Diabetes & Metabolism Journal

Sulwon Lecture 2024

Basic and Translational Research
Overcoming β-Cell Dysfunction in Type 2 Diabetes Mellitus: CD36 Inhibition and Antioxidant System: Il Rae Park, Yong Geun Chung, Kyu Chang Won; Diabetes Metab J. 2025;49(1):1-12. Published online January 1, 2025; DOI: https://doi.org/10.4093/dmj.2024.0796

736 View
80 Download

Abstract PDF PubReader ePub: Type 2 diabetes mellitus (T2DM) is marked by chronic hyperglycemia, gradually worsening β-cell failure, and insulin resistance. Glucotoxicity and oxidative stress cause β-cell failure by increasing reactive oxygen species (ROS) production, impairing insulin secretion, and disrupting transcription factors such as pancreatic and duodenal homeobox 1 (PDX-1) and musculoaponeurotic fibrosarcoma oncogene family A (MafA). Cluster determinant 36 (CD36), an essential glycoprotein responsible for fatty acid uptake, exacerbates oxidative stress and induces the apoptosis of β-cells under hyperglycemic conditions through pathways involving ceramide, thioredoxin-interacting protein (TXNIP), and Rac1-nicotinamide adenine dinucleotide phosphate oxidase (NOX)-mediated redoxosome formation. Targeting CD36 pathways has emerged as a promising therapeutic strategy. Oral hypoglycemic agents, such as metformin, teneligliptin, and pioglitazone, have shown protective effects on β-cells by enhancing antioxidant defenses. These agents reduce glucotoxicity via mechanisms such as suppressing CD36 expression and stabilizing mitochondrial function. Additionally, novel insights into the glutathione antioxidant system and its role in β-cell survival underscore its therapeutic potential. This review focuses on the key contribution of oxidative stress and CD36 to β-cell impairment, the therapeutic promise of antioxidants, and the need for further research to apply these findings in clinical practice. Promising strategies targeting these mechanisms may help preserve β-cell function and slow T2DM progression.

Original Articles

Lifestyle
Impact of Meal Frequency on Insulin Resistance in Middle-Aged and Older Adults: A Prospective Cohort Study: Ha-Eun Ryu, Jong Hee Lee, Byoungjin Park, Seok-Jae Heo, Yu-Jin Kwon; Received July 22, 2024 Accepted September 7, 2024 Published online November 13, 2024; DOI: https://doi.org/10.4093/dmj.2024.0407 [Epub ahead of print]

587 View
23 Download

Abstract PDF Supplementary Material PubReader ePub: Background
Insulin resistance (IR) is central to metabolic disorders and significantly influenced by diet. Studies on meal frequency (MF) and metabolic indicators have shown mixed results. This study explores the link between MF and IR in middle-aged and older adults.
Methods
This prospective cohort study included 4,570 adults aged 40 to 69 years from the Korean Genome and Epidemiologic Study. MF were divided into two groups based on whether they consumed three or more, or fewer than three, meals daily. IR was evaluated using the homeostasis model assessment of insulin resistance (HOMA-IR); participants were classified as IR if their HOMA-IR value was ≥2.5. Multiple Cox proportional hazard regression analyses were conducted to examine the association between MF and the incidence of IR.
Results
After adjusting for all variables, individuals in the MF ≥3 group showed a reduced incidence of IR compared to those in the MF <3 group (hazard ratio, 0.880; 95% confidence interval, 0.782 to 0.990). Additionally, subgroup analyses by sex, diabetes mellitus (DM), and body mass index (BMI) showed that this association persisted only in men, individuals without DM, and those with a BMI <25.
Conclusion
Our findings indicate that a higher MF among middle-aged and older adults is associated with a reduced incidence of IR. However, this association was maintained only in men, individuals without DM, and those without obesity.

