Pub Date : 2024-06-24DOI: 10.1101/2024.06.24.24309093
Maria C Foss-Freitas, Donatella Gilio, Andre Monteiro da Rocha, Lynn Pais, Melanie O'Leary, Heidi L. Rehm, Adam Neidert, Miriam S. Udler, Patrick Seale, Elif A. Oral, Tae-Hwa Chun
We report a novel cause of partial lipodystrophy associated with early B cell factor 2 (EBF2) nonsense variant (EBF2 8:26033143 C>A, c.493G>T, p.E165X) in a patient with an atypical form of partial lipodystrophy. The patient presented with progressive adipose tissue loss and metabolic deterioration at pre-pubertal age. In vitro and in vivo disease modeling demonstrates that the EBF2 variant impairs adipogenesis, causing excess accumulation of undifferentiated CD34+ cells, extracellular matrix proteins, and inflammatory myeloid cells in subcutaneous adipose tissues. Thus, this EBF2 p.E165X variant disrupts adipose tissue structure and function, leading to the development of partial lipodystrophy syndrome.
{"title":"Early B-cell transcription factor-2 defect as a novel cause of lipodystrophy: disruption of the adipose tissue character and integrity.","authors":"Maria C Foss-Freitas, Donatella Gilio, Andre Monteiro da Rocha, Lynn Pais, Melanie O'Leary, Heidi L. Rehm, Adam Neidert, Miriam S. Udler, Patrick Seale, Elif A. Oral, Tae-Hwa Chun","doi":"10.1101/2024.06.24.24309093","DOIUrl":"https://doi.org/10.1101/2024.06.24.24309093","url":null,"abstract":"We report a novel cause of partial lipodystrophy associated with early B cell factor 2 (EBF2) nonsense variant (EBF2 8:26033143 C>A, c.493G>T, p.E165X) in a patient with an atypical form of partial lipodystrophy. The patient presented with progressive adipose tissue loss and metabolic deterioration at pre-pubertal age. In vitro and in vivo disease modeling demonstrates that the EBF2 variant impairs adipogenesis, causing excess accumulation of undifferentiated CD34+ cells, extracellular matrix proteins, and inflammatory myeloid cells in subcutaneous adipose tissues. Thus, this EBF2 p.E165X variant disrupts adipose tissue structure and function, leading to the development of partial lipodystrophy syndrome.","PeriodicalId":501419,"journal":{"name":"medRxiv - Endocrinology","volume":"144 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141529065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-24DOI: 10.1101/2024.06.23.24308327
Shamim Hossan, Md. Shahed Morshed, Hurjahan Banu, Muhammad Abul Hasanat
Background: Women with polycystic ovarian syndrome (PCOS) have hyperandrogenemia and insulin resistance, which predispose them to prothrombotic conditions. D-dimer is a global marker of hemostatic dysfunction that has a contentious relationship with PCOS. Objective: To assess the association of D-dimer with PCOS and its manifestations Methods: This case-control study enrolled 44 women with PCOS based on the International Evidence-based Guideline, 2018, and an equal number of matched healthy controls by convenient sampling. After obtaining informed consent, participants' clinical data was taken, and fasting blood was drawn to measure glucose, lipid profile, hormones, and D-dimer. D-dimer was analyzed by latex immunofluorescence assay. Results: The D-dimer levels and status were statistically similar between the study groups [PCOS vs. control: 0.11 (0.10-0.17) vs. 0.13 (0.10-0.22), median (IQR), p= 0.673]. D-dimer levels did not vary according to the different characteristics of women with PCOS (p>0.05). D-dimer levels had no significant correlations with various clinical and biochemical characteristics among women with PCOS (p>0.05). Conclusion: D-dimer has no significant association with PCOS or its manifestations.
