Type 2 diabetes mellitus (T2DM) is the most common group of metabolic disorders in the world, characterized by hyperglycemia that leads to severe short-term complications such as ketoacidosis, hyperosmolar hyperglycemic coma, and long-term microvascular complications that affect the eye, kidney, and nerves. Type 2 diabetes occurs due to resistance to insulin. AMPK (adenosine monophosphate-activated protein kinase) is an energy radar that controls various metabolic and physiological processes. It is dysregulated in major chronic diseases, such as diabetes. The focus of this review is on understanding the role of AMPK in type 2 diabetes mellitus, which helps ameliorate hyperglycemia and its complications. Medications for T2DM are designed to upregulate the AMPK signaling pathway to improve its microvascular and macrovascular complications. AMPK signaling interacts with PGC-1, PI3K/Akt, NOX4, NF-κB, and other molecular pathways to produce such protective effects. Thus, AMPK is emerging as one of the most auspicious targets for both the prevention and treatment of type 2 diabetes mellitus. Hence, this review focuses on the recent evidence of the role of AMPK signaling in type 2 diabetes mellitus pathogenesis and how to circumvent its complications.
{"title":"The role of AMPK signaling pathway in the pathogenesis of type 2 diabetes mellitus with its complications and related metabolic disorders","authors":"Kibur Hunie Tesfa , Chernet Desalegn Gebeyehu , Asrat Tadele Ewunetie , Endalkachew Gugsa , Amare Nigatu Zewdie , Gashaw Dessie , Hiwot Tezera Endale","doi":"10.1016/j.metop.2025.100397","DOIUrl":"10.1016/j.metop.2025.100397","url":null,"abstract":"<div><div>Type 2 diabetes mellitus (T2DM) is the most common group of metabolic disorders in the world, characterized by hyperglycemia that leads to severe short-term complications such as ketoacidosis, hyperosmolar hyperglycemic coma, and long-term microvascular complications that affect the eye, kidney, and nerves. Type 2 diabetes occurs due to resistance to insulin. AMPK (adenosine monophosphate-activated protein kinase) is an energy radar that controls various metabolic and physiological processes. It is dysregulated in major chronic diseases, such as diabetes. The focus of this review is on understanding the role of AMPK in type 2 diabetes mellitus, which helps ameliorate hyperglycemia and its complications. Medications for T2DM are designed to upregulate the AMPK signaling pathway to improve its microvascular and macrovascular complications. AMPK signaling interacts with PGC-1, PI3K/Akt, NOX4, NF-κB, and other molecular pathways to produce such protective effects. Thus, AMPK is emerging as one of the most auspicious targets for both the prevention and treatment of type 2 diabetes mellitus. Hence, this review focuses on the recent evidence of the role of AMPK signaling in type 2 diabetes mellitus pathogenesis and how to circumvent its complications.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"28 ","pages":"Article 100397"},"PeriodicalIF":2.7,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145121233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-11DOI: 10.1016/j.metop.2025.100395
Junjie Chang, Zhehua Zhou, Weiwei Hong, Shuting Li, Ze Zhu
Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are widely used in various manufacturing processes due to their exceptional chemical stability and hydrophobic properties. However, these substances tend to bioaccumulate in the environment and human tissues, posing significant health risks, including endocrine disruption, immune system impairment, and an increased risk of diabetes. Vitamin E, a powerful antioxidant, may potentially attenuate the adverse effects of PFAS on glucose metabolism. Therefore, we utilized data from the 2017–2018 National Health and Nutrition Examination Survey (NHANES), which includes measurements of vitamin E content in a subset of participants, to explore the relationship between PFAS exposures, vitamin E levels, and diabetes risk. Our analysis revealed significant variations in PFAS concentrations across different demographic groups, with males and older individuals exhibiting higher PFAS levels. Elevated PFAS concentrations were associated with an increased risk of diabetes, while vitamin E (specifically alpha-tocopherol) exhibited significant interaction effects with PFAS, modulating blood glucose levels. These findings provide compelling evidence linking PFAS exposures to diabetes risk and highlight the potential moderating role of vitamin E in mitigating PFAS-induced metabolic disturbances. Future research should focus on elucidating the underlying biological mechanisms through which PFAS exert their adverse effects and vitamin E exerts its protective actions, as well as conducting longitudinal studies to establish causality and further explore the complex interplay between PFAS exposures, antioxidant status, and metabolic health.