Technology/Device
Efficacy and Safety of Automated Insulin Delivery Systems in Patients with Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis: Wenqi Fan, Chao Deng, Ruoyao Xu, Zhenqi Liu, Richard David Leslie, Zhiguang Zhou, Xia Li; Received March 17, 2024 Accepted July 24, 2024 Published online November 13, 2024; DOI: https://doi.org/10.4093/dmj.2024.0130 [Epub ahead of print]

822 View
83 Download

Abstract PDF Supplementary Material PubReader ePub: Background
Automated insulin delivery (AID) systems studies are upsurging, half of which were published in the last 5 years. We aimed to evaluate the efficacy and safety of AID systems in patients with type 1 diabetes mellitus (T1DM).
Methods
We searched PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov until August 31, 2023. Randomized clinical trials that compared AID systems with other insulin-based treatments in patients with T1DM were considered eligible. Studies characteristics and glycemic metrics was extracted by three researchers independently.
Results
Sixty-five trials (3,623 patients) were included. The percentage of time in range (TIR) was 11.74% (95% confidence interval [CI], 9.37 to 14.12; P<0.001) higher with AID systems compared with control treatments. Patients on AID systems had more pronounced improvement of time below range when diabetes duration was more than 20 years (–1.80% vs. –0.86%, P=0.031) and baseline glycosylated hemoglobin lower than 7.5% (–1.93% vs. –0.87%, P=0.033). Dual-hormone full closed-loop systems revealed a greater improvement in TIR compared with hybrid closed-loop systems (–19.64% vs. –10.87%). Notably, glycemia risk index (GRI) (–3.74; 95% CI, –6.34 to –1.14; P<0.01) was also improved with AID therapy.
Conclusion
AID systems showed significant advantages compared to other insulin-based treatments in improving glucose control represented by TIR and GRI in patients with T1DM, with more favorable effect in euglycemia by dual-hormone full closedloop systems as well as less hypoglycemia for patients who are within target for glycemic control and have longer diabetes duration.

Metabolic Risk/Epidemiology
Comparison of SPISE and METS-IR and Other Markers to Predict Insulin Resistance and Elevated Liver Transaminases in Children and Adolescents: Kyungchul Song, Eunju Lee, Hye Sun Lee, Hana Lee, Ji-Won Lee, Hyun Wook Chae, Yu-Jin Kwon; Received June 7, 2024 Accepted August 2, 2024 Published online October 29, 2024; DOI: https://doi.org/10.4093/dmj.2024.0302 [Epub ahead of print]

633 View
36 Download

Abstract PDF Supplementary Material PubReader ePub: Background
Studies on predictive markers of insulin resistance (IR) and elevated liver transaminases in children and adolescents are limited. We evaluated the predictive capabilities of the single-point insulin sensitivity estimator (SPISE) index, metabolic score for insulin resistance (METS-IR), homeostasis model assessment of insulin resistance (HOMA-IR), the triglyceride (TG)/ high-density lipoprotein cholesterol (HDL-C) ratio, and the triglyceride-glucose index (TyG) for IR and alanine aminotransferase (ALT) elevation in this population.
Methods
Data from 1,593 participants aged 10 to 18 years were analyzed using a nationwide survey. Logistic regression analysis was performed with IR and ALT elevation as dependent variables. Receiver operating characteristic (ROC) curves were generated to assess predictive capability. Proportions of IR and ALT elevation were compared after dividing participants based on parameter cutoff points.
Results
All parameters were significantly associated with IR and ALT elevation, even after adjusting for age and sex, and predicted IR and ALT elevation in ROC curves (all P<0.001). The areas under the ROC curve of SPISE and METS-IR were higher than those of TyG and TG/HDL-C for predicting IR and were higher than those of HOMA-IR, TyG, and TG/HDL-C for predicting ALT elevation. The proportions of individuals with IR and ALT elevation were higher among those with METS-IR, TyG, and TG/ HDL-C values higher than the cutoff points, whereas they were lower among those with SPISE higher than the cutoff point.
Conclusion
SPISE and METS-IR are superior to TG/HDL-C and TyG in predicting IR and ALT elevation. Thus, this study identified valuable predictive markers for young individuals.

