Diabetes & Metabolism Journal

Original Articles

Basic research
Extracellular Vimentin Alters Energy Metabolism And Induces Adipocyte Hypertrophy: Ji-Hae Park, Soyeon Kwon, Young Mi Park; Received September 26, 2022 Accepted June 19, 2023 Published online September 26, 2023; DOI: https://doi.org/10.4093/dmj.2022.0332 [Epub ahead of print]

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Previous studies have reported that oxidative stress contributes to obesity characterized by adipocyte hypertrophy. However, mechanism has not been studied extensively. In the current study, we evaluated role of extracellular vimentin secreted by oxidized low-density lipoprotein (oxLDL) in energy metabolism in adipocytes.
Methods
We treated 3T3-L1-derived adipocytes with oxLDL and measured vimentin which was secreted in the media. We evaluated changes in uptake of glucose and free fatty acid, expression of molecules functioning in energy metabolism, synthesis of adenosine triphosphate (ATP) and lactate, markers for endoplasmic reticulum (ER) stress and autophagy in adipocytes treated with recombinant vimentin.
Results
Adipocytes secreted vimentin in response to oxLDL. Microscopic evaluation revealed that vimentin treatment induced increase in adipocyte size and increase in sizes of intracellular lipid droplets with increased intracellular triglyceride. Adipocytes treated with vimentin showed increased uptake of glucose and free fatty acid with increased expression of plasma membrane glucose transporter type 1 (GLUT1), GLUT4, and CD36. Vimentin treatment increased transcription of GLUT1 and hypoxia-inducible factor 1α (Hif-1α) but decreased GLUT4 transcription. Adipose triglyceride lipase (ATGL), peroxisome proliferator-activated receptor γ (PPARγ), sterol regulatory element-binding protein 1 (SREBP1), diacylglycerol O-acyltransferase 1 (DGAT1) and 2 were decreased by vimentin treatment. Markers for ER stress were increased and autophagy was impaired in vimentin-treated adipocytes. No change was observed in synthesis of ATP and lactate in the adipocytes treated with vimentin.
Conclusion
We concluded that extracellular vimentin regulates expression of molecules in energy metabolism and promotes adipocyte hypertrophy. Our results show that vimentin functions in the interplay between oxidative stress and metabolism, suggesting a mechanism by which adipocyte hypertrophy is induced in oxidative stress.

Technology/Device
Clinical and Lifestyle Determinants of Continuous Glucose Monitoring Metrics in Insulin-Treated Patients with Type 2 Diabetes Mellitus: Da Young Lee, Namho Kim, Inha Jung, So Young Park, Ji Hee Yu, Ji A Seo, Jihee Kim, Kyeong Jin Kim, Nam Hoon Kim, Hye Jin Yoo, Sin Gon Kim, Kyung Mook Choi, Sei Hyun Baik, Sung-Min Park, Nan Hee Kim; Diabetes Metab J. 2023;47(6):826-836. Published online August 24, 2023; DOI: https://doi.org/10.4093/dmj.2022.0273

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There was limited evidence to evaluate the association between lifestyle habits and continuous glucose monitoring (CGM) metrics. Thus, we aimed to depict the behavioral and metabolic determinants of CGM metrics in insulin-treated patients with type 2 diabetes mellitus (T2DM).
Methods
This is a prospective observational study. We analyzed data from 122 insulin-treated patients with T2DM. Participants wore Dexcom G6 and Fitbit, and diet information was identified for 10 days. Multivariate-adjusted logistic regression analysis was performed for the simultaneous achievement of CGM-based targets, defined by the percentage of time in terms of hyper, hypoglycemia and glycemic variability (GV). Intake of macronutrients and fiber, step counts, sleep, postprandial C-peptide-to-glucose ratio (PCGR), information about glucose lowering medications and metabolic factors were added to the analyses. Additionally, we evaluated the impact of the distribution of energy and macronutrient during a day, and snack consumption on CGM metrics.
Results
Logistic regression analysis revealed that female, participants with high PCGR, low glycosylated hemoglobin (HbA1c) and daytime step count had a higher probability of achieving all targets based on CGM (odds ratios [95% confidence intervals] which were 0.24 [0.09 to 0.65], 1.34 [1.03 to 1.25], 0.95 [0.9 to 0.99], and 1.15 [1.03 to 1.29], respectively). And participants who ate snacks showed a shorter period of hyperglycemia and less GV compared to those without.
Conclusion
We confirmed that residual insulin secretion, daytime step count, HbA1c, and women were the most relevant determinants of adequate glycemic control in insulin-treated patients with T2DM. In addition, individuals with snack consumption were exposed to lower times of hyperglycemia and GV.

