Anagliptin twice-daily regimen improves glycaemic variability in subjects with type 2 diabetes: A double-blind, randomized controlled trial.

AIM: To determine whether the twice-daily (BID) regimen is superior to the once-daily (QD) regimen for managing glycaemic variability by comparing the effects of anagliptin 100 mg BID versus sitagliptin 100 mg QD. MATERIALS AND METHODS: A double-blinded, randomized, multicentre study was performed in 89 patients with type 2 diabetes treated with metformin alone (6.5% < HbA1c < 8.5%). Subjects were randomly assigned to anagliptin 100 mg BID or sitagliptin 100 mg QD in a 1:1 ratio for 12 weeks. Continuous glucose monitoring was used to measure the mean amplitude of glycaemic excursion (MAGE) and postprandial time in range (TIR) before and after dipeptidyl peptidase-4 (DPP-4) inhibitor treatment to compare glycaemic variability. RESULTS: The decrease from baseline in MAGE at 12 weeks after DPP-4 inhibitor treatment was significantly greater in the anagliptin BID group than in the sitagliptin QD group (P < .05); -30.4 ± 25.6 mg/dl (P < .001) in the anagliptin group versus -9.5 ± 38.0 mg/dl (P = .215) in the sitagliptin group. The TIR after dinner increased by 33.0% ± 22.0% (P < .001) in the anagliptin group and by 14.6% ± 28.2% (P = .014) in the sitagliptin group, with a statistically significant difference (P = .009). No statistically significant differences were observed between the groups in the changes in HbA1c and fasting plasma glucose (FPG). CONCLUSIONS: The anagliptin BID regimen for the treatment of type 2 diabetes was superior in blood glucose control after dinner to improve glycaemic variability, as indicated by MAGE and TIR, but was equivalent to the QD regimen in terms of HbA1c and FPG.

Pancreatic fat accumulation is associated with decreased ß-cell function and deterioration in glucose tolerance in Korean adults.

AIMS: This study was designed to investigate the association between pancreatic fat content (PFC) and insulin secretory capacity as well as glucose tolerance in Korean adults. MATERIALS: A total of 39 participants (mean age 49.9 years, 53% males) without a previous history of diabetes, or those previously diagnosed as having diabetes but with less than 10 years of disease duration and no medication history were included. They were stratified according to the results of the oral glucose tolerance test (OGTT): normal glucose tolerance, prediabetes, and diabetes. METHODS: All participants underwent the proton magnetic resonance spectroscopy (1 H-MRS) to assess PFC. Insulin sensitivity and ß-cell function were measured by the frequently sampled intravenous glucose tolerance tests (FSIVGTT) and OGTT-derived indices. RESULTS: As glucose tolerance deteriorated, parameters such as Stumvoll index, oral glucose insulin sensitivity index, homeostatic model assessment (HOMA)-ß, insulinogenic index and oral disposition index from the OGTT, and acute insulin response to glucose (AIR) and disposition index (DI) from the FSIVGTT were decreased. PFC increased with deterioration in glucose tolerance (NGT: 12.0%, prediabetes: 23.7%, and diabetes: 31.9%). Correlation analysis indicated that glucose levels at 60 and 120 min during the OGTT were positively correlated with PFC. Also, there was a significant negative correlation between PFC and DI as well as AIR derived from the FSIVGTT. CONCLUSIONS: PFC evaluated by 1 H-MRS in Korean adults was higher in those diagnosed with diabetes than those with normal glucose tolerance status. PFC also showed a significant negative correlation with indices reflecting beta cell function.

Exendin-4, a glucagon-like peptide-1 receptor agonist, reduces hepatic steatosis and endoplasmic reticulum stress by inducing nuclear factor erythroid-derived 2-related factor 2 nuclear translocation.

