], 0.838 to 0.878) and nonsmokers (HR, 0.616; 95% CI, 0.606 to 0.625) after adjustment for multiple risk factors. The risk of diabetes gradually increased with amount of smoking in both quitters and current smokers. The risk of diabetes in heavy (HR, 1.119; 95% CI, 1.057 to 1.185) and extreme smokers (HR, 1.348; 95% CI, 1.275 to 1.425) among quitters was much higher compared to light smokers among current smokers.Conclusion: Smoking cessation was effective in reducing the risk of diabetes regardless of weight change. However, there was a potential dose-dependent association between smoking amount and the development of diabetes. Diabetes risk still remained in heavy and extreme smokers even after smoking cessation.

Background: Increased coronary artery calcification (CAC) has been reported in individuals with high levels of physical activity (PA). However, the association between increased CAC in a physically active population and cardiovascular mortality has not yet been well-established. This study aimed to investigate the association between PA levels and the presence or absence of CAC and cardiovascular mortality. Methods: A cohort study was conducted from 1 January 2011 to 30 December 2019. Mortality data were updated until 30 December 2020. The study population comprised 56,469 individuals who had completed the International Physical Activity Short Form Questionnaire and had undergone CAC score evaluation using a CT scan. We divided the participants into four groups: physically inactive individuals without CAC, physically inactive individuals with CAC, moderately active and health-enhancing physically active (HEPA) individuals without CAC, and moderately active and HEPA individuals with CAC. The primary outcome was cardiovascular mortality. The Cox proportional hazard model with confounding factor adjustment was conducted. Inverse probability of treatment weighting-based marginal-structural modelling was conducted. Results: The median follow-up duration was 6.60 years. The mean (SD) age of the study participants was 41.67 (±10.91) years, with 76.78% (n = 43,359) men. Compared with individuals without CAC, individuals with CAC demonstrated higher cardiovascular disease mortality regardless of PA level (Inactive and CAC > 0, HR 2.81, 95% CI: 1.76–19.19; moderately active and HEPA HR 3.27, 95% CI: 1.14–9.38). Conclusions: The presence of CAC might be associated with cardiovascular mortality regardless of PA level.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease, and yet the natural course remains unclear. Study population included 36,195 individuals who participated in a health-screening program and diagnosed with fatty liver by abdominal ultrasound. Participants were provided written information regarding fatty liver and advised to make lifestyle changes. Ultrasound was repeated after at least 6 months. After a mean follow up of 4.9 years (±3.4), 19.6% resolved their fatty liver. Individuals who resolved were more likely female (22.9% vs. 12.3%), thinner (body mass index [BMI], 25.2 ± 2.7 vs. 26 ± 2.7), and with lower HOMA-IR (1.4 vs. 1.7) (P .70.001). Decrease in BMI predicted resolution of fatty liver with 42% of those in the top quartile of BMI decline resolving compared with 5.7% in the lowest quartile (odds ratio [OR] (95% confidence interval [CI]) 15.65 (14.13–17.34), P P

Obesity increases the risks of diabetes, hypertension, and cardiovascular diseases, ultimately contributing to mortality. Korean Society for the Study of Obesity (KSSO) was established to improve the management of obesity through research and education; to that end, the Committee of Clinical Practice Guidelines of KSSO reviews systemic evidence using expert panels to develop clinical guidelines. The clinical practice guidelines for obesity were revised in 2018 using National Health Insurance Service Health checkup data from 2006 to 2015. Following these guidelines, we added a category, class III obesity, which includes individuals with body mass index (BMI) ≥35 kg/m². Agreeing with the International Federation for the Surgery of Obesity and Metabolic Disorders, Asian Pacific Chapter consensus, we determined that bariatric surgery is indicated for Korean patients with BMI ≥35 kg/m² and for Korean patients with BMI ≥30 kg/m² who have comorbidities. The new guidelines focus on guiding clinicians and patients to manage obesity more effectively. Our recommendations and treatment algorithms can serve as a guide for the evaluation, prevention, and management of overweight and obesity.

