Katherine E. Wakelin, Rebecca K. Read, Ashely Y. Williams, Rachel R. Francois-Walcott, Nicola O'Donnell, Rose-Marie Satherley, Megan P. Harrington, Mary John, Christina J. Jones
Background
Research suggests that the wellbeing of caregivers of children with Type 1 Diabetes can influence child health outcomes. Therefore, the aim was to conduct a systematic review and meta-analysis to estimate the effect of psychological interventions for families of children with Type 1 Diabetes on caregiver and child functioning.
Methods
A systematic search of the literature identified 58 randomized controlled trials (RCTs) that met inclusion. Study quality was assessed using the Cochrane Risk-of-Bias Tool.
Results
Fifty-one trials had sufficient data to be included in the meta-analysis, analyzing nine variables (caregiver and child psychological distress, diabetes distress, family conflict and child quality of life (QoL), diabetes QoL and blood glucose) over three timepoints (post-intervention, short-term and long-term follow-up). Results from 10 (n = 550), three (n = 347) and 16 RCTs (n = 1631) respectively indicated that psychological interventions significantly reduced caregiver psychological distress post-intervention (SMD = −0.64, 95% CI = −1.15, −0.12), child psychological distress post-intervention (SMD = −0.34, 95% CI = −0.55, −0.31) and child blood glucose at short-term follow-up (SMD = −0.11, 95% CI = −0.21, −0.01), relative to controls.
Conclusions
Participants allocated to controls showed greater reductions in caregiver diabetes family conflict at short-and long-term follow−up than those assigned to psychological interventions. This was explained by significant baseline differences influencing a small number of studies. Studies were highly heterogenous regarding outcome measures, follow-ups, and interventions, with high concerns of bias often observed, reflecting the complexity of real−world clinical practice. Findings are promising. Appropriately powered RCTs with robust randomization are recommended to investigate the significance of effects, whilst considering dose response.
{"title":"The Effectiveness of Psychological Interventions for Families of Children With Type 1 Diabetes on Caregiver and Child Functioning: A Systematic Review and Meta-Analysis","authors":"Katherine E. Wakelin, Rebecca K. Read, Ashely Y. Williams, Rachel R. Francois-Walcott, Nicola O'Donnell, Rose-Marie Satherley, Megan P. Harrington, Mary John, Christina J. Jones","doi":"10.1111/1753-0407.70112","DOIUrl":"https://doi.org/10.1111/1753-0407.70112","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Research suggests that the wellbeing of caregivers of children with Type 1 Diabetes can influence child health outcomes. Therefore, the aim was to conduct a systematic review and meta-analysis to estimate the effect of psychological interventions for families of children with Type 1 Diabetes on caregiver and child functioning.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A systematic search of the literature identified 58 randomized controlled trials (RCTs) that met inclusion. Study quality was assessed using the Cochrane Risk-of-Bias Tool.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fifty-one trials had sufficient data to be included in the meta-analysis, analyzing nine variables (caregiver and child psychological distress, diabetes distress, family conflict and child quality of life (QoL), diabetes QoL and blood glucose) over three timepoints (post-intervention, short-term and long-term follow-up). Results from 10 (<i>n</i> = 550), three (<i>n</i> = 347) and 16 RCTs (<i>n</i> = 1631) respectively indicated that psychological interventions significantly reduced caregiver psychological distress post-intervention (SMD = −0.64, 95% CI = −1.15, −0.12), child psychological distress post-intervention (SMD = −0.34, 95% CI = −0.55, −0.31) and child blood glucose at short-term follow-up (SMD = −0.11, 95% CI = −0.21, −0.01), relative to controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Participants allocated to controls showed greater reductions in caregiver diabetes family conflict at short-and long-term follow−up than those assigned to psychological interventions. This was explained by significant baseline differences influencing a small number of studies. Studies were highly heterogenous regarding outcome measures, follow-ups, and interventions, with high concerns of bias often observed, reflecting the complexity of real−world clinical practice. Findings are promising. Appropriately powered RCTs with robust randomization are recommended to investigate the significance of effects, whilst considering dose response.</p>\u0000 </section>\u0000 </div>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"17 6","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1753-0407.70112","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300168","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}
Obesity represents a critical global health challenge, marked by escalating prevalence and comorbidities such as cardiovascular disease, type 2 diabetes, chronic kidney disease, musculoskeletal disorders, and certain cancers [1]. The continuous development of antiobesity medications (AOMs), which demonstrate significant weight loss effects, presents new opportunities for the treatment of obesity [2]. On August 8, 2024, a search of the Informa Database identified a total of 2120 trials for AOMs, indicating that the research on AOMs is active and receiving significant attention.
Over the past 30 years, the number of clinical trials on AOMs has experienced significant fluctuations, peaking in 2023–2024 (Figure 1A). The number of clinical trials entering phases III–IV and phases I–II/III was comparable (48.5% vs. 50.9%), underscoring the development of novel AOMs derived from established therapies. Eventually, a total of 20 indications were identified in these trials, of which the top 10 were listed in Figure 1B. The majority of indications were Non-diabetic overweight or obesity (41.6%), followed closely by Diabetes-related overweight or obesity (41.0%). Among trials targeting non-diabetic overweight or obesity, only 35.6% reached phase III/IV, indicating this field is still in early-stage exploration. Figure 1C illustrates the distribution of clinical trials for AOMs based on their mechanisms of action and targets. Nutrient-stimulated hormone (NuSH) single receptor agonists dominate the landscape, accounting for 26.14% of trials, highlighting their significant research focus. Other AOMs, which target leptin, ghrelin, mitochondrial uncouplers, and growth differentiation factor 15 (GDF15), follow closely at 19.94%. In recent years, as the number of clinical trials on AOMs has steadily increased, the proportion of combined therapies has also risen, suggesting that this will be a future trend (Figure 1D). Recent advancements have been characterized by a surge in clinical trials targeting various mechanisms of action, as depicted in Figure 1E. Glucagon-like peptide-1 (GLP-1) receptor agonists have emerged as a leading class, with Semaglutide and Liraglutide being the most extensively studied drugs classified as NuSH single receptor agonists. Meanwhile, peptides and molecular conjugates with dual-agonist and triple-agonist actions, such as Tirzepatide and Retatrutide, are currently under investigation and appear to have the strongest potential as anti-obesity medications [3]. Advances in incretin biology have driven the development of approved GLP-1 receptor agonists over recent decades. To date, the FDA has approved three NuSH-based AOMs: Liraglutide, Semaglutide, and Tirzepatide.
