Background: Limited evidence exists to support any specific medication over others to prevent dementia in older patients with type 2 diabetes (T2D). We investigated whether treatment with sodium-glucose cotransporter 2 (SGLT-2) inhibitors is associated with a lower risk of incident dementia and all-cause mortality, relative to dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RA).
Methods: In this retrospective, active-comparator cohort study, we used data from the TriNetX electronic health records network. Our primary cohort comprised patients with T2D aged ≥50 years, registered between January 2012 and December 2022. Patients with a history of dementia were excluded. We used Kaplan-Meier survival analysis to estimate the incidence of dementia and all-cause mortality in our cohort after they had used glucose-lowering drugs for at least 12 months. Propensity score matching was performed to balance the SGLT-2 inhibitor, DPP-4 inhibitor and GLP-1 RA cohorts. Subgroup analyses for sex and age were also conducted.
Results: Our first cohort comprised 193 948 patients treated with metformin and SGLT-2 inhibitors and an equal number of patients treated with metformin and DPP-4 inhibitors. In this cohort, the risk of dementia and all-cause mortality was lower in patients treated with SGLT-2 inhibitors than in those treated with DPP-4 inhibitors (hazard ratio [HR]: 0.62, 95% confidence interval [CI]: 0.59-0.65, for dementia; HR: 0.54, 95% CI: 0.52-0.56, for all-cause mortality). Our second cohort comprised 165 566 patients treated with metformin and SGLT-2 inhibitors and an equal number of patients treated with metformin and GLP-1 RAs. In this cohort, the risk of dementia and all-cause mortality was lower in those treated with SGLT-2 inhibitors than in those treated with GLP-1 RAs (HR: 0.92, 95% CI: 0.87-0.98, for dementia; HR: 0.88, 95% CI: 0.85-0.91, for all-cause mortality).
Conclusions: The use of SGLT-2 inhibitor was associated with a lower risk of incident dementia and all-cause mortality in older adults with T2D compared to DPP-4 inhibitor and GLP-1 RA.
{"title":"Association of sodium-glucose cotransporter 2 inhibitors with risk of incident dementia and all-cause mortality in older patients with type 2 diabetes: A retrospective cohort study using the TriNetX US collaborative networks.","authors":"Yen-Wei Pai, I-Chieh Chen, Jun-Fu Lin, Xiao-Hui Chen, Hsin-Hua Chen, Ming-Hong Chang, Jin-An Huang, Ching-Heng Lin","doi":"10.1111/dom.15918","DOIUrl":"https://doi.org/10.1111/dom.15918","url":null,"abstract":"<p><strong>Background: </strong>Limited evidence exists to support any specific medication over others to prevent dementia in older patients with type 2 diabetes (T2D). We investigated whether treatment with sodium-glucose cotransporter 2 (SGLT-2) inhibitors is associated with a lower risk of incident dementia and all-cause mortality, relative to dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RA).</p><p><strong>Methods: </strong>In this retrospective, active-comparator cohort study, we used data from the TriNetX electronic health records network. Our primary cohort comprised patients with T2D aged ≥50 years, registered between January 2012 and December 2022. Patients with a history of dementia were excluded. We used Kaplan-Meier survival analysis to estimate the incidence of dementia and all-cause mortality in our cohort after they had used glucose-lowering drugs for at least 12 months. Propensity score matching was performed to balance the SGLT-2 inhibitor, DPP-4 inhibitor and GLP-1 RA cohorts. Subgroup analyses for sex and age were also conducted.</p><p><strong>Results: </strong>Our first cohort comprised 193 948 patients treated with metformin and SGLT-2 inhibitors and an equal number of patients treated with metformin and DPP-4 inhibitors. In this cohort, the risk of dementia and all-cause mortality was lower in patients treated with SGLT-2 inhibitors than in those treated with DPP-4 inhibitors (hazard ratio [HR]: 0.62, 95% confidence interval [CI]: 0.59-0.65, for dementia; HR: 0.54, 95% CI: 0.52-0.56, for all-cause mortality). Our second cohort comprised 165 566 patients treated with metformin and SGLT-2 inhibitors and an equal number of patients treated with metformin and GLP-1 RAs. In this cohort, the risk of dementia and all-cause mortality was lower in those treated with SGLT-2 inhibitors than in those treated with GLP-1 RAs (HR: 0.92, 95% CI: 0.87-0.98, for dementia; HR: 0.88, 95% CI: 0.85-0.91, for all-cause mortality).</p><p><strong>Conclusions: </strong>The use of SGLT-2 inhibitor was associated with a lower risk of incident dementia and all-cause mortality in older adults with T2D compared to DPP-4 inhibitor and GLP-1 RA.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152708","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}
Aim: To analyse data from the All of Us Research Program to evaluate the real-world application and long-term effectiveness of semaglutide in treating type 2 diabetes and obesity patients in a large population.