Background Large waist circumference (WC) is a risk factor for several site-specific cancers, but a large-scale systematic investigation across all common cancers adjusted for potential confounders has not been conducted. This study aimed to evaluate the possible links between WC and common cancers. Methods We prospectively examined the association between WC and the risk of cancers in a 7-year cohort study of nearly 22.9 million Korean adults. Using the claims database merged with the national health check-up data, we fitted proportional hazard models to investigate associations between WC and 23 of the most common cancers, with adjustment for potential confounders, including body mass index (BMI). We also evaluated the modification of BMI on the relationships between WC and the incidence of cancer. Results A total of 769,871 cancer cases were identified. WC was positively associated with 18 of 23 cancers, and the effects varied substantially by site in each sex. The modification of BMI on the WC-cancer association also varied across the cancer site; in most cases it mitigated the association. For cancers of the oral cavity, larynx, oesophagus, lung, and premenopausal breast, the BMI adjustment reversed the association toward being positive (all Ptrend

BACKGROUND Hypoglycemia is an important complication in the treatment of patients with diabetes. We surveyed the insight by patients with diabetes into hypoglycemia, their hypoglycemia avoidance behavior, and their level of worry regarding hypoglycemia. METHODS A survey of patients with diabetes, who had visited seven tertiary referral centers in Daegu or Gyeongsangbuk-do, Korea, between June 2014 and June 2015, was conducted. The survey contained questions about personal history, symptoms, educational experience, self-management, and attitudes about hypoglycemia. RESULTS Of 758 participants, 471 (62.1%) had experienced hypoglycemia, and 250 (32.9%) had experienced hypoglycemia at least once in the month immediately preceding the study. Two hundred and forty-two (31.8%) of the participants had received hypoglycemia education at least once, but only 148 (19.4%) knew the exact definition of hypoglycemia. Hypoglycemic symptoms identified by the participants were dizziness (55.0%), sweating (53.8%), and tremor (40.8%). They mostly chose candy (62.1%), chocolate (37.7%), or juice (36.8%) as food for recovering hypoglycemia. Participants who had experienced hypoglycemia had longer duration of diabetes and a higher proportion of insulin usage. The mean scores for hypoglycemia avoidance behavior and worry about hypoglycemia were 21.2±10.71 and 23.38±13.19, respectively. These scores tended to be higher for participants with higher than 8% of glycosylated hemoglobin, insulin use, and experience of emergency room visits. CONCLUSION Many patients had experienced hypoglycemia and worried about it. We recommend identifying patients that are anxious about hypoglycemia and educating them about what to do when they develop hypoglycemic symptoms, especially those who have a high risk of hypoglycemia.

Although postmenopausal breast cancer (BC) risk has been linked to adiposity, associations between adiposity and premenopausal BC remain unclear. To address this question, we investigated the association of BC risk with measures of adiposity, including body mass index (BMI) and waist circumference (WC), in a large cohort of Asian women. We used a nationwide cohort of adult Korean women selected from the National Health Insurance Corporation database merged with national health examination data from 2009 to 2015. A total of 11,227,948 women were tracked to retrospectively identify incident cases of BC. Our analysis used Cox proportional hazards models to calculate hazard ratios and assess the association of BC risk with BMI and/or WC in both pre- and postmenopausal women. BMI and WC were robustly associated with increased risk for postmenopausal BC (ptrend

Aims Urine albumin creatinine ratio (UACR) is a reliable index of urinary albumin excretion. Elevated UACR is known to be associated with increased risk for diabetes complications. However there is only limited information about the predictability of UACR within normal range for diabetes. Therefore, this study was designed to investigate the association between UACR within the normal range and the development of diabetes. Methods The 1410 non-diabetic Korean men with UACR within the normal range were identified in 2005 and followed-up until 2010. All subjects were classified into four categories according to their baseline level of UACR, from the lowest to the highest quartile. Cox proportional hazards analysis was used to evaluate the independent hazard ratios (HRs) for diabetes according to the UACR levels of their quartile group. Results During follow-up, diabetes developed in 114 out of 1410 subjects (8.1%), and incidence of diabetes increased in proportion to the level of UACR (quartile 1; 4.5%, quartile 2; 7.9%, quartile 3: 8.8%, quartile 4: 11.1%, p = 0.002). The subjects with incident diabetes had a higher UACR than those without incident diabetes (6.6 ± 5.5 μg/mg v 5.3 ± 4.2 μg/mg, p = 0.013). When quartile 1 was considered as the reference, HRs (95% confidential interval) for diabetes was higher in quartile 2 (1.04; 0.45–2.38), quartile 3 (1.09; 0.47–2.52) and quartile 4 (2.16; 1.02–4.57), even after adjusting for other potential confounders. Conclusions Elevated UACR, even within the normal range, could predict the future development of diabetes.

