Syed Rohan Ali, Aabir Imran, Aaila Haider, Kiran Mehtab, Muneeba Anees, Muhammad Hammad ul Haq, Muhammad Umer, Sawera Khan, Kainat Athar, Muhammad Hasan
{"title":"Unveiling Insulin Fear: Awareness, Myths and Practices Surrounding Injectable Insulin among working women suffering from Type 2 Diabetes Mellitus","authors":"Syed Rohan Ali, Aabir Imran, Aaila Haider, Kiran Mehtab, Muneeba Anees, Muhammad Hammad ul Haq, Muhammad Umer, Sawera Khan, Kainat Athar, Muhammad Hasan","doi":"10.1101/2024.07.09.24310042","DOIUrl":"https://doi.org/10.1101/2024.07.09.24310042","url":null,"abstract":"Objective: This study aims to investigate the factors contributing to the reluctance in initiating and continuing insulin therapy among working women diagnosed with type 2 diabetes mellitus in karachi.\u0000Background: A significant number of patients with type 2 diabetes do not achieve adequate control with maximum oral treatments. Early introduction of insulin has been shown to reduce diabetes-related complications. The purpose of this research is to assess the demographic characteristics, clinical factors, and attitudes of type 2 diabetes patients towards initiating insulin therapy. Currently, there is limited data available on insulin therapy for diabetes patients, particularly in Karachi. Therefore, additional randomized and prospective clinical trials are necessary to expand our knowledge and enable healthcare providers to make informed treatment decisions for diabetic patients in this region. Notably, there are various misconceptions surrounding insulin therapy, leading to refusal and delayed initiation, presenting a challenge to healthcare providers. Psychological insulin resistance is also prevalent among diabetic patients, hindering insulin therapy initiation and adherence.\u0000Methods: A cross-sectional study will be conducted, involving a sample size of 384 diabetic female patients, determined using RAOSOFT software based on an estimated population size of 200,000. The sample will be selected through non-probability purposive sampling from Darul Sehat Hospital and healthcare clinics within an 8-month period from June 2023 to January 2024. Informed verbal consent will be obtained from each patient, and the validity of the questionnaire will be assessed. Data will be collected using a structured questionnaire distributed by the researcher. Statistical analysis will be performed using SPSS Version 22 with a 95% confidence interval, 5% margin of error, and a significance level set at 0.05. The relationship between insulin usage and demographic characteristics and clinical data will be evaluated using the χ2 or t-test and logistic regression, with age, educational status, religion, type of job, and diabetes control history as potential effect modifiers.\u0000Result:The data highlights increasing insulin use with disease progression (p = 0.002) and its association with higher education (p = 0.003), indicating awareness. Challenges like injection discomfort among older patients (p = 0.004) and cultural beliefs affecting insulin use (p = 0.005) underscore the need for targeted education and support.\u0000Conclusion: The findings of this study reveal that factors contributing to insulin noncompliance among patients with type 2 diabetes include illiteracy, non-diabetic treatment regimens, misconceptions, no private place for women, fear of cameras. Unhygienic environment. and irrational fear of insulin injections, medication costs, availability issues, concerns about long-term use, lack of family support, poor patient health, infrequent medical visits, and challe","PeriodicalId":501419,"journal":{"name":"medRxiv - Endocrinology","volume":"418 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141573003","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}
Stina Ramne, Mario García-Ureña, Matthew P Gillum, Lars Ängquist, Torben Hansen, Jordi Merino, Niels Grarup
{"title":"Diet pattern determines circulating FGF21 levels while distinct FGF21 variants influence diet pattern and FGF21 levels","authors":"Stina Ramne, Mario García-Ureña, Matthew P Gillum, Lars Ängquist, Torben Hansen, Jordi Merino, Niels Grarup","doi":"10.1101/2024.07.08.24309818","DOIUrl":"https://doi.org/10.1101/2024.07.08.24309818","url":null,"abstract":"Experimental and genetic studies suggest that FGF21 modulates macronutrient and alcohol preferences. However, FGF21's regulation of human appetite remains elusive. To address this gap in translation, we investigated the relationships between plasma FGF21 levels, FGF21 genetic variation and habitual macronutrient intake in a large human population. We show that the main macronutrient-associated variant rs838133 and