Diabetes & Metabolism Journal

Review

Basic Research
Regulation of Cellular Senescence in Type 2 Diabetes Mellitus: From Mechanisms to Clinical Applications: Kanako Iwasaki, Cristian Abarca, Cristina Aguayo-Mazzucato; Diabetes Metab J. 2023;47(4):441-453. Published online March 6, 2023; DOI: https://doi.org/10.4093/dmj.2022.0416; Funded: Institutional Startup Funds, National Institutes of Health, Joslin Diabetes Center, Thomas J Beatson Jr foundation, Richard and Susan Smith Family Foundation, Manpei Suzuki Diabetes Foundation

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Abstract PDF PubReader ePub Crossref - TDM

Cellular senescence is accelerated by hyperglycemia through multiple pathways. Therefore, senescence is an important cellular mechanism to consider in the pathophysiology of type 2 diabetes mellitus (T2DM) and an additional therapeutic target. The use of drugs that remove senescent cells has led to improvements in blood glucose levels and diabetic complications in animal studies. Although the removal of senescent cells is a promising approach for the treatment of T2DM, two main challenges limit its clinical application: the molecular basis of cellular senescence in each organ is yet to be understood, and the specific effect of removing senescent cells in each organ has to be determined. This review aims to discuss future applications of targeting senescence as a therapeutic option in T2DM and elucidate the characteristics of cellular senescence and senescence-associated secretory phenotype in the tissues important for regulating glucose levels: pancreas, liver, adipocytes, and skeletal muscle.

Citations

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The Effect of Long-Term Passage on Porcine SMCs’ Function and the Improvement of TGF-β1 on Porcine SMCs’ Secretory Function in Late Passage
Yan-Yan Zheng, Ze-Nan Hu, Zheng Liu, Yi-Chen Jiang, Ren-Peng Guo, Shi-Jie Ding, Guang-Hong Zhou
Foods.2023; 12(14): 2682. CrossRef
Exploring the Relationship between Cellular Senescence Markers and Aging-Related Diseases
怡罗
Advances in Clinical Medicine.2023; 13(08): 12298. CrossRef

Original Articles

Lifestyle
Ultra-Processed Food Consumption and Obesity in Korean Adults: Jee-Seon Shim, Kyoung Hwa Ha, Dae Jung Kim, Hyeon Chang Kim; Diabetes Metab J. 2023;47(4):547-558. Published online April 26, 2023; DOI: https://doi.org/10.4093/dmj.2022.0026; Funded: National Research Foundation of Korea, Ministry of Education, National Research Foundation of Korea, Ministry of Science and ICT

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Abstract PDF PubReader ePub Crossref - TDM

Background
This study aimed to investigate the association between consumption of ultra-processed foods (UPF) and obesity in Korean adults.
Methods
We included the Cardiovascular and Metabolic Diseases Etiology Research Center cohort study baseline data of adults aged 30 to 64 years who completed a validated food frequency questionnaire. UPF was defined using the NOVA food classification. Multivariable linear and logistic regression analyses were performed to assess the association of dietary energy contribution of UPF with obesity indicators (body mass index [BMI], obesity, waist circumference [WC], and abdominal obesity).
Results
Consumption of UPF accounted for 17.9% of total energy intake and obesity and abdominal obesity prevalence was 35.4% and 30.2%, respectively. Compared with those in the lowest quartile of UPF consumption, adults in the highest quartile had greater BMI (β=0.36; 95% confidence interval [CI], 0.15 to 0.56), WC (β=1.03; 95% CI, 0.46 to 1.60), higher odds of having obesity (odds ratio [OR], 1.24; 95% CI, 1.07 to 1.45), and abdominal obesity (OR, 1.34; 95% CI, 1.14 to 1.57), after adjusting for sociodemographic characteristics, health-related behaviors, and family history of diseases. Dose-response associations between UPF consumption and obesity indicators were consistently found (all P trend <0.01). However, the strength of association was halved for all obesity indicators after further adjustments for total energy intake and overall diet quality score, and the trend toward association for obesity and WC disappeared.
Conclusion
Our finding supports the evidence that consumption of UPF is positively associated with obesity among Korean adults.

Citations

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Diet quality partially mediates the association between ultraprocessed food consumption and adiposity indicators
Jee‐Seon Shim, Kyoung Hwa Ha, Dae Jung Kim, Hyeon Chang Kim
Obesity.2023; 31(9): 2430. CrossRef

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; Funded: National Research Foundation of Korea, Department of Pharmacy, College of Pharmacy, Ewha Womans University

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Abstract PDF Supplementary Material PubReader ePub Crossref - TDM: 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.

