Diabetes & Metabolism Journal

Original Articles

Complications
The Causal Relationship and Association between Biomarkers, Dietary Intake, and Diabetic Retinopathy: Insights from Mendelian Randomization and Cross-Sectional Study: Xuehao Cui, Dejia Wen, Jishan Xiao, Xiaorong Li; Received November 17, 2024 Accepted December 12, 2024 Published online March 31, 2025; DOI: https://doi.org/10.4093/dmj.2024.0731 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Diabetic retinopathy (DR) is a major cause of vision loss, linked to hyperglycemia, oxidative stress, and inflammation. Despite advancements in DR treatments, approximately 40% of patients do not respond effectively, underscoring the need for novel, noninvasive biomarkers to predict DR risk and progression. This study investigates causal relationships between specific biomarkers, dietary factors, and DR development using Mendelian randomization (MR) and cross-sectional data.
Methods
We conducted a two-phase analysis combining MR and cross-sectional methods. First, MR analysis examined causal associations between 35 biomarkers, 226 dietary factors, and DR progression using data from the UK Biobank and Genome-Wide Association Study (GWAS) datasets. Second, a cross-sectional study with National Health and Nutrition Examination Survey (NHANES) and a clinical cohort from Tianjin Medical University Eye Hospital validated findings and explored biomarkers’ predictive capabilities through a nomogram-based prediction model.
Results
MR analysis identified eight biomarkers (e.g., glycosylated hemoglobin [HbA1c], high-density lipoprotein cholesterol [HDL-C]) with significant causal links to DR. Inflammatory markers and metabolic factors, such as high glucose and HDL-C levels, were strongly associated with DR risk and progression. Specific dietary factors, like cheese intake, exhibited protective roles, while alcohol intake increased DR risk. Validation within NHANES and Tianjin cohorts supported these causal associations.
Conclusion
This study elucidates causal relationships between biomarkers, dietary habits, and DR progression, emphasizing the potential for personalized dietary interventions to prevent or manage DR. Findings support the use of HDL-C, HbA1c, and dietary factors as biomarkers or therapeutics in DR, though further studies are needed for broader applicability.

Complications
Does 10-Year Atherosclerotic Cardiovascular Disease Risk Predict Incident Diabetic Nephropathy and Retinopathy in Patients with Type 2 Diabetes Mellitus? Results from Two Prospective Cohort Studies in Southern China: Jiaheng Chen, Yu Ting Li, Zimin Niu, Zhanpeng He, Yao Jie Xie, Jose Hernandez, Wenyong Huang, Harry H.X. Wang, on Behalf of the Guangzhou Diabetic Eye Study Group; Diabetes Metab J. 2025;49(2):298-310. Published online February 4, 2025; DOI: https://doi.org/10.4093/dmj.2024.0239

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Background
Diabetic macrovascular and microvascular complications often coexist and may share similar risk factors and pathological pathways. We aimed to investigate whether 10-year atherosclerotic cardiovascular disease (ASCVD) risk, which is commonly assessed in diabetes management, can predict incident diabetic nephropathy (DN) and retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM).
Methods
This prospective cohort study enrolled 2,891 patients with clinically diagnosed T2DM who were free of ASCVD, nephropathy, or retinopathy at baseline in the Guangzhou (2017–2022) and Shaoguan (2019–2021) Diabetic Eye Study in southern China. The 10-year ASCVD risk was calculated by the Prediction for ASCVD Risk in China (China-PAR) equations. Multivariable- adjusted Cox proportional hazard models were developed to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). The area under the receiver operating characteristic curve (AUC) was used to evaluate predictive capability.
Results
During follow-up, a total of 171 cases of DN and 532 cases of DR were documented. Each 1% increment in 10-year ASCVD risk was associated with increased risk of DN (pooled HR, 1.122; 95% CI, 1.094 to 1.150) but not DR (pooled HR, 0.996; 95% CI, 0.979 to 1.013). The model demonstrated acceptable performance in predicting new-onset DN (pooled AUC, 0.670; 95% CI, 0.628 to 0.715). These results were consistent across cohorts and subgroups, with the association appearing to be more pronounced in women.
Conclusion
Ten-year ASCVD risk predicts incident DN but not DR in our study population with T2DM. Regular monitoring of ASCVD risk in routine diabetes practice may add to the ability to enhance population-based prevention for both macrovascular and microvascular diseases, particularly among women.

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Investigation of the Potential Association Between Atherosclerotic Cardiovascular Disease Risk Score and Diabetic Retinopathy in Patients with Type 2 Diabetes: A Cross-Sectional Study
Chrysa Agapitou, Theodoros N. Sergentanis, Effie G. Papageorgiou, Panagiotis Theodossiadis, Ignatios Ikonomidis, Vaia Lambadiari, Irini Chatziralli
Biomedicines.2025; 13(3): 633. CrossRef

