Long-term efficacy and safety of enavogliflozin in Korean people with type 2 diabetes: A 52-week extension of a Phase 3 randomized controlled trial.

AIMS: To evaluate the long-term safety and efficacy of enavogliflozin monotherapy (0.3 mg/day) in individuals with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: Following a 24-week randomized, double-blind treatment period with enavogliflozin 0.3 mg/day (n = 77) or placebo (n = 69), consenting participants received enavogliflozin 0.3 mg/day for an additional 28 weeks during an open-label extension (OLE) period. The safety and efficacy of enavogliflozin were assessed at Week 52. RESULTS: A total of 37 participants continued enavogliflozin (maintenance group), and 26 participants switched from placebo to enavogliflozin (switch group). No additional adverse drug reactions related to enavogliflozin were observed during the OLE period. At Week 52, glycated haemoglobin (HbA1c) and fasting plasma glucose were significantly lower than at the baseline, by 0.9% and 24.9 mg/dL, respectively, in the maintenance group (p < 0.0001 for both), and by 0.7% and 18.0 mg/dL, respectively, in the switch group (p < 0.0001 and p = 0.002). The proportions of participants reaching HbA1c 7.0% (53 mmol/mol) at Week 52 were 69.4% in the maintenance group and 65.4% in the switch group. A significant increase in urine glucose-to-creatinine ratio was observed at Week 52, by 84.9 g/g and 67.1 g/g in the maintenance and switch groups, respectively (p < 0.0001 for both). Body weight in both groups decreased significantly (p < 0.0001) from baseline to Week 52, by 3.5 kg and 3.8 kg in the maintenance and switch groups, respectively. CONCLUSIONS: Enavogliflozin 0.3 mg monotherapy provides long-term glycaemic control in T2DM and is safe and well tolerated during a 52-week treatment period.

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

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

Efficacy and safety of enavogliflozin, a novel SGLT2 inhibitor, in Korean people with type 2 diabetes: A 24-week, multicentre, randomized, double-blind, placebo-controlled, phase III trial.

AIMS: To evaluate the efficacy and safety of a novel sodium-glucose cotransporter 2 inhibitor, enavogliflozin 0.3 mg monotherapy, in Korean people with type 2 diabetes mellitus (T2DM) inadequately controlled with diet and exercise. MATERIALS AND METHODS: This study was a randomized, double-blind, placebo-controlled trial conducted in 23 hospitals. Individuals with haemoglobin A1c (HbA1c) of 7.0%-10.0% after at least 8 weeks of diet and exercise modification were randomized to receive enavogliflozin 0.3 mg (n = 83) or placebo (n = 84) for 24 weeks. The primary outcome was a change in HbA1c at week 24 from baseline. Secondary outcomes included the proportion of participants achieving HbA1c <7.0%, change in fasting glucose, body weight and lipid levels. Adverse events were investigated throughout the study. RESULTS: At week 24, the placebo-adjusted mean change in HbA1c from baseline in the enavogliflozin group was -0.99% (95% confidence interval -1.24%, -0.74%). The proportions of patients achieving HbA1c <7.0% (71% vs. 24%) at week 24 was significantly higher in the enavogliflozin group (p < .0001). Placebo-adjusted mean changes in fasting plasma glucose (-40.1 mg/dl) and body weight (-2.5 kg) at week 24 were statistically significant (p < .0001). In addition, a significant decrease in blood pressure, low-density lipoprotein cholesterol, triglyceride, and homeostasis model assessment of insulin resistance were observed, along with a significant increase in high-density lipoprotein cholesterol. No significant increase in treatment-related adverse events was observed for enavogliflozin. CONCLUSIONS: Monotherapy with enavogliflozin 0.3 mg improved glycaemic control in people with T2DM. Enavogliflozin therapy also exerted beneficial effects on body weight, blood pressure and lipid profile.

Efficacy and safety of monotherapy with enavogliflozin in Korean patients with type 2 diabetes mellitus: Results of a 12-week, multicentre, randomized, double-blind, placebo-controlled, phase 2 trial.

