Journal of Diabetes最新文献

{"title":"The Potential of SARMs and Antimyostatin Agents in Addressing Lean Body Mass Loss From GLP-1 Agonists: A Literature Review","authors":"Jimmy Wen,&nbsp;Ubaid Ansari,&nbsp;Mouhamad Shehabat,&nbsp;Zaid Ansari,&nbsp;Burhaan Syed,&nbsp;Adam Razick,&nbsp;Daniel Razick,&nbsp;Muzammil Akhtar,&nbsp;Eldo Frezza","doi":"10.1111/1753-0407.70119","DOIUrl":"https://doi.org/10.1111/1753-0407.70119","url":null,"abstract":"<p>Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated substantial weight loss effects among patients with diabetes and obesity. However, given the rapid weight loss induced, there is concern about the total change in body composition, including lean body mass (LBM). Current literature on these effects contains significant heterogeneity, with some studies reporting a loss of 40%–60% of LBM and others reporting 15% or less. To combat this, selective androgen receptor modulators (SARMs) have become a popular candidate. Given their androgen receptor selectivity, SARMs have notable anabolic properties and proposed improved safety profiles over traditional anabolic compounds. Several of these agents, such as enobosarm, have been investigated in clinical trials involving older patient populations or patients with cachexia or sarcopenia secondary to chronic diseases. Furthermore, other agents to maintain or enhance LBM, such as antimyostatin agents, are also under investigation. Exploring this potential synergy could lead to better weight loss and body composition management in patients using GLP-1 RAs for diabetes or weight loss therapy. This review aims to evaluate the potential benefits and uses of SARMs in ameliorating the body composition changes induced by GLP-1 RAs. Other investigational agents to retain or increase muscle mass and the future possibilities of these drugs will be discussed.</p>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"17 8","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1753-0407.70119","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-Traditional Lipid Parameters and Risk of Adverse Pregnancy Outcomes in Gestational Diabetes Mellitus: Mediation by Maternal Metabolites","authors":"Jing-yi Guo,&nbsp;Dan-dan Yan,&nbsp;Wei Chen,&nbsp;Su-na Wang,&nbsp;Yan-wei Zheng,&nbsp;Wei-tuo Zhang,&nbsp;Cheng Hu,&nbsp;Ming-juan Luo,&nbsp;Xiang-tian Yu","doi":"10.1111/1753-0407.70118","DOIUrl":"https://doi.org/10.1111/1753-0407.70118","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To examine the association between non-traditional lipid parameters and adverse pregnancy outcomes (APOs) in women with gestational diabetes mellitus (GDM) and the mediating role of maternal serum metabolites during pregnancy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>This prospective observational study enrolled 399 women with GDM. Multivariate logistic regression was used to examine the association between non-traditional lipid parameters and APOs risk. Additionally, we assessed the mediating role of single and composite maternal serum metabolites during pregnancy using causal mediation analysis and high-dimensional mediation analysis, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>APOs were observed in 12.0% (<i>N</i> = 48) of participants. Seven non-traditional lipid parameters, except for the RC/HDL-C ratio, were associated with APOs risk, with the highest estimate for the atherogenic index of plasma (AIP) (OR = 3.873, 95% CI: 1.079–13.934, <i>p</i> = 0.037) after adjusting for confounders. Maternal metabolic markers mediated these associations, with mediation effect proportions of 21.9%–39.4%. Seven key metabolic markers were identified as potential mediators primarily involved in the biosynthesis of the unsaturated fatty acids pathway. Gene set variation analysis revealed significant differences in the positive regulation of this pathway between the APO and normal pregnancy outcome groups (<i>p</i> = 0.015).