Cardiovascular Risk/Epidemiology
Normalized Creatinine-to-Cystatin C Ratio and Risk of Cardiometabolic Multimorbidity in Middle-Aged and Older Adults: Insights from the China Health and Retirement Longitudinal Study: Honglin Sun, Zhenyu Wu, Guang Wang, Jia Liu; Received May 2, 2024 Accepted November 15, 2024 Published online January 20, 2025; DOI: https://doi.org/10.4093/dmj.2024.0100 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Normalized creatinine-to-cystatin C ratio (NCCR) was reported to approximate relative skeletal muscle mass and diabetes risk. However, the association between NCCR and cardiometabolic multimorbidity (CMM) remains elusive. This study aimed to explore their relationship in a large-scale prospective cohort.
Methods
This study included 5,849 middle-age and older participants from the China Health and Retirement Longitudinal Study (CHARLS) enrolled between 2011 and 2012. The baseline NCCR was determined as creatinine (mg/dL)/cystatin C (mg/L)×10/body mass (kg). CMM was defined as the simultaneous occurrence of two or more of the following conditions: heart disease, stroke, and type 2 diabetes mellitus. Logistic regression analysis and Cox regression analysis were employed to estimate the relationship between NCCR and CMM. The joint effect of body mass index and NCCR on the risk of CMM were further analyzed.
Results
During a median 4-year follow-up, 227 (3.9%) participants developed CMM. The risk of CMM was significantly decreased with per standard deviation increase of NCCR (odds ratio, 0.72; 95% confidence interval, 0.62 to 0.85) after adjustment for confounders (P<0.001). Further sex-specific analysis found significant negative associations between NCCR and CMM in female either without or with one CMM component at baseline, which was attenuated in males but remained statistically significant among those with one basal CMM component. Notably, non-obese individuals with high NCCR levels had the lowest CMM risk compared to obese counterparts with low NCCR levels in both genders.
Conclusion
High NCCR was independently associated with reduced risk of CMM in middle-aged and older adults in China, particularly females.

Metabolic Risk/Epidemiology
Longitudinal Association of Changes in Metabolic Syndrome with Cognitive Function: 12-Year Follow-up of the Guangzhou Biobank Cohort Study: Yu Meng Tian, Wei Sen Zhang, Chao Qiang Jiang, Feng Zhu, Ya Li Jin, Shiu Lun Au Yeung, Jiao Wang, Kar Keung Cheng, Tai Hing Lam, Lin Xu; Diabetes Metab J. 2025;49(1):60-79. Published online October 29, 2024; DOI: https://doi.org/10.4093/dmj.2024.0117

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The association of changes in metabolic syndrome (MetS) with cognitive function remains unclear. We explored this association using prospective and Mendelian randomization (MR) studies.
Methods
MetS components including high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), waist circumference (WC), fasting plasma glucose (FPG), and triglycerides were measured at baseline and two follow-ups, constructing a MetS index. Immediate, delayed memory recall, and cognitive function along with its dimensions were assessed by immediate 10- word recall test (IWRT) and delayed 10-word recall test (DWRT), and mini-mental state examination (MMSE), respectively, at baseline and follow-ups. Linear mixed-effect model was used. Additionally, the genome-wide association study (GWAS) of MetS was conducted and one-sample MR was performed to assess the causality between MetS and cognitive function.
Results
Elevated MetS index was associated with decreasing annual change rates (decrease) in DWRT and MMSE scores, and with decreases in attention, calculation and recall dimensions. HDL-C was positively associated with an increase in DWRT scores, while SBP and FPG were negatively associated. HDL-C showed a positive association, whereas WC was negatively associated with increases in MMSE scores, including attention, calculation and recall dimensions. Interaction analysis indicated that the association of MetS index on cognitive decline was predominantly observed in low family income group. The GWAS of MetS identified some genetic variants. MR results showed a non-significant causality between MetS and decrease in DWRT, IWRT, nor MMSE scores.
Conclusion
Our study indicated a significant association of MetS and its components with declines in memory and cognitive function, especially in delayed memory recall.

Metabolic Risk/Epidemiology
Healthy Lifestyle and the Risk of Metabolic Dysfunction-Associated Fatty Liver Disease: A Large Prospective Cohort Study: Qing Chang, Yixiao Zhang, Tingjing Zhang, Zuyun Liu, Limin Cao, Qing Zhang, Li Liu, Shaomei Sun, Xing Wang, Ming Zhou, Qiyu Jia, Kun Song, Yang Ding, Yuhong Zhao, Kaijun Niu, Yang Xia; Diabetes Metab J. 2024;48(5):971-982. Published online March 19, 2024; DOI: https://doi.org/10.4093/dmj.2023.0133

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Background
The incidence density of metabolic dysfunction-associated fatty liver disease (MAFLD) and the effect of a healthy lifestyle on the risk of MAFLD remain unknown. We evaluated the prevalence and incidence density of MAFLD and investigated the association between healthy lifestyle and the risk of MAFLD.
Methods
A cross-sectional analysis was conducted on 37,422 participants to explore the prevalence of MAFLD. A cohort analysis of 18,964 individuals was conducted to identify the incidence of MAFLD, as well as the association between healthy lifestyle and MAFLD. Cox proportional hazards regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI) with adjustments for confounding factors.
Results
The prevalence of MAFLD, non-alcoholic fatty liver disease, and their comorbidities were 30.38%, 28.09%, and 26.13%, respectively. After approximately 70 thousand person-years of follow-up, the incidence densities of the three conditions were 61.03, 55.49, and 51.64 per 1,000 person-years, respectively. Adherence to an overall healthy lifestyle was associated with a 19% decreased risk of MAFLD (HR, 0.81; 95% CI, 0.72 to 0.92), and the effects were modified by baseline age, sex, and body mass index (BMI). Subgroup analyses revealed that younger participants, men, and those with a lower BMI experienced more significant beneficial effects from healthy lifestyle.
Conclusion
Our results highlight the beneficial effect of adherence to a healthy lifestyle on the prevention of MAFLD. Health management for improving dietary intake, physical activity, and smoking and drinking habits are critical to improving MAFLD.