Materials and methods: We identified patients prescribed semaglutide and analysed differences in route of administration and the time on semaglutide. For individuals diagnosed with obesity, we measured changes in body mass index (BMI) and weight from baseline, while measured changes in HbA1c for those patients with type 2 diabetes. We also examined the occurrence of newly diagnosed common adverse events from taking semaglutide.
Results: For 3739 semaglutide patients, those on injectable semaglutide (3364 patients) averaged 301.54 days on the medication, with 20.36% having no end date, while those on oral semaglutide (435 patients) averaged 172.48 days, with 24.60% having no end date. We found average decreases of 1.54 kg/m2 in BMI, 4.65 kg in weight and 0.75% in HbA1c for semaglutide users. The decreases were larger in participants taking injectable formulation, probably because of higher starting values. Over time, improvements in these outcomes diminished, but the values remained significantly lower than baseline levels. Approximately only 1.0% of patients reported newly diagnosed common adverse events.
Conclusions: Consistent with clinical trial findings, this real-world data analysis showed that semaglutide was well tolerated and that, for a large population, it effectively reduced BMI, body weight and HbA1c, albeit to smaller magnitudes than observed in clinical trials. These findings provide valuable insights into real-world experience and the long-term effectiveness of semaglutide.
{"title":"Semaglutide use in people with obesity and type 2 diabetes from real-world utilization data: An analysis of the All of US Program.","authors":"Craig S Mayer, Paul Fontelo","doi":"10.1111/dom.15911","DOIUrl":"https://doi.org/10.1111/dom.15911","url":null,"abstract":"<p><strong>Aim: </strong>To analyse data from the All of Us Research Program to evaluate the real-world application and long-term effectiveness of semaglutide in treating type 2 diabetes and obesity patients in a large population.</p><p><strong>Materials and methods: </strong>We identified patients prescribed semaglutide and analysed differences in route of administration and the time on semaglutide. For individuals diagnosed with obesity, we measured changes in body mass index (BMI) and weight from baseline, while measured changes in HbA1c for those patients with type 2 diabetes. We also examined the occurrence of newly diagnosed common adverse events from taking semaglutide.</p><p><strong>Results: </strong>For 3739 semaglutide patients, those on injectable semaglutide (3364 patients) averaged 301.54 days on the medication, with 20.36% having no end date, while those on oral semaglutide (435 patients) averaged 172.48 days, with 24.60% having no end date. We found average decreases of 1.54 kg/m<sup>2</sup> in BMI, 4.65 kg in weight and 0.75% in HbA1c for semaglutide users. The decreases were larger in participants taking injectable formulation, probably because of higher starting values. Over time, improvements in these outcomes diminished, but the values remained significantly lower than baseline levels. Approximately only 1.0% of patients reported newly diagnosed common adverse events.</p><p><strong>Conclusions: </strong>Consistent with clinical trial findings, this real-world data analysis showed that semaglutide was well tolerated and that, for a large population, it effectively reduced BMI, body weight and HbA1c, albeit to smaller magnitudes than observed in clinical trials. These findings provide valuable insights into real-world experience and the long-term effectiveness of semaglutide.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152712","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}
Aim: To examine the likelihood of mortality or rehospitalization following acute coronary syndrome with glyburide versus gliclazide use in adults with type 2 diabetes undergoing cardiac catheterization.
Research design and methods: This retrospective cohort study used clinical data linked with administrative health data from Alberta, Canada between April 2008 and March 2021. Three methods were used to define exposure to glyburide and gliclazide in the year before catheterization. Multivariable logistic regression was used to compare the likelihood of a composite outcome of 1-year mortality or rehospitalization with use of glyburide versus use of gliclazide.
Results: A total of 11 140 individuals with type 2 diabetes had a cardiac catheterization for acute coronary syndrome. Their mean age was 66 years and 31% were female. In the year before catheterization, 5% used glyburide and 19% used gliclazide. Any glyburide or gliclazide exposure in the year before catheterization was associated with a similar likelihood of all-cause mortality or rehospitalization (adjusted odds ratio [aOR] 1.14, 95% confidence interval [CI] 0.93-1.41; p = 0.20). However, current glyburide exposure (aOR 1.37, 95% CI 1.06-1.79; p = 0.018) and long exposure to glyburide (aOR 1.37, 95% CI 1.03-1.83; p = 0.030) were associated with a higher likelihood of the composite outcome compared to current and long exposure to gliclazide, respectively.
Conclusions: Current and long exposure to glyburide was associated with a greater likelihood of mortality or rehospitalization following cardiac catheterization for acute coronary syndrome, when compared to similar gliclazide exposure definitions. This study adds further evidence of the need to avoid using glyburide if a sulphonylurea is required for type 2 diabetes management.