Activation of endoplasmic reticulum (ER) stress is involved in the development of nonalcoholic fatty liver disease. Glucagon-like peptide-1 (GLP-1) has been reported to reduce hepatic steatosis, but the underlying mechanism has not been fully elucidated. Here, we investigated whether exendin-4 (EX-4), a GLP-1 receptor analogue, improves hepatic steatosis through ER stress reduction. Furthermore, we explored which ER stress pathway is involved in this process, with a focus on the protein kinase RNA-like ER kinase (PERK)-nuclear factor erythroid-derived 2-related factor 2 (Nrf2) pathway. EX-4 treatment reduced hepatic lipid accumulation by suppressing the expression of lipogenic genes and restoring the expression of ß-oxidation genes in palmitate-treated HepG2 cells and high fat diet (HFD)-fed mice. In addition, EX-4 treatment suppressed hepatic ER stress activation in HFD-fed mice and tunicamycin-treated mice. In particular, EX-4 treatment restored HFD- and tunicamycin-induced Nrf2 nuclear translocation to control levels. Inhibition of Nrf2 by siRNA enhanced phosphorylation of PERK and eukaryotic translation initiation factor 2α (eIF2α), as well as other substrates of the PERK pathway. Nrf2 knockdown also inhibited the protective effects of EX-4 against lipid accumulation, ER stress activation, and cell death in palmitate-treated HepG2 cells. EX-4 treatment prevents hepatic steatosis and improves cell survival by regulating hepatic lipid metabolism and reducing ER stress activation, and Nrf2 plays an essential role in the protective effect of GLP-1 on hepatic steatosis.

Long-term effects on glycaemic control and ß-cell preservation of early intensive treatment in patients with newly diagnosed type 2 diabetes: A multicentre randomized trial.

AIM: To determine the effects of early intensive glycaemic control with intensive insulin treatment (IIT) or initial combined oral antidiabetic drug (COAD) therapy on long-term glycaemic control and the preservation of ß-cell function in people with type 2 diabetes mellitus (T2DM). METHODS: Newly diagnosed drug-naïve patients with T2DM from 8 outpatient diabetes centres were randomized to receive either IIT (n = 50; glargine/glulisine) or COAD (n = 47; glimepiride/metformin) as intensive treatment until the termination criteria to ensure euglycaemia were met. After intensive treatment, the patients completed a follow-up period with either lifestyle modification (LSM) alone or rescue therapy to maintain target glycated haemoglobin levels of <7% (53 mmol/mol) up to week 104. The primary outcomes were analysed after excluding participants who were anti-glutamic acid decarboxylase autoantibody-positive. RESULTS: Both intensive treatment methods were effective for short-term glycaemic control, but improvements in the disposition index (DI) were significantly greater in the IIT group than in the COAD group (P = .021). During the follow-up period after intensive treatment, the two groups significantly differed in rescue method regarding the maintenance of comparable levels of glycaemic control (P = .010) and more participants who received IIT exhibited well-controlled glycaemia with LSM alone. Additionally, the IIT group maintained a higher DI than the COAD group during the follow-up period. Cox regression analysis showed that the IIT method was associated with a 52.5% lower risk of failing to maintain drug-free glycaemic remission compared with the COAD method (P = .015). CONCLUSIONS: The findings indicate that outpatient clinic-based IIT to ensure euglycaemia in newly diagnosed patients with T2DM might be an effective initial therapeutic option for improvements in ß-cell function and glycaemic control over the long term, without serious adverse events.

Efficacy and safety of evogliptin monotherapy in patients with type 2 diabetes and moderately elevated glycated haemoglobin levels after diet and exercise.

AIMS: To evaluate the efficacy and safety of evogliptin, a newly developed dipeptidyl peptidase-4 inhibitor, in patients with type 2 diabetes (T2D) inadequately controlled by diet and exercise. MATERIALS AND METHODS: In this randomized, double-blind, placebo-controlled, parallel-group, multicentre, phase III study, 160 patients with T2D were assigned to either evogliptin 5 mg or placebo for 24 weeks. The primary endpoint was the mean change in glycated haemoglobin (HbA1c) from baseline to week 24. RESULTS: The mean baseline HbA1c levels were similar in the evogliptin and the placebo groups (7.20% ± 0.56% vs 7.20% ± 0.63%, respectively). At week 24, evogliptin significantly reduced HbA1c levels from baseline compared with placebo (-0.23% vs 0.05%, respectively, P < .0001). Additionally, the proportion of patients achieving HbA1c <6.5% was significantly higher in the evogliptin group than in the placebo group (33.3% vs 15.2%; P = .008). The overall incidence of adverse events, including hypoglycaemia, was similar in the 2 groups. CONCLUSIONS: In this 24-week study, once-daily evogliptin monotherapy significantly improved glycaemic control and was well tolerated in patients with T2D.

Efficacy and safety of gemigliptin, a dipeptidyl peptidase-4 inhibitor, in patients with type 2 diabetes mellitus inadequately controlled with combination treatment of metformin and sulphonylurea: a 24-week, multicentre, randomized, double-blind, placebo-controlled study (TROICA study).

