Safety and Effectiveness of Empagliflozin in Korean Patients with Type 2 Diabetes Mellitus: Results from a Nationwide Post-Marketing Surveillance

Background@#To evaluate the safety and effectiveness of empagliflozin in routine clinical settings, we collected and assessed the clinical profiles of Korean patients with type 2 diabetes mellitus. @*Methods@#This was a post-marketing surveillance study of empagliflozin 10 and 25 mg. Information on adverse events and adverse drug reactions (ADRs) was collected as safety data sets. Available effectiveness outcomes, including glycosylated hemoglobin (HbA1c) level, fasting plasma glucose, body weight, and blood pressure, were assessed. @*Results@#The incidence rate of ADRs was 5.14% in the safety dataset (n=3,231). Pollakiuria, pruritis genital, and weight loss were the most common ADRs. ADRs of special interest accounted for only 1.18%, and there were no serious events that led to mortality or hospitalization. In the effectiveness data set (n=2,567), empagliflozin significantly reduced the mean HbA1c level and body weight during the study period by –0.68%±1.39% and –1.91±3.37 kg (both P<0.0001), respectively. In addition, shorter disease duration, absence of dyslipidemia, and higher baseline HbA1c levels were identified as the clinical features characteristic of a “responder” to empagliflozin therapy. @*Conclusion@#Empagliflozin is a safe and potent glucose-lowering drug in routine use among Korean patients with type 2 diabetes mellitus. It is expected to have better glycemic efficacy in Korean patients with poorly controlled type 2 diabetes mellitus.

Efficacy and Safety of Pioglitazone versus Glimepiride after Metformin and Alogliptin Combination Therapy: A Randomized, Open-Label, Multicenter, Parallel-Controlled Study

BACKGROUND@#There is limited information regarding the optimal third-line therapy for managing type 2 diabetes mellitus (T2DM) that is inadequately controlled using dual combination therapy. This study assessed the efficacy and safety of pioglitazone or glimepiride when added to metformin plus alogliptin treatment for T2DM.@*METHODS@#This multicenter, randomized, active-controlled trial (ClinicalTrials.gov: NCT02426294) recruited 135 Korean patients with T2DM that was inadequately controlled using metformin plus alogliptin. The patients were then randomized to also receive pioglitazone (15 mg/day) or glimepiride (2 mg/day) for a 26-week period, with dose titration was permitted based on the investigator's judgement.@*RESULTS@#Glycosylated hemoglobin levels exhibited similar significant decreases in both groups during the treatment period (pioglitazone: −0.81%, P<0.001; glimepiride: −1.05%, P<0.001). However, the pioglitazone-treated group exhibited significantly higher high density lipoprotein cholesterol levels (P<0.001) and significantly lower homeostatic model assessment of insulin resistance values (P<0.001). Relative to pioglitazone, adding glimepiride to metformin plus alogliptin markedly increased the risk of hypoglycemia (pioglitazone: 1/69 cases [1.45%], glimepiride: 14/66 cases [21.21%]; P<0.001).@*CONCLUSION@#Among patients with T2DM inadequately controlled using metformin plus alogliptin, the addition of pioglitazone provided comparable glycemic control and various benefits (improvements in lipid profiles, insulin resistance, and hypoglycemia risk) relative to the addition of glimepiride.

Experience of taking Oral Contraceptives in Adult Women

PURPOSE: The purpose of this study was to explore essences and meanings of using oral contraceptives among adult women. METHODS: The interview was conducted with 20 adult women who lived in Seoul, Gyeongi Province, Jeolla Province, Chungcheong Province, and Gangwon Province. Participants with the experience of using oral contraceptives for contraception were selected by convenience sampling. Semi-structured interviews were conducted for data collection. The data were analyzed using Colaizzi's method. RESULTS: Five themes revealed: ‘Lack of information and knowledge regarding oral contraceptives’, ‘Inconvenient and difficult purchase process of oral contraceptives’, ‘Pressure and fear regarding other people's reaction’, ‘Self-centered thinking toward the use of oral contraceptives’, ‘A need for a change in public awareness and policy’. CONCLUSION: A change in society's perception about oral contraceptives is required for safe contraceptives use. Therefore, it is necessary to educate the correct usage of oral contraceptives, and to develop a program for changing the paradigm of sex education.