the FGF21 cis-pQTL rs838131, both in the FGF21 gene, are distinct genetic signals. Effect directions also suggest that the influence of FGF21 variation on macronutrient intake appear more complex than by direct mediation through plasma FGF21. Only when considering this complexity at FGF21, is plasma FGF21 estimated to reduce alcohol and increase protein and fat intake using mendelian randomization. Importantly, plasma FGF21 levels are also markedly elevated by high alcohol and low protein intake. This supports the diet-regulatory mechanism of FGF21 in humans, but highlights the need for mechanistic characterization of the FGF21 genetic region.","PeriodicalId":501419,"journal":{"name":"medRxiv - Endocrinology","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141577708","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}
{"title":"Sex-, and neurodegeneration-dependent effect modification in the association between thyroid function and cognitive impairment in non-depressed, non-demented elderly","authors":"Asma Hallab, Alzheimer's Disease Neuroimaging Initiative","doi":"10.1101/2024.07.04.24309827","DOIUrl":"https://doi.org/10.1101/2024.07.04.24309827","url":null,"abstract":"Introduction: Understanding the particularities of thyroid-cognition interactions in the elderly is crucial in assessing the risks and evaluating therapeutic options.\u0000Methods: Cross-sectional analyses where participants from Alzheimer s Disease Neuroimaging Initiative (ADNI) with mild cognitive impairment (MCI) and healthy controls (HC), with complete neurocognitive tests, thyroid stimulating hormone (TSH) <10 uIU/mL, and geriatric depression scale (GDS) <5 were eligible. Linear and logistic regression models, including testing for non-linearity, were performed. Sex and neurodegeneration-related stratifications were explored. Results: Of the total 1845 participants, with a median age of 73 (IQR: 68, 78); 887 (48%) were females, and 1056 (57%) had MCI. The median TSH level was 1.70 uIU/mL (IQR: 1.15, 2.40). There was a significant association between TSH and cognition only in males (adj. Beta Males: -0.40; 95% CI: -0.74, -0.07; p-value: 0.019). The odds of being diagnosed with MCI at baseline decreased with higher TSH levels in the total study population (adj. OR Total: 0.87; 95% CI: 0.79, 0.95; p-value: 0.002), and in males (adj. OR Males: 0.80; 95% CI: 0.70, 0.92; p-value: 0.001). The median TSH value was a significant cutoff in this association. Conclusions: The association between thyroid function and cognitive decline in the elderly is subject to a sex-driven effect modification and depends on a cutoff value.","PeriodicalId":501419,"journal":{"name":"medRxiv - Endocrinology","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141573079","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}
Garrett Ash, Soohyun Nam, Matthew A Stults-Kolehmainen, Adrian D Haughton, Carolyn Turek, Annette Chmielewski, Michael Shelver, Julien S Baker, Stuart A Weinzimer, Laura M Nally
{"title":"Facilitating the Virtual Exercise Games for Youth with T1D (ExerT1D) Peer Intervention: Protocol Development and Feasibility","authors":"Garrett Ash, Soohyun Nam, Matthew A Stults-Kolehmainen, Adrian D Haughton, Carolyn Turek, Annette Chmielewski, Michael Shelver, Julien S Baker, Stuart A Weinzimer, Laura M Nally","doi":"10.1101/2024.07.03.24309308","DOIUrl":"https://doi.org/10.1101/2024.07.03.24309308","url":null,"abstract":"Introduction\u0000Barriers to moderate-to-vigorous physical activity (MVPA) for adolescents with type 1 diabetes (T1D) include physiology, transition to autonomy, and diabetes-specific stigma. Opportunities for T1D peer activities with T1D role model support are limited. To address this need, our single-arm pilot study tested the Virtual Exercise Games for Youth with T1D (ExerT1D) for feasibility. Methods\u0000Participants (n=15) were mean age 15.6 [SD 1.5] years, 7 non-Hispanic white, 6 female, 2 non-binary, mean A1c 8.9%±2.2%. The program included an MVPA videogame, physician-led education regarding managing T1D around MVPA, objective habitual MVPA goal-setting , and T1D management skills guided by young adult instructors living with T1D.\u0000Results\u0000For feasibility, 13/15 participants attended 10/12 sessions. Participant perceptions of the program, comfort, instructors, and group cohesion were rated high/very high (4.2±0.5 to 4.8±0.3 out of 5). Motivation for the videogame was also high (4.1±0.4 out of 5). Instructor-adolescent interactions related to building T1D management skills were rated as excellent for 78% of sessions. Similarly, sharing knowledge and experiences were rated as excellent for 68% of sessions. However, adolescent-adolescent interactions were poor (communication 29% excellent, peer interactions 8% excellent). The most reported barriers to participation were negative mood and oversleeping. No participants experienced diabetic ketoacidosis, severe hypoglycemia, or injuries during the study period. Compared to baseline, glycemic metrics appeared to decrease during and post-intervention (d= -0.72, -1.12).