William C Knowler, Haiying Chen, Judy L Bahnson, Steven E Kahn, Cora E Lewis, David M Nathan, Robert G Nelson, Scott J Pilla, John P Bantle
{"title":"Within and post-trial effects of an intensive lifestyle intervention on kidney disease in adults with overweight or obesity and type 2 diabetes mellitus: a secondary analysis of the Look AHEAD clinical trial.","authors":"William C Knowler, Haiying Chen, Judy L Bahnson, Steven E Kahn, Cora E Lewis, David M Nathan, Robert G Nelson, Scott J Pilla, John P Bantle","doi":"10.1136/bmjdrc-2024-004079","DOIUrl":"10.1136/bmjdrc-2024-004079","url":null,"abstract":"<p><strong>Introduction: </strong>The Look AHEAD randomized clinical trial reported that an 8-year intensive lifestyle intervention (ILI) compared with diabetes support and education (DSE) in adults aged 45-76 years with type 2 diabetes and overweight/obesity delayed kidney disease progression. Here, we report long-term post-intervention follow-up for the trial's secondary outcome of kidney disease.</p><p><strong>Research design and methods: </strong>We examined effects of ILI (n=2570) versus DSE (n=2575) on decline in estimated glomerular filtration rate (eGFR) to <45 mL/min/1.73 m<sup>2</sup> or need for kidney replacement therapy (KRT: dialysis or kidney transplant) during intervention and post-intervention follow-up (median 15.6 years overall).</p><p><strong>Results: </strong>Incidence of eGFR <45 mL/min/1.73 m<sup>2</sup> was lower in ILI during the intervention (HR=0.80, 95% CI=0.66 to 0.98) but not post-intervention (HR=1.03, 0.86 to 1.23) or overall (HR=0.92, 0.80 to 1.04). There were no significant treatment group differences in KRT. In prespecified subgroup analyses, age×treatment interactions were significant over total follow-up: p=0.001 for eGFR <45 mL/min/1.73 m<sup>2</sup> and p=0.01 for KRT. The 2205 participants aged >60 years at baseline had benefit in both kidney outcomes during intervention and overall (HR=0.75, 0.62 to 0.90 for eGFR <45 mL/min/1.73 m<sup>2</sup>; HR=0.62, 0.43 to 0.91 for KRT). The absolute treatment effects were greater post-intervention: ILI reduced the rate of eGFR <45 mL/min/1.73 m<sup>2</sup> by 0.46 and 0.76 cases/100 person-years during and post-intervention, respectively; and reduced KRT by 0.15 and 0.21 cases/100 person-years. The younger participants experienced no such post-intervention benefits.</p><p><strong>Conclusions: </strong>ILI reduced kidney disease progression during and following the active intervention in persons aged ≥60 years. ILI should be considered for reducing kidney disease incidence in older persons with type 2 diabetes.</p>","PeriodicalId":9151,"journal":{"name":"BMJ Open Diabetes Research & Care","volume":"12 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11141171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141178963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Kidney outcomes of SGLT2 inhibitors among older patients with diabetic kidney disease in real-world clinical practice: the Japan Chronic Kidney Disease Database Ex.","authors":"Kaori Kitaoka, Yuichiro Yano, Hajime Nagasu, Hiroshi Kanegae, Noriharu Chishima, Hiroki Akiyama, Kouichi Tamura, Naoki Kashihara","doi":"10.1136/bmjdrc-2024-004115","DOIUrl":"10.1136/bmjdrc-2024-004115","url":null,"abstract":"<p><strong>Introduction: </strong>We compared the kidney outcomes between patients with diabetic kidney disease (DKD) aged ≥75 years initiating sodium-glucose cotransporter 2 (SGLT2) inhibitors versus other glucose-lowering drugs, additionally presenting with or without proteinuria.</p><p><strong>Research design and methods: </strong>Using the Japan Chronic Kidney Disease Database, we developed propensity scores, implementing a 1:1 matching protocol. The primary outcome included the decline rate in estimated glomerular filtration rate (eGFR), and secondary outcomes incorporated a composite of a 40% reduction in eGFR or progression to end-stage kidney disease.