背景：患有多囊卵巢综合征（PCOS）的妇女会出现高雄激素血症和胰岛素抵抗，从而容易导致血栓形成。D-二聚体是止血功能障碍的全球标志物，与多囊卵巢综合征的关系存在争议：目的：评估 D-二聚体与多囊卵巢综合征及其表现的关系：这项病例对照研究根据《2018年国际循证指南》招募了44名患有多囊卵巢综合征的女性，并通过方便抽样的方式招募了同等数量的匹配健康对照者。在获得知情同意后，采集参与者的临床数据，并抽取空腹血测量血糖、血脂、激素和D-二聚体。D-二聚体采用乳胶免疫荧光测定法进行分析：结果：研究组之间的 D-二聚体水平和状态在统计学上相似[多囊卵巢综合征组 vs. 对照组：0.11 (0.10-0.17) vs. 0.13 (0.10-0.22)，中位数（IQR），p= 0.673]。D-二聚体水平与多囊卵巢综合症妇女的不同特征无关（p>0.05）。D-二聚体水平与多囊卵巢综合征妇女的各种临床和生化特征无明显相关性（p>0.05）：结论：D-二聚体与多囊卵巢综合征或其表现无明显关联。
{"title":"Serum D-dimer level in women with polycystic ovary syndrome","authors":"Shamim Hossan, Md. Shahed Morshed, Hurjahan Banu, Muhammad Abul Hasanat","doi":"10.1101/2024.06.23.24308327","DOIUrl":"https://doi.org/10.1101/2024.06.23.24308327","url":null,"abstract":"Background: Women with polycystic ovarian syndrome (PCOS) have hyperandrogenemia and insulin resistance, which predispose them to prothrombotic conditions. D-dimer is a global marker of hemostatic dysfunction that has a contentious relationship with PCOS.\u0000Objective: To assess the association of D-dimer with PCOS and its manifestations\u0000Methods: This case-control study enrolled 44 women with PCOS based on the International Evidence-based Guideline, 2018, and an equal number of matched healthy controls by convenient sampling. After obtaining informed consent, participants' clinical data was taken, and fasting blood was drawn to measure glucose, lipid profile, hormones, and D-dimer. D-dimer was analyzed by latex immunofluorescence assay.\u0000Results: The D-dimer levels and status were statistically similar between the study groups [PCOS vs. control: 0.11 (0.10-0.17) vs. 0.13 (0.10-0.22), median (IQR), p= 0.673]. D-dimer levels did not vary according to the different characteristics of women with PCOS (p>0.05). D-dimer levels had no significant correlations with various clinical and biochemical characteristics among women with PCOS (p>0.05).\u0000Conclusion: D-dimer has no significant association with PCOS or its manifestations.","PeriodicalId":501419,"journal":{"name":"medRxiv - Endocrinology","volume":"36 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141515892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-21DOI: 10.1101/2024.06.19.24309106
Arrigo F. G. Cicero, Patrizia Giovanni Uboldi, Giangiacomo Beretta, Federica Fogacci, Elisa Grandi, Monika Svecla, Giuseppe Danilo Norata
Red yeast rice (RYR) is a traditional Chinese product obtained by fermenting rice with the yeast Monascus purpureus and contains monacolin K, which is chemically identical to lovastatin, a drug with cholesterol-lowering activity. The European Food Safety Authority (EFSA) has evaluated the safety and efficacy of RYR supplements for managing cholesterol levels. In 2018, EFSA published a scientific opinion on the use of monacolin K from RYR in food supplements, concluding that monacolins from RYR may raise significant safety concerns at a use level of 10 mg/ day. Following that, the European Commission declared in 2022 that RYR products must contain less than 3 mg of monacolins for daily consumption. The aim of this work was to perform a comprehensive profiling of plasma markers of muscle and liver dysfunction by extensive untargeted plasma proteomics in healthy volunteers with suboptimal cholesterolaemia who were randomly assigned to receive a dietary supplement containing RYR (total monacolin <3 mg) or placebo for one month. No changes in classical markers of liver (AST, ALT) or muscle (CPK) function were detected in the plasma samples of patients treated with the supplement compared to placebo. Interestingly, the analysis of circulating proteins marking an early acute response in the liver, such as serum amyloid A4, orosomucoid 2, haptoglobin-related protein, prothrombin, α-1-antitrypsin, α-2-HS-glycoprotein, serum amyloid P (APCS), orosomucoid 1, c-reactive protein (CRP) and α-2-macroglobulin confirmed an overlapping profile in the two groups. Similarly, the analysis of ryanodine receptor 1, titin, dystrophin and myosin 7 again showed a similar profile in the two groups. These data indicate that a low dose of monacolin K (<3 mg/day) in subjects with suboptimal cholesterolaemia does not increase levels of markers of liver and skeletal muscle function in plasma, excluding a deleterious effect of monacolin K on these tissues.