\u0000Conclusion\u0000ExerT1D facilitated unprecedented T1D peer support achievements by engaging diverse youth with T1D in an MVPA program led by T1D role models. Larger studies are needed to assess if this intervention can improve glycemic measures and reduce diabetes-specific stigma.","PeriodicalId":501419,"journal":{"name":"medRxiv - Endocrinology","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141577707","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}
{"title":"Preventive dental visits and health literacy in patients with diabetes: a nationwide cross-sectional study","authors":"Kyoko Saito, Yuki Kawai, Hirono Ishikawa, Takahiro Tabuchi, Keisuke Kuwahara","doi":"10.1101/2024.07.01.24309770","DOIUrl":"https://doi.org/10.1101/2024.07.01.24309770","url":null,"abstract":"Aim: This cross-sectional study examined the association between health literacy and preventive dental visits in patients with diabetes. Methods: We used cross-sectional data from the Japan COVID-19 and Society Internet Survey (JACSIS), a web-based nationwide survey. The participants were 1,441 patients reporting to have diabetes in 2020. Health literacy was measured using the validated scales for health literacy. Preventive dental visits in the past 12 months were self-reported. We estimated the multivariable-adjusted prevalence ratio (PR) for preventive dental visits. Results: Over 50% of the patients had preventive dental visits in the past 12 months, and approximately one-third had high health literacy. Compared with the low health literacy group, the high health literacy group was more likely to engage in preventive dental visits (the multivariable-adjusted PR associated with high health literacy: 1.12 [95% confidence interval: 1.01 to 1.23]). Similar results were obtained when health literacy was treated as a continuous variable. Conclusions: The present data from the JACSIS showed that health literacy was positively associated with preventive dental visits among patients with diabetes.","PeriodicalId":501419,"journal":{"name":"medRxiv - Endocrinology","volume":"2014 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141548057","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}
Edwin A. Homan, Ankit Gilani, Alfonso Rubio-Navarro, Maya A. Johnson, Eric Cortada, Renan Pereira de Lima, Lisa Stoll, James C Lo
{"title":"Complement 3a Receptor 1 on Macrophages and Kupffer cells is not required for the Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease","authors":"Edwin A. Homan, Ankit Gilani, Alfonso Rubio-Navarro, Maya A. Johnson, Eric Cortada, Renan Pereira de Lima, Lisa Stoll, James C Lo","doi":"10.1101/2024.06.26.24309550","DOIUrl":"https://doi.org/10.1101/2024.06.26.24309550","url":null,"abstract":"Together with obesity and type 2 diabetes, metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global epidemic. Activation of the complement system and infiltration of macrophages has been linked to progression of metabolic liver disease. The role of complement receptors in macrophage activation and recruitment in MASLD remains poorly understood. In human and mouse, <em>C3AR1</em> in the iver is expressed primarily in Kupffer cells, but is downregulated in humans with MASLD compared to obese controls. To test the role of complement 3a receptor (C3aR1) on macrophages and liver resident macrophages in MASLD, we generated mice deficient in C3aR1 on all macrophages (C3aR1-MϕKO) or specifically in liver Kupffer cells (C3aR1-KpKO) and subjected them to a model of metabolic steatotic liver disease. We show that macrophages account for the vast majority of <em>C3ar1 </em>expression in the liver. Overall, C3aR1-MϕKO and C3aR1-KpKO mice have similar body weight gain without significant alterations in glucose homeostasis, hepatic steatosis and fibrosis, compared to controls on a MASLD-inducing diet. This study demonstrates that C3aR1 deletion in macrophages or Kupffer cells, the predominant liver cell type expressing <em>C3aR1</em>, has no significant effect on liver steatosis, inflammation or fibrosis in a dietary MASLD model.","PeriodicalId":501419,"journal":{"name":"medRxiv - Endocrinology","volume":"161 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141504636","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}