Background/Aims: The aim was to determine which of three sets of metabolic syndrome (MetS) criteria (International Diabetes Federation [IDF], National Cholesterol Education Program Adult Treatment Panel III [ATP III], and European Group for the Study of Insulin Resistance [EGIR]) best predicts the coronary artery calcification (CAC) score in a cross-sectional study. This has not been evalu ated in previous studies. Methods: A total of 24,060 subjects were screened for CAC by multi-detector computed tomography. The presence of CAC was defined as a CAC score > 0. The odds ratio for the presence of CAC was analyzed for three different sets of MetS criteria and according to number of MetS components. Results: CAC was observed in 12.6% (3,037) of the subjects. Patients with MetS, as defined by the IDF, ATP III, and EGIR criteria, had a CAC rate of 23.0%, 25.1%, and 29.5%, respectively (p < 0.001). Comparisons of C statistics for multivariate regression models revealed no significant difference among the three sets of cri teria. After adjustment for risk factors, the ATP III criteria produced a slightly higher odds ratio for CAC compared with the other criteria, but this difference was not significant. The risk factor-adjusted odds ratio for the presence of CAC increased from 1 to 1.679 as the number of MetS components defined by ATP III increased from 0 to ≥ 3 (p for trend < 0.001). Conclusions: The presence of MetS was associated with the presence of CAC. There was no significant difference among the three sets of MetS criteria in terms of the ability to predict CAC. An increase in the number of MetS components was associated with an increased odds of CAC.

Metabolically healthy obesity (MHO) is a new concept in which an individual may exhibit an obese phenotype in the absence of any metabolic abnormalities. There are a number of definitions of MHO that utilize a variety of components. The findings of clinical and basic studies indicate that subjects with MHO do not exhibit an increased mortality, an increased risk of cardiovascular disease, or an increased risk of type 2 diabetes mellitus, as compared to normal-weight controls. Although these findings imply that metabolic health is a more important factor than obesity, several studies have shown that subjects with MHO have a similar risk of metabolic or cardiovascular diseases as those with metabolically unhealthy obesity. Thus, there is still debate regarding not only the implications of the MHO phenotype but its very existence. Accordingly, future studies should focus on developing a unified definition of MHO and distinguishing subjects who will be at a high risk for metabolic and cardiovascular diseases.

Although postmenopausal breast cancer (BC) risk has been linked to adiposity, associations between adiposity and premenopausal BC remain unclear. To address this question, we investigated the association of BC risk with measures of adiposity, including body mass index (BMI) and waist circumference (WC), in a large cohort of Asian women. We used a nationwide cohort of adult Korean women selected from the National Health Insurance Corporation database merged with national health examination data from 2009 to 2015. A total of 11,227,948 women were tracked to retrospectively identify incident cases of BC. Our analysis used Cox proportional hazards models to calculate hazard ratios and assess the association of BC risk with BMI and/or WC in both pre- and postmenopausal women. BMI and WC were robustly associated with increased risk for postmenopausal BC (p

