Higher levels of remnant cholesterol (Rem-C) are associated with diabetic conditions, serving as a treatment target and surrogate marker for identifying high-risk groups for diabetes mellitus (DM) onset. However, the effect of Rem-C on DM onset based on sex and age remains unclear. We aimed to examine the association between Rem-C levels and DM onset, stratified by sex and age.
Methods
In this health checkup-based retrospective cohort study, we analyzed data from 13,952 participants who underwent medical checkups two or more times at the Ehime General Health Care Association between April 2003 and March 2021, a non-hospital facility where health care services are provided to company employees and local residents. The mean follow-up period was 4.66 years. Cox proportional hazard models were used to assess the association between Rem-C and DM onset.
Results
In the multivariate analysis, higher Rem-C levels were associated with DM onset in individuals aged <50 years (men: adjusted hazard ratio [aHR] = 1.81, 95% CI: 1.46–2.20; women: aHR = 2.13, 95% CI: 1.18–3.37). However, this association was not observed in those aged ≥50 years. Triglycerides (TG) were also significantly associated with DM onset in younger adults, with slightly higher predictive ability (AUC) than Rem-C, particularly among younger women. Sensitivity analyses using continuous age as a variable showed similar trends.
Conclusions
Rem-C and TG may be useful predictors of DM onset in younger adults, with TG showing slightly better performance. Age-specific strategies may improve early DM prevention.
{"title":"Effect of remnant cholesterol on the onset of diabetes mellitus","authors":"Teruki Miyake, Shinya Furukawa, Ayumi Kanamoto, Osamu Yoshida, Yoshimasa Murakami, Masumi Miyazaki, Akihito Shiomi, Sho Ishikawa, Yuki Numata, Hironobu Nakaguchi, Yoshiko Nakamura, Mitsuhito Koizumi, Takao Watanabe, Yasunori Yamamoto, Hirohito Mori, Eiji Takeshita, Teru Kumagi, Yoshio Ikeda, Masanori Abe, Bunzo Matsuura, Takeru Iwata, Yoichi Hiasa","doi":"10.1111/jdi.70163","DOIUrl":"10.1111/jdi.70163","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Higher levels of remnant cholesterol (Rem-C) are associated with diabetic conditions, serving as a treatment target and surrogate marker for identifying high-risk groups for diabetes mellitus (DM) onset. However, the effect of Rem-C on DM onset based on sex and age remains unclear. We aimed to examine the association between Rem-C levels and DM onset, stratified by sex and age.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this health checkup-based retrospective cohort study, we analyzed data from 13,952 participants who underwent medical checkups two or more times at the Ehime General Health Care Association between April 2003 and March 2021, a non-hospital facility where health care services are provided to company employees and local residents. The mean follow-up period was 4.66 years. Cox proportional hazard models were used to assess the association between Rem-C and DM onset.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the multivariate analysis, higher Rem-C levels were associated with DM onset in individuals aged <50 years (men: adjusted hazard ratio [aHR] = 1.81, 95% CI: 1.46–2.20; women: aHR = 2.13, 95% CI: 1.18–3.37). However, this association was not observed in those aged ≥50 years. Triglycerides (TG) were also significantly associated with DM onset in younger adults, with slightly higher predictive ability (AUC) than Rem-C, particularly among younger women. Sensitivity analyses using continuous age as a variable showed similar trends.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Rem-C and TG may be useful predictors of DM onset in younger adults, with TG showing slightly better performance. Age-specific strategies may improve early DM prevention.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 1","pages":"120-128"},"PeriodicalIF":3.0,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.70163","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145375805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p>To the Editor,</p><p>We read with great interest the article by Ito <i>et al</i>.<span><sup>1</sup></span> on the relationship between diabetic peripheral neuropathy (DPN) and muscle strength in patients with type 2 diabetes. The meta-analysis greatly improves our understanding of the association between DPN and lower limb strength by analyzing previous research and adding to it. Although the article provides great insight into the topic, we have found certain limitations that may have affected the results of this study.</p><p>Firstly, the studies included in the article have vastly different diagnostic criteria for diagnosing DPN. Some have opted for NCS while others have used a mix of techniques. This approach complicates comparisons as there is a chance of misclassification bias. Recent studies suggest that methods like Quantitative Sensory Testing (QST) can be used to assess the sensory loss that occurs before any of the muscular symptoms, and Nerve Conduction Studies serve as a standard tool to assess peripheral nerve function<span><sup>2</sup></span>. There is no mention of a uniform criteria applied to assess and diagnose DPN. Hence, a standard criteria for diagnosis would have improved reproducibility and accuracy.</p><p>Secondly, there is no discussion about the underlying mechanisms that contribute to this association. The study reports strength outcomes but does not address potential mediators such as reduced muscle mass (detectable via MRI or DEXA), motor unit loss, or neuromuscular junction dysfunction. Chronic high blood sugar and oxidative stress damage nerves and blood vessels, disrupting nerve–muscle communication and reducing muscle function; all of these may contribute to the outcome<span><sup>3</sup></span>. Therefore, a detailed discussion about these underlying mechanisms would greatly strengthen the study's interpretation. Integrating the use of imaging and other tools may help with the clinical aspect of future research.</p><p>Third, the absence of longitudinal cohort data restricts the ability to draw logical conclusions. Cross-sectional studies cannot differentiate whether worsening of neuropathy leads to muscle decline or if it is related to poor glycemic control. Studies with repeated measures of DPN severity and muscle strength would allow us to follow its effects over time and improve our understanding of its progression. DPN clearly reduces LEMS in older type 2 diabetic patients within 4 years. It also results in loss of LEMS and decrease in mobility due to DPN. For that reason, DPN examination should be considered, with glycemic control and LEMS maintained at a high level to ensure quality of life in type 2 diabetic patients<span><sup>4</sup></span>.</p><p>In conclusion, indeed the article highlights an important link between DPN and muscular weakness; addressing these methodological issues—uniform diagnostic criteria, mechanistic analysis, and longitudinal follow-up—would considerably strengthen future research