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Non-traditional lipid parameters were positively associated with APOs risk in women with GDM. Maternal serum metabolites, predominantly involved in the biosynthesis of unsaturated fatty acids, contribute to these associations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"17 8","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1753-0407.70118","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144751305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Abnormal Glucose Metabolism and Inflammation With Prognosis in Patients With Acute Coronary Syndrome","authors":"Chong Zhang,&nbsp;Wenjin Peng,&nbsp;Tianqi Wang,&nbsp;Meng Ning,&nbsp;Yi Chen,&nbsp;Yingwu Liu","doi":"10.1111/1753-0407.70134","DOIUrl":"https://doi.org/10.1111/1753-0407.70134","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In acute coronary syndrome (ACS) patients, the relationship between abnormal glucose metabolism markers, such as the triglyceride-glucose (TyG) index and stress hyperglycemia ratio (SHR), and inflammatory markers remains unclear. Furthermore, their interaction and impact on long-term prognosis have yet to be investigated in clinical cohorts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, K-means clustering was performed on the TyG index, SHR, and inflammatory markers, including high mobility group box-1 protein, platelet-derived growth factor, phenylacetylglutamine, lysophosphatidic acid, and citrullinated histone H3. A Cox proportional hazards model was used to assess the association between cluster phenotypes and 1-year major adverse cardiovascular events (MACE) risk in ACS patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 363 ACS patients, 62 developed MACE during the 1-year follow-up. SHR correlated positively with the TyG index and inflammatory markers. K-means clustering identified two phenotypes: normal glucose metabolism/low inflammation and abnormal glucose metabolism/high inflammation. Multivariable Cox analysis showed the latter was strongly linked to MACE (adjusted hazard ratio: 3.84, 95% confidence interval: 1.93–7.64), and early guideline-directed medical therapy reduced MACE risk in this high-risk group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>ACS patients with abnormal glucose metabolism and high inflammation have a higher long-term MACE risk than those with normal glucose metabolism and low inflammation. Early guideline-directed medical therapy, alongside anti-inflammatory therapy and hypoglycemic agents, may improve long-term outcomes in this high-risk group.</p>\u0000 </section>\u0000 </div>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"17 8","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1753-0407.70134","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Association Between Subclinical Atherosclerosis Serum Markers and Oxidative DNA Damage in Normoglycemic Normotolerant Offspring of Diabetic Parents","authors":"Masoumeh Rahimi,&nbsp;Farhad Ghadiri Soufi,&nbsp;Shabnaz Koochakkhani,&nbsp;Behnaz Rahnama Inchehsablagh,&nbsp;Abnoos Azarbad,&nbsp;Masoumeh Mahmoudi,&nbsp;Masoumeh Kheirandish,&nbsp;Farideh Jalali Mashayekhi,&nbsp;Ebrahim Eftekhar","doi":"10.1111/1753-0407.70133","DOIUrl":"https://doi.org/10.1111/1753-0407.70133","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>It has been shown that offspring of type 2 diabetic parents have a high risk for developing diabetes and atherosclerosis, but the exact mechanism is unclear. In the present study, the possible association between oxidative stress and subclinical atherosclerosis serum markers in this population was investigated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>LDL/HDL ratio, triglyceride-glucose index (TyG), atherogenic index of plasma (AIP), single-point insulin sensitivity estimator (SPISE) index, oxidized LDL (Ox-LDL), intercellular adhesion molecules (ICAM-1 and E-selectin), as well as the marker of oxidative DNA damage were compared among 150 offspring of diabetic parents (90 normoglycemic and normotolerant offspring, 31 offspring with impaired fasting glucose (IFG), and 29 offspring with impaired glucose tolerance (IGT)), and 40 age-and sex-matched healthy control individuals. The control subjects were among individuals with no family history of diabetes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>All three groups with diabetic parents, that is, norm-offspring, IFG, and IGT groups, had higher serum levels of Ox-LDL, ICAM-1, and 