BACKGROUND Urinary albumin levels and hypertension (HTN) are independently associated with an increased risk of all-cause mortality. The effect of albuminuria on mortality in the absence or presence of HTN is uncertain. This study aimed to evaluate the effect of albuminuria and HTN on all-cause and cardiovascular disease (CVD) mortality. METHODS Mortality outcomes for 32,653 Koreans enrolled in a health screening including measurements of the urinary albumin/creatinine ratio (UACR) at baseline and median follow-up of 5.13 years. Receiver operating characteristic curve analyses were performed in UACR and the cut-point was 5.42 mg/g. The participants for UACR at the cut-point of 5.42 μg/mg were categorized into UACR < 5.42 or UACR ≥ 5.42. HTN status was categorized as No HTN or HTN (defined as the absence or presence HTN). RESULTS The median (interquartile) baseline UACRs were higher in those who died than in survivors. Subjects with a UACR ≥ 5.42 mg/g without or with HTN showed a similar increased risk for all-cause mortality and CVD mortality, even after adjusting for known CVD risk factors compared to those with no HTN/UACR < 5.42 (reference), (all-cause mortality; hazard ratio [HR] 1.48; 95% confidence interval [CI] 1.02–2.15: HR 1.47; 95% CI 0.94–2.32, respectively), (CVD mortality; HR 5.75; 95% CI 1.54–21.47: HR 5.87; 95% CI 1.36–25.29) CONCLUSIONS The presence of urinary albumin and HTN is a significant determinant of CVD and death. Urinary albumin might be more attributable to CVD and all-cause mortality than HTN.

Obesity increases the risks of diabetes, hypertension, and cardiovascular diseases, ultimately contributing to mortality. Korean Society for the Study of Obesity (KSSO) was established to improve the management of obesity through research and education; to that end, the Committee of Clinical Practice Guidelines of KSSO reviews systemic evidence using expert panels to develop clinical guidelines. The clinical practice guidelines for obesity were revised in 2018 using National Health Insurance Service Health checkup data from 2006 to 2015. Following these guidelines, we added a category, class III obesity, which includes individuals with body mass index (BMI) ≥35 kg/m

There have been several reports about the clinical association between type 2 diabetes mellitus (DM) and nonalcoholic fatty liver disease (NAFLD). However, most of the studies were about the unilateral effects of type 2 DM on NAFLD, and studies on the reverse relation are rare. Thus, this study was designed to investigate the effect of NAFLD on type 2 DM. We conducted a prospective cohort study on 25,232 Korean men without type 2 DM for 5 years. We serially checked the various metabolic factors including fasting glucose and hemoglobin A1c (HbA1c), and monitored the development of type 2 DM. The incidence rate of type 2 DM was compared according to the degree of NAFLD (normal, mild, and moderate to severe), and a Cox proportional hazards model was used to measure the hazard ratios (HRs) of NAFLD on type 2 DM. The incidence rate of type 2 DM increased according to the degree of NAFLD (normal: 7.0%, mild: 9.8%, moderate to severe: 17.8%, P < 0.001). Even after adjusting for other multiple covariates, the HRs (95% confidence interval [CI]) for type 2 DM development was higher in the mild group (1.09; 0.81-1.48) and moderate to severe group (1.73; 1.00-3.01) compared to the normal group, respectively (P for trend

Background: Tumor necrosis factor (TNF)-α is associated with insulin resistance and systemic inflammatory responses. The aim of this study was to investigate the relationship between TNF-α and the development of nonalcoholic fatty liver disease (NAFLD) in a longitudinal study. Methods: Three hundred and sixty-three apparently healthy subjects (mean age, 40.5±6.1 years; male, 57.6%) without NAFLD were enrolled in 2003. Anthropometric and laboratory measurements were performed. The participants were grouped into tertiles according to their serum TNF-α levels from samples taken in 2003. At a 4-year follow-up, we compared the odds ratios (ORs) of the development of NAFLD according to the tertiles of TNF-α levels measured in 2003. Results: At the 4-year follow-up, the cumulative incidence of NAFLD was 29.2% (106/363). The group that developed NAFLD had higher levels of TNF-α than those in the group without NAFLD (3.65±1.79 pg/mL vs. 3.15±1.78 pg/mL; P=0.016). When the 2003 serum TNF-α levels were categorized into tertiles: incidence of NAFLD observed in 2007 was significantly higher with increasing tertiles (22.6%, 35.8%, and 41.5%, respectively; P

Recent data suggest that variations in calcium intake may influence body weight and composition; however, the relationship between daily calcium intake and muscle mass has not been well established. The objective of this study was to assess the relationship between daily calcium intake and sarcopenia. We analyzed data for older adults (over 60 years) from the fourth Korea National Health and Nutrition Examination Survey (KNHANES) conducted in 2009. A total of 1339 Non-Obese (BMI between 18.5 and 25 kg/m2), older adults (592 men and 707 women) were enrolled. Dietary variables were assessed using a nutrition survey that used a 24-hour recall method. Daily calcium intake based on the consumption of each food item was calculated. Sarcopenia was defined as an appendicular skeletal muscle mass divided by body weight less than 2 SD below the sex-specific mean for young adults. We found that daily calcium intake was negatively correlated with total body fat percentage and positively correlated with appendicular skeletal mass (p