{"title":"The moderating role of vitamin E in the association between PFAS exposures and diabetes risk: Evidence from the NHANES 2017–2018","authors":"Junjie Chang, Zhehua Zhou, Weiwei Hong, Shuting Li, Ze Zhu","doi":"10.1016/j.metop.2025.100395","DOIUrl":"10.1016/j.metop.2025.100395","url":null,"abstract":"<div><div>Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are widely used in various manufacturing processes due to their exceptional chemical stability and hydrophobic properties. However, these substances tend to bioaccumulate in the environment and human tissues, posing significant health risks, including endocrine disruption, immune system impairment, and an increased risk of diabetes. Vitamin E, a powerful antioxidant, may potentially attenuate the adverse effects of PFAS on glucose metabolism. Therefore, we utilized data from the 2017–2018 National Health and Nutrition Examination Survey (NHANES), which includes measurements of vitamin E content in a subset of participants, to explore the relationship between PFAS exposures, vitamin E levels, and diabetes risk. Our analysis revealed significant variations in PFAS concentrations across different demographic groups, with males and older individuals exhibiting higher PFAS levels. Elevated PFAS concentrations were associated with an increased risk of diabetes, while vitamin E (specifically alpha-tocopherol) exhibited significant interaction effects with PFAS, modulating blood glucose levels. These findings provide compelling evidence linking PFAS exposures to diabetes risk and highlight the potential moderating role of vitamin E in mitigating PFAS-induced metabolic disturbances. Future research should focus on elucidating the underlying biological mechanisms through which PFAS exert their adverse effects and vitamin E exerts its protective actions, as well as conducting longitudinal studies to establish causality and further explore the complex interplay between PFAS exposures, antioxidant status, and metabolic health.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"28 ","pages":"Article 100395"},"PeriodicalIF":2.7,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145050611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-03DOI: 10.1016/j.metop.2025.100393
Jing He , Ying-chuan Yin , Wang Zhang , Xiao-hong Shi , Cui-ling Zhu
Background
Type 2 diabetes mellitus is increasingly prevalent and often accompanied by vitamin D insufficiency. Prolactin, once considered solely lactogenic, has emerged as a metabolic regulator, yet its relationship with vitamin D in T2DM remains unclear.
Methods
We conducted a cross-sectional study of 221 male T2DM patients aged 25–75 years recruited between January 2022 and December 2024. Serum 25-hydroxyvitamin D (25(OH)D) and prolactin were measured, defining vitamin D sufficiency as ≥ 20 ng/mL. Associations were evaluated using group comparisons, Spearman correlation and multivariable regression adjusting for confounders. Restricted cubic splines assessed nonlinearity and thresholds. Causality was examined via Mendelian randomization employing 227 25(OH)D-associated variants.
Results
Vitamin D deficiency affected 59.7 % of participants. Median prolactin levels were higher in vitamin D-sufficient than in deficient patients. Serum 25(OH)D correlated positively with prolactin and remained significant after adjustment. Spline analysis suggested a nonlinear relationship with an inflection of 18.48 ng/mL: below this threshold prolactin decreased as 25(OH)D increased, whereas above it prolactin rose steeply. Mendelian randomization provided evidence for a causal association: the inverse variance weighted estimate was non-significant, but MR-Egger and weighted median analyses indicated a significant link without pleiotropy or heterogeneity.
Conclusion
These findings demonstrate a nonlinear, threshold-dependent association between vitamin D status and prolactin in male T2DM. Levels of 25(OH)D at 18.48 ng/mL were associated with suppressed prolactin, while sufficient concentrations enhanced prolactin, suggesting that maintaining adequate vitamin D may modulate prolactin and benefit metabolic outcomes. Further research is warranted to validate these observations.