8-hydroxy-2′-deoxyguanosine (8-OHdG) than the controls. In the whole population, ICAM-1 correlated with Ox-LDL, fasting plasma glucose (FPG) and 8-OHdG, and Ox-LDL correlated with LDL/HDL, fasting plasma glucose, TyG index, and 8-OHdG after adjustment for age, sex, and BMI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study shows that subclinical atherosclerosis and oxidative DNA damage are present in normotolerant normoglycemic offspring of type 2 diabetic parents, and they progress with impaired fasting glucose and/or impaired glucose tolerance. Also, our results indicate that a marker of subclinical atherosclerosis, ICAM-1, was directly correlated with the DNA damage marker, 8-OHdG.</p>\u0000 </section>\u0000 </div>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"17 8","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1753-0407.70133","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene-Smoking Interaction in Insulin Sensitivity and β-Cell Function Among Normal Glucose Tolerance Individuals","authors":"Pan Gu,&nbsp;Shuai Zheng,&nbsp;Sijie Zhang,&nbsp;Jie Yuan,&nbsp;Hao Hong,&nbsp;Jinglan Dai,&nbsp;Jingyi Zhao,&nbsp;Kuanfeng Xu,&nbsp;Tao Yang,&nbsp;Qi Fu,&nbsp;Sipeng Shen,&nbsp;Hao Dai","doi":"10.1111/1753-0407.70131","DOIUrl":"https://doi.org/10.1111/1753-0407.70131","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To identify genetic loci that exhibit potential interactions with smoking status on insulin sensitivity and islet β-cell function within normal glucose tolerance (NGT) populations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>All participants underwent an OGTT to confirm NGT status, followed by assessments of insulin sensitivity and β-cell function. Analyses were performed in NGT participants from Nanjing (<i>N</i> = 4808) and Jurong (<i>N</i> = 508) for discovery and validation, respectively. Smoking status was categorized into nonsmokers and smokers. After excluding ineligible individuals, a two-stage genome-wide interaction association analysis (GWIS) was conducted in NGT individuals, with the discovery phase (<i>N</i> = 1377) identifying gene–environment interactions and the validation phase (<i>N</i> = 485) confirming significant loci. Subsequent analyses included stratified analysis and expression quantitative trait locus (eQTL) colocalization.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>GWIS identified ten SNPs in three loci, including rs4713207 (<i>OR14J1</i>, <i>P</i>_meta = 3.95 × 10⁻⁸) for insulin resistance, rs17708475 (<i>NKAIN2, P</i>_meta = 4.83 × 10⁻⁸) for insulin sensitivity, and rs201613 (<i>MYH3, P</i>_meta = 1.05 × 10⁻⁸) for disposition index. Stratified analyses revealed differential effects of smoking across genotypes at these loci. Specifically, smoking was associated with increased insulin resistance in rs4713207 homozygotes (<i>p</i> = 2.15 × 10⁻⁵), while an opposite effect was observed in wild-type individuals (<i>p</i> = 0.022). Colocalization analysis indicated that the smoking-related interaction near rs4713207 is driven by a shared causal variant influencing <i>HCG4</i> (PP.H4 = 0.70) and <i>ZNF311</i> (PP.H4 = 0.74) expression in the pancreas.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings reveal gene-smoking interactions that affect insulin sensitivity and β-cell function, providing new insights into the heterogeneity of metabolic phenotypes and advancing personalized risk assessment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"17 7","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1753-0407.70131","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144714801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fatty Acid Binding Protein 4 Regulates the Antigen-Presenting Function of Dendritic Cells Resulting in T Cell Priming in Streptozotocin-Induced Type 1 Diabetes Mice","authors":"Hailan Zou,&nbsp;Lingxiang Xie,&nbsp;Jingyi Hu,&nbsp;Rong Zhang,&nbsp;Yanfei Wang,&nbsp;Aimin Xu,&nbsp;Zhiguang Zhou,&nbsp;Xiaoyu Xiao,&nbsp;Yang Xiao","doi":"10.1111/1753-0407.70123","DOIUrl":"https://doi.org/10.1111/1753-0407.70123","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Type 1 diabetes is an autoimmune disease with progressive destruction of insulin-producing β cells