AIMS: To assess the efficacy and safety of gemigliptin, a dipeptidyl peptidase-4 inhibitor, added to metformin and sulphonylurea in patients with type 2 diabetes (T2DM). MATERIALS AND METHODS: We conducted a randomized, double-blind, placebo-controlled trial in 219 Korean patients inadequately controlled with metformin and glimepiride. Participants were randomized to gemigliptin 50 mg once daily or placebo added to metformin and glimepiride. The primary endpoint was change in glycated haemoglobin (HbA1c) level from baseline to week 24. RESULTS: The baseline HbA1c was 8.2% in both groups. The addition of gemigliptin to metformin and glimepiride significantly reduced HbA1c levels at week 24 compared with placebo (between-group difference in adjusted mean change -0.87%, 95% confidence interval [CI] -1.09% to -0.64%). Fasting plasma glucose level was also significantly reduced with gemigliptin (-0.93 mmol/L, 95% CI -1.50 to -0.35 mmol/L), and a higher proportion of participants achieved an HbA1c level of <7% (39.3% vs 5.5%; P <.001) in the gemigliptin group than in the placebo group. Total cholesterol and LDL cholesterol were modestly but significantly reduced in the gemigliptin group compared with the placebo group (-0.21 mmol/L, 95% CI -0.38 to -0.03 mmol/L for total cholesterol, -0.18 mmol/L, 95% CI -0.34 to -0.01 mmol/L for LDL cholesterol). The incidence of hypoglycaemia was 9.4% in the gemigliptin group and 2.7% in the placebo group. CONCLUSIONS: Gemigliptin significantly improved glycaemic control in patients with T2DM inadequately controlled with metformin and sulphonylurea. The incidence of hypoglycaemia was higher with gemigliptin than with placebo, which highlights the importance of optimal dose adjustment for sulphonylurea.

Comparison of the Efficacy of Ezetimibe Combination Therapy and High-Intensity Statin Monotherapy in Type 2 Diabetes.

CONTEXT: Low-density lipoprotein cholesterol (LDL-C)-lowering therapy is considerably important in preventing cardiovascular disease (CVD) among patients with diabetes. Studies comparing CVD, stroke, and mortality outcomes of low- or moderate-intensity statins with ezetimibe combination therapy and high-intensity statin monotherapy in patients with diabetes remain lacking. OBJECTIVE: This study compared the primary prevention effect of myocardial infarction (MI), stroke, and all-cause death between combination therapy of low- or moderate-intensity statins and ezetimibe and high-intensity statin monotherapy in patients with diabetes using the Korean National Health Insurance claims database. METHODS: Patients aged ≥20 years with type 2 diabetes and dyslipidemia were enrolled. The combination therapy of low- or moderate-intensity statin and ezetimibe was compared with high-intensity statin monotherapy after a propensity score-matched analysis. The incidence of composite outcomes consisting of MI, stroke, and all-cause death and each component were analyzed. RESULTS: In moderate-intensity statin therapy with ezetimibe combination therapy, LDL-C (74 ± 37.9 mg/dL vs 80.8 ± 38.8 mg/dL, P < .001) and the incidence of composite outcomes were lower (hazard ratio 0.85, 95% CI 0.74-0.98) than those in high-intensity statin monotherapy. Meanwhile, no significant difference was observed in the LDL-C levels and composite outcomes between low-intensity statins with ezetimibe combination therapy and high-intensity statin monotherapy. CONCLUSION: Adding ezetimibe to a moderate-intensity statin in patients with type 2 diabetes has a greater LDL-C-lowering effect and greater primary prevention of composite outcomes than that of high-intensity statin monotherapy.

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.

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 Metformin and Atorvastatin Combination Therapy vs. Monotherapy with Either Drug in Type 2 Diabetes Mellitus and Dyslipidemia Patients (ATOMIC): Double-Blinded Randomized Controlled Trial.

Background: It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia. Methods: This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment. Results: After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. -0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (-55.20% vs. -7.69%, P<0.001) without previously unknown adverse drug events. Conclusion: The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin's preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.

Optimal serum concentration of 25-hydroxyvitamin D for bone health in older Korean adults.

