Pub Date : 2025-11-05DOI: 10.1016/j.jdiacomp.2025.109214
Soo Lim , Cheol Young Park , In Kyung Jeong , Ji Sung Yoon , Sang Yong Kim , Eun Seok Kang , Junghyun Noh , Kyu Yeon Hur , Sungrae Kim
Aims
Sodium-glucose cotransporter-2 (SGLT2) inhibitors offer cardiovascular and renal benefits beyond glycemic control. However, their effect on glucose variability (GV) in drug-naïve individuals with type 2 diabetes (T2D) is not well established. This study compared the effects of empagliflozin versus metformin on GV and metabolic outcomes.
Methods
In this multicenter, open-label, randomized study, 46 drug-naïve adults with T2D (HbA1c 6.5 %–10.0 %) received empagliflozin (10 mg/day; n = 23) or metformin (1000 mg/day; n = 23) for 12 weeks. The primary outcome was change in mean amplitude of glucose excursions (MAGE), assessed by continuous glucose monitoring. Secondary outcomes included standard deviation of glucose, time-in-range (TIR), metabolic parameters, and safety.
Results
At Week 12, empagliflozin significantly reduced MAGE (−19.58 mg/dL; 95 % CI: −30.62, −8.53) compared with metformin (−4.33 mg/dL; 95 % CI: −7.98, −0.68) (n = 19 vs. n = 18, respectively). TIR improved in both groups, with no significant between-group differences. Empagliflozin treatment led to greater reductions in body weight and waist circumference, along with increases in HDL-cholesterol and decreases in triglyceride and uric acid levels. The decrease in HbA1c from baseline was greater in the empagliflozin group (−1.15 % [95 % CI: −1.44, −0.85]) than in the metformin group (−0.78 % [95 % CI: −1.02, −0.54]), resulting in a statistically significant between-group difference (p = 0.049). Adverse events were mild and comparable between groups.
Conclusions
Empagliflozin significantly reduced GV and provided additional metabolic benefits in drug-naïve individuals with T2D. These findings support its potential utility in early diabetes management, particularly in targeting glycemic variability.
{"title":"Empagliflozin versus metformin for glucose variability and metabolic outcomes in drug-naïve type 2 diabetes: The EMPA-FIT study","authors":"Soo Lim , Cheol Young Park , In Kyung Jeong , Ji Sung Yoon , Sang Yong Kim , Eun Seok Kang , Junghyun Noh , Kyu Yeon Hur , Sungrae Kim","doi":"10.1016/j.jdiacomp.2025.109214","DOIUrl":"10.1016/j.jdiacomp.2025.109214","url":null,"abstract":"<div><h3>Aims</h3><div>Sodium-glucose cotransporter-2 (SGLT2) inhibitors offer cardiovascular and renal benefits beyond glycemic control. However, their effect on glucose variability (GV) in drug-naïve individuals with type 2 diabetes (T2D) is not well established. This study compared the effects of empagliflozin versus metformin on GV and metabolic outcomes.</div></div><div><h3>Methods</h3><div>In this multicenter, open-label, randomized study, 46 drug-naïve adults with T2D (HbA1c 6.5 %–10.0 %) received empagliflozin (10 mg/day; <em>n</em> = 23) or metformin (1000 mg/day; <em>n</em> = 23) for 12 weeks. The primary outcome was change in mean amplitude of glucose excursions (MAGE), assessed by continuous glucose monitoring. Secondary outcomes included standard deviation of glucose, time-in-range (TIR), metabolic parameters, and safety.</div></div><div><h3>Results</h3><div>At Week 12, empagliflozin significantly reduced MAGE (−19.58 mg/dL; 95 % CI: −30.62, −8.53) compared with metformin (−4.33 mg/dL; 95 % CI: −7.98, −0.68) (<em>n</em> = 19 vs. <em>n</em> = 18, respectively). TIR improved in both groups, with no significant between-group differences. Empagliflozin treatment led to greater reductions in body weight and waist circumference, along with increases in HDL-cholesterol and decreases in triglyceride and uric acid levels. The decrease in HbA1c from baseline was greater in the empagliflozin group (−1.15 % [95 % CI: −1.44, −0.85]) than in the metformin group (−0.78 % [95 % CI: −1.02, −0.54]), resulting in a statistically significant between-group difference (<em>p</em> = 0.049). Adverse events were mild and comparable between groups.</div></div><div><h3>Conclusions</h3><div>Empagliflozin significantly reduced GV and provided additional metabolic benefits in drug-naïve individuals with T2D. These findings support its potential utility in early diabetes management, particularly in targeting glycemic variability.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"40 1","pages":"Article 109214"},"PeriodicalIF":3.1,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145505024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-04DOI: 10.1016/j.jdiacomp.2025.109213
Shigehiro Katayama , Stefan D Anker , Dalong Zhu , SungGyun Kim , Ming-Ju Wu , Daiji Kawanami , Peter Rossing , Luis Miguel Ruilope , Christiane Ahlers , Meike Brinker , Amaninder Mann , Yunjing Tian , Satoshi Yamashita , Bertram Pitt , on behalf of the FIDELIO-DKD and FIGARO-DKD Investigators
Aims
Define the effect of finerenone on kidney function within the overall FIDELITY Asian subpopulation.
Methods
This FIDELITY pooled subanalysis assessed the following outcomes in the Asian subpopulation: chronic estimated glomerular filtration rate (eGFR) slope, urine albumin-to-creatinine ratio (UACR) from baseline to month 4, time to UACR regression, and safety.
