Diabetes & Metabolism Journal

Original Articles

Pharmacotherapy
Study Design and Protocol for a Randomized Controlled Trial of Enavogliflozin to Evaluate Cardiorenal Outcomes in Type 2 Diabetes (ENVELOP): Nam Hoon Kim, Soo Lim, In-Kyung Jeong, Eun-Jung Rhee, Jun Sung Moon, Ohk-Hyun Ryu, Hyuk-Sang Kwon, Jong Chul Won, Sang Soo Kim, Sang Yong Kim, Bon Jeong Ku, Heung Yong Jin, Sin Gon Kim, Bong-Soo Cha, on Behalf of Investigators of ENVELOP Study; Diabetes Metab J. 2025;49(2):225-234. Published online January 6, 2025; DOI: https://doi.org/10.4093/dmj.2024.0238

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Abstract PDF Supplementary Material PubReader ePub: Background
The novel sodium-glucose cotransporter-2 (SGLT2) inhibitor enavogliflozin effectively lowers glycosylated hemoglobin levels and body weights without the increased risk of serious adverse events; however, the long-term clinical benefits of enavogliflozin in terms of cardiovascular and renal outcomes have not been investigated.
Methods
This study is an investigator-initiated, multicenter, randomized, pragmatic, open-label, active-controlled, non-inferiority trial. Eligible participants are adults (aged ≥19 years) with type 2 diabetes mellitus (T2DM) who have a history of, or are at risk of, cardiovascular disease. A total of 2,862 participants will be randomly assigned to receive either enavogliflozin or other SGLT2 inhibitors with proven cardiorenal benefits, such as dapagliflozin or empagliflozin. The primary endpoint is the time to the first occurrence of a composite of major adverse cardiovascular or renal events (Clinical Research Information Service registration number: KCT0009243).
Conclusion
This trial will determine whether enavogliflozin is non-inferior to dapagliflozin or empagliflozin in terms of cardiorenal outcomes in patients with T2DM and cardiovascular risk factors. This study will elucidate the role of enavogliflozin in preventing vascular complications in patients with T2DM.

Pathophysiology
Recent Glycemia Is a Major Determinant of β-Cell Function in Type 2 Diabetes Mellitus: Ji Yoon Kim, Jiyoon Lee, Sin Gon Kim, Nam Hoon Kim; Diabetes Metab J. 2024;48(6):1135-1146. Published online June 17, 2024; DOI: https://doi.org/10.4093/dmj.2023.0359

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Background
Progressive deterioration of β-cell function is a characteristic of type 2 diabetes mellitus (T2DM). We aimed to investigate the relative contributions of clinical factors to β-cell function in T2DM.
Methods
In a T2DM cohort of 470 adults (disease duration 0 to 41 years), β-cell function was estimated using insulinogenic index (IGI), disposition index (DI), oral disposition index (DIO), and homeostasis model assessment of β-cell function (HOMA-B) derived from a 75 g oral glucose tolerance test (OGTT). The relative contributions of age, sex, disease duration, body mass index, glycosylated hemoglobin (HbA1c) levels (at the time of the OGTT), area under the curve of HbA1c over time (HbA1c AUC), coefficient of variation in HbA1c (HbA1c CV), and antidiabetic agents use were compared by standardized regression coefficients. Longitudinal analyses of these indices were also performed.
Results
IGI, DI, DI_O, and HOMA-B declined over time (P<0.001 for all). Notably, HbA1c was the most significant factor affecting IGI, DI, DIO, and HOMA-B in the multivariable regression analysis. Compared with HbA1c ≥9%, DI was 1.9-, 2.5-, 3.7-, and 5.5-fold higher in HbA1c of 8%–<9%, 7%–<8%, 6%–<7%, and <6%, respectively, after adjusting for confounding factors (P<0.001). Conversely, β-cell function was not affected by the type or duration of antidiabetic agents, HbA1c AUC, or HbA1c CV. The trajectories of the IGI, DI, DIO, and HOMA-B mirrored those of HbA1c.
Conclusion
β-Cell function declines over time; however, it is flexible, being largely affected by recent glycemia in T2DM.

