Pub Date : 2025-03-01Epub Date: 2025-02-12DOI: 10.1016/j.diabet.2025.101623
Mingyang Sun , Xiaoling Wang , Zhongyuan Lu , Yitian Yang , Shuang Lv , Mengrong Miao , Wan-Ming Chen , Szu-Yuan Wu , Jiaqiang Zhang
Background
Type 2 diabetes mellitus (T2DM) is associated with an elevated risk of dementia, including Alzheimer's disease (AD) and vascular dementia (VaD). While sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists have shown neuroprotective potential, comparative data on their efficacy in dementia prevention remain scarce.
Methods
- We conducted a retrospective cohort study using the TriNetX database, including 307,103 SGLT2 inhibitor users and 348,686 GLP-1 receptor agonist users with T2DM. Propensity score matching yielded 221,883 pairs with balanced baseline characteristics. The primary outcome was overall dementia incidence, with secondary outcomes including AD, VaD, and all-cause mortality. Hazard ratios (HRs) were calculated using Cox proportional hazards models.
Results
SGLT2 inhibitors were associated with a significantly lower incidence of overall dementia compared to GLP-1 receptor agonists (2.7 % vs. 3.6 %; HR, 0.92; 95 % CI, 0.89–0.95). The risk of VaD (HR, 0.89; 95 % CI, 0.84–0.95) and AD (HR, 0.90; 95 % CI, 0.86–0.94) was also reduced with SGLT2 inhibitors. All-cause mortality was lower in the SGLT2 group (3.6 % vs. 4.6 %; HR, 0.95; 95 % CI, 0.92–0.98). No significant difference was observed in other dementia subtypes (HR, 0.96; 95 % CI, 0.91–1.01).
Conclusions
In this large, real-world cohort, SGLT2 inhibitors demonstrated superior efficacy over GLP-1 receptor agonists in reducing the risks of overall dementia, VaD, and AD among patients with T2DM. These findings support the preferential use of SGLT2 inhibitors in mitigating dementia risk in this population, though randomized controlled trials are warranted for confirmation.
{"title":"Comparative effectiveness of SGLT2 inhibitors and GLP-1 receptor agonists in preventing Alzheimer's disease, vascular dementia, and other dementia types among patients with type 2 diabetes","authors":"Mingyang Sun , Xiaoling Wang , Zhongyuan Lu , Yitian Yang , Shuang Lv , Mengrong Miao , Wan-Ming Chen , Szu-Yuan Wu , Jiaqiang Zhang","doi":"10.1016/j.diabet.2025.101623","DOIUrl":"10.1016/j.diabet.2025.101623","url":null,"abstract":"<div><h3>Background</h3><div>Type 2 diabetes mellitus (T2DM) is associated with an elevated risk of dementia, including Alzheimer's disease (AD) and vascular dementia (VaD). While sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists have shown neuroprotective potential, comparative data on their efficacy in dementia prevention remain scarce.</div></div><div><h3>Methods</h3><div><em>-</em> We conducted a retrospective cohort study using the TriNetX database, including 307,103 SGLT2 inhibitor users and 348,686 GLP-1 receptor agonist users with T2DM. Propensity score matching yielded 221,883 pairs with balanced baseline characteristics. The primary outcome was overall dementia incidence, with secondary outcomes including AD, VaD, and all-cause mortality. Hazard ratios (HRs) were calculated using Cox proportional hazards models.</div></div><div><h3>Results</h3><div>SGLT2 inhibitors were associated with a significantly lower incidence of overall dementia compared to GLP-1 receptor agonists (2.7 % vs. 3.6 %; HR, 0.92; 95 % CI, 0.89–0.95). The risk of VaD (HR, 0.89; 95 % CI, 0.84–0.95) and AD (HR, 0.90; 95 % CI, 0.86–0.94) was also reduced with SGLT2 inhibitors. All-cause mortality was lower in the SGLT2 group (3.6 % vs. 4.6 %; HR, 0.95; 95 % CI, 0.92–0.98). No significant difference was observed in other dementia subtypes (HR, 0.96; 95 % CI, 0.91–1.01).</div></div><div><h3>Conclusions</h3><div>In this large, real-world cohort, SGLT2 inhibitors demonstrated superior efficacy over GLP-1 receptor agonists in reducing the risks of overall dementia, VaD, and AD among patients with T2DM. These findings support the preferential use of SGLT2 inhibitors in mitigating dementia risk in this population, though randomized controlled trials are warranted for confirmation.</div></div>","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":"51 2","pages":"Article 101623"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01Epub Date: 2025-01-18DOI: 10.1016/j.diabet.2025.101607
Boyuan Wang , Ivy Lynn Mak , Kiki Sze Nga Liu , Edmond Pui Hang Choi , Cindy Lo Kuen Lam , Eric Yuk Fai Wan
Objective
This study aimed to evaluate the association between type 2 diabetes mellitus (T2DM) onset age and risk of cardiovascular disease (CVD) and mortality.
Method
Two retrospective cohort studies were conducted using the electronic health records from the United Kingdom (UK) and Hong Kong (HK) on adults without CVD. During 2008-2013, 128,918 and 185,646 patients with new-onset T2DM were assigned to the T2DM group, and 5,052,770 and 3,159,396 patients without T2DM were included as controls in the UK and HK cohort, respectively. Patients were stratified into six age groups. Multivariable Cox regression, adjusted for baseline characteristics and fine stratification weights, was used to estimate the hazard ratios (HRs) and 95 % confidence intervals (CIs) for each outcome.
