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Contributions of Hepatic Insulin Resistance and Islet β-Cell Dysfunction to the Blood Glucose Spectrum in Newly Diagnosed Type 2 Diabetes Mellitus
Mengge Yang, Ying Wei, Jia Liu, Ying Wang, Guang Wang
Diabetes Metab J. 2026;50(2):432-433.   Published online February 5, 2026
DOI: https://doi.org/10.4093/dmj.2024.0537.c1
Corrects: Diabetes Metab J 2025;49(4):883
  • 425 View
  • 34 Download
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Original Articles
Pharmacotherapy
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Novel Insights into the Causal Relationship between Antidiabetic Drugs and Adverse Perinatal Outcomes: A Mendelian Randomization Study
Chang Su, Xueqing He, Xiaona Chang, Juan Tian, Guang Wang, Jia Liu
Diabetes Metab J. 2025;49(6):1242-1251.   Published online June 2, 2025
DOI: https://doi.org/10.4093/dmj.2024.0521
  • 3,062 View
  • 164 Download
  • 1 Web of Science
  • 1 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Hyperglycemia during pregnancy increases the risk of adverse perinatal outcomes and birth defects. Evidence regarding the long-term safety of antidiabetic drugs during pregnancy is still lacking.
Methods
A two-sample Mendelian randomization (MR) study was performed to assess the causal association between six antidiabetic drug targets (ABCC8, DPP4, INSR, GLP1R, PPARG, and SLC5A2) and seven adverse perinatal outcomes and five congenital malformation outcomes. Inverse variance weighted (IVW) was adopted as the main MR method, and sensitivity analysis using traditional MR methods was performed to evaluate the robustness of the results.
Results
We observed strong evidence that sodium-glucose cotransporter 2 (SGLT2) inhibitors (odds ratio [OR], 0.084; 95% confidence interval [CI], 0.009 to 0.834; P=0.034) reduces the risk of preterm birth; genetic variation in sulfonylurea drug targets (OR, 0.015; 95% CI, 2.50E-04 to 0.919; P=0.045) and genetic variation in thiazolidinedione drug targets (OR, 0.007; 95% CI, 4.16E-04 to 0.121; P=0.001) reduced the risk of eclampsia/preeclampsia; glucagon-like peptide 1 (GLP-1) analogues target (β=–0.549; 95% CI, –0.958 to –0.140; P=0.009) was inversely associated with fetal birth weight; thiazolidinedione target was inversely associated with gestational age (β=–0.952; 95% CI, –1.785 to –0.118; P=0.025); SGLT2 inhibitors reduced the risk of cardiocirculatory malformations (OR, 0.001; 95% CI, 8.75E-06 to 0.126; P=0.005).
Conclusion
Most antidiabetic drugs are safe when used during the perinatal period. Of note, GLP-1 analogues may lead to a risk of low birth weight, while thiazolidinediones may lead to a reduction in fetal gestational age.

Citations

Citations to this article as recorded by  
  • Prenatal chemical exposures and fetal growth: a narrative review of gene-environment interactions (2025)
    Sumitaka Kobayashi, Fumihiro Sata, Yasuaki Saijo, Reiko Kishi
    Pediatric Research.2026;[Epub]     CrossRef
Others
Article image
Contributions of Hepatic Insulin Resistance and Islet β-Cell Dysfunction to the Blood Glucose Spectrum in Newly Diagnosed Type 2 Diabetes Mellitus
Mengge Yang, Ying Wei, Jia Liu, Ying Wang, Guang Wang
Diabetes Metab J. 2025;49(4):883-892.   Published online February 13, 2025
DOI: https://doi.org/10.4093/dmj.2024.0537
Correction in: Diabetes Metab J 2026;50(2):432
  • 7,380 View
  • 288 Download
  • 9 Web of Science
  • 13 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Our previous studies have investigated the role of hepatic insulin resistance (hepatic IR) and islet β-cell function in the pathogenesis of diabetes. This study aimed to explore the contributions of hepatic IR and islet β-cell dysfunction to the blood glucose spectrum in patients with newly diagnosed type 2 diabetes mellitus.
Methods
Hepatic IR was assessed by the hepatic insulin resistance index (HIRI). Islet β-cell function was assessed by insulin secretion- sensitivity index-2 (ISSI2). The associations between blood glucose spectrum and hepatic IR and ISSI2 were analyzed.
Results
A total of 707 patients with new-onset diabetes were included. The fasting blood glucose (FBG) and 30 minutes postload blood glucose elevated with rising HIRI (both P for trend <0.001). The FBG, 30 minutes, 2 hours, and 3 hours post-load blood glucose elevated with decreasing ISSI2 quartiles (all P for trend <0.001). There was a negative correlation between ISSI2 and HIRI after adjusting blood glucose levels (r=–0.199, P<0.001).
Conclusion
Hepatic IR mainly contributed to FBG and early-phase postprandial plasma glucose, whereas β-cell dysfunction contributed to fasting and postprandial plasma glucose at each phase.