Citations

Citations to this article as recorded by

The Importance of Treating Hyperglycemia in β-Cell Dysfunction of Type 2 Diabetes Mellitus
Arim Choi, Kyung-Soo Kim
Diabetes & Metabolism Journal.2024; 48(6): 1056. CrossRef

Drug/Regimen
Efficacy and Safety of Metformin and Atorvastatin Combination Therapy vs. Monotherapy with Either Drug in Type 2 Diabetes Mellitus and Dyslipidemia Patients (ATOMIC): Double-Blinded Randomized Controlled Trial: Jie-Eun Lee, Seung Hee Yu, Sung Rae Kim, Kyu Jeung Ahn, Kee-Ho Song, In-Kyu Lee, Ho-Sang Shon, In Joo Kim, Soo Lim, Doo-Man Kim, Choon Hee Chung, Won-Young Lee, Soon Hee Lee, Dong Joon Kim, Sung-Rae Cho, Chang Hee Jung, Hyun Jeong Jeon, Seung-Hwan Lee, Keun-Young Park, Sang Youl Rhee, Sin Gon Kim, Seok O Park, Dae Jung Kim, Byung Joon Kim, Sang Ah Lee, Yong-Hyun Kim, Kyung-Soo Kim, Ji A Seo, Il Seong Nam-Goong, Chang Won Lee, Duk Kyu Kim, Sang Wook Kim, Chung Gu Cho, Jung Han Kim, Yeo-Joo Kim, Jae-Myung Yoo, Kyung Wan Min, Moon-Kyu Lee; Diabetes Metab J. 2024;48(4):730-739. Published online May 20, 2024; DOI: https://doi.org/10.4093/dmj.2023.0077

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

Citations

Citations to this article as recorded by

Real-world safety evaluation of atorvastatin: insights from the US FDA adverse event reporting system (FAERS)
Hongbing Wan, Xiuxiu Xu, Dasong Yi, Kexin Shuai
Expert Opinion on Drug Safety.2025; 24(3): 305. CrossRef
Exploration of metformin-based drug combination for mitigating diabetes-associated atherosclerotic diseases
Biao Qu, Zheng Li, Wei Hu
World Journal of Diabetes.2025;[Epub] CrossRef

Lifestyle
Enhancing Diabetes Care through a Mobile Application: A Randomized Clinical Trial on Integrating Physical and Mental Health among Disadvantaged Individuals: Jae Hyun Bae, Eun Hee Park, Hae Kyung Lee, Kun Ho Yoon, Kyu Chang Won, Hyun Mi Kim, Sin Gon Kim; Diabetes Metab J. 2024;48(4):790-801. Published online February 2, 2024; DOI: https://doi.org/10.4093/dmj.2023.0298

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Background
This study examines integrating physical and mental healthcare for disadvantaged persons with type 2 diabetes mellitus and mild-to-moderate depression in the community, using a mobile application within a public-private-academic partnership.
Methods
The Korean Diabetes Association has developed a mobile application combining behavioral activation for psychological well-being and diabetes self-management, with conventional medical therapy. Participants were randomly assigned to receive the application with usual care or only usual care. Primary outcomes measured changes in psychological status and diabetes selfmanagement through questionnaires at week 12 from the baseline. Secondary outcomes assessed glycemic and lipid control, with psychological assessments at week 16.
Results
Thirty-nine of 73 participants completed the study (20 and 19 in the intervention and control groups, respectively) and were included in the analysis. At week 12, the intervention group showed significant reductions in depression severity and perceived stress compared to the control group. Additionally, they reported increased perceived social support and demonstrated improved diabetes self-care behavior. These positive effects persisted through week 16, with the added benefit of reduced anxiety. While fasting glucose levels in the intervention group tended to improve, no other significant differences were observed in laboratory assessments between the groups.
Conclusion
This study provides compelling evidence for the potential efficacy of a mobile application that integrates physical and mental health components to address depressive symptoms and enhance diabetes self-management in disadvantaged individuals with type 2 diabetes mellitus and depression. Further research involving larger and more diverse populations is warranted to validate these findings and solidify their implications.