Results
In total, 2858 (22.0 %) participants included in FIDELITY were Asian. Chronic eGFR slope was reduced with finerenone compared with placebo in the Asian subpopulation; least-squares mean between-group difference was 1.08 mL/min/1.73 m2 (95 % confidence interval 0.53–1.63; p = 0.0002). Greater reductions in chronic eGFR slope were also observed for finerenone compared with placebo when analyzed according to baseline UACR. Finerenone treatment reduced UACR from baseline to month 4 by 34 %. This treatment effect was seen regardless of baseline eGFR, systolic blood pressure, glycated hemoglobin, body mass index, sodium-glucose co-transporter-2 inhibitor use, and glucagon-like peptide-1 receptor agonist use. Regression from high to normal albuminuria was seen in 39.5 % of all Asian participants treated with finerenone versus 14.8 % receiving placebo. Treatment-emergent adverse events were similar between finerenone and placebo, and hyperkalemia was manageable.
Conclusion
Finerenone slows eGFR decline and lowers UACR in Asian participants with chronic kidney disease and type 2 diabetes.
{"title":"Efficacy and safety of finerenone in Asian patients with type 2 diabetes and chronic kidney disease: A FIDELITY analysis by baseline kidney function","authors":"Shigehiro Katayama , Stefan D Anker , Dalong Zhu , SungGyun Kim , Ming-Ju Wu , Daiji Kawanami , Peter Rossing , Luis Miguel Ruilope , Christiane Ahlers , Meike Brinker , Amaninder Mann , Yunjing Tian , Satoshi Yamashita , Bertram Pitt , on behalf of the FIDELIO-DKD and FIGARO-DKD Investigators","doi":"10.1016/j.jdiacomp.2025.109213","DOIUrl":"10.1016/j.jdiacomp.2025.109213","url":null,"abstract":"<div><h3>Aims</h3><div>Define the effect of finerenone on kidney function within the overall FIDELITY Asian subpopulation.</div></div><div><h3>Methods</h3><div>This FIDELITY pooled subanalysis assessed the following outcomes in the Asian subpopulation: chronic estimated glomerular filtration rate (eGFR) slope, urine albumin-to-creatinine ratio (UACR) from baseline to month 4, time to UACR regression, and safety.</div></div><div><h3>Results</h3><div>In total, 2858 (22.0 %) participants included in FIDELITY were Asian. Chronic eGFR slope was reduced with finerenone compared with placebo in the Asian subpopulation; least-squares mean between-group difference was 1.08 mL/min/1.73 m<sup>2</sup> (95 % confidence interval 0.53–1.63; <em>p</em> = 0.0002). Greater reductions in chronic eGFR slope were also observed for finerenone compared with placebo when analyzed according to baseline UACR. Finerenone treatment reduced UACR from baseline to month 4 by 34 %. This treatment effect was seen regardless of baseline eGFR, systolic blood pressure, glycated hemoglobin, body mass index, sodium-glucose co-transporter-2 inhibitor use, and glucagon-like peptide-1 receptor agonist use. Regression from high to normal albuminuria was seen in 39.5 % of all Asian participants treated with finerenone versus 14.8 % receiving placebo. Treatment-emergent adverse events were similar between finerenone and placebo, and hyperkalemia was manageable.</div></div><div><h3>Conclusion</h3><div>Finerenone slows eGFR decline and lowers UACR in Asian participants with chronic kidney disease and type 2 diabetes.</div><div><strong>Trial registration number:</strong> FIDELIO-DKD (NCT02540993); FIGARO-DKD (NCT02545049).</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"40 1","pages":"Article 109213"},"PeriodicalIF":3.1,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145604290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This study aimed to identify noninvasive biomarkers for predicting the effectiveness of multifactorial management in individual cases of diabetic kidney disease (DKD).
Methods
This multicenter, retrospective–prospective observational study included patients with type 2 diabetes and DKD. Candidate biomarkers were evaluated within 1 year of enrollment. Deceleration in the rate of decline in the estimated glomerular filtration rate (eGFR) was defined as an indicator of prognostic improvement in DKD. The correlation between candidate biomarkers and baseline eGFR, as well as with eGFR decline, was analyzed. Furthermore, candidate biomarkers were compared between the groups with and without a deceleration in eGFR decline.
Results
Serum soluble thrombomodulin (sTM) levels, urinary liver-type fatty acid-binding protein excretion, kidney size, and renal surface irregularities were found to be independently associated with baseline eGFR. Serum sTM levels and urinary type IV collagen excretion were independently associated with eGFR decline. Furthermore, the eGFR decline rate during the first 2 years of the observation period was independently associated with the later deceleration of eGFR decline. Additionally, the probability of deceleration in eGFR decline was higher among patients who experienced a more rapid eGFR decline early in the observation period. However, a biomarker that could predict the likelihood of deceleration in eGFR decline could not be identified.
Conclusions
We identified four noninvasive biomarkers that independently correlated with the eGFR, among which urinary type IV collagen excretion and serum sTM levels were particularly useful in predicting eGFR decline.