AIMS: The study aimed to evaluate and compare the efficacy and safety of enavogliflozin, a newly developed sodium-glucose cotransporter 2 inhibitor, with placebo in Korean patients with type 2 diabetes mellitus. MATERIALS AND METHODS: Patients with glycated haemoglobin (HbA1c) of 7.0-10.0%, entered a 2-week placebo run-in period, and were randomized to receive once-daily enavogliflozin (0.1, 0.3 or 0.5 mg) or placebo for 12 weeks. The primary efficacy endpoint was the change in HbA1c from baseline at week 12. RESULTS: Overall, 194 patients were included in the full analysis set [placebo, n = 46; enavogliflozin (0.1 mg, n = 49; 0.3 mg, n = 50; 0.5 mg, n = 49)]. Patients receiving 0.1, 0.3 and 0.5 mg enavogliflozin showed significantly reduced HbA1c compared with those receiving placebo at week 12 (-0.79%, -0.89%, -0.92% and -0.08%, respectively; p < .001 vs. placebo). Mean changes in fasting plasma glucose from baseline at week 12 were -30.5, -31.1, -35.0 and 4.9 mg/dl in patients receiving enavogliflozin doses and placebo, respectively. The proportion of patients achieving HbA1c <7.0% at week 12 was significantly higher in the three enavogliflozin groups than in the placebo group (42.9%, 44.0%, 61.2% and 17.4%, respectively). A higher proportion of patients showed HbA1c reduction by >0.5% after receiving enavogliflozin doses than those receiving placebo (61.2%, 72.0%, 65.3% and 26.1%, respectively). There were no significant differences in incidences of adverse events of hypoglycaemia and genital infection between the groups. CONCLUSIONS: Once-daily enavogliflozin monotherapy for 12 weeks is an effective, safe, and well-tolerated treatment for Korean patients with type 2 diabetes mellitus.

Tetrabromobisphenol A Promotes the Osteoclastogenesis of RAW264.7 Cells Induced by Receptor Activator of NF-kappa B Ligand In Vitro.

BACKGROUND: Tetrabromobisphenol A (TBBPA), one of the most widely used brominated flame-retardants, is a representative persistent organic pollutants group. Studies on TBBPA toxicity have been conducted using various target cells; however, few studies have investigated TBBPA toxicity in bone cells. Therefore, this study investigated the in vitro effects of TBBPA on osteoclasts, a cell type involved in bone metabolism. METHODS: RAW264.7 cells were cultured in medium containing 50 ng/mL receptor activator of nuclear factor kappa B ligand (RANKL) and varying concentrations of TBBPA. To evaluate the effects of TBBPA on the differentiation and function of osteoclasts, osteoclast-specific gene expression, tartrate-resistant acid phosphatase (TRAP) activity, bone resorbing activity, mitochondrial membrane potential (MMP) and mitochondrial superoxide were measured. RESULTS: The presence of 20 µ TBBPA significantly increased TRAP activity in RANKL-stimulated RAW264.7 cells, the bone resorbing activity of osteoclasts, and the gene expression of Akt2, nuclear factor of activated T-cells cytoplasmic 1, and chloride channel voltage-sensitive 7. However, TBBPA treatment caused no change in the expression of carbonic anhydrase II, cathepsin K, osteopetrosis-associated transmembrane protein 1, Src, extracellular signal-related kinase, GAB2, c-Fos, or matrix metalloproteinase 9. Furthermore, 20 µ TBBPA caused a significant decrease in MMP and a significant increase in mitochondrial superoxide production. CONCLUSION: This study suggests that TBBPA promotes osteoclast differentiation and activity. The mechanism of TBBPA-stimulated osteoclastogenesis might include increased expression of several genes involved in osteoclast differentiation and reactive oxygen species production.

Perfluorooctanoic acid induces mitochondrial dysfunction in MC3T3-E1 osteoblast cells.