Citations

Citations to this article as recorded by

Social determinants of health and type 2 diabetes in Asia
Kyunghun Sung, Seung‐Hwan Lee
Journal of Diabetes Investigation.2025;[Epub] CrossRef

Reviews

Metabolic Risk/Epidemiology
Role of Fenofibrate Use in Dyslipidemia and Related Comorbidities in the Asian Population: A Narrative Review: Chaicharn Deerochanawong, Sin Gon Kim, Yu-Cheng Chang; Diabetes Metab J. 2024;48(2):184-195. Published online January 26, 2024; DOI: https://doi.org/10.4093/dmj.2023.0168

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Hypertriglyceridemia and decreased high-density lipoprotein cholesterol (HDL-C) persist despite statin therapy, contributing to residual atherosclerotic cardiovascular disease (ASCVD) risk. Asian subjects are metabolically more susceptible to hypertriglyceridemia than other ethnicities. Fenofibrate regulates hypertriglyceridemia, raises HDL-C levels, and is a recommended treatment for dyslipidemia. However, data on fenofibrate use across different Asian regions are limited. This narrative review summarizes the efficacy and safety data of fenofibrate in Asian subjects with dyslipidemia and related comorbidities (diabetes, metabolic syndrome, diabetic retinopathy, and diabetic nephropathy). Long-term fenofibrate use resulted in fewer cardiovascular (CV) events and reduced the composite of heart failure hospitalizations or CV mortality in type 2 diabetes mellitus. Fenofibrate plays a significant role in improving irisin resistance and microalbuminuria, inhibiting inflammatory responses, and reducing retinopathy incidence. Fenofibrate plus statin combination significantly reduced composite CV events risk in patients with metabolic syndrome and demonstrated decreased triglyceride and increased HDL-C levels with an acceptable safety profile in those with high CV or ASCVD risk. Nevertheless, care is necessary with fenofibrate use due to possible hepatic and renal toxicities in vulnerable individuals. Long-term trials and real-world studies are needed to confirm the clinical benefits of fenofibrate in the heterogeneous Asian population with dyslipidemia.

Citations

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Triterpenoids from ilicis rotundae cortex ameliorate hyperlipidemia by affecting bile acids-hepatointestinal FXR axis
Wei Zeng, Mengjia Sun, Jiamin Cao, Caixin Chen, Shiqin Jiang, Yuanyuan Wang, Weiqun Yang, Zhongxiang Zhao, Jing Jin
Phytomedicine.2025; 139: 156537. CrossRef
Targeting of AMPK/MTOR signaling in the management of atherosclerosis: Outmost leveraging
Hayder M. Al-kuraishy, Ghassan M. Sulaiman, Mayyadah H. Mohsin, Hamdoon A. Mohammed, Retaj A. Dawood, Ali K. Albuhadily, Ali I. Al-Gareeb, Salim Albukhaty, Mosleh M. Abomughaid
International Journal of Biological Macromolecules.2025; 309: 142933. CrossRef
Fenofibrate to prevent amputation and reduce vascular complications in patients with diabetes: FENO-PREVENT
Eu Jeong Ku, Bongseong Kim, Kyungdo Han, Seung-Hwan Lee, Hyuk-Sang Kwon
Cardiovascular Diabetology.2024;[Epub] CrossRef
The role of DGAT1 and DGAT2 in tumor progression via fatty acid metabolism: A comprehensive review
Leisheng Wang, Shiwei Xu, Mengzhen Zhou, Hao Hu, Jinyou Li
International Journal of Biological Macromolecules.2024; 278: 134835. CrossRef
An exploratory investigation of lipid-lowering potential of spirulina ( Arthrospira platensis ) targeting apoprotein-E in chronic hyperlipidemic wistar albino rats
Anum Nazir, Mahr Un Nisa, Mohamed H. Mahmoud, Ahmed M. El-Gazzar, Eliasse Zongo
Cogent Food & Agriculture.2024;[Epub] CrossRef
Advances in Understanding Diabetic Kidney Disease Progression and the Mechanisms of Acupuncture Intervention
Jinyi Shan, Ziyi Cao, Siming Yu
International Journal of General Medicine.2024; Volume 17: 5593. CrossRef

Pathophysiology
Attention to Innate Circadian Rhythm and the Impact of Its Disruption on Diabetes: Da Young Lee, Inha Jung, So Young Park, Ji Hee Yu, Ji A Seo, Kyeong Jin Kim, Nam Hoon Kim, Hye Jin Yoo, Sin Gon Kim, Kyung Mook Choi, Sei Hyun Baik, Nan Hee Kim; Diabetes Metab J. 2024;48(1):37-52. Published online January 3, 2024; DOI: https://doi.org/10.4093/dmj.2023.0193

