Effects of dapagliflozin compared with glimepiride on body composition in Asian patients with type 2 diabetes inadequately controlled with metformin: The BEYOND study.

AIMS: To evaluate the effect of dapagliflozin on body composition such as total body fat (BF) mass, abdominal visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) areas compared with glimepiride in Korean patients with type 2 diabetes. MATERIALS AND METHODS: This was a 52-week, multicentre, randomized, parallel-group, open-label, Phase IV (NCT02564926) study. Patients with inadequate glycaemic control (glycated haemoglobin ≥7.0% and <10.0%) on metformin monotherapy (≥1000 mg/day) were randomized 1:1 to receive dapagliflozin 10 mg/day or glimepiride 1-2 mg/day for 12 months as an add-on to metformin. Baseline and end of study body composition evaluations included dual-energy X-ray absorptiometry and abdominal computed tomography scans. RESULTS: Of 124 enrolled patients from 14 centres, 121 received study treatment (dapagliflozin: 60; glimepiride: 61) and 106 (85.5%) completed the study. Over 52 weeks, the dapagliflozin group showed the following differences versus the glimepiride group: -2.59 kg BF mass, -1.94% BF%, -17.55 cm2 VAT area, -18.39 cm2 SAT area, -0.46% glycated haemoglobin, -18.25 mg/dl fasting blood glucose, -3.7 kg weight, -2.21 cm waist circumference, -1.37 kg/m2 body mass index, -6.81 mmHg systolic blood pressure and +657.71 ng/ml in adiponectin; all were statistically significant. Both groups had similar incidences of adverse events; however, hypoglycaemic events were mainly (12 of 15) reported in the glimepiride group. CONCLUSION: Dapagliflozin reduced total BF mass, abdominal VAT and SAT areas, and showed better glycaemic control than glimepiride. Being safe and well-tolerated, dapagliflozin appears to be a more favourable alternative to sulphonylureas as add-on therapy after metformin monotherapy failure in Korean patients with type 2 diabetes.

The increased amount of coffee consumption lowers the incidence of fatty liver disease in Korean men.

BACKGROUND AND AIMS: Coffee is known to have a beneficial effect on various liver diseases. The aim of this retrospective longitudinal study was to investigate an association between the amount of coffee consumption and the incidence of fatty liver disease in Korean adults. METHODS AND RESULTS: Data from a total of 91,436 male and female subjects with the mean follow-up period of 2.8 years were analyzed. The incidence of fatty liver was not associated with the amount of coffee consumption at baseline, but it was associated with the change in the amount of coffee consumption at the follow-up period. Multiple linear regression analyses showed that hazard ratios for incidence of fatty liver disease were significantly low in "increase" group comparing with "no change" group in fully adjusted model. When a subgroup analysis by gender was conducted, similar significant results were observed in male subjects, but not in females. CONCLUSIONS: The increment in the amount of coffee consumption is associated with the lower incidence of fatty liver in Korean men and suggests that increasing the coffee consumption may have a protective effect on fatty liver.

Association between atherogenic index of plasma and coronary artery calcification progression in Korean adults.

BACKGROUND: Dyslipidemia is a well-known risk factor for cardiovascular disease (CVD). Recently, atherogenic index of plasma (AIP) has been proposed as a novel predictive marker for CVD, and few cross sectional studies have demonstrated a relationship between AIP and coronary artery disease. The present study investigated the association between AIP and the progression of coronary artery calcification (CAC) in Korean adults without CVD. METHODS: A total of 1124 participants who had undergone CAC measurement at least twice by multi-detector computed tomography (CT) at a health check-up center were enrolled. Their anthropometric measurements and various cardiovascular risk factors were assessed. AIP was defined as the base 10 logarithm of the ratio of the concentration of triglyceride (TG) to high-density lipoprotein-cholesterol (HDL-C). CAC progression was defined as either incident CAC in a CAC-free population at baseline, or an increase of ≥2.5 units between the square roots of the baseline and follow-up coronary artery calcium scores (CACS) in subjects with detectable CAC at baseline. RESULTS: CAC progression was observed in 290 subjects (25.8%) during the mean follow-up of 4.2 years. All subjects were stratified into three groups according to AIP. There were significant differences in cardiovascular parameters among groups at baseline. The follow-up CAC and the incidence of CAC progression increased gradually with rising AIP tertiles. In logistic regression analysis, the odds ratio for CAC progression was 2.27 when comparing the highest to the lowest tertile of AIP (95% CI: 1.61-3.19; P for trend < 0.01). However, this association was attenuated after adjustment for multiple risk factors (P for trend = 0.67). CONCLUSIONS: There is a significant correlation between AIP and the progression of CAC in subjects without CVD. Although AIP was not an independent predictor of CAC progression, AIP should be considered when estimating the current as well as future CVD risk, along with other traditional risk factors.