Optimal vitamin D concentrations for bone health have not been determined in the Korean population. The aim of this study was to define serum 25-hydroxyvitamin D (25[OH]D) concentrations that indicate insufficiency among older Korean adults as measured by serum intact parathyroid hormone (iPTH) concentrations and bone mineral density (BMD). We analyzed data from the Fourth Korea National Health and Nutrition Examination Survey (KNHANES IV-3), which was conducted in Korea in 2009. We enrolled 1,451 men and 1,870 women aged 49 years and above. After adjusting for variables that could potentially affect serum 25(OH)D concentrations, we found that serum iPTH concentrations began to increase at serum 25(OH)D concentrations below 12.1 ng/mL (30.2 nmol/L). In addition, total-femur BMD increased until serum 25(OH)D concentrations dropped below 20.4 ng/mL (50.9 nmol/L); no significant changes were observed thereafter. Assuming that serum 25(OH)D concentrations below 12.1 and 20.4 ng/mL represent vitamin D insufficiency, the prevalences of vitamin D insufficiency were 8.7 and 50.4 % in men and 17.9 and 66.3 % in women, respectively. Serum 25(OH)D cutoff values of 12.1 ng/mL (OR = 1.26) and 20.4 ng/mL (OR = 1.54) were associated with osteoporosis (P < 0.01); osteoporosis was not associated with a 25(OH)D cutoff value of 30 ng/mL (75.0 nmol/L). In conclusion, serum 25(OH)D concentrations of 20 ng/mL might be sufficient for bone health in older Korean adults.

Subtypes of type 2 diabetes and their association with outcomes in Korean adults - A cluster analysis of community-based prospective cohort.

BACKGROUND: Little is known about the subtypes of type 2 diabetes (T2D) and their association with clinical outcomes in Asians. METHODS: We performed data-driven cluster analysis in patients with newly diagnosed drug-naive T2D (n = 756) from the Korean Genome and Epidemiology Study. Clusters were based on five variables (age at diagnosis, BMI, HbA1c, and HOMA2 ß-cell function, and insulin resistance). RESULTS: We identified four clusters of patients with T2D according to k-means clustering: cluster 1 (22.4 %, severe insulin-resistant diabetes [SIRD]), cluster 2 (32.7 %, mild age-related diabetes [MARD]), cluster 3 (32.7 %, mild obesity-related diabetes [MOD]), and cluster 4 (12.3 %, severe insulin-deficient diabetes [SIDD]). During 14 years of follow-up, individuals in the SIDD cluster had the highest risk of initiation of glucose-lowering therapy compared to individuals in the other three clusters. Individuals in the MARD and SIDD clusters showed the highest risk of chronic kidney disease and cardiovascular disease, and individuals in the MOD clusters showed the lowest risk after adjusting for other risk factors (P < 0.05). CONCLUSIONS: Patients with T2D can be categorized into four subgroups with different glycemic deterioration and risks of diabetes complications. Individualized management might be helpful for better clinical outcomes in Asian patients with different T2D subgroups.

Peroxisome proliferator-activated receptor γ activation ameliorates liver fibrosis-differential action of transcription factor EB and autophagy on hepatocytes and stellate cells.

BACKGROUND: Peroxisome proliferator-activated receptor γ (PPARγ) activation suppresses HSC activation and liver fibrosis. Moreover, autophagy is implicated in hepatic lipid metabolism. Here, we determined whether PPARγ activation ameliorates HSC activation by downregulating transcription factor EB (TFEB)-mediated autophagy. METHODS AND RESULTS: Atg7 or Tfeb knockdown in human HSC line LX-2 cells downregulated the expression of fibrogenic markers including α smooth muscle actin, glial fibrillary acidic protein, and collagen type 1. Conversely, Atg7 or Tfeb overexpression upregulated fibrogenic marker expression. Rosiglitazone (RGZ)-mediated PPARγ activation and/or overexpression in LX-2 cells and primary HSCs decreased autophagy, as indicated by LC3B conversion, total and nuclear-TFEB contents, mRFP-LC3 and BODIPY 493/503 colocalization, and GFP-LC3 and LysoTracker colocalization. RGZ treatment decreased liver fat content, liver enzyme levels, and fibrogenic marker expression in high-fat high-cholesterol diet-fed mice. Electron microscopy showed that RGZ treatment restored the high-fat high-cholesterol diet-mediated lipid droplet decrease and autophagic vesicle induction in primary HSCs and liver tissues. However, TFEB overexpression in LX-2 cells offset the aforementioned effects of RGZ on autophagic flux, lipid droplets, and fibrogenic marker expression. CONCLUSIONS: Activation of PPARγ with RGZ ameliorated liver fibrosis and downregulation of TFEB and autophagy in HSCs may be important for the antifibrotic effects of PPARγ activation.