{"title":"Letter to the Editor in response to the article ‘Association between diabetic peripheral neuropathy and lower limb muscle strength in patients with type 2 diabetes mellitus: A systematic review and meta-analysis’","authors":"Sudais Bin Sohaib, Huzaifah Ahmed","doi":"10.1111/jdi.70188","DOIUrl":"10.1111/jdi.70188","url":null,"abstract":"<p>To the Editor,</p><p>We read with great interest the article by Ito <i>et al</i>.<span><sup>1</sup></span> on the relationship between diabetic peripheral neuropathy (DPN) and muscle strength in patients with type 2 diabetes. The meta-analysis greatly improves our understanding of the association between DPN and lower limb strength by analyzing previous research and adding to it. Although the article provides great insight into the topic, we have found certain limitations that may have affected the results of this study.</p><p>Firstly, the studies included in the article have vastly different diagnostic criteria for diagnosing DPN. Some have opted for NCS while others have used a mix of techniques. This approach complicates comparisons as there is a chance of misclassification bias. Recent studies suggest that methods like Quantitative Sensory Testing (QST) can be used to assess the sensory loss that occurs before any of the muscular symptoms, and Nerve Conduction Studies serve as a standard tool to assess peripheral nerve function<span><sup>2</sup></span>. There is no mention of a uniform criteria applied to assess and diagnose DPN. Hence, a standard criteria for diagnosis would have improved reproducibility and accuracy.</p><p>Secondly, there is no discussion about the underlying mechanisms that contribute to this association. The study reports strength outcomes but does not address potential mediators such as reduced muscle mass (detectable via MRI or DEXA), motor unit loss, or neuromuscular junction dysfunction. Chronic high blood sugar and oxidative stress damage nerves and blood vessels, disrupting nerve–muscle communication and reducing muscle function; all of these may contribute to the outcome<span><sup>3</sup></span>. Therefore, a detailed discussion about these underlying mechanisms would greatly strengthen the study's interpretation. Integrating the use of imaging and other tools may help with the clinical aspect of future research.</p><p>Third, the absence of longitudinal cohort data restricts the ability to draw logical conclusions. Cross-sectional studies cannot differentiate whether worsening of neuropathy leads to muscle decline or if it is related to poor glycemic control. Studies with repeated measures of DPN severity and muscle strength would allow us to follow its effects over time and improve our understanding of its progression. DPN clearly reduces LEMS in older type 2 diabetic patients within 4 years. It also results in loss of LEMS and decrease in mobility due to DPN. For that reason, DPN examination should be considered, with glycemic control and LEMS maintained at a high level to ensure quality of life in type 2 diabetic patients<span><sup>4</sup></span>.</p><p>In conclusion, indeed the article highlights an important link between DPN and muscular weakness; addressing these methodological issues—uniform diagnostic criteria, mechanistic analysis, and longitudinal follow-up—would considerably strengthen future research","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 1","pages":"189-190"},"PeriodicalIF":3.0,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.70188","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145375880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Few studies have assessed whether dynamic kidney function prior to sodium–glucose cotransporter-2 inhibitor (SGLT2i) initiation influenced subsequent renal outcomes. Thus, the study aimed to investigate whether combining estimated glomerular filtration rate (eGFR) slope and urinary albumin/creatinine ratio (UACR) change prior to using SGLT2i contributes to subsequent kidney outcomes.
Materials and Methods
This retrospective cohort study utilized data from the Kaohsiung Medical University Hospital Research Database (KMUHRD) in Taiwan. We identified 975 SGLT2i new users with type 2 diabetes from 2016 to 2020, who had an eGFR >60 mL/min/1.73 m2 and UACR <30 mg/g 1 year prior to using SGLT2i. Patients were categorized into four groups based on an eGFR decline rate of 2.5 mL/min/1.73 m2/year and a UACR increase of 30%. The primary study outcomes included a >30% eGFR decline with a drop in eGFR categories and a >43% UACR increase with progression in UACR categories.
Results
After SGLT2i treatment, compared with the non-progressive renal function group, the glomerular injury group significantly lowered the risk of eGFR decline (adjusted hazard ratio [95% CI] 0.384 [0.199, 0.740]) and UACR progression (adjusted hazard ratio [95% CI] 0.514 [0.313, 0.846]). In addition, for those with a major eGFR decline before starting SGLT2i, significant improvements in the eGFR slope (P < 0.05) were observed after the treatment, irrespective of UACR increase.
Conclusions
Early initiation of SGLT2i among type 2 diabetes patients with low-risk renal disease progression and glomerular injury renal status may prevent them from progressing into chronic kidney disease.
{"title":"The impact of dynamic kidney function prior to using sodium–glucose cotransporter-2 inhibitors in type 2 diabetes patients with low-risk renal disease progression","authors":"Yen-Chen Chiu, Wanchana Singhan, Surarong Chinwong, Dujrudee Chinwong, Shang-Jyh Hwang, Yaw-Bin Huang","doi":"10.1111/jdi.70180","DOIUrl":"10.1111/jdi.70180","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims/Introduction</h3>\u0000 \u0000 <p>Few studies have assessed whether dynamic kidney function prior to sodium–glucose cotransporter-2 inhibitor (SGLT2i) initiation influenced subsequent renal outcomes. Thus, the study aimed to investigate whether combining estimated glomerular filtration rate (eGFR) slope and urinary albumin/creatinine ratio (UACR) change prior to using SGLT2i contributes to subsequent kidney outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>This retrospective cohort study utilized data from the Kaohsiung Medical University Hospital Research Database (KMUHRD) in Taiwan. We identified 975 SGLT2i new users with type 2 diabetes from 2016 to 2020, who had an eGFR >60 mL/min/1.73 m<sup>2</sup> and UACR <30 mg/g 1 year prior to using SGLT2i. Patients were categorized into four groups based on an eGFR decline rate of 2.5 mL/min/1.73 m<sup>2</sup>/year and a UACR increase of 30%. The primary study outcomes included a >30% eGFR decline with a drop in eGFR categories and a >43% UACR increase with progression in UACR categories.