Drug/Regimen
Risk of Diabetic Retinopathy between Sodium-Glucose Cotransporter-2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists: Tzu-Yi Lin, Eugene Yu-Chuan Kang, Shih-Chieh Shao, Edward Chia-Cheng Lai, Sunir J. Garg, Kuan-Jen Chen, Je-Ho Kang, Wei-Chi Wu, Chi-Chun Lai, Yih-Shiou Hwang; Diabetes Metab J. 2023;47(3):394-404. Published online March 6, 2023; DOI: https://doi.org/10.4093/dmj.2022.0221

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Background
To compare risk of diabetic retinopathy (DR) between patients taking sodium-glucose cotransporter-2 inhibitors (SGLT2is) and those taking glucagon-like peptide-1 receptor agonists (GLP1-RAs) in routine care.
Methods
This retrospective cohort study emulating a target trial included patient data from the multi-institutional Chang Gung Research Database in Taiwan. Totally, 33,021 patients with type 2 diabetes mellitus using SGLT2is and GLP1-RAs between 2016 and 2019 were identified. 3,249 patients were excluded due to missing demographics, age <40 years, prior use of any study drug, a diagnosis of retinal disorders, a history of receiving vitreoretinal procedure, no baseline glycosylated hemoglobin, or no follow-up data. Baseline characteristics were balanced using inverse probability of treatment weighting with propensity scores. DR diagnoses and vitreoretinal interventions served as the primary outcomes. Occurrence of proliferative DR and DR receiving vitreoretinal interventions were regarded as vision-threatening DR.
Results
There were 21,491 SGLT2i and 1,887 GLP1-RA users included for the analysis. Patients receiving SGLT2is and GLP-1 RAs exhibited comparable rate of any DR (subdistribution hazard ratio [SHR], 0.90; 95% confidence interval [CI], 0.79 to 1.03), whereas the rate of proliferative DR (SHR, 0.53; 95% CI, 0.42 to 0.68) was significantly lower in the SGLT2i group. Also, SGLT2i users showed significantly reduced risk of composite surgical outcome (SHR, 0.58; 95% CI, 0.48 to 0.70).
Conclusion
Compared to those taking GLP1-RAs, patients receiving SGLT2is had a lower risk of proliferative DR and vitreoretinal interventions, although the rate of any DR was comparable between the SGLT2i and GLP1-RA groups. Thus, SGLT2is may be associated with a lower risk of vision-threatening DR but not DR development.

Citations

Citations to this article as recorded by

Risk of Diabetic Retinopathy between Sodium-Glucose Cotransporter-2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists (Diabetes Metab J 2023;47:394-404)
Tzu-Yi Lin, Eugene Yu-Chuan Kang, Shih-Chieh Shao, Edward Chia-Cheng Lai, Yih-Shiou Hwang
Diabetes & Metabolism Journal.2023; 47(4): 573. CrossRef
Risk of Diabetic Retinopathy between Sodium-Glucose Cotransporter-2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists (Diabetes Metab J 2023;47:394-404)
Jihee Ko, Sun Joon Moon
Diabetes & Metabolism Journal.2023; 47(4): 571. CrossRef

Technology/Device
Glycemia according to the Use of Continuous Glucose Monitoring among Adults with Type 1 Diabetes Mellitus in Korea: A Real-World Study: You-Bin Lee, Minjee Kim, Jae Hyeon Kim; Diabetes Metab J. 2023;47(3):405-414. Published online March 6, 2023; DOI: https://doi.org/10.4093/dmj.2022.0032

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Background
We explored the association between continuous glucose monitoring (CGM) use and glycemia among adults with type 1 diabetes mellitus (T1DM) and determined the status of CGM metrics among adults with T1DM using CGM in the real-world.
Methods
For this propensity-matched cross-sectional study, individuals with T1DM who visited the outpatient clinic of the Endocrinology Department of Samsung Medical Center between March 2018 and February 2020 were screened. Among them, 111 CGM users (for ≥9 months) were matched based on propensity score considering age, sex, and diabetes duration in a 1:2 ratio with 203 CGM never-users. The association between CGM use and glycemic measures was explored. In a subpopulation of CGM users who had been using official applications (not “do-it-yourself” software) such that Ambulatory Glucose Profile data for ≥1 month were available (n=87), standardized CGM metrics were summarized.
Results
Linear regression analyses identified CGM use as a determining factor for log-transformed glycosylated hemoglobin. The fully-adjusted odds ratio (OR) and 95% confidence interval (CI) for uncontrolled glycosylated hemoglobin (>8%) were 0.365 (95% CI, 0.190 to 0.703) in CGM users compared to never-users. The fully-adjusted OR for controlled glycosylated hemoglobin (<7%) was 1.861 (95% CI, 1.119 to 3.096) in CGM users compared to never-users. Among individuals who had been using official applications for CGM, time in range (TIR) values within recent 30- and 90-day periods were 62.45%±16.63% and 63.08%±15.32%, respectively.
Conclusion
CGM use was associated with glycemic control status among Korean adults with T1DM in the real-world, although CGM metrics including TIR might require further improvement among CGM users.

Citations

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Navigating the Seas of Glycemic Control: The Role of Continuous Glucose Monitoring in Type 1 Diabetes Mellitus
Jun Sung Moon
Diabetes & Metabolism Journal.2023; 47(3): 345. CrossRef

Drug/Regimen
Efficacy and Safety of Enavogliflozin versus Dapagliflozin as Add-on to Metformin in Patients with Type 2 Diabetes Mellitus: A 24-Week, Double-Blind, Randomized Trial: Kyung Ah Han, Yong Hyun Kim, Doo Man Kim, Byung Wan Lee, Suk Chon, Tae Seo Sohn, In Kyung Jeong, Eun-Gyoung Hong, Jang Won Son, Jae Jin Nah, Hwa Rang Song, Seong In Cho, Seung-Ah Cho, Kun Ho Yoon; Diabetes Metab J. 2023;47(6):796-807. Published online February 9, 2023; DOI: https://doi.org/10.4093/dmj.2022.0315