Aamir Ijaz, Muhammad Usman Anjum, Farhan Ahmed, Shamaila Najeeb Piracha, Farzana Habib, Muhammad Bilal Shaukat, Sara Najeeb, Najma Qureshi
{"title":"Establishment of Reference Values of Markers of Non-Thyroidal Illness Syndrome on a State-of-the-Art Fully Automated ABEI-Based Chemiluminescence System","authors":"Aamir Ijaz, Muhammad Usman Anjum, Farhan Ahmed, Shamaila Najeeb Piracha, Farzana Habib, Muhammad Bilal Shaukat, Sara Najeeb, Najma Qureshi","doi":"10.1101/2024.06.26.24309539","DOIUrl":"https://doi.org/10.1101/2024.06.26.24309539","url":null,"abstract":"Background: Non-Thyroidal Illness Syndrome (NTIS), previously called Euthyroid Sick Syndrome has always been a diagnostic dilemma for Chemical Pathologists and treating physicians. Combination of four test i.e. Reverse Triiodothyronine (rT3), Free Triiodothyronine (fT3), Free Thyroxine (fT4) and Thyroid Stimulating Hormone (TSH) can be helpful to diagnose NTIS in critically ill patients. We need, however, to determine the reference values found in a reference population, free of any thyroidal as well as non-thyroidal illness.\u0000Methods and Materials: Initially, 266 adult volunteers were included in the study from Mohi Uddin Islamic Medical College Mirpur AJ&K (MIMC) and Mohi Uddin Teaching Hospital Mirpur AJ&K (MOTH) after taking written informed consent. About 124 volunteers were selected (males 61; females 63) after exclusion of the volunteers with one or more of the exclusion criteria. Blood specimens were collected and analyzed for rT3, fT3, fT4 and TSH using Maglumi X8 (S nibe, China), an ABEI (N-(aminobutil)-N-(ethyl)-isoluminol) based analyzer at Pathology Laboratory MOTH.\u0000Results: Reference values of rT3, fT3, fT4 and TSH were found to be 13.3 – 19.8 ng/dL\u0000(0.2 – 0.30 nmol/L); 2.65 - 4.15 pg/mL (4.08 - 6.39 pmol/L);10.6 - 16.2 pg/mL (13.64– 20.84 pmol/L) and 0.43 - 3.98 mIU/mL (0.43 – 3.98 mIU/L), respectively.\u0000Conclusion: Reference values determined in our own population should be used when diagnosing and monitoring NTIS and other thyroid disorders","PeriodicalId":501419,"journal":{"name":"medRxiv - Endocrinology","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141504638","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}
{"title":"The efficacy of Tripterygium Glycosides in the treatment of Chinese patients with thyroid-associated orbitopathy: A systematic review and meta-analysis","authors":"Mingzhe Li, Bingchen Wei, Tianshu Gao, Chenghan Gao","doi":"10.1101/2024.06.18.24309103","DOIUrl":"https://doi.org/10.1101/2024.06.18.24309103","url":null,"abstract":"<strong>Objective</strong> This study aims to conduct a systematic review of the effectiveness and safety of Tripterygium Glycosides interventions in the treatment of Chinese patients with thyroid-associated orbitopathy (TAO).","PeriodicalId":501419,"journal":{"name":"medRxiv - Endocrinology","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141504637","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}
Karin C Wu, Po-Hung Wu, Galateia Kazakia, Sheena Patel, Dennis M Black, Thomas F Lang, Tiffany Y Kim, Nicole J King, Thomas J Hoffmann, Hanling Chang, Gaia Linfield, Sarah Palilla, Stanley J Rogers, Jonathan T Carter, Andrew M Posselt, Anne L Schafer
{"title":"Skeletal effects of sleeve gastrectomy, by sex and menopausal status and in comparison to Roux-en-Y gastric bypass surgery","authors":"Karin C Wu, Po-Hung Wu, Galateia Kazakia, Sheena Patel, Dennis M Black, Thomas F Lang, Tiffany Y Kim, Nicole J King, Thomas J Hoffmann, Hanling Chang, Gaia Linfield, Sarah Palilla, Stanley J Rogers, Jonathan T Carter, Andrew M Posselt, Anne L Schafer","doi":"10.1101/2024.06.25.24309368","DOIUrl":"https://doi.org/10.1101/2024.06.25.24309368","url":null,"abstract":"Context: Roux-en-Y gastric bypass (RYGB) has deleterious effects on bone mass, microarchitecture, and strength. Data are lacking on the skeletal effects of sleeve gastrectomy (SG), now the most commonly performed bariatric surgical procedure. Objective: We examined changes in bone turnover, areal and volumetric bone mineral density (aBMD, vBMD), and appendicular bone microarchitecture and estimated strength after SG. We compared the results to those previously reported after RYGB, hypothesizing lesser effects after SG than RYGB.\u0000Design, Setting, Participants: Prospective observational cohort study of 54 adults with obesity undergoing SG at an academic center.