Claudia Ha-Ting Tam, Ying Wang, Chi Chiu Wang, Lai Yuk Yuen, Cadmon King-Poo Lim, Junhong Leng, Ling Wu, Alex Chi-Wai Ng, Yong Hou, Kit Ying Tsoi, Hui Wang, Risa Ozaki, Albert Martin Li, Qingqing Wang, Juliana Chung-Ngor Chan, Yan Chou Ye, Wing Hung Tam, Xilin Yang, Ronald Ching-Wan Ma
{"title":"Identification and Potential Clinical Utility of Common Genetic Variants in Gestational Diabetes among Chinese Pregnant Women.","authors":"Claudia Ha-Ting Tam, Ying Wang, Chi Chiu Wang, Lai Yuk Yuen, Cadmon King-Poo Lim, Junhong Leng, Ling Wu, Alex Chi-Wai Ng, Yong Hou, Kit Ying Tsoi, Hui Wang, Risa Ozaki, Albert Martin Li, Qingqing Wang, Juliana Chung-Ngor Chan, Yan Chou Ye, Wing Hung Tam, Xilin Yang, Ronald Ching-Wan Ma","doi":"10.4093/dmj.2024.0139","DOIUrl":"10.4093/dmj.2024.0139","url":null,"abstract":"<p><strong>Backgruound: </strong>The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications.</p><p><strong>Methods: </strong>We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants.</p><p><strong>Results: </strong>Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI], 1.38 to 1.96), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals.</p><p><strong>Conclusion: </strong>Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.</p>","PeriodicalId":11153,"journal":{"name":"Diabetes & Metabolism Journal","volume":" ","pages":"128-143"},"PeriodicalIF":6.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11788552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Seung-Ah Lee, Subin Kim, Seog-Young Kim, Jong Yoen Park, Hye Seung Jung, Sung Soo Chung, Kyong Soo Park
{"title":"In Vivo Differentiation of Endogenous Bone Marrow-Derived Cells into Insulin-Producing Cells Using Four Soluble Factors.","authors":"Seung-Ah Lee, Subin Kim, Seog-Young Kim, Jong Yoen Park, Hye Seung Jung, Sung Soo Chung, Kyong Soo Park","doi":"10.4093/dmj.2024.0174","DOIUrl":"10.4093/dmj.2024.0174","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":11153,"journal":{"name":"Diabetes & Metabolism Journal","volume":" ","pages":"150-159"},"PeriodicalIF":6.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11788547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yu Meng Tian, Wei Sen Zhang, Chao Qiang Jiang, Feng Zhu, Ya Li Jin, Shiu Lun Au Yeung, Jiao Wang, Kar Keung Cheng, Tai Hing Lam, Lin Xu
{"title":"Longitudinal Association of Changes in Metabolic Syndrome with Cognitive Function: 12-Year Follow-up of the Guangzhou Biobank Cohort Study.","authors":"Yu Meng Tian, Wei Sen Zhang, Chao Qiang Jiang, Feng Zhu, Ya Li Jin, Shiu Lun Au Yeung, Jiao Wang, Kar Keung Cheng, Tai Hing Lam, Lin Xu","doi":"10.4093/dmj.2024.0117","DOIUrl":"10.4093/dmj.2024.0117","url":null,"abstract":"<p><strong>Backgruound: </strong>The association of changes in metabolic syndrome (MetS) with cognitive function remains unclear. We explored this association using prospective and Mendelian randomization (MR) studies.</p><p><strong>Methods: </strong>MetS components including high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), waist circumference (WC), fasting plasma glucose (FPG), and triglycerides were measured at baseline and two follow-ups, constructing a MetS index. Immediate, delayed memory recall, and cognitive function along with its dimensions were assessed by immediate 10- word recall test (IWRT) and delayed 10-word recall test (DWRT), and mini-mental state examination (MMSE), respectively, at baseline and follow-ups. Linear mixed-effect model was used. Additionally, the genome-wide association study (GWAS) of MetS was conducted and one-sample MR was performed to assess the causality between MetS and cognitive function.