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Impact of Remnant Cholesterol on the Risk for End-Stage Renal Disease in Type 2 Diabetes Mellitus: A Nationwide Population-Based Cohort Study (Diabetes Metab J 2025;49:1106-15)
Eun Roh, Ji Hye Heo, Kyung-Do Han, Jun Goo Kang
Diabetes Metab J. 2026;50(1):203-204.   Published online January 1, 2026
DOI: https://doi.org/10.4093/dmj.2025.1052
  • 1,378 View
  • 32 Download
PDFPubReader   ePub   
Review
Lifestyle and Behavioral Interventions
Article image
Optimizing Physical Activity Strategies for Older Adults with Diabetes
Hyeon-Jin Yu, Doyoun Hong, Kyuho Kim, Ji Hye Heo, Dong-Hyeok Cho, Yoshitaka Hashimoto, Jae-Seung Yun
Diabetes Metab J. 2025;49(6):1178-1197.   Published online November 1, 2025
DOI: https://doi.org/10.4093/dmj.2025.0967
  • 3,480 View
  • 162 Download
  • 1 Web of Science
  • 1 Crossref
AbstractAbstract PDFPubReader   ePub   
The increasing prevalence of diabetes among older adults has emerged as a major socioeconomic burden. This population is highly heterogeneous, ranging from functionally independent to severely impaired individuals, making it difficult to establish standardized recommendations. Physical activity (PA) is a cornerstone of diabetes management; however, current exercise guidelines do not adequately address the wide spectrum of functional capacities observed in older adults. For those with physical limitations, relatively simple activities such as walking, breaking up sedentary time, incorporating movement into daily routines, and aquatic exercise have been proposed, yet supporting evidence remains limited. This review summarizes the pathophysiologic mechanisms of metabolic and functional changes associated with aging and diabetes—including sarcopenia, altered body composition, and cardiovascular decline—and comprehensively discusses the benefits and precautions of various exercise modalities, tailored recommendations according to diabetes-related complications, and key clinical considerations. We further classified older adults with diabetes into three functional levels, individuals in good health, those with some comorbidities or mild disabilities, and those with high comorbidities and/or functional impairment, and proposed corresponding physical activity strategies for each level. Finally, we highlight practical and feasible approaches, including walking, interrupting sedentary behavior, daily functional movements, and aquatic exercise, to enhance clinical applicability for individuals with reduced physical capacity. These tailored, function-based strategies may help older adults with diabetes achieve safer, more effective, and sustainable improvements in glycemic control and overall health.

Citations

Citations to this article as recorded by  
  • Predictors of Adherence to Physical Activity Among Adults with Diabetes
    Amil Kusain Tan, Ajatshatru Pathak, Shiela M. Strauss
    The Journal for Nurse Practitioners.2026; 22(6): 105778.     CrossRef
Original Articles
Complications
Article image
Impact of Remnant Cholesterol on the Risk for End-Stage Renal Disease in Type 2 Diabetes Mellitus: A Nationwide Population-Based Cohort Study
Eun Roh, Ji Hye Heo, Han Na Jung, Kyung-Do Han, Jun Goo Kang, Seong Jin Lee, Sung-Hee Ihm
Diabetes Metab J. 2025;49(5):1106-1115.   Published online May 21, 2025
DOI: https://doi.org/10.4093/dmj.2024.0406
  • 3,608 View
  • 153 Download
  • 3 Web of Science
  • 2 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Remnant cholesterol (remnant-C) has been linked to the risk of various vascular diseases, but the association between remnant-C and end-stage renal disease (ESRD) in patients with type 2 diabetes mellitus (T2DM) remains unclear.
Methods
Using a nationwide cohort, a total of 2,537,149 patients with T2DM without ESRD, who had participated in the national health screening in 2009, were enrolled and followed up until 2020. Low-density lipoprotein cholesterol (LDL-C) levels were assessed by the Martin-Hopkins method, and remnant-C was calculated as total cholesterol–LDL-C–high-density lipoprotein cholesterol.
Results
During a median follow-up period of 10.3 years, 26,246 patients with T2DM (1.03%) developed ESRD. Participants in the upper quartile of remnant-C had a higher risk of ESRD, with hazard ratios of 1.12 (95% confidence interval [CI], 1.08 to 1.17), 1.20 (95% CI, 1.15 to 1.24), and 1.33 (95% CI, 1.26 to 1.41) in the second, third, and fourth quartile, compared with the lowest quartile, in multivariable-adjusted analyses. The positive association between remnant-C and ESRD remained consistent, irrespective of age, sex, presence of pre-existing comorbidities, and use of anti-dyslipidemic medications. The increased risk of ESRD was more pronounced in high-risk subgroups, including those with hypertension, chronic kidney disease, obesity, and a longer duration of diabetes.
Conclusion
These findings suggest that remnant-C profiles in T2DM have a predictive role for future progression of ESRD, independent of traditional risk factors for renal dysfunction.