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Background
Enavogliflozin is a novel sodium-glucose cotransporter-2 inhibitor currently under clinical development. This study evaluated the efficacy and safety of enavogliflozin as an add-on to metformin in Korean patients with type 2 diabetes mellitus (T2DM) against dapagliflozin.
Methods
In this multicenter, double-blind, randomized, phase 3 study, 200 patients were randomized to receive enavogliflozin 0.3 mg/day (n=101) or dapagliflozin 10 mg/day (n=99) in addition to ongoing metformin therapy for 24 weeks. The primary objective of the study was to prove the non-inferiority of enavogliflozin to dapagliflozin in glycosylated hemoglobin (HbA1c) change at week 24 (non-inferiority margin of 0.35%) (Clinical trial registration number: NCT04634500).
Results
Adjusted mean change of HbA1c at week 24 was –0.80% with enavogliflozin and –0.75% with dapagliflozin (difference, –0.04%; 95% confidence interval, –0.21% to 0.12%). Percentages of patients achieving HbA1c <7.0% were 61% and 62%, respectively. Adjusted mean change of fasting plasma glucose at week 24 was –32.53 and –29.14 mg/dL. An increase in urine glucose-creatinine ratio (60.48 vs. 44.94, P<0.0001) and decrease in homeostasis model assessment of insulin resistance (–1.85 vs. –1.31, P=0.0041) were significantly greater with enavogliflozin than dapagliflozin at week 24. Beneficial effects of enavogliflozin on body weight (–3.77 kg vs. –3.58 kg) and blood pressure (systolic/diastolic, –5.93/–5.41 mm Hg vs. –6.57/–4.26 mm Hg) were comparable with those of dapagliflozin, and both drugs were safe and well-tolerated.
Conclusion
Enavogliflozin added to metformin significantly improved glycemic control in patients with T2DM and was non-inferior to dapagliflozin 10 mg, suggesting enavogliflozin as a viable treatment option for patients with inadequate glycemic control on metformin alone.

Citations

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Role of novel sodium glucose co-transporter-2 inhibitor enavogliflozin in type-2 diabetes: A systematic review and meta-analysis
Deep Dutta, B.G. Harish, Beatrice Anne, Lakshmi Nagendra
Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2023; 17(8): 102816. CrossRef
Characteristics of the Latest Therapeutic Agent for Diabetes
Nuri Yun
The Journal of Korean Diabetes.2023; 24(3): 148. CrossRef
Prospects of using sodium-glucose co-transporter-2 (SGLT-2) inhibitors in patients with metabolic-associated fatty liver disease (MAFLD)
Iryna Kostitska, Nadia Protas, Liliia Petrovska
Diabetes Obesity Metabolic Syndrome.2023; (5): 8. CrossRef

Reviews

Technology/Device
Advances in Continuous Glucose Monitoring and Integrated Devices for Management of Diabetes with Insulin-Based Therapy: Improvement in Glycemic Control: Jee Hee Yoo, Jae Hyeon Kim; Diabetes Metab J. 2023;47(1):27-41. Published online January 12, 2023; DOI: https://doi.org/10.4093/dmj.2022.0271

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Continuous glucose monitoring (CGM) technology has evolved over the past decade with the integration of various devices including insulin pumps, connected insulin pens (CIPs), automated insulin delivery (AID) systems, and virtual platforms. CGM has shown consistent benefits in glycemic outcomes in type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) treated with insulin. Moreover, the combined effect of CGM and education have been shown to improve glycemic outcomes more than CGM alone. Now a CIP is the expected future technology that does not need to be worn all day like insulin pumps and helps to calculate insulin doses with a built-in bolus calculator. Although only a few clinical trials have assessed the effectiveness of CIPs, they consistently show benefits in glycemic outcomes by reducing missed doses of insulin and improving problematic adherence. AID systems and virtual platforms made it possible to achieve target glycosylated hemoglobin in diabetes while minimizing hypoglycemia, which has always been challenging in T1DM. Now fully automatic AID systems and tools for diabetes decisions based on artificial intelligence are in development. These advances in technology could reduce the burden associated with insulin treatment for diabetes.