Brief Report

Type 1 Diabetes
In Vivo Differentiation of Endogenous Bone Marrow-Derived Cells into Insulin-Producing Cells Using Four Soluble Factors: Seung-Ah Lee, Subin Kim, Seog-Young Kim, Jong Yoen Park, Hye Seung Jung, Sung Soo Chung, Kyong Soo Park; Diabetes Metab J. 2025;49(1):150-159. Published online October 24, 2024; DOI: https://doi.org/10.4093/dmj.2024.0174

835 View
57 Download

Abstract PDF Supplementary Material PubReader ePub: Four soluble factors—putrescine, glucosamine, nicotinamide, and signal transducer and activator of transcription 3 (STAT3) inhibitor BP-1-102—were shown to differentiate bone marrow mononucleated cells (BMNCs) into functional insulin-producing cells (IPCs) in vitro. Transplantation of these IPCs improved hyperglycemia in diabetic mice. However, the role of endogenous BMNC regeneration in this effect was unclear. This study aimed to evaluate the effect of these factors on in vivo BMNC differentiation into IPCs in diabetic mice. Mice were orally administered the factors for 5 days, twice at 2-week intervals, and monitored for 45–55 days. Glucose tolerance, glucose-stimulated insulin secretion, and pancreatic insulin content were measured. Chimeric mice harboring BMNCs from insulin promoter luciferase/green fluorescent protein (GFP) transgenic mice were used to track endogenous BMNC fate. These factors lowered blood glucose levels, improved glucose tolerance, and enhanced insulin secretion. Immunostaining confirmed IPCs in the pancreas, showing the potential of these factors to induce β-cell regeneration and improve diabetes treatment.

Review

Cardiovascular Risk/Epidemiology
Artificial Light at Night and Type 2 Diabetes Mellitus: Jong-Ha Baek, Yong Zhu, Chandra L. Jackson, Yong-Moon Mark Park; Diabetes Metab J. 2024;48(5):847-863. Published online September 1, 2024; DOI: https://doi.org/10.4093/dmj.2024.0237

4,098 View
288 Download
1 Web of Science
2 Crossref

Abstract PDF PubReader ePub

The widespread and pervasive use of artificial light at night (ALAN) in our modern 24-hour society has emerged as a substantial disruptor of natural circadian rhythms, potentially leading to a rise in unhealthy lifestyle-related behaviors (e.g., poor sleep; shift work). This phenomenon has been associated with an increased risk of type 2 diabetes mellitus (T2DM), which is a pressing global public health concern. However, to date, reviews summarizing associations between ALAN and T2DM have primarily focused on the limited characteristics of exposure (e.g., intensity) to ALAN. This literature review extends beyond prior reviews by consolidating recent studies from 2000 to 2024 regarding associations between both indoor and outdoor ALAN exposure and the incidence or prevalence of T2DM. We also described potential biological mechanisms through which ALAN modulates glucose metabolism. Furthermore, we outlined knowledge gaps and investigated how various ALAN characteristics beyond only light intensity (including light type, timing, duration, wavelength, and individual sensitivity) influence T2DM risk. Recognizing the detrimental impact of ALAN on sleep health and the behavioral correlates of physical activity and dietary patterns, we additionally summarized studies investigating the potential mediating role of each component in the relationship between ALAN and glucose metabolism. Lastly, we proposed implications of chronotherapies and chrononutrition for diabetes management in the context of ALAN exposure.

Citations

Citations to this article as recorded by

Impact of bedroom light exposure on glucose metabolic markers and the role of circadian-dependent meal timing: A population-based cross-sectional study
Qi Li, Yu-xiang Xu, Xiu-zhen Lu, Yu-ting Shen, Yu-hui Wan, Pu-yu Su, Fang-biao Tao, Xin Chen, Ying Sun
Ecotoxicology and Environmental Safety.2025; 290: 117589. CrossRef
Circadian Deregulation: Back Facing the Sun Toward Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Development
Mariana Verdelho Machado
Nutrients.2024; 16(24): 4294. CrossRef