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After SGLT2i treatment, compared with the non-progressive renal function group, the glomerular injury group significantly lowered the risk of eGFR decline (adjusted hazard ratio [95% CI] 0.384 [0.199, 0.740]) and UACR progression (adjusted hazard ratio [95% CI] 0.514 [0.313, 0.846]). In addition, for those with a major eGFR decline before starting SGLT2i, significant improvements in the eGFR slope (<i>P</i> < 0.05) were observed after the treatment, irrespective of UACR increase.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Early initiation of SGLT2i among type 2 diabetes patients with low-risk renal disease progression and glomerular injury renal status may prevent them from progressing into chronic kidney disease.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"16 12","pages":"2173-2181"},"PeriodicalIF":3.0,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.70180","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145306614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p>Dear Editor,</p><p>We read with interest the secondary analysis by Wang <i>et al</i>.<span><sup>1</sup></span> titled “A 90 g/day low-carbohydrate diet improved glycemic control without decreasing frailty in older patients with type 2 diabetes,” published in the Journal of Diabetes Investigation (2025). The study addresses a highly relevant clinical question concerning dietary management and frailty in an aging diabetic population. However, several methodological limitations merit careful consideration when interpreting the validity and generalizability of the findings.</p><p>Firstly, the study suffers from a critically small sample size (<i>n</i> = 44 randomized, <i>n</i> = 42 analyzed), which severely limits the statistical power to detect meaningful differences, particularly for multidimensional outcomes like frailty<span><sup>2</sup></span>. For instance, the nonsignificant difference in HbA1c change between groups (−1.55% vs −0.97%, <i>P</i> = 0.097) may reflect a Type II error rather than a true absence of effect, especially since the original RCT with a larger sample did find a significant difference. Similarly, frailty transitions—a complex outcome requiring substantial power—were likely underpowered to detect clinically meaningful changes, as evidenced by the wide confidence intervals and unstable proportions in frailty categories. To strengthen future research, a priori sample size calculation specific to frailty outcomes and the use of more sensitive, continuous frailty instruments are recommended.</p><p>Secondly, the randomization process may have been compromised, as suggested by baseline imbalances in key demographic variables. Although not statistically significant, marital status differed notably between groups (15% single/widowed in TDD vs 40.9% in LCD, <i>P</i> = 0.063), which could influence social support, dietary adherence, and health behaviors. Such imbalances, even if incidental, may introduce confounding and bias the estimated effects of the dietary intervention<span><sup>3</sup></span>. Reporting a CONSORT flow diagram with detailed randomization procedures and using stratified or adaptive randomization methods in future studies would improve group comparability and internal validity.</p><p>Lastly, the assessment of frailty was limited to only two time points (baseline and 18 months) without interim measurements, which fails to capture dynamic changes and may miss short-term improvements or deteriorations in frailty status. Frailty is a mutable condition, and infrequent assessments reduce the ability to identify trends or causal pathways related to dietary changes<span><sup>4</sup></span>. Incorporating more frequent frailty assessments—for example, every 6 months—and using objective, continuous measures of physical performance (e.g., repeated gait speed or grip strength tests) would provide a more nuanced understanding of intervention effects over time.</p><p>In conclusion, while the study addresses an important clini
亲爱的编辑，我们饶有兴趣地阅读了Wang等人发表在《糖尿病调查杂志》（2025）上的一篇题为《90克/天的低碳水化合物饮食改善老年2型糖尿病患者的血糖控制而不减少虚弱》的第二篇分析。该研究解决了一个高度相关的临床问题，即饮食管理和老年糖尿病人群的虚弱。然而，在解释研究结果的有效性和普遍性时，一些方法上的局限性值得仔细考虑。首先，该研究的样本量非常小（随机n = 44，分析n = 42），这严重限制了检测有意义差异的统计能力，特别是对于虚弱等多维结果。例如，各组之间HbA1c变化的不显著差异（- 1.55% vs - 0.97%, P = 0.097）可能反映了II型误差，而不是真正的没有影响，特别是因为原始RCT的大样本确实发现了显著差异。同样，虚弱的转变——一个需要大量能量的复杂结果——可能不足以检测到临床有意义的变化，正如在虚弱类别中广泛的置信区间和不稳定的比例所证明的那样。为了加强未来的研究，建议对脆弱性结果进行先验的样本量计算，并使用更灵敏、连续的脆弱性工具。其次，随机化过程可能受到损害，正如关键人口变量的基线不平衡所表明的那样。虽然没有统计学意义，但各组之间的婚姻状况差异显著（TDD中单身/丧偶占15%，LCD中单身/丧偶占40.9%,P = 0.063），这可能影响社会支持、饮食依从性和健康行为。这种不平衡，即使是偶然的，也可能使饮食干预的估计效果产生混淆和偏差。报告具有详细随机化程序的CONSORT流程图，并在未来的研究中使用分层或自适应随机化方法，将提高组间可比性和内部有效性。最后，虚弱的评估仅限于两个时间点（基线和18个月），没有临时测量，无法捕捉动态变化，可能会错过虚弱状态的短期改善或恶化。虚弱是一种易变的状态，不频繁的评估降低了识别与饮食变化相关的趋势或因果途径的能力。结合更频繁的虚弱评估——例如，每6个月一次——并使用客观的、连续的身体表现测量（例如，重复的步态速度或握力测试），将提供对干预效果的更细致的理解。总之，虽然该研究解决了一个重要的临床问题，但有限的样本量、潜在的随机化不平衡和不频繁的虚弱评估削弱了其研究结果的稳健性。在未来的研究中解决这些问题对于得出关于饮食干预在减轻老年糖尿病患者虚弱和改善代谢健康方面的作用的可靠结论至关重要。作者声明无利益冲突。研究方案的批准：无。知情同意：无。注册批准日期及注册编号。研究/试验：无。动物研究：无。数据共享不适用于本文，因为本研究没有创建或分析新的数据。
{"title":"Critical methodological concerns regarding the secondary analysis of a low-carbohydrate diet trial on frailty in older diabetic patients","authors":"Li Zhou, Yinyin Fu","doi":"10.1111/jdi.70183","DOIUrl":"10.1111/jdi.70183","url":null,"abstract":"<p>Dear Editor,</p><p>We read with interest the secondary analysis by Wang <i>et al</i>.<span><sup>1</sup></span> titled “A 90 g/day low-carbohydrate diet improved glycemic control without decreasing frailty in older patients with type 2 diabetes,” published in the Journal of Diabetes Investigation (2025). The study addresses a highly relevant clinical question concerning dietary management and frailty in an aging diabetic population. However, several methodological limitations merit careful consideration when interpreting the validity and generalizability of the findings.