Background: Administration of pancreatic endoplasmic reticulum kinase inhibitor (PERKi) improved insulin secretion and hyperglycemia in obese diabetic mice. In this study, autophagic balance was studied whether to mediate it. Methods: Human islets were isolated from living patients without diabetes. PERKi GSK2606414 effects were evaluated in the islets under glucolipotoxicity by palmitate. Islet insulin contents and secretion were measured. Autophagic flux was assessed by microtubule associated protein 1 light chain 3 (LC3) conversion, a red fluorescent protein (RFP)-green fluorescent protein (GFP)- LC3 tandem assay, and P62 levels. For mechanical analyses, autophagy was suppressed using 3-methyladenine in mouse islets. Small interfering RNA for an autophagy-related gene autophagy related 7 (Atg7) was transfected to interfere autophagy. Results: PERKi administration to mice decreased diabetes-induced P62 levels in the islets. Glucolipotoxicity significantly increased PERK phosphorylation by 70% and decreased insulin contents by 50% in human islets, and addition of PERKi (40 to 80 nM) recovered both. PERKi also enhanced glucose-stimulated insulin secretion (6-fold). PERKi up-regulated LC3 conversion suppressed by glucolipotoxicity, and down-regulated P62 contents without changes in P62 transcription, indicating enhanced autophagic flux. Increased autophagosome-lysosome fusion by PERKi was visualized in mouse islets, where PERKi enhanced ATG7 bound to LC3. Suppression of Atg7 eliminated PERKi-induced insulin contents and secretion. Conclusion This study provided functional changes of human islets with regard to autophagy under glucolipotoxicity, and suggested modulation of autophagy as an anti-diabetic mechanism of PERKi.

Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

In May 2023, the Committee of Clinical Practice Guidelines of the Korean Diabetes Association published the revised clinical practice guidelines for Korean adults with diabetes and prediabetes. We incorporated the latest clinical research findings through a comprehensive systematic literature review and applied them in a manner suitable for the Korean population. These guidelines are designed for all healthcare providers nationwide, including physicians, diabetes experts, and certified diabetes educators who manage patients with diabetes or individuals at risk of developing diabetes. Based on recent changes in international guidelines and the results of a Korean epidemiological study, the recommended age for diabetes screening has been lowered. In collaboration with the relevant Korean medical societies, recently revised guidelines for managing hypertension and dyslipidemia in patients with diabetes have been incorporated into this guideline. An abridgment containing practical information on patient education and systematic management in the clinic was published separately.

Primary aldosteronism (PA) is a common, yet underdiagnosed cause of secondary hypertension. It is characterized by an overproduction of aldosterone, leading to hypertension and/or hypokalemia. Despite affecting between 5.9% and 34% of patients with hypertension, PA is frequently missed due to a lack of clinical awareness and systematic screening, which can result in significant cardiovascular complications. To address this, medical societies have developed clinical practice guidelines to improve the management of hypertension and PA. The Korean Endocrine Society, drawing on a wealth of research, has formulated new guidelines for PA. A task force has been established to prepare PA guidelines, which encompass epidemiology, pathophysiology, clinical presentation, diagnosis, treatment, and follow-up care. The Korean clinical guidelines for PA aim to deliver an evidence-based protocol for PA diagnosis, treatment, and patient monitoring. These guidelines are anticipated to ease the burden of this potentially curable condition.

Although pancreatic endoplasmic reticulum kinase (PERK) is indispensable to beta cells, low-dose PERK inhibitor improved glucose- stimulated insulin secretion (GSIS) and hyperglycemia in diabetic mice. Current study examined if partial deletion of Perk (Perk+/-) recapitulated the effects of PERK inhibitor, on the contrary to the complete deletion. Perk+/- mice and wild-type controls were fed with a high-fat diet (HFD) for 23 weeks. Glucose tolerance was evaluated along with serum insulin levels and islet morphology. Perk+/- mice on normal chow were comparable to wild-type mice in various metabolic features. HFD-induced obesity was not influenced by Perk reduction; however, HFD-induced glucose intolerance was significantly improved since 15-week HFD. HFD-induced compromises in GSIS were relieved by Perk reduction, accompanied by reductions in phosphorylated PERK and activating transcription factor 4 (ATF4) in the islets. Meanwhile, HFD-induced islet expansion was not significantly affected. In summary, partial deletion of Perk improved glucose tolerance and GSIS impaired by diet-induced obesity, without changes in body weights or islet mass.