\u0000Main Outcome Measure(s): Skeletal characterization with biochemical markers of bone turnover, dual-energy X-ray absorptiometry (DXA), quantitative computed tomography (QCT), and high-resolution peripheral QCT (HR-pQCT) was performed preoperatively and 6- and 12-months postoperatively. Results: Over 12 months, mean percentage weight loss was 28.8%. Bone turnover marker levels increased, and total hip aBMD decreased -8.0% (95% CI -9.1%, -6.7%, p<0.01). Spinal aBMD and vBMD declines were larger in postmenopausal women than men. Tibial and radial trabecular and cortical microstructure worsened, as did tibial estimated strength, particularly in postmenopausal women. When compared to data from a RYGB cohort with identical design and measurements, some SG biochemical, vBMD, and radial microstructural parameters were smaller, while other changes were not.\u0000Conclusions: Bone mass, microstructure, and strength decrease after SG. Some skeletal parameters change less after SG than after RYGB, while for others, we find no evidence for smaller effects after SG. Postmenopausal women may be at highest risk of skeletal consequences after SG.","PeriodicalId":501419,"journal":{"name":"medRxiv - Endocrinology","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141515927","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}
Peter Hanlon, Elaine Butterly, Lili Wei, Heather Wightman, Saleh Ali M Almazam, Khalid Alsallumi, Jamie Crowther, Ryan McChrystal, Heidi Rennison, Katherine Hughes, Jim Lewsey, Robert Lindsay, Stuart McGurnaghan, John Petrie, Laurie A Tomlinson, Sarah Wild, Amanda Adler, Naveed Sattar, David Phillippo, Sofia Dias, Nicky Welton, David A McAllister
{"title":"Age- and sex- differences in efficacy of treatments for type 2 diabetes: Network meta-analysis of aggregate and individual level data","authors":"Peter Hanlon, Elaine Butterly, Lili Wei, Heather Wightman, Saleh Ali M Almazam, Khalid Alsallumi, Jamie Crowther, Ryan McChrystal, Heidi Rennison, Katherine Hughes, Jim Lewsey, Robert Lindsay, Stuart McGurnaghan, John Petrie, Laurie A Tomlinson, Sarah Wild, Amanda Adler, Naveed Sattar, David Phillippo, Sofia Dias, Nicky Welton, David A McAllister","doi":"10.1101/2024.06.23.24309242","DOIUrl":"https://doi.org/10.1101/2024.06.23.24309242","url":null,"abstract":"Importance\u0000Sodium glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor analogues (GLP1ra) and dipeptidyl peptidase-4 inhibitors (DPP4i) improve hyperglycaemia and, in the case of SGLT2i and GLP1ra, reduce the risk of major adverse cardiovascular events (MACE) in type 2 diabetes. It is not clear whether efficacy varies by age or sex. Objective\u0000Assess whether age or sex are associated with differences in efficacy of SGL2i, GLP1ra and DPP4i.\u0000Data sources\u0000Medline, Embase and clinical trial registries.\u0000Study selection\u0000Two independent reviewers screened for randomised controlled trials of SGLT2i/GLP1ra/DPP4i, compared to placebo/active comparator, in adults with type 2 diabetes. Data extraction and synthesis\u0000We sought individual participant data (IPD) all eligible studies. Where IPD were available, we modelled age- and sex-treatment interactions for each trial. Otherwise, we assessed age-sex distributions along with results from aggregate trial data. IPD and aggregate findings were combined in a Bayesian network meta-analysis.\u0000Main outcome measures\u0000HbA1c and MACE. Results\u0000We identified 616 eligible trials (604 reporting HbA1c, 23 reporting MACE) and obtained IPD for 75 trials (6 reporting MACE). Mean age was 59.0 (10.7) years and 64.0 (8.6) in HbA1c and MACE trials, respectively. Proportions of female were 43.1% and 44.0% in HbA1c and MACE trials, respectively. SGLT2i reduced HbA1c by 0.5-1.0% overall compared to placebo. This reduction versus placebo was attenuated in older participants (change in HbA1c 0.25 percentage-points less for 75-year-olds compared to 45-year-olds). SGLT2i showed greater relative efficacy in MACE risk reduction among older than younger people. This finding was sensitive to the exclusion of one of the IPD MACE trials, however, in all sensitivity analyses, SGLT2i were either as efficacious or more efficacious in older participants. There was no consistently significant difference in efficacy by age for GLP1ra or DPP4i for HbA1c or MACE, nor were there consistent significant sex differences for any class.\u0000Conclusion\u0000Newer glucose-lowering drugs are efficacious across age and sex groups. SGLT2i are more cardioprotective in older than younger people despite smaller HbA1c reductions. Age alone should not be a barrier to treatments with proven cardiovascular benefit providing they are well tolerated align with patient priorities.","PeriodicalId":501419,"journal":{"name":"medRxiv - Endocrinology","volume":"125 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141515891","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}