</p><p>Firstly, the study suffers from a critically small sample size (<i>n</i> = 44 randomized, <i>n</i> = 42 analyzed), which severely limits the statistical power to detect meaningful differences, particularly for multidimensional outcomes like frailty<span><sup>2</sup></span>. For instance, the nonsignificant difference in HbA1c change between groups (−1.55% vs −0.97%, <i>P</i> = 0.097) may reflect a Type II error rather than a true absence of effect, especially since the original RCT with a larger sample did find a significant difference. Similarly, frailty transitions—a complex outcome requiring substantial power—were likely underpowered to detect clinically meaningful changes, as evidenced by the wide confidence intervals and unstable proportions in frailty categories. To strengthen future research, a priori sample size calculation specific to frailty outcomes and the use of more sensitive, continuous frailty instruments are recommended.</p><p>Secondly, the randomization process may have been compromised, as suggested by baseline imbalances in key demographic variables. Although not statistically significant, marital status differed notably between groups (15% single/widowed in TDD vs 40.9% in LCD, <i>P</i> = 0.063), which could influence social support, dietary adherence, and health behaviors. Such imbalances, even if incidental, may introduce confounding and bias the estimated effects of the dietary intervention<span><sup>3</sup></span>. Reporting a CONSORT flow diagram with detailed randomization procedures and using stratified or adaptive randomization methods in future studies would improve group comparability and internal validity.</p><p>Lastly, the assessment of frailty was limited to only two time points (baseline and 18 months) without interim measurements, which fails to capture dynamic changes and may miss short-term improvements or deteriorations in frailty status. Frailty is a mutable condition, and infrequent assessments reduce the ability to identify trends or causal pathways related to dietary changes<span><sup>4</sup></span>. Incorporating more frequent frailty assessments—for example, every 6 months—and using objective, continuous measures of physical performance (e.g., repeated gait speed or grip strength tests) would provide a more nuanced understanding of intervention effects over time.</p><p>In conclusion, while the study addresses an important clini","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.70183","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145297867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p>Obesity has become one of the most pressing global health challenges of the 21st century, contributing to a broad spectrum of noncommunicable diseases, including type 2 diabetes, cardiovascular disorders, steatotic liver disease, certain cancers, and musculoskeletal complications. Its prevalence continues to rise worldwide, imposing substantial burdens on health systems and societies. At the same time, remarkable advances have been made in recent years, with the development of highly effective pharmacotherapies acting on receptors related to glucagon-like peptide-1 (GLP-1) and with the refinement of bariatric and metabolic surgery. These breakthroughs have transformed the therapeutic landscape and highlighted the importance of precise disease definitions to identify patients most likely to benefit from intervention.</p><p>In light of these developments and broader challenges, an international commission convened by <i>The Lancet Diabetes & Endocrinology</i> recently proposed the concept of “clinical obesity” as a means of refining how obesity should be defined and addressed<span><sup>1</sup></span>. They argued that defining obesity solely by body mass index (BMI) is inadequate, as BMI fails to capture the heterogeneous health risks associated with excess adiposity. Instead, the report emphasized the need to consider both fat distribution and the functional consequences of adiposity.</p><p>Within this framework, excess adiposity is divided into two categories: <i>preclinical obesity</i>, where there is excess adiposity without demonstrable impairment, and <i>clinical obesity</i>, where adiposity has already produced organ or tissue dysfunction and/or limitations in age-adjusted daily living activities. By introducing these categories, the authors sought to clearly distinguish between individuals at risk and those already experiencing disease due to obesity (Figure 1).</p><p>The commission also stressed that this new framework should lay the foundation for a future international consensus. Implementation, they suggested, will require global harmonization of definitions and approaches, while also allowing regional adaptation to account for country-specific epidemiology, health systems, and resources. Thus, the proposal represents an aspirational step intended to guide future clinical practice and policy. At this stage, however, it remains primarily a conceptual framework, and its translation into tangible outcomes will depend on subsequent international and regional efforts.</p><p>This definition emphasizes the central role of visceral fat and accommodates ethnic differences in susceptibility to obesity-related disease. The pathological significance of visceral fat was identified in Japan, and this concept is now widely recognized as globally relevant<span><sup>4</sup></span>. By requiring evidence of functional impairment or high-risk adiposity, it provides a pragmatic approach to prioritizing individuals for medical intervention.</p><p>Jap
肥胖已成为21世纪最紧迫的全球健康挑战之一，导致了广泛的非传染性疾病，包括2型糖尿病、心血管疾病、脂肪变性肝病、某些癌症和肌肉骨骼并发症。它在世界范围内的流行率继续上升，给卫生系统和社会造成了沉重负担。与此同时，近年来，随着作用于胰高血糖素样肽-1 （GLP-1）相关受体的高效药物治疗的发展以及减肥和代谢手术的完善，胰高血糖素样肽-1的治疗取得了显著进展。这些突破改变了治疗领域，并强调了精确的疾病定义对于确定最有可能从干预中受益的患者的重要性。鉴于这些发展和更广泛的挑战，由《柳叶刀糖尿病与内分泌学》召集的一个国际委员会最近提出了“临床肥胖”的概念，作为改进肥胖应该如何定义和处理的一种手段。他们认为，仅仅通过身体质量指数（BMI）来定义肥胖是不够的，因为BMI无法捕捉到与过度肥胖相关的各种健康风险。相反，该报告强调需要同时考虑脂肪分布和肥胖的功能后果。在这个框架内，过度肥胖分为两类：临床前肥胖，即存在过度肥胖，但没有明显的损害；临床肥胖，即肥胖已经产生器官或组织功能障碍和/或限制了年龄调整后的日常生活活动。通过引入这些分类，作者试图明确区分有风险的个体和已经因肥胖而患病的个体（图1）。委员会还强调，这一新框架应为未来的国际共识奠定基础。他们建议，实施将需要全球统一定义和方法，同时也允许区域适应，以考虑到具体国家的流行病学、卫生系统和资源。因此，该建议代表了一个旨在指导未来临床实践和政策的理想步骤。然而，在目前阶段，它主要仍然是一个概念框架，将其转化为具体成果将取决于随后的国际和区域努力。这一定义强调了内脏脂肪的核心作用，并适应了对肥胖相关疾病易感性的种族差异。内脏脂肪的病理意义是在日本发现的，现在这一概念被广泛认为是全球相关的4。通过要求功能障碍或高风险肥胖的证据，它提供了一种实用的方法来优先考虑个人的医疗干预。2015年亚洲-大洋洲肥胖问题会议上关于肥胖疾病的国际声明（名古屋声明）进一步强调了日本的先锋作用。这一声明促进了“肥胖疾病”概念的传播，并强调了需要治疗的有并发症的肥胖和需要预防的无并发症的肥胖之间的区别。日本早期的倡议有助于塑造东亚的区域视角，这些努力通过相互学术交流得到加强。例如，韩国和台湾已经制定了自己的诊断标准和管理指南，其中包括较低的BMI阈值，并强调代谢风险6,7。这些指南考虑到肥胖相关的合并症和代谢并发症在临床决策中的重要性。这一区域演变反映了东亚肥胖的共同特征和特定人群特征。自2000年以来，JASSO定期更新其肥胖疾病管理指南，最近一次是在2022年。这些指南根据疾病严重程度提出了明确的诊断标准、治疗目标和减肥目标3。日本也在2013年建立了肥胖医学专家认证制度（日语：Himan-sho senmon-i， senmon-i的意思是认证专家），并不断扩大。这一系统确保了医生管理肥胖拥有标准化的专业知识。重要的是，该框架与公共健康保险直接相关：诊断为肥胖疾病的个人可获得抗肥胖药物治疗和减肥/代谢手术的报销。这一综合框架很可能巩固了日本的独特地位，使其成为世界上为数不多的将抗肥胖药物治疗纳入公共健康保险报销的国家之一。 除全球开发项目外，一项日韩联合试验（semaglutide, STEP6）8和一项日本独立试验（tizepatide, SURMOUNT-J）9是专门根据肥胖症概念和JASSO指南设计的。这些试验的结果在支持监管部门批准方面发挥了决定性作用。因此，Wegovy（西马鲁肽）和Zepbound（替西帕肽）在特定条件下获得了日本公共健康保险的报销。此外，他们的包装说明书明确列出了JASSO定义的11种与肥胖相关的健康障碍。诊断标准、医生培训和肥胖医疗保险之间的这种一致性在国际上并不常见，它代表了一种疾病管理的综合模式。JASSO还开发了一个全国性的肥胖疾病数据基础设施，称为J-ORBIT（基于电子健康记录的日本肥胖研究）10。J-ORBIT直接从电子病历中提取临床数据，可以收集各种真实世界的证据。