{"title":"Glyburide use is associated with a greater likelihood of mortality or rehospitalization after acute coronary syndrome compared to gliclazide use in adults with type 2 diabetes: A cohort study.","authors":"Wentong Long, Peter E Light, Scot H Simpson","doi":"10.1111/dom.15917","DOIUrl":"https://doi.org/10.1111/dom.15917","url":null,"abstract":"<p><strong>Aim: </strong>To examine the likelihood of mortality or rehospitalization following acute coronary syndrome with glyburide versus gliclazide use in adults with type 2 diabetes undergoing cardiac catheterization.</p><p><strong>Research design and methods: </strong>This retrospective cohort study used clinical data linked with administrative health data from Alberta, Canada between April 2008 and March 2021. Three methods were used to define exposure to glyburide and gliclazide in the year before catheterization. Multivariable logistic regression was used to compare the likelihood of a composite outcome of 1-year mortality or rehospitalization with use of glyburide versus use of gliclazide.</p><p><strong>Results: </strong>A total of 11 140 individuals with type 2 diabetes had a cardiac catheterization for acute coronary syndrome. Their mean age was 66 years and 31% were female. In the year before catheterization, 5% used glyburide and 19% used gliclazide. Any glyburide or gliclazide exposure in the year before catheterization was associated with a similar likelihood of all-cause mortality or rehospitalization (adjusted odds ratio [aOR] 1.14, 95% confidence interval [CI] 0.93-1.41; p = 0.20). However, current glyburide exposure (aOR 1.37, 95% CI 1.06-1.79; p = 0.018) and long exposure to glyburide (aOR 1.37, 95% CI 1.03-1.83; p = 0.030) were associated with a higher likelihood of the composite outcome compared to current and long exposure to gliclazide, respectively.</p><p><strong>Conclusions: </strong>Current and long exposure to glyburide was associated with a greater likelihood of mortality or rehospitalization following cardiac catheterization for acute coronary syndrome, when compared to similar gliclazide exposure definitions. This study adds further evidence of the need to avoid using glyburide if a sulphonylurea is required for type 2 diabetes management.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152709","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}
Michael S Kelly, Emily M Scopelliti, Kaylee E Goodson, Ching Mann Anne Lo, Huelena X Nguyen, Barbara Simon
Aims: Tirzepatide is a first-in-class combination glucose-dependent insulinotropic polypeptide (GIP) receptor agonist and glucagon-like peptide 1 receptor agonist (GLP1-RA) approved for treatment of adults with type 2 diabetes mellitus (T2DM) and chronic weight management. The aim of this analysis was to assess the real-world efficacy of tirzepatide in patients with T2DM.
Methods: This retrospective observational study evaluated patients with T2DM from a large urban academic medical centre who received at least 3 months of continuous tirzepatide treatment. The primary outcome was change in A1C from following tirzepatide treatment. Secondary outcomes included change in body weight and body mass index (BMI) after tirzepatide was initiated.
Results: A total of 1896 patient charts were reviewed, and 612 patients were evaluated for the primary outcome. Over a median time period of 10.4 months, treatment with tirzepatide resulted in a mean A1C reduction of 1.02 ± 1.48% (p < 0.001). A total of 570 patients were evaluated for the secondary outcomes. Tirzepatide was associated with a mean reduction in body weight of 7.3 ± 9.3 kg (p < 0.001) and a mean reduction in BMI of 2.5 kg/m2. Greater A1C lowering and weight loss was observed in patients without prior GLP1-RA treatment compared to those switched to tirzepatide from GLP1-RA.
Conclusions: In a real-world population of US patients with T2DM, tirzepatide was associated with clinically and statistically significant reductions in A1C and body weight. Greater reductions in both A1C and body weight were observed among patients who were GLP1-RA naïve compared to patients switched from GLP1-RA to tirzepatide.
{"title":"Real-world evaluation of the effects of tirzepatide in patients with type 2 diabetes mellitus.","authors":"Michael S Kelly, Emily M Scopelliti, Kaylee E Goodson, Ching Mann Anne Lo, Huelena X Nguyen, Barbara Simon","doi":"10.1111/dom.15934","DOIUrl":"https://doi.org/10.1111/dom.15934","url":null,"abstract":"<p><strong>Aims: </strong>Tirzepatide is a first-in-class combination glucose-dependent insulinotropic polypeptide (GIP) receptor agonist and glucagon-like peptide 1 receptor agonist (GLP1-RA) approved for treatment of adults with type 2 diabetes mellitus (T2DM) and chronic weight management. The aim of this analysis was to assess the real-world efficacy of tirzepatide in patients with T2DM.</p><p><strong>Methods: </strong>This retrospective observational study evaluated patients with T2DM from a large urban academic medical centre who received at least 3 months of continuous tirzepatide treatment. The primary outcome was change in A1C from following tirzepatide treatment. Secondary outcomes included change in body weight and body mass index (BMI) after tirzepatide was initiated.</p><p><strong>Results: </strong>A total of 1896 patient charts were reviewed, and 612 patients were evaluated for the primary outcome. Over a median time period of 10.4 months, treatment with tirzepatide resulted in a mean A1C reduction of 1.02 ± 1.48% (p < 0.001). A total of 570 patients were evaluated for the secondary outcomes. Tirzepatide was associated with a mean reduction in body weight of 7.3 ± 9.3 kg (p < 0.001) and a mean reduction in BMI of 2.5 kg/m<sup>2</sup>. Greater A1C lowering and weight loss was observed in patients without prior GLP1-RA treatment compared to those switched to tirzepatide from GLP1-RA.</p><p><strong>Conclusions: </strong>In a real-world population of US patients with T2DM, tirzepatide was associated with clinically and statistically significant reductions in A1C and body weight. Greater reductions in both A1C and body weight were observed among patients who were GLP1-RA naïve compared to patients switched from GLP1-RA to tirzepatide.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152711","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}
Martin Haluzík, Mohammed E Al-Sofiani, Alice Y Y Cheng, Felipe Lauand, Lydie Melas-Melt, Julio Rosenstock
Aim: To evaluate the efficacy of a fixed-ratio combination of insulin glargine 100 U/mL plus lixisenatide (iGlarLixi) in people with type 2 diabetes (T2D) using derived time-in-range (dTIR).