Brief Report

Technology/Device
Effectiveness of Predicted Low-Glucose Suspend Pump Technology in the Prevention of Hypoglycemia in People with Type 1 Diabetes Mellitus: Real-World Data Using DIA:CONN G8: Jee Hee Yoo, Ji Yoon Kim, Jae Hyeon Kim; Diabetes Metab J. 2025;49(1):144-149. Published online August 28, 2024; DOI: https://doi.org/10.4093/dmj.2024.0039

991 View
71 Download

Abstract PDF Supplementary Material PubReader ePub: We evaluated the effectiveness of the predictive low-glucose suspend (PLGS) algorithm in the DIA:CONN G8. Forty people with type 1 diabetes mellitus (T1DM) who used a DIA:CONN G8 for at least 2 months with prior experience using pumps without and with PLGS were retrospectively analyzed. The objective was to assess the changes in time spent in hypoglycemia (percent of time below range [%TBR]) before and after using PLGS. The mean age, sensor glucose levels, glucose threshold for suspension, and suspension time were 31.1±22.8 years, 159.7±23.2 mg/dL, 81.1±9.1 mg/dL, and 111.9±79.8 min/day, respectively. Overnight %TBR <70 mg/dL was significantly reduced after using the algorithm (differences=0.3%, from 1.4%±1.5% to 1.1%±1.2%, P=0.045). The glycemia risk index (GRI) improved significantly by 4.2 (from 38.8±20.9 to 34.6±19.0, P=0.002). Using the PLGS did not result in a change in the hyperglycemia metric (all P>0.05). Our findings support the PLGS in DIA:CONN G8 as an effective algorithm to improve night-time hypoglycemia and GRI in people with T1DM.

Original Articles

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

2,145 View
143 Download
1 Crossref

Abstract PDF Supplementary Material PubReader ePub

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

Metabolic Risk/Epidemiology
A Prospective 1-Year Follow-up of Glycemic Status and C-Peptide Levels of COVID-19 Survivors with Dysglycemia in Acute COVID-19 Infection: David Tak Wai Lui, Chi Ho Lee, Ying Wong, Carol Ho Yi Fong, Kimberly Hang Tsoi, Yu Cho Woo, Kathryn Choon Beng Tan; Diabetes Metab J. 2024;48(4):763-770. Published online March 11, 2024; DOI: https://doi.org/10.4093/dmj.2023.0175

1,906 View
151 Download

Abstract PDF PubReader ePub: Background
We evaluated changes in glycemic status, over 1 year, of coronavirus disease 2019 (COVID-19) survivors with dysglycemia in acute COVID-19.
Methods
COVID-19 survivors who had dysglycemia (defined by glycosylated hemoglobin [HbA1c] 5.7% to 6.4% or random glucose ≥10.0 mmol/L) in acute COVID-19 were recruited from a major COVID-19 treatment center from September to October 2020. Matched non-COVID controls were recruited from community. The 75-g oral glucose tolerance test (OGTT) were performed at baseline (6 weeks after acute COVID-19) and 1 year after acute COVID-19, with HbA1c, insulin and C-peptide measurements. Progression in glycemic status was defined by progression from normoglycemia to prediabetes/diabetes, or prediabetes to diabetes.
Results
Fifty-two COVID-19 survivors were recruited. Compared with non-COVID controls, they had higher C-peptide (P< 0.001) and trend towards higher homeostasis model assessment of insulin resistance (P=0.065). Forty-three COVID-19 survivors attended 1-year reassessment. HbA1c increased from 5.5%±0.3% to 5.7%±0.2% (P<0.001), with increases in glucose on OGTT at fasting (P=0.089), 30-minute (P=0.126), 1-hour (P=0.014), and 2-hour (P=0.165). At baseline, 19 subjects had normoglycemia, 23 had prediabetes, and one had diabetes. Over 1 year, 10 subjects (23.8%; of 42 non-diabetes subjects at baseline) had progression in glycemic status. C-peptide levels remained unchanged (P=0.835). Matsuda index decreased (P=0.007) and there was a trend of body mass index increase from 24.4±2.7 kg/m² to 25.6±5.2 (P=0.083). Subjects with progression in glycemic status had more severe COVID-19 illness than non-progressors (P=0.030). Reassessment was not performed in the control group.
Conclusion
Subjects who had dysglycemia in acute COVID-19 were characterized by insulin resistance. Over 1 year, a quarter had progression in glycemic status, especially those with more severe COVID-19. Importantly, there was no significant deterioration in insulin secretory capacity.