Association between triglyceride glucose index and arterial stiffness in Korean adults.

BACKGROUND: The triglyceride glucose (TyG) index has been suggested as a simple surrogate marker of insulin resistance. However, there are limited data regarding the association between the TyG index and arterial stiffness in adults. Therefore, we evaluated the relationship between the TyG index and arterial stiffness as measured based on brachial ankle pulse wave velocity (baPWV) in Korean adults. METHODS: A total of 3587 subjects were enrolled in this study. Anthropometric and cardiovascular risk factors were measured. The TyG index was calculated as ln[fasting triglycerides(mg/dl) × fasting glucose(mg/dl)/2], and the insulin resistance index of homeostasis model assessment (HOMA-IR) was estimated. Arterial stiffness was determined by measuring baPWV. RESULTS: The subjects were stratified into four groups based on the TyG index. There were significant differences in cardiovascular parameters among the groups; the mean baPWV increased significantly with increasing TyG index. According to the logistic regression analysis after adjusting for multiple risk factors, the odds ratio (95% CI) for increased baPWV (> 75th percentile) for the highest and lowest quartiles of the TyG index was 2.92 (1.92-4.44) in men and 1.84 (1.15-2.96) in women, and the odds ratio for increased baPWV for the highest and lowest quartiles of the HOMA-IR was 1.80 (1.17-2.78) in men and 1.46 (1.06-2.47) in women, respectively. CONCLUSION: The TyG index is more independently associated with increased arterial stiffness than HOMA-IR in Korean adults.

Fetal bovine serum-free cryopreservation methods for clinical banking of human adipose-derived stem cells.

The use of fetal bovine serum (FBS) as a cryopreservation supplement is not suitable for the banking of mesenchymal stem cells (MSCs) due to the risk of transmission of disease as well as xenogeneic immune reactions in the transplanted host. Here, we investigated if human serum albumin (HSA), human serum (HS), or knockout serum replacement (KSR) can replace FBS for the cryopreservation of MSCs. In addition, we examined the characteristics of MSCs after multiple rounds of cryopreservation. Human adipose-derived stem cells (ASCs) cryopreserved with three FBS replacements, 9% HSA, 90% HS, or 90% KSR, in combination with 10% dimethyl sulfoxide (Me2SO) maintained stem cell properties including growth, immunophenotypes, gene expression patterns, and the potential to differentiate into adipogenic, osteogenic, and chondrogenic lineages, similar to ASCs frozen with FBS. Moreover, the immunophenotype, gene expression, and differentiation capabilities of ASCs were not altered by up to four freeze-thaw cycles. However, the performance of three or four freeze-thaw cycles significantly reduced the proliferation ability of ASCs, as indicated by the longer population doubling time and reduced colony-forming unit-fibroblast frequency. Together, our results suggest that HSA, HS, or KSR can replace FBS for the cryopreservation of ASCs, without altering their stemness, and should be processed with no more than two freeze-thaw cycles for clinical approaches.

Smart Care Based on Telemonitoring and Telemedicine for Type 2 Diabetes Care: Multi-Center Randomized Controlled Trial.

BACKGROUND: This study was performed to determine the effectiveness of the Smart Care service on glucose control based on telemedicine and telemonitoring compared with conventional treatment in patients with type 2 diabetes. MATERIALS AND METHODS: This 24-week prospective multi-center randomized controlled trial involved 338 adult patients with type 2 diabetes at four university hospitals in South Korea. The patients were randomly assigned to a control group (group A, n = 113), a telemonitoring group (group B, n = 113), or a telemedicine group (group C, n = 112). Patients in the telemonitoring group visited the outpatient clinic regularly, accompanied by an additional telemonitoring service that included remote glucose monitoring with automated patient decision support by text. Remote glucose monitoring was identical in the telemedicine group, but assessment by outpatient visits was replaced by video conferencing with an endocrinologist. RESULTS: The adjusted net reductions in HbA1c concentration after 24 weeks were similar in the conventional, telemonitoring, and telemedicine groups (-0.66% ± 1.03% vs. -0.66% ± 1.09% vs. -0.81% ± 1.05%; p > 0.05 for each pairwise comparison). Fasting glucose concentrations were lower in the telemonitoring and telemedicine groups than in the conventional group. Rates of hypoglycemia were lower in the telemedicine group than in the other two groups, and compliance with medication was better in the telemonitoring and telemedicine than in the conventional group. No serious adverse events were associated with telemedicine. CONCLUSIONS: Telehealthcare was as effective as conventional care at improving glycemia in patients with type 2 diabetes without serious adverse effects.