Additionally, further management of obesity necessitates personalized therapies and multimodal strategies, as long-term maintenance of weight loss is challenging for most people. Combination therapies, like the integration
肥胖是一项重大的全球健康挑战，其特点是心血管疾病、2型糖尿病、慢性肾脏疾病、肌肉骨骼疾病和某些癌症等患病率和合并症不断上升。抗肥胖药物（AOMs）的不断发展，显示出显著的减肥效果，为肥胖的治疗提供了新的机会。2024年8月8日，通过对Informa数据库的检索，发现AOMs的试验总数为2120个，表明AOMs的研究非常活跃，受到了极大的关注。在过去30年中，AOMs的临床试验数量经历了显著波动，在2023-2024年达到峰值（图1A）。进入III - iv期和I-II /III期的临床试验数量相当（48.5% vs 50.9%），强调了源自既定疗法的新型AOMs的发展。最终，这些试验共确定了20个适应症，其中排名前10位的见图1B。大多数适应症为非糖尿病性超重或肥胖（41.6%），其次为糖尿病相关超重或肥胖（41.0%）。在针对非糖尿病性超重或肥胖的试验中，只有35.6%达到III/IV期，表明该领域仍处于早期探索阶段。图1C显示了基于AOMs作用机制和靶点的临床试验分布。营养刺激激素（NuSH）单受体激动剂占主导地位，占试验的26.14%，突出了其重要的研究重点。其他靶向瘦素、胃饥饿素、线粒体解偶联剂和生长分化因子15 （GDF15）的AOMs紧随其后，占19.94%。近年来，随着AOMs临床试验数量的稳步增加，联合治疗的比例也在上升，这将是未来的趋势（图1D）。最近的进展特点是针对各种作用机制的临床试验激增，如图1E所示。胰高血糖素样肽-1 （GLP-1）受体激动剂已成为一类领先的药物，其中Semaglutide和Liraglutide是被分类为NuSH单受体激动剂的研究最广泛的药物。与此同时，具有双激动剂和三激动剂作用的多肽和分子偶联物，如替西帕肽和利特鲁肽，目前正在研究中，似乎具有最大的抗肥胖药物潜力b[3]。近几十年来，肠促胰岛素生物学的进步推动了批准的GLP-1受体激动剂的发展。迄今为止，FDA已经批准了三种基于nush的AOMs：利拉鲁肽、Semaglutide和替西帕肽。此外，肥胖的进一步管理需要个性化治疗和多模式策略，因为长期维持体重减轻对大多数人来说是具有挑战性的。联合治疗，如AOMs或减肥手术的整合，以及生活方式的改变，代表了未来治疗发展的方向。与此同时，针对非糖尿病超重或肥胖患者的研究也得到了关注，这反映了公众对肥胖的兴趣日益浓厚，以及新型AOMs的不断发展。总之，随着新型AOMs的开发和临床经验的增加，肥胖治疗将变得更加有效，帮助患者提高生活质量，减轻肥胖相关合并症的负担。刘丹录：概念化、数据整理、形式分析、调查、方法论、撰写原稿。陈毅：监督、审定、撰稿编辑、项目管理、资金获取。根据国际医学期刊编辑委员会（ICMJE）的最新指南，所有作者都对所报道的研究的构思、设计、执行或解释做出了重大贡献。作者没有什么可报告的。作者没有什么可报告的。作者声明无利益冲突。
{"title":"A New Era in Obesity Treatment: The Evolution of Antiobesity Medications (AOMs) Based on Clinical Trials","authors":"Danlu Liu, Yi Chen","doi":"10.1111/1753-0407.70115","DOIUrl":"https://doi.org/10.1111/1753-0407.70115","url":null,"abstract":"<p>Obesity represents a critical global health challenge, marked by escalating prevalence and comorbidities such as cardiovascular disease, type 2 diabetes, chronic kidney disease, musculoskeletal disorders, and certain cancers [<span>1</span>]. The continuous development of antiobesity medications (AOMs), which demonstrate significant weight loss effects, presents new opportunities for the treatment of obesity [<span>2</span>]. On August 8, 2024, a search of the Informa Database identified a total of 2120 trials for AOMs, indicating that the research on AOMs is active and receiving significant attention.</p><p>Over the past 30 years, the number of clinical trials on AOMs has experienced significant fluctuations, peaking in 2023–2024 (Figure 1A). The number of clinical trials entering phases III–IV and phases I–II/III was comparable (48.5% vs. 50.9%), underscoring the development of novel AOMs derived from established therapies. Eventually, a total of 20 indications were identified in these trials, of which the top 10 were listed in Figure 1B. The majority of indications were Non-diabetic overweight or obesity (41.6%), followed closely by Diabetes-related overweight or obesity (41.0%). Among trials targeting non-diabetic overweight or obesity, only 35.6% reached phase III/IV, indicating this field is still in early-stage exploration. Figure 1C illustrates the distribution of clinical trials for AOMs based on their mechanisms of action and targets. Nutrient-stimulated hormone (NuSH) single receptor agonists dominate the landscape, accounting for 26.14% of trials, highlighting their significant research focus. Other AOMs, which target leptin, ghrelin, mitochondrial uncouplers, and growth differentiation factor 15 (GDF15), follow closely at 19.94%. In recent years, as the number of clinical trials on AOMs has steadily increased, the proportion of combined therapies has also risen, suggesting that this will be a future trend (Figure 1D). Recent advancements have been characterized by a surge in clinical trials targeting various mechanisms of action, as depicted in Figure 1E. Glucagon-like peptide-1 (GLP-1) receptor agonists have emerged as a leading class, with Semaglutide and Liraglutide being the most extensively studied drugs classified as NuSH single receptor agonists. Meanwhile, peptides and molecular conjugates with dual-agonist and triple-agonist actions, such as Tirzepatide and Retatrutide, are currently under investigation and appear to have the strongest potential as anti-obesity medications [<span>3</span>]. Advances in incretin biology have driven the development of approved GLP-1 receptor agonists over recent decades. To date, the FDA has approved three NuSH-based AOMs: Liraglutide, Semaglutide, and Tirzepatide.</p><p>Additionally, further management of obesity necessitates personalized therapies and multimodal strategies, as long-term maintenance of weight loss is challenging for most people. Combination therapies, like the integration ","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"17 6","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1753-0407.70115","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300169","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}