Citations

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Impact of healthy lifestyles on the risk of metabolic dysfunction‐associated steatotic liver disease among adults with comorbid hypertension and diabetes: Novel insight from a largely middle‐aged and elderly cohort in South China
Jun‐Yan Xi, Yi‐Jing Wang, Xiao‐Heng Li, Nuo‐Min Sun, Rui‐Qi Ming, Hua‐Ling Yan, Huan‐Le Cai, Jian‐Jun Bai, Yi‐Ning Xiang, Jing Gu, Xiao Lin, Gang Liu, Yuan‐Tao Hao
Diabetes, Obesity and Metabolism.2025; 27(5): 2800. CrossRef
Diagnostic indicators and lifestyle interventions of metabolic-associated fatty liver disease
Tianzhu Chen, Xiang Qin, Jianping Jiang, Beihui He
Frontiers in Nutrition.2024;[Epub] CrossRef
Sex differences in pathogenesis and treatment of dyslipidemia in patients with type 2 diabetes and steatotic liver disease
Tatjana Ábel, Béla Benczúr, Éva Csajbókné Csobod
Frontiers in Medicine.2024;[Epub] CrossRef
Associations of traditional healthy lifestyle and sleep quality with metabolic dysfunction-associated fatty liver disease: two population-based studies
Jialu Yang, Qi Zhang, Wanying Zhao, Bingqi Ye, Siqi Li, Zhuoyu Zhang, Jingmeng Ju, Jialin He, Min Xia, Tiantian Xiong, Yan Liu
Nutrition & Diabetes.2024;[Epub] CrossRef

Drug/Regimen
Safety and Effectiveness of Dulaglutide in the Treatment of Type 2 Diabetes Mellitus: A Korean Real-World Post-Marketing Study: Jeonghee Han, Woo Je Lee, Kyu Yeon Hur, Jae Hyoung Cho, Byung Wan Lee, Cheol-Young Park; Diabetes Metab J. 2024;48(3):418-428. Published online February 2, 2024; DOI: https://doi.org/10.4093/dmj.2023.0030

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Background
To investigate the real-world safety and effectiveness of dulaglutide in Korean adults with type 2 diabetes mellitus (T2DM).
Methods
This was a real-world, prospective, non-interventional post-marketing safety study conducted from May 26, 2015 to May 25, 2021 at 85 Korean healthcare centers using electronic case data. Data on patients using dulaglutide 0.75 mg/0.5 mL or the dulaglutide 1.5 mg/0.5 mL single-use pens were collected and pooled. The primary objective was to report the frequency and proportion of adverse and serious adverse events that occurred. The secondary objective was to monitor the effectiveness of dulaglutide at 12 and 24 weeks by evaluating changes in glycosylated hemoglobin (HbA1c ), fasting plasma glucose, and body weight.
Results
Data were collected from 3,067 subjects, and 3,022 subjects who received ≥1 dose (of any strength) of dulaglutide were included in the safety analysis set (53% female, mean age 56 years; diabetes duration 11.2 years, mean HbA1c 8.8%). The number of adverse events reported was 819; of these, 68 (8.3%) were serious adverse events. One death was reported. Adverse events were mostly mild in severity; 60.81% of adverse events were considered related to dulaglutide. This study was completed by 72.73% (2,198/3,022) of subjects. At 12/24 weeks there were significant (P<0.0001) reductions from baseline in least-squares mean HbA1c (0.96%/0.95%), fasting blood glucose (26.24/24.43 mg/dL), and body weight (0.75/1.21 kg).
Conclusion
Dulaglutide was generally well tolerated and effective in real-world Korean individuals with T2DM. The results from this study contribute to the body of evidence for dulaglutide use in this population.

Citations

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One-year Efficacy and Safety of Dulaglutide in Patients with Type 2 Diabetes and Chronic Kidney Disease: A Retrospective Study of Asian Patients
Myung Jin Kim, Hwi Seung Kim, Yun Kyung Cho, Chang Hee Jung, Woo Je Lee
Clinical Therapeutics.2024; 46(9): 683. CrossRef
Safety and Effectiveness of Naltrexone-Bupropion in Korean Adults with Obesity: Post-Marketing Surveillance Study
Young Lyu, Hongyup Ahn, Sangmo Hong, Cheol-Young Park
Drug Design, Development and Therapy.2024; Volume 18: 5255. CrossRef

Review

Metabolic Risk/Epidemiology
Hepatic Fibrosis and Cancer: The Silent Threats of Metabolic Syndrome: Scott L. Friedman; Diabetes Metab J. 2024;48(2):161-169. Published online January 26, 2024; DOI: https://doi.org/10.4093/dmj.2023.0240

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Metabolic dysfunction-associated steatotic (fatty) liver disease (MASLD), previously termed non-alcoholic fatty liver disease, is a worldwide epidemic that can lead to hepatic inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The disease is typically a component of the metabolic syndrome that accompanies obesity, and is often overlooked because the liver manifestations are clinically silent until late-stage disease is present (i.e., cirrhosis). Moreover, Asian populations, including Koreans, have a higher fraction of patients who are lean, yet their illness has the same prognosis or worse than those who are obese. Nonetheless, ongoing injury can lead to hepatic inflammation and ballooning of hepatocytes as classic features. Over time, fibrosis develops following activation of hepatic stellate cells, the liver’s main fibrogenic cell type. The disease is usually more advanced in patients with type 2 diabetes mellitus, indicating that all diabetic patients should be screened for liver disease. Although there has been substantial progress in clarifying pathways of injury and fibrosis, there no approved therapies yet, but current research seeks to uncover the pathways driving hepatic inflammation and fibrosis, in hopes of identifying new therapeutic targets. Emerging molecular methods, especially single cell sequencing technologies, are revolutionizing our ability to clarify mechanisms underlying MASLD-associated fibrosis and HCC.