{"title":"A nonlinear, causal link between serum 25-hydroxyvitamin D and prolactin in type 2 diabetes: Evidence from clinical and Mendelian randomization analyses","authors":"Jing He , Ying-chuan Yin , Wang Zhang , Xiao-hong Shi , Cui-ling Zhu","doi":"10.1016/j.metop.2025.100393","DOIUrl":"10.1016/j.metop.2025.100393","url":null,"abstract":"<div><h3>Background</h3><div>Type 2 diabetes mellitus is increasingly prevalent and often accompanied by vitamin D insufficiency. Prolactin, once considered solely lactogenic, has emerged as a metabolic regulator, yet its relationship with vitamin D in T2DM remains unclear.</div></div><div><h3>Methods</h3><div>We conducted a cross-sectional study of 221 male T2DM patients aged 25–75 years recruited between January 2022 and December 2024. Serum 25-hydroxyvitamin D (25(OH)D) and prolactin were measured, defining vitamin D sufficiency as ≥ 20 ng/mL. Associations were evaluated using group comparisons, Spearman correlation and multivariable regression adjusting for confounders. Restricted cubic splines assessed nonlinearity and thresholds. Causality was examined via Mendelian randomization employing 227 25(OH)D-associated variants.</div></div><div><h3>Results</h3><div>Vitamin D deficiency affected 59.7 % of participants. Median prolactin levels were higher in vitamin D-sufficient than in deficient patients. Serum 25(OH)D correlated positively with prolactin and remained significant after adjustment. Spline analysis suggested a nonlinear relationship with an inflection of 18.48 ng/mL: below this threshold prolactin decreased as 25(OH)D increased, whereas above it prolactin rose steeply. Mendelian randomization provided evidence for a causal association: the inverse variance weighted estimate was non-significant, but MR-Egger and weighted median analyses indicated a significant link without pleiotropy or heterogeneity.</div></div><div><h3>Conclusion</h3><div>These findings demonstrate a nonlinear, threshold-dependent association between vitamin D status and prolactin in male T2DM. Levels of 25(OH)D at 18.48 ng/mL were associated with suppressed prolactin, while sufficient concentrations enhanced prolactin, suggesting that maintaining adequate vitamin D may modulate prolactin and benefit metabolic outcomes. Further research is warranted to validate these observations.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"28 ","pages":"Article 100393"},"PeriodicalIF":2.7,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145009940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01DOI: 10.1016/j.metop.2025.100394
Dimitrios Tsilingiris , Theodora Stratigou , Dimitrios Kounatidis , Natalia G. Vallianou , Irene Karampela , Maria Dalamaga
Background
Subclinical hypothyroidism (SH) has been linked to an increased cardiovascular risk, though the specific contributing factors remain unclear.
Methods
We studied 120 consecutive adults with SH and 120 euthyroid controls matched for age, gender, and date of blood draw. Smoking status did not differ between groups. Groups were compared on clinical and laboratory data, lipid, insulin resistance (IR), glycemic, and liver steatosis/fibrosis indices, 10-year and lifetime cardiovascular risk (SCORE2, LIFE-CVD), as well as atherogenic and additional markers (lipoprotein(a), homocysteine, fibrinogen, highly sensitive C-reactive protein, apolipoproteins A1/B). A subset of individuals with SH and ≥TSH ≥10 mIU/L (n = 16) was followed up after L-thyroxine supplementation.
Results
SH subjects had a more adverse cardiovascular profile, with worse lipid, glycemic, IR, and hepatic markers, and higher 10-year (5.3 % vs. 4.1 % and 3.8 % vs. 2.8 %) and lifetime (28.5 % vs. 23.0 %) cardiovascular risk (all p < 0.05). Complementary markers were also elevated in SH (p < 0.01). Estimated absolute risk reductions from atorvastatin 20 mg were greater in SH (1.3 % vs. 0.9 % p = 0.008 and 7.7 % vs. 6.2 %, p < 0.001). The differences were more pronounced in severe SH (TSH ≥10). L-thyroxine led to modest risk amelioration (−0.21 % and −1.18 %), primarily owing to total/LDL cholesterol reductions.
Conclusions
SH is linked to a more adverse cardiovascular, metabolic and hepatic profile, indicating its potential as a candidate risk modifier. Intensive risk factor management is warranted, along with L-thyroxine supplementation in selected cases.