Emerging evidence suggests the presence of distinct endotypes of Type 1 diabetes mellitus (T1DM): T1DE1 in individuals diagnosed at age < 7 years in contrast to T1DE2 in those diagnosed at ≥ 13 years of age. We aimed to comprehensively explore the phenotypic heterogeneity of T1DM with respect to the age-related endotypes.
Methods
This cross-sectional study was conducted in China and involved 1204 children newly diagnosed with T1DM who were admitted to the pediatric department of a tertiary hospital from January 1, 2010 to December 31, 2023. The patients were divided into three age groups: < 7 years (T1DE1), 7–12 years, and ≥ 13 years (T1DE2). A comparison was made among the age groups regarding demographic characteristics, glucose metabolism, β-cell autoimmunity, and metabolic decompensation.
Results
Patients under 7 years exhibited a shorter symptom duration before diagnosis, along with the lowest fasting and postprandial C-peptide and C-peptide to glucose ratio levels and the highest postprandial glucose levels. They also showed the highest insulin autoantibody positivity rate and creatine kinase-MB levels. In contrast, patients aged 13 and older had the highest HbA1c levels and glutamate decarboxylase antibody positivity rate. In addition, this group showed the highest prevalence of TPOAb and TgAb positivity, as well as the largest proportion of abnormal liver function cases.
Conclusions
The study illustrates age-specific phenotypic heterogeneity in pediatric T1DM, indicating the presence of distinct endotypes. Further investigation of these endotypes may offer more evidence for the precise treatment of T1DM.
{"title":"Phenotypic Spectrum at Diagnosis of Age-Related Endotypes of Type 1 Diabetes Mellitus: A Cross-Sectional Study in China","authors":"Qiaoli Zhou, Xueqin Zheng, Chenguang Ma, Wei Gu","doi":"10.1111/1753-0407.70111","DOIUrl":"https://doi.org/10.1111/1753-0407.70111","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Emerging evidence suggests the presence of distinct endotypes of Type 1 diabetes mellitus (T1DM): T1DE1 in individuals diagnosed at age < 7 years in contrast to T1DE2 in those diagnosed at ≥ 13 years of age. We aimed to comprehensively explore the phenotypic heterogeneity of T1DM with respect to the age-related endotypes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This cross-sectional study was conducted in China and involved 1204 children newly diagnosed with T1DM who were admitted to the pediatric department of a tertiary hospital from January 1, 2010 to December 31, 2023. The patients were divided into three age groups: < 7 years (T1DE1), 7–12 years, and ≥ 13 years (T1DE2). A comparison was made among the age groups regarding demographic characteristics, glucose metabolism, β-cell autoimmunity, and metabolic decompensation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients under 7 years exhibited a shorter symptom duration before diagnosis, along with the lowest fasting and postprandial C-peptide and C-peptide to glucose ratio levels and the highest postprandial glucose levels. They also showed the highest insulin autoantibody positivity rate and creatine kinase-MB levels. In contrast, patients aged 13 and older had the highest HbA1c levels and glutamate decarboxylase antibody positivity rate. In addition, this group showed the highest prevalence of TPOAb and TgAb positivity, as well as the largest proportion of abnormal liver function cases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The study illustrates age-specific phenotypic heterogeneity in pediatric T1DM, indicating the presence of distinct endotypes. Further investigation of these endotypes may offer more evidence for the precise treatment of T1DM.</p>\u0000 </section>\u0000 </div>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"17 6","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1753-0407.70111","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264421","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}
Mingxin Bai, Donge Yan, Ruixue Feng, Xingwu Ran, Dawei Chen, Chun Wang, Lihong Chen, Shuang Lin, Sen He, Yan Liu, Murong Wu, Zhiyi Lei, Yun Gao
Background
Previous studies have shown that vitamin D deficiency was associated with both cardiac autonomic dysfunction and the development of diabetic foot (DF). However, the impact of vitamin D levels on heart rate variability (HRV) in individuals with DF, a high-risk group, remains unclear. We explored the association between vitamin D status and HRV in individuals with DF.