Methods: Participant-level data from LixiLan-L, LixiLan-O and LixiLan-G were pooled and dTIR (70-180 mg/dL), derived time-above-range (> 180 mg/dL) and derived time-below-range (dTBR; < 70 mg/dL) were calculated from participant seven-point self-monitored blood glucose profiles.
Results: This pooled analysis included data from 2420 participants receiving iGlarLixi (n = 1093), iGlar (n = 836), Lixi (n = 234) or a glucagon-like peptide-1 receptor agonist (GLP-1 RA) (n = 257). Numerically greater improvements in least square (LS) means dTIR were seen from baseline to end of treatment (EOT) with iGlarLixi (25.7%) versus iGlar (15.8%), Lixi (11.7%) or GLP-1 RA (16.2%). At EOT, the mean (standard deviation) dTBR was 0.71% ± 3.4%, 0.61% ± 3.2%, 0.08% ± 1.0% and 0.0% ± 0.0% for iGlarLixi, iGlar, Lixi and GLP-1 RA, respectively. In a subgroup analysis, participants aged younger than 65 years (n = 1690) and 65 years or older (n = 713) showed numerically greater improvements in LS means dTIR from baseline to EOT with iGlarLixi versus iGlar, Lixi or GLP-1 RA.
Conclusions: iGlarLixi achieved improvements in dTIR, with low dTBR values, providing further evidence to inform clinical outcomes with the use of iGlarLixi.
{"title":"Time-in-range derived from self-measured blood glucose in people with type 2 diabetes advancing to iGlarLixi: A participant-level pooled analysis of three phase 3 LixiLan randomized controlled trials.","authors":"Martin Haluzík, Mohammed E Al-Sofiani, Alice Y Y Cheng, Felipe Lauand, Lydie Melas-Melt, Julio Rosenstock","doi":"10.1111/dom.15811","DOIUrl":"https://doi.org/10.1111/dom.15811","url":null,"abstract":"<p><strong>Aim: </strong>To evaluate the efficacy of a fixed-ratio combination of insulin glargine 100 U/mL plus lixisenatide (iGlarLixi) in people with type 2 diabetes (T2D) using derived time-in-range (dTIR).</p><p><strong>Methods: </strong>Participant-level data from LixiLan-L, LixiLan-O and LixiLan-G were pooled and dTIR (70-180 mg/dL), derived time-above-range (> 180 mg/dL) and derived time-below-range (dTBR; < 70 mg/dL) were calculated from participant seven-point self-monitored blood glucose profiles.</p><p><strong>Results: </strong>This pooled analysis included data from 2420 participants receiving iGlarLixi (n = 1093), iGlar (n = 836), Lixi (n = 234) or a glucagon-like peptide-1 receptor agonist (GLP-1 RA) (n = 257). Numerically greater improvements in least square (LS) means dTIR were seen from baseline to end of treatment (EOT) with iGlarLixi (25.7%) versus iGlar (15.8%), Lixi (11.7%) or GLP-1 RA (16.2%). At EOT, the mean (standard deviation) dTBR was 0.71% ± 3.4%, 0.61% ± 3.2%, 0.08% ± 1.0% and 0.0% ± 0.0% for iGlarLixi, iGlar, Lixi and GLP-1 RA, respectively. In a subgroup analysis, participants aged younger than 65 years (n = 1690) and 65 years or older (n = 713) showed numerically greater improvements in LS means dTIR from baseline to EOT with iGlarLixi versus iGlar, Lixi or GLP-1 RA.</p><p><strong>Conclusions: </strong>iGlarLixi achieved improvements in dTIR, with low dTBR values, providing further evidence to inform clinical outcomes with the use of iGlarLixi.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152713","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}
Aims: To explore the potential of N-terminal pro-B natriuretic peptide (NTproBNP) in identifying adverse outcomes, particularly cardiovascular adverse outcomes, in a population with obesity, and to establish a risk prediction model.