Citations

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Glycemic Outcomes During Early Use of the MiniMed™ 780G Advanced Hybrid Closed-Loop System with Guardian™ 4 Sensor
Toni L. Cordero, Zheng Dai, Arcelia Arrieta, Fang Niu, Melissa Vella, John Shin, Andrew S. Rhinehart, Jennifer McVean, Scott W. Lee, Robert H. Slover, Gregory P. Forlenza, Dorothy I. Shulman, Rodica Pop-Busui, James R. Thrasher, Mark S. Kipnes, Mark P. Ch
Diabetes Technology & Therapeutics.2023; 25(9): 652. CrossRef
Navigating the Seas of Glycemic Control: The Role of Continuous Glucose Monitoring in Type 1 Diabetes Mellitus
Jun Sung Moon
Diabetes & Metabolism Journal.2023; 47(3): 345. CrossRef
APSec1.0: Innovative Security Protocol Design with Formal Security Analysis for the Artificial Pancreas System
Jiyoon Kim, Jongmin Oh, Daehyeon Son, Hoseok Kwon, Philip Virgil Astillo, Ilsun You
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Continuous Glucose Monitoring (CGM) and Metabolic Control in a Cohort of Patients with Type 1 Diabetes and Coeliac Disease
Flavia Amaro, Maria Alessandra Saltarelli, Marina Primavera, Marina Cerruto, Stefano Tumini
Endocrines.2023; 4(3): 595. CrossRef
Comparison of Glycemia Risk Index with Time in Range for Assessing Glycemic Quality
Ji Yoon Kim, Jee Hee Yoo, Jae Hyeon Kim
Diabetes Technology & Therapeutics.2023;[Epub] CrossRef
The Benefits Of Continuous Glucose Monitoring In Pregnancy
Jee Hee Yoo, Jae Hyeon Kim
Endocrinology and Metabolism.2023; 38(5): 472. CrossRef
The Growing Challenge of Diabetes Management in an Aging Society
Seung-Hwan Lee
Diabetes & Metabolism Journal.2023; 47(5): 630. CrossRef
Recent advances in artificial intelligence-assisted endocrinology and diabetes
Ioannis T. Oikonomakos, Ranjit M. Anjana, Viswanathan Mohan, Charlotte Steenblock, Stefan R. Bornstein
Exploration of Endocrine and Metabolic Disease.2023; 1(1): 16. CrossRef

Pathophysiology
Renoprotective Mechanism of Sodium-Glucose Cotransporter 2 Inhibitors: Focusing on Renal Hemodynamics: Nam Hoon Kim, Nan Hee Kim; Diabetes Metab J. 2022;46(4):543-551. Published online July 27, 2022; DOI: https://doi.org/10.4093/dmj.2022.0209

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Diabetic kidney disease (DKD) is a prevalent renal complication of diabetes mellitus that ultimately develops into end-stage kidney disease (ESKD) when not managed appropriately. Substantial risk of ESKD remains even with intensive management of hyperglycemia and risk factors of DKD and timely use of renin-angiotensin-aldosterone inhibitors. Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce hyperglycemia primarily by inhibiting glucose and sodium reabsorption in the renal proximal tubule. Currently, their effects expand to prevent or delay cardiovascular and renal adverse events, even in those without diabetes. In dedicated renal outcome trials, SGLT2 inhibitors significantly reduced the risk of composite renal adverse events, including the development of ESKD or renal replacement therapy, which led to the positioning of SGLT2 inhibitors as the mainstay of chronic kidney disease management. Multiple mechanisms of action of SGLT2 inhibitors, including hemodynamic, metabolic, and anti-inflammatory effects, have been proposed. Restoration of tubuloglomerular feedback is a plausible explanation for the alteration in renal hemodynamics induced by SGLT2 inhibition and for the associated renal benefit. This review discusses the clinical rationale and mechanism related to the protection SGLT2 inhibitors exert on the kidney, focusing on renal hemodynamic effects.

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Acta Diabetologica.2023; 60(3): 435. CrossRef
Effects of sodium-glucose cotransporter 2 inhibitors on renal risk factors in patients with abnormal glucose metabolism: a meta-analysis of randomized controlled trials
Mengnan Li, Jian Zhang, Guimei Yang, Jiaxin Zhang, Minmin Han, Yi Zhang, Yunfeng Liu
European Journal of Clinical Pharmacology.2023; 79(6): 859. CrossRef
Age at Mortality in Patients with Type 2 Diabetes Who Underwent Kidney Transplantation: An Analysis of Data from the Korean National Health Insurance and Statistical Information Service, 2006 to 2018
Sun Ok Song, Eugene Han, Kang Ju Son, Bong-Soo Cha, Byung-Wan Lee
Journal of Clinical Medicine.2023; 12(9): 3160. CrossRef
Exposure–Response Analysis of the Sodium–Glucose Cotransporter-2 Inhibitors Dapagliflozin and Empagliflozin on Kidney Hemodynamics in Patients with Type 2 Diabetes
Sjoukje van der Hoek, Jeroen V. Koomen, Erik J. M. van Bommel, Charlotte M. Mosterd, Rosalie A. Scholtes, Anne C. Hesp, Jasper Stevens, Daniel H. van Raalte, Hiddo J. L. Heerspink
Journal of Personalized Medicine.2023; 13(5): 747. CrossRef
Osteopontin as a Biomarker in Chronic Kidney Disease
Satyesh K. Sinha, Michael Mellody, Maria Beatriz Carpio, Robert Damoiseaux, Susanne B. Nicholas
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Hye Jin Chun, Eun Ran Kim, Minyoung Lee, Da Hyun Choi, Soo Hyun Kim, Eugene Shin, Jin-Hong Kim, Jin Won Cho, Dai Hoon Han, Bong-Soo Cha, Yong-ho Lee
Metabolism.2023; 145: 155612. CrossRef
Synthesis and biological profile of benzoxazolone derivatives
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Original Articles

Drug/Regimen
Safety and Effectiveness of Empagliflozin in Korean Patients with Type 2 Diabetes Mellitus: Results from a Nationwide Post-Marketing Surveillance: Jun Sung Moon, Nam Hoon Kim, Jin Oh Na, Jae Hyoung Cho, In-Kyung Jeong, Soon Hee Lee, Ji-Oh Mok, Nan Hee Kim, Dong Jin Chung, Jinhong Cho, Dong Woo Lee, Sun Woo Lee, Kyu Chang Won; Diabetes Metab J. 2023;47(1):82-91. Published online June 20, 2022; DOI: https://doi.org/10.4093/dmj.2021.0356

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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.