{"title":"Effects of low-dose monacolin K on the circulating proteome in individuals with suboptimal cholesterolaemia: A randomised clinical trial","authors":"Arrigo F. G. Cicero, Patrizia Giovanni Uboldi, Giangiacomo Beretta, Federica Fogacci, Elisa Grandi, Monika Svecla, Giuseppe Danilo Norata","doi":"10.1101/2024.06.19.24309106","DOIUrl":"https://doi.org/10.1101/2024.06.19.24309106","url":null,"abstract":"Red yeast rice (RYR) is a traditional Chinese product obtained by fermenting rice with the yeast Monascus purpureus and contains monacolin K, which is chemically identical to lovastatin, a drug with cholesterol-lowering activity. The European Food Safety Authority (EFSA) has evaluated the safety and efficacy of RYR supplements for managing cholesterol levels. In 2018, EFSA published a scientific opinion on the use of monacolin K from RYR in food supplements, concluding that monacolins from RYR may raise significant safety concerns at a use level of 10 mg/ day. Following that, the European Commission declared in 2022 that RYR products must contain less than 3 mg of monacolins for daily consumption. The aim of this work was to perform a comprehensive profiling of plasma markers of muscle and liver dysfunction by extensive untargeted plasma proteomics in healthy volunteers with suboptimal cholesterolaemia who were randomly assigned to receive a dietary supplement containing RYR (total monacolin <3 mg) or placebo for one month.\u0000No changes in classical markers of liver (AST, ALT) or muscle (CPK) function were detected in the plasma samples of patients treated with the supplement compared to placebo. Interestingly, the analysis of circulating proteins marking an early acute response in the liver, such as serum amyloid A4, orosomucoid 2, haptoglobin-related protein, prothrombin, α-1-antitrypsin, α-2-HS-glycoprotein, serum amyloid P (APCS), orosomucoid 1, c-reactive protein (CRP) and α-2-macroglobulin confirmed an overlapping profile in the two groups. Similarly, the analysis of ryanodine receptor 1, titin, dystrophin and myosin 7 again showed a similar profile in the two groups. These data indicate that a low dose of monacolin K (<3 mg/day) in subjects with suboptimal cholesterolaemia does not increase levels of markers of liver and skeletal muscle function in plasma, excluding a deleterious effect of monacolin K on these tissues.","PeriodicalId":501419,"journal":{"name":"medRxiv - Endocrinology","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141515893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-21DOI: 10.1101/2024.06.20.24309152
Catherine Russon, Michael Allen, Michael Saunby, Richard M Pulsford, Neil Vaughan, Matthew Cocks, Jonathan L Low, Katie L Hesketh, Robert C Andrews
Background: Continuous Glucose Monitoring (CGM) systems have revolutionized diabetes management by providing real-time blood glucose tracking. However, there is a need for openly accessible tools that can analyze CGM data in relation to specific events like meals or exercise, which often require extensive technical skills to interpret, thus restricting its broader use among researchers and clinicians. Developing user-friendly web applications to facilitate this analysis could significantly broaden accessibility and utility. Method: Diametrics was built with a focus on ease-of-use and versatility. The application's efficacy was validated against iglu, an established R tool with a no-code web app for CGM analysis, using data from 418 participants from three studies. The unique period-specific analysis feature was demonstrated through an illustrative case study. Results: Diametrics proved effective at replicated established CGM metrics, demonstrating high concordance with iglu. The platform supports a wide range of CGM devices, accommodates data in various formats, and offers extensive customization in the analysis settings. The case study highlighted Diametrics' ability to integrate exercise-related data with CGM readings, enabling detailed analyses of how different exercise types, intensities, and times of day impact glucose levels. Conclusions: Diametrics is a freely available, reproducible, user-friendly, and accurate web-based tool for CGM data analysis with a unique capability to analyze data over specific time periods. With its intuitive design and open-source accessibility, Diametrics provides a valuable resource in diabetes research and management, empowering users of various technical levels to perform complex analyses with ease.