Methods
A total of 458 individuals with DF were assessed for vitamin D levels by 25-hydroxyvitamin D (25(OH)D) and evaluated for cardiovascular autonomic function using both time and frequency domains of the HRV measures. Multivariate regression analysis and restricted cubic spline regression were employed to examine the associations.
Results
Vitamin D levels were positively associated with HRV indices in people with DF, including standard deviation of the normal sinus interval (SDNN), standard deviation of the 5-min average RR intervals (SDANN), low-frequency power (LF), high-frequency power (HF), and the LF/HF ratio (all p < 0.05). The associations between serum 25(OH)D and cardiac autonomic dysfunction were nonlinear. When 25(OH)D levels were < 50 nmol/L, the odds ratio (OR) for predicted cardiac autonomic dysfunction per SD increase in 25(OH)D was 0.56 (95% CI, 0.44–0.72). However, no significant effect was observed when 25(OH)D levels exceeded 50 nmol/L.
Conclusions
This study demonstrates that lower 25(OH)D levels are associated with reduced HRV in individuals with DF. Specifically, when 25(OH)D levels fall below 50 nmol/L, the risk of cardiac autonomic dysfunction in people with DF significantly increases.
{"title":"Nonlinear Association Between Serum 25-Hydroxyvitamin D and Cardiac Autonomic Dysfunction in Diabetic Foot: A Threshold Effect on Heart Rate Variability","authors":"Mingxin Bai, Donge Yan, Ruixue Feng, Xingwu Ran, Dawei Chen, Chun Wang, Lihong Chen, Shuang Lin, Sen He, Yan Liu, Murong Wu, Zhiyi Lei, Yun Gao","doi":"10.1111/1753-0407.70109","DOIUrl":"https://doi.org/10.1111/1753-0407.70109","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Previous studies have shown that vitamin D deficiency was associated with both cardiac autonomic dysfunction and the development of diabetic foot (DF). However, the impact of vitamin D levels on heart rate variability (HRV) in individuals with DF, a high-risk group, remains unclear. We explored the association between vitamin D status and HRV in individuals with DF.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 458 individuals with DF were assessed for vitamin D levels by 25-hydroxyvitamin D (25(OH)D) and evaluated for cardiovascular autonomic function using both time and frequency domains of the HRV measures. Multivariate regression analysis and restricted cubic spline regression were employed to examine the associations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Vitamin D levels were positively associated with HRV indices in people with DF, including standard deviation of the normal sinus interval (SDNN), standard deviation of the 5-min average RR intervals (SDANN), low-frequency power (LF), high-frequency power (HF), and the LF/HF ratio (all <i>p</i> < 0.05). The associations between serum 25(OH)D and cardiac autonomic dysfunction were nonlinear. When 25(OH)D levels were < 50 nmol/L, the odds ratio (OR) for predicted cardiac autonomic dysfunction per SD increase in 25(OH)D was 0.56 (95% CI, 0.44–0.72). However, no significant effect was observed when 25(OH)D levels exceeded 50 nmol/L.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study demonstrates that lower 25(OH)D levels are associated with reduced HRV in individuals with DF. Specifically, when 25(OH)D levels fall below 50 nmol/L, the risk of cardiac autonomic dysfunction in people with DF significantly increases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"17 6","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1753-0407.70109","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144244780","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}
Sohail Aziz, Sabariah Noor Harun, Siti Maisharah Sheikh Ghadzi
Background
Estimated glomerular filtration rate (eGFR) is a key clinical marker for assessing kidney complications in type 2 diabetes mellitus (T2DM). This study aimed to develop and validate a disease progression model of eGFR in Malaysian T2DM patients, with and without diabetic nephropathy (DN).
Methods
Retrospective data from 251 patients (3241 observations) were analyzed using NONMEM software. Baseline eGFR was assessed without covariates, and both linear and non-linear models were tested. Model selection was based on the likelihood ratio test (5% significance level), objective function value (OFV), visual predictive check (VPC), relative standard error, and scientific plausibility. External validation was performed using data from 109 patients.
Results
A linear model best described disease progression, with a baseline eGFR of 84.6 mL/min/1.73 m2 and a decline rate of −0.0041 mL/min/1.73 m2/year. Cardiovascular disease (CVD) reduced eGFR by 1.05 mL/min/1.73 m2/year, while fasting blood sugar (FBS) above 7.4 mmol/L correlated with an additional decline of 0.043 mL/min/1.73 m2/year. Angiotensin receptor blockers (ARBs) improved eGFR by 0.4 mL/min/1.73 m2/year, whereas statins and metformin contributed improvements of 0.34 and 0.32 mL/min/1.73 m2/year, respectively. External validation confirmed model consistency with observed data.
Conclusion
Glycaemic control and CVD significantly impact eGFR decline. ARBs, statins, and metformin help preserve kidney function. Effective glycaemic management is crucial in slowing kidney deterioration, especially in T2DM patients at risk for DN.