Methods: The data for this study were obtained from the National Health and Nutrition Examination Survey (NHANES) for 6772 participants without heart failure, for the years 1999 to 2004. Multivariable Cox regression models, cubic spline restricted models and Kaplan-Meier curves were used to evaluate the relationship between NTproBNP and both all-cause mortality and cardiovascular mortality. Predictive models were established using seven machine learning methods, and evaluation was conducted using precision, recall, F1 score, accuracy, and area under the curve (AUC) values.
Results: During the population follow-up, out of 6772 participants, 1554 died, with 365 deaths attributed to cardiovascular disease. After adjusting for relevant covariates, NTproBNP levels ≥300 pg/mL were positively associated with both all-cause mortality (hazard ratio [HR] 3.00, 95% confidence interval [CI] 2.48, 3.67) and cardiovascular mortality (HR 6.05, 95% CI 3.67, 9.97), and remained significant across different body mass index (BMI) strata. However, in participants without abdominal obesity, the correlation between NTproBNP and cardiovascular mortality was significantly reduced. Among the seven machine learning methods, logistic regression demonstrated better predictive performance for both all-cause mortality (AUC 0.86925) and cardiovascular mortality (AUC 0.85115). However, establishing accurate cardiovascular mortality prediction models for non-abdominal obese individuals proved challenging.
Conclusion: The study showed that NTproBNP can serve as a predictive factor for all-cause mortality and cardiovascular mortality in individuals with different BMIs, including obese individuals. However, significant cardiovascular mortality correlation was observed only for NTproBNP levels ≥300 pg/mL, and only among participants with abdominal obesity.
{"title":"Association of N-terminal pro-B natriuretic peptide with all-cause mortality and cardiovascular mortality in obese and non-obese populations and the development of a machine learning prediction model: National Health and Nutrition Examination Survey (NHANES) 1999-2004.","authors":"Han Zhou, Chen Yang, Jingjie Li, Lin Sun","doi":"10.1111/dom.15927","DOIUrl":"https://doi.org/10.1111/dom.15927","url":null,"abstract":"<p><strong>Aims: </strong>To explore the potential of N-terminal pro-B natriuretic peptide (NTproBNP) in identifying adverse outcomes, particularly cardiovascular adverse outcomes, in a population with obesity, and to establish a risk prediction model.</p><p><strong>Methods: </strong>The data for this study were obtained from the National Health and Nutrition Examination Survey (NHANES) for 6772 participants without heart failure, for the years 1999 to 2004. Multivariable Cox regression models, cubic spline restricted models and Kaplan-Meier curves were used to evaluate the relationship between NTproBNP and both all-cause mortality and cardiovascular mortality. Predictive models were established using seven machine learning methods, and evaluation was conducted using precision, recall, F1 score, accuracy, and area under the curve (AUC) values.</p><p><strong>Results: </strong>During the population follow-up, out of 6772 participants, 1554 died, with 365 deaths attributed to cardiovascular disease. After adjusting for relevant covariates, NTproBNP levels ≥300 pg/mL were positively associated with both all-cause mortality (hazard ratio [HR] 3.00, 95% confidence interval [CI] 2.48, 3.67) and cardiovascular mortality (HR 6.05, 95% CI 3.67, 9.97), and remained significant across different body mass index (BMI) strata. However, in participants without abdominal obesity, the correlation between NTproBNP and cardiovascular mortality was significantly reduced. Among the seven machine learning methods, logistic regression demonstrated better predictive performance for both all-cause mortality (AUC 0.86925) and cardiovascular mortality (AUC 0.85115). However, establishing accurate cardiovascular mortality prediction models for non-abdominal obese individuals proved challenging.</p><p><strong>Conclusion: </strong>The study showed that NTproBNP can serve as a predictive factor for all-cause mortality and cardiovascular mortality in individuals with different BMIs, including obese individuals. However, significant cardiovascular mortality correlation was observed only for NTproBNP levels ≥300 pg/mL, and only among participants with abdominal obesity.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142138775","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}
Zubin Punthakee, Stephanie Hall, Natalia McInnes, Diana Sherifali, Kate Tsiplova, Faith R Kirabo, Thomas P P Ransom, Stewart B Harris, Heather A Lochnan, Ronald J Sigal, Mahua Ghosh, Tamara Spaic, Hertzel C Gerstein
Aim: To evaluate the effect on type 2 diabetes remission of short-term intensive metabolic intervention consisting of frequent dietary, exercise and diabetes management coaching, metformin and fixed-ratio insulin degludec/liraglutide.
Methods: In a multicentre open-label randomized controlled trial, insulin-naïve participants within 5 years of diabetes diagnosis were assigned to a 16-week remission intervention regimen or standard care, and followed for relapse of diabetes and sustained remission for an additional year after stopping glucose-lowering drugs.