Drug/Regimen
Efficacy and Safety of IDegAsp in a Real-World Korean Population with Type 2 Diabetes Mellitus: Shinae Kang, Yu-Bae Ahn, Tae Keun Oh, Won-Young Lee, Sung Wan Chun, Boram Bae, Amine Dahaoui, Jin Sook Jeong, Sungeun Jung, Hak Chul Jang; Diabetes Metab J. 2024;48(5):929-936. Published online February 27, 2024; DOI: https://doi.org/10.4093/dmj.2023.0297

2,803 View
226 Download
1 Web of Science
1 Crossref

Abstract PDF Supplementary Material PubReader ePub

Background
This study investigated the real-world efficacy and safety of insulin degludec/insulin aspart (IDegAsp) in Korean adults with type 2 diabetes mellitus (T2DM), whose insulin treatment was switched to IDegAsp.
Methods
This was a multicenter, retrospective, observational study comprising two 26-week treatment periods, before and after switching to IDegAsp, respectively. Korean adults with uncontrolled T2DM treated with basal or premix insulin (±oral antidiabetic drugs) were enrolled. The primary objective was to compare the degree of glycosylated hemoglobin (HbA1c) change in each 26-week observation period. The analyses included changes in HbA1c, fasting plasma glucose (FPG), body weight, proportion of participants achieving HbA1c <7.0%, hypoglycemic events, and total daily insulin dose (ClinicalTrials.gov, number NCT04656106).
Results
In total, 196 adults (mean age, 65.95 years; mean T2DM duration, 18.99 years) were analyzed. The change in both HbA1c and FPG were significantly different between the pre-switching and the post-switching period (0.28% vs. –0.51%, P<0.001; 5.21 mg/dL vs. –23.10 mg/dL, P=0.005), respectively. After switching, the rate of achieving HbA1c <7.0% was significantly improved (5.10% at baseline vs. 11.22% with IDegAsp, P=0.012). No significant differences (before vs. after switching) were observed in body weight change, and total daily insulin dose. The rates of overall and severe hypoglycemia were similar in the two periods.
Conclusion
In real-world clinical practice in Korea, the change of insulin regimen to IDegAsp was associated with an improvement in glycemic control without increase of hypoglycemia, supporting the use of IDegAsp for patients with T2DM uncontrolled with basal or premix insulin.

Citations

Citations to this article as recorded by

Switching from Premixed Insulin to Insulin Degludec/Insulin Aspart for the Management of Type 2 Diabetes Mellitus: Implications of a Real-World Study on Insulin Degludec Dosing
Yiming Wu, Junqing Zhang, Ang Li
Diabetes Therapy.2024; 15(12): 2515. CrossRef

Sulwon Lecture 2023

Metabolic Risk/Epidemiology
Insulin Resistance, Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus: Clinical and Experimental Perspective: Inha Jung, Dae-Jeong Koo, Won-Young Lee; Diabetes Metab J. 2024;48(3):327-339. Published online February 2, 2024; DOI: https://doi.org/10.4093/dmj.2023.0350

4,692 View
493 Download
3 Web of Science
3 Crossref

Abstract PDF PubReader ePub

It has been generally accepted that insulin resistance (IR) and reduced insulin secretory capacity are the basic pathogenesis of type 2 diabetes mellitus (T2DM). In addition to genetic factors, the persistence of systemic inflammation caused by obesity and the associated threat of lipotoxicity increase the risk of T2DM. In particular, the main cause of IR is obesity and subjects with T2DM have a higher body mass index (BMI) than normal subjects according to recent studies. The prevalence of T2DM with IR has increased with increasing BMI during the past three decades. According to recent studies, homeostatic model assessment of IR was increased compared to that of the 1990s. Rising prevalence of obesity in Korea have contributed to the development of IR, non-alcoholic fatty liver disease and T2DM and cutting this vicious cycle is important. My colleagues and I have investigated this pathogenic mechanism on this theme through clinical and experimental studies over 20 years and herein, I would like to summarize some of our studies with deep gratitude for receiving the prestigious 2023 Sulwon Award.