Citations

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Comparison of the Pharmacokinetics, Safety, and Tolerability of Two Empagliflozin Formulations in Healthy Korean Subjects
Xu Jiang, Sungyeun Bae, Deok Yong Yoon, Shin Jung Park, Jaeseong Oh, Joo-Youn Cho, Kyung-Sang Yu
Drug Design, Development and Therapy.2023; Volume 17: 2137. CrossRef
Comparative safety of different sodium-glucose transporter 2 inhibitors in patients with type 2 diabetes: a systematic review and network meta-analysis of randomized controlled trials
Chun Xing Li, Li Yan Liu, Chen Xiao Zhang, Xu Hua Geng, Si Meng Gu, Yu Qiao Wang, Hua Liu, Qing Xie, Shuo Liang
Frontiers in Endocrinology.2023;[Epub] CrossRef

Drug/Regimen
Real-World Prescription Patterns and Barriers Related to the Use of Sodium-Glucose Cotransporter 2 Inhibitors among Korean Patients with Type 2 Diabetes Mellitus and Cardiovascular Disease: Jong Ha Baek, Ye Seul Yang, Seung-Hyun Ko, Kyung Do Han, Jae Hyeon Kim, Min Kyong Moon, Jong Suk Park, Byung-Wan Lee, Tae Jung Oh, Suk Chon, Jong Han Choi, Kyu Yeon Hur, Committee of Clinical Practice Guidelines, Korean Diabetes Association; Diabetes Metab J. 2022;46(5):701-712. Published online June 3, 2022; DOI: https://doi.org/10.4093/dmj.2022.0002

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Background
To evaluate prescription trends and clinical factors of the sodium-glucose cotransporter 2 inhibitors (SGLT2i) use according to the presence of atherosclerotic cardiovascular disease (ASCVD) or heart failure (HF) in Korean patients with type 2 diabetes mellitus (T2DM).
Methods
Prescription patterns of SGLT2i use between 2015 and 2019 were determined using the Korean National Health Insurance Service database of claims.
Results
Of all patients with T2DM (n=4,736,493), the annual prescription rate of SGLT2i increased every year in patients with ASCVD (from 2.2% to 10.7%) or HF (from 2.0% to 11.1%). After the first hospitalization for ASCVD (n=518,572), 13.7% (n=71,259) of patients initiated SGLT2i with a median of 10.6 months. After hospitalization for HF (n=372,853), 11.2% (n=41,717) of patients initiated SGLT2i after a median of 8.8 months. In multivariate regression for hospitalization, older age (per 10 years, odds ratio [OR], 0.57; 95% confidence interval [CI], 0.56 to 0.57), lower household income (OR, 0.93; 95% CI, 0.92 to 0.95), rural residents (OR, 0.95; 95% CI, 0.93 to 0.97), and dipeptidyl peptidase-4 inhibitor (DPP-4i) users (OR, 0.82; 95% CI, 0.81 to 0.84) were associated with lesser initiation of SGLT2i in ASCVD. Additionally, female gender (OR, 0.97; 95% CI, 0.95 to 0.99) was associated with lesser initiation of SGLT2i in HF.
Conclusion
The prescription rate of SGLT2i increased gradually up to 2019 but was suboptimal in patients with ASCVD or HF. After the first hospitalization for ASCVD or HF, older age, female gender, low household income, rural residents, and DPP-4i users were less likely to initiate SGLT2i.

Citations

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Prescribing patterns of SGLT-2 inhibitors for patients with heart failure: A two-center analysis
Teja Chakrala, Roshni O. Prakash, Justin Kim, Hanzhi Gao, Umar Ghaffar, Jaymin Patel, Alex Parker, Bhagwan Dass
American Heart Journal Plus: Cardiology Research and Practice.2023; 28: 100286. CrossRef
Risk of developing chronic kidney disease in young-onset Type 2 diabetes in Korea
Joonyub Lee, Seung-Hwan Lee, Kun-Ho Yoon, Jae Hyoung Cho, Kyungdo Han, Yeoree Yang
Scientific Reports.2023;[Epub] CrossRef
Comparison of SGLT2 inhibitors with DPP-4 inhibitors combined with metformin in patients with acute myocardial infarction and diabetes mellitus
Young Sang Lyu, Seok Oh, Jin Hwa Kim, Sang Yong Kim, Myung Ho Jeong
Cardiovascular Diabetology.2023;[Epub] CrossRef
Effectiveness and safety of sodium–glucose cotransporter 2 inhibitors in Asian populations
Kyoung Hwa Ha, Dae Jung Kim
Journal of Diabetes Investigation.2023;[Epub] CrossRef
Severe hypoglycemia as a risk factor for cardiovascular outcomes in patients with type 2 diabetes: is it preventable?
Seung-Hyun Ko
Cardiovascular Prevention and Pharmacotherapy.2022; 4(3): 106. CrossRef
Association between the Diabetes Drug Cost and Cardiovascular Events and Death in Korea: A National Health Insurance Service Database Analysis
Seung Min Chung, Ji-In Lee, Eugene Han, Hyun-Ae Seo, Eonju Jeon, Hye Soon Kim, Ji Sung Yoon
Endocrinology and Metabolism.2022; 37(5): 759. CrossRef