Results: A total of 159 participants aged 57 ± 10 years, with diabetes duration 2.6 ± 1.5 years, body mass index 33.5 ± 6.5 kg/m2, and glycated haemoglobin (HbA1c) level 53 ± 7 mmol/mol were randomized and analysed (79 intervention, 80 control). At the end of the 16-week intervention period, compared to controls, intervention participants achieved lower HbA1c levels (40 ± 4 vs. 51 ± 7 mmol/mol; p < 0.0001), and lost more weight (3.3 ± 4.4% vs. 1.9 ± 3.0%; p = 0.02). There was a lower hazard of diabetes relapse overall in the intervention group compared to controls (hazard ratio 0.63, 95% confidence interval [CI] 0.45, 0.88; p = 0.007), although this was not sustained over time. Remission rates in the intervention group were not significantly higher than in the control group at 12 weeks (17.7% vs. 12.5%, relative risk [RR] 1.42, 95% CI 0.67, 3.00; p = 0.36) or at 52 weeks (6.3% vs. 3.8%, RR 1.69, 95% CI 0.42, 6.82) following the intervention period.
Conclusions: An intensive remission-induction intervention including fixed-ratio insulin degludec/liraglutide reduced the risk of type 2 diabetes relapse within 1 year without sustained remission.
{"title":"Evaluating remission of type 2 diabetes using a metabolic intervention including fixed-ratio insulin degludec and liraglutide: A randomized controlled trial.","authors":"Zubin Punthakee, Stephanie Hall, Natalia McInnes, Diana Sherifali, Kate Tsiplova, Faith R Kirabo, Thomas P P Ransom, Stewart B Harris, Heather A Lochnan, Ronald J Sigal, Mahua Ghosh, Tamara Spaic, Hertzel C Gerstein","doi":"10.1111/dom.15926","DOIUrl":"https://doi.org/10.1111/dom.15926","url":null,"abstract":"<p><strong>Aim: </strong>To evaluate the effect on type 2 diabetes remission of short-term intensive metabolic intervention consisting of frequent dietary, exercise and diabetes management coaching, metformin and fixed-ratio insulin degludec/liraglutide.</p><p><strong>Methods: </strong>In a multicentre open-label randomized controlled trial, insulin-naïve participants within 5 years of diabetes diagnosis were assigned to a 16-week remission intervention regimen or standard care, and followed for relapse of diabetes and sustained remission for an additional year after stopping glucose-lowering drugs.</p><p><strong>Results: </strong>A total of 159 participants aged 57 ± 10 years, with diabetes duration 2.6 ± 1.5 years, body mass index 33.5 ± 6.5 kg/m<sup>2</sup>, and glycated haemoglobin (HbA1c) level 53 ± 7 mmol/mol were randomized and analysed (79 intervention, 80 control). At the end of the 16-week intervention period, compared to controls, intervention participants achieved lower HbA1c levels (40 ± 4 vs. 51 ± 7 mmol/mol; p < 0.0001), and lost more weight (3.3 ± 4.4% vs. 1.9 ± 3.0%; p = 0.02). There was a lower hazard of diabetes relapse overall in the intervention group compared to controls (hazard ratio 0.63, 95% confidence interval [CI] 0.45, 0.88; p = 0.007), although this was not sustained over time. Remission rates in the intervention group were not significantly higher than in the control group at 12 weeks (17.7% vs. 12.5%, relative risk [RR] 1.42, 95% CI 0.67, 3.00; p = 0.36) or at 52 weeks (6.3% vs. 3.8%, RR 1.69, 95% CI 0.42, 6.82) following the intervention period.</p><p><strong>Conclusions: </strong>An intensive remission-induction intervention including fixed-ratio insulin degludec/liraglutide reduced the risk of type 2 diabetes relapse within 1 year without sustained remission.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142138776","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}
Lei Peng, Jiajia Shen, Lurong Li, Jiahao Liu, Xingzhou Jiang, Guoxin Zhang, Yuanyuan Li
Aim: Low birthweight is an issue during pregnancy associated with an increased risk of developing liver disease later in life. Previous Mendelian randomisation (MR) studies which explored this issue have not isolated the direct impact of the foetus on birthweight. In the present study, MR was used to assess whether direct foetal effects on birthweight were causally associated with liver structure, function and disease risk independent of intrauterine effects.
Materials and methods: We extracted single nucleotide polymorphisms (SNPs) from genome-wide association studies (GWAS) about direct foetal-affected birthweight (321 223 cases) to conduct univariable and multivariable MR analyses to explore the relationships between birthweight and 4 liver structure measures, 9 liver function measures and 18 liver diseases. A two-step MR analysis was used to further assess and quantify the mediating effects of the mediators.
Results: When isolating direct foetal effects, genetically predicted lower birthweight was associated with a higher risk of non-alcoholic fatty liver disease (NAFLD) (odds ratios [OR], 95% confidence interval [CI]: 1.61, 1.29-2.02, p < 0.001), higher magnetic resonance imaging [MRI] proton density fat fraction (PDFF) and higher serum gamma glutamyltransferase (GGT). Two-step MR identified two candidate mediators that partially mediate the direct foetal effect of lower birthweight on NAFLD, including fasting insulin (proportion mediated: 22.29%) and triglycerides (6.50%).