</p><p><strong>Results: </strong>Elevated MetS index was associated with decreasing annual change rates (decrease) in DWRT and MMSE scores, and with decreases in attention, calculation and recall dimensions. HDL-C was positively associated with an increase in DWRT scores, while SBP and FPG were negatively associated. HDL-C showed a positive association, whereas WC was negatively associated with increases in MMSE scores, including attention, calculation and recall dimensions. Interaction analysis indicated that the association of MetS index on cognitive decline was predominantly observed in low family income group. The GWAS of MetS identified some genetic variants. MR results showed a non-significant causality between MetS and decrease in DWRT, IWRT, nor MMSE scores.</p><p><strong>Conclusion: </strong>Our study indicated a significant association of MetS and its components with declines in memory and cognitive function, especially in delayed memory recall.</p>","PeriodicalId":11153,"journal":{"name":"Diabetes & Metabolism Journal","volume":" ","pages":"60-79"},"PeriodicalIF":6.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11788543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Diabetes in Korean Adults: Prevalence, Management, and Comorbidities.","authors":"Sung Hoon Yu","doi":"10.4093/dmj.2024.0844","DOIUrl":"10.4093/dmj.2024.0844","url":null,"abstract":"","PeriodicalId":11153,"journal":{"name":"Diabetes & Metabolism Journal","volume":"49 1","pages":"22-23"},"PeriodicalIF":6.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11788548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chang-Myung Oh, Ji-In Bang, Sang Yoon Lee, Jae Kyung Lee, Jee Won Chai, So Won Oh
{"title":"An Analysis of Age-Related Body Composition Changes and Metabolic Patterns in Korean Adults Using FDG-PET/CT Health Screening Data.","authors":"Chang-Myung Oh, Ji-In Bang, Sang Yoon Lee, Jae Kyung Lee, Jee Won Chai, So Won Oh","doi":"10.4093/dmj.2024.0057","DOIUrl":"10.4093/dmj.2024.0057","url":null,"abstract":"<p><strong>Backgruound: </strong>F-18-fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT) can be used to measure bone mineral density (BMD), cross-sectional muscle area (CSMA), Hounsfield units (HU) of liver and muscle, subcutaneous adipose tissue (SAT), abdominal visceral adipose tissue (VAT), and glucose metabolism. The present study aimed to identify age-related changes in body composition and glucose metabolism in Korean using opportunistic FDG-PET/CT imaging.</p><p><strong>Methods: </strong>We analyzed FDG-PET/CT, clinical history, and laboratory data abstracted from the medical records of patients who underwent health screening at a single institute between 2017 and 2022.</p><p><strong>Results: </strong>In total, 278 patients were included in the analysis (male:female=140:138). Age and body mass index were positively correlated in female, but negatively correlated in male. BMD decreased with age more in female, and CSMA decreased with age more in male. Muscle HU decreased with age for both sexes. In female, SAT and VAT increased with age; and in male, SAT decreased slightly while VAT remained stable. Muscle glucose metabolism showed no association with age in male but increased with age in female. CSMA correlated positively with BMD overall; and positively correlated with VAT and SAT in male only. In female only, both SAT and VAT showed negative correlations with glucose metabolism and correlated positively with muscle glucose metabolism. Liver HU values were inversely correlated with VAT, especially in female; and positively correlated with muscle glucose metabolism in female only.</p><p><strong>Conclusion: </strong>FDG-PET/CT demonstrated distinct patterns of age-related changes in body composition and glucose metabolism, with significant differences between sexes.</p>","PeriodicalId":11153,"journal":{"name":"Diabetes & Metabolism Journal","volume":" ","pages":"92-104"},"PeriodicalIF":6.