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The Triad of Risk: Linking MASLD, Cardiovascular Disease and Type 2 Diabetes; From Pathophysiology to Treatment
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Role of triggering receptor expressed on myeloid cells 2 in the pathogenesis of non-alcoholic fatty liver disease
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World Journal of Hepatology.2025;[Epub] CrossRef
Efficacy of measuring natural killer-activating receptor ligands to predict the pathogenesis of metabolic dysfunction-associated steatotic liver disease
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Prognostic Impact of Metabolic Syndrome and Steatotic Liver Disease in Hepatocellular Carcinoma Using Machine Learning Techniques
Sergio Gil-Rojas, Miguel Suárez, Pablo Martínez-Blanco, Ana M. Torres, Natalia Martínez-García, Pilar Blasco, Miguel Torralba, Jorge Mateo
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Interplay between YAP/TAZ and metabolic dysfunction-associated steatotic liver disease progression
Na Young Lee, Myeung Gi Choi, Eui Jin Lee, Ja Hyun Koo
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New Biomarkers in Liver Fibrosis: A Pass through the Quicksand?
Marzia Tagliaferro, Mariapaola Marino, Valerio Basile, Krizia Pocino, Gian Ludovico Rapaccini, Gabriele Ciasca, Umberto Basile, Valeria Carnazzo
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Diagnostics.2024; 14(16): 1837. CrossRef
Conditional deletion of CEACAM1 in hepatic stellate cells causes their activation
Harrison T. Muturi, Hilda E. Ghadieh, Suman Asalla, Sumona G. Lester, Getachew D. Belew, Sobia Zaidi, Raziyeh Abdolahipour, Abhishek P. Shrestha, Agnes O. Portuphy, Hannah L. Stankus, Raghd Abu Helal, Stefaan Verhulst, Sergio Duarte, Ali Zarrinpar, Leo A.
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The impact of traditional Chinese medicine and dietary compounds on modulating gut microbiota in hepatic fibrosis: A review
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Original Articles

Drug/Regimen
Comparative Efficacy of Rosuvastatin Monotherapy and Rosuvastatin/Ezetimibe Combination Therapy on Insulin Sensitivity and Vascular Inflammatory Response in Patients with Type 2 Diabetes Mellitus: Ji Hye Han, Kyong Hye Joung, Jun Choul Lee, Ok Soon Kim, Sorim Choung, Ji Min Kim, Yea Eun Kang, Hyon-Seung Yi, Ju Hee Lee, Bon Jeong Ku, Hyun Jin Kim; Diabetes Metab J. 2024;48(1):112-121. Published online January 3, 2024; DOI: https://doi.org/10.4093/dmj.2022.0402

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Background
Type 2 diabetes mellitus (T2DM) induces endothelial dysfunction and inflammation, which are the main factors for atherosclerosis and cardiovascular disease. The present study aimed to compare the effects of rosuvastatin monotherapy and rosuvastatin/ezetimibe combination therapy on lipid profile, insulin sensitivity, and vascular inflammatory response in patients with T2DM.
Methods
A total of 101 patients with T2DM and dyslipidemia were randomized to either rosuvastatin monotherapy (5 mg/day, n=47) or rosuvastatin/ezetimibe combination therapy (5 mg/10 mg/day, n=45) and treated for 12 weeks. Serum lipids, glucose, insulin, soluble intercellular adhesion molecule-1 (sICAM-1), and peroxiredoxin 4 (PRDX4) levels were determined before and after 12 weeks of treatment.
Results
The reduction in low density lipoprotein cholesterol (LDL-C) by more than 50% from baseline after treatment was more in the combination therapy group. The serum sICAM-1 levels increased significantly in both groups, but there was no difference between the two groups. The significant changes in homeostasis model assessment of insulin resistance (HOMA-IR) and PRDX4 were confirmed only in the subgroup in which LDL-C was reduced by 50% or more in the combination therapy group. However, after adjusting for diabetes mellitus duration and hypertension, the changes in HOMA-IR and PRDX4 were not significant between the two groups.
Conclusion
Although rosuvastatin/ezetimibe combination therapy had a greater LDL-C reduction effect than rosuvastatin monotherapy, it had no additional effects on insulin sensitivity and vascular inflammatory response. Further studies are needed on the effect of long-term treatment with ezetimibe on insulin sensitivity and vascular inflammatory response.