Perfluorooctanoic acid (PFOA), a stable organic perfluorinated compound, is an emerging persistent organic pollutant, found widely in human and wildlife populations. Recent evidence suggests that exposure to environmental toxicants can be associated with higher risks of osteoporosis and fractures. We studied the cellular toxicology of PFOA in MC3T3-E1osteoblast cells. To examine the effect of PFOA, we measured cell viability, reactive oxygen species (ROS), mitochondrial superoxide, and mitochondrial parameters including adenosine triphosphate (ATP) level, mitochondrial membrane potential (MMP), cardiolipin content, and cytochrome c release in MC3T3-E1 cells. Incubating MC3T3-E1 cells in different concentrations of PFOA for 48 h resulted in a concentration-dependent decrease in cell viability and significant inductions of ROS and mitochondrial superoxide. Moreover, PFOA induced MMP collapse, cardiolipin peroxidation, cytochrome c release, and decreased ATP levels, which in turn induced apoptosis or necrosis. When osteoblast differentiation markers were assessed, PFOA treatment caused a significant reduction in alkaline phosphatase activity, collagen synthesis, and mineralization in the cells. In summary, we found an ROS- and mitochondria-mediated pathway for the induction of cell damage by PFOA in MC3T3-E1 cells. Together, our results indicate that mitochondrial toxicity could be a plausible mechanism for the toxic effects of PFOA on osteoblast function.

Tetrabromobisphenol A induces cellular damages in pancreatic ß-cells in vitro.

Tetrabromobisphenol A (TBBPA) is a well-known organobrominated flame retardant. TBBPA has been detected in the environment. The roles played by environmental pollutants in increasing the prevalence of metabolic syndrome are attracting increasing concern. In the present work, we investigated the effects of TBBPA on rat pancreatic ß-cells (the RIN-m5F cell line). RIN-m5F cells were incubated with different concentrations of TBBPA for 48 h, and cell viability and the extent of apoptosis were determined. We also measured the levels of inflammatory cytokines, reactive oxygen species (ROS), mitochondrial adenosine triphosphate (ATP), and cardiolipin, as well as the extent of cytochrome c release from mitochondria. TBBPA reduced the ATP level, induced cardiolipin peroxidation and cytochrome c release, and triggered apoptotic cell death. Moreover, TBBPA increased the levels of inflammatory cytokines (TNF-α and IL-1ß), nitric oxide, intracellular ROS, and mitochondrial superoxide. Together, our results indicate that TBBPA damages pancreatic ß-cells by triggering mitochondrial dysfunction and inducing apoptosis.

Exposure to tetrabromobisphenol A induces cellular dysfunction in osteoblastic MC3T3-E1 cells.

This study was undertaken to investigate the possible involvement of oxidative stress in tetrabromobisphenol A (TBBPA)-induced toxicity in osteoblastic MC3T3-E1 cells. To examine the potential effect of TBBPA on cultured osteoblastic cells, we measured cell viability, apoptosis, reactive oxygen species (ROS), mitochondrial superoxide, and mitochondrial parameters including adenosine triphosphate (ATP) level, cardiolipin content, cytochrome c release, cyclophilin levels, and differentiation markers in osteoblastic MC3T3-E1 cells. TBBPA exposure for 48 h caused the apoptosis and cytotoxicity of MC3T3-E1 cells. TBBPA also induced ROS and mitochondrial superoxide production in a concentration-dependent manner. These results suggest that TBBPA induces osteoblast apoptosis and ROS production, resulting in bone diseases. Moreover, TBBPA induced cardiolipin peroxidation, cytochrome c release, and decreased ATP levels which induced apoptosis or necrosis. TBBPA decreased the differentiation markers, collagen synthesis, alkaline phosphatase activity, and calcium deposition in cells. Additionally, TBBPA decreased cyclophilin A and B releases. Taken together, these data support the notion that TBBPA inhibits osteoblast function and has detrimental effects on osteoblasts through a mechanism involving oxidative stress and mitochondrial dysfunction.

Change in somatostatinergic tone of acromegalic patients according to the size of growth hormone-producing pituitary tumors.