Review

Guideline/Fact Sheet
Comprehensive Understanding for Application in Korean Patients with Type 2 Diabetes Mellitus of the Consensus Statement on Carbohydrate-Restricted Diets by Korean Diabetes Association, Korean Society for the Study of Obesity, and Korean Society of Hypertension: Jong Han Choi, Jee-Hyun Kang, Suk Chon; Diabetes Metab J. 2022;46(3):377-390. Published online May 25, 2022; DOI: https://doi.org/10.4093/dmj.2022.0051

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The Joint Committee of the Korean Diabetes Association, the Korean Society for the Study of Obesity, and the Korean Society of Hypertension announced a consensus statement on carbohydrate-restricted diets and intermittent fasting, representing an emerging and popular dietary pattern. In this statement, we recommend moderately-low-carbohydrate or low-carbohydrate diets, not a very-low-carbohydrate diet, for patients with type 2 diabetes mellitus. These diets can be considered a dietary regimen to improve glycemic control and reduce body weight in adults with type 2 diabetes mellitus. This review provides the detailed results of a meta-analysis and systematic literature review on the potential harms and benefits of carbohydrate-restricted diets in patients with diabetes. We expect that this review will help experts and patients by fostering an in-depth understanding and appropriate application of carbohydrate-restricted diets in the comprehensive management of diabetes.

Citations

Citations to this article as recorded by

Medical nutrition therapy for diabetes mellitus
Suk Chon
Journal of the Korean Medical Association.2023; 66(7): 421. CrossRef

Original Article

Others
Fasting Glucose Variability and the Risk of Dementia in Individuals with Diabetes: A Nationwide Cohort Study: Da Young Lee, Jaeyoung Kim, Sanghyun Park, So Young Park, Ji Hee Yu, Ji A Seo, Nam Hoon Kim, Hye Jin Yoo, Sin Gon Kim, Kyung Mook Choi, Sei Hyun Baik, Kyungdo Han, Nan Hee Kim; Diabetes Metab J. 2022;46(6):923-935. Published online May 24, 2022; DOI: https://doi.org/10.4093/dmj.2021.0346

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Background
We investigated whether fasting glucose (FG) variability could predict the risk of dementia.
Methods
This cohort study analyzed data from Koreans with diabetes after at least three health examinations by the Korean National Health Insurance Corporation between 2005 and 2010, which included at least one examination between 2009 and 2010. A total of 769,554 individuals were included, excluding those aged <40 years and those with dementia. FG variability was measured using the variability independent of the mean (FG-VIM). The incidence of dementia was defined by the International Classification of Diseases 10th Revision codes and prescription of anti-dementia medication and was subdivided into Alzheimer’s disease (AD) and vascular dementia (VD).
Results
During the 6.9-year follow-up, 54,837, 41,032, and 6,892 cases of all-cause dementia, AD, and VD, respectively, were identified. Cox proportional regression analyses showed that as the FG-VIM quartile increased, the risk of dementia serially increased after adjustment for metabolic factors, income status, and diabetes-related characteristics, including the mean FG. Participants in FG-VIM quartile 4 showed a 18%, 19%, and 17% higher risk for all-cause dementia, AD, and VD, respectively, than those in quartile 1; this particularly included non-obese patients with a longer duration of diabetes, high FG levels, dyslipidemia, and those taking glucose-lowering medications. Conversely, the baseline FG status and dementia showed a U-shaped association.
Conclusion
Increased FG variability over 5 years can predict the risk of dementia in individuals with diabetes in Korea. This finding was more pronounced in patients with less favorable metabolic profiles.

Citations

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The Association of Glucose Variability and Dementia Incidence in Latinx Adults with Type 2 Diabetes: A Retrospective Study
Heather Cuevas, Elizabeth Muñoz, Divya Nagireddy, Jeeyeon Kim, Grace Ganucheau, Fathia Alomoush
Clinical Nursing Research.2023; 32(2): 249. CrossRef
The effects of long-term cumulative HbA1c exposure on the development and onset time of dementia in the patients with type 2 diabetes mellitus: Hospital based retrospective study (2005–2021)
Sunyoung Cho, Choon Ok Kim, Bong-soo Cha, Eosu Kim, Chung Mo Nam, Min-Gul Kim, Min Soo Park
Diabetes Research and Clinical Practice.2023; 201: 110721. CrossRef
Physiological Mechanisms Inherent to Diabetes Involved in the Development of Dementia: Alzheimer’s Disease
Himan Mohamed-Mohamed, Victoria García-Morales, Encarnación María Sánchez Lara, Anabel González-Acedo, Teresa Pardo-Moreno, María Isabel Tovar-Gálvez, Lucía Melguizo-Rodríguez, Juan José Ramos-Rodríguez
Neurology International.2023; 15(4): 1253. CrossRef

Short Communication

Technology/Device
Comparison of Laser and Conventional Lancing Devices for Blood Glucose Measurement Conformance and Patient Satisfaction in Diabetes Mellitus: Jung A Kim, Min Jeong Park, Eyun Song, Eun Roh, So Young Park, Da Young Lee, Jaeyoung Kim, Ji Hee Yu, Ji A Seo, Kyung Mook Choi, Sei Hyun Baik, Hye Jin Yoo, Nan Hee Kim; Diabetes Metab J. 2022;46(6):936-940. Published online March 30, 2022; DOI: https://doi.org/10.4093/dmj.2021.0293