这包括验证11种肥胖相关健康障碍的临床相关性，并支持不断完善的诊断标准。在肥胖治疗的深刻变化中，这样的系统为未来的研究和临床实践提供了宝贵的基础。临床肥胖的国际结构和日本肥胖疾病框架都认识到，当过度肥胖导致切实的健康损害时，肥胖就成为一种疾病，而不是在任意的BMI阈值（图1）1,3。两人都主张超越BMI，将身体脂肪分布和器官功能纳入临床决策。关键的分歧依然存在。临床肥胖的概念强调功能损害和日常生活的限制作为中心诊断要素。相比之下，JASSO将特定的肥胖相关健康障碍和内脏脂肪性肥胖定义为诊断标准。这反映了日本的流行病学现实：东亚人群在相对较低的BMI水平上出现代谢和心血管并发症，通常是由内脏脂肪引起的。日本的长期经验提供了一些具有全球意义的教训。首先，肥胖症概念的早期采用和制度化表明，这种框架可以有效地整合到国家指南、专家培训和保险系统中超过二十年。第二，日本的做法强调了针对特定人群的适应的重要性，因为诊断阈值必须反映脂肪分布和疾病风险的种族和地区差异。第三，政策整合也至关重要，因为将诊断标准与保险报销联系起来可以确保公平获得循证治疗。最后，日本建立了一个全国性的登记处，如J-ORBIT，说明了学术协会主导的数据基础设施如何产生真实世界的证据，从而连接临床实践、研究和政策。肥胖的挑战不仅需要有效的治疗方法，还需要强有力的、有临床意义的定义。日本对肥胖疾病的开创性采用说明了这样的框架如何能够形成指导方针，为培训提供信息，指导保险覆盖范围，并支持研究。随着全球社会完善临床肥胖的概念，承认并学习日本超过四分之一世纪的经验将丰富国际共识，并加速发展有效、公平的肥胖治疗方法。这项工作没有得到特别的资助。已获得Noster Inc.、Nippon Boehringer Ingelheim Co., Ltd.、Eli Lilly Japan K.K.、Abbott Diabetes Care UK Ltd.、Sumitomo Pharma Co., Ltd.和Teijin Pharma Ltd.的资助或合同；住友制药有限公司、日本勃林格殷格翰制药有限公司、雅培日本公司和诺和诺德制药有限公司的讲座或教育活动的奖金；在日本肥胖研究学会（JASSO）担任指导委员会主席；并报告了来自和田制药株式会社、诺和诺德制药株式会社、住友制药株式会社、武田制药株式会社和帝人制药株式会社的机构捐赠/奖学金。I.S.获得了Novo Nordisk Pharma Ltd， Teijin Pharma Limited, Mochida Pharmaceutical Co., Ltd, koowa Kirin Co., Ltd, Sumitomo Pharma Co., Ltd, Rohto Pharmaceutical Co., Ltd, Kobayashi Pharmaceutical Co., Ltd，日清食品控股有限公司，Kubara Honke Group Co.， Ltd和LC Cancerscan Inc.的资助或合同；包括（但不限于）ARKRAY， MSD, Astellas Pharma, AstraZeneca, Abbott Japan Co., Ltd., Ono Pharmaceut
{"title":"Clinical obesity and Himan-sho (obesity disease): Lessons from Japan's 25 years of experience toward a new era of obesity care","authors":"Wataru Ogawa, Iichiro Shimomura, Toshimasa Yamauchi, Koutaro Yokote","doi":"10.1111/jdi.70178","DOIUrl":"10.1111/jdi.70178","url":null,"abstract":"<p>Obesity has become one of the most pressing global health challenges of the 21st century, contributing to a broad spectrum of noncommunicable diseases, including type 2 diabetes, cardiovascular disorders, steatotic liver disease, certain cancers, and musculoskeletal complications. Its prevalence continues to rise worldwide, imposing substantial burdens on health systems and societies. At the same time, remarkable advances have been made in recent years, with the development of highly effective pharmacotherapies acting on receptors related to glucagon-like peptide-1 (GLP-1) and with the refinement of bariatric and metabolic surgery. These breakthroughs have transformed the therapeutic landscape and highlighted the importance of precise disease definitions to identify patients most likely to benefit from intervention.</p><p>In light of these developments and broader challenges, an international commission convened by <i>The Lancet Diabetes & Endocrinology</i> recently proposed the concept of “clinical obesity” as a means of refining how obesity should be defined and addressed<span><sup>1</sup></span>. They argued that defining obesity solely by body mass index (BMI) is inadequate, as BMI fails to capture the heterogeneous health risks associated with excess adiposity. Instead, the report emphasized the need to consider both fat distribution and the functional consequences of adiposity.</p><p>Within this framework, excess adiposity is divided into two categories: <i>preclinical obesity</i>, where there is excess adiposity without demonstrable impairment, and <i>clinical obesity</i>, where adiposity has already produced organ or tissue dysfunction and/or limitations in age-adjusted daily living activities. By introducing these categories, the authors sought to clearly distinguish between individuals at risk and those already experiencing disease due to obesity (Figure 1).</p><p>The commission also stressed that this new framework should lay the foundation for a future international consensus. Implementation, they suggested, will require global harmonization of definitions and approaches, while also allowing regional adaptation to account for country-specific epidemiology, health systems, and resources. Thus, the proposal represents an aspirational step intended to guide future clinical practice and policy. At this stage, however, it remains primarily a conceptual framework, and its translation into tangible outcomes will depend on subsequent international and regional efforts.</p><p>This definition emphasizes the central role of visceral fat and accommodates ethnic differences in susceptibility to obesity-related disease. The pathological significance of visceral fat was identified in Japan, and this concept is now widely recognized as globally relevant<span><sup>4</sup></span>. By requiring evidence of functional impairment or high-risk adiposity, it provides a pragmatic approach to prioritizing individuals for medical intervention.</p><p>Jap","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 1","pages":"5-8"},"PeriodicalIF":3.0,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.70178","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145297955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p>To the Editor,</p><p>I read with great interest the article by Wang <i>et al</i>., which assessed the effects of an 18-month, 90 g/day low-carbohydrate diet (LCD) in older adults with type 2 diabetes<span><sup>1</sup></span>. Running a nutritional trial of such length in an elderly cohort is demanding, and the investigators deserve recognition for achieving excellent retention and generating valuable long-term data. The reported improvements in HbA1c (−0.5% vs –0.2% in controls), 2-h post-meal glucose, and waist circumference, all without worsening frailty, are noteworthy. These findings are especially relevant given the growing burden of diabetes in older adults, where nutrition strategies that support metabolic health while maintaining physical function are urgently required.</p><p>However, two considerations need to be taken into account before the benefits can be ascribed solely to carbohydrate restriction. First, the Medication Effect Score dropped substantially in the LCD group at 18 months (−0.45 ± 0.71). A reduction in antihyperglycemic drugs can itself alter glycemic outcomes, particularly when treatment withdrawal follows clinical improvement. Previous systematic reviews of carbohydrate-restricted diets have emphasized that medication de-escalation frequently accounts for a significant share of the observed benefit<span><sup>2</sup></span>. Without considering medication intensity or separating results by treatment modification, it is difficult to isolate the direct impact of the diet.