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Abstract PDF PubReader ePub: Novel strategies are required to reduce the risk of developing diabetes and/or clinical outcomes and complications of diabetes. In this regard, the role of the circadian system may be a potential candidate for the prevention of diabetes. We reviewed evidence from animal, clinical, and epidemiological studies linking the circadian system to various aspects of the pathophysiology and clinical outcomes of diabetes. The circadian clock governs genetic, metabolic, hormonal, and behavioral signals in anticipation of cyclic 24-hour events through interactions between a “central clock” in the suprachiasmatic nucleus and “peripheral clocks” in the whole body. Currently, circadian rhythmicity in humans can be subjectively or objectively assessed by measuring melatonin and glucocorticoid levels, core body temperature, peripheral blood, oral mucosa, hair follicles, rest-activity cycles, sleep diaries, and circadian chronotypes. In this review, we summarized various circadian misalignments, such as altered light-dark, sleep-wake, rest-activity, fasting-feeding, shift work, evening chronotype, and social jetlag, as well as mutations in clock genes that could contribute to the development of diabetes and poor glycemic status in patients with diabetes. Targeting critical components of the circadian system could deliver potential candidates for the treatment and prevention of type 2 diabetes mellitus in the future.

Original Articles

Drug Regimen
The Efficacy and Safety of Moderate-Intensity Rosuvastatin with Ezetimibe versus High-Intensity Rosuvastatin in High Atherosclerotic Cardiovascular Disease Risk Patients with Type 2 Diabetes Mellitus: A Randomized, Multicenter, Open, Parallel, Phase 4 Study: Jun Sung Moon, Il Rae Park, Sang Soo Kim, Hye Soon Kim, Nam Hoon Kim, Sin Gon Kim, Seung Hyun Ko, Ji Hyun Lee, Inkyu Lee, Bo Kyeong Lee, Kyu Chang Won; Diabetes Metab J. 2023;47(6):818-825. Published online November 24, 2023; DOI: https://doi.org/10.4093/dmj.2023.0171

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Background
To investigate the efficacy and safety of moderate-intensity rosuvastatin/ezetimibe combination compared to highintensity rosuvastatin in high atherosclerotic cardiovascular disease (ASCVD) risk patients with type 2 diabetes mellitus (T2DM).
Methods
This study was a randomized, multicenter, open, parallel phase 4 study, and enrolled T2DM subjects with an estimated 10-year ASCVD risk ≥7.5%. The primary endpoint was the low-density lipoprotein cholesterol (LDL-C) change rate after 24-week rosuvastatin 10 mg/ezetimibe 10 mg treatment was non-inferior to that of rosuvastatin 20 mg. The achievement proportion of 10-year ASCVD risk <7.5% or comprehensive lipid target (LDL-C <70 mg/dL, non-high-density lipoprotein cholesterol <100 mg/dL, and apolipoprotein B <80 mg/dL) without discontinuation, and several metabolic parameters were explored as secondary endpoints.
Results
A hundred and six participants were assigned to each group. Both groups showed significant reduction in % change of LDL-C from baseline at week 24 (–63.90±6.89 vs. –55.44±6.85, combination vs. monotherapy, p=0.0378; respectively), but the combination treatment was superior to high-intensity monotherapy in LDL-C change (%) from baseline (least square [LS] mean difference, –8.47; 95% confidence interval, –16.44 to –0.49; p=0.0378). The combination treatment showed a higher proportion of achieved comprehensive lipid targets rather than monotherapy (85.36% vs. 62.22% in monotherapy, p=0.015). The ezetimibe combination significantly improved homeostasis model assessment of β-cell function even without A1c changes (LS mean difference, 17.13; p=0.0185).
Conclusion
In high ASCVD risk patients with T2DM, the combination of moderate-intensity rosuvastatin and ezetimibe was not only non-inferior but also superior to improving dyslipidemia with additional benefits compared to high-intensity rosuvastatin monotherapy.