Relationship between the triglyceride glucose index and coronary artery calcification in Korean adults.

BACKGROUND: The triglyceride glucose (TyG) index has been considered a simple surrogate marker of insulin resistance. However, few studies have investigated the relationship between the TyG index and coronary artery calcification (CAC). Thus, we investigated the relationship between the TyG index and CAC in healthy Korean adults. METHODS: In total, 4319 participants who underwent cardiac computed tomography (CT) in a health promotion center were enrolled. Anthropometric profiles and multiple cardiovascular risk factors were measured. The TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2], and the insulin resistance index of homeostasis model assessment (HOMA-IR) was estimated. The CAC was measured using multidetector CT, and CAC presence was defined as an Agatston score of >0. RESULTS: All subjects were stratified into four groups based on their TyG indices. Significant differences were observed in cardiovascular parameters among the groups, and the prevalence of CAC significantly increased with increasing TyG index. In the logistic regression analysis after adjustment for multiple risk factors, the odds ratio for the prevalence of CAC, when comparing the highest and lowest quartiles of the TyG index was 1.95 (95% CI 1.23-3.11; P for trend = 0.01); the odds ratio for the prevalence of CAC, when comparing the highest and lowest quartiles of HOMA-IR was 1.64 (95% CI 1.12-2.40; P for trend = 0.04). In the receiver operating characteristics analysis, the TyG index was superior to HOMA-IR in predicting CAC. CONCLUSION: The TyG index is more independently associated with the presence of coronary artery atherosclerosis than is HOMA-IR in healthy Korean adults.

Serum ferritin levels are associated with arterial stiffness in healthy Korean adults.

Although an association between serum ferritin and atherosclerosis has been suggested, limited epidemiologic data are available regarding the association between ferritin and arterial stiffness in healthy adults. A total of 2932 healthy subjects were enrolled in this study. Anthropometric and biochemical profiles including ferritin were measured. The arterial stiffness was measured using brachial-ankle pulse wave velocity (baPWV). Serum ferritin levels were classified into quartiles and baPWV values gradually increased with each ferritin quartile. Multiple regression analysis showed that ferritin levels were independently correlated with baPWV. After adjusting for multiple risk factors, as compared with the lowest quartile, the odds ratios for high baPWV (>75(th) percentile) were 1.15 (0.84-1.56), 1.37 (0.97-1.73), and 1.46 (1.29-2.17) among men (p for trend < 0.05) and 1.24 (0.87-1.79), 1.53 (1.09-2.16), and 1.80 (1.25-2.82) among women (p for trend < 0.05), for the second, third, and fourth quartiles of ferritin, respectively. In conclusion, serum ferritin levels are independently associated with arterial stiffness in healthy Korean adults.

Undiagnosed diabetes is prevalent in younger adults and associated with a higher risk cardiometabolic profile compared to diagnosed diabetes.