Results
New-onset T2DM was associated with increased CVD and mortality risk, but the risks decreased with age. Compared to those without T2DM in the same age groups, the HR (95 % CI) for CVD in the UK cohort was 3.22 (2.80, 3.71), 1.21 (1.15, 1.26), and 0.99 (0.93, 1.05) for T2DM individuals at ages 18–39, 60–69, and ≥ 80, respectively. Similarly, the HR (95 % CI) for mortality among new-onset T2DM patients was 2.41 (2.06, 2.83) for age 18–39, 1.40 (1.34, 1.46) for age 60–69, and 1.12 (1.08, 1.16) for age ≥ 80. Results from the HK cohort showed a similar pattern.
Conclusion
Young onset of T2DM is associated with a significant impact on cardiovascular health later in life. This highlights the importance of the prevention of DM in young adults.
{"title":"Association between Type 2 Diabetes onset age and risk of cardiovascular disease and mortality: Two cohort studies from United Kingdom and Hong Kong","authors":"Boyuan Wang , Ivy Lynn Mak , Kiki Sze Nga Liu , Edmond Pui Hang Choi , Cindy Lo Kuen Lam , Eric Yuk Fai Wan","doi":"10.1016/j.diabet.2025.101607","DOIUrl":"10.1016/j.diabet.2025.101607","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to evaluate the association between type 2 diabetes mellitus (T2DM) onset age and risk of cardiovascular disease (CVD) and mortality.</div></div><div><h3>Method</h3><div>Two retrospective cohort studies were conducted using the electronic health records from the United Kingdom (UK) and Hong Kong (HK) on adults without CVD. During 2008-2013, 128,918 and 185,646 patients with new-onset T2DM were assigned to the T2DM group, and 5,052,770 and 3,159,396 patients without T2DM were included as controls in the UK and HK cohort, respectively. Patients were stratified into six age groups. Multivariable Cox regression, adjusted for baseline characteristics and fine stratification weights, was used to estimate the hazard ratios (HRs) and 95 % confidence intervals (CIs) for each outcome.</div></div><div><h3>Results</h3><div>New-onset T2DM was associated with increased CVD and mortality risk, but the risks decreased with age. Compared to those without T2DM in the same age groups, the HR (95 % CI) for CVD in the UK cohort was 3.22 (2.80, 3.71), 1.21 (1.15, 1.26), and 0.99 (0.93, 1.05) for T2DM individuals at ages 18–39, 60–69, and ≥ 80, respectively. Similarly, the HR (95 % CI) for mortality among new-onset T2DM patients was 2.41 (2.06, 2.83) for age 18–39, 1.40 (1.34, 1.46) for age 60–69, and 1.12 (1.08, 1.16) for age ≥ 80. Results from the HK cohort showed a similar pattern.</div></div><div><h3>Conclusion</h3><div>Young onset of T2DM is associated with a significant impact on cardiovascular health later in life. This highlights the importance of the prevention of DM in young adults.</div></div>","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":"51 2","pages":"Article 101607"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143018722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Current guidelines recommend assessing glycemic control using continuous glucose monitoring (CGM), which provides a comprehensive glycemic profile to supplement HbA1c measurement. However, the association between CGM-derived metrics and risk of adverse kidney outcomes is not entirely clear. This retrospective cohort study included 1274 patients with type 2 diabetes hospitalized from July 2020 to December 2022, with a median follow-up time of 923 days. Monitor using CGM at baseline and evaluate renal function indicators of participants at baseline and end of follow-up. Multiple CGM-derived metrics, particularly time in range (TIR) and glucose coefficient of variation (CV), were calculated from 3-day glucose profiles obtained from CGM. Relevant clinical data was collected from clinical records and/or patient interviews. The primary outcome was chronic-kidney-disease (CKD) progression. Secondary outcomes included worsening of albuminuria and, all-cause mortality and major-adverse-cardiac-events(MACE). Multivariate regression models were employed to analyze the association between CGM-derived indices, particularly TIR and CV, and the risk of adverse kidney outcomes. We demonstrated that the lower TIR categories had a remarkably increased risk of CKD progression, with a HR per 10 % increment of 0.90 (95 %CI:0.83–0.91). Conversely, higher CV was positively related to the subsequent risk of CKD progression, with an HR per 10 % increment of 1.30 (95 %CI:1.07–1.59). These results were consistent across various subgroups and sensitivity analyses. This study found that TIR and CV are significantly associated with CKD progression, proteinuria deterioration, all-cause mortality, and the risk of MACE. These findings have elasticity in adjusting for multiple covariates and have been confirmed in different subgroups and sensitivity analyses.