Basic Research
Pharmacologic Activation of Angiotensin-Converting Enzyme II Alleviates Diabetic Cardiomyopathy in db/db Mice by Reducing Reactive Oxidative Stress: Donghyun Kim, Wooju Jeong, Yumin Kim, Jibeom Lee, Sung Woo Cho, Chang-Myung Oh, Raekil Park; Diabetes Metab J. 2023;47(4):487-499. Published online April 25, 2023; DOI: https://doi.org/10.4093/dmj.2022.0125; Funded: National Research Foundation of Korea, Ministry of Education, Korea Health Industry Development Institute, Samjin pharm Co., Ministry of Health and Welfare

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Abstract PDF Supplementary Material PubReader ePub Crossref - TDM: Background
Diabetes mellitus is one of the most common chronic diseases worldwide, and cardiovascular disease is the leading cause of morbidity and mortality in diabetic patients. Diabetic cardiomyopathy (DCM) is a phenomenon characterized by a deterioration in cardiac function and structure, independent of vascular complications. Among many possible causes, the renin-angiotensin-aldosterone system and angiotensin II have been proposed as major drivers of DCM development. In the current study, we aimed to investigate the effects of pharmacological activation of angiotensin-converting enzyme 2 (ACE2) on DCM.
Methods
The ACE2 activator diminazene aceturate (DIZE) was administered intraperitoneally to male db/db mice (8 weeks old) for 8 weeks. Transthoracic echocardiography was used to assess cardiac mass and function in mice. Cardiac structure and fibrotic changes were examined using histology and immunohistochemistry. Gene and protein expression levels were examined using quantitative reverse transcription polymerase chain reaction and Western blotting, respectively. Additionally, RNA sequencing was performed to investigate the underlying mechanisms of the effects of DIZE and identify novel potential therapeutic targets for DCM.
Results
Echocardiography revealed that in DCM, the administration of DIZE significantly improved cardiac function as well as reduced cardiac hypertrophy and fibrosis. Transcriptome analysis revealed that DIZE treatment suppresses oxidative stress and several pathways related to cardiac hypertrophy.
Conclusion
DIZE prevented the diabetes mellitus-mediated structural and functional deterioration of mouse hearts. Our findings suggest that the pharmacological activation of ACE2 could be a novel treatment strategy for DCM.

Cardiovascular Risk/Epidemiology
Glycemic Control and Adverse Clinical Outcomes in Patients with Chronic Kidney Disease and Type 2 Diabetes Mellitus: Results from KNOW-CKD: Ga Young Heo, Hee Byung Koh, Hyung Woo Kim, Jung Tak Park, Tae-Hyun Yoo, Shin-Wook Kang, Jayoun Kim, Soo Wan Kim, Yeong Hoon Kim, Su Ah Sung, Kook-Hwan Oh, Seung Hyeok Han; Diabetes Metab J. 2023;47(4):535-546. Published online April 25, 2023; DOI: https://doi.org/10.4093/dmj.2022.0112; Funded: Korea Centers for Disease Control and Prevention

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Abstract PDF Supplementary Material PubReader ePub Crossref - TDM

Background
The optimal level of glycosylated hemoglobin (HbA1c) to prevent adverse clinical outcomes is unknown in patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM).
Methods
We analyzed 707 patients with CKD G1-G5 without kidney replacement therapy and T2DM from the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD), a nationwide prospective cohort study. The main predictor was time-varying HbA1c level at each visit. The primary outcome was a composite of development of major adverse cardiovascular events (MACEs) or all-cause mortality. Secondary outcomes included the individual endpoint of MACEs, all-cause mortality, and CKD progression. CKD progression was defined as a ≥50% decline in the estimated glomerular filtration rate from baseline or the onset of end-stage kidney disease.
Results
During a median follow-up of 4.8 years, the primary outcome occurred in 129 (18.2%) patients. In time-varying Cox model, the adjusted hazard ratios (aHRs) for the primary outcome were 1.59 (95% confidence interval [CI], 1.01 to 2.49) and 1.99 (95% CI, 1.24 to 3.19) for HbA1c levels of 7.0%–7.9% and ≥8.0%, respectively, compared with <7.0%. Additional analysis of baseline HbA1c levels yielded a similar graded association. In secondary outcome analyses, the aHRs for the corresponding HbA1c categories were 2.17 (95% CI, 1.20 to 3.95) and 2.26 (95% CI, 1.17 to 4.37) for MACE, and 1.36 (95% CI, 0.68 to 2.72) and 2.08 (95% CI, 1.06 to 4.05) for all-cause mortality. However, the risk of CKD progression did not differ between the three groups.
Conclusion
This study showed that higher HbA1c levels were associated with an increased risk of MACE and mortality in patients with CKD and T2DM.