The aim of this study was to investigate the relationship between somatostatinergic tone (SST) and the size of growth hormone (GH)-producing pituitary tumors. GH levels of 29 patients with newly diagnosed acromegaly were measured using a 75-gram oral glucose tolerance test (OGTT), an insulin tolerance test (ITT), and an octreotide suppression test (OST). Differences between GH levels during the ITT and the OGTT (ΔGHIO), and between the OGTT and the OST at the same time point (ΔGHOS) were compared according to the size of the tumor and the response pattern to the OST. ΔGHIO of macroadenomas (n=22) was non-significantly higher than those of microadenomas while ΔGHOS of macroadenomas were significantly higher than those of microadenomas. According to further analyses of macroadenomas based on the response pattern to the OST, GH levels during the ITT were significantly higher in non-responders. ΔGHOS showed near-significant differences between responders and non-responders. In conclusion, as the size of the pituitary tumor increases, the effect of glucose on SST appears to be attenuated. Macroadenomas that are non-responders to the OST possess a portion of GH secretion exceeding the range of regulation by SST.

Apigenin attenuates 2-deoxy-D-ribose-induced oxidative cell damage in HIT-T15 pancreatic ß-cells.

Glucose toxicity contributes to progressive ß-cell failure and the development of overt diabetes. Oxidative stress is an important aspect of glucose toxicity in pancreatic ß-cells. We investigated whether the flavonoid apigenin protects pancreatic ß-cells from 2-deoxy-D-ribose (dRib)-induced oxidative cell damage. HIT-T15 pancreatic ß-cells were cultured with or without apigenin in the presence of dRib. Time- and dose-dependent cell viability was monitored using a cell counting kit (CCK-8), while the induction of apoptosis was analyzed using a cell death enzyme-linked immunosorbent assay (ELISA) kit. Mitochondrial membrane potential (ΔΨ(m)) was determined using the JC-1 kit. Intracellular oxidative stress was measured by fluorometric analysis of DCFH oxidation using 2',7'-dichlorofluorescin diacetate (DCFH-DA) as the probe. In addition, the DNA binding activity of the oxidative stress-related transcriptional factors nuclear factor-κB (NF-κB) and activator protein 1 (AP-1) were analyzed. dRib reduced cell survival and ΔΨ(m), while it markedly increased intracellular levels of reactive oxygen species (ROS), apoptosis, and the activity of the oxidative stress-related transcription factors NF-κB and AP-1. However, pretreatment of cells with apigenin attenuated all the dRib-induced effects. The anti-oxidants, N-acetyl-L-cysteine (NAC) and alpha lipoic acid (ALA), also prevented both dRib-induced oxidative damage and activation of NF-κB and AP-1. Taken together, these results suggest that apigenin attenuates dRib-induced cell damage in pancreatic ß-cells via oxidative stress-related signaling.

Evaluation of the effectiveness of sarpogrelate on the surrogate markers for macrovascular complications in patients with type 2 diabetes.

Sarpogrelate, a selective 5-HT(2) receptor antagonist, is known to have a significant effect on antiplatelet action. This study was a double-blinded, randomized, paralleled multicenter trial to compare the effects of sarpogrelate and aspirin on preventing macrovascular complications in patients with type 2 diabetes. The subjects were randomly assigned to either the sarpogrelateor the aspirin group. The baseline parameters for macrovascular complications, such as intima media thickness (IMT), ankle-brachial index (ABI), IL-6, serotonin, adiponectin, and hsCRP, were measured before drug administration. Changes were compared at 6 and 12 months after the administration of each drug. A total of 127 subjects (63 in the sarpogrelate group and 64 in the aspirin group) were pooled during the study period. No significant differences were found in baseline IMT or in other predictors of macrovascular complications. The mean IMT increased in both groups after 12 months, but there was no significant difference between the two groups. No significant change was found in the other predictors of macrovascular complications nor in the incidence of drug-related adverse events between the two groups. During the study period, no significant differences were found between the sarpogrelate group and aspirin group in the clinical indices or in the safety of the subjects related to macrovascular complications. This suggests that sarpogrelate may be clinically useful for the primary prevention of macrovascular complications in patients with type 2 diabetes.