{"title":"Diametrics: A User-Friendly Web Tool for Custom Analysis of Continuous Glucose Monitoring Data","authors":"Catherine Russon, Michael Allen, Michael Saunby, Richard M Pulsford, Neil Vaughan, Matthew Cocks, Jonathan L Low, Katie L Hesketh, Robert C Andrews","doi":"10.1101/2024.06.20.24309152","DOIUrl":"https://doi.org/10.1101/2024.06.20.24309152","url":null,"abstract":"Background: Continuous Glucose Monitoring (CGM) systems have revolutionized diabetes management by providing real-time blood glucose tracking. However, there is a need for openly accessible tools that can analyze CGM data in relation to specific events like meals or exercise, which often require extensive technical skills to interpret, thus restricting its broader use among researchers and clinicians. Developing user-friendly web applications to facilitate this analysis could significantly broaden accessibility and utility.\u0000Method: Diametrics was built with a focus on ease-of-use and versatility. The application's efficacy was validated against iglu, an established R tool with a no-code web app for CGM analysis, using data from 418 participants from three studies. The unique period-specific analysis feature was demonstrated through an illustrative case study.\u0000Results: Diametrics proved effective at replicated established CGM metrics, demonstrating high concordance with iglu. The platform supports a wide range of CGM devices, accommodates data in various formats, and offers extensive customization in the analysis settings. The case study highlighted Diametrics' ability to integrate exercise-related data with CGM readings, enabling detailed analyses of how different exercise types, intensities, and times of day impact glucose levels.\u0000Conclusions: Diametrics is a freely available, reproducible, user-friendly, and accurate web-based tool for CGM data analysis with a unique capability to analyze data over specific time periods. With its intuitive design and open-source accessibility, Diametrics provides a valuable resource in diabetes research and management, empowering users of various technical levels to perform complex analyses with ease.","PeriodicalId":501419,"journal":{"name":"medRxiv - Endocrinology","volume":"76 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141529064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-21DOI: 10.1101/2024.06.20.24309238
Li Li, Cheng-bo Li, Li Zhu, Jiang Zhu
Objective— This research aimed to explore the correlation between serum Neurofilament Light Chain (NfL) levels and Cognitive Function in diabetic participants. Methods — Utilizing cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) 2013 to 2014, 173 individuals aged 60 years and above with diabetes were included in the analysis. Cognitive function was measured using the Animal Fluency exercise. Weighted multivariate linear regression analysis and a restricted cubic spline model were employed to assess the association between serum NfL levels and Animal Fluency Score (CFDAST) in diabetic patients.Results— Serum NfL was categorized into weighted tertiles, with participants divided into groups Q1, Q2, and Q3. Significant differences in serum NfL were observed among the groups (P < 0.01). Participants in group Q3 exhibited higher levels of hemoglobin A1c and were older compared to groups Q1 and Q2 (P < 0.01). Furthermore, when serum NfL was treated as a continuous variable, it was found to have a negative correlation with CFDAST score (P < 0.01). Group Q1 had a higher CFDAST score than group Q3, as well as group Q2 (p for trend = 0.0021). A nonlinear relationship was observed between serum NfL and CFDAST score, displaying an inverted 'U-shaped' curve (P-overall = 0.01, P-for-non-linear = 0.0026). Conclusions— Serum NfL has the potential to serve as a clinical biomarker for early detection of cognitive impairment in diabetic individuals aged over 60 years.