Citations

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Combining Ezetimibe and Rosuvastatin: Impacts on Insulin Sensitivity and Vascular Inflammation in Patients with Type 2 Diabetes Mellitus
Eun Roh
Diabetes & Metabolism Journal.2024; 48(1): 55. 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
A Comparison of Rosuvastatin Monotherapy and Rosuvastatin Plus Ezetimibe Combination Therapy in Patients With Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials
Samuel K Dadzie, Godfrey Tabowei, Mandeep Kaur, Saeed Ahmed, Aayushi Thakur, Khaldoun Khreis, Monika Bai, Adil Amin
Cureus.2024;[Epub] CrossRef
The Pleiotropic Effects of Lipid-Modifying Interventions: Exploring Traditional and Emerging Hypolipidemic Therapies
Dimitris Kounatidis, Nikolaos Tentolouris, Natalia G. Vallianou, Iordanis Mourouzis, Irene Karampela, Theodora Stratigou, Eleni Rebelos, Marina Kouveletsou, Vasileios Stamatopoulos, Eleni Tsaroucha, Maria Dalamaga
Metabolites.2024; 14(7): 388. CrossRef

Basic Research
DWN12088, A Prolyl-tRNA Synthetase Inhibitor, Alleviates Hepatic Injury in Nonalcoholic Steatohepatitis: Dong-Keon Lee, Su Ho Jo, Eun Soo Lee, Kyung Bong Ha, Na Won Park, Deok-Hoon Kong, Sang-In Park, Joon Seok Park, Choon Hee Chung; Diabetes Metab J. 2024;48(1):97-111. Published online January 3, 2024; DOI: https://doi.org/10.4093/dmj.2022.0367

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Background
Nonalcoholic steatohepatitis (NASH) is a liver disease caused by obesity that leads to hepatic lipoapoptosis, resulting in fibrosis and cirrhosis. However, the mechanism underlying NASH is largely unknown, and there is currently no effective therapeutic agent against it. DWN12088, an agent used for treating idiopathic pulmonary fibrosis, is a selective prolyl-tRNA synthetase (PRS) inhibitor that suppresses the synthesis of collagen. However, the mechanism underlying the hepatoprotective effect of DWN12088 is not clear. Therefore, we investigated the role of DWN12088 in NASH progression.
Methods
Mice were fed a chow diet or methionine-choline deficient (MCD)-diet, which was administered with DWN12088 or saline by oral gavage for 6 weeks. The effects of DWN12088 on NASH were evaluated by pathophysiological examinations, such as real-time quantitative reverse transcription polymerase chain reaction, immunoblotting, biochemical analysis, and immunohistochemistry. Molecular and cellular mechanisms of hepatic injury were assessed by in vitro cell culture.
Results
DWN12088 attenuated palmitic acid (PA)-induced lipid accumulation and lipoapoptosis by downregulating the Rho-kinase (ROCK)/AMP-activated protein kinase (AMPK)/sterol regulatory element-binding protein-1c (SREBP-1c) and protein kinase R-like endoplasmic reticulum kinase (PERK)/α subunit of eukaryotic initiation factor 2 (eIF2α)/activating transcription factor 4 (ATF4)/C/EBP-homologous protein (CHOP) signaling cascades. PA increased but DWN12088 inhibited the phosphorylation of nuclear factor-κB (NF-κB) p65 (Ser536, Ser276) and the expression of proinflammatory genes. Moreover, the DWN12088 inhibited transforming growth factor β (TGFβ)-induced pro-fibrotic gene expression by suppressing TGFβ receptor 1 (TGFβR1)/Smad2/3 and TGFβR1/glutamyl-prolyl-tRNA synthetase (EPRS)/signal transducer and activator of transcription 6 (STAT6) axis signaling. In the case of MCD-diet-induced NASH, DWN12088 reduced hepatic steatosis, inflammation, and lipoapoptosis and prevented the progression of fibrosis.
Conclusion
Our findings provide new insights about DWN12088, namely that it plays an important role in the overall improvement of NASH. Hence, DWN12088 shows great potential to be developed as a new integrated therapeutic agent for NASH.

Citations

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EPRS1-mediated fibroblast activation and mitochondrial dysfunction promote kidney fibrosis
Seung Seob Son, Hee Seul Jeong, Seong-Woo Lee, Eun Soo Lee, Jeong Geon Lee, Ji-Hye Lee, Jawoon Yi, Mi Ju Park, Min Sun Choi, Donghyeong Lee, Sin Young Choi, Jiheon Ha, Jeong Suk Kang, Nam-Jun Cho, Samel Park, Hyo-Wook Gil, Choon Hee Chung, Joon Seok Park,
Experimental & Molecular Medicine.2024; 56(12): 2673. CrossRef

Basic Research
Alantolactone Attenuates Renal Fibrosis via Inhibition of Transforming Growth Factor β/Smad3 Signaling Pathway: Kyeong-Min Lee, Yeo Jin Hwang, Gwon-Soo Jung; Diabetes Metab J. 2024;48(1):72-82. Published online January 3, 2024; DOI: https://doi.org/10.4093/dmj.2022.0231