{"title":"Disease Progression Modeling of Estimated Glomerular Filtration Rate (eGFR): A Pharmacometrics Approach","authors":"Sohail Aziz, Sabariah Noor Harun, Siti Maisharah Sheikh Ghadzi","doi":"10.1111/1753-0407.70104","DOIUrl":"https://doi.org/10.1111/1753-0407.70104","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Estimated glomerular filtration rate (eGFR) is a key clinical marker for assessing kidney complications in type 2 diabetes mellitus (T2DM). This study aimed to develop and validate a disease progression model of eGFR in Malaysian T2DM patients, with and without diabetic nephropathy (DN).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Retrospective data from 251 patients (3241 observations) were analyzed using NONMEM software. Baseline eGFR was assessed without covariates, and both linear and non-linear models were tested. Model selection was based on the likelihood ratio test (5% significance level), objective function value (OFV), visual predictive check (VPC), relative standard error, and scientific plausibility. External validation was performed using data from 109 patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A linear model best described disease progression, with a baseline eGFR of 84.6 mL/min/1.73 m<sup>2</sup> and a decline rate of −0.0041 mL/min/1.73 m<sup>2</sup>/year. Cardiovascular disease (CVD) reduced eGFR by 1.05 mL/min/1.73 m<sup>2</sup>/year, while fasting blood sugar (FBS) above 7.4 mmol/L correlated with an additional decline of 0.043 mL/min/1.73 m<sup>2</sup>/year. Angiotensin receptor blockers (ARBs) improved eGFR by 0.4 mL/min/1.73 m<sup>2</sup>/year, whereas statins and metformin contributed improvements of 0.34 and 0.32 mL/min/1.73 m<sup>2</sup>/year, respectively. External validation confirmed model consistency with observed data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Glycaemic control and CVD significantly impact eGFR decline. ARBs, statins, and metformin help preserve kidney function. Effective glycaemic management is crucial in slowing kidney deterioration, especially in T2DM patients at risk for DN.</p>\u0000 </section>\u0000 </div>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"17 6","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1753-0407.70104","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144220305","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}
William Hou, Katherine R. Tuttle, Weining Shen, Andrew Reikes, Jonathan H. Watanabe
Aims
In patients with new onset type 2 diabetes, this study aimed to analyze glucose-lowering medication use patterns between 2014 and 2022.
Materials and Methods
This retrospective study included adults with incident type 2 diabetes in the University of California Health System between 2014 and 2022. We determined medications used within 1 year of diagnosis and evaluated statistical evidence of use pattern changes via Mann–Kendall trend tests. Four categories of high-risk patients requiring cardio-kidney-metabolic protection were also evaluated in stratified analyses based on 2024 ADA guidelines.
Results
Of 40 150 patients with incident type 2 diabetes, 38.5% initiated glucose-lowering medication within 1 year. Metformin remained the most used medication from 2014 to 2022. From 2014 to 2022, usage of GLP-1 receptor agonists and SGLT-2 inhibitors increased exponentially. GLP-1 receptor agonist use increased from below 2.5%–21%. While SGLT-2 inhibitor use increased from less than 2.5%–14%. This growth coincided with a decline in sulfonylurea usage. Among high-risk, insulin was most prevalent in those with heart failure or chronic kidney disease. However, usage of insulin declined overall in all groups. Utilization of SGLT-2 inhibitors was particularly high in patients with prior heart failure.
Conclusions
In adults with new onset type 2 diabetes, GLP-1 receptor agonist and SGLT-2 inhibitor utilization has markedly increased, coordinating with evolving guidelines that emphasize cardiovascular and chronic kidney disease management. However, overall adoption rates of these medications remain low based on indicated populations. Sulfonylurea use declined while metformin remains the most frequently initiated treatment.
{"title":"Trends in Pharmacological Treatment of Patients With New Onset Type 2 Diabetes: Usage Patterns in an Evolving Guideline Landscape","authors":"William Hou, Katherine R. Tuttle, Weining Shen, Andrew Reikes, Jonathan H. Watanabe","doi":"10.1111/1753-0407.70108","DOIUrl":"https://doi.org/10.1111/1753-0407.70108","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>In patients with new onset type 2 diabetes, this study aimed to analyze glucose-lowering medication use patterns between 2014 and 2022.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>This retrospective study included adults with incident type 2 diabetes in the University of California Health System between 2014 and 2022. We determined medications used within 1 year of diagnosis and evaluated statistical evidence of use pattern changes via Mann–Kendall trend tests. Four categories of high-risk patients requiring cardio-kidney-metabolic protection were also evaluated in stratified analyses based on 2024 ADA guidelines.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 40 150 patients with incident type 2 diabetes, 38.5% initiated glucose-lowering medication within 1 year. Metformin remained the most used medication from 2014 to 2022. From 2014 to 2022, usage of GLP-1 receptor agonists and SGLT-2 inhibitors increased exponentially. GLP-1 receptor agonist use increased from below 2.5%–21%. While SGLT-2 inhibitor use increased from less than 2.5%–14%. This growth coincided with a decline in sulfonylurea usage. Among high-risk, insulin was most prevalent in those with heart failure or chronic kidney disease. However, usage of insulin declined overall in all groups. Utilization of SGLT-2 inhibitors was particularly high in patients with prior heart failure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In adults with new onset type 2 diabetes, GLP-1 receptor agonist and SGLT-2 inhibitor utilization has markedly increased, coordinating with evolving guidelines that emphasize cardiovascular and chronic kidney disease management. However, overall adoption rates of these medications remain low based on indicated populations. Sulfonylurea use declined while metformin remains the most frequently initiated treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"17 6","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1753-0407.70108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144206933","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}
Baomin Wang, Ziyan Wang, Yumei Yang, Melody Yuen Man Ho, Runyue Yang, Huizi Yang, Siyi Liu, Huige Lin, Kenneth King Yip Cheng, Xiaomu Li
Background
Pancreatic β-cells function deteriorates during aging, leading to increased risk of type 2 diabetes. We and others previously demonstrated that p53 activation triggers β-cell senescence and dysfunction in aging, but how its activity is controlled remains incompletely understood. Metabolites are not only by-products of metabolic pathways but also function as messengers to regulate various biological pathways. Taurine, a non-proteinogenic amino acid derived from cysteine, has demonstrated anti-aging effects in multiple cell types and tissues. Nevertheless, its role in β-cell senescence remains unclear.