BACKGROUND: A substantial percentage of patients have undiagnosed diabetes. We investigated the demographic characteristics and cardiometabolic profiles of subjects with undiagnosed diabetes. METHODS: A cross-sectional study with nationally representative samples of 25490 subjects aged ≥ 20 years from the KHNANES 2008 to 2011, which applied a complex, multistage, probability proportional to size sampling design. Subjects were categorized as having normal glucose (n = 16880), impaired fasting glucose (n = 5771), undiagnosed diabetes (n = 713), or diagnosed diabetes (n = 2126). Hyper low-density lipoprotein cholesterolemia was individually evaluated by the 2004 Adult Treatment Panel III guidelines and predicted risk of cardiovascular disease was estimated from the Framingham model. RESULTS: Among overall subjects with diabetes, the prevalence of undiagnosed diabetes was markedly increased in younger adults compared to older adults (49% in diabetic subjects <50 years vs 23% in diabetic subjects ≥50 years, P < .001), suggesting significant discrepancies in age-based screening. Patients with undiagnosed diabetes were also more likely to have undiagnosed or uncontrolled hypertension and hyper-low-density lipoprotein cholesterolemia. Individuals with undiagnosed diabetes had a significantly higher predicted 10-year Framingham cardiovascular disease risk than those with diagnosed diabetes (11% vs 8% in <50 years, 33% vs 30% in ≥50 years; both P < .001). Patients with undiagnosed diabetes were also more likely to have multiple cardiovascular risk factors including obesity, smoking and uncontrolled hypertension. CONCLUSIONS: People with undiagnosed diabetes have a higher predicted risk for cardiovascular disease compared to those with diagnosed diabetes. Intensive screening for diabetes in younger adults should be stressed in public healthcare to reduce the burden of modifiable cardiometabolic risk among individuals with undiagnosed diabetes.

The effects of aerobic exercise training on serum osteocalcin, adipocytokines and insulin resistance on obese young males.

OBJECTIVE: Osteocalcin has been proposed to be a novel link between bone and energy metabolism. Previous studies showed its relations to exercise, body fat and glucose metabolism, but their interrelationship remains inconslusive. We evaluated the changes in osteocalcin level following 8-week exercise programme and assessed how they are related to concomitant changes in body fat composition, insulin resistance and various adipocytokines in a single centre, randomized and prospective design. STUDY DESIGN AND METHODS: A total of 39 young obese, otherwise healthy males were randomly assigned to control (n = 10) and exercise (n = 29) groups. Subjects in Exercise group were on 8-week supervised exercise training programme of four sessions per week. Body fat compositions were analysed using whole body bone mineral density, various metabolic parameters, osteocalcin and adipocytokines were assessed from fasting blood samples before and after 8-week exercise programme. RESULTS: Body fat reduction following exercise significantly increased serum total (1·51 ± 0·36 vs 1·69 ± 0·39 mmol/l, P = 0·01, baseline vs postexercise) and undercarboxylated osteocalcin level (0·44 ± 0·14 vs 0·64 ± 0·26 mmol/l, P < 0·01), and the increase in osteocalcin was in negative correlations with changes in body weight, BMI and body fat percentage as well as HOMA-IR and leptin (all P < 0·05). The changes in osteocalcin and leptin were not independent predictors of changes in insulin resistance and osteocalcin, respectively. CONCLUSIONS: In a physiological axis of bone-fat-energy metabolism, exercise-induced body fat reduction and improved insulin sensitivity were accompanied by an increase in serum osteocalcin and leptin levels, but other factors also seem to be involved in this interrelationship.

Normal-weight obesity is associated with increased risk of subclinical atherosclerosis.

BACKGROUND: Subjects with normal body mass index (BMI) but elevated amounts of body fat (normal-weight obesity; NWO) show cardiometabolic dysregulation compared to subjects with normal BMI and normal amounts of body fat (normal-weight lean; NWL). In this study, we aimed to evaluate whether NWO individuals have higher rates of subclinical atherosclerosis compared to NWL subjects. METHODS: From a large-scale health checkup system, we identified 2078 normal weight (18.5 ≤ BMI < 25 kg/m(2)) subjects with no previous history of coronary artery disease who underwent analysis of atherosclerosis using coronary computed tomography angiography (CCTA) and pulse wave velocity (PWV). NWO was defined as normal BMI and highest tertile of body fat percentage by sex (men ≥ 25. 4 % and women ≥ 31.4 %). CCTA was performed using a 64-detector row CT. A plaque was defined as a structure >1 mm(2) within and/or adjacent to the vessel lumen and classified according to the presence/proportion of intraplaque calcification. RESULTS: NWO subjects (n = 283) demonstrated metabolic dysregulation compared to NWL individuals (n = 1795). After adjusting for age, sex, and smoking, NWO individuals showed higher PWV values than NWL individuals (1474.0 ± 275.4 vs. 1380.7 ± 234.3 cm/s, p = 0.006 by ANCOVA). Compared with NWL subjects, NWO subjects had a higher prevalence of soft plaques even after age, sex, and smoking adjustment (21.6% vs. 14.5%, p = 0.039 by ANCOVA). The PWV value and the log{(number of segments with plaque) + 1} showed a positive correlation with numerous parameters such as age, systolic blood pressure, visceral fat, fasting glucose level, serum triglyceride level, and C-reactive protein (CRP) in contrast to the negative correlation with high-density lipoprotein-cholesterol level. The visceral fat was an independent determinant of log{(number of segments with plaque) + 1} (ß = 0.027, SE = 0.011, p = 0.016) even after adjustment for other significant factors. Most importantly, NWO was an independent risk factor for the presence of soft plaques (odds ratio 1.460, 95 % confidence interval 1.027-2.074, p = 0.035) even after further adjustment for multiple factors associated with atherosclerosis (blood pressure, blood glucose, lipid level, CRP, medication, smoking status, physical activity). CONCLUSIONS: NWO individuals carry a higher incidence of subclinical atherosclerosis compared with NWL individuals, regardless of other clinical risk factors for atherosclerosis.