{"title":"Continuous glucose monitoring‑derived time in range and CV are associated with elevated risk of adverse kidney outcomes for patients with type 2 diabetes","authors":"Qin Zhang , Shucai Xiao , Fang Zou , Xiaojuan Jiao , Yunfeng Shen","doi":"10.1016/j.diabet.2025.101616","DOIUrl":"10.1016/j.diabet.2025.101616","url":null,"abstract":"<div><div>Current guidelines recommend assessing glycemic control using continuous glucose monitoring (CGM), which provides a comprehensive glycemic profile to supplement HbA1c measurement. However, the association between CGM-derived metrics and risk of adverse kidney outcomes is not entirely clear. This retrospective cohort study included 1274 patients with type 2 diabetes hospitalized from July 2020 to December 2022, with a median follow-up time of 923 days. Monitor using CGM at baseline and evaluate renal function indicators of participants at baseline and end of follow-up. Multiple CGM-derived metrics, particularly time in range (TIR) and glucose coefficient of variation (CV), were calculated from 3-day glucose profiles obtained from CGM. Relevant clinical data was collected from clinical records and/or patient interviews. The primary outcome was chronic-kidney-disease (CKD) progression. Secondary outcomes included worsening of albuminuria and, all-cause mortality and major-adverse-cardiac-events(MACE). Multivariate regression models were employed to analyze the association between CGM-derived indices, particularly TIR and CV, and the risk of adverse kidney outcomes. We demonstrated that the lower TIR categories had a remarkably increased risk of CKD progression, with a HR per 10 % increment of 0.90 (95 %CI:0.83–0.91). Conversely, higher CV was positively related to the subsequent risk of CKD progression, with an HR per 10 % increment of 1.30 (95 %CI:1.07–1.59). These results were consistent across various subgroups and sensitivity analyses. This study found that TIR and CV are significantly associated with CKD progression, proteinuria deterioration, all-cause mortality, and the risk of MACE. These findings have elasticity in adjusting for multiple covariates and have been confirmed in different subgroups and sensitivity analyses.</div></div>","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":"51 2","pages":"Article 101616"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143401140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01Epub Date: 2025-02-07DOI: 10.1016/j.diabet.2025.101622
Louise Bodier , Maela Le Lous , Hélène Isly , Christèle Derrien , Patricia Vaduva
Aim
Gestational diabetes, characterized by impaired glucose tolerance occurring or diagnosed during pregnancy, is a significant public health concern. When lifestyle and dietary measures fail (30 % of women), insulin is the standard treatment. Oral antidiabetic agents, such as metformin (Glucophage) and glibenclamide, could provide a promising alternative. The aim here was to evaluate the effectiveness and safety of these treatments in gestational diabetes.
Methods
This study is based on a systematic literature review. A keyword search for "metformin (Glucophage)," "glibenclamide," "pregnancy," and "gestational diabetes" was conducted in the PubMed and Google Scholar databases from 2013 to 2023.
Results
A total of 45 studies were selected and analyzed. metformin (Glucophage) appears to offer a combination of effectiveness in glycemic control and maternal and neonatal safety. Compared to insulin, it reduces maternal weight gain, lowers maternal hypoglycemia rates, and shows a tendency to reduce gestational hypertension and preeclampsia. Additionally, infants born to mothers on metformin (Glucophage) are less likely to be macrosomic, experience fewer neonatal hypoglycemic episodes, and require fewer admissions to intensive care units. On the other hand, glibenclamide seems effective in glycemic control but is associated with higher rates of macrosomia and neonatal hypoglycemia.
Conclusion
Metformin (Glucophage) appears to be a promising alternative to insulin for treating gestational diabetes, while uncertainties remain regarding the safety of glibenclamide.
{"title":"Efficacy and safety of pharmacological treatments for gestational diabetes: a systematic review comparing metformin with glibenclamide and insulin","authors":"Louise Bodier , Maela Le Lous , Hélène Isly , Christèle Derrien , Patricia Vaduva","doi":"10.1016/j.diabet.2025.101622","DOIUrl":"10.1016/j.diabet.2025.101622","url":null,"abstract":"<div><h3>Aim</h3><div>Gestational diabetes, characterized by impaired glucose tolerance occurring or diagnosed during pregnancy, is a significant public health concern. When lifestyle and dietary measures fail (30 % of women), insulin is the standard treatment. Oral antidiabetic agents, such as metformin (Glucophage) and glibenclamide, could provide a promising alternative. The aim here was to evaluate the effectiveness and safety of these treatments in gestational diabetes.</div></div><div><h3>Methods</h3><div>This study is based on a systematic literature review. A keyword search for \"metformin (Glucophage),\" \"glibenclamide,\" \"pregnancy,\" and \"gestational diabetes\" was conducted in the PubMed and Google Scholar databases from 2013 to 2023.</div></div><div><h3>Results</h3><div>A total of 45 studies were selected and analyzed. metformin (Glucophage) appears to offer a combination of effectiveness in glycemic control and maternal and neonatal safety. Compared to insulin, it reduces maternal weight gain, lowers maternal hypoglycemia rates, and shows a tendency to reduce gestational hypertension and preeclampsia. Additionally, infants born to mothers on metformin (Glucophage) are less likely to be macrosomic, experience fewer neonatal hypoglycemic episodes, and require fewer admissions to intensive care units. On the other hand, glibenclamide seems effective in glycemic control but is associated with higher rates of macrosomia and neonatal hypoglycemia.</div></div><div><h3>Conclusion</h3><div>Metformin (Glucophage) appears to be a promising alternative to insulin for treating gestational diabetes, while uncertainties remain regarding the safety of glibenclamide.</div></div>","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":"51 2","pages":"Article 101622"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143384848","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}
Pub Date : 2025-03-01Epub Date: 2025-02-15DOI: 10.1016/j.diabet.2025.101626
Pien Rawee , Daan Kremer , Amarens Van der Vaart , Daan J Touw , Peter R Van Dijk , Martin H de Borst , Stephan JL Bakker , Michele F Eisenga
Aim
Iron is known to play a role in glucose homeostasis, and diabetes is highly prevalent in patients with iron overload. Here, we investigated whether ferritin and hepcidin (as parameters of iron status) are associated with the development of post-transplant diabetes in kidney transplant recipients, a population in which around 10 % is known to have high iron status.