Citations

Citations to this article as recorded by  
  • Impact of Remnant Cholesterol on the Risk for End-Stage Renal Disease in Type 2 Diabetes Mellitus: A Nationwide Population-Based Cohort Study (Diabetes Metab J 2025;49:1106-15)
    Jun Hwa Hong
    Diabetes & Metabolism Journal.2026; 50(1): 190.     CrossRef
  • A Narrative Review of Remnant Cholesterol as an Independent Atherogenic Lipoprotein in Type 2 Diabetes: Pathophysiology and Clinical Implications
    Ramdhani Natsir, Eli Halimah, Ajeng Diantini, Jutti Levita
    Therapeutics and Clinical Risk Management.2026; Volume 22: 1.     CrossRef
Drug/Regimen
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Pioglitazone as Add-on Therapy in Patients with Type 2 Diabetes Mellitus Inadequately Controlled with Dapagliflozin and Metformin: Double-Blind, Randomized, Placebo-Controlled Trial
Ji Hye Heo, Kyung Ah Han, Jun Hwa Hong, Hyun-Ae Seo, Eun-Gyoung Hong, Jae Myung Yu, Hye Seung Jung, Bong-Soo Cha
Diabetes Metab J. 2024;48(5):937-948.   Published online February 2, 2024
DOI: https://doi.org/10.4093/dmj.2023.0314
  • 23,599 View
  • 801 Download
  • 11 Web of Science
  • 14 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
This study assessed the efficacy and safety of triple therapy with pioglitazone 15 mg add-on versus placebo in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin and dapagliflozin.
Methods
In this multicenter, double-blind, randomized, phase 3 study, patients with T2DM with an inadequate response to treatment with metformin (≥1,000 mg/day) plus dapagliflozin (10 mg/day) were randomized to receive additional pioglitazone 15 mg/day (n=125) or placebo (n=125) for 24 weeks. The primary endpoint was the change in glycosylated hemoglobin (HbA1c) levels from baseline to week 24 (ClinicalTrials.gov identifier: NCT05101135).
Results
At week 24, the adjusted mean change from baseline in HbA1c level compared with placebo was significantly greater with pioglitazone treatment (–0.47%; 95% confidence interval, –0.61 to –0.33; P<0.0001). A greater proportion of patients achieved HbA1c <7% or <6.5% at week 24 with pioglitazone compared to placebo as add-on to 10 mg dapagliflozin and metformin (56.8% vs. 28% for HbA1c <7%, and 23.2% vs. 9.6% for HbA1c <6.5%; P<0.0001 for all). The addition of pioglitazone also significantly improved triglyceride, highdensity lipoprotein cholesterol levels, and homeostatic model assessment of insulin resistance levels, while placebo did not. The incidence of treatment-emergent adverse events was similar between the groups, and the incidence of fluid retention-related side effects by pioglitazone was low (1.5%).
Conclusion
Triple therapy with the addition of 15 mg/day of pioglitazone to dapagliflozin plus metformin was well tolerated and produced significant improvements in HbA1c in patients with T2DM inadequately controlled with dapagliflozin plus metformin.