Citations

Citations to this article as recorded by

γ-Glutamylcysteine restores glucolipotoxicity-induced islet β-cell apoptosis and dysfunction via inhibiting endoplasmic reticulum stress
Jinyi Zhou, Yingying Shi, Lishuang Zhao, Rong Wang, Lan Luo, Zhimin Yin
Toxicology and Applied Pharmacology.2025; 495: 117206. CrossRef
Strategy for treating MAFLD: Electroacupuncture alleviates hepatic steatosis and fibrosis by enhancing AMPK mediated glycolipid metabolism and autophagy in T2DM rats
Haoru Duan, Shanshan Song, Rui Li, Suqin Hu, Shuting Zhuang, Shaoyang liu, Xiaolu Li, Wei Gao
Diabetology & Metabolic Syndrome.2024;[Epub] CrossRef
Metabolic Dysfunction-Associated Steatotic Liver Disease in Type 2 Diabetes Mellitus: A Review and Position Statement of the Fatty Liver Research Group of the Korean Diabetes Association
Jaehyun Bae, Eugene Han, Hye Won Lee, Cheol-Young Park, Choon Hee Chung, Dae Ho Lee, Eun-Hee Cho, Eun-Jung Rhee, Ji Hee Yu, Ji Hyun Park, Ji-Cheol Bae, Jung Hwan Park, Kyung Mook Choi, Kyung-Soo Kim, Mi Hae Seo, Minyoung Lee, Nan-Hee Kim, So Hun Kim, Won-
Diabetes & Metabolism Journal.2024; 48(6): 1015. CrossRef

Original Articles

Drug/Regimen
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

7,015 View
488 Download
1 Crossref

Abstract PDF Supplementary Material PubReader 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

Ideal Combination of Oral Hypoglycemic Agents for Patients with Type 2 Diabetes Mellitus
Hye Soon Kim
Diabetes & Metabolism Journal.2024; 48(5): 882. CrossRef

Metabolic Risk/Epidemiology
Harnessing Metabolic Indices as a Predictive Tool for Cardiovascular Disease in a Korean Population without Known Major Cardiovascular Event: Hyun-Jin Kim, Byung Sik Kim, Yonggu Lee, Sang Bong Ahn, Dong Wook Kim, Jeong-Hun Shin; Diabetes Metab J. 2024;48(3):449-462. Published online February 1, 2024; DOI: https://doi.org/10.4093/dmj.2023.0197

2,684 View
233 Download
2 Web of Science
2 Crossref

Abstract PDF Supplementary Material PubReader ePub

Background
This study evaluated the usefulness of indices for metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), and insulin resistance (IR), as predictive tools for cardiovascular disease in middle-aged Korean adults.
Methods
The prospective data obtained from the Ansan-Ansung cohort database, excluding patients with major adverse cardiac and cerebrovascular events (MACCE). The primary outcome was the incidence of MACCE during the follow-up period.
Results
A total of 9,337 patients were included in the analysis, of whom 1,130 (12.1%) experienced MACCE during a median follow-up period of 15.5 years. The metabolic syndrome severity Z-score, metabolic syndrome severity score, hepatic steatosis index, and NAFLD liver fat score were found to significantly predict MACCE at values above the cut-off point and in the second and third tertiles. Among these indices, the hazard ratios of the metabolic syndrome severity score and metabolic syndrome severity Z-score were the highest after adjusting for confounding factors. The area under the receiver operating characteristic curve (AUC) of the 10-year atherosclerotic cardiovascular disease (ASCVD) score for predicting MACCE was 0.716, and the metabolic syndrome severity Z-score had an AUC of 0.619.
Conclusion
The metabolic syndrome severity score is a highly reliable indicator and was closely associated with the 10-year ASCVD risk score in predicting MACCE in the general population. Given the specific characteristics and limitations of metabolic syndrome severity scores as well as the indices of NAFLD and IR, a more practical scoring system that considers these factors is essential to achieve greater accuracy in forecasting cardiovascular outcomes.