Methods
Untargeted metabolomic analysis was used to determine differential metabolites in pancreatic islets of mice during aging. In vitro, β-cell lines MIN6 and INS-1E were treated with taurine and its transporter inhibitor, followed by measurement of senescence-related markers. Multiple experimental techniques, such as LC–MS/MS, co-immunoprecipitation, DARTS analysis, and LiP-MS, were used to study the mechanistic actions of taurine.
Results
Untargeted metabolomic analysis showed that taurine and taurocholic acid were significantly upregulated in aged islets. Pretreatment with taurine inhibited naturally aging, chemically induced senescent and inflammatory program, oxidative stress, and defective insulin secretion in pancreatic β-cells. SLC6A6 transporter was required to mediate exogenous taurine uptake, and inhibition of SLC6A6 abolished the anti-senescent effects of taurine. Taurine bound with CKDN2AIP and inhibited its interaction with p53, thereby promoting p53 degradation and suppressing the p53-dependent senescent program.
Conclusion
Our findings suggest that increasing β-cell taurine uptake might be a feasible approach to preserve β-cell function by targeting the p53-dependent senescent response.
{"title":"Taurine Alleviates Pancreatic β-Cell Senescence by Inhibition of p53 Pathway","authors":"Baomin Wang, Ziyan Wang, Yumei Yang, Melody Yuen Man Ho, Runyue Yang, Huizi Yang, Siyi Liu, Huige Lin, Kenneth King Yip Cheng, Xiaomu Li","doi":"10.1111/1753-0407.70100","DOIUrl":"https://doi.org/10.1111/1753-0407.70100","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Pancreatic β-cells function deteriorates during aging, leading to increased risk of type 2 diabetes. We and others previously demonstrated that p53 activation triggers β-cell senescence and dysfunction in aging, but how its activity is controlled remains incompletely understood. Metabolites are not only by-products of metabolic pathways but also function as messengers to regulate various biological pathways. Taurine, a non-proteinogenic amino acid derived from cysteine, has demonstrated anti-aging effects in multiple cell types and tissues. Nevertheless, its role in β-cell senescence remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Untargeted metabolomic analysis was used to determine differential metabolites in pancreatic islets of mice during aging. In vitro, β-cell lines MIN6 and INS-1E were treated with taurine and its transporter inhibitor, followed by measurement of senescence-related markers. Multiple experimental techniques, such as LC–MS/MS, co-immunoprecipitation, DARTS analysis, and LiP-MS, were used to study the mechanistic actions of taurine.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Untargeted metabolomic analysis showed that taurine and taurocholic acid were significantly upregulated in aged islets. Pretreatment with taurine inhibited naturally aging, chemically induced senescent and inflammatory program, oxidative stress, and defective insulin secretion in pancreatic β-cells. SLC6A6 transporter was required to mediate exogenous taurine uptake, and inhibition of SLC6A6 abolished the anti-senescent effects of taurine. Taurine bound with CKDN2AIP and inhibited its interaction with p53, thereby promoting p53 degradation and suppressing the p53-dependent senescent program.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings suggest that increasing β-cell taurine uptake might be a feasible approach to preserve β-cell function by targeting the p53-dependent senescent response.</p>\u0000 </section>\u0000 </div>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"17 6","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1753-0407.70100","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197211","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}
Events of cardiovascular disease (CVD) remain a critical concern in patients with Type 2 diabetes mellitus (T2D). Over 17 years, this study analyzed time changes in the 5-year incidence of myocardial infarction (MI), chronic coronary heart disease (CHD), transient ischemic attack (TIA), and ischemic stroke (IS).
Methods
This retrospective cohort study was conducted using the Disease Analyzer database, including patients aged ≥ 18 years with at least 12 months of no prior CVD with new-onset T2D in 2001–2006 (n = 10 162) and in 2013–2018 (n = 30 486), matched 1:3 by age and sex. Kaplan–Meier survival analysis estimated the 5-year cumulative incidence of the outcomes. Multivariable Cox regression models assessed temporal changes, adjusted for comorbidities.
Results
The incidence of CHD and TIA significantly declined in 2013–2018 compared to 2001–2006, with HRs of 0.68 (95% CI: 0.63–0.73; p < 0.001) and 0.63 (95% CI: 0.52–0.76; p < 0.001), respectively. Reductions were more pronounced in women and older patients. Surprisingly, MI incidence showed only a trend of reduction (HR: 0.82; 95% CI: 0.68–0.99; p = 0.045) and IS incidence was not different (HR: 0.97; 95% CI: 0.85–1.12; p = 0.722) between time periods.
Conclusions
This study is the first to report time trends in CVD incidence in new-onset T2D in Germany. From 2001 to 2018, the 5-year incidence of CHD and TIA decreased in new-onset T2D, reflecting demographic-specific advancements in diabetes and cardiovascular care. However, the stable incidence of IS and MI underscores a persistent challenge in prevention strategies in patients with prediabetes and T2D.