{"title":"The association between NfL and Cognitive Functioning in older adults diagnosed diabetes: a cross-sectional analysis from NHANES","authors":"Li Li, Cheng-bo Li, Li Zhu, Jiang Zhu","doi":"10.1101/2024.06.20.24309238","DOIUrl":"https://doi.org/10.1101/2024.06.20.24309238","url":null,"abstract":"Objective— This research aimed to explore the correlation between serum Neurofilament Light Chain (NfL) levels and Cognitive Function in diabetic participants.\u0000Methods — Utilizing cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) 2013 to 2014, 173 individuals aged 60 years and above with diabetes were included in the analysis. Cognitive function was measured using the Animal Fluency exercise. Weighted multivariate linear regression analysis and a restricted cubic spline model were employed to assess the association between serum NfL levels and Animal Fluency Score (CFDAST) in diabetic patients.Results— Serum NfL was categorized into weighted tertiles, with participants divided into groups Q1, Q2, and Q3. Significant differences in serum NfL were observed among the groups (P < 0.01). Participants in group Q3 exhibited higher levels of hemoglobin A1c and were older compared to groups Q1 and Q2 (P < 0.01). Furthermore, when serum NfL was treated as a continuous variable, it was found to have a negative correlation with CFDAST score (P < 0.01). Group Q1 had a higher CFDAST score than group Q3, as well as group Q2 (p for trend = 0.0021). A nonlinear relationship was observed between serum NfL and CFDAST score, displaying an inverted 'U-shaped' curve (P-overall = 0.01, P-for-non-linear = 0.0026).\u0000Conclusions— Serum NfL has the potential to serve as a clinical biomarker for early detection of cognitive impairment in diabetic individuals aged over 60 years.","PeriodicalId":501419,"journal":{"name":"medRxiv - Endocrinology","volume":"28 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141515894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Leptin is a fat cell-derived hormone involved in satiety and body weight regulation. It also plays a critical regulatory role in the insulin-glucose regulatory system by modulating glucose metabolism and energy homeostasis. However, existing insulin-glucose models often fail to consider the impact of body weight indicators mainly body mass index (BMI) and plasma leptin. To address this limitation, we propose augmenting the ordinary differential equations (ODE) of the Oral Minimal Model (OMM) with an additional equation, incorporating leptin as well as supplementary terms and parameters. By estimating the model parameters, the model behaviour is aligned with the observed data of glucose, insulin and leptin for individuals with type 2 diabetes mellitus (T2DM). Based on model behaviour, revised indices formulated from Oral Glucose Tolerance Test (OGTT) data by including BMI and fasting leptin values are found to have a better correlation with existing indices. Additionally, parameter sensitivity analysis is performed to investigate the influence of the model parameters on the observed variables. Validation of the augmented model with clinical data (without leptin) demonstrates a superior fit to glucose and insulin data compared to the base model. This model emphasizes the intricate associations between leptin, glucose, and insulin concentrations with a potential for developing targeted interventions and therapies for T2DM. Notably, this manuscript introduces the first ODE-based model that incorporates leptin and BMI in the insulin-glucose pathway.