{"title":"Cardiometabolic risk profiles in subclinical hypothyroidism, and the potential impact of statin therapy: A cross-sectional and longitudinal study","authors":"Dimitrios Tsilingiris , Theodora Stratigou , Dimitrios Kounatidis , Natalia G. Vallianou , Irene Karampela , Maria Dalamaga","doi":"10.1016/j.metop.2025.100394","DOIUrl":"10.1016/j.metop.2025.100394","url":null,"abstract":"<div><h3>Background</h3><div>Subclinical hypothyroidism (SH) has been linked to an increased cardiovascular risk, though the specific contributing factors remain unclear.</div></div><div><h3>Methods</h3><div>We studied 120 consecutive adults with SH and 120 euthyroid controls matched for age, gender, and date of blood draw. Smoking status did not differ between groups. Groups were compared on clinical and laboratory data, lipid, insulin resistance (IR), glycemic, and liver steatosis/fibrosis indices, 10-year and lifetime cardiovascular risk (SCORE2, LIFE-CVD), as well as atherogenic and additional markers (lipoprotein(a), homocysteine, fibrinogen, highly sensitive C-reactive protein, apolipoproteins A1/B). A subset of individuals with SH and ≥TSH ≥10 mIU/L (n = 16) was followed up after L-thyroxine supplementation.</div></div><div><h3>Results</h3><div>SH subjects had a more adverse cardiovascular profile, with worse lipid, glycemic, IR, and hepatic markers, and higher 10-year (5.3 % vs. 4.1 % and 3.8 % vs. 2.8 %) and lifetime (28.5 % vs. 23.0 %) cardiovascular risk (all p < 0.05). Complementary markers were also elevated in SH (p < 0.01). Estimated absolute risk reductions from atorvastatin 20 mg were greater in SH (1.3 % vs. 0.9 % p = 0.008 and 7.7 % vs. 6.2 %, p < 0.001). The differences were more pronounced in severe SH (TSH ≥10). L-thyroxine led to modest risk amelioration (−0.21 % and −1.18 %), primarily owing to total/LDL cholesterol reductions.</div></div><div><h3>Conclusions</h3><div>SH is linked to a more adverse cardiovascular, metabolic and hepatic profile, indicating its potential as a candidate risk modifier. Intensive risk factor management is warranted, along with L-thyroxine supplementation in selected cases.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"27 ","pages":"Article 100394"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145007661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01DOI: 10.1016/j.metop.2025.100383
Salya F. Alfadli , Yazeed S. Alotaibi , Maha J. Aqdi , Latifah A. Almozan , Zahra B. Alzubaidi , Hammad A. Altemani , Lama S. Alrashidi , Shaden D. Almutairi , Hussain A. Alabdullah , Alaa A. Almehmadi , Abdulrahman L. Alanzi , Ahmed Y. Azzam
{"title":"Corrigendum to “Effectiveness of continuous glucose monitoring systems on glycemic control in adults with type 1 diabetes: A systematic review and meta-analysis” [Metabol. Open 27 (2025) 100382]","authors":"Salya F. Alfadli , Yazeed S. Alotaibi , Maha J. Aqdi , Latifah A. Almozan , Zahra B. Alzubaidi , Hammad A. Altemani , Lama S. Alrashidi , Shaden D. Almutairi , Hussain A. Alabdullah , Alaa A. Almehmadi , Abdulrahman L. Alanzi , Ahmed Y. Azzam","doi":"10.1016/j.metop.2025.100383","DOIUrl":"10.1016/j.metop.2025.100383","url":null,"abstract":"","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"27 ","pages":"Article 100383"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145049335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Malnutrition and chronic inflammation are common in chronic kidney disease (CKD) and contribute to disease progression and mortality. While the prognostic nutritional index (PNI), geriatric nutritional risk index (GNRI), and controlling nutritional status (CONUT) scores assess nutritional status, their predictive values for CKD progression and mortality in individuals with diabetes, particularly independent of tumor necrosis factor receptor 2 (TNFR2), remains unclear. This study aimed to evaluate whether these markers predict outcomes beyond TNFR2.
Subjects/methods
We analyzed 640 individuals with diabetes, stratified by PNI quartiles (Q1 vs. Q2–4). Serum TNFR2 was measured using enzyme-linked immunosorbent assay. Nutritional status was assessed using PNI, GNRI, and CONUT scores. Cox proportional hazards models adjusted for covariates including TNFR2 examined associations between nutritional markers and a kidney event (≥30 % decline in estimated glomerular filtration rate), mortality, and a composite outcome.
Results
The mean age was 65 years; 53.9 % were male. Over median follow-ups of 5.3 and 5.4-years, 75 (11.7 %) experienced a kidney event and 44 (6.9 %) died. A total of 112 (17.5 %) experienced the composite outcome. All three markers were independently associated with a kidney event (PNI: hazard ratio [HR], 1.84; 95 % confidence interval [CI], 1.13–3.02) and a composite outcome (PNI: HR, 1.94; 95 % CI, 1.30–2.89). GNRI was the only marker independently associated with mortality (HR, 2.90; 95 % CI, 1.56–5.37).
Conclusions
PNI, GNRI, and CONUT scores strongly predict adverse outcomes in diabetes, emphasizing the importance of nutritional evaluation. Targeted nutritional interventions may improve prognosis.