Gyejibokryeong-Hwan improves recovery of injured muscles in mouse model of muscle contusion.

OBJECTIVE: To investigate the effects of Gyejibokryeong-Hwan (Guizhifuling-wan, GBH) on muscle injury in a mouse model of muscle contusion. METHODS: C57/BL6 mouse biceps femoris muscles were injured using the drop-mass method and injured animals were treated orally with GBH (50, 100, or 500 mg/kg) once a day for 7 d. Open field and treadmill running tests were performed to assess functional recovery from muscle injury. The production of pro-inflammatory cytokines was examined by enzyme-linked immunosorbent assay and Western blotting analysis. Expression of the muscle regeneration biomarkers, myoblast determination (MyoD), myogenic factor 5 (Myf5), and smooth muscle actin (α-SMA), in the biceps femoris muscle was investigated at the protein and mRNA level by Western blotting and real time-PCR, respectively. Histological analysis was performed using hematoxylin and eosin staining. Finally, myosin heavy chain production was investigated in differentiated C2C12 myoblasts in the presence of GBH. RESULTS: GBH treatment markedly improved locomotion and running behavior. GBH significantly inhibited the secretion of monocyte chemoattractant protein-1 into the bloodstream in muscle-contused animals. The levels of MyoD, Myf5, and α-SMA protein and mRNA were significantly up-regulated by GBH in injured muscle tissue. Histological studies suggested that GBH facilitated recovery from muscle damage. However, GBH did not induce the production of myosin heavy chain in vitro. CONCLUSION: Overall, the present study suggested that GBH improves the recovery of the injured muscles in the mouse model of muscle contusion.

Prooxidative effects of green tea polyphenol (-)-epigallocatechin-3-gallate on the HIT-T15 pancreatic beta cell line.

Epigallocatechin-3-gallate (EGCG) is the main polyphenolic constituent in green tea and is believed to function as an antioxidant. However, increasing evidence indicates that EGCG produces reactive oxygen species (ROS) and subsequent cell death. In this study, we investigated the prooxidative effects of EGCG on the HIT-T15 pancreatic beta cell line. Dose-dependent cell viability was monitored with the cell counting kit-8 assay, while the induction of apoptosis was analyzed by a cell death ELISA kit and comet assay. Extracellular H(2)O(2) was determined using the Amplex Red Hydrogen Peroxide Assay Kit. Intracellular oxidative stress was measured by fluorometric analysis of 2',7'-dichlorofluorescin (DCFH) oxidation using DCFH diacetate (DA) as the probe. Treatment with EGCG (5-100 microM) decreased the viability of pancreatic beta cells, caused concomitant increases in apoptotic cell death, and increased the production of H(2)O(2) and ROS. Catalase, the iron-chelating agent diethylenetriaminepentaacetic acid, and the Fe(II)-specific chelator o-phenanthroline all suppressed the effects of EGCG, indicating the involvement of both H(2)O(2) and Fe(II) in the mechanism of action of EGCG. The antioxidant N-acetyl-cysteine and alpha-lipoic acid also suppressed the effects of EGCG. Furthermore, EGCG did not scavenge exogenous H(2)O(2), but rather, it synergistically increased H(2)O(2)-induced oxidative cell damage in pancreatic beta cells. Together, these findings suggest that in the HIT-T15 pancreatic beta cell line, EGCG mediated the generation of H(2)O(2), triggering Fe(II)-dependent formation of a highly toxic radical that in turn induced oxidative cell damage.

Kaempferol protects HIT-T15 pancreatic beta cells from 2-deoxy-D-ribose-induced oxidative damage.