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Abstract PDF PubReader ePub: Self-monitoring of capillary blood glucose is important for controlling diabetes. Recently, a laser lancing device (LMT-1000) that can collect capillary blood without skin puncture was developed. We enrolled 150 patients with type 1 or 2 diabetes mellitus. Blood sampling was performed on the same finger on each hand using the LMT-1000 or a conventional lancet. The primary outcome was correlation between glucose values using the LMT-1000 and that using a lancet. And we compared the pain and satisfaction of the procedures. The capillary blood sampling success rates with the LMT-1000 and lancet were 99.3% and 100%, respectively. There was a positive correlation (r=0.974, P<0.001) between mean blood glucose levels in the LMT-1000 (175.8±63.0 mg/dL) and conventional lancet samples (172.5±63.6 mg/dL). LMT-1000 reduced puncture pain by 75.0% and increased satisfaction by 80.0% compared to a lancet. We demonstrated considerable consistency in blood glucose measurements between samples from the LMT-1000 and a lancet, but improved satisfaction and clinically significant pain reduction were observed with the LMT-1000 compared to those with a lancet.

Review

Others
Links between Thyroid Disorders and Glucose Homeostasis: Young Sil Eom, Jessica R. Wilson, Victor J. Bernet; Diabetes Metab J. 2022;46(2):239-256. Published online March 24, 2022; DOI: https://doi.org/10.4093/dmj.2022.0013

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Thyroid disorders and diabetes mellitus often coexist and are closely related. Several studies have shown a higher prevalence of thyroid disorders in patients with diabetes mellitus and vice versa. Thyroid hormone affects glucose homeostasis by impacting pancreatic β-cell development and glucose metabolism through several organs such as the liver, gastrointestinal tract, pancreas, adipose tissue, skeletal muscles, and the central nervous system. The present review discusses the effect of thyroid hormone on glucose homeostasis. We also review the relationship between thyroid disease and diabetes mellitus: type 1, type 2, and gestational diabetes, as well as guidelines for screening thyroid function with each disorder. Finally, we provide an overview of the effects of antidiabetic drugs on thyroid hormone and thyroid disorders.

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Christopher James Watson, Jonathan A. Edlow
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Relationship of Glucose, C-peptide, Leptin, and BDNF in Maternal and Umbilical Vein Blood in Type-1 Diabetes
Josip Delmis, Slavko Oreskovic, Vesna Elvedji Gasparovic, Mirta Starcevic, Mislav Herman, Nada Dessardo, Vito Starcevic, Marina Ivanisevic
Nutrients.2023; 15(3): 600. CrossRef
Isolated Maternal Hypothyroxinemia May be Associated with Insulin Requirement in Gestational Diabetes Mellitus
Ömercan Topaloğlu, Mehmet Uzun, Seda Nur Topaloğlu, Ibrahim Sahin
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Association of urinary iodine concentration with prediabetes/diabetes in adults: Analysis of the NHANES 2005–2016
Jingmin Chen, Huanzhu Liang, Yuxuan Tan, Lin Wen, Ziang Guo, Jiyu Nie, Xiaoxiao Lin, Feng Huang, Jie Wang, Puyi Xing, Lihong Nie, Lihong Wang, Chunxia Jing
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Central sensitivity to thyroid hormones is reduced in youths with overweight or obesity and impaired glucose tolerance
Procolo Di Bonito, Domenico Corica, Maria Rosaria Licenziati, Anna Di Sessa, Emanuele Miraglia del Giudice, Maria Felicia Faienza, Valeria Calcaterra, Francesca Franco, Giulio Maltoni, Giuliana Valerio, Malgorzata Wasniewska
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Association of thyroid stimulating hormone and time in range with risk of diabetic retinopathy in euthyroid type 2 diabetes
Yaxin Wang, Jingyi Lu, Jiaying Ni, Ming Wang, Yun Shen, Wei Lu, Wei Zhu, Yuqian Bao, Jian Zhou
Diabetes/Metabolism Research and Reviews.2023;[Epub] CrossRef
The circadian rhythm: an influential soundtrack in the diabetes story
Amirali Hariri, Mina Mirian, Ali Zarrabi, Mohammad Kohandel, Maryam Amini-Pozveh, Amir Reza Aref, Aliye Tabatabaee, Pranav Kumar Prabhakar, Ponnurengam Malliappan Sivakumar
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Folate deficiency may increase the risk for elevated TSH in patients with type 2 diabetes mellitus
Lin Lin, Yushan Du, Guanyu Niu, Shuangbo Xia, Jufen Liu
BMC Endocrine Disorders.2023;[Epub] CrossRef
L- Thyroxine ameliorates renal function in thyroidectomized diabetic nephropathy rats through downregulation of TGF- β1, Ang II and ET-1 expression
Zeinab H. El-Said, Sherihan I. Gouda, Hebatallah A. Mahgoub, S El_desouky, Neven A. Ebrahim
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Preventive Effect of Molecular Iodine in Pancreatic Disorders from Hypothyroid Rabbits
Julia Rodríguez-Castelán, Evangelina Delgado-González, Esteban Rodríguez-Benítez, Francisco Castelán, Estela Cuevas-Romero, Brenda Anguiano, Michael C. Jeziorski, Carmen Aceves
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Hypothyroidism increases angiotensinogen gene expression associated with vascular smooth muscle cells cholesterol metabolism dysfunction and aorta remodeling in Psammomys obesus
Samia Neggazi, Nadjiba Hamlat, Sihem Berdja, Saliha Boumaza, Leila Smail, Michel Beylot, Souhila Aouichat-Bouguerra
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The Correlation Between Thyroid Parameters and the Ratios of Neutrophil/Lymphocyte and Platelet/Lymphocyte in Euthyroid Type 2 Diabetic Patients
Hui Chen, Jun-Qiang Ju, Xiao-Wu Qian, Zheng-Tai Zhu, Chun-Zhi Zhao, Zhe Liu
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Recep Soslu, Abdullah Uysal, Meltem Devrilmez, İsmail Can Çuvalcıoğlu, Ali Ahmet Doğan, Sülbiye Karaburgu, Murat Taş
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Francesca Gorini, Cristina Vassalle
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Ping Zhu, Guojuan Lao, Chuping Chen, Lihui Luo, Jing Gu, Jianmin Ran
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Original Article