Methods
Prospective data from the TransplantLines Insulin Resistance and Inflammation Biobank and Cohort Study from the University Medical Center Groningen, the Netherlands were evaluated, involving stable adult kidney transplant recipients > 1 year after transplantation. Associations between ferritin and hepcidin levels, as markers of iron status, and incident post-transplant diabetes were analyzed by multivariable Cox regression models, followed by the exploration of potential clinical cut-offs of ferritin levels related to the risk of post-transplant diabetes.
Results
Of the included 443 kidney transplant recipients (age 50 ± 12 years, 44 % women, median 6.1 [3.0 – 12.1] years after transplantation), 65 kidney transplant recipients (15 %) developed post-transplant diabetes during a median follow-up of 9.6 [6.3 – 10.2] years. In contrast to hepcidin levels, ferritin levels were significantly associated with incident post-transplant diabetes, independent of adjustment for potential confounders (HR per 50 µg/l, 1.08; 95 % CI 1.02 – 1.14). When analyzing specific clinical cut-offs of ferritin levels, kidney transplant recipients with a ferritin > 500 µg/l (n=40) had more than twice the risk of developing post-transplant diabetes, compared to kidney transplant recipients with ferritin < 100 µg/l (HR, 2.81; 95 % CI 1.04 – 7.55).
Conclusions
Increased levels of ferritin are independently associated with a higher risk of post-transplant diabetes in kidney transplant recipients. Especially, kidney transplant recipients with ferritin levels > 500 µg/l, seem susceptible to the development of post-transplant diabetes over time.
{"title":"Increased ferritin levels are associated with incident diabetes after kidney transplantation: A prospective cohort study","authors":"Pien Rawee , Daan Kremer , Amarens Van der Vaart , Daan J Touw , Peter R Van Dijk , Martin H de Borst , Stephan JL Bakker , Michele F Eisenga","doi":"10.1016/j.diabet.2025.101626","DOIUrl":"10.1016/j.diabet.2025.101626","url":null,"abstract":"<div><h3>Aim</h3><div>Iron is known to play a role in glucose homeostasis, and diabetes is highly prevalent in patients with iron overload. Here, we investigated whether ferritin and hepcidin (as parameters of iron status) are associated with the development of post-transplant diabetes in kidney transplant recipients, a population in which around 10 % is known to have high iron status.</div></div><div><h3>Methods</h3><div>Prospective data from the TransplantLines Insulin Resistance and Inflammation Biobank and Cohort Study from the University Medical Center Groningen, the Netherlands were evaluated, involving stable adult kidney transplant recipients > 1 year after transplantation. Associations between ferritin and hepcidin levels, as markers of iron status, and incident post-transplant diabetes were analyzed by multivariable Cox regression models, followed by the exploration of potential clinical cut-offs of ferritin levels related to the risk of post-transplant diabetes.</div></div><div><h3>Results</h3><div>Of the included 443 kidney transplant recipients (age 50 ± 12 years, 44 % women, median 6.1 [3.0 – 12.1] years after transplantation), 65 kidney transplant recipients (15 %) developed post-transplant diabetes during a median follow-up of 9.6 [6.3 – 10.2] years. In contrast to hepcidin levels, ferritin levels were significantly associated with incident post-transplant diabetes, independent of adjustment for potential confounders (HR per 50 µg/l, 1.08; 95 % CI 1.02 – 1.14). When analyzing specific clinical cut-offs of ferritin levels, kidney transplant recipients with a ferritin > 500 µg/l (n=40) had more than twice the risk of developing post-transplant diabetes, compared to kidney transplant recipients with ferritin < 100 µg/l (HR, 2.81; 95 % CI 1.04 – 7.55).</div></div><div><h3>Conclusions</h3><div>Increased levels of ferritin are independently associated with a higher risk of post-transplant diabetes in kidney transplant recipients. Especially, kidney transplant recipients with ferritin levels > 500 µg/l, seem susceptible to the development of post-transplant diabetes over time.</div></div>","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":"51 2","pages":"Article 101626"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143442796","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}
To analyze in a population of persons with type 1 diabetes (PwT1D) ambulatory glucose profile (AGP) parameters – including glycemia risk index (GRI) – for six months after hybrid closed loop (HCL) initiation in a multisite out-of-hospital French center (CIRDIA). We calculated the percentage of people reaching glucose targets and determined a GRI threshold that could identify patients reaching targets.