Purpose: To derive the optimized intraocular lens (IOL) constants from automated and manifest refraction after cataract surgery in Korean patients, and to evaluate whether there is a difference in optimized IOL constants according to the refraction method. Methods: This retrospective multicenter cohort study enrolled 4,103 eyes of 4,103 patients who underwent phacoemulsification and in-the-bag IOL implantation at 18 institutes. Optimized IOL constants for the SRK/T, Holladay, Hoffer Q, and Haigis formulas were calculated via autorefraction or manifest refraction of samples using the same biometry and IOL. The IOL constants derived from autorefraction and manifest refraction were compared. Results: Of the 4,103 eyes, the majority (62.9%) were measured with an IOLMaster 500 followed by an IOLMaster 700 (15.2%). A total of 33 types of IOLs were used, and the Tecnis ZCB00 was the most frequently used (53.0%). There was no statistically significant difference in IOL constants derived from autorefraction and manifest refraction when IOL constants were optimized with a large number of study subjects. On the other hand, optimized IOL constants derived from autorefraction were significantly smaller than those from manifest refraction when the number of subjects was small. Conclusions It became possible to use the IOL constants optimized from Koreans to calculate the IOL power. However, if the IOL constant is optimized using autorefraction in a small sample group, the IOL constant tends to be small, which may lead to refractive error after surgery.

Purpose: In this trial, we investigated the efficacy and safety of adjuvant letrozole for hormone receptor (HR)-positive breast cancer. Here, we report the clinical outcome in postmenopausal women with HR-positive breast cancer treated with adjuvant letrozole according to estrogen receptor (ER) expression levels. Methods: In this multi-institutional, open-label, observational study, postmenopausal patients with HR-positive breast cancer received adjuvant letrozole (2.5 mg/daily) for 5 years unless they experienced disease progression or unacceptable toxicity or withdrew their consent. The patients were stratified into the following 3 groups according to ER expression levels using a modified Allred score (AS): low, intermediate, and high (AS 3–4, 5–6, and 7–8, respectively). ER expression was centrally reviewed. The primary objective was the 5-year disease-free survival (DFS) rate. Results: Between April 25, 2010, and February 5, 2014, 440 patients were enrolled. With a median follow-up of 62.0 months, the 5-year DFS rate in all patients was 94.2% (95% confidence interval [CI], 91.8–96.6). The 5-year DFS and recurrence-free survival (RFS) rates did not differ according to ER expression; the 5-year DFS rates were 94.3% and 94.1%in the low-to-intermediate and high expression groups, respectively (p = 0.6), and the corresponding 5-year RFS rates were 95.7% and 95.4%, respectively (p = 0.7). Furthermore, 25 patients discontinued letrozole because of drug toxicity. Conclusion Treatment with adjuvant letrozole showed very favorable treatment outcomes and good tolerability among Korean postmenopausal women with ER-positive breast cancer, independent of ER expression.

Purpose: In this trial, we investigated the efficacy and safety of adjuvant letrozole for hormone receptor (HR)-positive breast cancer. Here, we report the clinical outcome in postmenopausal women with HR-positive breast cancer treated with adjuvant letrozole according to estrogen receptor (ER) expression levels. Methods: In this multi-institutional, open-label, observational study, postmenopausal patients with HR-positive breast cancer received adjuvant letrozole (2.5 mg/daily) for 5 years unless they experienced disease progression or unacceptable toxicity or withdrew their consent. The patients were stratified into the following 3 groups according to ER expression levels using a modified Allred score (AS): low, intermediate, and high (AS 3–4, 5–6, and 7–8, respectively). ER expression was centrally reviewed. The primary objective was the 5-year disease-free survival (DFS) rate. Results: Between April 25, 2010, and February 5, 2014, 440 patients were enrolled. With a median follow-up of 62.0 months, the 5-year DFS rate in all patients was 94.2% (95% confidence interval [CI], 91.8–96.6). The 5-year DFS and recurrence-free survival (RFS) rates did not differ according to ER expression; the 5-year DFS rates were 94.3% and 94.1%in the low-to-intermediate and high expression groups, respectively (p = 0.6), and the corresponding 5-year RFS rates were 95.7% and 95.4%, respectively (p = 0.7). Furthermore, 25 patients discontinued letrozole because of drug toxicity. Conclusion Treatment with adjuvant letrozole showed very favorable treatment outcomes and good tolerability among Korean postmenopausal women with ER-positive breast cancer, independent of ER expression.