Cardiovascular Risk/Epidemiology
Comparative Effects of Sodium-Glucose Cotransporter 2 Inhibitor and Thiazolidinedione Treatment on Risk of Stroke among Patients with Type 2 Diabetes Mellitus: Seung Eun Lee, Hyewon Nam, Han Seok Choi, Hoseob Kim, Dae-Sung Kyoung, Kyoung-Ah Kim; Diabetes Metab J. 2022;46(4):567-577. Published online February 8, 2022; DOI: https://doi.org/10.4093/dmj.2021.0160

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Background
Although cardiovascular outcome trials using sodium-glucose cotransporter-2 inhibitors (SGLT-2i) showed a reduction in risk of 3-point major adverse cardiovascular events (MACE), they did not demonstrate beneficial effects on stroke risk. Additionally, meta-analysis showed SGLT-2i potentially had an adverse effect on stroke risk. Contrarily, pioglitazone, a type of thiazolidinedione (TZD), has been shown to reduce recurrent stroke risk. Thus, we aimed to compare the effect of SGLT-2i and TZD on the risk of stroke in type 2 diabetes mellitus (T2DM) patients.
Methods
Using the Korean National Health Insurance Service data, we compared a 1:1 propensity score-matched cohort of patients who used SGLT-2i or TZD from January 2014 to December 2018. The primary outcome was stroke. The secondary outcomes were myocardial infarction (MI), cardiovascular death, 3-point MACE, and heart failure (HF).
Results
After propensity-matching, each group included 56,794 patients. Baseline characteristics were well balanced. During the follow-up, 862 patients were newly hospitalized for stroke. The incidence rate of stroke was 4.11 and 4.22 per 1,000 person-years for the TZD and SGLT-2i groups respectively. The hazard ratio (HR) of stroke was 1.054 (95% confidence interval [CI], 0.904 to 1.229) in the SGLT-2i group compared to the TZD group. There was no difference in the risk of MI, cardiovascular death, 3-point MACE between groups. Hospitalization for HF was significantly decreased in SGLT-2i-treated patients (HR, 0.645; 95% CI, 0.466 to 0.893). Results were consistent regardless of prior cardiovascular disease.
Conclusion
In this real-world data, the risk of stroke was comparable in T2DM patients treated with SGLT-2i or TZD.

Citations

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Lobeglitazone, a novel thiazolidinedione, for secondary prevention in patients with ischemic stroke: a nationwide nested case-control study
Joonsang Yoo, Jimin Jeon, Minyoul Baik, Jinkwon Kim
Cardiovascular Diabetology.2023;[Epub] CrossRef

Review

Metabolic Risk/Epidemiology
Gestational Diabetes Mellitus: Diagnostic Approaches and Maternal-Offspring Complications: Joon Ho Moon, Hak Chul Jang; Diabetes Metab J. 2022;46(1):3-14. Published online January 27, 2022; DOI: https://doi.org/10.4093/dmj.2021.0335

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Graphical Abstract Abstract PDF PubReader ePub

Gestational diabetes mellitus (GDM) is the most common complication during pregnancy and is defined as any degree of glucose intolerance with onset or first recognition during pregnancy. GDM is associated with adverse pregnancy outcomes and long-term offspring and maternal complications. For GDM screening and diagnosis, a two-step approach (1-hour 50 g glucose challenge test followed by 3-hour 100 g oral glucose tolerance test) has been widely used. After the Hyperglycemia and Adverse Pregnancy Outcome study implemented a 75 g oral glucose tolerance test in all pregnant women, a one-step approach was recommended as an option for the diagnosis of GDM after 2010. The one-step approach has more than doubled the incidence of GDM, but its clinical benefit in reducing adverse pregnancy outcomes remains controversial. Long-term complications of mothers with GDM include type 2 diabetes mellitus and cardiovascular disease, and complications of their offspring include childhood obesity and glucose intolerance. The diagnostic criteria of GDM should properly classify women at risk for adverse pregnancy outcomes and long-term complications. The present review summarizes the strengths and weaknesses of the one-step and two-step approaches for the diagnosis of GDM based on recent randomized controlled trials and observational studies. We also describe the long-term maternal and offspring complications of GDM.

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