{"title":"Identification of biomarkers to predict renal function decline and its deceleration in patients with type 2 diabetes and diabetic kidney disease","authors":"Motonobu Nishimura , Kazuya Yonezawa , Morio Sawamura , Tsuyoshi Tanaka , Yuichi Yamamoto , Hideki Taki , Masako Hatao , Masaya Takeda , Kazuyuki Hida , Junko Koide , Miho Saito , Nobuyuki Koriyama , Tomokazu Watanabe , Ryo Nakajima , Yoshiharu Hoshiyama","doi":"10.1016/j.jdiacomp.2025.109208","DOIUrl":"10.1016/j.jdiacomp.2025.109208","url":null,"abstract":"<div><h3>Aims</h3><div>This study aimed to identify noninvasive biomarkers for predicting the effectiveness of multifactorial management in individual cases of diabetic kidney disease (DKD).</div></div><div><h3>Methods</h3><div>This multicenter, retrospective–prospective observational study included patients with type 2 diabetes and DKD. Candidate biomarkers were evaluated within 1 year of enrollment. Deceleration in the rate of decline in the estimated glomerular filtration rate (eGFR) was defined as an indicator of prognostic improvement in DKD. The correlation between candidate biomarkers and baseline eGFR, as well as with eGFR decline, was analyzed. Furthermore, candidate biomarkers were compared between the groups with and without a deceleration in eGFR decline.</div></div><div><h3>Results</h3><div>Serum soluble thrombomodulin (sTM) levels, urinary liver-type fatty acid-binding protein excretion, kidney size, and renal surface irregularities were found to be independently associated with baseline eGFR. Serum sTM levels and urinary type IV collagen excretion were independently associated with eGFR decline. Furthermore, the eGFR decline rate during the first 2 years of the observation period was independently associated with the later deceleration of eGFR decline. Additionally, the probability of deceleration in eGFR decline was higher among patients who experienced a more rapid eGFR decline early in the observation period. However, a biomarker that could predict the likelihood of deceleration in eGFR decline could not be identified.</div></div><div><h3>Conclusions</h3><div>We identified four noninvasive biomarkers that independently correlated with the eGFR, among which urinary type IV collagen excretion and serum sTM levels were particularly useful in predicting eGFR decline.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"40 1","pages":"Article 109208"},"PeriodicalIF":3.1,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145458822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-24DOI: 10.1016/j.jdiacomp.2025.109206
Isabella Lindegaard Jørgensen , Anne Cathrine Baun Thuesen , Tine Dalsgaard Clausen , Lene Ringholm , Elisabeth R. Mathiesen , Torben Hansen , Peter Damm
Aims
At Rigshospitalet, Copenhagen, Denmark, pregnancy management for women with GCK-MODY is guided by markedly elevated glucose levels and fetal overgrowth, while management for women with HNF1A-MODY follows guidelines for type 1 and type 2 diabetes. We aimed to evaluate current treatment strategies for pregnant women with GCK- or HNF1A-MODY.
Methods
We conducted a retrospective population-based cohort study of 18 consecutive pregnancies in 11 women with GCK-MODY and 17 consecutive pregnancies in 11 women with HNF1A-MODY, matched with 140 pregnancies in 133 women with type 2 diabetes, referred to Rigshospitalet, Copenhagen, between June 2011 and December 2023. Glycemia, pregnancy- and perinatal outcomes were compared using generalized estimating equation models.
Results
In pregnancies in women with GCK-MODY, median HbA1c levels remained stable from early in pregnancy (< 20 weeks) to late in pregnancy (45 to 46 mmol/mol), while decreasing in pregnancies in women with HNF1A-MODY (41 to 37 mmol/mol) and type 2 diabetes (47 to 41 mmol/mol). The prevalence of hypertensive disorders (5.6 vs. 35.0 %), preterm delivery (0 % vs. 17.9 %), and large for gestational age (16.7 % vs. 35.7 %), were lower in pregnancies in women with GCK-MODY compared to type 2 diabetes, though not statistically significant. Pregnancy- and perinatal outcomes were comparable between pregnancies in women with HNF1A-MODY and type 2 diabetes.
Conclusions
In women with GCK-MODY, pregnancy outcomes were reassuring supporting the current treatment strategy. In women with HNF1A-MODY, guidelines for type 1 and type 2 diabetes resulted in glycemic control within target and pregnancy outcomes similar to type 2 diabetes.
目的：在丹麦哥本哈根的Rigshospitalet， gckmody妇女的妊娠管理以血糖水平明显升高和胎儿过度生长为指导，而HNF1A-MODY妇女的管理遵循1型和2型糖尿病的指导方针。我们的目的是评估GCK-或HNF1A-MODY孕妇的当前治疗策略。方法：在2011年6月至2023年12月期间，我们进行了一项基于人群的回顾性队列研究，纳入了11名gcg - mody患者的18次连续妊娠和11名HNF1A-MODY患者的17次连续妊娠，并与哥本哈根Rigshospitalet的133名2型糖尿病患者的140次妊娠相匹配。使用广义估计方程模型比较血糖、妊娠和围产期结局。结果：在GCK-MODY患者的妊娠中，HbA1c水平中位数从妊娠早期（< 20周）到妊娠后期（45 ~ 46 mmol/mol）保持稳定，而在HNF1A-MODY患者（41 ~ 37 mmol/mol）和2型糖尿病患者（47 ~ 41 mmol/mol）的妊娠中保持下降。与2型糖尿病患者相比，GCK-MODY患者妊娠期间高血压疾病（5.6% vs. 35.0%）、早产（0% vs. 17.9%）和胎龄大（16.7% vs. 35.7%）的患病率较低，但无统计学意义。HNF1A-MODY和2型糖尿病孕妇的妊娠和围产期结局具有可比性。结论：在患有GCK-MODY的妇女中，妊娠结局令人放心，支持当前的治疗策略。在患有HNF1A-MODY的女性中，1型和2型糖尿病的指南导致血糖控制在目标范围内，妊娠结局与2型糖尿病相似。
{"title":"Glycemia, management and outcomes of pregnant women with maturity-onset diabetes of the young – a single-center case series","authors":"Isabella Lindegaard Jørgensen , Anne Cathrine Baun Thuesen , Tine Dalsgaard Clausen , Lene Ringholm , Elisabeth R. Mathiesen , Torben Hansen , Peter Damm","doi":"10.1016/j.jdiacomp.2025.109206","DOIUrl":"10.1016/j.jdiacomp.2025.109206","url":null,"abstract":"<div><h3>Aims</h3><div>At Rigshospitalet, Copenhagen, Denmark, pregnancy management for women with GCK-MODY is guided by markedly elevated glucose levels and fetal overgrowth, while management for women with HNF1A-MODY follows guidelines for type 1 and type 2 diabetes. We aimed to evaluate current treatment strategies for pregnant women with GCK- or HNF1A-MODY.