Effects of blood lead levels on airflow limitations in Korean adults: findings from the 5th KNHNES 2011.

This study aimed to examine whether blood levels of heavy metals, such as lead, mercury and cadmium, are related with pulmonary function in Korean adults. This investigation included 870 Korean adults (≥ 40 years) who received pulmonary function testing in the Korea National Health and Nutrition Examination Survey (KNHANES) V-2, 2011. Data of blood levels of heavy metals, pulmonary function tests and anthropometric measurements were acquired. Blood lead levels showed inverse correlations with the FEV1/FVC ratio before (r = -0.276, p < 0.001) and after adjustment of multiple compounding factors (r = -0.115, p = 0.001). A logistic multiple regression analysis revealed that blood lead levels were a significant influencing factor for the FEV1/FVC ratio (ß = -0.017, p = 0.001, adjusted R(2) = 0.267). The odds ratios (ORs) for the FEV1/FVC ratio were significantly lower in the highest tertile group of the blood lead levels than in the lowest tertile group in Model 1 (OR = 0.007, 95% CI = 0.000-0.329) and Model 2 (OR = 0.006, 95% CI = 0.000-0.286). These findings imply that environmental exposure to lead might be an important factor that may cause airflow limitations in Korean adults.

Composition of dietary macronutrient intake is not associated with prevalence of coronary artery calcification in healthy Korean adults.

BACKGROUND AND AIMS: There is little information supporting the relationships between macronutrients and pre-clinical atherosclerosis. The aim of this study was to identify whether dietary macronutrient content is related with CAC. METHODS: 10,793 healthy Korean adults in a cohort were enrolled. Subjects were divided into CAC (CAC score >0) or non-CAC group (CAC score = 0). Intake of energy, carbohydrate (CHO), protein and fat were obtained using food frequency questionnaire (FFQ). Macronutrient composition was expressed as the ratio of energy from each macronutrient to total energy. Subjects were classified into three groups according to tertiles of intake for each macronutrient. To investigate the association between macronutrient intake and CAC, multiple regression analysis was conducted according to tertile groups of each macronutrient. RESULTS: The prevalence of CAC significantly differed among tertile groups of CHO and fat intake in men (p < 0.001, p < 0.01) and women (p < 0.05, p < 0.01). However, multiple logistic regression analysis revealed that the odds ratios (ORs) for CAC were not significantly different among tertile groups of each macronutrient intake after adjustment in men (CHO: OR = 0.965 [95% CI = 0.826-1.129]; protein: OR = 1.029 [95% CI = 0.881-1.201]; fat: OR = 1.015 [95% CI = 0.868-1.188]) and women (CHO: OR = 1.158 [95% CI = 0.550-2.438]; protein: OR = 1.261 [95% CI = 0.629-2.528]; fat: OR = 0.625 [95% CI = 0.286-1.365]). CONCLUSIONS: The prevalence of CAC may not be associated with composition of dietary macronutrient intake in in healthy Korean adults.

Transplantation of insulin-secreting cells differentiated from human adipose tissue-derived stem cells into type 2 diabetes mice.