{"title":"Leptin augmented model to include the role of obesity in insulin-glucose regulatory system for T2DM subjects","authors":"MANOJA RAJALAKSHMI ARAVINDAKSHAN, Devleena Ghosh, Chittaranjan Mandal, Jit Sarkar, Sujay Krishna Maity, Partha Chakrabarti","doi":"10.1101/2024.06.18.24309097","DOIUrl":"https://doi.org/10.1101/2024.06.18.24309097","url":null,"abstract":"Leptin is a fat cell-derived hormone involved in satiety and body weight regulation. It also plays a critical regulatory role in the insulin-glucose regulatory system by modulating glucose metabolism and energy homeostasis. However, existing insulin-glucose models often fail to consider the impact of body weight indicators mainly body mass index (BMI) and plasma leptin. To address this limitation, we propose augmenting the ordinary differential equations (ODE) of the Oral Minimal Model (OMM)\u0000with an additional equation, incorporating leptin as well as supplementary terms and parameters. By estimating the model parameters, the model behaviour is aligned with the observed data of glucose, insulin and leptin for individuals with type 2 diabetes mellitus (T2DM). Based on model behaviour, revised indices formulated from Oral Glucose Tolerance Test (OGTT) data by including BMI and fasting leptin values are found\u0000to have a better correlation with existing indices. Additionally, parameter\u0000sensitivity analysis is performed to investigate the influence of the model\u0000parameters on the observed variables. Validation of the augmented model\u0000with clinical data (without leptin) demonstrates a superior fit to glucose and insulin data compared to the base model. This model emphasizes the intricate associations between leptin, glucose, and insulin concentrations with a potential for developing targeted interventions and therapies\u0000for T2DM. Notably, this manuscript introduces the first ODE-based model that incorporates leptin and BMI in the insulin-glucose pathway.","PeriodicalId":501419,"journal":{"name":"medRxiv - Endocrinology","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141515926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-19DOI: 10.1101/2024.06.18.24309073
Emmanuel Arthur Mfundo, Alphonce Ignace Marealle, Goodluck G. Nyondo, Martine A. Manguzu, Deus Buma, Peter Kunambi, Ritah F Mutagonda
Background Poor glycemic control in diabetic chronic kidney disease (CKD) patients on maintenance hemodialysis is of great challenge, resulting in increased risk of morbidity and mortality. This study aimed to determine the prevalence and determinants of poor glycemic control among diabetic CKD patients on maintenance hemodialysis. Methodology A cross-sectional study was conducted in 12 dialysis centers located in four regions of Tanzania from March to June 2023. The study population was diabetic CKD patients above 18 years on maintenance hemodialysis for three months or more. A consecutive sampling technique was used for patient recruitment, and a semi-structured questionnaire was used to collect data. The primary outcome was poor glycemic control which was considered when glycated hemoglobin (HbA1c) levels were < 6% or >8%. Statistical Package for Social Sciences (SPSS) version 23 was used for data analysis. Univariate and multivariable regression models were used to evaluate the determinants of poor glycemic control. A p-value <0.05 was considered statistically significant. Results Out of 233 enrolled patients, the overall prevalence of poor glycemic control was 55.4%, whereby 27.0% had HbA1c <6% and 28.33% had HbA1c >8%. A high risk of HbA1c >8% was observed among patients who were on antidiabetic medication (2.16 (95% CI: 1.06– 4.41) p = 0.035) and those attending dialysis sessions less than 3 times a week (1.59 (95% CI: 1.02– 2.48) p = 0.04). While the predictor of HbA1c <6% was the type of dialyzer used (0.57 (95% CI 0.36 – 0.87) p = 0.020). Conclusion There is a high prevalence of poor glycemic control among diabetic CKD patients. Patients who were on antidiabetic medication and those who had less than three dialysis sessions had a high risk of HbA1c >8%. In contrast, those dialyzed using glucose-free dialysates had a high risk of HbA1c <6%.