</div></div><div><h3>Methods</h3><div>We conducted a retrospective population-based cohort study of 18 consecutive pregnancies in 11 women with GCK-MODY and 17 consecutive pregnancies in 11 women with HNF1A-MODY, matched with 140 pregnancies in 133 women with type 2 diabetes, referred to Rigshospitalet, Copenhagen, between June 2011 and December 2023. Glycemia, pregnancy- and perinatal outcomes were compared using generalized estimating equation models.</div></div><div><h3>Results</h3><div>In pregnancies in women with GCK-MODY, median HbA1c levels remained stable from early in pregnancy (< 20 weeks) to late in pregnancy (45 to 46 mmol/mol), while decreasing in pregnancies in women with HNF1A-MODY (41 to 37 mmol/mol) and type 2 diabetes (47 to 41 mmol/mol). The prevalence of hypertensive disorders (5.6 vs. 35.0 %), preterm delivery (0 % vs. 17.9 %), and large for gestational age (16.7 % vs. 35.7 %), were lower in pregnancies in women with GCK-MODY compared to type 2 diabetes, though not statistically significant. Pregnancy- and perinatal outcomes were comparable between pregnancies in women with HNF1A-MODY and type 2 diabetes.</div></div><div><h3>Conclusions</h3><div>In women with GCK-MODY, pregnancy outcomes were reassuring supporting the current treatment strategy. In women with HNF1A-MODY, guidelines for type 1 and type 2 diabetes resulted in glycemic control within target and pregnancy outcomes similar to type 2 diabetes.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"40 1","pages":"Article 109206"},"PeriodicalIF":3.1,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145445117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-23DOI: 10.1016/j.jdiacomp.2025.109207
Jiali Guo , Zhongyu Li , Rodrigo M. Carrillo-Larco , Daniel S. Hsia , Jessica L. Harding , Mohammed K. Ali , Jithin Sam Varghese
Aims
To identify subtypes of newly diagnosed youth-onset T2D using cluster analysis.
Methods
A cross-sectional study included participants with T2D (duration ≤1 year) aged 10–19 years from the SEARCH for Diabetes in Youth Study (n = 304; 47.4 %) and aged 10–17 years from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (n = 337; 52.6 %) study before intervention allocation. We examined variables available in routine clinical practice. Main outcomes were data-driven subtypes identified using k-means clustering.
Results
Among 641 participants with youth-onset T2D, 58.2 % were female. The analysis revealed three youth-onset subtypes: 48.5 % had obesity-related T2D (yOD), 18.7 % had insulin deficient T2D (yIDD), and 32.7 % had insulin resistant T2D (yIRD). The yOD subtype was characterized by high BMI and low HbA1c. The yIDD exhibited low fasting C-peptide levels, high HDL cholesterol, and high HbA1c. The yIRD subtype had high BMI, high fasting C-peptide, and high blood pressures compared to other subtypes. A higher prevalence of distal symmetric polyneuropathy was observed at diagnosis among yIDD and yIRD subtypes, relative to the yOD subtype.
Conclusions
Three subtypes of youth-onset T2D were identified with different clinical characteristics. Management of youth-onset T2D may require tailored strategies by subtype.
目的：通过聚类分析确定新诊断的青年发病T2D亚型。方法：一项横断面研究纳入了干预分配前10-19岁的T2D（持续时间≤1年）参与者（n = 304; 47.4%）和10-17岁的参与者（n = 337; 52.6%），参与者来自青年糖尿病搜索研究（SEARCH for Diabetes in Youth study）。我们检查了常规临床实践中可用的变量。主要结果是使用k-means聚类确定的数据驱动亚型。结果：641例青年发病T2D患者中，58.2%为女性。分析揭示了三种青年发病亚型：48.5%为肥胖相关T2D (yOD)， 18.7%为胰岛素缺乏型T2D (yIDD)， 32.7%为胰岛素抵抗型T2D （yIRD）。yOD亚型以高BMI和低HbA1c为特征。yIDD表现出低空腹c肽水平，高HDL胆固醇和高HbA1c。与其他亚型相比，yIRD亚型具有高BMI，高空腹c肽和高血压。相对于yOD亚型，yIDD和yIRD亚型在诊断时观察到远端对称多神经病变的患病率更高。结论：青年发病T2D可分为三种亚型，各有不同的临床特征。青年发病T2D的管理可能需要根据亚型量身定制的策略。
{"title":"Data-driven subtypes of newly diagnosed youth-onset type 2 diabetes in the USA","authors":"Jiali Guo , Zhongyu Li , Rodrigo M. Carrillo-Larco , Daniel S. Hsia , Jessica L. Harding , Mohammed K. Ali , Jithin Sam Varghese","doi":"10.1016/j.jdiacomp.2025.109207","DOIUrl":"10.1016/j.jdiacomp.2025.109207","url":null,"abstract":"<div><h3>Aims</h3><div>To identify subtypes of newly diagnosed youth-onset T2D using cluster analysis.</div></div><div><h3>Methods</h3><div>A cross-sectional study included participants with T2D (duration ≤1 year) aged 10–19 years from the SEARCH for Diabetes in Youth Study (<em>n</em> = 304; 47.4 %) and aged 10–17 years from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (<em>n</em> = 337; 52.6 %) study before intervention allocation. We examined variables available in routine clinical practice. Main outcomes were data-driven subtypes identified using k-means clustering.</div></div><div><h3>Results</h3><div>Among 641 participants with youth-onset T2D, 58.2 % were female. The analysis revealed three youth-onset subtypes: 48.5 % had obesity-related T2D (yOD), 18.7 % had insulin deficient T2D (yIDD), and 32.7 % had insulin resistant T2D (yIRD). The yOD subtype was characterized by high BMI and low HbA1c. The yIDD exhibited low fasting C-peptide levels, high HDL cholesterol, and high HbA1c. The yIRD subtype had high BMI, high fasting C-peptide, and high blood pressures compared to other subtypes. A higher prevalence of distal symmetric polyneuropathy was observed at diagnosis among yIDD and yIRD subtypes, relative to the yOD subtype.</div></div><div><h3>Conclusions</h3><div>Three subtypes of youth-onset T2D were identified with different clinical characteristics. Management of youth-onset T2D may require tailored strategies by subtype.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"40 1","pages":"Article 109207"},"PeriodicalIF":3.1,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145445093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-21DOI: 10.1016/j.jdiacomp.2025.109205
Fulden Sari , Zilan Bazancir-Apaydın , Süleyman Sari , Mehmet Can Sari , Şenol Çelik
Aim
Swallowing difficulties are increasingly recognized as a significant yet underreported complication of diabetes mellitus (DM), with evidence suggesting that more than 50 % of patients with the condition may be affected. This study aimed to assess the impact of swallowing disorders on the quality of life in DM patients, to identify other factors influencing swallowing disorders, and to determine the cut-off score for the SWAL-QOL questionnaire in these patients using data mining methods.