Repeated Glucose Deprivation/Reperfusion Induced PC-12 Cell Death through the Involvement of FOXO Transcription Factor

BACKGROUND: Cognitive impairment and brain damage in diabetes is suggested to be associated with hypoglycemia. The mechanisms of hypoglycemia-induced neural death and apoptosis are not clear and reperfusion injury may be involved. Recent studies show that glucose deprivation/reperfusion induced more neuronal cell death than glucose deprivation itself. The forkhead box O (FOXO) transcription factors are implicated in the regulation of cell apoptosis and survival, but their role in neuronal cells remains unclear. We examined the role of FOXO transcription factors and the involvement of the phosphatidylinositol 3-kinase (PI3K)/Akt and apoptosis-related signaling pathways in PC-12 cells exposed to repeated glucose deprivation/reperfusion. METHODS: PC-12 cells were exposed to control (Dulbecco's Modified Eagle Medium [DMEM] containing 25 mM glucose) or glucose deprivation/reperfusion (DMEM with 0 mM glucose for 6 hours and then DMEM with 25 mM glucose for 18 hours) for 5 days. MTT assay and Western blot analysis were performed for cell viability, apoptosis, and the expression of survival signaling pathways. FOXO3/4',6-diamidino-2-phenylindole staining was done to ascertain the involvement of FOXO transcription factors in glucose deprivation/reperfusion conditions. RESULTS: Compared to PC-12 cells not exposed to hypoglycemia, cells exposed to glucose deprivation/reperfusion showed a reduction of cell viability, decreased expression of phosphorylated Akt and Bcl-2, and an increase of cleaved caspase-3 expression. Of note, FOXO3 protein was localized in the nuclei of glucose deprivation/reperfusion cells but not in the control cells. CONCLUSION: Repeated glucose deprivation/reperfusion caused the neuronal cell death. Activated FOXO3 via the PI3K/Akt pathway in repeated glucose deprivation/reperfusion was involved in genes related to apoptosis.

A Case of Fulminant Type 1 Diabetes during Pregnancy / 임상당뇨병

Fulminant type 1 diabetes is characterized by acute onset, no evidence of islet-related autoantibodies, low glycated hemoglobin(HbA1c) level at onset, and metabolic complications such as diabetic ketoacidosis. Fulminant type 1 diabetes development during pregnancy can result in severe maternal and fetal complications. Most of the patients with fulminant type 1 diabetes during pregnancy have been reported in Japan. In Korea, reports of fulminant type 1 diabetes during pregnancy are uncommon. We report a 36-year-old Korean woman with fulminant type 1 diabetes developed at 32 weeks of gestation who demonstrate a good outcome.

Co-Culture of alpha TC-6 Cells and beta TC-1 Cells: Morphology and Function

BACKGROUND: In vitro experiments using only beta-cell lines instead of islets are limited because pancreatic islets are composed of four different types of endocrine cells. Several recent studies have focused on cellular interactions among these cell types, especially alpha- and beta-cells. Because islet isolation needs time and experience, we tested a simple co-culture system with alpha- and beta-cells. Their morphology and function were assessed by comparison to each single cell culture and pancreatic islets. METHODS: alpha TC-6 cells and beta TC-1 cells were maintained in Dulbecco's Minimal Essential Medium containing 5 mM glucose and 10% fetal bovine serum. Cells were mixed at a 1:1 ratio (5x10(5)) in 6-well plates and cultured for 24, 48, and 72 hours. After culture, cells were used for insulin and glucagon immunoassays and tested for glucose-stimulated insulin secretion (GSIS). RESULTS: alpha TC-6 and beta TC-1 cells became condensed by 24 hours and were more strongly compacted after 48 hours. beta TC-1 cells showed both beta-beta and beta-alpha cell contacts. GSIS increased with increasing glucose concentration in co-cultured cells, which showed lower secreted insulin levels than beta TC-1 cells alone. The increase in the secreted insulin/insulin content ratio was significantly lower for co-cultured cells than for beta-cells alone (P=0.04). Compared to islets, the alpha-/beta-cell co-culture showed a higher ratio of GSIS to insulin content, but the difference was not statistically significant (P=0.09). CONCLUSION: alpha TC-6 and beta TC-1 cells in the co-culture system showed cell-to-cell contacts and a similar stimulated insulin secretion pattern to islets. The co-culture system may be used to better mimic pancreatic islets in in vitro assessments.