Citations

Citations to this article as recorded by  
  • Lobeglitazone improves glycaemic control as add‐on therapy to empagliflozin plus metformin in patients with type 2 diabetes mellitus: A double‐blind, randomised, placebo‐controlled trial
    Da Hea Seo, Kyung Wan Min, Ho Sang Sohn, Sang Yong Kim, In‐Kyung Jeong, Cheol‐Young Park, Kun‐Ho Yoon, So Hun Kim, Bong‐Soo Cha
    Diabetes, Obesity and Metabolism.2026; 28(1): 728.     CrossRef
  • Sodium‐glucose cotransporter 2 inhibitor ameliorates thiazolidinedione‐induced fluid retention through vascular leakage reduction in white adipose tissue
    Ji Yoon Kim, Hye‐Min Jang, Hye‐Jin Lee, Ah Hyeon Lee, Dong‐Hoon Kim, Sin Gon Kim, Nam Hoon Kim
    Diabetes, Obesity and Metabolism.2026; 28(3): 1764.     CrossRef
  • Efficacy and safety of fixed-dose dapagliflozin–pioglitazone in Indian adults with type 2 diabetes: results from the randomized phase 3 PRO-1 trial
    Awadhesh Kumar Singh, Krishna G Seshadri, A G Unnikrishnan, Jothydev Kesavadev, Sanjay Kalra, Shashank R Joshi, Kaushik Pandit, Rakesh K Sahay, Vijay K Panikar, Ambrish Mithal, Smriti Gadia, Thamburaj Anthuvan
    Diabetology & Metabolic Syndrome.2026;[Epub]     CrossRef
  • Lipid metabolism in homeostasis and disease
    Zhenghao Li, Wende Deng, Lanxuan Yang, Changheng Tang, Jian-Min Yue, Olivia Monteiro, Daniel T. Baptista-Hon, Ting Li
    Signal Transduction and Targeted Therapy.2026;[Epub]     CrossRef
  • Efficacy and Safety of High-Dose Pioglitazone as Add-on Therapy in Patients with Type 2 Diabetes Mellitus Inadequately Controlled with Dapagliflozin and Metformin: Double-Blind, Randomized, Placebo-Controlled Trial
    Jun Hwa Hong, Kyung Ah Han, You-Cheol Hwang, Eun-Gyoung Hong, Hae Jin Kim, Chang Beom Lee, Ho Chan Cho, Jong Chul Won, Hun-Sung Kim, Eui-Hyun Kim, Gwanpyo Koh, Kwang Hyun Ahn, Kyong Soo Park
    Diabetes & Metabolism Journal.2026; 50(2): 320.     CrossRef
  • Cannabisin A and B from hemp seed hulls improve glucose homeostasis by re-engaging insulin, leptin, and AMPK pathways via selective PTP1B inhibition
    Jang Hoon Kim, Sang Seop Lee, Sang Hoon Lee, Kyong Hwan Bang, Jin Yu, Yong Goo Kim, Sung Yeon Kim, Ik Soo Lee, Yung Choon Yoo
    Phytomedicine.2026; 154: 158054.     CrossRef
  • Efficacy and Safety of Pioglitazone Add‐On in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin and Dapagliflozin: A Systematic Review and Meta‐Analysis of Randomised Controlled Trials
    Ubaid Khan, Zuhair Majeed, Muhammad Haris Khan, Ahmed Bostamy Elsnhory, Ahmed Mazen Amin, Anum Nawaz, Ahmed Raza, Hafiz Muhammad Waqas Siddque, Mustafa Turkmani, Mohamed Abuelazm
    Endocrinology, Diabetes & Metabolism.2025;[Epub]     CrossRef
  • Pioglitazone as Add-On to Metformin and Dapagliflozin Yields Significant Enhancements in Glycemic Control in Poorly Controlled Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials
    Sara Sabbagh, Ahmed Hegazy, Ahmed Adel, Abdullah Ali, Mohamed Alquddosy, Sara Khalid, Abdallah M Ibrahim, Ahmed Mohamed, Abdelrahman Mostafa, Ahmed Hassan, Ola Mohamed, Rawan Mesbah, Osama Osman, Mohamed Hamouda Elkasaby
    Cureus.2025;[Epub]     CrossRef
  • Triple oral therapy with metformin, DPP‐4 inhibitor, and SGLT2 inhibitor for adults with type 2 diabetes: Consensus recommendations of a Chinese expert panel (version 2025)
    Miao Yu, Tong Wang, Chun Xu, Yan Bi, Ling Gao, Guang Wang, Guangda Xiang, Yaoming Xue, Tao Yang, Deying Kang, Zhiguang Zhou, Lixin Guo, Xinhua Xiao
    Diabetes, Obesity and Metabolism.2025; 27(S9): 3.     CrossRef
  • Thiazolidinediones for people with chronic kidney disease and diabetes
    Patrizia Natale, Suetonia C Green, David J Tunnicliffe, Giovanni Pellegrino, Tadashi Toyama, Pantelis Sarafidis, Giovanni FM Strippoli
    Cochrane Database of Systematic Reviews.2025;[Epub]     CrossRef
  • Targeting adipose remodeling: Synergistic mechanisms of drugs and adipose-derived stem cells in obese type 2 diabetes mellitus
    Cheng Luo, Xian-Mei Yu, Liang-Yan Hua, Mei-Qi Zeng, Hui Xu, Cheng-Zheng Duan, Shi-Yu Xu, Da Sun, Li-Ya Ye, Dong-Juan He
    World Journal of Stem Cells.2025;[Epub]     CrossRef
  • Efficacy and safety of pioglitazone versus dapagliflozin as an add-on to metformin and alogliptin combination therapy: the EPIDOTE study
    Kyuho Kim, Seung-Hyun Ko, Jae-Seung Yun, Kwan-Woo Lee, Eun Sook Kim, In-Kyung Jeong, Jae Hyeon Kim, Sang Yong Kim, Kyu Chang Won, Mikyung Kim, Bong-Soo Cha, Sungrae Kim, Sung Hee Choi, Eun-Jung Rhee, Sin Gon Kim, Bo Hyun Kim, Kang Seo Park, Young-Cheol Ju
    Scientific Reports.2025;[Epub]     CrossRef
  • Identification and validation of biomarkers related to mitochondria-associated endoplasmic reticulum membranes in type 2 diabetes mellitus using peripheral blood transcriptomics
    Sufen Li, Yanqiong Yan, Qianjun Luo, Ruifei Tian, Jiahe Yan
    European Journal of Medical Research.2025;[Epub]     CrossRef
  • Ideal Combination of Oral Hypoglycemic Agents for Patients with Type 2 Diabetes Mellitus
    Hye Soon Kim
    Diabetes & Metabolism Journal.2024; 48(5): 882.     CrossRef

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