in islets of Langerhans of the pancreas. However, the early pathogenic factors triggering the recruitment and activation of innate immune cells remain unclear. A study reported that FABP4 accelerates the onset of type 1 diabetes in NOD mice by inducing the polarization of proinflammatory macrophages and their infiltration into pancreatic islets. Nonetheless, the role of FABP4 in mediating crosstalk between innate immunity and adaptive immunity in T1D is unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Intraperitoneal injections of streptozotocin were used to establish a type 1 diabetes mouse model. Blood glucose was monitored, and intraperitoneal glucose tolerance test (IPGTT) was conducted to compare glucose homeostasis. The peripheral immune cells were detected using flow cytometry. Mixed lymphocyte reactions were applied to examine the function of FABP4 on antigen-presenting in dendritic cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that genetic ablation of <i>FABP4</i> in mice alleviated STZ-induced diabetic damage by reducing diabetogenic T lymphocytes and their production of inflammatory cytokines. In vitro studies, <i>FABP4</i> deficiency dendritic cells expressed lower properties of CD86 and CD80, showing impaired antigen-presenting functions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Genetic ablation of FABP4 in mice alleviated STZ-induced diabetic damage by impairing the antigen-presenting function of dendritic cells through downregulating the phosphorylation levels of the ERK and JNK pathways.</p>\u0000 </section>\u0000 </div>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"17 7","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1753-0407.70123","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of HMGCS2 Expression and TG Lipidomics in the Perirenal Adipose Tissue of Obese Diabetic Nephropathy Mice","authors":"Yuhong Huang,&nbsp;Miao Zeng,&nbsp;Mengxue Yang,&nbsp;Xiaodi Zheng,&nbsp;Lulu Jin,&nbsp;Rui Zhang,&nbsp;Yueyue Wu,&nbsp;Fei Li,&nbsp;Bo Yang,&nbsp;Jun Liu","doi":"10.1111/1753-0407.70125","DOIUrl":"https://doi.org/10.1111/1753-0407.70125","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Renal HMGCS2 upregulation is associated with lipid deposition. However, the expression pattern and role of Hmgcs2 in the perirenal adipose tissue (PRAT) is not clear. This study was designed to elucidate the contribution of Hmgcs2 in the pathogenesis of obese diabetic kidney disease mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>12-week-old db/db (diabetic) and db/m (control) mice were fed high-fat or normal diets, respectively. At 12, 16, and 20 weeks, mice (<i>n</i> = 4/group/timepoint) were euthanized for metabolic profiling (body weight, blood glucose, urinary ACR) and tissue collection (kidney, PRAT). Tissues were analyzed for TNF-α mRNA (qPCR), HMGCS2 expression (IHC/WB/IF), lipid deposition (Oil Red O), and histopathology (HE staining). PRAT triglycerides (colorimetric assay) and lipidomics (UPLC–MS/MS) were assessed. HMGCS2-knockout mice (CRISPR-generated) underwent metabolic tests (OGTT/ITT) before terminal tissue analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>(1) Compared with db/mPRAT, db/db PRAT had significantly enlarged adipocytes and increased TG content. The expression of HMGCS2 in renal and PRAT was significantly greater in db/db mice. (2) Hmgcs2 was equally expressed in db/db renal and PRAT. PRAT expansion increases the inflammatory factor TNF-α, which occurs earlier in PRAT than in renal tissue.(3) Genetic ablation of HMGCS2 in mice significantly decreased renal and PRAT TG accumulation, concomitant with attenuated inflammation. (4) LC–MS/MS analysis revealed that TGs are the main PRAT lipid component. Db/db PRAT TG content was significantly greater than that in db/m. Db/db proximal PRAT TG content is greater than that of the distal region, with seven upregulated TG lipid molecules (TG (38:3)+NH4, TG (50:5)+NH4, TG (52:12e)+Na, TG (56:9e)+H, TG (57:6e)+H, FA (18:1)+H, and ST (m45:3)+NH4), among which TG (38:3) has the highest expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study strongly suggests that lipids, especially TGs, are deposited in the kidneys and PRAT of DKD mice, with proximal–distal PRAT differences. HMGCS2 may be involved in kidneys and PRAT TG deposition. PRAT-lipid-metabolism-induced inflammation may occur before blood-glucose-related kidney damage.