During the progression of Type 2 diabetes, glucose toxicity is likely to contribute importantly to progressive beta cell failure. Oxidative stress is an important aspect of glucose toxicity in pancreatic beta cells, and reducing sugars, such as 2-deoxy-D-ribose (dRib), produce reactive oxygen species. Furthermore, many of the biological properties of flavonoids are likely to be related to their antioxidant and free-radical scavenging abilities. Accordingly, in the present study, we investigated whether kaempferol (a flavonol) protects beta cells from dRib-induced oxidative damage. HIT-T15 cells were cultured with various concentrations of dRib for 24h. Cell survivals, amounts of reactive oxygen species (ROS) generated, apoptosis, and lipid peroxidation were measured. dRib was found to dose-dependently reduce cell survival and to markedly increase intracellular ROS levels, apoptosis, and lipid peroxidation. However, kaempferol (10 microM) suppressed dRib (20 mM) induced intracellular ROS, apoptosis, and lipid peroxidation. So, we demonstrate that kaempferol reduces dRib-mediated beta cell damage interfering with ROS metabolism and protective effects against lipid peroxidation. Our findings indicate that kaempferol protects HIT-T15 cells from dRib-induced associated oxidative damage.

Generalized acanthosis nigricans related to type B insulin resistance syndrome: a case report.

Acanthosis nigricans (AN) is a cutaneous marker for many underlying states such as endocrine abnormality, obesity, certain drugs, and malignancy. Generalized AN is a rare condition and is commonly seen in adults with an underlying malignancy. The type B insulin resistance syndrome, a rare autoimmune disorder, is caused by the autoantibodies to the insulin receptor. Patients typically present with hyperglycemia but also may present with hypoglycemia. We report a rare case of a 36-year-old man with generalized AN and type B insulin resistance syndrome with hypoglycemia.

Diagnosis and Treatment of Growth Hormone Deficiency: A Position Statement from Korean Endocrine Society and Korean Society of Pediatric Endocrinology.

Growth hormone (GH) deficiency is caused by congenital or acquired causes and occurs in childhood or adulthood. GH replacement therapy brings benefits to body composition, exercise capacity, skeletal health, cardiovascular outcomes, and quality of life. Before initiating GH replacement, GH deficiency should be confirmed through proper stimulation tests, and in cases with proven genetic causes or structural lesions, repeated GH stimulation testing is not necessary. The dosing regimen of GH replacement therapy should be individualized, with the goal of minimizing side effects and maximizing clinical improvements. The Korean Endocrine Society and the Korean Society of Pediatric Endocrinology have developed a position statement on the diagnosis and treatment of GH deficiency. This position statement is based on a systematic review of evidence and expert opinions.

Analysis of diabetes quality assessment findings and future directions for the appropriate management of diabetes in Korea.

BACKGROUND/AIMS: Due to recent increases in the disease burden of diabetes mellitus, the Health Insurance Review and Assessment Service (HIRA) of Korea implemented a quality assessment of the treatment of diabetes to improve patient care. The present study was conducted to identify any changes after the implementation of the diabetes quality assessment (DQA). METHODS: The present study evaluated eight quality assessment indicators that were proposed by the HIRA in all patients with diabetes who visited a university hospital in Korea between 2009 and 2014. The indicators were statistically compared according to the characteristics of the subjects. RESULTS: There were several significant differences in the indicators among the subjects according to their demographic characteristics. Female patients had a higher continuity of treatment (COT) than that of male patients, and the insulin-treated group had a higher COT than that of the non-treated group, as well as a higher rate of undergoing the diabetes complication tests (DCTs). Patients between 40 and 80 years of age had the highest COT, while patients under 40 years of age had the lowest COT but the highest rate of taking the DCTs. Patients receiving treatment from an endocrinologist exhibited higher numbers of DCTs performed but displayed lower proportions for the prescription indicators. CONCLUSION: The present analysis of the DQA findings revealed that endocrinologists combine prevention and management of diabetes complications with measures for glycemic control. Thus, the effective management of diabetes likely entails systematic joint treatment regimens that involve an endocrinologist.

Medical Treatment with Somatostatin Analogues in Acromegaly: Position Statement.