Aims Low-grade inflammation and lipotoxicity contribute to insulin resistance and islet secretory dysfunction that lead to insulin deficiency. We analyzed the associations of several adipocytokines measured at baseline with glycemic progression in non-diabetic Korean subjects after a 4-year follow-up. Methods In 479 non-diabetic Korean subjects who underwent medical screening in 2003, serum tumor necrosis factor (TNF)-α, interleukin (IL)-6, retinol-binding protein (RBP)-4, monocyte chemoattractant protein (MCP)-1, visfatin and fatty acid-binding protein (FABP)-4 were measured at baseline. After 4 years, changes in glycemia were assessed. Results Among the subjects, 79.2% maintained their baseline glycemic status, 14.6% progressed to worse glycemic status (impaired fasting glucose (IFG) to diabetes, normoglycemia to IFG or normoglycemia to diabetes) and 5.8% regressed to normoglycemia after 4 years. Baseline TNF-α and FABP4 showed the highest values in the progression group. In the logistic regression analyses with glycemic progression as the dependent variable and TNF-α and FABP4 as independent variables in separate models, TNF-α and FABP4 individually predicted glycemic progression after adjustment for confounding variables. When both adipocytokines were included in the same model, only FABP4 significantly predicted glycemic progression after 4 years. Conclusions TNF-α and FABP4 were significant predictors for glycemic progression in 4 years, with FABP4 being the stronger predictor.

The aim of this study is to investigate whether the beneficial effect of exendin-4 on hepatic steatosis is mediated by β-catenin signaling. After the HepG2 human hepatoma cells were treated with PA for 24 hours, total triglycerides levels were increased in a dose-dependent manner, and the expression levels of perilipin family members were upregulated in cells treated with 400 μM PA. For our in vitro model of hepatic steatosis, HepG2 cells were treated with 400 μM palmitic acid (PA) in the presence or absence of 100 nM exendin-4 for 24 hours. PA increased the expression of lipogenic genes, such as sterol regulatory element-binding protein 1c (SREBP-1c), peroxisome proliferator-activated receptor gamma (PPARγ), stearoyl-CoA desaturase 1 (SCD1), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) and triglyceride synthesis-involved genes, such as diacylglycerol acyltransferase 1 (DGAT1) and diacylglycerol acyltransferase 2 (DGAT2) in HepG2 cells, whereas exendin-4 treatment significantly prevented the upregulation of SREBP-1c, PPARγ, SCD1, FAS, ACC, DGAT1 and DGAT2. Moreover, exendin-4 treatment increased the expression of phosphorylated glycogen synthase kinase-3 beta (GSK-3β) in the cytosolic fraction and the expression of β-catenin and transcription factor 4 (TCF4) in the nuclear fraction. In addition, siRNA-mediated inhibition of β-catenin upregulated the expression of lipogenic transcription factors. The protective effects of exendin-4 on intracellular triglyceride content and total triglyceride levels were not observed in cells treated with the β-catenin inhibitor IWR-1. These data suggest that exendin-4 treatment improves hepatic steatosis by inhibiting lipogenesis via activation of Wnt/β-catenin signaling.