Citations

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The Beneficial Effect of Glycemic Control against Adverse Outcomes in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease
Dong-Hwa Lee
Diabetes & Metabolism Journal.2023; 47(4): 484. CrossRef

Metabolic Risk/Epidemiology
The Risk of Type 2 Diabetes Mellitus according to Changes in Obesity Status in Late Middle-Aged Adults: A Nationwide Cohort Study of Korea: Joon Ho Moon, Yeonhoon Jang, Tae Jung Oh, Se Young Jung; Diabetes Metab J. 2023;47(4):514-522. Published online April 25, 2023; DOI: https://doi.org/10.4093/dmj.2022.0159; Funded: Kyobo Insurance Company

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Abstract PDF Supplementary Material PubReader ePub Crossref - TDM: Background
Although obesity is a well-known risk factor of type 2 diabetes mellitus (T2DM), there is scant data on discriminating the contribution of previous obesity and recent weight gain on developing T2DM.
Methods
We analyzed the Korean National Health Insurance Service-Health Screening Cohort data from 2002 to 2015 where Korean residents underwent biennial health checkups. Participants were classified into four groups according to their obesity status (body mass index [BMI] ≥25 kg/m²) before and after turning 50 years old: maintaining normal (MN), becoming obese (BO), becoming normal (BN), and maintaining obese (MO). Cox proportional hazards regression model was used to estimate the risk of T2DM factoring in the covariates age, sex, BMI, presence of impaired fasting glucose or hypertension, family history of diabetes, and smoking status.
Results
A total of 118,438 participants (mean age, 52.5±1.1 years; men, 45.2%) were prospectively evaluated for incident T2DM. A total of 7,339 (6.2%) participants were diagnosed with T2DM during a follow-up period of 4.8±2.6 years. Incidence rates of T2DM per 1,000 person-year were 9.20 in MN, 14.81 in BO, 14.42 in BN, 21.38 in MO. After factoring in covariates, participants in the groups BN (adjusted hazard ratio [aHR], 1.15; 95% confidence interval [CI], 1.04 to 1.27) and MO (aHR, 1.14; 95% CI, 1.06 to 1.24) were at increased risk of developing T2DM compared to MN, whereas BO (hazard ratio, 1.06; 95% CI, 0.96 to 1.17) was not.
Conclusion
Having been obese before 50 years old increased the risk of developing T2DM in the future, but becoming obese after 50 did not. Therefore, it is important to maintain normal weight from early adulthood to prevent future metabolic perturbations.

Others
Change Profiles and Functional Targets of MicroRNAs in Type 2 Diabetes Mellitus Patients with Obesity: Guanhua Lu, Huanhuan Gao, Zhiyong Dong, Shuwen Jiang, Ruixiang Hu, Cunchuan Wang; Diabetes Metab J. 2023;47(4):559-570. Published online April 25, 2023; DOI: https://doi.org/10.4093/dmj.2022.0226; Funded: The First Affiliated Hospital of Jinan University

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Abstract PDF Supplementary Material PubReader ePub Crossref - TDM: Background
MicroRNAs (miRNAs) exert an essential contribution to obesity and type 2 diabetes mellitus (T2DM). This study aimed to investigate the differences of miRNAs in the presence and absence of T2DM in patients with obesity, as well as before and after bariatric surgery in T2DM patients with obesity. Characterization of the common changes in both was further analyzed.
Methods
We enrolled 15 patients with obesity but without T2DM and 15 patients with both obesity and T2DM. Their preoperative clinical data and serum samples were collected, as well as 1 month after bariatric surgery. The serum samples were analyzed by miRNA sequencing, and the miRNAs profiles and target genes characteristics were compared.
Results
Patients with T2DM had 16 up-regulated and 32 down-regulated miRNAs compared to patients without T2DM. Improvement in metabolic metrics after bariatric surgery of T2DM patients with obesity was correlated with changes in miRNAs, as evidenced by the upregulation of 20 miRNAs and the downregulation of 30 miRNAs. Analysis of the two miRNAs profiles identified seven intersecting miRNAs that showed opposite changes. The target genes of these seven miRNAs were substantially enriched in terms or pathways associated with T2DM.
Conclusion
We determined the expression profiles of miRNAs in the obese population, with and without diabetes, before and after bariatric surgery. The miRNAs that intersected in the two comparisons were discovered. Both the miRNAs discovered and their target genes were closely associated with T2DM, demonstrating that they might be potential targets for the regulation of T2DM.