{"title":"Time Trends in Cardiovascular Event Incidence in New-Onset Type 2 Diabetes: A Population-Based Cohort Study From Germany","authors":"Theresia Sarabhai, Karel Kostev","doi":"10.1111/1753-0407.70099","DOIUrl":"https://doi.org/10.1111/1753-0407.70099","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Events of cardiovascular disease (CVD) remain a critical concern in patients with Type 2 diabetes mellitus (T2D). Over 17 years, this study analyzed time changes in the 5-year incidence of myocardial infarction (MI), chronic coronary heart disease (CHD), transient ischemic attack (TIA), and ischemic stroke (IS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective cohort study was conducted using the Disease Analyzer database, including patients aged ≥ 18 years with at least 12 months of no prior CVD with new-onset T2D in 2001–2006 (<i>n</i> = 10 162) and in 2013–2018 (<i>n</i> = 30 486), matched 1:3 by age and sex. Kaplan–Meier survival analysis estimated the 5-year cumulative incidence of the outcomes. Multivariable Cox regression models assessed temporal changes, adjusted for comorbidities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The incidence of CHD and TIA significantly declined in 2013–2018 compared to 2001–2006, with HRs of 0.68 (95% CI: 0.63–0.73; <i>p</i> < 0.001) and 0.63 (95% CI: 0.52–0.76; <i>p</i> < 0.001), respectively. Reductions were more pronounced in women and older patients. Surprisingly, MI incidence showed only a trend of reduction (HR: 0.82; 95% CI: 0.68–0.99; <i>p</i> = 0.045) and IS incidence was not different (HR: 0.97; 95% CI: 0.85–1.12; <i>p</i> = 0.722) between time periods.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study is the first to report time trends in CVD incidence in new-onset T2D in Germany. From 2001 to 2018, the 5-year incidence of CHD and TIA decreased in new-onset T2D, reflecting demographic-specific advancements in diabetes and cardiovascular care. However, the stable incidence of IS and MI underscores a persistent challenge in prevention strategies in patients with prediabetes and T2D.</p>\u0000 </section>\u0000 </div>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"17 6","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1753-0407.70099","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144190835","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}
Yujun He, Xiaoyi Wang, Lu Li, Minhui Liu, Yachao Wu, Ru Chen, Jiujie He, Wei Mai, Xiaojun Li
Background
Diabetic kidney disease (DKD) is a prevalent and severe complication of diabetes that significantly impacts global health and quality of life. Most DKD is attributable to type 2 diabetes; therefore, chronic type 2 DKD warrants further examination.
Objective
To deliver targeted assistance in alleviating the worldwide, regional, and national burden of chronic type 2 DKD, we executed a survey assessing the prevalence of chronic type 2 DKD utilizing the Global Burden of Disease, Injury, and Risk Factors (GBD) database.
Methods
We examined the temporal trends of chronic type 2 DKD prevalence over the past 30 years using the 2021 GBD database, analyzed the trends by population, epidemiological change, and aging, and quantified cross-country health inequalities. Additionally, we forecasted the trend during the subsequent two decades.
Results
In 2021, there were over 107 million cases of chronic type 2 DKD globally, reflecting an 85.11% rise from 58 million cases in 1990. The age-standardized rate (ASR) declined with an estimated annual percentage change of 0.17% per annum. Epidemiological change and population expansion are the primary factors influencing the alterations. The contributions of epidemiological change, population, and aging vary with alterations in the sociodemographic index (SDI). Significant health inequalities were observed across 204 countries and territories, with the slope index of inequality increasing over time. The forecast for the worldwide burden of chronic type 2 DKD from 2020 to 2040 suggests a significant rise in case numbers, while the alterations in ASR remain largely stable.
Conclusions
These findings indicate the significant disease burden of chronic type 2 DKD, necessitating more targeted and effective interventions for its prevention and management.
{"title":"Global, Regional, and National Prevalence of Chronic Type 2 Diabetic Kidney Disease From 1990 to 2021: A Trend and Health Inequality Analyses Based on the Global Burden of Disease Study 2021","authors":"Yujun He, Xiaoyi Wang, Lu Li, Minhui Liu, Yachao Wu, Ru Chen, Jiujie He, Wei Mai, Xiaojun Li","doi":"10.1111/1753-0407.70098","DOIUrl":"https://doi.org/10.1111/1753-0407.70098","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Diabetic kidney disease (DKD) is a prevalent and severe complication of diabetes that significantly impacts global health and quality of life. Most DKD is attributable to type 2 diabetes; therefore, chronic type 2 DKD warrants further examination.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To deliver targeted assistance in alleviating the worldwide, regional, and national burden of chronic type 2 DKD, we executed a survey assessing the prevalence of chronic type 2 DKD utilizing the Global Burden of Disease, Injury, and Risk Factors (GBD) database.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We examined the temporal trends of chronic type 2 DKD prevalence over the past 30 years using the 2021 GBD database, analyzed the trends by population, epidemiological change, and aging, and quantified cross-country health inequalities. Additionally, we forecasted the trend during the subsequent two decades.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In 2021, there were over 107 million cases of chronic type 2 DKD globally, reflecting an 85.11% rise from 58 million cases in 1990. The age-standardized rate (ASR) declined with an estimated annual percentage change of 0.17% per annum. Epidemiological change and population expansion are the primary factors influencing the alterations. The contributions of epidemiological change, population, and aging vary with alterations in the sociodemographic index (SDI). Significant health inequalities were observed across 204 countries and territories, with the slope index of inequality increasing over time. The forecast for the worldwide burden of chronic type 2 DKD from 2020 to 2040 suggests a significant rise in case numbers, while the alterations in ASR remain largely stable.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings indicate the significant disease burden of chronic type 2 DKD, necessitating more targeted and effective interventions for its prevention and management.</p>\u0000 </section>\u0000 </div>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"17 5","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1753-0407.70098","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144108834","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}