Safety and Clinical Outcomes of Insulin Degludec in Korean Patients with Diabetes in Real-World Practices: A Prospective, Observational Study.

INTRODUCTION: To investigate the safety and effectiveness of insulin degludec (IDeg) in a real-world population of Korean patients with diabetes requiring insulin therapy. METHODS: This was a multicenter, prospective, single-arm, open-label, non-interventional study. Patients aged ≥ 12 months and treated with previous glucose-lowering medications were eligible to switch to IDeg. The primary endpoint was the incidence of adverse events (AEs), and the secondary endpoints were changes in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), postprandial glucose (PPG), and target HbA1c < 7.0%. RESULTS: In total, 3225 and 2450 patients were included in the safety analysis set (SAS) and effectiveness analysis set (EAS), respectively. The mean baseline HbA1c and duration of diabetes were 9.4% and 13.0 years, respectively. Adverse events were reported in 740 patients (22.9%); the majority were mild and resolved. Significant improvements were observed in HbA1c, FPG, and PPG at week 26 (all p < 0.0001). The target of HbA1c < 7% was achieved in 22.2% of patients at week 26. CONCLUSION: In real-world clinical practice, 26 weeks of IDeg treatment resulted in significant reductions in glycemic parameters with a low incidence of AEs in Korean patients with diabetes. No new safety signals were observed. CLINICAL TRIALS REGISTRY AND REGISTRATION NUMBER: This trial is registered under ClinicalTrials.gov (NCT02779413) and the universal trial number is [U1111-1176-2287].

Optimal range of triglyceride values to estimate serum low density lipoprotein cholesterol concentration in Korean adults: the Korea National Health and Nutrition Examination Survey, 2009.

The aims of this study were to investigate the validity of Friedewald's formula and to propose a range of triglyceride values over which the formula can be used without significant error. This was a cross-sectional analysis of 1,929 subjects (946 males and 983 females) aged 20 yr and older using data of the Korea National Health and Nutrition Examination Survey in 2009. Estimated total number was considered to be 10,633,655 (5,846,384 males and 4,787,271 females). Calculated and directly-measured low density lipoprotein cholesterol (LDL-C) values were highly correlated (r = 0.96); however, significant differences were observed between the directly-measured and calculated LDL-C concentrations. Subjects in the underestimated group (10.5%) had higher dysmetabolic profiles than those in the overestimated group (11.4%). Although serum triglyceride level showed the greatest independent association with differences between the calculated and directly-measured LDL-C concentrations, no statistically significant differences were noted when triglyceride concentration was between 36 and 298 mg/dL (93.2%). In conclusion, Friedewald's formula accurately estimates directly-measured serum LDL-C concentration in Korean adults. However, the formula can be applied to subjects with serum triglyceride concentrations from 36 to 298 mg/dL without significant error.

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

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

Trends in the Prevalence of Obesity and Its Phenotypes Based on the Korea National Health and Nutrition Examination Survey from 2007 to 2017 in Korea.

This study used data from the Korea National Health and Nutrition Examination Survey IV-VII from 2007 to identify the prevalence of obesity and its phenotypes (metabolically unhealthy obesity [MUO] and metabolically healthy obesity [MHO]) and their secular changes. The prevalence of obesity in Korea increased with significant secular changes observed (ß=0.326, P trend <0.01) between 2007 and 2017, and especially in men (ß=0.682, P trend <0.001) but not in women. The changes in the prevalence of obesity during the study period were different between men and women (P=0.001). The prevalence of MUO significantly increased only in men (ß=0.565, P trend <0.01), while that of MHO increased only in women (ß=0.179, P<0.05), especially in the younger age group (ß=0.308, P<0.01).

The efficacy and safety of Dendropanax morbifera leaf extract on the metabolic syndrome: a 12-week, placebo controlled, double blind, and randomized controlled trial.