Methods
This was a retrospective study conducted in the CIRDIA, a multisite (n=7) out-of-hospital HCL initiation center. AGP metrics for the 14 previous days were manually extracted from HCL platforms at initiation (M0), 3 ± 1 months (M3) and 6 ± 1 months (M6). PwT1D were considered as reaching efficacy and safety targets (EST) if time-in-range was > 70 %, GMI was < 7 %, time-below-range (TBR)<70 was < 4 % and TBR<54 was < 1 %. GRI was calculated and ROC analyses were performed to set a GRI threshold that could identify patients reaching EST.
Results
Six-month data were available for 136 persons. The percentage of PwT1D reaching glucose targets at respectively M0, M3 and M6 were for EST: 6.6 %, 40.4 % and 39.7 %. GRI decreased from 56.0 ± 20.9 to 30.1 ± 14.1 and 30.6 ± 13.8. ROC analyses showed that the best GRI value to detect patients who reached EST was GRI <26. A threshold set at this level had very good specificity (92 %) and negative predictive value (93 %) to identify those who do need further intensive support with HCL.
Conclusion
Setting a GRI threshold at 26 could be helpful to detect with a single number, potentially automatically calculated by CGM platforms, PwT1D who require further support.
{"title":"Glycemia Risk Index (GRI) and international glucose targets before and 6 months after initiation of hybrid closed loop system in the CIRDIA, a French multisite out-of-hospital center","authors":"Sylvie Picard , Blandine Courbebaisse , Joëlle Dupont , Fabienne Amiot-Chapoutot , Emmanuelle Lecornet-Sokol , Estelle Personeni , François Mougel , Clara Bouché , Françoise Giroud , Sandrine Lablanche , Sophie Borot","doi":"10.1016/j.diabet.2025.101617","DOIUrl":"10.1016/j.diabet.2025.101617","url":null,"abstract":"<div><h3>Aims</h3><div>To analyze in a population of persons with type 1 diabetes (PwT1D) ambulatory glucose profile (AGP) parameters – including glycemia risk index (GRI) – for six months after hybrid closed loop (HCL) initiation in a multisite out-of-hospital French center (CIRDIA). We calculated the percentage of people reaching glucose targets and determined a GRI threshold that could identify patients reaching targets.</div></div><div><h3>Methods</h3><div>This was a retrospective study conducted in the CIRDIA, a multisite (<em>n</em>=7) out-of-hospital HCL initiation center. AGP metrics for the 14 previous days were manually extracted from HCL platforms at initiation (M0), 3 ± 1 months (M3) and 6 ± 1 months (M6). PwT1D were considered as reaching efficacy and safety targets (EST) if time-in-range was > 70 %, GMI was < 7 %, time-below-range (TBR)<sup><70</sup> was < 4 % and TBR<sup><54</sup> was < 1 %. GRI was calculated and ROC analyses were performed to set a GRI threshold that could identify patients reaching EST.</div></div><div><h3>Results</h3><div>Six-month data were available for 136 persons. The percentage of PwT1D reaching glucose targets at respectively M0, M3 and M6 were for EST: 6.6 %, 40.4 % and 39.7 %. GRI decreased from 56.0 ± 20.9 to 30.1 ± 14.1 and 30.6 ± 13.8. ROC analyses showed that the best GRI value to detect patients who reached EST was GRI <26. A threshold set at this level had very good specificity (92 %) and negative predictive value (93 %) to identify those who do need further intensive support with HCL.</div></div><div><h3>Conclusion</h3><div>Setting a GRI threshold at 26 could be helpful to detect with a single number, potentially automatically calculated by CGM platforms, PwT1D who require further support.</div></div>","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":"51 2","pages":"Article 101617"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143369769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01Epub Date: 2025-01-14DOI: 10.1016/j.diabet.2025.101612
André J. Scheen
Background
Obesity is an increasing public health problem because of its high prevalence and associated morbidity and mortality. Two weight-loss strategies are currently used, either bariatric surgery or pharmacological therapy with glucagon-like peptide-1 receptor agonists (GLP-1RAs). Preclinical studies in rodents suggested an increased risk of additive disorders after bariatric surgery contrasting with a reduced risk with GLP-1RAs.
Methods
An extensive literature search to detect clinical studies that investigated the prevalence of addictive disorders (food addiction, alcohol abuse, smoking, cannabis, cocaine, opioid use) following bariatric surgery or GLP-1RA therapy in obese patients.
Results
In observational cohort studies, the prevalence of alcohol use disorder was twofold higher after > 2 years following surgery (eleven studies, mainly with gastric bypass) whereas it was reduced roughly by half with GLP-1RA therapy (five studies, mainly with semaglutide). Similar findings were reported with other addictive disorders. An addiction transfer from food addiction to other addictive disorders is hypothesized to explain the increased risk after bariatric surgery. Several mechanisms are proposed to explain the favorable findings reported with GLP-1RAs, i.e. effects on the dopamine reward pathway, central GABA (gamma-aminobutyric acid) release, negative emotional stress associated with food/drug restriction and/or neuronal inflammation.
Conclusion
Available data from observational cohort studies confirm an increased risk of addictive disorders following bariatric surgery, contrasting with a reduced risk with GLP-1RA therapy. Both physicians and patients should be informed of the higher risk post-surgery whereas available promising results with GLP-1RAs should be confirmed in ongoing dedicated randomized controlled trials before any official indication.