Reviews

Basic Research
Rediscovering Primary Cilia in Pancreatic Islets: Eun Young Lee, Jing W. Hughes; Diabetes Metab J. 2023;47(4):454-469. Published online April 28, 2023; DOI: https://doi.org/10.4093/dmj.2022.0442; Funded: National Research Foundation of Korea, Ministry of Science and ICT, National Institutes of Health, Doris Duke Charitable Foundation, National Institutes of Health

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Abstract PDF PubReader ePub Crossref - TDM: Primary cilia are microtubule-based sensory and signaling organelles on the surfaces of most eukaryotic cells. Despite their early description by microscopy studies, islet cilia had not been examined in the functional context until recent decades. In pancreatic islets as in other tissues, primary cilia facilitate crucial developmental and signaling pathways in response to extracellular stimuli. Many human developmental and genetic disorders are associated with ciliary dysfunction, some manifesting as obesity and diabetes. Understanding the basis for metabolic diseases in human ciliopathies has been aided by close examination of cilia action in pancreatic islets at cellular and molecular levels. In this article, we review the evidence for ciliary expression on islet cells, known roles of cilia in pancreas development and islet hormone secretion, and summarize metabolic manifestations of human ciliopathy syndromes. We discuss emerging data on primary cilia regulation of islet cell signaling and the structural basis of cilia-mediated cell crosstalk, and offer our interpretation on the role of cilia in glucose homeostasis and human diseases.

Cardiovascular Risk/Epidemiology
The Role of Echocardiography in Evaluating Cardiovascular Diseases in Patients with Diabetes Mellitus: Sun Hwa Lee, Jae-Hyeong Park; Diabetes Metab J. 2023;47(4):470-483. Published online July 27, 2023; DOI: https://doi.org/10.4093/dmj.2023.0036; Funded: Jeonbuk National University

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Abstract PDF PubReader ePub Crossref - TDM: Patients with diabetes mellitus are highly susceptible to cardiovascular complications, which are directly correlated with cardiovascular morbidity and mortality. In addition to coronary artery disease, there is growing awareness of the risk and prevalence of heart failure (HF) in patients with diabetes. Echocardiography is an essential diagnostic modality commonly performed in patients with symptoms suggestive of cardiovascular diseases (CVD), such as dyspnea or chest pain, to establish or rule out the cause of symptoms. Conventional echocardiographic parameters, such as left ventricular ejection fraction, are helpful not only for diagnosing CVD but also for determining severity, treatment strategy, prognosis, and response to treatment. Echocardiographic myocardial strain, a novel echocardiographic technique, enables the detection of early changes in ventricular dysfunction before HF symptoms develop. This article aims to review the role of echocardiography in evaluating CVD in patients with diabetes mellitus and how to use it in patients with suspected cardiac diseases.

Basic Research
Mitochondrial-Encoded Peptide MOTS-c, Diabetes, and Aging-Related Diseases: Byung Soo Kong, Changhan Lee, Young Min Cho; Diabetes Metab J. 2023;47(3):315-324. Published online February 24, 2023; DOI: https://doi.org/10.4093/dmj.2022.0333; Funded: Seoul National University Hospital, Ministry of Science and ICT, National Institutes of Health

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Abstract PDF PubReader ePub Crossref - TDM: Mitochondria are complex metabolic organelles with manifold pathophysiological implications in diabetes. Currently published mitochondrial-encoded peptides, which are expressed from the mitochondrial open reading frame of the 12S ribosomal RNA type-c (MOTS-c), 16S rRNA (humanin and short humanin like peptide 1-6 [SHLP1-6]), or small human mitochondrial open reading frame over serine tRNA (SHMOOSE) are associated with regulation of cellular metabolism and insulin action in age-related diseases, such as type 2 diabetes mellitus. This review focuses mainly on recent advances in MOTS-c research with regards to diabetes, including both type 1 and type 2. The emerging understanding of MOTS-c in diabetes may provide insight into the development of new therapies for diabetes and other age or senescence-related diseases.