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Background
Renal fibrosis is characterized by the accumulation of extracellular matrix proteins and interstitial fibrosis. Alantolactone is known to exert anticancer, anti-inflammatory, antimicrobial and antifungal effects; however, its effects on renal fibrosis remains unknown. Here, we investigated whether alantolactone attenuates renal fibrosis in mice unilateral ureteral obstruction (UUO) and evaluated the effect of alantolactone on transforming growth factor (TGF) signaling pathway in renal cells.
Methods
To evaluate the therapeutic effect of alantolactone, cell counting kit-8 (CCK-8) assay, histological staining, Western blot analysis, and real-time quantitative polymerase chain reaction were performed in UUO kidneys in vivo and in TGF-β-treated renal cells in vitro.
Results
Alantolactone (0.25 to 4 µM) did not affect the viability of renal cells. Mice orally administered 5 mg/kg of alantolactone daily for 15 days did not show mortality or liver toxicity. Alantolactone decreased UUO-induced blood urea nitrogen and serum creatinine levels. In addition, it significantly alleviated renal tubulointerstitial damage and fibrosis and decreased collagen type I, fibronectin, and α-smooth muscle actin (α-SMA) expression in UUO kidneys. In NRK-49F cells, alantolactone inhibited TGF-βstimulated expression of fibronectin, collagen type I, plasminogen activator inhibitor-1 (PAI-1), and α-SMA. In HK-2 cells, alantolactone inhibited TGF-β-stimulated expression of collagen type I and PAI-1. Alantolactone inhibited UUO-induced phosphorylation of Smad3 in UUO kidneys. In addition, it not only decreased TGF-β secretion but also Smad3 phosphorylation and translocation to nucleus in both kidney cell lines.
Conclusion
Alantolactone improves renal fibrosis by inhibiting the TGF-β/Smad3 signaling pathway in obstructive nephropathy. Thus, alantolactone is a potential therapeutic agent for chronic kidney disease.

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TGF-β-Based Therapies for Treating Ocular Surface Disorders
Fernando T. Ogata, Sudhir Verma, Vivien J. Coulson-Thomas, Tarsis F. Gesteira
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Alantolactone alleviates epithelial-mesenchymal transition by regulating the TGF-β/STAT3 signaling pathway in renal fibrosis
Yeo Jin Hwang, Gwon-Soo Jung, Kyeong-Min Lee
Heliyon.2024; 10(16): e36253. CrossRef
Sodium Phenylbutyrate Attenuates Cisplatin-Induced Acute Kidney Injury Through Inhibition of Pyruvate Dehydrogenase Kinase 4
Chang Joo Oh, Wooyoung Choi, Ha Young Lee, In-Kyu Lee, Min-Ji Kim, Jae-Han Jeon
Biomedicines.2024; 12(12): 2815. CrossRef

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.

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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
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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
Does Rosuvastatin/Ezetimibe Combination Therapy Offer Potential Benefits for Glucose Metabolism beyond Lipid-Lowering Efficacy in T2DM?
Il Rae Park, Jun Sung Moon
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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
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Basic Research
Beneficial Effects of a Curcumin Derivative and Transforming Growth Factor-β Receptor I Inhibitor Combination on Nonalcoholic Steatohepatitis: Kyung Bong Ha, Eun Soo Lee, Na Won Park, Su Ho Jo, Soyeon Shim, Dae-Kee Kim, Chan Mug Ahn, Choon Hee Chung; Diabetes Metab J. 2023;47(4):500-513. Published online April 25, 2023; DOI: https://doi.org/10.4093/dmj.2022.0110

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Background
Curcumin 2005-8 (Cur5-8), a derivative of curcumin, improves fatty liver disease via AMP-activated protein kinase activation and autophagy regulation. EW-7197 (vactosertib) is a small molecule inhibitor of transforming growth factor β (TGF-β) receptor I and may scavenge reactive oxygen species and ameliorate fibrosis through the SMAD2/3 canonical pathway. This study aimed to determine whether co-administering these two drugs having different mechanisms is beneficial.
Methods
Hepatocellular fibrosis was induced in mouse hepatocytes (alpha mouse liver 12 [AML12]) and human hepatic stellate cells (LX-2) using TGF-β (2 ng/mL). The cells were then treated with Cur5-8 (1 μM), EW-7197 (0.5 μM), or both. In animal experiments were also conducted during which, methionine-choline deficient diet, Cur5-8 (100 mg/kg), and EW-7197 (20 mg/kg) were administered orally to 8-week-old C57BL/6J mice for 6 weeks.
Results
TGF-β-induced cell morphological changes were improved by EW-7197, and lipid accumulation was restored on the administration of EW-7197 in combination with Cur5-8. In a nonalcoholic steatohepatitis (NASH)-induced mouse model, 6 weeks of EW-7197 and Cur5-8 co-administration alleviated liver fibrosis and improved the nonalcoholic fatty liver disease (NAFLD) activity score.
Conclusion
Co-administering Cur5-8 and EW-7197 to NASH-induced mice and fibrotic hepatocytes reduced liver fibrosis and steatohepatitis while maintaining the advantages of both drugs. This is the first study to show the effect of the drug combination against NASH and NAFLD. Similar effects in other animal models will confirm its potential as a new therapeutic agent.