{"title":"Weight loss therapy and addiction: Increased risk after bariatric surgery but reduced risk with GLP-1 receptor agonists","authors":"André J. Scheen","doi":"10.1016/j.diabet.2025.101612","DOIUrl":"10.1016/j.diabet.2025.101612","url":null,"abstract":"<div><h3>Background</h3><div>Obesity is an increasing public health problem because of its high prevalence and associated morbidity and mortality. Two weight-loss strategies are currently used, either bariatric surgery or pharmacological therapy with glucagon-like peptide-1 receptor agonists (GLP-1RAs). Preclinical studies in rodents suggested an increased risk of additive disorders after bariatric surgery contrasting with a reduced risk with GLP-1RAs.</div></div><div><h3>Methods</h3><div>An extensive literature search to detect clinical studies that investigated the prevalence of addictive disorders (food addiction, alcohol abuse, smoking, cannabis, cocaine, opioid use) following bariatric surgery or GLP-1RA therapy in obese patients.</div></div><div><h3>Results</h3><div>In observational cohort studies, the prevalence of alcohol use disorder was twofold higher after > 2 years following surgery (eleven studies, mainly with gastric bypass) whereas it was reduced roughly by half with GLP-1RA therapy (five studies, mainly with semaglutide). Similar findings were reported with other addictive disorders. An addiction transfer from food addiction to other addictive disorders is hypothesized to explain the increased risk after bariatric surgery. Several mechanisms are proposed to explain the favorable findings reported with GLP-1RAs, i.e. effects on the dopamine reward pathway, central GABA (gamma-aminobutyric acid) release, negative emotional stress associated with food/drug restriction and/or neuronal inflammation.</div></div><div><h3>Conclusion</h3><div>Available data from observational cohort studies confirm an increased risk of addictive disorders following bariatric surgery, contrasting with a reduced risk with GLP-1RA therapy. Both physicians and patients should be informed of the higher risk post-surgery whereas available promising results with GLP-1RAs should be confirmed in ongoing dedicated randomized controlled trials before any official indication.</div></div>","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":"51 2","pages":"Article 101612"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01Epub Date: 2025-02-03DOI: 10.1016/j.diabet.2025.101621
Maxime Carpentier , Matthieu Wargny , Mikaël Croyal , Cédric Le May , Sarra Smati , Edith Bigot-Corbel , Samy Hadjadj , Bertrand Cariou
Aim
Observational studies in the general population suggest that low concentrations of lipoprotein (a) [Lp(a)] are associated with an increased risk of type 2 diabetes. Here, we aim to determine whether Lp(a) plasma concentration and Kringle-IV (K-IV) repeat polymorphism were associated with new-onset diabetes (NOD) in individuals with prediabetes.
Methods
IT-DIAB is an observational, prospective study including 303 participants with impaired fasting glucose (fasting plasma glucose [FPG]: 110–125 mg/dl) followed annually for 5 years. The primary endpoint was the development of NOD, defined as a first FPG value ≥ 126 mg/dl during follow-up. Lp(a) concentrations were measured by immunoturbidimetry, apo(a) concentrations and the number of K-IV domains by mass spectrometry. Survival analyses for NOD were modeled using Kaplan-Meier curves and a multivariable Cox model, after binarization on threshold values of Lp(a) or K-IV.
Results
Among the participants, 113 (37%) developed NOD during follow-up. The concentrations of Lp(a) and the number of K-IV domains were not significantly different according to NOD status. Similarly, the percentage of patients with a non-detectable (≤ 7 nmol/l) or elevated (>125 nmol/l) Lp(a) concentration was similar between those with or without NOD: 68.1 vs 63.7% (P = 0.46) and 8.8 vs 8.9% (P > 0.99), respectively. Kaplan-Meier curves and Cox models did not show any association between Lp(a) concentration (threshold 7 nmol/l and 125 nmol/l) or number of K-IV domain (threshold 23) and the risk of NOD.
Conclusion
In a high-risk population, Lp(a) concentration or polymorphic size do not appear to be substantially associated with type 2 diabetes risk.