Citations

Citations to this article as recorded by

Association between mixed exposure to per- and polyfluoroalkyl substances and metabolic syndrome in Korean adults: Data from the Korean National environmental health survey cycle 4
Seung Min Chung, Kyun Hoo Kim, Jun Sung Moon, Kyu Chang Won
International Journal of Hygiene and Environmental Health.2024; 261: 114427. CrossRef
Estimated pulse wave velocity as a forefront indicator of developing metabolic syndrome in Korean adults
Hyun-Jin Kim, Byung Sik Kim, Dong Wook Kim, Jeong-Hun Shin
The Korean Journal of Internal Medicine.2024; 39(4): 612. CrossRef

Pathophysiology
Deficiency of ASGR1 Alleviates Diet-Induced Systemic Insulin Resistance via Improved Hepatic Insulin Sensitivity: Xiaorui Yu, Jiawang Tao, Yuhang Wu, Yan Chen, Penghui Li, Fan Yang, Miaoxiu Tang, Abdul Sammad, Yu Tao, Yingying Xu, Yin-Xiong Li; Diabetes Metab J. 2024;48(4):802-815. Published online February 1, 2024; DOI: https://doi.org/10.4093/dmj.2023.0124

2,449 View
133 Download
1 Crossref

Abstract PDF Supplementary Material PubReader ePub

Background
Insulin resistance (IR) is the key pathological basis of many metabolic disorders. Lack of asialoglycoprotein receptor 1 (ASGR1) decreased the serum lipid levels and reduced the risk of coronary artery disease. However, whether ASGR1 also participates in the regulatory network of insulin sensitivity and glucose metabolism remains unknown.
Methods
The constructed ASGR1 knockout mice and ASGR1^-/- HepG2 cell lines were used to establish the animal model of metabolic syndrome and the IR cell model by high-fat diet (HFD) or drug induction, respectively. Then we evaluated the glucose metabolism and insulin signaling in vivo and in vitro.
Results
ASGR1 deficiency ameliorated systemic IR in mice fed with HFD, evidenced by improved insulin intolerance, serum insulin, and homeostasis model assessment of IR index, mainly contributed from increased insulin signaling in the liver, but not in muscle or adipose tissues. Meanwhile, the insulin signal transduction was significantly enhanced in ASGR1^-/- HepG2 cells. By transcriptome analyses and comparison, those differentially expressed genes between ASGR1 null and wild type were enriched in the insulin signal pathway, particularly in phosphoinositide 3-kinase-AKT signaling. Notably, ASGR1 deficiency significantly reduced hepatic gluconeogenesis and glycogenolysis.
Conclusion
The ASGR1 deficiency was consequentially linked with improved hepatic insulin sensitivity under metabolic stress, hepatic IR was the core factor of systemic IR, and overcoming hepatic IR significantly relieved the systemic IR. It suggests that ASGR1 is a potential intervention target for improving systemic IR in metabolic disorders.