Currently, there are limited ways to preserve or recover insulin secretory capacity in human pancreas. We evaluated the efficacy of cell therapy using insulin-secreting cells differentiated from human eyelid adipose tissue-derived stem cells (hEAs) into type 2 diabetes mice. After differentiating hEAs into insulin-secreting cells (hEA-ISCs) in vitro, cells were transplanted into a type 2 diabetes mouse model. Serum levels of glucose, insulin and c-peptide were measured, and changes of metabolism and inflammation were assessed in mice that received undifferentiated hEAs (UDC group), differentiated hEA-ISCs (DC group), or sham operation (sham group). Human gene expression and immunohistochemical analysis were done. DC group mice showed improved glucose level, and survival up to 60 days compared to those of UDC and sham group. Significantly increased levels of human insulin and c-peptide were detected in sera of DC mice. RT-PCR and immunohistochemical analysis showed human gene expression and the presence of human cells in kidneys of DC mice. When compared to sham mice, DC mice exhibited lower levels of IL-6, triglyceride and free fatty acids as the control mice. Transplantation of hEA-ISCs lowered blood glucose level in type 2 diabetes mice by increasing circulating insulin level, and ameliorating metabolic parameters including IL-6.

Subclinical vascular inflammation in subjects with normal weight obesity and its association with body fat: an 18 F-FDG-PET/CT study.

BACKGROUND: Although body mass index (BMI) is the most widely accepted parameter for defining obesity, recent studies have indicated a unique set of patients who exhibit normal BMI and excess body fat (BF), which is termed as normal weight obesity (NWO). Increased BF is an established risk factor for atherosclerosis. However, it is unclear whether NWO subjects already have a higher degree of vascular inflammation compared to normal weight lean (NWL) subjects; moreover, the association of BF with vascular inflammation in normal weight subjects is largely unknown. METHODS: NWO and NWL subjects (n = 82 in each group) without any history of significant vascular disease were identified from a 3-year database of consecutively recruited patients undergoing 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG-PET/CT) at a self-referred Healthcare Promotion Program. The degree of subclinical vascular inflammation was evaluated using the mean and maximum target-to-background ratios (TBRmean and TBRmax) of the carotid artery, which were measured by 18 F-FDG-PET/CT (a noninvasive tool for assessing vascular inflammation). RESULTS: We found that metabolically dysregulation was greater in NWO subjects than in NWL subjects, with a significantly higher blood pressure, higher fasting glucose level, and worse lipid profile. Moreover, NWO subjects exhibited higher TBR than NWL subjects (TBRmean: 1.33 ± 0.16 versus 1.45 ± 0.19, p < 0.001; TBRmax: 1.52 ± 0.23 versus 1.67 ± 0.25, p < 0.001). TBR was significantly associated with total BF (TBRmean: r = 0.267, p = 0.001; TBRmax: r = 0.289, p < 0.001), age (TBRmean: r = 0.170, p = 0.029; TBRmax: r = 0.165, p = 0.035), BMI (TBRmean: r = 0.184, p = 0.018; TBRmax: r = 0.206, p = 0.008), and fasting glucose level (TBRmean: r = 0.157, p = 0.044; TBRmax: r = 0.182, p = 0.020). In multiple linear regression analysis, BF was an independent determinant of TBRmean and TBRmax, after adjusting for age, BMI, and fasting glucose level (TBRmean: regression coefficient = 0.020, p = 0.008; TBRmax: regression coefficient = 0.028, p = 0.005). Compared to NWL, NWO was also independently associated with elevated TBRmax values, after adjusting for confounding factors (odds ratio = 2.887, 95% confidence interval 1.206-6.914, p = 0.017). CONCLUSIONS: NWO is associated with a higher degree of subclinical vascular inflammation, of which BF is a major contributing factor. These results warrant investigations for subclinical atherosclerosis in NWO patients.

Follistatin-like 1 is a myokine regulating lipid mobilization during endurance exercise and recovery.

OBJECTIVE: The aim of this study was to investigate the role of the follistatin-like 1 (Fstl1) and disco-interacting protein 2 homolog A (DIP2a) axis in relation to lipid metabolism during and after endurance exercise and to elucidate the mechanisms underlying the metabolic effects of Fstl1 on adipocytes, considering its regulation by exercise and muscle mass and its link to obesity. METHODS: Twenty-nine sedentary males participated in endurance exercise, and blood samples were collected during and after the exercise. Body composition, Fstl1, glycerol, epinephrine, growth hormone, and atrial natriuretic peptide were measured. 3T3-L1 adipocytes, with or without DIP2a knockdown, were treated with Fstl1 to assess glycerol release, cyclic AMP/cyclic GMP production, and hormone sensitive lipase phosphorylation. The association between DIP2a gene expression levels in human adipose tissues and exercise-induced lipolysis was examined. RESULTS: Fstl1 levels significantly increased during endurance exercise and following recovery, correlating with lean body mass and lipolysis. In 3T3-L1 adipocytes, Fstl1 increased glycerol release, cyclic GMP production, and hormone sensitive lipase activation, but these effects were attenuated by DIP2a knockdown. DIP2a gene expression in human adipose tissues correlated with serum glycerol concentrations during endurance exercise. CONCLUSIONS: Fstl1 is a myokine facilitating lipid mobilization during and after endurance exercise through DIP2a-mediated lipolytic effects in adipocytes.