Traditional lipid measures are known to be associated with incident type 2 diabetes.Our objective was to assess the independent association between lipid profiles and the development of type 2 diabetes in nondiabetic Korean subjects over a 4-yr period.A total of 5577 Koreans without diabetes who underwent consecutive comprehensive health check-ups annually for 5 yr were enrolled. We measured concentrations of total cholesterol (TC), triglyceride (TG), apolipoprotein B (apoB), apolipoprotein A-I, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) and calculated lipid ratios. The association between incident type 2 diabetes and the initial values for lipid ratios and other lipoprotein components was examined.Over the course of 4 yr, 330 subjects (5.9%) developed type 2 diabetes. TC, LDL-C, TG, non-HDL, apoB, apoB to apolipoprotein A-I ratio, TC to HDL ratio, TG to HDL ratio, LDL to HDL ratio and apoB to HDL ratio were associated with incident type 2 diabetes in multivariate analysis after adjustment for age and gender. Of these, the ratio of TC to HDL and apoB to HDL showed a significant association with increased risk of type 2 diabetes, compared with other lipoprotein parameters: odds ratio (1.340, 95% confidence interval 1.166-1.538; and 1.338, 95% confidence interval 1.162-1.540), respectively. The odds ratio for the development of type 2 diabetes increased significantly as the tertiles of the baseline ratio of TC to HDL and apoB to HDL increased from the first to the third tertile.This study suggests that lipid and lipoprotein profiles can be independently associated with later development of type 2 diabetes in nondiabetic Korean adults in a longitudinal analysis.

Background: Hypertension is common in patients with type 2 diabetes, affecting up to 60% of patients. The Korean Diabetes Association performed a nationwide survey about prevalence, awareness and control of hypertension among diabetic Koreans. Methods: The current survey included 3,859 diabetic patients recruited from 43 hospitals in Korea. Age, gender, height, weight and blood pressure (BP) were measured by standard methods. Data on fasting plasma glucose, glycosylated hemoglobin (HbA1c), awareness of hypertension, and compliance of antihypertensive medication were collected via interview and reviewed using patient medical records. Results: A total of 57.5% of all patients were >60 years old. Their mean HbA1c was 7.6±1.5%. Among antihypertensive medi cation users, 39.9% had

BackgroundRecent studies have suggested that metabolic health may contribute more to the atherosclerosis than obesity. The aim of this study is to compare coronary artery calcium scores (CACS) among patients with different metabolic health and obesity status.MethodsA health-screening program of 24,063 participants (mean age 41 years) was conducted, and CACS was assessed by multi-detector computerized tomography (MDCT). Being metabolically healthy was defined as having fewer than two of the following risk factors: high blood pressure, high fasting blood glucose, high triglyceride, low high-density lipoprotein cholesterol, highest decile of homeostasis model assessment-insulin resistance (HOMA-IR) index, and highest decile of high-sensitivity C-reactive protein (hs-CRP). Obesity status was defined as body mass index (BMI) higher than 25 kg/m(2). Analyses were performed in four groups divided according to metabolic health and obesity: metabolically healthy non-obese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy non-obese (MUHNO), and metabolically unhealthy obese (MUHO).ResultsMean values of CACS in the four groups were significantly different, except those between MHNO and MHO and between MUHNO and MUHO. When multinomial logistic regression analysis was performed with five CACS categories as the dependent variables and after adjusting for age, sex, and smoking status, the MHO, MUHNO, and MUHO groups showed significantly increased odds ratio for increasing CACS categories compared with no calcification status (5.221 for CACS >400 in MUHO group with 95% CI 2.856∼5.032 with MHNO group as the reference). When other variables including the metabolic parameters were included in the same model, the risks were attenuated.ConclusionMetabolic health is more closely associated with subclinical atherosclerosis than obesity as assessed by CACS.

Background: We investigated the association of coronary artery calcium score (CACS) with body composition and insulin resistance in apparently healthy Korean adults. Methods: Nine hundred forty-five participants (mean age, 48.9 years; 628 men) in a medical check-up program were selected for analysis. Body composition was assessed by bioelectrical impedance analysis (BIA). Insulin resistance was evaluated using the homeostasis model assessment of insulin resistance (HOMA-IR). The CACS was assessed by multidetector computed tomography. Results: One hundred forty-six subjects (15.4%) showed coronary artery calcification and 148 subjects (15.7%) had metabolic syndrome. CACS showed a significant positive correlation with age, fasting glucose level, waist circumference (WC), blood pressure, hemoglobin A1c, HOMA-IR, and waist-hip ratio (WHR) assessed by BIA. CACS had a negative correlation with high density lipoprotein cholesterol (HDL-C). Subjects with high CACS showed significantly higher mean WHRs and lower mean values for lean body mass compared with subjects without coronary artery calcification. In logistic regression analyses with coronary artery calcification as the dependent variable, the highest quartile of WHR showed a 3.125-fold increased odds ratio for coronary artery calcification compared with the lowest quartile after adjustment for confounding variables. When receiver operating characteristics analyses were performed with coronary artery calcification as the result variable, WHR showed the largest area under the curve (AUC) value among other variables except for age and WC in women (AUC=0.696 for WHR, 0.790 for age, and 0.719 for WC in women). Conclusion: In our study population of apparently healthy Korean adults, WHR was the most significant predictor for coronary artery calcification among other confounding factors, suggesting that it may have implication as a marker for early atherosclerosis.