</p><p>Second, individuals assigned to the LCD arm reported a mean rise of about 450 kcal/week in physical activity. This difference carries clinical importance. Meta-analyses show that structured exercise programs reduce HbA1c by roughly 0.67%, while lifestyle advice combined with dietary support yields reductions of about 0.43%<span><sup>3</sup></span>. Physical activity also decreases visceral fat—one of the favorable outcomes in the LCD group. Because the trial was open-label, it is plausible that participants encouraged to follow the LCD also became more engaged in activity. Unless these behavioral shifts are taken into account, improvements may reflect exercise effects in addition to dietary change.</p><p>Future investigations could strengthen causal interpretation by using models that adjust for both medication intensity and activity changes or by performing sensitivity analyses limited to participants without therapy modifications. These strategies would help clarify the extent to which the LCD itself contributed to the metabolic improvements reported.</p><p>Respectfully,</p><p>The author declares no conflict of interest.</p><p>Approval of the research protocol: N/A.</p><p>Informed Consent: N/A.</p><p>Registry and the Registration No. of the study/trial: N/A.</p><p>Animal Studies: N/A.</p><p>The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy
致编辑，我怀着极大的兴趣阅读了Wang等人的文章，该文章评估了18个月90克/天的低碳水化合物饮食（LCD）对老年2型糖尿病患者的影响。在老年人群中进行如此长时间的营养试验是有要求的，研究者应该得到认可，因为他们取得了出色的保留和产生了有价值的长期数据。值得注意的是，HbA1c （- 0.5% vs -0.2%）、餐后2小时血糖和腰围的改善均未导致虚弱恶化。考虑到老年人糖尿病负担的增加，这些发现尤其相关，因为老年人迫切需要在维持身体功能的同时支持代谢健康的营养策略。然而，在将益处完全归因于限制碳水化合物之前，需要考虑两点。第一，LCD组用药效果评分在18个月时显著下降（- 0.45±0.71）。减少降糖药物本身可以改变血糖结果，特别是当临床改善后停药时。以前对碳水化合物限制饮食的系统回顾强调，药物减少通常占观察到的益处的很大一部分2。如果不考虑用药强度或通过治疗调整分离结果，很难分离出饮食的直接影响。第二，被分配到LCD组的人报告说，他们每周的体力活动平均增加了约450千卡。这种差异具有临床重要性。荟萃分析显示，有组织的锻炼计划可使HbA1c降低约0.67%，而生活方式建议结合饮食支持可使HbA1c降低约0.43%3。体育锻炼也能减少内脏脂肪——这是LCD组的一个有利结果。因为试验是开放标签的，所以被鼓励遵循LCD的参与者也变得更加投入到活动中来，这似乎是合理的。除非将这些行为转变考虑在内，否则除了饮食改变外，改善可能还反映了锻炼的效果。未来的调查可以通过使用调整药物强度和活动变化的模型，或通过对未修改治疗的参与者进行敏感性分析，来加强因果解释。这些策略将有助于阐明LCD本身在多大程度上促进了所报道的代谢改善。恕我直言，作者声明无利益冲突。研究方案的批准：无。知情同意：无。注册处及注册编号研究/试验：无。动物研究：无。支持本研究结果的数据可向通讯作者索取。由于隐私或道德限制，这些数据不会公开。
{"title":"Letter to the editor in response to ‘A 90 g/day low-carbohydrate diet improved glycemic control without decreasing frailty in older patients with type 2 diabetes’ by Wang et al.","authors":"Muhammad Farhan","doi":"10.1111/jdi.70182","DOIUrl":"10.1111/jdi.70182","url":null,"abstract":"<p>To the Editor,</p><p>I read with great interest the article by Wang <i>et al</i>., which assessed the effects of an 18-month, 90 g/day low-carbohydrate diet (LCD) in older adults with type 2 diabetes<span><sup>1</sup></span>. Running a nutritional trial of such length in an elderly cohort is demanding, and the investigators deserve recognition for achieving excellent retention and generating valuable long-term data. The reported improvements in HbA1c (−0.5% vs –0.2% in controls), 2-h post-meal glucose, and waist circumference, all without worsening frailty, are noteworthy. These findings are especially relevant given the growing burden of diabetes in older adults, where nutrition strategies that support metabolic health while maintaining physical function are urgently required.</p><p>However, two considerations need to be taken into account before the benefits can be ascribed solely to carbohydrate restriction. First, the Medication Effect Score dropped substantially in the LCD group at 18 months (−0.45 ± 0.71). A reduction in antihyperglycemic drugs can itself alter glycemic outcomes, particularly when treatment withdrawal follows clinical improvement. Previous systematic reviews of carbohydrate-restricted diets have emphasized that medication de-escalation frequently accounts for a significant share of the observed benefit<span><sup>2</sup></span>. Without considering medication intensity or separating results by treatment modification, it is difficult to isolate the direct impact of the diet.</p><p>Second, individuals assigned to the LCD arm reported a mean rise of about 450 kcal/week in physical activity. This difference carries clinical importance. Meta-analyses show that structured exercise programs reduce HbA1c by roughly 0.67%, while lifestyle advice combined with dietary support yields reductions of about 0.43%<span><sup>3</sup></span>. Physical activity also decreases visceral fat—one of the favorable outcomes in the LCD group. Because the trial was open-label, it is plausible that participants encouraged to follow the LCD also became more engaged in activity. Unless these behavioral shifts are taken into account, improvements may reflect exercise effects in addition to dietary change.</p><p>Future investigations could strengthen causal interpretation by using models that adjust for both medication intensity and activity changes or by performing sensitivity analyses limited to participants without therapy modifications. These strategies would help clarify the extent to which the LCD itself contributed to the metabolic improvements reported.</p><p>Respectfully,</p><p>The author declares no conflict of interest.</p><p>Approval of the research protocol: N/A.</p><p>Informed Consent: N/A.</p><p>Registry and the Registration No. of the study/trial: N/A.</p><p>Animal Studies: N/A.</p><p>The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy ","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"17 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.70182","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaohui Li, Yuhua Wei, Dandan Sun, Hongmei Xu, Chun Mu, Di Bao, Yingying Li, Qiuling Xing
Aims
To develop a diagnostic model of insulin-related lipohypertrophy for patients with diabetes mellitus.
Materials and Methods
A cross-sectional study was performed. Between December 2021 and November 2022, a total of 395 diabetic patients treated with insulin were enrolled from a tertiary hospital in Tianjin, China. Demographic and clinical factors were collected, and patients were assessed for lipohypertrophy by ultrasound scanning. The rate of lipohypertrophy was investigated, and a nomogram was developed based on a logistic regression model. SPSS 26.0 and R Studio 2022.12.0+353 3.6.3 were used to analyze the data.
Results
89.6% (354/395) patients were identified with lipohypertrophy. In this study, 693 lipohypertrophy sites in lipohypertrophy patients and 91.5% (634/693) lipohypertrophy were distributed at the abdomen. Self-injection, duration of insulin injection, and incorrect rotation were selected as predictors to develop a lipohypertrophy diagnosed diagnostic nomogram model of lipohypertrophy in diabetic patients treated with insulin. The accuracy, calibration, and clinical applicability of the model are good; thus, it fits well.
Conclusions
A nomogram including three easily available factors (self-injection, duration of insulin injection, and incorrect rotation) was developed, and it can be used in diabetes management among diabetes patients treated with insulin.