{"title":"Independent predictive role of nutritional markers in kidney function decline and mortality in diabetes","authors":"Tomohito Gohda , Nozomu Kamei , Marenao Tanaka , Masato Furuhashi , Tatsuya Sato , Mitsunobu Kubota , Michiyoshi Sanuki , Risako Mikami , Koji Mizutani , Yusuke Suzuki , Maki Murakoshi","doi":"10.1016/j.metop.2025.100386","DOIUrl":"10.1016/j.metop.2025.100386","url":null,"abstract":"<div><h3>Background</h3><div>Malnutrition and chronic inflammation are common in chronic kidney disease (CKD) and contribute to disease progression and mortality. While the prognostic nutritional index (PNI), geriatric nutritional risk index (GNRI), and controlling nutritional status (CONUT) scores assess nutritional status, their predictive values for CKD progression and mortality in individuals with diabetes, particularly independent of tumor necrosis factor receptor 2 (TNFR2), remains unclear. This study aimed to evaluate whether these markers predict outcomes beyond TNFR2.</div></div><div><h3>Subjects/methods</h3><div>We analyzed 640 individuals with diabetes, stratified by PNI quartiles (Q1 vs. Q2–4). Serum TNFR2 was measured using enzyme-linked immunosorbent assay. Nutritional status was assessed using PNI, GNRI, and CONUT scores. Cox proportional hazards models adjusted for covariates including TNFR2 examined associations between nutritional markers and a kidney event (≥30 % decline in estimated glomerular filtration rate), mortality, and a composite outcome.</div></div><div><h3>Results</h3><div>The mean age was 65 years; 53.9 % were male. Over median follow-ups of 5.3 and 5.4-years, 75 (11.7 %) experienced a kidney event and 44 (6.9 %) died. A total of 112 (17.5 %) experienced the composite outcome. All three markers were independently associated with a kidney event (PNI: hazard ratio [HR], 1.84; 95 % confidence interval [CI], 1.13–3.02) and a composite outcome (PNI: HR, 1.94; 95 % CI, 1.30–2.89). GNRI was the only marker independently associated with mortality (HR, 2.90; 95 % CI, 1.56–5.37).</div></div><div><h3>Conclusions</h3><div>PNI, GNRI, and CONUT scores strongly predict adverse outcomes in diabetes, emphasizing the importance of nutritional evaluation. Targeted nutritional interventions may improve prognosis.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"27 ","pages":"Article 100386"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145007660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01DOI: 10.1016/j.metop.2025.100392
Akira Mima, Takahiro Nakamoto, Keishi Matsumoto, Yuta Saito, Takaaki Morikawa, Shinji Lee
Introduction
Studies have examined the effect of dapagliflozin, a sodium-glucose co-transporter-2 (SGLT2) inhibitor, on chronic kidney disease (CKD), including immunoglobulin A nephropathy (IgAN). Dapagliflozin decreases albuminuria and slows the decline in estimated glomerular filtration rate (eGFR). However, its renoprotective effects may not be observed in all patients with IgAN in real-world clinical practice. In this study, we aimed to investigate the potential relationship between renal histopathology analyzed using imaging software and the renoprotective effects of dapagliflozin.
Methods
The mesangial matrix fraction (Mes Fx) in patients with IgAN was analyzed using Image-J, an imaging software. The relationships between eGFR slope decline, changes in urinary protein, and the degree of Mes Fx before and after dapagliflozin treatment were investigated.
Results
A significant correlation was evident between the degree of Mes Fx and eGFR slope decline in patients with IgAN. Furthermore, it was suggested that when the Mes Fx exceeded 10 % of the total glomerular surface area, the effect of dapagliflozin in slowing the eGFR decline was unclear.
Conclusions
However, it should be noted that this study has limitations, including the absence of a control group, the small data size, and its pilot study nature. Therefore, it cannot be stated unequivocally that dapagliflozin's efficacy is definitively demonstrated by Mes Fx predictive role.