Methods
This cross-sectional study analyzed 150 DM patients, assessing swallowing assessment using the EAT-10, quality of life with the SWAL-QOL, and swallowing difficulty through the Visual Analogue Scale (VAS).
Results
Patients with dysphagia exhibited significantly lower scores across multiple SWAL-QOL subgroups-including General Burden, Food Selection, Eating Duration, Eating Desire, Fear of Eating, Sleep, Fatigue, Communication, Mental Health, Social Functioning, and the total SWAL-QOL score compared to non-dysphagic patients (p < 0.001). The Swallowing Difficulty-VAS score was significantly elevated in dysphagic patients (p < 0.001). EAT-10 scores were correlated with Swallowing Difficulty-VAS and SWAL-QOL subgroups, including General Burden, Food Selection, Eating Duration, Eating Desire, Fear of Eating, Sleep, Fatigue, Communication, Mental Health, Social Functioning, and the total score. The SWAL-QOL total score cut-off of 65.7 was identified for DM patients with dysphagia.
Conclusions
Close monitoring of these symptoms by clinicians is essential, and targeted rehabilitation interventions are strongly recommended to improve both swallowing function and overall quality of life in this population.
{"title":"Assessing the impact of dysphagia on quality of life and determining SWAL-QOL cut-off scores in diabetes mellitus patients: a data mining approach","authors":"Fulden Sari , Zilan Bazancir-Apaydın , Süleyman Sari , Mehmet Can Sari , Şenol Çelik","doi":"10.1016/j.jdiacomp.2025.109205","DOIUrl":"10.1016/j.jdiacomp.2025.109205","url":null,"abstract":"<div><h3>Aim</h3><div>Swallowing difficulties are increasingly recognized as a significant yet underreported complication of diabetes mellitus (DM), with evidence suggesting that more than 50 % of patients with the condition may be affected. This study aimed to assess the impact of swallowing disorders on the quality of life in DM patients, to identify other factors influencing swallowing disorders, and to determine the cut-off score for the SWAL-QOL questionnaire in these patients using data mining methods.</div></div><div><h3>Methods</h3><div>This cross-sectional study analyzed 150 DM patients, assessing swallowing assessment using the EAT-10, quality of life with the SWAL-QOL, and swallowing difficulty through the Visual Analogue Scale (VAS).</div></div><div><h3>Results</h3><div>Patients with dysphagia exhibited significantly lower scores across multiple SWAL-QOL subgroups-including General Burden, Food Selection, Eating Duration, Eating Desire, Fear of Eating, Sleep, Fatigue, Communication, Mental Health, Social Functioning, and the total SWAL-QOL score compared to non-dysphagic patients (p < 0.001). The Swallowing Difficulty-VAS score was significantly elevated in dysphagic patients (p < 0.001). EAT-10 scores were correlated with Swallowing Difficulty-VAS and SWAL-QOL subgroups, including General Burden, Food Selection, Eating Duration, Eating Desire, Fear of Eating, Sleep, Fatigue, Communication, Mental Health, Social Functioning, and the total score. The SWAL-QOL total score cut-off of 65.7 was identified for DM patients with dysphagia.</div></div><div><h3>Conclusions</h3><div>Close monitoring of these symptoms by clinicians is essential, and targeted rehabilitation interventions are strongly recommended to improve both swallowing function and overall quality of life in this population.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 12","pages":"Article 109205"},"PeriodicalIF":3.1,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145359893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-20DOI: 10.1016/j.jdiacomp.2025.109202
Salwa Dilfari Pohan , Rani Sauriasari , Baitha Palanggatan Maggadani , Taufiq Indra Rukmana , Farah Mahdiyah , Fathia Yusrina , Sri Hayati , Richard Johari James , Mohd Salleh Rofiee , Teh Lay Kek , Mohd Zaki Salleh
Objectives
This study investigated the relationship between serum metabolomic profiles and diabetic kidney disease (DKD) risk in patients with type 2 diabetes mellitus (T2DM) stratified into three KDIGO-defined risk categories.