Citations

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Clinical study on the effect of jejunoileal side-to-side anastomosis on metabolic parameters in patients with type 2 diabetes
Ji-Kui Wang, Di Zhang, Jin-Feng Wang, Wan-Lin Lu, Jing-Yuan Wang, Shi-Feng Liang, Ran Liu, Jing-Xin Jiang, Hong-Tao Li, Xuan Yang
World Journal of Diabetes.2025;[Epub] CrossRef
Overcoming β-Cell Dysfunction in Type 2 Diabetes Mellitus: CD36 Inhibition and Antioxidant System
Il Rae Park, Yong Geun Chung, Kyu Chang Won
Diabetes & Metabolism Journal.2025; 49(1): 1. CrossRef
Neuroprotective Effect of Rosuvastatin Calcium Combined with Hyperbaric Oxygen Mediated p38MAPK Pathway in Rats with Leukoaraiosis
Yafeng Shi, Gemin Zhu, Jun Yan, Linxin Zhang, Yongku Du, Zhuoqiong Bian, Jing Fan
Cell Biochemistry and Biophysics.2025;[Epub] CrossRef
Ezetimibe plus statin combination versus double-dose statin in patients with dyslipidemia and atherosclerotic cardiovascular disease risk: a comprehensive systematic review and meta-analysis of 47 randomized controlled trials
Abdelrahman Mahmoud, Hazem Mohamed Salamah, Hazem Rezq, Yazan Al-Mohtasib, Ali Ashraf Salah Ahmed, Mohamed R. Abdelraouf, Ahmed Mazen Amin, Ahmed A. Ibrahim, Yasmine Adel Mohammed, Omar Ahmed Abdelwahab, Majd M. AlBarakat, Salem Elshenawy, Husam Abu Suili
Baylor University Medical Center Proceedings.2025; : 1. CrossRef
Does Rosuvastatin/Ezetimibe Combination Therapy Offer Potential Benefits for Glucose Metabolism beyond Lipid-Lowering Efficacy in T2DM?
Il Rae Park, Jun Sung Moon
Diabetes & Metabolism Journal.2024; 48(3): 387. CrossRef
Efficacy and safety of double-dose statin monotherapy versus moderate-intensity statin combined with ezetimibe dual therapy in diabetic patients: a systematic review and meta-analysis of randomized controlled trials
Aman Goyal, Muhammad Daoud Tariq, Hritvik Jain, Abhigan Babu Shrestha, Laveeza Fatima, Romana Riyaz, Hritik Raj Yadav, Darsh Safi, Abdul Qahar K. Yasinzai, Rozi Khan, Amir Humza Sohail, Mohamed Daoud, Abu Baker Sheikh
Cardiovascular Endocrinology & Metabolism.2024;[Epub] CrossRef
Efficacy and safety of moderate-intensity rosuvastatin plus ezetimibe versus high-intensity rosuvastatin monotherapy in the treatment of composite cardiovascular events with hypercholesterolemia: A meta-analysis
Lingyan Liu, Yongkun Deng, Lei Li, Xingbiao Yang, Zhaoheng Yin, Yong Lai, Jaspinder Kaur
PLOS ONE.2024; 19(11): e0310696. CrossRef

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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Background
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.

Citations

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Explanatory variables of objectively measured 24-h movement behaviors in people with prediabetes and type 2 diabetes: A systematic review
Lotte Bogaert, Iris Willems, Patrick Calders, Eveline Dirinck, Manon Kinaupenne, Marga Decraene, Bruno Lapauw, Boyd Strumane, Margot Van Daele, Vera Verbestel, Marieke De Craemer
Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2024; 18(4): 102995. CrossRef

Cardiovascular Risk/Epidemiology
Comparison of on-Statin Lipid and Lipoprotein Levels for the Prediction of First Cardiovascular Event in Type 2 Diabetes Mellitus: Ji Yoon Kim, Jimi Choi, Sin Gon Kim, Nam Hoon Kim; Diabetes Metab J. 2023;47(6):837-845. Published online August 23, 2023; DOI: https://doi.org/10.4093/dmj.2022.0217