Breast metastases from an extramammary primary tumor are very rare and the prognosis for such patients is generally poor. We report here on a case of a 42-year-old female with metastasis of non-small cell lung cancer to the breast, and she is now being followed up on an outpatient basis. In 2004, she presented with a solitary pulmonary nodule in the left lung, and this lesion had been noted to have gradually increased in size over time. The final pathological diagnosis was adenocarcinoma, and the diagnosis was made by performing percutaneous needle aspiration and lobectomy of the left upper lobe. Adjuvant chemotherapy and radiotherapy were given. Unfortunately, a nodule in the left breast was noted three years later, and metastatic non-small-cell lung cancer to the breast was diagnosed by excisional biopsy. Making the correct diagnosis to distinguish a primary breast carcinoma from a metastatic one is important, because the therapeutic plan and outcome for these two types of cancer are quite different.

성지방 상승이 관찰되었다. 폐경 여성에서 이러한 지질대사 이상이 나타나는 이유 중 유전적 원인이 많은 기여를 하는 것으로 알려져 있다. Kim 등[4]은 폐경 후 여성에서 APOA5의 유전자 다형성으로 인한 지질대사 이상이 대사증후군에 미치는 영향을 설명하고자 하 였다. 국내에서도 최근 APOA5 유전자형과 관상동맥질환 및 당뇨병과의 연관성에 대한 연구가 일부 보고된 바 있고[9,10], APOA5 유전자형 과 대사증후군의 연관성에 대해서는 외국에서의 보고들은 있었으 나[11-13], 국내에서는 대사증후군과의 관련성에 대한 연구는 보고 된 바 없었다. Kim 등[4]의 연구 결과에 의하면, APOA5 -1131T>C 유전자 다형성에 따른 대사증후군 유병률의 비교에서, TT 유전자형 이 27.09%로 TC와 CC 유전자형의 38.46%와 45.71%에 비해 유의적 으로 낮게 나타났다. 대사증후군 위험인자를 이용한 회귀분석에서 도 CC 유전자형의 위험도가 TT 유전자형에 비해 3배 높게 나타났으 며 중성지방에서 APOA5 1131C carrier 유전자형인 CC와 TC+CC의 교차비는 각각 2.39와 1.85로 유의적인 위험도 증가를 보고하고 있 다. 그러나, 고밀도지단백질 콜레스테롤은 APOA5 유전자 다형성에 의한 영향보다 중성지방에 의해 직접적으로 영향을 받는 것으로 나 타난 것으로 분석되었다. 이는 Jang 등[14]이 한국인 관상동맥질환자 및 대조군에서 관찰한 같은 유전자 위의 연구 결과와 유사한 것으 로서, TC 또는 CC 유전자형을 가진 군에서 TT군에 비해 혈중 중성 지방 농도가 높았다. 혈중 APOA5 단백 농도는 TT군에서 제일 높았 고 TT, TC, CC의 순서대로 유의하게 낮게 관찰되었으며, 관상동맥질