Methods
Serum samples from 48 patients were analyzed using untargeted liquid chromatography–quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). Participants were classified into low (n = 16), moderate (n = 16), and high (n = 16) DKD risk groups according to KDIGO guidelines. Differential metabolites were identified based on p-value, log fold change, and variable importance in projection (VIP), and subsequently subjected to pathway enrichment analysis.
Results
Comparative analysis revealed five differential metabolites between low- and moderate-risk groups, three between moderate- and high-risk groups, and three between low- and high-risk groups. Notably, sphinganine, arachidonic acid, and ornithine were progressively downregulated, whereas AFMK, L-arginine, lactosylceramide (LacCer), and lysophosphatidylcholine (lysoPC) were upregulated with increasing DKD risk. These metabolites mapped to disturbed pathways, including arginine and proline metabolism, sphingolipid metabolism, glycerophospholipid metabolism, arachidonic acid metabolism, and tryptophan metabolism.
Conclusion
This study highlights progressive alterations in amino acid, lipid, and inflammatory pathways across DKD risk categories, suggesting that these stage-specific metabolomic signatures may serve as putative biomarkers for detection and monitoring of DKD progression in T2DM.
{"title":"Serum analysis of type 2 diabetes mellitus patients with low, moderate, and high risk of diabetic kidney disease using LC-MS metabolomics approach","authors":"Salwa Dilfari Pohan , Rani Sauriasari , Baitha Palanggatan Maggadani , Taufiq Indra Rukmana , Farah Mahdiyah , Fathia Yusrina , Sri Hayati , Richard Johari James , Mohd Salleh Rofiee , Teh Lay Kek , Mohd Zaki Salleh","doi":"10.1016/j.jdiacomp.2025.109202","DOIUrl":"10.1016/j.jdiacomp.2025.109202","url":null,"abstract":"<div><h3>Objectives</h3><div>This study investigated the relationship between serum metabolomic profiles and diabetic kidney disease (DKD) risk in patients with type 2 diabetes mellitus (T2DM) stratified into three KDIGO-defined risk categories.</div></div><div><h3>Methods</h3><div>Serum samples from 48 patients were analyzed using untargeted liquid chromatography–quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). Participants were classified into low (<em>n</em> = 16), moderate (n = 16), and high (n = 16) DKD risk groups according to KDIGO guidelines. Differential metabolites were identified based on <em>p</em>-value, log fold change, and variable importance in projection (VIP), and subsequently subjected to pathway enrichment analysis.</div></div><div><h3>Results</h3><div>Comparative analysis revealed five differential metabolites between low- and moderate-risk groups, three between moderate- and high-risk groups, and three between low- and high-risk groups. Notably, sphinganine, arachidonic acid, and ornithine were progressively downregulated, whereas AFMK, L-arginine, lactosylceramide (LacCer), and lysophosphatidylcholine (lysoPC) were upregulated with increasing DKD risk. These metabolites mapped to disturbed pathways, including arginine and proline metabolism, sphingolipid metabolism, glycerophospholipid metabolism, arachidonic acid metabolism, and tryptophan metabolism.</div></div><div><h3>Conclusion</h3><div>This study highlights progressive alterations in amino acid, lipid, and inflammatory pathways across DKD risk categories, suggesting that these stage-specific metabolomic signatures may serve as putative biomarkers for detection and monitoring of DKD progression in T2DM.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"40 1","pages":"Article 109202"},"PeriodicalIF":3.1,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145569414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-19DOI: 10.1016/j.jdiacomp.2025.109203
Sameer Badri Al-Mhanna , Barry A. Franklin , John M. Jakicic , Emmanuel Stamatakis , Linda S. Pescatello , Deborah Riebe , Walter R. Thompson , James S. Skinner , Sheri R. Colberg , Jonathan K. Ehrman , George S. Metsios , Norsuhana Omar , Nouf H. Alkhamees , Bodor Bin Sheeha , Abdullah F. Alghannam , Alexios Batrakoulis
Purpose
This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the effects of aerobic exercise on cardiometabolic health-related indices in patients with type 2 diabetes and concurrent overweight/obesity (diabesity).
Methods
PubMed, Web of Science, Scopus, Science Direct, Cochrane Library, and Google Scholar databases were searched from inception to October 2024. The search strategy included the following keywords: diabetes, aerobic exercise, and endurance training. RCTs comparing aerobic exercise training ≥2 weeks in duration to standard treatment were considered eligible. Participants were adults with diabesity.
Results
A total of 1391 middle-aged/older adult patients (55 % females) were included in 34 RCTs. Body mass index [standardized mean differences (SMD) -0.18 kg/m2, 95 % confidence intervals (CI) -0.36 to −0.01]. waist circumference (SMD -0.23 cm, 95 % CI -0.44 to −0.03), body fat (SMD -0.30 %, 95 % CI -0.59 to −0.01), fasting blood glucose (SMD -0.49 mmol/L, 95 % CI -0.72 to −0.27), glycated hemoglobin (SMD -0.79 %, 95 % CI -1.17 to −0.41), fasting insulin (SMD -0.44 mIU/L, 95 % CI -0.72 to −0.15), homeostatic model assessment for insulin resistance (SMD -0.72, 95 % CI -1.09 to −0.35), high-density lipoprotein cholesterol (SMD 0.32 mg/dL, 95 % CI 0.01 to 0.63), triglycerides (SMD -0.33 mg/dL, 95 % CI -0.63 to −0.04), and total cholesterol (SMD -0.28 mg/dL, 95 % CI -0.47 to −0.10) improved compared with standard treatment.
Conclusions
These results underscore the beneficial role of aerobic exercise as a non-pharmacological intervention in managing and treating patients with diabesity when compared to standard treatment, despite the presence of considerable uncertainty in several outcomes.