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Abstract PDF Supplementary Material PubReader ePub: Background
A substantial cardiovascular disease risk remains even after optimal statin therapy. Comparative predictiveness of major lipid and lipoprotein parameters for cardiovascular events in patients with type 2 diabetes mellitus (T2DM) who are treated with statins is not well documented.
Methods
From the Korean Nationwide Cohort, 11,900 patients with T2DM (≥40 years of age) without a history of cardiovascular disease and receiving moderate- or high-intensity statins were included. The primary outcome was the first occurrence of major adverse cardiovascular events (MACE) including ischemic heart disease, ischemic stroke, and cardiovascular death. The risk of MACE was estimated according to on-statin levels of low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), highdensity lipoprotein cholesterol (HDL-C), and non-HDL-C.
Results
MACE occurred in 712 patients during a median follow-up period of 37.9 months (interquartile range, 21.7 to 54.9). Among patients achieving LDL-C levels less than 100 mg/dL, the hazard ratios for MACE per 1-standard deviation change in ontreatment values were 1.25 (95% confidence interval [CI], 1.07 to 1.47) for LDL-C, 1.31 (95% CI, 1.09 to 1.57) for non-HDL-C, 1.05 (95% CI, 0.91 to 1.21) for TG, and 1.16 (95% CI, 0.98 to 1.37) for HDL-C, after adjusting for potential confounders and lipid parameters mutually. The predictive ability of on-statin LDL-C and non-HDL-C for MACE was prominent in patients at high cardiovascular risk or those with LDL-C ≥70 mg/dL.
Conclusion
On-statin LDL-C and non-HDL-C levels are better predictors of the first cardiovascular event than TG or HDL-C in patients with T2DM.

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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A Narrative Review: Relationship Between Glycemic Variability and Emerging Complications of Diabetes Mellitus
Xinxin Wang, Yanli Cao
Biomolecules.2025; 15(2): 188. CrossRef
Fasting glucose variability and risk of dementia in Parkinson’s disease: a 9-year longitudinal follow-up study of a nationwide cohort
Sung Hoon Kang, Yunjin Choi, Su Jin Chung, Seok-Joo Moon, Chi Kyung Kim, Ji Hyun Kim, Kyungmi Oh, Joon Shik Yoon, Sang Won Seo, Geum Joon Cho, Seong-Beom Koh
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Vishal Chavda, Dhananjay Yadav, Snehal Patel, Minseok Song
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Fang Cao, Fushuang Yang, Jian Li, Wei Guo, Chongheng Zhang, Fa Gao, Xinxin Sun, Yi Zhou, Wenfeng Zhang
Diabetology & Metabolic Syndrome.2024;[Epub] CrossRef
Effect of glucose variability on the mortality of adults aged 75 years and over during the first year of the COVID-19 pandemic
Miguel A. Salinero-Fort, F. Javier San Andrés-Rebollo, Juan Cárdenas-Valladolid, José Mostaza, Carlos Lahoz, Fernando Rodriguez-Artalejo, Paloma Gómez-Campelo, Pilar Vich-Pérez, Rodrigo Jiménez-García, José M. de-Miguel-Yanes, Javier Maroto-Rodriguez, Bel
BMC Geriatrics.2024;[Epub] CrossRef
Association of remnant cholesterol with risk of dementia: a nationwide population-based cohort study in South Korea
Ji Hye Heo, Han Na Jung, Eun Roh, Kyung-do Han, Jun Goo Kang, Seong Jin Lee, Sung-Hee Ihm
The Lancet Healthy Longevity.2024; 5(8): e524. CrossRef
Glycated Hemoglobin A1c Time in Range and Dementia in Older Adults With Diabetes
Patricia C. Underwood, Libin Zhang, David C. Mohr, Julia C. Prentice, Richard E. Nelson, Andrew E. Budson, Paul R. Conlin
JAMA Network Open.2024; 7(8): e2425354. CrossRef
Early Detection of Dementia in Populations With Type 2 Diabetes: Predictive Analytics Using Machine Learning Approach
Phan Thanh Phuc, Phung-Anh Nguyen, Nam Nhat Nguyen, Min-Huei Hsu, Nguyen Quoc Khanh Le, Quoc-Viet Tran, Chih-Wei Huang, Hsuan-Chia Yang, Cheng-Yu Chen, Thi Anh Hoa Le, Minh Khoi Le, Hoang Bac Nguyen, Christine Y Lu, Jason C Hsu
Journal of Medical Internet Research.2024; 26: e52107. CrossRef
Increased Risk of Alzheimer's Disease With Glycemic Variability: A Systematic Review and Meta-Analysis
Paul Nichol G Gonzales, Encarnita R Ampil, Joseree-Ann S Catindig-Dela Rosa, Steven G Villaraza, Ma. Lourdes C Joson
Cureus.2024;[Epub] CrossRef
The Association of Glucose Variability and Dementia Incidence in Latinx Adults with Type 2 Diabetes: A Retrospective Study
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Response