{"title":"Prevalence and determinants of poor glycemic control among diabetic chronic kidney disease patients on maintenance hemodialysis in Tanzania","authors":"Emmanuel Arthur Mfundo, Alphonce Ignace Marealle, Goodluck G. Nyondo, Martine A. Manguzu, Deus Buma, Peter Kunambi, Ritah F Mutagonda","doi":"10.1101/2024.06.18.24309073","DOIUrl":"https://doi.org/10.1101/2024.06.18.24309073","url":null,"abstract":"Background Poor glycemic control in diabetic chronic kidney disease (CKD) patients on maintenance hemodialysis is of great challenge, resulting in increased risk of morbidity and mortality. This study aimed to determine the prevalence and determinants of poor glycemic control among diabetic CKD patients on maintenance hemodialysis. Methodology A cross-sectional study was conducted in 12 dialysis centers located in four regions of Tanzania from March to June 2023. The study population was diabetic CKD patients above 18 years on maintenance hemodialysis for three months or more. A consecutive sampling technique was used for patient recruitment, and a semi-structured questionnaire was used to collect data. The primary outcome was poor glycemic control which was considered when glycated hemoglobin (HbA1c) levels were < 6% or >8%. Statistical Package for Social Sciences (SPSS) version 23 was used for data analysis. Univariate and multivariable regression models were used to evaluate the determinants of poor glycemic control. A p-value <0.05 was considered statistically significant. Results Out of 233 enrolled patients, the overall prevalence of poor glycemic control was 55.4%, whereby 27.0% had HbA1c <6% and 28.33% had HbA1c >8%. A high risk of HbA1c >8% was observed among patients who were on antidiabetic medication (2.16 (95% CI: 1.06– 4.41) p = 0.035) and those attending dialysis sessions less than 3 times a week (1.59 (95% CI: 1.02– 2.48) p = 0.04). While the predictor of HbA1c <6% was the type of dialyzer used (0.57 (95% CI 0.36 – 0.87) p = 0.020). Conclusion There is a high prevalence of poor glycemic control among diabetic CKD patients. Patients who were on antidiabetic medication and those who had less than three dialysis sessions had a high risk of HbA1c >8%. In contrast, those dialyzed using glucose-free dialysates had a high risk of HbA1c <6%.","PeriodicalId":501419,"journal":{"name":"medRxiv - Endocrinology","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141515895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background Curcumin, which is derived from turmeric root and is widely utilized in Asian cuisines, exhibits notable anti-inflammatory effects. Its consumption has proven beneficial in alleviating inflammation-related disorders such as ulcerative colitis, rheumatoid arthritis, and esophagitis. These anti-inflammatory properties might also provide advantages in reducing cardiovascular complications, such as atherosclerosis, which is particularly prevalent among diabetic individuals. This study aimed to evaluate the efficacy of curcumin in decreasing the risk of atherogenesis in obese patients with type 2 diabetes.
{"title":"Curcumin Extract Diminishes Atherogenic Risk in Type 2 Diabetes Mellitus Patients With Obesity","authors":"Metha Yaikwawong, Laddawan Jansarikit, Siwanon Jirawatnotai, Somlak Chuengsamarn","doi":"10.1101/2024.05.30.24308243","DOIUrl":"https://doi.org/10.1101/2024.05.30.24308243","url":null,"abstract":"<strong>Background</strong> Curcumin, which is derived from turmeric root and is widely utilized in Asian cuisines, exhibits notable anti-inflammatory effects. Its consumption has proven beneficial in alleviating inflammation-related disorders such as ulcerative colitis, rheumatoid arthritis, and esophagitis. These anti-inflammatory properties might also provide advantages in reducing cardiovascular complications, such as atherosclerosis, which is particularly prevalent among diabetic individuals. This study aimed to evaluate the efficacy of curcumin in decreasing the risk of atherogenesis in obese patients with type 2 diabetes.","PeriodicalId":501419,"journal":{"name":"medRxiv - Endocrinology","volume":"104 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141253525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-28DOI: 10.1101/2024.05.28.24308009
Yujian Liang, Charlie G.Y. Lim, Scott C. Ritchie, Nicolas Bertin, Jin-Fang Chai, Jiali Yao, Yun Li, E Shyong Tai, Rob M. van Dam, Xueling Sim
Type 2 diabetes (T2D) is a major global concern, with Asia at its epicenter in recent years. Proteins, products of gene transcription, serve as dynamic biomarkers for pinpointing perturbed pathways in disease development. To understand the protein function in incident T2D, we examined the association of 4,775 plasma proteins with incident T2D in a Singapore multi-ethnic cohort of 1,659 Asian participants (539 cases and 1,120 controls). Our analysis revealed 522 proteins that were associated with incident T2D after adjusting for age, sex, and ethnicity. Among the 522 proteins associated with incident T2D, the change in 205 plasma proteins, observed in parallel with the development of T2D at baseline and six-years follow-up, were further associated with incident T2D. The associated proteins showed enrichment in neuron generation, glycosaminoglycan binding, and insulin-like growth factor binding. Two-sample Mendelian randomization analysis suggested three plasma proteins, GSTA1, INHBC, and FGL1, play causal roles in the development of T2D, with colocalization evidence supporting GSTA1 and INHBC. Our findings reveal plasma protein profiles linked to the onset of T2D in Asian populations, offering insights into the biological mechanisms of T2D development.