目的：建立糖尿病患者胰岛素相关性脂肪肥大的诊断模型。材料和方法：采用横断面研究。在2021年12月至2022年11月期间，共有395名接受胰岛素治疗的糖尿病患者从中国天津的一家三级医院入组。收集人口统计学和临床因素，并通过超声扫描评估患者是否存在脂肪肥大。研究了脂肪肥厚率，并根据logistic回归模型建立了nomogram。采用SPSS 26.0和R Studio 2022.12.0+353 3.6.3对数据进行分析。结果：89.6%（354/395）的患者被诊断为脂肪肥大。本研究中，肥胖患者脂肪增厚部位693个，91.5%（634/693）脂肪增厚部位分布在腹部。选择自我注射、胰岛素注射持续时间和不正确旋转作为预测因子，建立胰岛素治疗糖尿病患者的脂肪肥大诊断nomogram模型。模型的准确性、校正性和临床适用性较好；因此，它很适合。结论：建立了包含自我注射、胰岛素注射持续时间和不正确旋转3个容易获得的因素的nomogram，可用于胰岛素治疗的糖尿病患者的糖尿病管理。
{"title":"Development of a diagnostic model of insulin-related lipohypertrophy for patients with diabetes mellitus","authors":"Xiaohui Li, Yuhua Wei, Dandan Sun, Hongmei Xu, Chun Mu, Di Bao, Yingying Li, Qiuling Xing","doi":"10.1111/jdi.70156","DOIUrl":"10.1111/jdi.70156","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To develop a diagnostic model of insulin-related lipohypertrophy for patients with diabetes mellitus.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>A cross-sectional study was performed. Between December 2021 and November 2022, a total of 395 diabetic patients treated with insulin were enrolled from a tertiary hospital in Tianjin, China. Demographic and clinical factors were collected, and patients were assessed for lipohypertrophy by ultrasound scanning. The rate of lipohypertrophy was investigated, and a nomogram was developed based on a logistic regression model. SPSS 26.0 and R Studio 2022.12.0+353 3.6.3 were used to analyze the data.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>89.6% (354/395) patients were identified with lipohypertrophy. In this study, 693 lipohypertrophy sites in lipohypertrophy patients and 91.5% (634/693) lipohypertrophy were distributed at the abdomen. Self-injection, duration of insulin injection, and incorrect rotation were selected as predictors to develop a lipohypertrophy diagnosed diagnostic nomogram model of lipohypertrophy in diabetic patients treated with insulin. The accuracy, calibration, and clinical applicability of the model are good; thus, it fits well.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>A nomogram including three easily available factors (self-injection, duration of insulin injection, and incorrect rotation) was developed, and it can be used in diabetes management among diabetes patients treated with insulin.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"16 12","pages":"2182-2190"},"PeriodicalIF":3.0,"publicationDate":"2025-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.70156","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145278509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The renoprotective effects of luseogliflozin, a sodium-glucose cotransporter 2 inhibitor, in patients with renal dysfunction are unexamined. We evaluated the efficacy of luseogliflozin in slowing renal function decline among patients with type 2 diabetes mellitus and moderate to severe renal dysfunction.
Materials and Methods
In a multicenter, randomized, open-label, controlled clinical trial, patients with type 2 diabetes mellitus and an estimated glomerular filtration rate based on serum creatinine (eGFRcreat) of 15–45 mL/min/1.73 m2 were randomized into luseogliflozin or control groups. The primary endpoint was the change in eGFRcreat from baseline to 104 weeks. Secondary endpoints included eGFRcreat and eGFRcreat slope changes from 4 to 104 weeks (chronic eGFRcreat slope).
Results
Among 152 participants, eGFRcreat change from baseline to 104 weeks did not significantly differ between groups. The luseogliflozin group showed a significant decrease in eGFRcreat from 2 to 12 weeks compared to the control group; the largest decline occurred at 4 weeks (initial eGFR decline). There were no differences between groups thereafter. The chronic eGFRcreat slope was less negative in the luseogliflozin group compared to the control group (not significant). Conversely, subgroup analysis indicated that the difference in chronic eGFRcreat slope between groups was significantly greater (with a less negative or even positive slope observed in the luseogliflozin group compared to the control group) among patients with eGFRcreat <30 mL/min/1.73 m2, urinary albumin/creatinine ratio <30 mg/g creatinine, systolic blood pressure <130 mmHg, or females.
Conclusions
Although the primary endpoint did not reach statistical significance, luseogliflozin may provide renoprotective benefits in patients with type 2 diabetes mellitus and moderate-to-severe renal impairment, potentially by slowing eGFRcreat decline post-initial decline.
{"title":"Efficacy of luseogliflozin for renal function preservation in patients with type 2 diabetes mellitus and impaired renal function: A randomized open-label clinical trial (RESOLUTION study)","authors":"Munehiro Kitada, Masao Toyoda, Osamu Sekine, Daisuke Suzuki, Yosuke Okada, Yoshikata Morita, Hideki Nishimura, Hiroaki Satoh, Hideki Kamiya, Toshinari Takamura, Motohide Isono, Takeshi Onoue, Hiroshi Arima, Kenichi Tanaka, Masaji Miyamoto, Yasushi Omura, Daisuke Yabe, Takehiro Kato, Akimichi Asano, Yutaka Wakasa, Satoshi Miyamoto, Shinji Kume, Tomohiko Ito, Shin-ichi Araki, Atsushi Nakagawa, RESOLUTION Study Investigators","doi":"10.1111/jdi.70173","DOIUrl":"10.1111/jdi.70173","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The renoprotective effects of luseogliflozin, a sodium-glucose cotransporter 2 inhibitor, in patients with renal dysfunction are unexamined. We evaluated the efficacy of luseogliflozin in slowing renal function decline among patients with type 2 diabetes mellitus and moderate to severe renal dysfunction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>In a multicenter, randomized, open-label, controlled clinical trial, patients with type 2 diabetes mellitus and an estimated glomerular filtration rate based on serum creatinine (eGFRcreat) of 15–45 mL/min/1.73 m<sup>2</sup> were randomized into luseogliflozin or control groups. The primary endpoint was the change in eGFRcreat from baseline to 104 weeks. Secondary endpoints included eGFRcreat and eGFRcreat slope changes from 4 to 104 weeks (chronic eGFRcreat slope).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 152 participants, eGFRcreat change from baseline to 104 weeks did not significantly differ between groups. The luseogliflozin group showed a significant decrease in eGFRcreat from 2 to 12 weeks compared to the control group; the largest decline occurred at 4 weeks (initial eGFR decline). There were no differences between groups thereafter. The chronic eGFRcreat slope was less negative in the luseogliflozin group compared to the control group (not significant). Conversely, subgroup analysis indicated that the difference in chronic eGFRcreat slope between groups was significantly greater (with a less negative or even positive slope observed in the luseogliflozin group compared to the control group) among patients with eGFRcreat <30 mL/min/1.73 m<sup>2</sup>, urinary albumin/creatinine ratio <30 mg/g creatinine, systolic blood pressure <130 mmHg, or females.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Although the primary endpoint did not reach statistical significance, <b>l</b>useogliflozin may provide renoprotective benefits in patients with type 2 diabetes mellitus and moderate-to-severe renal impairment, potentially by slowing eGFRcreat decline post-initial decline.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"16 12","pages":"2160-2172"},"PeriodicalIF":3.0,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.70173","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Investigate the impact and mechanism of semaglutide (Sema) combined with high-intensity interval training (HIIT) on hepatic glucose/lipid metabolism in db/db mice using untargeted metabolomics.