Time to Reach Target Glycosylated Hemoglobin Is Associated with Long-Term Durable Glycemic Control and Risk of Diabetic Complications in Patients with Newly Diagnosed Type 2 Diabetes Mellitus: A 6-Year Observational Study (Diabetes Metab J 2021;45:368-78): Kyoung Jin Kim, Jimi Choi, Jae Hyun Bae, Kyeong Jin Kim, Hye Jin Yoo, Ji A Seo, Nan Hee Kim, Kyung Mook Choi, Sei Hyun Baik, Sin Gon Kim, Nam Hoon Kim; Diabetes Metab J. 2021;45(4):617-618. Published online July 30, 2021; DOI: https://doi.org/10.4093/dmj.2021.0152

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Original Articles

COVID-19
Use of Renin-Angiotensin-Aldosterone System Inhibitors and Severe COVID-19 Outcomes in Patients with Hypertension: A Nationwide Cohort Study: Jae Hyun Bae, Sun Kyu Choi, Nam Hoon Kim, Juneyoung Lee, Sin Gon Kim; Diabetes Metab J. 2021;45(3):430-438. Published online February 22, 2021; DOI: https://doi.org/10.4093/dmj.2020.0279

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Background
Angiotensin-converting enzyme 2 facilitates the entry of severe acute respiratory syndrome coronavirus 2 into the human body. We investigated the association of renin-angiotensin-aldosterone system (RAAS) inhibitor use with severe coronavirus disease 2019 (COVID-19) outcomes in hypertensive patients.
Methods
We identified hypertensive patients with confirmed COVID-19 from the Korean Health Insurance Review and Assessment Service from inception to May 15, 2020. The primary outcome was the composite of intensive care unit (ICU) admission, invasive mechanical ventilation (IMV), continuous renal replacement therapy (CRRT), extracorporeal membrane oxygenation (ECMO), and death from COVID-19. The individual components were evaluated as secondary outcomes.
Results
Of 1,374 hypertensive patients with COVID-19, 1,076 (78.3%) and 298 (21.7%) were users and never-users of RAAS inhibitors, respectively. The RAAS inhibitor users were not associated with the risk of the primary outcome (adjusted odds ratio [aOR], 0.72; 95% confidence interval [CI], 0.46 to 1.10). The risk of ICU admission was significantly lower in the users than the never-users (aOR, 0.44; 95% CI, 0.24 to 0.84). The RAAS inhibitors were beneficial only in ICU admissions that did not require IMV (aOR, 0.28; 95% CI, 0.14 to 0.58). The risk of death from COVID-19 was comparable between the groups (aOR, 1.09; 95% CI, 0.64 to 1.85). We could not evaluate the risks of CRRT and ECMO owing to the small number of events.
Conclusion
RAAS inhibitor use was not associated with the composite of severe outcomes in the hypertensive patients with COVID-19 but significantly lowered the risk of ICU admission, particularly in patients who did not require IMV.

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Complications
Time to Reach Target Glycosylated Hemoglobin Is Associated with Long-Term Durable Glycemic Control and Risk of Diabetic Complications in Patients with Newly Diagnosed Type 2 Diabetes Mellitus: A 6-Year Observational Study: Kyoung Jin Kim, Jimi Choi, Jae Hyun Bae, Kyeong Jin Kim, Hye Jin Yoo, Ji A Seo, Nan Hee Kim, Kyung Mook Choi, Sei Hyun Baik, Sin Gon Kim, Nam Hoon Kim; Diabetes Metab J. 2021;45(3):368-378. Published online October 20, 2020; DOI: https://doi.org/10.4093/dmj.2020.0046