Citations

Citations to this article as recorded by  
  • Interaction between insulin resistance and depression in predicting cardiovascular risk: Evidence from a longitudinal study
    Siyu Chen, Lijing Yang, Yu Zhou, Hao Yu
    Diabetes & Vascular Disease Research.2026;[Epub]     CrossRef
  • Engineering the pancreatic niche: Mechanobiological insights into stem cell-derived β-cell therapy for diabetes mellitus
    Swaminadhan Dandapani, Yongsung Hwang
    Mechanobiology.2026;[Epub]     CrossRef
  • Associations of adipose tissue insulin resistance with fasting blood glucose and HbA1c in adults without diabetes
    Ying Wei, Yong Tian, Ruixiang Cui, Ying Wang, Jia Liu, Guang Wang
    Diabetes, Obesity and Metabolism.2026;[Epub]     CrossRef
  • Advancing in vitro vascular wall modelling using digital light processing to study hyperglycemia-driven cell changes
    Ianina Pokholenko, Marguerite Meeremans, Sandra Van Vlierberghe, Nele Pien, Catharina De Schauwer
    Frontiers in Bioengineering and Biotechnology.2026;[Epub]     CrossRef
  • GLDC attenuates liver ischemia-reperfusion injury by inhibiting macrophage recruitment and activation via PTBP1/P2RY6
    Zhitao Li, Li Jin, Yuan Fang, Siming Qu, Bo Yuan, Kai Gan, Hanfei Huang
    Cellular Signalling.2025; 135: 111976.     CrossRef
  • The Physiological and Pathological Mechanisms of LIN2, LIN7, LIN10 and Their Tripartite Complex
    Yangyang Shang, Xinyi Gan, Yue Dang, Jie Liu, Peijun Liu
    Journal of Cellular and Molecular Medicine.2025;[Epub]     CrossRef
  • Cinnamic Acid: A Shield Against High-Fat-Diet-Induced Liver Injury—Exploring Nrf2’s Protective Mechanisms
    Asmahan Taher Alahdal, Laila Naif Al-Harbi, Ghedeir M. Alshammari, Ali Saleh, Mohammed Abdo Yahya
    International Journal of Molecular Sciences.2025; 26(16): 7940.     CrossRef
  • Sodium Butyrate Ameliorated Bile Acid Metabolism in Diabetes Mellitus by PI3K/AKT Signaling Pathway via the Gut–Liver Axis
    Tingting Zhao, Xi Zhang, Qian Xiang, Yadi Liu, Xuling Li, Junling Gu, Wenqian Zhang, Zhe Wang, Yiran Li, Xiaoshan Lai, Yonghua Zhao, Youhua Xu
    Current Issues in Molecular Biology.2025; 47(9): 732.     CrossRef
  • Chronic Intermittent Low-Pressure Hypoxia Suppresses Inflammation and Regulates Glycolipids by Modulating Mitochondrial Respiration in db/db Mice
    Xin Jiang, Keqing Yuan, Xiaofeng Ge, Lili Yu, Yufei Cui, Lianhai Jin, Ying Chang
    Metabolites.2025; 15(11): 707.     CrossRef
  • Expanding horizons: the role of robotic surgery in modern transplantation practices
    Arya Afrooghe, Pedram Pirmoradian, Moein Ghasemi, Benyamin Mohammadi, Mahya Soleymani Mehranjani, Elham Ahmadi, Seyed Amir Miratashi Yazdi
    Journal of Robotic Surgery.2025;[Epub]     CrossRef
  • Elevated PEDF promotes the occurrence of diabetes mellitus via suppressing GSIS by downregulating the SNARE complex
    Zhen Zhao, Yandan Tan, Jie Fang, Gan Xia, Junchen Li, Qilong Tang, Wanting Xie, Tianxiao Gao, Zhenzhen Fang, Ti Zhou, Xia Yang, Guoquan Gao, Weiwei Qi
    Communications Biology.2025;[Epub]     CrossRef
  • Distinct Circulating Biomarker Profiles Associated with Type 2 Diabetes in a Regional Cohort—A Cross-Sectional Study
    Abdullah Alsrhani, Muhammad Atif, Aisha Farhana
    Metabolites.2025; 15(12): 776.     CrossRef
  • Application and Predictive Potential of Novel Insulin Resistance Assessment Indices in Metabolic Diseases
    莹莹 郑
    Advances in Clinical Medicine.2025; 15(12): 2174.     CrossRef
Cardiovascular Risk/Epidemiology
Article image
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
Diabetes Metab J. 2025;49(3):448-461.   Published online January 20, 2025
DOI: https://doi.org/10.4093/dmj.2024.0100
  • 9,976 View
  • 440 Download
  • 7 Web of Science
  • 9 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   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.