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Xing Wan, Jingyuan Ma, He Bai, Xuyang Hu, Yanna Ma, Mingjian Zhao, Jifeng Liu, Zhijun Duan
Biomolecules.2025; 15(1): 140. CrossRef
Hepatoprotective and Fat-Accumulation-Reductive Effects of Curcumin on Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Jasmine Harumi Sabini, Kris Herawan Timotius
Current Issues in Molecular Biology.2025; 47(3): 159. CrossRef
Thiazole isomers as potential ALK5 inhibitors alleviate P2X7R-mediated inflammation during liver fibrosis
Xue-Li Jiang, Chuang Liu, Zi-Ying Zhan, Xiao-Qi Lan, Yan-Ling Wu, Ji-Xing Nan, Cheng-Hua Jin, Li-Hua Lian
International Immunopharmacology.2025; 153: 114472. CrossRef
Molecular Pathways Governing the Termination of Liver Regeneration
Lianne R. de Haan, Rowan F. van Golen, Michal Heger
Pharmacological Reviews.2024; 76(3): 500. CrossRef
Nicotinate-curcumin improves NASH by inhibiting the AKR1B10/ACCα-mediated triglyceride synthesis
Xiu-lian Lin, Ya-ling Zeng, Jie Ning, Zhe Cao, Lan-lan Bu, Wen-Jing Liao, Zhi-min Zhang, Tan-jun Zhao, Rong-geng Fu, Xue-Feng Yang, Yong-zhen Gong, Li-Mei Lin, De-liang Cao, Cai-ping Zhang, Duan-fang Liao, Ya-Mei Li, Jian-Guo Zeng
Lipids in Health and Disease.2024;[Epub] CrossRef
The pivotal role of dysregulated autophagy in the progression of non-alcoholic fatty liver disease
Qiaohui Shen, Ming Yang, Song Wang, Xingyu Chen, Sulan Chen, Rui Zhang, Zhuang Xiong, Yan Leng
Frontiers in Endocrinology.2024;[Epub] CrossRef

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.

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Impact of glucagon‐like peptide‐1 receptor agonists on diabetic retinopathy: A meta‐analysis of clinical studies emphasising retinal changes as a primary outcome
Ishani Kapoor, Swara M. Sarvepalli, David A. D'Alessio, Majda Hadziahmetovic
Clinical & Experimental Ophthalmology.2025; 53(1): 67. CrossRef
SGLT2 inhibitors and diabetic retinopathy: Insights from the management of nephropathy
Maria S. Varughese, Lakshminarayanan Varadhan
Eye.2025; 39(2): 213. CrossRef
Impact of Obstructive Sleep Apnea on Diabetic Retinopathy Progression and Systemic Complications
Ehsan Rahimy, Euna B. Koo, Karen M. Wai, Cassie A. Ludwig, Andrea L. Kossler, Prithvi Mruthyunjaya
American Journal of Ophthalmology.2025; 270: 93. CrossRef
An update on ocular effects of antidiabetic medications
Elham Sadeghi, Elham Rahmanipour, Nicola Valsecchi, Saloni Kapoor, Maria Vittoria Cicinelli, Jay Chhablani
Survey of Ophthalmology.2025;[Epub] CrossRef
Glucagon-like peptide-1 receptor agonists and the eye
David L. Zhang, Avni P. Finn
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Incretin‐based drugs and the risk of diabetic retinopathy among individuals with type 2 diabetes: A systematic review and meta‐analysis of observational studies
Samuel Igweokpala, Naheemot Olaoluwa Sule, Antonios Douros, Oriana H. Y. Yu, Kristian B. Filion
Diabetes, Obesity and Metabolism.2024; 26(2): 721. CrossRef
Association of sodium–glucose cotransporter‐2 inhibitors and the risk of retinal vascular occlusion: A real‐world retrospective cohort study in Taiwan
Tzu‐Yi Lin, Eugene Yu‐Chuan Kang, Shih‐Chieh Shao, Edward Chia‐Cheng Lai, Nan‐Kai Wang, Sunir J. Garg, Kuan‐Jen Chen, Je‐Ho Kang, Wei‐Chi Wu, Chi‐Chun Lai, Yih‐Shiou Hwang
Diabetes/Metabolism Research and Reviews.2024;[Epub] CrossRef
Risk of rotator cuff tear and rotator cuff repair surgery comparison between sodium-glucose cotransporter 2 inhibitors and glucagon like peptide-1 receptor agonists: A real-world study
Yu-Chi Su, Pei-Chun Hsieh, Edward Chia-Cheng Lai, Yu-Ching Lin
Diabetes & Metabolism.2024; 50(2): 101522. CrossRef
Optimising renal risk parameters in type 2 diabetes mellitus: Perspectives from a retinal viewpoint
Sarita Jacob, George I. Varughese
Clinical Medicine.2024; 24(2): 100031. CrossRef
Risk of diabetic retinopathy and diabetic macular oedema with sodium–glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists in type 2 diabetes: a real-world data study from a global federated database
Aikaterini Eleftheriadou, David Riley, Sizheng S. Zhao, Philip Austin, Gema Hernández, Gregory Y. H. Lip, Timothy L. Jackson, John P. H. Wilding, Uazman Alam
Diabetologia.2024; 67(7): 1271. CrossRef
Impact of GLP-1 Agonists and SGLT-2 Inhibitors on Diabetic Retinopathy Progression: An Aggregated Electronic Health Record Data Study
Karen M. Wai, Kapil Mishra, Euna Koo, Cassie Ann Ludwig, Ravi Parikh, Prithvi Mruthyunjaya, Ehsan Rahimy
American Journal of Ophthalmology.2024; 265: 39. CrossRef
Comparative Effectiveness of Glucagon-Like Peptide-1 Receptor Agonists, Sodium-Glucose Cotransporter 2 Inhibitors, Dipeptidyl Peptidase-4 Inhibitors, and Sulfonylureas for Sight-Threatening Diabetic Retinopathy
Andrew J. Barkmeier, Jeph Herrin, Kavya Sindhu Swarna, Yihong Deng, Eric C. Polley, Guillermo E. Umpierrez, Rodolfo J. Galindo, Joseph S. Ross, Mindy M. Mickelson, Rozalina G. McCoy
Ophthalmology Retina.2024; 8(10): 943. CrossRef
Association Between Pentoxifylline Use and Diabetic Retinopathy in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease: A Multi-Institutional Cohort Study
Tzu-Yi Lin, Eugene Yu-Chuan Kang, Nan-Kai Wang, Je-Ho Kang, Kuan-Jen Chen, Wei-Chi Wu, Chi-Chun Lai, Yih-Shiou Hwang
Biomedical Journal.2024; : 100771. CrossRef
Association between sodium-glucose cotransporter 2 inhibitors and eye disorders: a systematic review and meta-analysis
Bo Xu, Bo Kang, Fan Tang, Jiecan Zhou, Zunbo He
Expert Review of Clinical Pharmacology.2024; 17(10): 949. CrossRef
Comparison of the Risk of Diabetic Retinopathy Between Sodium-Glucose Cotransporter-2 Inhibitors and Dipeptidyl Peptidase-4 Inhibitors in Patients with Type 2 Diabetes Mellitus in Japan: A Retrospective Analysis of Real-World Data
Masaya Koshizaka, Tomoaki Tatsumi, Fumiko Kiyonaga, Yoshinori Kosakai, Yoko Yoshinaga, Mami Shintani-Tachi
Diabetes Therapy.2024; 15(11): 2401. CrossRef
NOVEL AGENTS IN THE MANAGEMENT OF DIABETES AND RISK OF WORSENING DIABETIC RETINOPATHY
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Bowen Zhao, Yin Zhao, Xufang Sun
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David A. Antonetti, Cheng-Mao Lin, Sumathi Shanmugam, Heather Hager, Manjing Cao, Xuwen Liu, Alyssa Dreffs, Adam Habash, Steven F. Abcouwer
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Frontiers in Cell and Developmental Biology.2024;[Epub] 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)
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
Sodium-Glucose Cotransporter 2 Inhibitors and Risk of Retinopathy in Patients With Type 2 Diabetes
Fu-Shun Yen, James Cheng-Chung Wei, Teng-Shun Yu, Yu-Tung Hung, Chih-Cheng Hsu, Chii-Min Hwu
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Cardiovascular Risk/Epidemiology
The Ratio of Estimated Glomerular Filtration Rate Based on Cystatin C and Creatinine Reflecting Cardiovascular Risk in Diabetic Patients: Ah Reum Khang, Min Jin Lee, Dongwon Yi, Yang Ho Kang; Diabetes Metab J. 2023;47(3):415-425. Published online March 6, 2023; DOI: https://doi.org/10.4093/dmj.2022.0177