Real-World Outcomes of Individualized Targeted Therapy with Insulin Glargine 300 Units/mL in Insulin-Naïve Korean People with Type 2 Diabetes: TOBE Study.

INTRODUCTION: The TOujeo BEyond glucose control (TOBE) study evaluated clinical outcomes with insulin glargine 300 units/mL (Gla-300) in insulin-naïve Korean people with type 2 diabetes mellitus (T2DM) in a real-world setting. METHODS: This 24-week, prospective, non-interventional, multicenter, open-label, single-arm, observational study included adults aged ≥ 20 years with T2DM suboptimally controlled with oral hypoglycemic agents and/or glucagon-like peptide 1 receptor agonists who require basal insulin. Eligible participants were assigned to either general target glycated hemoglobin (HbA1c < 7%) or individualized target groups as per physician's discretion considering guidelines and participants' characteristics. The primary endpoint was the proportion of participants achieving the HbA1c target (individualized or general) at 24 weeks. RESULTS: Among 369 participants, 19.5% (72/369) of participants achieved the HbA1c target at week 24; 37.5% (33/88) in the individualized and 13.9% (39/281) in the general target group. In both target groups, similar reductions in fasting plasma glucose and body weight were observed, with low incidence of hypoglycemia, and T2DM duration was significantly shorter in participants who did versus those who did not achieve the target HbA1c (individualized target group: 9.6 ± 8.0 versus 13.1 ± 8.4 years, P = 0.0454; general target group: 10.2 ± 8.6 versus 12.8 ± 7.4 years, P = 0.0378). CONCLUSIONS: This study showed that initiation of insulin therapy with Gla-300 in people with T2DM using an individualized approach is more effective in achieving an HbA1c target. Moreover, earlier initiation of insulin therapy in people with suboptimally controlled T2DM may increase the success rate of glycemic control. A graphical abstract is available with this article.

Despite various efforts in managing diabetes, individuals with type 2 diabetes mellitus (T2DM) encounter numerous challenges to achieve good glycemic control. The major cause is failure to initiate insulin therapy in a timely manner, primarily because of the fear of hypoglycemia. Insulin glargine 300 units/mL (Gla-300) has smooth and prolonged activity resulting in stable and sustained glycemic control, thus reducing the risk of hypoglycemia. Studies on efficacy and safety of Gla-300 in various populations have been published globally. However, there are limited real-world studies in Asian populations. This study evaluated effectiveness and safety of Gla-300 in Korean people with T2DM who were not on insulin prior to this study but were taking oral glucose-lowering medications. The participants were assigned to two groups: general glycated hemoglobin (HbA1c) target (HbA1c < 7%) and individualized HbA1c target according to the participant's characteristics. Results showed that Gla-300 helped to achieve the glycemic target more effectively using an individualized approach. In both groups, similar reductions in fasting plasma glucose and body weight were observed, with low incidence of hypoglycemia. People who achieve glycemic target had a shorter duration of T2DM than those who did not achieve their glycemic target. This suggests that earlier insulin initiation may be a better approach and may increase the success rate of insulin therapy.

Efficacy and Safety of Alogliptin-Pioglitazone Combination for Type 2 Diabetes Mellitus Poorly Controlled with Metformin: A Multicenter, Double-Blind Randomized Trial.