</p>\u0000 </section>\u0000 </div>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"17 7","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1753-0407.70125","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144695763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on “Time Trends in Cardiovascular Event Incidence in New-Onset Type 2 Diabetes: A Population-Based Cohort Study From Germany”","authors":"Saraswati Sah,&nbsp;Rachana Mehta,&nbsp;Ranjana Sah","doi":"10.1111/1753-0407.70130","DOIUrl":"https://doi.org/10.1111/1753-0407.70130","url":null,"abstract":"&lt;p&gt;We read with great interest the study by Sarabhai et al., which provides valuable insights into the temporal evolution of cardiovascular events in newly diagnosed type 2 diabetes (T2D) patients in Germany over a 17-year period [&lt;span&gt;1&lt;/span&gt;]. Although the reduction in the 5-year incidence of coronary heart disease (CHD) and transient ischemic attack (TIA) is encouraging, we believe several methodological and conceptual limitations deserve further discussion to contextualize the findings.&lt;/p&gt;&lt;p&gt;First, the study's exclusion of laboratory parameters such as glycated hemoglobin (HbA1c), lipid panels, and renal function significantly constrains the capacity to adjust for the quality of glycemic and metabolic control—central determinants of cardiovascular outcomes in T2D [&lt;span&gt;2, 3&lt;/span&gt;]. Reliance solely on ICD-10 codes, though validated for primary diagnoses, does not differentiate between stable and unstable angina, nor does it account for silent myocardial infarctions, which are prevalent in diabetic populations [&lt;span&gt;4&lt;/span&gt;]. This coding limitation may partially explain the paradoxically unchanged incidence of myocardial infarction (MI) despite improvements in CHD.&lt;/p&gt;&lt;p&gt;Second, the use of chronic obstructive pulmonary disease (COPD) as a proxy for smoking status introduces exposure misclassification. Smoking is a potent modifiable risk factor for both MI and ischemic stroke (IS) [&lt;span&gt;5&lt;/span&gt;], and its secular decline in Germany over this period likely contributed to cardiovascular risk reduction. Without direct smoking data, the differential attribution of risk to diabetes-specific interventions versus population-wide trends remains unresolved.&lt;/p&gt;&lt;p&gt;Third, the apparent stability in MI and IS incidence may also be an artifact of cohort composition rather than a true epidemiological plateau. Although the authors matched for age and sex, no stratification by socioeconomic status, regional healthcare access, or medication use—particularly statins and antihypertensives—was undertaken. These variables influence the uptake and effectiveness of cardioprotective interventions [&lt;span&gt;6&lt;/span&gt;]. Furthermore, the analysis does not disaggregate event timing within the five-year follow-up, thereby overlooking early versus late event clustering, which may offer clues about legacy effects from undiagnosed prediabetes.&lt;/p&gt;&lt;p&gt;Fourth, the demographic distribution masks evolving baseline risk. Although mean age and sex proportions remained unchanged, the increased prevalence of hypertension and obesity in the later cohort signals rising baseline cardiovascular risk. Paradoxically, these upward shifts might dilute the observable impact of improved care. Consequently, the unchanged IS and MI rates may reflect counterbalancing effects between therapeutic progress and population-level risk escalation.&lt;/p&gt;&lt;p&gt;Finally, the study's conclusion that CHD and TIA reduction reflects successful diabetes management may overstate causality. CHD includes chronic, often","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"17 7","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1753-0407.70130","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144687929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Author Response to the Comment on “Time Trends in Cardiovascular Event Incidence in New-Onset Type 2 Diabetes: A Population-Based Cohort Study From Germany”","authors":"Theresia Sarabhai,&nbsp;Karel Kostev","doi":"10.1111/1753-0407.70128","DOIUrl":"https://doi.org/10.1111/1753-0407.70128","url":null,"abstract":"&lt;p&gt;We sincerely thank the authors of the comment and appreciate the opportunity to respond to clarify specific aspects of our study.