目的对随机对照试验（RCTs）进行系统回顾和荟萃分析，旨在评估有氧运动对2型糖尿病合并超重/肥胖（糖尿病）患者心脏代谢相关指标的影响。方法检索spubmed、Web of Science、Scopus、Science Direct、Cochrane Library和谷歌Scholar数据库，检索时间为建库至2024年10月。搜索策略包括以下关键词：糖尿病、有氧运动和耐力训练。比较持续时间≥2周的有氧运动训练与标准治疗的rct被认为是合格的。参与者是患有糖尿病的成年人。结果34项随机对照试验共纳入1391例中老年患者，其中女性占55%。体重指数[标准化平均差(SMD) -0.18 kg/m2, 95%置信区间(CI) -0.36至- 0.01]。腰围(SMD -0.23厘米,95% CI -0.44−0.03),脂肪(SMD -0.30%, 95% CI -0.59−0.01)、空腹血糖(SMD -0.49更易/ L, 95%置信区间-0.72 - 0.27−)、糖化血红蛋白(SMD -0.79%, 95% CI -1.17−0.41)、空腹胰岛素(SMD -0.44个人/ L, 95% CI -0.72−0.15),稳态模型评估胰岛素抵抗(SMD -0.72, 95% CI -1.09−0.35),高密度脂蛋白胆固醇(SMD 0.32 mg / dL, 95%可信区间0.01到0.63),甘油三酯(SMD -0.33 mg / dL,95% CI -0.63至- 0.04)，总胆固醇（SMD -0.28 mg/dL, 95% CI -0.47至- 0.10）与标准治疗相比有所改善。结论：与标准治疗相比，这些结果强调了有氧运动作为一种非药物干预在管理和治疗糖尿病患者方面的有益作用，尽管在一些结果中存在相当大的不确定性。
{"title":"Impact of aerobic exercise on cardiometabolic health in patients with diabesity: A systematic review and meta-analysis of randomized controlled trials","authors":"Sameer Badri Al-Mhanna , Barry A. Franklin , John M. Jakicic , Emmanuel Stamatakis , Linda S. Pescatello , Deborah Riebe , Walter R. Thompson , James S. Skinner , Sheri R. Colberg , Jonathan K. Ehrman , George S. Metsios , Norsuhana Omar , Nouf H. Alkhamees , Bodor Bin Sheeha , Abdullah F. Alghannam , Alexios Batrakoulis","doi":"10.1016/j.jdiacomp.2025.109203","DOIUrl":"10.1016/j.jdiacomp.2025.109203","url":null,"abstract":"<div><h3>Purpose</h3><div>This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the effects of aerobic exercise on cardiometabolic health-related indices in patients with type 2 diabetes and concurrent overweight/obesity (diabesity).</div></div><div><h3>Methods</h3><div>PubMed, Web of Science, Scopus, Science Direct, Cochrane Library, and Google Scholar databases were searched from inception to October 2024. The search strategy included the following keywords: diabetes, aerobic exercise, and endurance training. RCTs comparing aerobic exercise training ≥2 weeks in duration to standard treatment were considered eligible. Participants were adults with diabesity.</div></div><div><h3>Results</h3><div>A total of 1391 middle-aged/older adult patients (55 % females) were included in 34 RCTs. Body mass index [standardized mean differences (SMD) -0.18 kg/m<sup>2</sup>, 95 % confidence intervals (CI) -0.36 to −0.01]. waist circumference (SMD -0.23 cm, 95 % CI -0.44 to −0.03), body fat (SMD -0.30 %, 95 % CI -0.59 to −0.01), fasting blood glucose (SMD -0.49 mmol/L, 95 % CI -0.72 to −0.27), glycated hemoglobin (SMD -0.79 %, 95 % CI -1.17 to −0.41), fasting insulin (SMD -0.44 mIU/L, 95 % CI -0.72 to −0.15), homeostatic model assessment for insulin resistance (SMD -0.72, 95 % CI -1.09 to −0.35), high-density lipoprotein cholesterol (SMD 0.32 mg/dL, 95 % CI 0.01 to 0.63), triglycerides (SMD -0.33 mg/dL, 95 % CI -0.63 to −0.04), and total cholesterol (SMD -0.28 mg/dL, 95 % CI -0.47 to −0.10) improved compared with standard treatment.</div></div><div><h3>Conclusions</h3><div>These results underscore the beneficial role of aerobic exercise as a non-pharmacological intervention in managing and treating patients with diabesity when compared to standard treatment, despite the presence of considerable uncertainty in several outcomes.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 12","pages":"Article 109203"},"PeriodicalIF":3.1,"publicationDate":"2025-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145359892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-18DOI: 10.1016/j.jdiacomp.2025.109201
Yasmine Ibrahim Elhenawy , Rasha Adel Thabet , Marwa G.A. Hegazy , Shymaa Ayed El-Morsy , Yasmeen AbdelAziz Fereig
Aim
Evaluate the oxidant-antioxidant balance and the efficacy of Alpha-lipoic acid (ALA) as an adjuvant therapy for diabetic nephropathy (DN) among individuals with type 1 diabetes (T1D).
Materials and methods
A 3 months prospective randomized controlled trial including 50 participants with DN randomly allocated (1:1) to one of two arms; an interventional arm receiving 300 mg/day of ALA (n = 25) and a non-interventional arm (n = 25). Initial assessments included HbA1c, urinary albumin excretion rate (UAER), malondialdehyde (MDA), and total antioxidant capacity (TAC). Baseline data was compared with 50 participants with T1D without DN and 50 healthy controls.