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Background
To evaluate the association of time to reach the target glycosylated hemoglobin (HbA1c) level with long-term durable glycemic control and risk of diabetic complications in patients with newly diagnosed type 2 diabetes mellitus (T2DM).
Methods
In a longitudinal observational cohort, 194 patients with T2DM newly diagnosed between January 2011 and March 2013 were followed up over 6 years. Patients were classified according to the time needed to reach the target HbA1c (<7.0%): <3, 3 to 6 (early achievement group), and ≥6 months (late achievement group). Risks of microvascular complications including diabetic retinopathy, nephropathy, and neuropathy as well as macrovascular events including ischemic heart disease, ischemic stroke, and peripheral arterial disease were assessed by multivariable Cox proportional hazards analysis.
Results
During a median follow-up of 6.53 years, 66 microvascular and 14 macrovascular events occurred. Maintenance of durable glycemic control over 6 years was more likely in the early achievement groups than in the late achievement group (34.5%, 30.0%, and 16.1% in <3, 3 to 6, and ≥6 months, respectively, P=0.039). Early target HbA1c achievement was associated with lower risk of composite diabetic complications (adjusted hazard ratio [HR, 0.47; 95% confidence interval [CI], 0.26 to 0.86 in <3 months group) (adjusted HR, 0.50; 95% CI, 0.23 to 1.10 in 3 to 6 months group, in reference to ≥6 months group). Similar trends were maintained for risks of microvascular and macrovascular complications, although statistical significance was not reached for macrovascular complications.
Conclusion
Early target HbA1c achievement was associated with long-term durable glycemic control and reduced risk of diabetic complications in newly diagnosed T2DM.

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Metabolic Risk/Epidemiology
Age- and Sex-Related Differential Associations between Body Composition and Diabetes Mellitus: Eun Roh, Soon Young Hwang, Jung A Kim, You-Bin Lee, So-hyeon Hong, Nam Hoon Kim, Ji A Seo, Sin Gon Kim, Nan Hee Kim, Kyung Mook Choi, Sei Hyun Baik, Hye Jin Yoo; Diabetes Metab J. 2021;45(2):183-194. Published online June 16, 2020; DOI: https://doi.org/10.4093/dmj.2019.0171

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Background

The age- and sex-related differences on the impacts of body composition on diabetes mellitus (DM) remain uncertain.

Methods

The fourth and fifth Korea National Health and Nutrition Examination Survey included 15,586 subjects over 30 years of age who completed dual-energy X-ray absorptiometry. We conducted a cross-sectional study to investigate whether muscle mass index (MMI), defined as appendicular skeletal muscle divided by body mass index (BMI), and fat mass index (FMI), defined as trunk fat mass divided by BMI, were differently associated with DM according to age and sex.

Results

In multivariate logistic regression, the risk for DM significantly increased across quartiles of FMI in men aged ≥70. Meanwhile, MMI showed a protective association with DM in men of the same age. The odds ratios (ORs) for the highest quartile versus the lowest quartile of FMI and MMI were 3.116 (95% confidence interval [CI], 1.405 to 6.914) and 0.295 (95% CI, 0.157 to 0.554), respectively. In women, the ORs of DM was significantly different across FMI quartiles in those over age 50. The highest quartile of FMI exhibited increased ORs of DM in subjects aged 50 to 69 (OR, 1.891; 95% CI, 1.229 to 2.908) and ≥70 (OR, 2.275; 95% CI, 1.103 to 4.69) compared to lowest quartile. However, MMI was not significantly associated with DM in women of all age groups.

Conclusion

Both FMI and MMI were independent risk factors for DM in men aged 70 years or more. In women over 50 years, FMI was independently associated with DM. There was no significant association between MMI and DM in women.

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Yiseul Lee, Nam-Kyoo Lim, Hyun-Young Park
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The Journal of Clinical Endocrinology & Metabolism.2023; 108(5): 1173. CrossRef
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Shanhu Qiu, Xue Cai, Yang Yuan, Bo Xie, Zilin Sun, Tongzhi Wu
Diabetes Research and Clinical Practice.2022; 189: 109939. CrossRef
Whole and segmental body composition changes during mid-follicular and mid-luteal phases of the menstrual cycle in recreationally active young women
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Review

Drug/Regimen
Fibrates Revisited: Potential Role in Cardiovascular Risk Reduction: Nam Hoon Kim, Sin Gon Kim; Diabetes Metab J. 2020;44(2):213-221. Published online April 23, 2020; DOI: https://doi.org/10.4093/dmj.2020.0001

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Abstract PDF PubReader

Fibrates, peroxisome proliferator-activated receptor-α agonists, are potent lipid-modifying drugs. Their main effects are reduction of triglycerides and increase in high-density lipoprotein levels. Several randomized controlled trials have not demonstrated their benefits on cardiovascular risk reduction, especially as an “add on” to statin therapy. However, subsequent analyses by major clinical trials, meta-analyses, and real-world evidence have proposed their potential in specific patient populations with atherogenic dyslipidemia and metabolic syndrome. Here, we have reviewed and discussed the accumulated data on fibrates to understand their current status in cardiovascular risk management.

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