See Article on Page 277-284 Disturbed sleep was recently proposed as a novel risk factor for type 2 diabetes mellitus (T2DM). Experimental restriction of sleep to 4 hours per night for 6 nights resulted in impaired glucose tolerance in healthy young adults [1]. Because diabetes carries a high risk of cardiovascular mortality, the impact of sleep restriction on glucose regulation suggests a mechanism linking short sleep time and increased mortality. The term sleep-disordered breathing (SDB) encompasses a range of breathing abnormalities that occur during sleep. These include obstructive sleep apnea (OSA), central sleep apnea, and periodic breathing. SDB may be more common in people with T2DM. Some risk factors for diabetes, including obesity, visceral adiposity, and advancing age are also associated with SDB. Evidence from a growing body of research suggests that SDB is associated with adverse cardiovascular disease (CVD) risk factors and outcomes including hypertension and myocardial infarction. Similarly, CVD risk is substantially elevated among people with diabetes. Since diabetes and SDB not only share important risk factors, but may also be associated with CVD, the two conditions may be related to one another [2-5]. Recent research has demonstrated the likelihood of a relationship between T2DM and OSA, the most common form of SDB. The International Diabetes Federation (IDF) [6] consensus statement on sleep apnea and T2DM raises awareness of the association between the two conditions, which has significant implications on public health and on the lives of individuals. According to the IDF, estimates suggest that up to 40% of people with OSA have diabetes [3,6], but the incidence of new cases of diabetes in people with OSA is not known. In people who have diabetes, the prevalence of OSA may be up to 23%, and the prevalence of some form of SDB may be as high as 58%. Overweight and obesity may play a role, but some recent studies have shown that the association between SDB and diabetes is independent of overweight/obesity. OSA may affect glycemic control in people with T2DM, and it is associated with a range of cardiovascular complications such as hypertension, stroke, and heart failure. Although early studies indicated a possible causal association between the presence of OSA and the development of T2DM, several of these studies had significant limitations including small sample size, highly selected population, inadequate adjustment for confounders, and use of surrogate measures such as snoring to assess OSA. The Wisconsin Sleep Cohort Study showed a significant cross-sectional association between OSA and T2DM for all degrees of OSA, which was preserved in participants with moderate to severe OSA after adjustment for obesity (odds ratio, 2.3) [7]. However, the longitudinal data from the same study showed that after adjusting for obesity, OSA at baseline was not a significant predictor for the development of diabetes over 4 years. In this issue, Shim et al. [8] reported that sleep disorder (SD) was prevalent in Korean patients with T2DM and that OSA could aggravate the risk of cardiovascular disease. They enrolled 784 patients with T2DM and measured sleep quality using the self-administered Pittsburgh Sleep Quality Index and determined the risk of OSA using the Berlin Questionnaire. The findings from this study are important because few studies have investigated the association between sleep quality and the risk of OSA, particularly in Asians. Among the patients, 38.4% had poor sleep quality and 15.8% were at high risk for OSA. The frequency of risk for OSA was higher in patients who were obese compared to nonobese patients, and the logistic regression analysis revealed male gender and body mass index as independent predictors of risk for OSA. OSA is common in patients with T2DM, and identifying the mechanisms that underlie this condition and determining the effective treatment options are important. Laboratory studies in healthy subjects have shown that low cerebral glucose utilization, elevated sympathetic activity, high evening cortisol levels, alterations in growth hormone release, and elevated markers of inflammation mediate the adverse effects of reduced sleep duration and quality on glucose metabolism. Several strategies for the management of SD and cardiovascular risk factors in T2DM exist. First, weight loss has been shown to be associated with improvements in the apnea-hypopnea index. Thus, weight loss is a primary treatment strategy for OSA in patient who are overweight or obese. Second, many studies have investigated whether treatment of OSA with continuous positive airway pressure (CPAP) improves glucose metabolism and glycemic control. The results, however, of studies on OSA treatment in patients with T2DM have been equivocal. Harsch et al. [9] reported that CPAP produced a significant improvement in insulin sensitivity after 3 months, but had no effect on HbA1c. Milleron et al. [10] and Marin et al. [11] reported that treatment of OSA with CPAP affected a range of cardiovascular measures, and Mansfield et al. [12] showed that CPAP treatment reduced ventricular ectopy and improved cardiovascular outcomes in patients with heart failure. However, the argument that CPAP treatment significantly reduces insulin resistance and HbA1c still persists. This editorial has addressed the complex relationship between SD and T2DM and discussed the various mechanisms linking these two conditions. Despite the availability of diagnostic measures and effective treatment, many patients with SDB remain undiagnosed. Thus, SD continues to be a significant health risk for affected individuals and the general public. Awareness and timely initiation of an effective treatment may prevent potential deleterious cardiovascular effects of SD in patients with T2DM.