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11788554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Single-Cell Landscape and a Macrophage Subset Enhancing Brown Adipocyte Function in Diabetes (Diabetes Metab J 2024;48:885-900).","authors":"Yea Eun Kang, Ju Hee Lee","doi":"10.4093/dmj.2024.0739","DOIUrl":"10.4093/dmj.2024.0739","url":null,"abstract":"","PeriodicalId":11153,"journal":{"name":"Diabetes & Metabolism Journal","volume":"49 1","pages":"160-161"},"PeriodicalIF":6.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11788549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Shionone Inhibits Glomerular Fibirosis by Suppressing NLRP3 Related Inflammasome though SESN2-NRF2/ HO-1 Pathway.","authors":"Tian Xiao, Hanzhen Zhao, Yucong Wang, Mengyin Chen, Cong Wang, Chen Qiao","doi":"10.4093/dmj.2024.0024","DOIUrl":"10.4093/dmj.2024.0024","url":null,"abstract":"<p><strong>Backgruound: </strong>Diabetic nephropathy (DN) is the most common and serious complication of diabetes mellitus. Shionone (SH), an important triterpenoid compound in the root extract of Aster, might exert a protective effect in DN mice and high glucose cultivated glomerular podocytes. The current study aimed to unravel the underlying mechanism by which SH mitigates DN. We postulate that SH stimulates the expression of sestrin-2 (SESN2), a pivotal stress-inducible protein in the anti-inflammasome machinery.</p><p><strong>Methods: </strong>We utilized high-fat diet combined with streptozotocin (55 mg/kg intraperitoneal) for DN mice model, and high glucose (30 mM, 48 hours) cultured glomerular podocytes for DN cell model to evaluate the effect of SH. We also preformed experimentation on SESN2 deficiency models (SESN2 knockout mice and SESN2 siRNA in cells) to further prove our hypothesis.</p><p><strong>Results: </strong>The results demonstrated that SH effectively suppressed glomerular fibrosis, induced adenosine monophosphate-activated protein kinase (AMPK) phosphorylation, and inhibited NLR family pyrin domain containing 3 (NLRP3) activation. Furthermore, our findings revealed that SH exerted its anti-inflammatory effect through Sesn2-dependent nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation and subsequent activation of its downstream target heme oxygenase-1 (HO-1).</p><p><strong>Conclusion: </strong>In summary, our findings suggest that SH serves as a promising therapeutic agent for the treatment of DN-related glomerular fibrosis. SH enhances the expression of SESN2, attenuates α-smooth muscle actin accumulation, and suppresses NLRP3-related inflammation through the Nrf2/HO-1 signaling pathway.</p>","PeriodicalId":11153,"journal":{"name":"Diabetes & Metabolism Journal","volume":" ","pages":"34-48"},"PeriodicalIF":6.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11788555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xue Zhang, Yuhan Zhang, Yang Shi, Dou Shi, Min Niu, Xue Liu, Xing Liu, Zhiwei Yang, Xianxian Wu
{"title":"Kidney Gastrin/CCKBR Attenuates Type 2 Diabetes Mellitus by Inhibiting SGLT2-Mediated Glucose Reabsorption through Erk/NF-κB Signaling Pathway.","authors":"Xue Zhang, Yuhan Zhang, Yang Shi, Dou Shi, Min Niu, Xue Liu, Xing Liu, Zhiwei Yang, Xianxian Wu","doi":"10.4093/dmj.2023.0397","DOIUrl":"https://doi.org/10.4093/dmj.2023.0397","url":null,"abstract":"<p><strong>Background: </strong>Both sodium-glucose cotransporters (SGLTs) and Na+/H+ exchangers (NHEs) rely on a favorable Na-electrochemical gradient. Gastrin, through the cholecystokinin B receptor (CCKBR), can induce natriuresis and diuresis by inhibiting renal NHEs activity. The present study aims to unveil the role of renal CCKBR in diabetes through SGLT2-mediated glucose reabsorption.</p><p><strong>Methods: </strong>Renal tubule-specific Cckbr-knockout (CckbrCKO) mice and wild-type (WT) mice were utilized to investigate the effect of renal CCKBR on SGLT2 and systemic glucose homeostasis under normal diet, high-fat diet (HFD), and HFD with a subsequent injection of a low dose of streptozotocin. The regulation of SGLT2 expression by gastrin/CCKBR and the underlying mechanism was explored using human kidney (HK)-2 cells.