{"title":"Effect of dapagliflozin on eGFR slope in IgA nephropathy based on renal pathological assessment using image analysis software","authors":"Akira Mima, Takahiro Nakamoto, Keishi Matsumoto, Yuta Saito, Takaaki Morikawa, Shinji Lee","doi":"10.1016/j.metop.2025.100392","DOIUrl":"10.1016/j.metop.2025.100392","url":null,"abstract":"<div><h3>Introduction</h3><div>Studies have examined the effect of dapagliflozin, a sodium-glucose co-transporter-2 (SGLT2) inhibitor, on chronic kidney disease (CKD), including immunoglobulin A nephropathy (IgAN). Dapagliflozin decreases albuminuria and slows the decline in estimated glomerular filtration rate (eGFR). However, its renoprotective effects may not be observed in all patients with IgAN in real-world clinical practice. In this study, we aimed to investigate the potential relationship between renal histopathology analyzed using imaging software and the renoprotective effects of dapagliflozin.</div></div><div><h3>Methods</h3><div>The mesangial matrix fraction (Mes Fx) in patients with IgAN was analyzed using Image-J, an imaging software. The relationships between eGFR slope decline, changes in urinary protein, and the degree of Mes Fx before and after dapagliflozin treatment were investigated.</div></div><div><h3>Results</h3><div>A significant correlation was evident between the degree of Mes Fx and eGFR slope decline in patients with IgAN. Furthermore, it was suggested that when the Mes Fx exceeded 10 % of the total glomerular surface area, the effect of dapagliflozin in slowing the eGFR decline was unclear.</div></div><div><h3>Conclusions</h3><div>However, it should be noted that this study has limitations, including the absence of a control group, the small data size, and its pilot study nature. Therefore, it cannot be stated unequivocally that dapagliflozin's efficacy is definitively demonstrated by Mes Fx predictive role.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"28 ","pages":"Article 100392"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145020548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01DOI: 10.1016/j.metop.2025.100389
Faisal Alzenaidi , Osama Aldoweesh , Salman Alghofaili , Abdulaziz Fadel , Razan Ali Awad Lasloom , Dhay Alharbi , Faris Almalki , Atheer Ahmad Alkhairi , Maram Alharbi , Norah Ahmed Alhamdan , Ahmed Y. Azzam
Introduction
Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for depression in Alzheimer's disease (AD), however their effects on glucose metabolism remain poorly understood. We conducted a systematic review and meta-analysis to evaluate SSRI effects on brain glucose metabolism and metabolic adverse events in AD patients.
Methods
Following PRISMA 2020 guidelines, we searched multiple databases up to July 11, 2025 for studies investigating SSRI effects on glucose-related outcomes in AD patients. Despite significant heterogeneity in study designs and populations, we performed meta-analyses for adverse events and coordinate-based meta-analysis for neuroimaging data. We performed meta-analyses for adverse events and coordinate-based meta-analysis for neuroimaging data. Advanced Bayesian hierarchical modeling and Markov simulations projected long-term metabolic outcomes.
Results
Twelve studies with total included 7143 participants met our inclusion criteria, including nine randomized controlled trials and three observational studies. Brain FDG-PET revealed SSRI use restored dorsal raphe nucleus hypometabolism (standardized mean difference 0.87, 95 % CI: 0.52–1.22, P-value = 0.001). Meta-analysis demonstrated increased gastrointestinal adverse events (risk ratio 2.15, 95 % CI: 1.68–2.76, P-value<0.001, with moderate between-study heterogeneity), with sertraline showing highest rates. Citalopram 30 mg provided significant weight loss protection (risk ratio 0.13, 95 % CI: 0.02–0.98, P-value = 0.02), though this exceeds the recommended 20 mg maximum dose for elderly patients due to cardiac safety considerations. Long-term diabetes incidence showed no increased risk (hazard ratio 0.75, 95 % CI: 0.50–1.12, P-value = 0.15). Bayesian modeling revealed 85 % probability of beneficial brain metabolic effects and 89 % probability of citalopram superiority for weight protection.
Conclusions
SSRIs restore brain glucose metabolism in AD patients while causing manageable peripheral metabolic effects. Citalopram appears the best for weight-sensitive patients, while sertraline requires gastrointestinal monitoring. These findings support SSRI safety for metabolic outcomes in AD treatment, however longer-term studies with controlled metabolic outcomes are needed to confirm our findings. The observed citalopram weight protection benefit was documented at 30 mg daily, which exceeds recommended dosing limits for elderly patients due to cardiac safety concerns.