Results
T1D participants had significantly higher MDA and lower TAC levels compared to controls (P < 0.01). Within the T1D cohort, participants with DN showed significantly higher MDA and lower TAC levels (P < 0.01). MDA positively correlated with triglycerides (r = 0.53), UAER (r = 0.70), and HbA1c (r = 0.5) (p < 0.01), while TAC negatively correlated triglycerides (r = −0.41), UAER (r = −0.88), and HbA1c (r = −0.64) (p < 0.01). After 3 months of ALA supplementation, significant reductions in HbA1c, UAER, and MDA were observed, along with an increase in TAC (P < 0.01).
Conclusion
The study demonstrates that 3 months of ALA supplementation effectively reduced oxidative stress and UAER, demonstrating a potential role in protecting renal tissue from diabetes-induced oxidative damage.
{"title":"The role of oral alpha-lipoic acid as an adjuvant antioxidant therapy in diabetic nephropathy among children and adolescents with type 1 diabetes: a randomized controlled trial","authors":"Yasmine Ibrahim Elhenawy , Rasha Adel Thabet , Marwa G.A. Hegazy , Shymaa Ayed El-Morsy , Yasmeen AbdelAziz Fereig","doi":"10.1016/j.jdiacomp.2025.109201","DOIUrl":"10.1016/j.jdiacomp.2025.109201","url":null,"abstract":"<div><h3>Aim</h3><div>Evaluate the oxidant-antioxidant balance and the efficacy of Alpha-lipoic acid (ALA) as an adjuvant therapy for diabetic nephropathy (DN) among individuals with type 1 diabetes (T1D).</div></div><div><h3>Materials and methods</h3><div>A 3 months prospective randomized controlled trial including 50 participants with DN randomly allocated (1:1) to one of two arms; an interventional arm receiving 300 mg/day of ALA (<em>n</em> = 25) and a non-interventional arm (n = 25). Initial assessments included HbA1c, urinary albumin excretion rate (UAER), malondialdehyde (MDA), and total antioxidant capacity (TAC). Baseline data was compared with 50 participants with T1D without DN and 50 healthy controls.</div></div><div><h3>Results</h3><div>T1D participants had significantly higher MDA and lower TAC levels compared to controls (<em>P</em> < 0.01). Within the T1D cohort, participants with DN showed significantly higher MDA and lower TAC levels (<em>P</em> < 0.01). MDA positively correlated with triglycerides (<em>r</em> = 0.53), UAER (<em>r</em> = 0.70), and HbA1c (r = 0.5) (<em>p</em> < 0.01), while TAC negatively correlated triglycerides (<em>r</em> = −0.41), UAER (<em>r</em> = −0.88), and HbA1c (<em>r</em> = −0.64) (<em>p</em> < 0.01). After 3 months of ALA supplementation, significant reductions in HbA1c, UAER, and MDA were observed, along with an increase in TAC (<em>P</em> < 0.01).</div></div><div><h3>Conclusion</h3><div>The study demonstrates that 3 months of ALA supplementation effectively reduced oxidative stress and UAER, demonstrating a potential role in protecting renal tissue from diabetes-induced oxidative damage.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"40 1","pages":"Article 109201"},"PeriodicalIF":3.1,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145452046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-18DOI: 10.1016/j.jdiacomp.2025.109204
Emily Moroney , Monika A. Niewczas , Elif I. Ekinci , Richard J. MacIsaac
Multiple biomarkers have been associated with Diabetic Kidney Disease (DKD) progression and its associated exaggerated risk for cardiovascular events and mortality. Chronic inflammation plays an important role in the progression of DKD. Tumour Necrosis Factor alpha (TNF-α) is a central proinflammatory cytokine that binds to its soluble receptor (sTNFR) and has been implicated in the pathogenesis of DKD. sTNFRs are a family of membrane proteins that regulate gene expression and activate cell death pathways. They are involved in the immune system and can bind to cytokines related to TNF. Higher levels of the type 1 (sTNFR1) and type 2 (sTNFR2) receptor have consistently been associated with progressive DKD, notably rapid GFR decline and progression to kidney failure. They offer enhanced risk prediction for progressive DKD over and above established risk markers. Higher levels of sTNFR1 and sTNFR2 also predict incident cardiovascular disease and mortality in people with diabetes. Further studies are required to define the temporal relationship between changes in circulating sTNFR levels and progression of kidney function loss. The influence of medications with kidney protective effects on sTNFR levels also requires further investigation.
{"title":"Soluble tumor necrosis factor receptors (sTNFRs) as biomarkers for diabetic kidney disease","authors":"Emily Moroney , Monika A. Niewczas , Elif I. Ekinci , Richard J. MacIsaac","doi":"10.1016/j.jdiacomp.2025.109204","DOIUrl":"10.1016/j.jdiacomp.2025.109204","url":null,"abstract":"<div><div>Multiple biomarkers have been associated with Diabetic Kidney Disease (DKD) progression and its associated exaggerated risk for cardiovascular events and mortality. Chronic inflammation plays an important role in the progression of DKD. Tumour Necrosis Factor alpha (TNF-α) is a central proinflammatory cytokine that binds to its soluble receptor (sTNFR) and has been implicated in the pathogenesis of DKD. sTNFRs are a family of membrane proteins that regulate gene expression and activate cell death pathways. They are involved in the immune system and can bind to cytokines related to TNF. Higher levels of the type 1 (sTNFR1) and type 2 (sTNFR2) receptor have consistently been associated with progressive DKD, notably rapid GFR decline and progression to kidney failure. They offer enhanced risk prediction for progressive DKD over and above established risk markers. Higher levels of sTNFR1 and sTNFR2 also predict incident cardiovascular disease and mortality in people with diabetes. Further studies are required to define the temporal relationship between changes in circulating sTNFR levels and progression of kidney function loss. The influence of medications with kidney protective effects on sTNFR levels also requires further investigation.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"40 1","pages":"Article 109204"},"PeriodicalIF":3.1,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145420257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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