</p><p><strong>Results: </strong>CCKBR was downregulated in kidneys of diabetic mice. Compared with WT mice, CckbrCKO mice exhibited a greater susceptibility to obesity and diabetes when subjected to HFD. <italic>In vitro</italic> experiments using HK-2 cells revealed an upregulation of glucose transporters after incubation with high glucose, a response that was significantly attenuated following gastrin intervention. The glucose uptake from the culture medium of cells was altered accordingly. Moreover, gastrin administration effectively mitigated hyperglycemia in WT diabetic mice by inhibition of SGLT2 mediated glucose reabsorption, but this effect was compromised in the absence of CCKBR, as seen in CckbrCKO mice. Mechanistically, gastrin/CCKBR substantially reduced SGLT2 expression in HK-2 cells exposed to high glucose, via modulating Erk/nuclear factor-kappa B (NF-κB) pathway.</p><p><strong>Conclusion: </strong>Our study underscores the crucial role of renal gastrin/CCKBR in SGLT2 regulation and glucose reabsorption, and renal gastrin/CCKBR can be a promising therapeutic target for diabetes.</p>","PeriodicalId":11153,"journal":{"name":"Diabetes & Metabolism Journal","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Do Time-Dependent Repeated Measures of Anthropometric and Body Composition Indices Improve the Prediction of Incident Diabetes in the Cohort Study? Findings from a Community-Based Korean Genome and Epidemiology Study.","authors":"Hye Ah Lee, Hyesook Park, Bomi Park","doi":"10.4093/dmj.2024.0357","DOIUrl":"10.4093/dmj.2024.0357","url":null,"abstract":"<p><strong>Background: </strong>Cumulative evidence consistently shows that anthropometric and body composition measurements are strongly linked to the risk of incident diabetes, typically based on baseline measurements. This study aims to assess whether repeated measurements enhance the prediction of diabetes risk beyond baseline assessments alone.</p><p><strong>Methods: </strong>We utilized data from a 16-year population-based follow-up cohort within the Korean Genome and Epidemiology Study, comprising 6,030 individuals aged 40 to 69 years at baseline. We included eight indices: a body shape index (ABSI), body adiposity index (BAI), waist circumference (WC), body mass index (BMI), waist-to-hip ratio (WHR), weight-adjusted skeletal muscle index (SMI), percent body fat, and fat-to-muscle ratio. The effect of these measurements for incident diabetes was estimated using Harrell's C-indexes and hazard ratios with 95% confidence intervals, employing time-dependent Cox proportional hazard models.</p><p><strong>Results: </strong>Over the 16-year follow-up, 939 new diabetes cases were identified (cumulative incidence, 15.6%). The median number of indicator measurements per participant was eight. The basic model, including 10 features (sex, age, education levels, physical activity, alcohol intake, current smoking, total energy intake, dietary diversity score, and log-transformed C-reactive protein levels, and quartiles of unweighted genetic risk score at baseline), yielded a Harrell's C-index of 0.610. The highest C-index in repeated measurements was for WC (0.668) across the general population, weight-adjusted SMI in men, and WHR in women. However, except for ABSI and BAI, the diabetes predictive power of the other indicators was comparable. Additionally, repeated measurements of WC, BMI, and WHR in women were found to contribute to improved discrimination compared to baseline measurements, but not in men.</p><p><strong>Conclusion: </strong>Utilizing repeated measurements of general and central adiposity to predict diabetes may be helpful in predicting hidden risks, especially in women.</p>","PeriodicalId":11153,"journal":{"name":"Diabetes & Metabolism Journal","volume":" ","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}