Diabetes & Metabolism Journal

Original Article

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

Citations to this article as recorded by

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

Review

Pathophysiology
Regulation of Systemic Glucose Homeostasis by T Helper Type 2 Cytokines: Yea Eun Kang, Hyun Jin Kim, Minho Shong; Diabetes Metab J. 2019;43(5):549-559. Published online October 24, 2019; DOI: https://doi.org/10.4093/dmj.2019.0157

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Abstract PDF PubReader

Obesity results in an inflammatory microenvironment in adipose tissue, leading to the deterioration of tissue protective mechanisms. Although recent studies suggested the importance of type 2 immunity in an anti-inflammatory microenvironment in adipose tissue, the regulatory effects of T helper 2 (Th2) cytokines on systemic metabolic regulation are not fully understood. Recently, we identified the roles of the Th2 cytokine (interleukin 4 [IL-4] and IL-13)-induced adipokine, growth differentiation factor 15 (GDF15), in adipose tissue in regulating systemic glucose metabolism via signal transducer and activator of transcription 6 (STAT6) activation. Moreover, we showed that mitochondrial oxidative phosphorylation is required to maintain these macrophage-regulating autocrine and paracrine signaling pathways via Th2 cytokine-induced secretion of GDF15. In this review, we discuss how the type 2 immune response and Th2 cytokines regulate metabolism in adipose tissue. Specifically, we review the systemic regulatory roles of Th2 cytokines in metabolic disease and the role of mitochondria in maintenance of type 2 responses in adipose tissue homeostasis.

Citations

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Orchestration of the Adipose Tissue Immune Landscape by Adipocytes
David Bradley, Tuo Deng, Dharti Shantaram, Willa A. Hsueh
Annual Review of Physiology.2024; 86(1): 199. CrossRef
Growth and differentiation factor-15: A link between inflammaging and cardiovascular disease
Balázs Bence Nyárády, Loretta Zsuzsa Kiss, Zsolt Bagyura, Béla Merkely, Edit Dósa, Orsolya Láng, László Kőhidai, Éva Pállinger
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Jian Wu, Min Zhang, Allison Faircloth
Hemato.2022; 3(3): 422. CrossRef
Macrophage and Adipocyte Mitochondrial Dysfunction in Obesity-Induced Metabolic Diseases
Liwen Wang, Jie Hu, Haiyan Zhou
The World Journal of Men's Health.2021; 39(4): 606. CrossRef
Th2 Cytokines Increase the Expression of Fibroblast Growth Factor 21 in the Liver
Seul-Gi Kang, Seong-Eun Lee, Min-Jeong Choi, Joon-Young Chang, Jung-Tae Kim, Ben-Yuan Zhang, Yea-Eun Kang, Ju-Hee Lee, Hyon-Seung Yi, Minho Shong
Cells.2021; 10(6): 1298. CrossRef
Growth/Differentiation Factor-15 (GDF-15): From Biomarker to Novel Targetable Immune Checkpoint
Jörg Wischhusen, Ignacio Melero, Wolf Herman Fridman
Frontiers in Immunology.2020;[Epub] CrossRef
Transcriptional, Epigenetic and Metabolic Programming of Tumor-Associated Macrophages
Irina Larionova, Elena Kazakova, Marina Patysheva, Julia Kzhyshkowska
Cancers.2020; 12(6): 1411. CrossRef

Original Article

Others
Serum R-Spondin 1 Is a New Surrogate Marker for Obesity and Insulin Resistance: Yea Eun Kang, Ji Min Kim, Hyon-Seung Yi, Kyong Hye Joung, Ju Hee Lee, Hyun Jin Kim, Bon Jeong Ku; Diabetes Metab J. 2019;43(3):368-376. Published online October 23, 2018; DOI: https://doi.org/10.4093/dmj.2018.0066

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Background

Recent in vivo studies indicated that R-spondin 1 (RSPO1) regulates food intake and increases insulin secretion, but its role in humans remains unknown. This study investigated the association between serum levels of RSPO1 and diverse metabolic parameters in humans.

Methods

The study population consisted of 43 subjects with newly diagnosed diabetes mellitus, and 79 non-diabetic participants. Serum levels of RSPO1 were measured using the enzyme-linked immunosorbent assay. The relationships between circulating RSPO1 and diverse metabolic parameters were analyzed.

Results

Circulating RSPO1 levels increased to a greater extent in the obese group than in the lean group. Moreover, serum levels of RSPO1 were higher in the insulin-resistant group than in the insulin-sensitive group. Serum levels of RSPO1 were significantly correlated with a range of metabolic parameters including body mass index, fasting C-peptide, homeostasis model assessment of insulin resistance index, and lipid profile. Moreover, levels were significantly associated with insulin resistance and obesity in non-diabetic subjects.

Conclusion

This study demonstrated the association between serum levels of RSPO1 and a range of metabolic parameters in humans. Serum levels of RSPO1 are significantly related to obesity and insulin resistance, although the precise mechanisms remain unknown.

Citations

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Systems genetics analysis of human body fat distribution genes identifies adipocyte processes
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Life Science Alliance.2024; 7(7): e202402603. CrossRef
LGR4: A New Receptor Member in Endocrine and Metabolic Diseases
Ningning Zhang, Mingyang Yuan, Jiqiu Wang
Endocrine Reviews.2023; 44(4): 647. CrossRef
R-Spondin1 and tumor necrosis factor-alpha in infertile women with polycystic ovary syndrome: relationships with insulin resistance and other parameters
Tuğba GÜRBÜZ, Oya GÖKMEN, Asena AYAR MADENLİ, Berna DİLBAZ
Journal of Health Sciences and Medicine.2023; 6(2): 449. CrossRef
An early prediction model for type 2 diabetes mellitus based on genetic variants and nongenetic risk factors in a Han Chinese cohort
Jinjin Li, Qun Ye, Hongxiao Jiao, Wanyao Wang, Kai Zhang, Chen Chen, Yuan Zhang, Shuzhi Feng, Ximo Wang, Yubao Chen, Huailin Gao, Fengjiang Wei, Wei-Dong Li
Frontiers in Endocrinology.2023;[Epub] CrossRef
Emerging Therapeutic Strategies for Attenuating Tubular EMT and Kidney Fibrosis by Targeting Wnt/β-Catenin Signaling
Lichao Hu, Mengyuan Ding, Weichun He
Frontiers in Pharmacology.2022;[Epub] CrossRef
Does Serum R-Spondin-1 Play a Role in PCOS Pathophysiology?
Osman BAŞPINAR, Yasin ŞİMŞEK, Derya KOÇER, Oğuzhan Sıtkı DİZDAR, Hatice KAYIŞ TOPALOĞLU
Genel Tıp Dergisi.2022; 32(5): 490. CrossRef
Silencing of RSPO1 mitigates obesity-related renal fibrosis in mice by deactivating Wnt/β-catenin pathway
Xuesong Su, Guangyu Zhou, Mi Tian, Si Wu, Yanqiu Wang
Experimental Cell Research.2021; 405(2): 112713. CrossRef
Exosome miR‐27a‐3p secreted from adipocytes targets ICOS to promote antitumor immunity in lung adenocarcinoma
Xuehan Fan, Jingya Wang, Tingting Qin, Yujia Zhang, Wenting Liu, Kaiting Jiang, Dingzhi Huang
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Integrative Analyses of Genes Associated with Subcutaneous Insulin Resistance
Manoj Kumar Pujar, Basavaraj Vastrad, Chanabasayya Vastrad
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