目的：在普通人群中的观察性研究表明，低浓度脂蛋白(a) [Lp(a)]与2型糖尿病的风险增加有关。在这里，我们的目的是确定Lp(a)血浆浓度和Kringle-IV （K-IV）重复多态性是否与糖尿病前期个体的新发糖尿病（NOD）相关。方法：IT-DIAB是一项观察性前瞻性研究，包括303名空腹血糖受损（空腹血糖[FPG]: 110-125 mg/dl）的参与者，每年随访5年。主要终点是NOD的发展，定义为随访期间首次FPG值≥126 mg/dl。免疫比浊法测定Lp(a)浓度，质谱法测定载脂蛋白(a)浓度和K-IV结构域数量。在Lp(a)或K-IV阈值二值化后，使用Kaplan-Meier曲线和多变量Cox模型对NOD的生存分析进行建模。结果：在参与者中，113例（37%）在随访期间发生NOD。不同NOD状态下Lp(a)的浓度和K-IV结构域的数量无显著差异。同样，在有或没有NOD的患者中，Lp(a)浓度不可检测（≤7 nmol/l）或升高（>125 nmol/l）的患者比例相似：分别为68.1 vs 63.7% （P = 0.46）和8.8 vs 8.9% （P > 0.99）。Kaplan-Meier曲线和Cox模型未显示Lp(a)浓度（阈值为7 nmol/l和125 nmol/l）或K-IV结构域数量（阈值为23）与NOD风险之间存在任何关联。结论：在高危人群中，Lp(a)浓度或多态性大小似乎与2型糖尿病风险无关。
{"title":"Lp(a) concentration and polymorphic size are not associated with new onset diabetes in individuals with prediabetes","authors":"Maxime Carpentier , Matthieu Wargny , Mikaël Croyal , Cédric Le May , Sarra Smati , Edith Bigot-Corbel , Samy Hadjadj , Bertrand Cariou","doi":"10.1016/j.diabet.2025.101621","DOIUrl":"10.1016/j.diabet.2025.101621","url":null,"abstract":"<div><h3>Aim</h3><div>Observational studies in the general population suggest that low concentrations of lipoprotein (a) [Lp(a)] are associated with an increased risk of type 2 diabetes. Here, we aim to determine whether Lp(a) plasma concentration and Kringle-IV (K-IV) repeat polymorphism were associated with new-onset diabetes (NOD) in individuals with prediabetes.</div></div><div><h3>Methods</h3><div>IT-DIAB is an observational, prospective study including 303 participants with impaired fasting glucose (fasting plasma glucose [FPG]: 110–125 mg/dl) followed annually for 5 years. The primary endpoint was the development of NOD, defined as a first FPG value ≥ 126 mg/dl during follow-up. Lp(a) concentrations were measured by immunoturbidimetry, apo(a) concentrations and the number of K-IV domains by mass spectrometry. Survival analyses for NOD were modeled using Kaplan-Meier curves and a multivariable Cox model, after binarization on threshold values of Lp(a) or K-IV.</div></div><div><h3>Results</h3><div>Among the participants, 113 (37%) developed NOD during follow-up. The concentrations of Lp(a) and the number of K-IV domains were not significantly different according to NOD status. Similarly, the percentage of patients with a non-detectable (≤ 7 nmol/l) or elevated (>125 nmol/l) Lp(a) concentration was similar between those with or without NOD: 68.1 vs 63.7% (<em>P</em> = 0.46) and 8.8 vs 8.9% (<em>P</em> > 0.99), respectively. Kaplan-Meier curves and Cox models did not show any association between Lp(a) concentration (threshold 7 nmol/l and 125 nmol/l) or number of K-IV domain (threshold 23) and the risk of NOD.</div></div><div><h3>Conclusion</h3><div>In a high-risk population, Lp(a) concentration or polymorphic size do not appear to be substantially associated with type 2 diabetes risk.</div></div>","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":"51 2","pages":"Article 101621"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01Epub Date: 2025-01-07DOI: 10.1016/j.diabet.2025.101605
Yun Kyung Cho , Sehee Kim , Myung Jin Kim , Woo Je Lee , Ye-Jee Kim , Chang Hee Jung
Aim
We aimed to investigate whether sodium-glucose cotransporter-2 inhibitors (SGLT2is) are associated with a decreased risk of gastrointestinal (GI) cancers in patients with type 2 diabetes (T2D) compared to other glucose lowering medications (oGLMs).
Methods
This active-comparator, new-user cohort study used the nationwide National Health Insurance Service database of the Republic of Korea from September 2014 to June 2020. From 79,423 new users of SGLT2is and 294,707 new users of oGLMs, we used a propensity score to match 59,954 from each of these two treatment groups. We calculated hazard ratios (HRs) and 95 % confidence intervals (CIs) for the incidence of GI cancers, encompassing stomach, colorectal, liver, and pancreatic cancers.
Results
During the observation period, there were 814 and 916 GI cancers, and 794 and 1,140 deaths in the SGLT2is and oGLMs treatment groups, respectively. The use of SGLT2is was associated with a statistically significant reduction in the incidence of GI cancers, with an adjusted HR of 0.90 (95 % CI: 0.82 to 0.99). However, only the incidence of pancreatic cancer was significantly lower in SGLT2is users compared to non-users, with an adjusted HR of 0.72 (95 % CI: 0.55 - 0.95). In the entire cohort, the multivariable-adjusted HR for pancreatic cancer was 0.70 (95 % CI: 0.56 to 0.88).
Conclusion
For T2D patients, SGLT2i use was associated with a diminished pancreatic cancer risk compared to oGLMs. Future studies should ascertain the potential protective effect of SGLT2is against pancreatic cancer.