Conclusions: Our MR analysis reveals a direct causal association between lower birthweight and liver MRI PDFF, as well as the development of NAFLD, which persisted even after accounting for the potential influence of maternal factors. In addition, we identified fasting insulin and triglycerides as mediators linking birthweight and hepatic outcomes, providing insights for early clinical interventions.
目的:出生时体重过轻是一个与日后罹患肝病的风险增加有关的孕期问题。以往探讨这一问题的孟德尔随机化(MR)研究并未分离出胎儿对出生体重的直接影响。在本研究中,MR 被用来评估胎儿对出生体重的直接影响是否与肝脏结构、功能和疾病风险存在因果关系,而与宫内影响无关:我们从有关胎儿直接影响出生体重的全基因组关联研究(GWAS)中提取了单核苷酸多态性(SNPs),对出生体重与4种肝脏结构指标、9种肝功能指标和18种肝脏疾病之间的关系进行了单变量和多变量MR分析。采用两步磁共振分析法进一步评估和量化中介效应:结果:在分离胎儿的直接影响时,遗传预测的较低出生体重与较高的非酒精性脂肪肝(NAFLD)风险相关(几率比[OR],95%置信区间[CI]:1.61,1.29-2):1.61, 1.29-2.02, p 结论:我们的磁共振分析揭示了较低出生体重与肝脏磁共振成像 PDFF 以及非酒精性脂肪肝之间的直接因果关系,即使考虑了母体因素的潜在影响,这种因果关系依然存在。此外,我们还发现空腹胰岛素和甘油三酯是连接出生体重和肝脏结果的介质,这为早期临床干预提供了启示。
{"title":"Birthweight influences liver structure, function and disease risk: Evidence of a causal association.","authors":"Lei Peng, Jiajia Shen, Lurong Li, Jiahao Liu, Xingzhou Jiang, Guoxin Zhang, Yuanyuan Li","doi":"10.1111/dom.15910","DOIUrl":"https://doi.org/10.1111/dom.15910","url":null,"abstract":"<p><strong>Aim: </strong>Low birthweight is an issue during pregnancy associated with an increased risk of developing liver disease later in life. Previous Mendelian randomisation (MR) studies which explored this issue have not isolated the direct impact of the foetus on birthweight. In the present study, MR was used to assess whether direct foetal effects on birthweight were causally associated with liver structure, function and disease risk independent of intrauterine effects.</p><p><strong>Materials and methods: </strong>We extracted single nucleotide polymorphisms (SNPs) from genome-wide association studies (GWAS) about direct foetal-affected birthweight (321 223 cases) to conduct univariable and multivariable MR analyses to explore the relationships between birthweight and 4 liver structure measures, 9 liver function measures and 18 liver diseases. A two-step MR analysis was used to further assess and quantify the mediating effects of the mediators.</p><p><strong>Results: </strong>When isolating direct foetal effects, genetically predicted lower birthweight was associated with a higher risk of non-alcoholic fatty liver disease (NAFLD) (odds ratios [OR], 95% confidence interval [CI]: 1.61, 1.29-2.02, p < 0.001), higher magnetic resonance imaging [MRI] proton density fat fraction (PDFF) and higher serum gamma glutamyltransferase (GGT). Two-step MR identified two candidate mediators that partially mediate the direct foetal effect of lower birthweight on NAFLD, including fasting insulin (proportion mediated: 22.29%) and triglycerides (6.50%).</p><p><strong>Conclusions: </strong>Our MR analysis reveals a direct causal association between lower birthweight and liver MRI PDFF, as well as the development of NAFLD, which persisted even after accounting for the potential influence of maternal factors. In addition, we identified fasting insulin and triglycerides as mediators linking birthweight and hepatic outcomes, providing insights for early clinical interventions.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124361","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}
Liwan Fu, Hong Cheng, Jingfan Xiong, Pei Xiao, Xinying Shan, Yanyan Li, Yan Li, Xiaoyuan Zhao, Jie Mi
Objective: The aim was to investigate the mediating role of inflammatory biomarkers in the causal effect of body composition on glycaemic traits and type 2 diabetes.
Methods: A retrospective observational study and a Mendelian randomization (MR) study were used. Observational analyses were performed using data from 4717 Chinese children and adolescents aged 6-18 years who underwent dual-energy X-ray absorptiometry for body composition. MR analyses were based on summary statistics from UK Biobank, deCODE2021, Meta-Analysis of Glucose and Insulin-Related Traits Consortium (MAGIC) and other large consortiums. Inflammatory biomarkers included leptin, adiponectin, osteocalcin, fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH).