{"title":"Selective serotonin reuptake inhibitors and glucose metabolism in Alzheimer's disease and related dementias: A systematic review and meta-analysis of brain metabolic and adverse event data","authors":"Faisal Alzenaidi , Osama Aldoweesh , Salman Alghofaili , Abdulaziz Fadel , Razan Ali Awad Lasloom , Dhay Alharbi , Faris Almalki , Atheer Ahmad Alkhairi , Maram Alharbi , Norah Ahmed Alhamdan , Ahmed Y. Azzam","doi":"10.1016/j.metop.2025.100389","DOIUrl":"10.1016/j.metop.2025.100389","url":null,"abstract":"<div><h3>Introduction</h3><div>Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for depression in Alzheimer's disease (AD), however their effects on glucose metabolism remain poorly understood. We conducted a systematic review and meta-analysis to evaluate SSRI effects on brain glucose metabolism and metabolic adverse events in AD patients.</div></div><div><h3>Methods</h3><div>Following PRISMA 2020 guidelines, we searched multiple databases up to July 11, 2025 for studies investigating SSRI effects on glucose-related outcomes in AD patients. Despite significant heterogeneity in study designs and populations, we performed meta-analyses for adverse events and coordinate-based meta-analysis for neuroimaging data. We performed meta-analyses for adverse events and coordinate-based meta-analysis for neuroimaging data. Advanced Bayesian hierarchical modeling and Markov simulations projected long-term metabolic outcomes.</div></div><div><h3>Results</h3><div>Twelve studies with total included 7143 participants met our inclusion criteria, including nine randomized controlled trials and three observational studies. Brain FDG-PET revealed SSRI use restored dorsal raphe nucleus hypometabolism (standardized mean difference 0.87, 95 % CI: 0.52–1.22, P-value = 0.001). Meta-analysis demonstrated increased gastrointestinal adverse events (risk ratio 2.15, 95 % CI: 1.68–2.76, P-value<0.001, with moderate between-study heterogeneity), with sertraline showing highest rates. Citalopram 30 mg provided significant weight loss protection (risk ratio 0.13, 95 % CI: 0.02–0.98, P-value = 0.02), though this exceeds the recommended 20 mg maximum dose for elderly patients due to cardiac safety considerations. Long-term diabetes incidence showed no increased risk (hazard ratio 0.75, 95 % CI: 0.50–1.12, P-value = 0.15). Bayesian modeling revealed 85 % probability of beneficial brain metabolic effects and 89 % probability of citalopram superiority for weight protection.</div></div><div><h3>Conclusions</h3><div>SSRIs restore brain glucose metabolism in AD patients while causing manageable peripheral metabolic effects. Citalopram appears the best for weight-sensitive patients, while sertraline requires gastrointestinal monitoring. These findings support SSRI safety for metabolic outcomes in AD treatment, however longer-term studies with controlled metabolic outcomes are needed to confirm our findings. The observed citalopram weight protection benefit was documented at 30 mg daily, which exceeds recommended dosing limits for elderly patients due to cardiac safety concerns.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"27 ","pages":"Article 100389"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144922300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vitamin D deficiency is prevalent among monastic Orthodox populations, likely due to their sartorial habits and religious fasting rules. Data on supplementation in similar populations are lacking, including responses in restoring vitamin D sufficiency and to specific formulations of vitamin D supplements. This controlled study evaluated the efficacy of a daily oral vitamin D regimen, using oil-based drops and tablets, in restoring vitamin D status in a population of Orthodox nuns from Northern Greece, as well as assessing potential formulation-specific effects in the context of vitamin D supplementation.
Methods
A total of 41 Orthodox nuns practicing intermittent fasting received a daily dose of 2.500 IU vitamin D3 in either oil-based drops or tablets for 16 weeks and were compared to 40 matched controls without supplementation. Serum concentrations of 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), calcium, and albumin were measured at baseline and after 16 weeks in both groups.
Results
In the supplemented group, mean serum 25(OH)D concentrations increased significantly from 21.44 ± 9.08 ng/mL to 34.27 ± 10.33 ng/mL (p = 0.022), while PTH decreased from 66.18 ± 21.31 pg/mL to 50.71 ± 15.92 pg/mL (p = 0.018). The control group showed no significant changes in either 25(OH)D (23.90 ± 7.11 vs. 26.53 ± 9.14 ng/mL, p = 0.067) or PTH (41.75 ± 15.74 vs. 40.11 ± 13.56 pg/mL, p = 0.415). Multivariate regression—adjusting for baseline 25(OH)D, BMI, and body fat percentage—indicated that the form of supplementation (tablet vs. drops) was not an independent predictor of the change in vitamin D concentrations (β = +2.77, p = 0.456). The only statistically significant predictor was baseline 25(OH)D (β = −0.63, p < 0.001).
Conclusions
A daily regimen of oral vitamin D3, administered as either drops or tablets, is effective in significantly improving vitamin D status and reducing PTH concentrations in women adhering to intermittent fasting religious practices. These findings support targeted supplementation strategies in at-risk fasting populations, particularly those with vitamin D deficiency, regardless of the form of oral supplementation.