Background: Guidelines for switching to triple combination therapy directly after monotherapy failure are limited. This study investigated the efficacy, long-term sustainability, and safety of either mono or dual add-on therapy using alogliptin and pioglitazone for patients with type 2 diabetes mellitus (T2DM) who did not achieve their target glycemic range with metformin monotherapy. Methods: The Practical Evidence of Antidiabetic Combination Therapy in Korea (PEAK) was a multicenter, placebo-controlled, double-blind, randomized trial. A total of 214 participants were randomized to receive alogliptin+pioglitazone (Alo+Pio group, n=70), alogliptin (Alo group, n=75), or pioglitazone (Pio group, n=69). The primary outcome was the difference in glycosylated hemoglobin (HbA1c) levels between the three groups at baseline to 24 weeks. For durability, the achievement of HbA1c levels <7% and <6.5% was compared in each group. The number of adverse events was investigated for safety. Results: After 24 weeks of treatment, the change of HbA1c in the Alo+Pio, Alo, and Pio groups were -1.38%±0.08%, -1.03%±0.08%, and -0.84%±0.08%, respectively. The Alo+Pio group had significantly lower HbA1c levels than the other groups (P=0.0063, P<0.0001) and had a higher proportion of patients with target HbA1c achievement. In addition, insulin sensitivity and ß-cell function, lipid profiles, and other metabolic indicators were also improved. There were no significant safety issues in patients treated with triple combination therapy. Conclusion: Early combination triple therapy showed better efficacy and durability than the single add-on (dual) therapy. Therefore, combination therapy with metformin, alogliptin, and pioglitazone is a valuable early treatment option for T2DM poorly controlled with metformin monotherapy.

Gastrectomy for early gastric cancer is associated with decreased cardiovascular mortality in association with postsurgical metabolic changes.

BACKGROUND: Bariatric surgery effectively induces weight loss and resolves cardiovascular comorbidities in obese patients. We investigated cardiovascular and all-cause mortality in patients who underwent gastrectomies for early gastric cancer (EGC) and analyzed the changes in metabolic parameters after surgery. METHODS: A total of 2,477 patients who underwent gastrectomies for EGC between 1995 and 2004 were enrolled in the study and followed for mortality through 2007. Standardized mortality ratios (SMRs) were calculated using sex- and age-matched mortality in the general Korean population in 2005. Effects of gastrectomy on changes in body weight and metabolic parameters were investigated in 51 of the patients before and after surgery. RESULTS: During the 15,096.4 person-years of follow-up, 244 deaths were recorded. The all-cause mortality was not significantly different from that of the general population (SMR [95 % confidence interval (CI)] = 1.01 [0.89 - 1.14]); however, cardiovascular mortality was significantly lower (SMR = 0.35 [0.22 - 0.53]). In the 51 patients included in the second part of the study, significant reductions in body weight and visceral fat areas occurred after surgery, regardless of whether the patients were previously obese. Triglycerides, LDL-cholesterol, and plasminogen activator inhibitor-1 levels were significantly decreased, whereas HDL-cholesterol and adiponectin levels were increased. Carotid intima-media thickness also was significantly decreased in previously obese and nonobese patients. CONCLUSIONS: Patients with EGC who undergo gastrectomy have a lower cardiovascular mortality but similar all-cause mortality as that of the general population. In these patients, a significant reduction in body weight and visceral fat after surgery may improve impaired lipid metabolism and prevent atherosclerotic changes.

The association of insulin resistance and carotid atherosclerosis with thigh and calf circumference in patients with type 2 diabetes.

BACKGROUND: The relationship between body composition parameters such as thigh and calf circumference and insulin resistance or atherosclerosis in type 2 diabetes is poorly understood. The aim of this study was to investigate the relationship between insulin resistance, atherosclerosis, and thigh and calf circumference in patients with type 2 diabetes. METHODS: A total of 4,427 subjects with type 2 diabetes were enrolled in this study. Insulin sensitivity was assessed according the rate constant for plasma glucose disappearance (Kitt) determined via the short insulin tolerance test. Biochemical and anthropometric profiles were measured according to a standardized protocol. Visceral fat thickness and carotid intima media thickness (IMT) were measured by ultrasonography. RESULTS: Insulin sensitivity index (Kitt) was significantly correlated with weight adjusted thigh and calf circumference. Thigh circumference was inversely associated with IMT in men and women and calf circumference was negatively correlated with IMT in women. Multiple stepwise regression analysis revealed that thigh circumference was independently correlated with insulin sensitivity index (Kitt) and IMT. Furthermore, in multivariate logistic regression analysis, thigh circumference was an independent determinant factor for carotid atherosclerosis in patients with type 2 diabetes even after adjusting for other cardiovascular risk factors. CONCLUSIONS: Thigh and calf circumference were correlated with insulin resistance and carotid atherosclerosis, and thigh circumference was independently associated with insulin resistance and carotid atherosclerosis in patients with type 2 diabetes.