Original Articles

Metabolic Risk/Epidemiology
Novel Asian-Specific Visceral Adiposity Indices Are Associated with Chronic Kidney Disease in Korean Adults: Jonghwa Jin, Hyein Woo, Youngeun Jang, Won-Ki Lee, Jung-Guk Kim, In-Kyu Lee, Keun-Gyu Park, Yeon-Kyung Choi; Diabetes Metab J. 2023;47(3):426-436. Published online March 6, 2023; DOI: https://doi.org/10.4093/dmj.2022.0099; Funded: National Research Foundation of Korea, Ministry of Science and ICT, Ministry of Health and Welfare

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Abstract PDF Supplementary Material PubReader ePub Crossref - TDM

Background
The Chinese visceral adiposity index (CVAI) and new visceral adiposity index (NVAI) are novel indices of visceral adiposity used to predict metabolic and cardiovascular diseases in Asian populations. However, the relationships of CVAI and NVAI with chronic kidney disease (CKD) have not been investigated. We aimed to characterize the relationships of CVAI and NVAI with the prevalence of CKD in Korean adults.
Methods
A total of 14,068 participants in the 7th Korea National Health and Nutrition Examination Survey (6,182 men and 7,886 women) were included. Receiver operating characteristic (ROC) analyses were employed to compare the associations between indices of adiposity and CKD, and a logistic regression model was used to characterize the relationships of CVAI and NVAI with CKD prevalence.
Results
The areas under the ROC curves for CVAI and NVAI were significantly larger than for the other indices, including the visceral adiposity index and lipid accumulation product, in both men and women (all P<0.001). In addition, high CVAI or NVAI was significantly associated with a high CKD prevalence in both men (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.31 to 3.48 in CVAI and OR, 6.47; 95% CI, 2.91 to 14.38 in NVAI, P<0.05) and women (OR, 4.87; 95% CI, 1.85 to 12.79 in CVAI and OR, 3.03; 95% CI, 1.35 to 6.82 in NVAI, P<0.05); this association remained significant after adjustment for multiple confounding factors in men and women.
Conclusion
CVAI and NVAI are positively associated with CKD prevalence in a Korean population. CVAI and NVAI may be useful for the identification of CKD in Asian populations, including in Korea.

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Association between Chinese visceral adiposity index and risk of stroke incidence in middle-aged and elderly Chinese population: evidence from a large national cohort study
Zenglei Zhang, Lin Zhao, Yiting Lu, Xu Meng, Xianliang Zhou
Journal of Translational Medicine.2023;[Epub] CrossRef

COVID-19
Safety of COVID-19 Vaccines among Patients with Type 2 Diabetes Mellitus: Real-World Data Analysis: Hye Jun Kim, Sang Jun Lee, Soonok Sa, Jung Ho Bae, Gyuseon Song, Chae Won Lee, Ju Hee Kim, Sung Ryul Shim, Myunghee Hong, Hyun Wook Han; Diabetes Metab J. 2023;47(3):356-365. Published online March 6, 2023; DOI: https://doi.org/10.4093/dmj.2022.0129; Funded: Ministry of Trade, Industry and Energy, National IT Industry Promotion Agency, Ministry of Science and ICT, National Research Foundation of Korea, Ministry of Education, Institute of Information and Communications Technology Planning and Evaluation, Korea Health Industry Development Institute, Ministry of Health and Welfare

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Abstract PDF Supplementary Material PubReader ePub Crossref - TDM

Background
Little is known about the adverse events (AEs) associated with coronavirus disease 2019 (COVID-19) vaccination in patients with type 2 diabetes mellitus (T2DM).
Methods
This study used vaccine AE reporting system data to investigate severe AEs among vaccinated patients with T2DM. A natural language processing algorithm was applied to identify people with and without diabetes. After 1:3 matching, we collected data for 6,829 patients with T2DM and 20,487 healthy controls. Multiple logistic regression analysis was used to calculate the odds ratio for severe AEs.
Results
After COVID-19 vaccination, patients with T2DM were more likely to experience eight severe AEs than controls: cerebral venous sinus thrombosis, encephalitis myelitis encephalomyelitis, Bell’s palsy, lymphadenopathy, ischemic stroke, deep vein thrombosis (DVT), thrombocytopenia (TP), and pulmonary embolism (PE). Moreover, patients with T2DM vaccinated with BNT162b2 and mRNA-1273 were more vulnerable to DVT and TP than those vaccinated with JNJ-78436735. Among patients with T2DM administered mRNA vaccines, mRNA-1273 was safer than BNT162b2 in terms of the risk of DVT and PE.
Conclusion
Careful monitoring of severe AEs in patients with T2DM may be necessary, especially for those related to thrombotic events and neurological dysfunctions after COVID-19 vaccination.