&lt;/p&gt;&lt;p&gt;First of all, we agree that laboratory parameters are key indicators of metabolic control and cardiovascular risk. Although the Disease Analyzer database includes laboratory data from a subset of practices, laboratory values were not consistently available over time and across patients in our cohort. Therefore, we opted not to include them in our analyses. To address this limitation, we adjusted for chronic comorbidities known to be associated with poor metabolic control, such as hypertension, dyslipidemia, and obesity (coded diagnoses). Previous studies demonstrated the validity of the Disease Analyzer database especially for case–control studies focusing on diabetes mellitus [&lt;span&gt;1&lt;/span&gt;]. Furthermore, by focusing on first cardiovascular events in a well-defined incident T2D cohort without prior CVD, we aimed to reduce confounding and improve internal validity despite the absence of uniformly available laboratory markers.&lt;/p&gt;&lt;p&gt;We acknowledge the potential limitations of relying solely on ICD-10 codes, as we stated in the manuscript. However, the Disease Analyzer database has been extensively validated and has demonstrated a high positive predictive value for major cardiovascular diagnoses, including MI [&lt;span&gt;1-3&lt;/span&gt;]. We appreciate the reference by Tsai et al. [&lt;span&gt;4&lt;/span&gt;], which highlights the strong validity of ICD-10-CM codes for identifying AMI subtypes. Although their work confirms excellent performance metrics, our interest was not the subtype but rather the trend in overall MI incidence.&lt;/p&gt;&lt;p&gt;Indeed, smoking is a critical risk factor. As stated, individual smoking status is not recorded in the Disease Analyzer database. We therefore followed established practice in using COPD as a proxy, recognizing its limitations. As noted in the literature, around 90% of patients with COPD are current or former smokers [&lt;span&gt;5&lt;/span&gt;]. However, not all smokers develop COPD, so COPD cannot fully replace smoking status, but provides an approximate indicator. We clearly acknowledged this limitation in the manuscript. Importantly, smoking prevalence in Germany has declined over the study period, which may have contributed to overall cardiovascular improvements. However, as these trends would influence both diabetic and nondiabetic populations alike, our interpretation focused on diabetes-specific outcomes in a matched T2D cohort.&lt;/p&gt;&lt;p&gt;We agree that socioeconomic status and medication use are important factors. Although these data were not available in sufficient detail in our database, our large, matched cohorts and adjustment for key comorbidities offer valuable insights into temporal patterns. The unchanged MI and IS incidence, despite improvements in CHD and TIA, likely reflects a balance between earlier vascular damage and therapeutic progress. Although we did not stratify events by time since diagno","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"17 7","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1753-0407.70128","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144687907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prescription Medication Expenditures for Patients With Diabetes in the United States: 2012–2021","authors":"Shanshan Li,&nbsp;Shaoxi Pan,&nbsp;Nan Xiao,&nbsp;Shaoxiang Jiang,&nbsp;Gorden G. Liu,&nbsp;Beini Lyu","doi":"10.1111/1753-0407.70106","DOIUrl":"https://doi.org/10.1111/1753-0407.70106","url":null,"abstract":"<p>Glucose-lowering medication expenditures per user by different payers among patients with diabetes.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"17 7","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1753-0407.70106","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673200","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}