Methods
Db/db mice were divided into model control, Sema alone, and Sema + HIIT groups, with db/m mice as controls. Sema (0.1 mg/kg/week) was administered subcutaneously, and the control group was subcutaneously injected with the same volume of distilled water. Engaging in HIIT swimming occurred for five consecutive days weekly. Weekly fasting plasma glucose (FPG), body mass, and food intake were assessed. After 8 weeks, blood/liver tissues were analyzed; liver metabolomics used LC–MS.
Results
Following an 8-week intervention, it was determined that the weight loss efficacy of Sema alone was suboptimal. The lowering of FPG did not differ significantly between the Sema alone and the combined intervention groups. The combined treatment demonstrated superior efficacy compared with Sema alone in enhancing liver weight, liver index, food intake, TG, TC, hepatic TG, and liver injury biomarkers (AST, ALT; P < 0.05). Histological findings indicated that the combination intervention markedly decreased fat vacuoles and inflammatory infiltration in hepatocytes (P < 0.001). A total of 721 differential metabolites were identified after the combined intervention, with primary alterations in amino acids and their derivatives, lipids, energy metabolism, and bile acids, encompassing key pathways such as the TCA cycle, amino acid metabolism, and bile acid metabolism.
Conclusions
Semaglutide combined with HIIT synergistically improves hepatic glucose and lipid metabolism in diabetic mice, providing a new treatment strategy for liver lipid disorders.
{"title":"Multi-pathway-driven hepatic protection: Semaglutide combined with HIIT counteracts diabetic liver injury in db/db mice","authors":"Wenjun Yu, Yongfu Liu, Shenglong Le, Yuxin Xiao, Xiaoyan Chen, Junhua Wang, Feng Gao","doi":"10.1111/jdi.70174","DOIUrl":"10.1111/jdi.70174","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Investigate the impact and mechanism of semaglutide (Sema) combined with high-intensity interval training (HIIT) on hepatic glucose/lipid metabolism in db/db mice using untargeted metabolomics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Db/db mice were divided into model control, Sema alone, and Sema + HIIT groups, with db/m mice as controls. Sema (0.1 mg/kg/week) was administered subcutaneously, and the control group was subcutaneously injected with the same volume of distilled water. Engaging in HIIT swimming occurred for five consecutive days weekly. Weekly fasting plasma glucose (FPG), body mass, and food intake were assessed. After 8 weeks, blood/liver tissues were analyzed; liver metabolomics used LC–MS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Following an 8-week intervention, it was determined that the weight loss efficacy of Sema alone was suboptimal. The lowering of FPG did not differ significantly between the Sema alone and the combined intervention groups. The combined treatment demonstrated superior efficacy compared with Sema alone in enhancing liver weight, liver index, food intake, TG, TC, hepatic TG, and liver injury biomarkers (AST, ALT; <i>P</i> < 0.05). Histological findings indicated that the combination intervention markedly decreased fat vacuoles and inflammatory infiltration in hepatocytes (<i>P</i> < 0.001). A total of 721 differential metabolites were identified after the combined intervention, with primary alterations in amino acids and their derivatives, lipids, energy metabolism, and bile acids, encompassing key pathways such as the TCA cycle, amino acid metabolism, and bile acid metabolism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Semaglutide combined with HIIT synergistically improves hepatic glucose and lipid metabolism in diabetic mice, providing a new treatment strategy for liver lipid disorders.</p>\u0000 </section>\u0000 </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"16 12","pages":"2145-2159"},"PeriodicalIF":3.0,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.70174","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
I read with great interest the article by Luo et al., ‘Associations between peripheral blood mitochondrial genomic variants and gestational diabetes mellitus and postpartum abnormal glucose metabolism’1. The authors are to be commended for exploring the relatively underinvestigated role of mitochondrial genomic variation in gestational diabetes mellitus (GDM). Their large sample size and combined analysis of genetic variants and copy number are clear strengths.
However, addressing certain methodological considerations could further strengthen the robustness of the study findings. First, the case–control design, as an observational study, restricts causal inference. The associations observed between mtDNA variants and GDM may reflect secondary effects of pregnancy-related metabolic stress rather than primary causes2.
Second, the study was limited to a single Chinese cohort. Because mitochondrial haplogroup distribution differs across ethnic groups, the generalizability of the findings to other populations may be limited3.
Furthermore, the analysis focused largely on the mtDNA D-loop, without a comprehensive evaluation of heteroplasmy or coding region variants. Heteroplasmy, in particular, can significantly influence mitochondrial function, and overlooking it may provide an incomplete picture4.
In conclusion, Luo et al. have made an important contribution linking mitochondrial variation to GDM, and their findings open promising avenues for future research. Future studies incorporating longitudinal follow-up, multi-ethnic cohorts, and full mitochondrial genome sequencing with functional validation would be valuable to advance understanding in this field.
None.
The authors declare no conflict of interest.
Approval of the research protocol: None.
Informed consent: None.
Registry and registration no. of the study/trial: None.
Animal studies: None.
Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.
{"title":"Letter to editor in response to ‘Associations between peripheral blood mitochondrial genomic variants and gestational diabetes mellitus and postpartum abnormal glucose metabolism’","authors":"Ameer Ahmed, Sajida Parveen","doi":"10.1111/jdi.70177","DOIUrl":"10.1111/jdi.70177","url":null,"abstract":"<p>Dear Editor,</p><p>I read with great interest the article by Luo <i>et al</i>., ‘Associations between peripheral blood mitochondrial genomic variants and gestational diabetes mellitus and postpartum abnormal glucose metabolism’<span><sup>1</sup></span>. The authors are to be commended for exploring the relatively underinvestigated role of mitochondrial genomic variation in gestational diabetes mellitus (GDM). Their large sample size and combined analysis of genetic variants and copy number are clear strengths.</p><p>However, addressing certain methodological considerations could further strengthen the robustness of the study findings. First, the case–control design, as an observational study, restricts causal inference. The associations observed between mtDNA variants and GDM may reflect secondary effects of pregnancy-related metabolic stress rather than primary causes<span><sup>2</sup></span>.</p><p>Second, the study was limited to a single Chinese cohort. Because mitochondrial haplogroup distribution differs across ethnic groups, the generalizability of the findings to other populations may be limited<span><sup>3</sup></span>.</p><p>Furthermore, the analysis focused largely on the mtDNA D-loop, without a comprehensive evaluation of heteroplasmy or coding region variants. Heteroplasmy, in particular, can significantly influence mitochondrial function, and overlooking it may provide an incomplete picture<span><sup>4</sup></span>.</p><p>In conclusion, Luo <i>et al</i>. have made an important contribution linking mitochondrial variation to GDM, and their findings open promising avenues for future research. Future studies incorporating longitudinal follow-up, multi-ethnic cohorts, and full mitochondrial genome sequencing with functional validation would be valuable to advance understanding in this field.</p><p>None.</p><p>The authors declare no conflict of interest.</p><p>Approval of the research protocol: None.</p><p>Informed consent: None.</p><p>Registry and registration no. of the study/trial: None.</p><p>Animal studies: None.</p><p>Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.</p>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"16 12","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.70177","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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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