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Tuberculosis vaccines update: Is an RNA-based vaccine feasible for tuberculosis?
Sasha E. Larsen, Susan L. Baldwin, Rhea N. Coler
International Journal of Infectious Diseases.2023; 130: S47. CrossRef
Neurological Disorders following COVID-19 Vaccination
Ying Yang, Lisu Huang
Vaccines.2023; 11(6): 1114. CrossRef

Basic Research
Role of SUMO-Specific Protease 2 in Leptin-Induced Fatty Acid Metabolism in White Adipocytes: Praise Chanmee Kim, Ji Seon Lee, Sung Soo Chung, Kyong Soo Park; Diabetes Metab J. 2023;47(3):382-393. Published online March 6, 2023; DOI: https://doi.org/10.4093/dmj.2022.0156; Funded: National Research Foundation of Korea, Ministry of Education

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Abstract PDF Supplementary Material PubReader ePub Crossref - TDM: Background
Leptin is a 16-kDa fat-derived hormone with a primary role in controlling adipose tissue levels. Leptin increases fatty acid oxidation (FAO) acutely through adenosine monophosphate-activated protein kinase (AMPK) and on delay through the SUMO-specific protease 2 (SENP2)–peroxisome proliferator-activated receptor δ/γ (PPARδ/γ) pathway in skeletal muscle. Leptin also directly increases FAO and decreases lipogenesis in adipocytes; however, the mechanism behind these effects remains unknown. Here, we investigated the role of SENP2 in the regulation of fatty acid metabolism by leptin in adipocytes and white adipose tissues.
Methods
The effects of leptin mediated by SENP2 on fatty acid metabolism were tested by siRNA-mediated knockdown in 3T3-L1 adipocytes. The role of SENP2 was confirmed in vivo using adipocyte-specific Senp2 knockout (Senp2-aKO) mice. We revealed the molecular mechanism involved in the leptin-induced transcriptional regulation of carnitine palmitoyl transferase 1b (Cpt1b) and long-chain acyl-coenzyme A synthetase 1 (Acsl1) using transfection/reporter assays and chromatin immunoprecipitation.
Results
SENP2 mediated the increased expression of FAO-associated enzymes, CPT1b and ACSL1, which peaked 24 hours after leptin treatment in adipocytes. In contrast, leptin stimulated FAO through AMPK during the initial several hours after treatment. In white adipose tissues, FAO and mRNA levels of Cpt1b and Acsl1 were increased by 2-fold 24 hours after leptin injection in control mice but not in Senp2-aKO mice. Leptin increased PPARα binding to the Cpt1b and Acsl1 promoters in adipocytes through SENP2.
Conclusion
These results suggest that the SENP2-PPARα pathway plays an important role in leptin-induced FAO in white adipocytes.

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; Funded: Chang Gung Memorial Hospital

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Abstract PDF Supplementary Material PubReader ePub Crossref - TDM

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.

Citations

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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

Sulwon Lecture 2022

Others
Opening the Precision Diabetes Care through Digital Healthcare: Joonyub Lee, Jin Yu, Kun-Ho Yoon; Diabetes Metab J. 2023;47(3):307-314. Published online March 29, 2023; DOI: https://doi.org/10.4093/dmj.2022.0386; Funded: Institute of Information and Communications Technology Planning and Evaluation, Ministry of Science and ICT, Ministry of Health and Welfare

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Abstract PDF PubReader ePub Crossref - TDM: The national healthcare systems of every country in the world cannot sustain the rise in healthcare expenditure caused by chronic diseases and their complications. To sustain the national healthcare system, a novel system should be developed to improve the quality of care and minimize healthcare costs. For 20 years, our team developed patient-communicating digital healthcare platforms and proved their efficacy. National scale randomized control trials are underway to systematically measure the efficacy and economic benefits of this digital health care system. Precision medicine aims to maximize effectiveness of disease management by considering individual variability. Digital health technologies enable precision medicine at a reasonable cost that was not available before. The government launched the “National Integrated Bio-big Data Project” which will collect diverse health data from the participants. Individuals will share their health information to physicians or researchers at their will by gateway named “My-Healthway.’ Taken together, now we stand in front of the evolution of medical care, so-called “Precision medicine.” led by various kinds of technologies and a huge amount of health information exchange. We should lead these new trends as pioneers, not as followers, to establish and implement the best care for our patients that can help them to withstand their devastating diseases.

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