维生素D缺乏症在修道院的东正教人群中很普遍，可能是由于他们的服装习惯和宗教禁食规定。缺乏在类似人群中补充维生素D的数据，包括恢复维生素D充足性和对维生素D补充剂特定配方的反应。这项对照研究评估了每日口服维生素D方案的功效，使用油基滴剂和片剂，在希腊北部的东正教修女群体中恢复维生素D状态，并评估了维生素D补充的潜在配方特定效果。方法41名实行间歇性禁食的东正教修女在16周内每天服用2500国际单位的维生素D3油基滴剂或片剂，并与40名不补充维生素D3的对照组进行比较。在基线和16周后测量两组血清25-羟基维生素D [25(OH)D]、甲状旁腺激素（PTH）、钙和白蛋白浓度。结果添加组血清25(OH)D浓度由21.44±9.08 ng/mL显著升高至34.27±10.33 ng/mL (p = 0.022)， PTH浓度由66.18±21.31 pg/mL显著降低至50.71±15.92 pg/mL （p = 0.018）。对照组25(OH)D（23.90±7.11∶26.53±9.14 ng/mL, p = 0.067）和PTH（41.75±15.74∶40.11±13.56 pg/mL, p = 0.415）无显著变化。多变量回归-调整基线25(OH)D、BMI和体脂百分比-表明补充形式（片剂vs滴剂）不是维生素D浓度变化的独立预测因子（β = +2.77, p = 0.456）。唯一具有统计学意义的预测因子是基线25(OH)D （β = - 0.63, p < 0.001）。结论每日口服维生素D3滴剂或片剂可显著改善间歇性禁食宗教活动妇女的维生素D状态，降低甲状旁腺激素浓度。这些发现支持在高危禁食人群，特别是维生素D缺乏症人群中采取有针对性的补充策略，无论口服补充剂的形式如何。
{"title":"Vitamin D3 supplementation in women practicing orthodox religious and intermittent fasting: A controlled study with formulation-specific effects","authors":"Spyridon N. Karras , Konstantinos Michalakis , Maria Kypraiou , Antonios Vlastos , Marios Anemoulis , Georgios Koukoulis , Zadalla Mouslech , Filotas Talidis , Costas Haitoglou , Evangelos G. Papanikolaou , Neoklis Georgopoulos , Georgios Tzimagiorgis","doi":"10.1016/j.metop.2025.100391","DOIUrl":"10.1016/j.metop.2025.100391","url":null,"abstract":"<div><h3>Background</h3><div>Vitamin D deficiency is prevalent among monastic Orthodox populations, likely due to their sartorial habits and religious fasting rules. Data on supplementation in similar populations are lacking, including responses in restoring vitamin D sufficiency and to specific formulations of vitamin D supplements. This controlled study evaluated the efficacy of a daily oral vitamin D regimen, using oil-based drops and tablets, in restoring vitamin D status in a population of Orthodox nuns from Northern Greece, as well as assessing potential formulation-specific effects in the context of vitamin D supplementation.</div></div><div><h3>Methods</h3><div>A total of 41 Orthodox nuns practicing intermittent fasting received a daily dose of 2.500 IU vitamin D3 in either oil-based drops or tablets for 16 weeks and were compared to 40 matched controls without supplementation. Serum concentrations of 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), calcium, and albumin were measured at baseline and after 16 weeks in both groups.</div></div><div><h3>Results</h3><div>In the supplemented group, mean serum 25(OH)D concentrations increased significantly from 21.44 ± 9.08 ng/mL to 34.27 ± 10.33 ng/mL (p = 0.022), while PTH decreased from 66.18 ± 21.31 pg/mL to 50.71 ± 15.92 pg/mL (p = 0.018). The control group showed no significant changes in either 25(OH)D (23.90 ± 7.11 vs. 26.53 ± 9.14 ng/mL, p = 0.067) or PTH (41.75 ± 15.74 vs. 40.11 ± 13.56 pg/mL, p = 0.415). Multivariate regression—adjusting for baseline 25(OH)D, BMI, and body fat percentage—indicated that the form of supplementation (tablet vs. drops) was not an independent predictor of the change in vitamin D concentrations (β = +2.77, p = 0.456). The only statistically significant predictor was baseline 25(OH)D (β = −0.63, p < 0.001).</div></div><div><h3>Conclusions</h3><div>A daily regimen of oral vitamin D3, administered as either drops or tablets, is effective in significantly improving vitamin D status and reducing PTH concentrations in women adhering to intermittent fasting religious practices. These findings support targeted supplementation strategies in at-risk fasting populations, particularly those with vitamin D deficiency, regardless of the form of oral supplementation.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"27 ","pages":"Article 100391"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144920162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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