The Korean Endocrine Society (KES) published clinical practice guidelines for the treatment of acromegaly in 2011. Since then, the number of acromegaly cases, publications on studies addressing medical treatment of acromegaly, and demands for improvements in insurance coverage have been dramatically increasing. In 2017, the KES Committee of Health Insurance decided to publish a position statement regarding the use of somatostatin analogues in acromegaly. Accordingly, consensus opinions for the position statement were collected after intensive review of the relevant literature and discussions among experts affiliated with the KES, and the Korean Neuroendocrine Study Group. This position statement includes the characteristics, indications, dose, interval (including extended dose interval in case of lanreotide autogel), switching and preoperative use of somatostatin analogues in medical treatment of acromegaly. The recommended approach is based on the expert opinions in case of insufficient clinical evidence, and where discrepancies among the expert opinions were found, the experts voted to determine the recommended approach.

Cardio-Ankle Vascular Index as a Surrogate Marker of Early Atherosclerotic Cardiovascular Disease in Koreans with Type 2 Diabetes Mellitus.

BACKGROUND: Carotid artery intima medial thickness (IMT), brachial-ankle pulse wave velocity (baPWV), and ankle-brachial index (ABI) are commonly used surrogate markers of subclinical atherosclerosis in patients with type 2 diabetes mellitus (T2DM). The cardio-ankle vascular index (CAVI) is a complement to the baPWV, which is affected by blood pressure. However, it is unclear which marker is the most sensitive predictor of atherosclerotic cardiovascular disease (ASCVD). METHODS: This was a retrospective non-interventional study that enrolled 219 patients with T2DM. The correlations among IMT, ABI, and CAVI as well as the relationship of these tests to the 10-year ASCVD risk were also analyzed. RESULTS: Among the 219 patients, 39 (17.8%) had ASCVD. In the non-ASCVD group, CAVI correlated significantly with IMT after adjusting for confounding variables, but ABI was not associated with CAVI or IMT. The analyses after dividing the non-ASCVD group into three subgroups according to the CAVI score (<8, ≥8 and <9, and ≥9) demonstrated the significant increase in the mean IMT, 10-year ASCVD risk and number of metabolic syndrome risk factors, and decrease in the mean ABI in the high-CAVI group. A high CAVI was an independent risk factor in the non-ASCVD group for both a high 10-year ASCVD risk (≥7.5%; odds ratio [OR], 2.42; P<0.001) and atherosclerosis (mean IMT ≥1 mm; OR, 1.53; P=0.007). CONCLUSION: In Korean patients with T2DM without ASCVD, CAVI was the most sensitive of several surrogate markers for the detection of subclinical atherosclerosis.

Insulin secretion and insulin resistance in newly diagnosed, drug naive prediabetes and type 2 diabetes patients with/without metabolic syndrome.

The relationships between insulin secretion and resistance in subjects with newly diagnosed prediabetes (preDM) and type 2 DM according to the presence of metabolic syndrome (MS) were controversial. We performed OGTT on 322 drug naive subjects with a history of hyperglycemia of < or =3 months, and divided into three groups, NGT, preDM (IFG and/or IGT), and T2DM. We also diagnosed these subjects with respect to MS according to ATP III criteria modified by Asia-Pacific guidelines and compared IGI and HOMA-IR. When compare groups stratified by the presence of MS, preDM and T2DM groups with MS showed significantly higher mean HOMA-IR and IGI than those without. When compare groups with respect to glucose tolerance, NGT, preDM, and T2DM subgroups in MS group showed significant higher HOMA-IR and lower IGI according to glucose tolerance. However, NGT, preDM, and T2DM subgroups in non-MS group showed a significant decrease in IGI but no significant difference in HOMA-IR as glucose tolerance worsened. In conclusion, deterioration in IGI and aggravation of HOMA-IR are both important in the primary pathogenesis of diabetes in those with MS. However, IGI deterioration may be the only important factor in the primary pathogenesis of T2DM in the absence of MS.