Citations

Citations to this article as recorded by

Experimental cell models of insulin resistance: overview and appraisal
Ying Yang, Ting-ting Wang, Hu-ai Xie, Ping Ping Hu, Pan Li
Frontiers in Endocrinology.2024;[Epub] CrossRef

Review

Pathophysiology
Primordial Drivers of Diabetes Heart Disease: Comprehensive Insights into Insulin Resistance: Yajie Fan, Zhipeng Yan, Tingting Li, Aolin Li, Xinbiao Fan, Zhongwen Qi, Junping Zhang; Diabetes Metab J. 2024;48(1):19-36. Published online January 3, 2024; DOI: https://doi.org/10.4093/dmj.2023.0110

6,405 View
293 Download
7 Web of Science
8 Crossref

Abstract PDF PubReader ePub

Insulin resistance has been regarded as a hallmark of diabetes heart disease (DHD). Numerous studies have shown that insulin resistance can affect blood circulation and myocardium, which indirectly cause cardiac hypertrophy and ventricular remodeling, participating in the pathogenesis of DHD. Meanwhile, hyperinsulinemia, hyperglycemia, and hyperlipidemia associated with insulin resistance can directly impair the metabolism and function of the heart. Targeting insulin resistance is a potential therapeutic strategy for the prevention of DHD. Currently, the role of insulin resistance in the pathogenic development of DHD is still under active research, as the pathological roles involved are complex and not yet fully understood, and the related therapeutic approaches are not well developed. In this review, we describe insulin resistance and add recent advances in the major pathological and physiological changes and underlying mechanisms by which insulin resistance leads to myocardial remodeling and dysfunction in the diabetic heart, including exosomal dysfunction, ferroptosis, and epigenetic factors. In addition, we discuss potential therapeutic approaches to improve insulin resistance and accelerate the development of cardiovascular protection drugs.

Citations

Citations to this article as recorded by

Different Associations between Lipid Levels and Risk for Heart Failure according to Diabetes Progression
Seung-Hwan Lee, Kyu Na Lee, Jong-Chan Youn, Hun Sung Kim, Kyungdo Han, Mee Kyoung Kim
Diabetes & Metabolism Journal.2025; 49(1): 105. CrossRef
Association between METS-IR and heart failure: a cross-sectional study
Xiaozhou Su, Chunli Zhao, Xianwei Zhang
Frontiers in Endocrinology.2024;[Epub] CrossRef
Insulin–Heart Axis: Bridging Physiology to Insulin Resistance
Alfredo Caturano, Raffaele Galiero, Erica Vetrano, Celestino Sardu, Luca Rinaldi, Vincenzo Russo, Marcellino Monda, Raffaele Marfella, Ferdinando Carlo Sasso
International Journal of Molecular Sciences.2024; 25(15): 8369. CrossRef
The web of intrigue: unraveling the role of NETosis within the gut-microbiome-immune-heart axis in acute myocardial infarction and heart failure
Tai Yasuda, Kate Deans, Aditi Shankar, Robert Chilton
Cardiovascular Endocrinology & Metabolism.2024;[Epub] CrossRef
Relationship between the Mediterranean Diet and Vascular Function in Subjects with and without Increased Insulin Resistance
Marta Gómez-Sánchez, Leticia Gómez-Sánchez, Rocío Llamas-Ramos, Emiliano Rodríguez-Sánchez, Luis García-Ortiz, Ruth Martí-Lluch, María Cortés Rodríguez, Inés Llamas-Ramos, Manuel A. Gómez-Marcos
Nutrients.2024; 16(18): 3106. CrossRef
Iron homeostasis and ferroptosis in human diseases: mechanisms and therapeutic prospects
Qin Ru, Yusheng Li, Lin Chen, Yuxiang Wu, Junxia Min, Fudi Wang
Signal Transduction and Targeted Therapy.2024;[Epub] CrossRef
The Role of Insulin Within the Socio-Psycho-Biological Framework in Type 2 Diabetes—A Perspective from Psychoneuroimmunology
Anne Wevers, Silvia San Roman-Mata, Santiago Navarro-Ledesma, Leo Pruimboom
Biomedicines.2024; 12(11): 2539. CrossRef
Targeting Cardiac Fibrosis in Diabetic Heart Failure: The Role of the EZH2, AMPK, and PPAR-γ Pathways (Diabetes Metab J 2024;48:716-29)
Jooyeop Lee, Joon Ho Moon
Diabetes & Metabolism Journal.2024; 48(6): 1176. CrossRef

First
Prev
Page of 22
Next
Last

Search