A Case of Type 2 Diabetes Mellitus Initially Presented as Monochorea Associated with Ketotic Hyperglycemia / 임상당뇨병

Monoballismus-monochorea is abnormal neurologic sign characterized by continuous, involuntary and irregular movement involving one extremity. Hyperglycemic ballism-chorea is predominantly observed in older type 2 diabetic patients and non-ketotic hyperglycemia, and is associated with contralateral striatal hyperintensities (i.e., putamen and caudate) on both brain CT and MRI. Movement disorders as the initial symptoms of diabetes mellitus are rare, especially in ketotic hyperglycemia. Here, we report one of these rare manifestations of transient monoballismus with during an episode of ketotic hyperglycemia without contralateral striatal abnormal findings on brain MRI in newly diagnosed diabetes mellitus.

Current Status of Prescription in Type 2 Diabetic Patients from General Hospitals in Busan

BACKGROUND: Data regarding the prescription status of individuals with diabetes are limited. This study was an analysis of participants from the relationship between cardiovascular disease and brachial-ankle pulse wave velocity in patients with type 2 diabetes (REBOUND) Study, which was a prospective multicenter cohort study recruited from eight general hospitals in Busan, Korea. We performed this study to investigate the current status of prescription in Korean type 2 diabetic patients. METHODS: Type 2 diabetic patients aged 30 years or more were recruited and data were collected for demographics, medical history, medications, blood pressure, and laboratory tests. RESULTS: Three thousands and fifty-eight type 2 diabetic patients were recruited. Mean age, duration of diabetes, and HbA1c were 59 years, 7.6 years, and 7.2%, respectively. Prevalence of hypertension was 66%. Overall, 7.3% of patients were treated with diet and exercise only, 68.2% with oral hypoglycemic agents (OHAs) only, 5.3% with insulin only, and 19.2% with both insulin and OHA. The percentage of patients using antihypertensive, antidyslipidemic, antiplatelet agents was similar as about 60%. The prevalence of statins and aspirin users was 52% and 32%, respectively. CONCLUSION: In our study, two thirds of type 2 diabetic patients were treated with OHA only, and one fifth with insulin plus OHA, and 5% with insulin only. More than half of the patients were using each of antihypertensive, antidyslipidemic, or antiplatelet agents. About a half of the patients were treated with statins and one third were treated with aspirin.

Low glibenclamide concentrations affect endoplasmic reticulum stress in INS-1 cells under glucotoxic or glucolipotoxic conditions

BACKGROUND/AIMS: beta-Cell apoptosis caused by increased endoplasmic reticulum (ER) stress is an important pathogenic component of type 2 diabetes mellitus. In theory, sulfonylureas, used for the treatment of diabetes, can contribute to ER stress. We assessed changes in ER stress in pancreatic beta-cells under glucotoxic or glucolipotoxic conditions using low concentrations of the sulfonylurea, glibenclamide (GB). METHODS: Low concentrations of GB (10 or 100 nM) were added to INS-1 cells cultured under glucotoxic or glucolipotoxic conditions. The degree of viability, level of apoptosis and levels of markers associated with ER stress were measured. RESULTS: Apoptosis decreased in response to low concentrations of GB under glucolipotoxic but not glucotoxic conditions. Most ER stress markers decreased upon the addition of GB. Under glucotoxic conditions, changes in the levels of ER stress markers were not consistent. However, all decreased significantly under glucolipotoxic conditions. CONCLUSIONS: Low concentrations of GB exerted antiapoptotic effects through the attenuation of ER stress under glucolipotoxic conditions.

Acculturative Stress, Depression and Drinking Problems of Korean International Students in the United States

PURPOSE: The purpose of this study was to identify predictors of drinking problems in Korean international students in the United States. METHODS: The subjects involved this study were 190 Korean international students in the United States. Data were measured using a drinking problems questionnaire, an acculturative stress scale for international student, and the CES-D. The collected data were analyzed using the SPSS/WIN 17.0 program to calculate mean, standard deviation, ANOVA, Sheffe test and pearson's correlation coefficient. and stepwise multiple regression. RESULTS: 1) The mean score of the degree of perceived acculturative stress was 2.15+/-0.63, of depression was 17.67+/-9.85, and of drinking problems was 15.03+/-15.52. 2) There were significant correlations between acculturative stress and drinking problems (r=.506, p<.001), between depression and drinking problems (r=.6726, p<.001), and between acculturative stress and depression (r=.453, p<.001). 3) In stepwise multiple regression analysis the most powerful predictor of drinking problems were acculturative stress (beta=.243, p<.001), and depression (beta=.562, p<.001). CONCLUSION: Based on the results, practical implications for reducing the acculturative stress and improving the psychological well-being of Korean students were discussed.