Results: In a retrospective observational study, increased fat mass had a positive effect on homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of pancreatic beta cell function (HOMA-β) through FGF23, whereas fat-free mass produced the opposite effects. PTH and osteocalcin played significant roles in the association of fat mass and fat-free mass with fasting glucose, fasting insulin and HOMA-IR (all p < 0.05). Mediation MR results indicated that childhood body mass index affected glycaemic traits through leptin and adiponectin. There existed a causal effect of fat-free mass on type 2 diabetes via FGF23 (indirect effect: OR [odds ratio]: 1.14 [95% CI, confidence interval: 1.01-1.28]) and adiponectin (OR: 0.85 [95% CI: 0.77-0.93]). Leptin mediated the causal association of fat mass (indirect effect: β: -0.05 [95% CI: -0.07, -0.02]) and fat-free mass (β: 0.03 [95% CI: 0.01, 0.04]) with fasting glucose.
Conclusions: Our findings suggest that different body compositions have differential influences on glycaemic traits and type 2 diabetes through distinct inflammatory biomarkers. The findings may be helpful in tailoring management of body composition based on inflammatory biomarkers with different glycaemic statuses.
目的目的是研究炎症生物标志物在身体成分对血糖特征和2型糖尿病的因果效应中的中介作用:方法:采用回顾性观察研究和孟德尔随机化(MR)研究。观察性分析使用了 4717 名 6-18 岁中国儿童和青少年的数据,这些儿童和青少年接受了双能 X 射线吸收测定法检测身体成分。MR分析基于英国生物库、deCODE2021、葡萄糖和胰岛素相关性状元分析联盟(MAGIC)和其他大型联盟的汇总统计数据。炎症生物标志物包括瘦素、脂肪连素、骨钙素、成纤维细胞生长因子23(FGF23)和甲状旁腺激素(PTH):在一项回顾性观察研究中,脂肪量的增加通过FGF23对胰岛素抵抗稳态模型评估(HOMA-IR)和胰岛β细胞功能稳态模型评估(HOMA-β)产生了积极影响,而无脂肪量则产生了相反的影响。PTH和骨钙素在脂肪量和无脂肪量与空腹血糖、空腹胰岛素和HOMA-IR的关系中发挥了重要作用(均为p 结论:PTH和骨钙素在脂肪量和无脂肪量与空腹血糖、空腹胰岛素和HOMA-IR的关系中发挥了重要作用:我们的研究结果表明,不同的身体成分会通过不同的炎症生物标志物对血糖特征和 2 型糖尿病产生不同的影响。这些发现可能有助于根据不同血糖状态下的炎症生物标志物对身体成分进行有针对性的管理。
{"title":"Mediating role of inflammatory biomarkers in the causal effect of body composition on glycaemic traits and type 2 diabetes.","authors":"Liwan Fu, Hong Cheng, Jingfan Xiong, Pei Xiao, Xinying Shan, Yanyan Li, Yan Li, Xiaoyuan Zhao, Jie Mi","doi":"10.1111/dom.15923","DOIUrl":"https://doi.org/10.1111/dom.15923","url":null,"abstract":"<p><strong>Objective: </strong>The aim was to investigate the mediating role of inflammatory biomarkers in the causal effect of body composition on glycaemic traits and type 2 diabetes.</p><p><strong>Methods: </strong>A retrospective observational study and a Mendelian randomization (MR) study were used. Observational analyses were performed using data from 4717 Chinese children and adolescents aged 6-18 years who underwent dual-energy X-ray absorptiometry for body composition. MR analyses were based on summary statistics from UK Biobank, deCODE2021, Meta-Analysis of Glucose and Insulin-Related Traits Consortium (MAGIC) and other large consortiums. Inflammatory biomarkers included leptin, adiponectin, osteocalcin, fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH).</p><p><strong>Results: </strong>In a retrospective observational study, increased fat mass had a positive effect on homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of pancreatic beta cell function (HOMA-β) through FGF23, whereas fat-free mass produced the opposite effects. PTH and osteocalcin played significant roles in the association of fat mass and fat-free mass with fasting glucose, fasting insulin and HOMA-IR (all p < 0.05). Mediation MR results indicated that childhood body mass index affected glycaemic traits through leptin and adiponectin. There existed a causal effect of fat-free mass on type 2 diabetes via FGF23 (indirect effect: OR [odds ratio]: 1.14 [95% CI, confidence interval: 1.01-1.28]) and adiponectin (OR: 0.85 [95% CI: 0.77-0.93]). Leptin mediated the causal association of fat mass (indirect effect: β: -0.05 [95% CI: -0.07, -0.02]) and fat-free mass (β: 0.03 [95% CI: 0.01, 0.04]) with fasting glucose.</p><p><strong>Conclusions: </strong>Our findings suggest that different body compositions have differential influences on glycaemic traits and type 2 diabetes through distinct inflammatory biomarkers. The findings may be helpful in tailoring management of body composition based on inflammatory biomarkers with different glycaemic statuses.</p>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124364","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}