Citations

Citations to this article as recorded by  
  • Normalized creatinine-to-cystatin C ratio and cardiovascular disease risk in populations with cardiovascular–kidney–metabolic syndrome stages 0–3: findings from a national and prospective cohort study
    Defei Chen, Yuhui Li, Tailin Ran, Fu Song, Zheng Yang, Weilin Tan, Qiuyi Lu, Lanxin Tang, Lining Yang, Dingqun Bai
    European Journal of Medical Research.2026;[Epub]     CrossRef
  • Association between the sarcopenia index and osteoarthritis: a cross-sectional and longitudinal study
    Xin Cai, Tianzuo Lan, Zong Jiang, Fang Tang, Haixia Fan
    European Journal of Medical Research.2026;[Epub]     CrossRef
  • Association of the triglyceride glucose-Chinese visceral adiposity index with incident cardiometabolic multimorbidity in middle-aged and older adults: a nationwide prospective cohort study
    Wenling Zheng, Ziyue Man, Yanping Ren, Yu Li, Xiaohong Zhu, Lan Wang, Xi Zhang, Guilin Hu, Yu Cao
    Cardiovascular Diabetology.2026;[Epub]     CrossRef
  • Normalized creatinine-to-cystatin C ratio and atherosclerotic cardiovascular disease risk in the UK Biobank
    Xiaoyan Liu, Huizhi Zhan, Yi Ou, Yuwen Shangguan, Jingbo Zhang
    European Journal of Preventive Cardiology.2026;[Epub]     CrossRef
  • Monitoring Sarcopenia With Incretin Receptor Activator Treatment
    Zachary T. Bloomgarden
    Journal of Diabetes.2025;[Epub]     CrossRef
  • Correlation Between Serum Creatinine-to-Cystatin C Ratio and Prognosis of Patients with Hip Fracture
    Wenbin Lu, Miaomiao Rao, Fan Jia, Wubin Chen, Bin Li, Jinjun Bian, Jiafeng Wang
    International Journal of General Medicine.2025; Volume 18: 4147.     CrossRef
  • Association between creatinine to cystatin C ratio and the incidence of depressive symptoms among middle-aged and older adults: insight from the CHARLS study
    Xiaohui Li, Guirong Song, Jiaqi Ding, Dongmei Hu, Ying Zhang, Guorong Li, Xiao Tang
    BMC Psychology.2025;[Epub]     CrossRef
  • Cardiometabolic multimorbidity in relation to the metabolic score for insulin resistance and creatinine-to-cystatin C ratio in a middle-aged and aged population
    Roushan Zhang, Jian Ma, Li Wang
    Frontiers in Endocrinology.2025;[Epub]     CrossRef
  • Elevated Serum Triglycerides Independently Predict Incident Falls in Middle‐Aged and Older Adults
    Kai Deng
    Geriatrics & Gerontology International.2025; 25(12): 1868.     CrossRef

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