Rosemary M. Hall, Amber Parry-Strong, David O'Sullivan, Jeremy D. Krebs, Olivier Gasser
<p>Higher intakes of dietary fiber have been associated with a reduced risk of developing Type 2 Diabetes (T2DM) and cardiovascular disease [<span>1, 2</span>]. Fiber supplementation improves overall glycaemia, with reductions in Hba1c and better insulin sensitivity [<span>3</span>]. However, there is significant reported heterogeneity on the effects of supplemental fiber on glycaemic outcomes for people with T2DM, potentially due to variations in absorption and metabolism. These differences, we believe, are worth examining more closely, especially considering the complexities of the gut microbiome, medications used in T2DM, and the role of the background diet [<span>3</span>].</p><p>In our recent study, we investigated the impact of supplemental fiber on glucose metabolism and glycemic control in people with pre-diabetes and T2DM who had a low habitual fiber intake. We recruited 30 participants with HbA1c levels ranging from 45 to 70 mmol/mol, and provided them with psyllium fiber supplements for 12 weeks.</p><p>Although we observed reductions in body mass index (BMI) and improvements in lipid profiles, HbA1c levels did not significantly improve overall. Surprisingly, participants taking metformin alone experienced an increase in HbA1c, while those not taking metformin experienced a slight reduction (Figure 1).</p><p>This discrepancy points to a critical issue: the potential interaction between metformin and fiber supplementation. Metformin, the most common medication for T2DM works by reducing hepatic glucose production and improving insulin sensitivity [<span>4</span>]. However, metformin primarily acts within the gastrointestinal tract, commonly producing gastrointestinal side-effects and may alter gut microbiome, with the potential to directly affect fiber absorption [<span>5</span>]. Our findings suggest that when combined with fiber supplementation, metformin may impair the metabolic benefits typically associated with fiber, alongside a potential detrimental effect on the glycaemic benefits of metformin.</p><p>This phenomenon is consistent with previous research. For example, a study by Tramontana et al. found that a high-fiber diet did not improve HbA1c in 78 patients with T2DM on metformin monotherapy [<span>6</span>], while other studies observed more promising results when fiber was combined with different medications [<span>7</span>]. These findings highlight the need for a more nuanced understanding of how dietary fiber interacts with both the gut microbiome and medications like metformin.</p><p>Moreover, the gut microbiota's role in metabolism is integral to the overall metabolic benefits. Dietary fiber, especially in the form of psyllium, is fermented by gut bacteria into short-chain fatty acids (SCFAs), which have been shown to improve immune function and reduce inflammation—factors that are crucial in managing T2DM [<span>7, 8</span>]. However, both metformin and fiber alter the gut microbiome in different ways, and this complex
{"title":"Potential Detrimental Interactions Between Metformin and Supplemental Dietary Fiber in Type 2 Diabetes","authors":"Rosemary M. Hall, Amber Parry-Strong, David O'Sullivan, Jeremy D. Krebs, Olivier Gasser","doi":"10.1111/1753-0407.70101","DOIUrl":"https://doi.org/10.1111/1753-0407.70101","url":null,"abstract":"<p>Higher intakes of dietary fiber have been associated with a reduced risk of developing Type 2 Diabetes (T2DM) and cardiovascular disease [<span>1, 2</span>]. Fiber supplementation improves overall glycaemia, with reductions in Hba1c and better insulin sensitivity [<span>3</span>]. However, there is significant reported heterogeneity on the effects of supplemental fiber on glycaemic outcomes for people with T2DM, potentially due to variations in absorption and metabolism. These differences, we believe, are worth examining more closely, especially considering the complexities of the gut microbiome, medications used in T2DM, and the role of the background diet [<span>3</span>].</p><p>In our recent study, we investigated the impact of supplemental fiber on glucose metabolism and glycemic control in people with pre-diabetes and T2DM who had a low habitual fiber intake. We recruited 30 participants with HbA1c levels ranging from 45 to 70 mmol/mol, and provided them with psyllium fiber supplements for 12 weeks.</p><p>Although we observed reductions in body mass index (BMI) and improvements in lipid profiles, HbA1c levels did not significantly improve overall. Surprisingly, participants taking metformin alone experienced an increase in HbA1c, while those not taking metformin experienced a slight reduction (Figure 1).</p><p>This discrepancy points to a critical issue: the potential interaction between metformin and fiber supplementation. Metformin, the most common medication for T2DM works by reducing hepatic glucose production and improving insulin sensitivity [<span>4</span>]. However, metformin primarily acts within the gastrointestinal tract, commonly producing gastrointestinal side-effects and may alter gut microbiome, with the potential to directly affect fiber absorption [<span>5</span>]. Our findings suggest that when combined with fiber supplementation, metformin may impair the metabolic benefits typically associated with fiber, alongside a potential detrimental effect on the glycaemic benefits of metformin.</p><p>This phenomenon is consistent with previous research. For example, a study by Tramontana et al. found that a high-fiber diet did not improve HbA1c in 78 patients with T2DM on metformin monotherapy [<span>6</span>], while other studies observed more promising results when fiber was combined with different medications [<span>7</span>]. These findings highlight the need for a more nuanced understanding of how dietary fiber interacts with both the gut microbiome and medications like metformin.</p><p>Moreover, the gut microbiota's role in metabolism is integral to the overall metabolic benefits. Dietary fiber, especially in the form of psyllium, is fermented by gut bacteria into short-chain fatty acids (SCFAs), which have been shown to improve immune function and reduce inflammation—factors that are crucial in managing T2DM [<span>7, 8</span>]. However, both metformin and fiber alter the gut microbiome in different ways, and this complex ","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"17 5","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1753-0407.70101","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144108865","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}
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