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Background
The ratio of estimated glomerular filtration rate (eGFR) based on cystatin C and creatinine (eGFR_{cystatin C}/eGF_Rcreatinine ratio) is related to accumulating atherosclerosis-promoting proteins and increased mortality in several cohorts.
Methods
We assessed whether the eGFR_{cystatin C}/eGFR_creatinine ratio is a predictor of arterial stiffness and sub-clinical atherosclerosis in type 2 diabetes mellitus (T2DM) patients, who were followed up during 2008 to 2016. GFR was estimated using an equation based on cystatin C and creatinine.
Results
A total of 860 patients were stratified according to their eGFR_{cystatin C}/eGF_Rcreatinine ratio (i.e., <0.9, 0.9–1.1 [a reference group], and >1.1). Intima-media thickness was comparable among the groups; however, presence of carotid plaque was frequent in the <0.9 group (<0.9 group, 38.3%; 0.9–1.1 group, 21.6% vs. >1.1 group, 17.2%, P<0.001). Brachial-ankle pulse wave velocity (baPWV) was faster in the <0.9 group (<0.9 group, 1,656.3±333.0 cm/sec; 0.9–1.1 group, 1,550.5±294.8 cm/sec vs. >1.1 group, 1,494.0±252.2 cm/sec, P<0.001). On comparing the <0.9 group with the 0.9–1.1 group, the multivariate-adjusted odds ratios of prevalence of high baPWV and carotid plaque were 2.54 (P=0.007) and 1.95 (P=0.042), respectively. Cox regression analysis demonstrated near or over 3-fold higher risks of the prevalence of high baPWV and carotid plaque in the <0.9 group without chronic kidney disease (CKD).
Conclusion
We concluded that eGFR_{cystatin C}/eGFR_creatinine ratio <0.9 was related to an increased risk of high baPWV and carotid plaque in T2DM patients, especially, those without CKD. Careful monitoring of cardiovascular disease is needed for T2DM patients with low eGFR_{cystatin C}/eGFR_creatinine ratio.

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Different ways of diagnosing selective glomerular hypofiltration syndromes such as shrunken pore syndrome and the associated increase in mortality
Anna Åkesson, Linnea Malmgren, Felicia Leion, Ulf Nyman, Anders Christensson, Jonas Björk, Anders Grubb
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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.

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Ji Yoon Kim, Sang-Man Jin, Sarah B. Andrade, Boyang Chen, Jae Hyeon Kim
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Kyung-Soo Kim, Seung-Hwan Lee, Won Sang Yoo, Cheol-Young Park
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