{"title":"Circulating proteomic profiles are associated with the onset of type 2 diabetes in a multi-ethnic Asian population – a longitudinal study","authors":"Yujian Liang, Charlie G.Y. Lim, Scott C. Ritchie, Nicolas Bertin, Jin-Fang Chai, Jiali Yao, Yun Li, E Shyong Tai, Rob M. van Dam, Xueling Sim","doi":"10.1101/2024.05.28.24308009","DOIUrl":"https://doi.org/10.1101/2024.05.28.24308009","url":null,"abstract":"Type 2 diabetes (T2D) is a major global concern, with Asia at its epicenter in recent years. Proteins, products of gene transcription, serve as dynamic biomarkers for pinpointing perturbed pathways in disease development. To understand the protein function in incident T2D, we examined the association of 4,775 plasma proteins with incident T2D in a Singapore multi-ethnic cohort of 1,659 Asian participants (539 cases and 1,120 controls). Our analysis revealed 522 proteins that were associated with incident T2D after adjusting for age, sex, and ethnicity. Among the 522 proteins associated with incident T2D, the change in 205 plasma proteins, observed in parallel with the development of T2D at baseline and six-years follow-up, were further associated with incident T2D. The associated proteins showed enrichment in neuron generation, glycosaminoglycan binding, and insulin-like growth factor binding. Two-sample Mendelian randomization analysis suggested three plasma proteins, GSTA1, INHBC, and FGL1, play causal roles in the development of T2D, with colocalization evidence supporting GSTA1 and INHBC. Our findings reveal plasma protein profiles linked to the onset of T2D in Asian populations, offering insights into the biological mechanisms of T2D development.","PeriodicalId":501419,"journal":{"name":"medRxiv - Endocrinology","volume":"95 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141197866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-27DOI: 10.1101/2024.05.26.24307947
Laurel Stell, Kent Heberer, Kyung Min Lee, Shoa Clarke, Wu Fan, Ilana Belitskaya-Levy, Julie A. Lynch, Hua Tang, Marijana Vujkovic, Donald Miller, Themistocles L. Assimes, Phil Tsao, Scott Damrauer, Kyong-mi Chang, Jennifer S. Lee, the VA Million Veteran Program
IMPORTANCE Clinical guidelines recommend against using glycated hemoglobin A1c (HbA1c) to assess glycemia in patients with two erythropoietic conditions: glucose-6-phosphate dehydrogenase (G6PD) deficiency or sickle cell disease. What remains elusive is quantifying the impact of genetic variants underlying these and other erythropoietic conditions on HbA1c levels as a clinical indicator of glycemic status.
{"title":"Non-glycemic genetic effects on HbA1c and clinical glycemic status in African ancestry: VA Million Veteran Program","authors":"Laurel Stell, Kent Heberer, Kyung Min Lee, Shoa Clarke, Wu Fan, Ilana Belitskaya-Levy, Julie A. Lynch, Hua Tang, Marijana Vujkovic, Donald Miller, Themistocles L. Assimes, Phil Tsao, Scott Damrauer, Kyong-mi Chang, Jennifer S. Lee, the VA Million Veteran Program","doi":"10.1101/2024.05.26.24307947","DOIUrl":"https://doi.org/10.1101/2024.05.26.24307947","url":null,"abstract":"<strong>IMPORTANCE</strong> Clinical guidelines recommend against using glycated hemoglobin A1c (HbA1c) to assess glycemia in patients with two erythropoietic conditions: glucose-6-phosphate dehydrogenase (G6PD) deficiency or sickle cell disease. What remains elusive is quantifying the impact of genetic variants underlying these and other erythropoietic conditions on HbA1c levels as a clinical indicator of glycemic status.","PeriodicalId":501419,"journal":{"name":"medRxiv - Endocrinology","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141167043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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