BACKGROUND/OBJECTIVES: The extract from Dendropanax morbifera exhibited diverse therapeutic potentials. We aimed to evaluate the efficacy and safety of D. morbifera leaf extract for improving metabolic parameters in human. SUBJECTS/METHODS: A 12-week, double blind, placebo-controlled and randomized trial included a total of 74 adults, and they were assigned to the placebo group (n = 38) or 700 mg/day of D. morbifera group (n = 36). The efficacy endpoints were changes in glycemic, lipid, obesity, and blood pressure (BP) parameters, in addition to the prevalence of metabolic syndrome (MetS) and the numbers of MetS components. Safety was assessed by monitoring adverse events (AEs). RESULTS: After 12 weeks of treatment, the hemoglobin A1c (HbA1c) level significantly decreased in the D. morbifera group compared to that of the placebo group (difference: -0.13 ± 0.20% vs. 0.00 ± 0.28%, P = 0.031; % of change: -2.27 ± 3.63% vs. 0.10 ± 5.10%, P = 0.025). The homeostatic model assessment for insulin resistance level also decreased significantly from its baseline in the D. morbifera group. The systolic BP of D. morbifera group decreased significantly than that of placebo group (difference: -3.9 ± 9.8 mmHg vs. 3.3 ± 11.7 mmHg, P = 0.005; % of change: -2.8 ± 7.7% vs. 3.3 ± 10.2%, P = 0.005). However, the lipid parameters and body composition including body weight did not differ between the groups. The prevalence of MetS (36.8% vs. 13.9%, P = 0.022) and the incidence of MetS (10.5% vs. 13.9%, P = 0.027) at 12 weeks was significantly lower in the D. morbifera group than it was in the placebo group. No serious AEs occurred in either group. CONCLUSIONS: Supplementation with D. morbifera extracts over a 12-week period improved metabolic parameters such as HbA1c and BP and reduced the prevalence of MetS. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0004672.

Assessment of glycemic lability and severity of hypoglycemia in Korean patients with type 1 diabetes.

Few studies have focused on the quantification of glycemic lability and hypoglycemic events in Asian patients with type 1 diabetes; therefore, we conducted a study to assess glycemic lability and the severity of hypoglycemia in type 1 diabetic patients in Korea. A total of 124 type 1 diabetic patients were enrolled. Several glycemic lability indexes and hypoglycemic indexes were calculated using four-week self-monitoring of blood glucose (SMBG) data. Due to the dependence of the lability index (LI) on the frequency of glucose measurements, we generated a modified LI by dividing by the number of SMBG measurements per day for a given patient. The numbers of patients in our study with a composite hypoglycemic score ≥ 1,047 or LI ≥ 433 mmol/L(2)/h•week(-1), which was found in a previous study to indicate high risk of severe hypoglycemia or lability, were 0 (0%) and 44 (35%), respectively. Compared to previously reported hypoglycemia indexes, the low blood glucose index was lower in our study. However, the glycemic lability indexes were similar to those in previous studies, with the exception of the LI. The modified LI and the average daily risk range (ADRR) showed higher concordance with other glycemic lability indexes than did the LI or mean amplitude of glycemic excursions (MAGE). The results showed that the hypoglycemic indexes in this study population were lower than the results from Ryan et al. Furthermore, the ADRR or modified LI were better measures for high risk of severe lability than were the LI and MAGE.

Statin use for primary prevention in patients with type 2 diabetes: Can it benefit all ages? - A nationwide propensity-matched cohort study.

AIMS: This study aims to investigate whether statin use is associated with a reduction in CVD and mortality in patients with type 2 diabetes without pre-existing CVD. METHODS: A propensity score-matched cohort analysis using retrospective data was created. Statin users received at least a 90-day prescription, and never used statin before initiation of the study. Statin non-users never received statin throughout the study. Primary outcome was a composite of myocardial infarction (MI), stroke, and all-cause death, and secondary outcome was an individual event. RESULTS: The propensity score matched cohort included 168,045 statin users and 168,045 non-users (mean age 57 years; median follow-up 5.0 years). Compared to statin non-users, the hazard ratio (HR) was 0.72 (95% confidence interval [CI] 0.70-0.73; P < 0.001) for composite outcomes, 0.80 (0.76-0.84; P < 0.001) for MI, 0.74 (0.71-0.76; P < 0.001) for stroke, and 0.68 (0.66-0.70; P < 0.001) for all-cause death in statin users. The risk reduction was most prominent in subjects aged 40-74 years, attenuated but significant in those aged ≥75 years, and not significant in those aged <40 years. CONCLUSIONS: Statin showed a protective effect against CVD and all-cause death in type 2 diabetes; this effect was reduced beyond the age of 75 years and disappeared in young patients aged <40 years.