{"title":"New users of sodium-glucose cotransporter 2 inhibitors are at low risk of incident pancreatic cancer: A nationwide population-based cohort study","authors":"Yun Kyung Cho , Sehee Kim , Myung Jin Kim , Woo Je Lee , Ye-Jee Kim , Chang Hee Jung","doi":"10.1016/j.diabet.2025.101605","DOIUrl":"10.1016/j.diabet.2025.101605","url":null,"abstract":"<div><h3>Aim</h3><div>We aimed to investigate whether sodium-glucose cotransporter-2 inhibitors (SGLT2is) are associated with a decreased risk of gastrointestinal (GI) cancers in patients with type 2 diabetes (T2D) compared to other glucose lowering medications (oGLMs).</div></div><div><h3>Methods</h3><div>This active-comparator, new-user cohort study used the nationwide National Health Insurance Service database of the Republic of Korea from September 2014 to June 2020. From 79,423 new users of SGLT2is and 294,707 new users of oGLMs, we used a propensity score to match 59,954 from each of these two treatment groups. We calculated hazard ratios (HRs) and 95 % confidence intervals (CIs) for the incidence of GI cancers, encompassing stomach, colorectal, liver, and pancreatic cancers.</div></div><div><h3>Results</h3><div>During the observation period, there were 814 and 916 GI cancers, and 794 and 1,140 deaths in the SGLT2is and oGLMs treatment groups, respectively. The use of SGLT2is was associated with a statistically significant reduction in the incidence of GI cancers, with an adjusted HR of 0.90 (95 % CI: 0.82 to 0.99). However, only the incidence of pancreatic cancer was significantly lower in SGLT2is users compared to non-users, with an adjusted HR of 0.72 (95 % CI: 0.55 - 0.95). In the entire cohort, the multivariable-adjusted HR for pancreatic cancer was 0.70 (95 % CI: 0.56 to 0.88).</div></div><div><h3>Conclusion</h3><div>For T2D patients, SGLT2i use was associated with a diminished pancreatic cancer risk compared to oGLMs. Future studies should ascertain the potential protective effect of SGLT2is against pancreatic cancer.</div></div>","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":"51 2","pages":"Article 101605"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01Epub Date: 2025-02-01DOI: 10.1016/j.diabet.2025.101618
Zhenyi Xu , Ruilang Lin , Xueying Ji , Chen Huang , Ce Wang , Yongfu Yu , Zhijun Bao
Aim
To examine the association between frailty and incident type 2 diabetes mellitus (T2DM), considering the joint effect of multimorbidity and genetic risk.
Methods
The study included 429,022 individuals in the UK Biobank. We used Cox regression with hazard ratio (HR) and 95 % confidence interval (CI) to 1) evaluate the associations of frailty with incident T2DM, 2) explore whether frailty and multimorbidity would have a joint effect, and 3) assess whether the associations were modified by genetic risk.
Results
Compared with non-frail individuals, prefrail and frail individuals were at higher risk of T2DM: HR[95 %CI] = 1.42 [1.38;1.47] for prefrailty and 1.81[1.70;1.92] for frailty. Five frailty components were associated with increased risk of T2DM: HR[95 %CI] = 1.21[1.17;1.26] for weight loss, 1.35[1.30;1.40] for exhaustion, 1.31[1.26;1.37] for low physical activity, 1.27[1.20;1.33] for low grip strength, and 1.47[1.41;1.52] for slow gait speed. The increased risks were more pronounced among frail individuals with more than three morbidities: HR[95 %CI] = 4.10[3.76;4.46]. Frail individuals at high genetic risk had a four and a half-fold greater risk of T2DM compared with non-frail individuals at low genetic risk: HR[95 %CI] = 4.54[4.14;4.97].
Conclusion
Frailty was associated with increased risk of T2DM, especially in individuals with higher number of morbidities and high genetic risk. Frailty may be an independent risk factor for T2DM and targeted strategies to prevent and manage frailty would contribute to reducing the risk of T2DM.
{"title":"Physical frailty, genetic predisposition, and type 2 diabetes mellitus","authors":"Zhenyi Xu , Ruilang Lin , Xueying Ji , Chen Huang , Ce Wang , Yongfu Yu , Zhijun Bao","doi":"10.1016/j.diabet.2025.101618","DOIUrl":"10.1016/j.diabet.2025.101618","url":null,"abstract":"<div><h3>Aim</h3><div>To examine the association between frailty and incident type 2 diabetes mellitus (T2DM), considering the joint effect of multimorbidity and genetic risk.</div></div><div><h3>Methods</h3><div>The study included 429,022 individuals in the UK Biobank. We used Cox regression with hazard ratio (HR) and 95 % confidence interval (CI) to 1) evaluate the associations of frailty with incident T2DM, 2) explore whether frailty and multimorbidity would have a joint effect, and 3) assess whether the associations were modified by genetic risk.</div></div><div><h3>Results</h3><div>Compared with non-frail individuals, prefrail and frail individuals were at higher risk of T2DM: HR[95 %CI] = 1.42 [1.38;1.47] for prefrailty and 1.81[1.70;1.92] for frailty. Five frailty components were associated with increased risk of T2DM: HR[95 %CI] = 1.21[1.17;1.26] for weight loss, 1.35[1.30;1.40] for exhaustion, 1.31[1.26;1.37] for low physical activity, 1.27[1.20;1.33] for low grip strength, and 1.47[1.41;1.52] for slow gait speed. The increased risks were more pronounced among frail individuals with more than three morbidities: HR[95 %CI] = 4.10[3.76;4.46]. Frail individuals at high genetic risk had a four and a half-fold greater risk of T2DM compared with non-frail individuals at low genetic risk: HR[95 %CI] = 4.54[4.14;4.97].</div></div><div><h3>Conclusion</h3><div>Frailty was associated with increased risk of T2DM, especially in individuals with higher number of morbidities and high genetic risk. Frailty may be an independent risk factor for T2DM and targeted strategies to prevent and manage frailty would contribute to reducing the risk of T2DM.</div></div>","PeriodicalId":11334,"journal":{"name":"Diabetes & metabolism","volume":"51 2","pages":"Article 101618"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143096878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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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