</p><p><strong>Results: </strong>At baseline, the mean age at initiation of SGLT2 inhibitors (n=348) or other glucose-lowering medications (n=348) was 77.7 years. The mean eGFR was 59.3 mL/min/1.73m<sup>2</sup> and proteinuria was 230 (33.0%) patients. Throughout the follow-up period, the mean annual rate of eGFR change was -0.80 mL/min/1.73 m<sup>2</sup>/year (95% CI -1.05 to -0.54) among SGLT2 inhibitors group and -1.78 mL/min/1.73 m<sup>2</sup>/year (95% CI -2.08 to -1.49) in other glucose-lowering drugs group (difference in the rate of eGFR decline between the groups was 0.99 mL/min/1.73 m<sup>2</sup>/year (95% CI 0.5 to 1.38)), favoring SGLT2 inhibitors (p<0.001). Composite renal outcomes were observed 38 in the SGLT2 inhibitors group and 57 in the other glucose-lowering medications group (HR 0.64, 95% CI 0.42 to 0.97). There was no evidence of an interaction between SGLT2 inhibitors initiation and proteinuria.</p><p><strong>Conclusions: </strong>The benefits of SGLT2 inhibitors on renal outcomes are also applicable to older patients with DKD aged≥75 years.</p>","PeriodicalId":9151,"journal":{"name":"BMJ Open Diabetes Research & Care","volume":"12 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11141184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141178931","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}
Asami Ueno, Yasuhiro Onishi, Koki Mise, Satoshi Yamaguchi, Ayaka Kanno, Ichiro Nojima, Chigusa Higuchi, Haruhito A Uchida, Kenichi Shikata, Satoshi Miyamoto, Atsuko Nakatsuka, Jun Eguchi, Kazuyuki Hida, Akihiro Katayama, Mayu Watanabe, Tatsuaki Nakato, Atsuhito Tone, Sanae Teshigawara, Takashi Matsuoka, Shinji Kamei, Kazutoshi Murakami, Ikki Shimizu, Katsuhito Miyashita, Shinichiro Ando, Tomokazu Nunoue, Jun Wada
{"title":"Plasma angiotensin-converting enzyme 2 (ACE2) is a marker for renal outcome of diabetic kidney disease (DKD) (U-CARE study 3).","authors":"Asami Ueno, Yasuhiro Onishi, Koki Mise, Satoshi Yamaguchi, Ayaka Kanno, Ichiro Nojima, Chigusa Higuchi, Haruhito A Uchida, Kenichi Shikata, Satoshi Miyamoto, Atsuko Nakatsuka, Jun Eguchi, Kazuyuki Hida, Akihiro Katayama, Mayu Watanabe, Tatsuaki Nakato, Atsuhito Tone, Sanae Teshigawara, Takashi Matsuoka, Shinji Kamei, Kazutoshi Murakami, Ikki Shimizu, Katsuhito Miyashita, Shinichiro Ando, Tomokazu Nunoue, Jun Wada","doi":"10.1136/bmjdrc-2024-004237","DOIUrl":"10.1136/bmjdrc-2024-004237","url":null,"abstract":"<p><strong>Introduction: </strong>ACE cleaves angiotensin I (Ang I) to angiotensin II (Ang II) inducing vasoconstriction via Ang II type 1 (AT1) receptor, while ACE2 cleaves Ang II to Ang (1-7) causing vasodilatation by acting on the Mas receptor. In diabetic kidney disease (DKD), it is still unclear whether plasma or urine ACE2 levels predict renal outcomes or not.</p><p><strong>Research design and methods: </strong>Among 777 participants with diabetes enrolled in the Urinary biomarker for Continuous And Rapid progression of diabetic nEphropathy study, the 296 patients followed up for 9 years were investigated. Plasma and urinary ACE2 levels were measured by the ELISA. The primary end point was a composite of a decrease of estimated glomerular filtration rate (eGFR) by at least 30% from baseline or initiation of hemodialysis or peritoneal dialysis. The secondary end points were a 30% increase or a 30% decrease in albumin-to-creatinine ratio from baseline to 1 year.</p><p><strong>Results: </strong>The cumulative incidence of the renal composite outcome was significantly higher in group 1 with lowest tertile of plasma ACE2 (p=0.040). Group 2 with middle and highest tertile was associated with better renal outcomes in the crude Cox regression model adjusted by age and sex (HR 0.56, 95% CI 0.31 to 0.99, p=0.047). Plasma ACE2 levels demonstrated a significant association with 30% decrease in ACR (OR 1.46, 95% CI 1.044 to 2.035, p=0.027) after adjusting for age, sex, systolic blood pressure, hemoglobin A1c, and eGFR.</p><p><strong>Conclusions: </strong>Higher baseline plasma ACE2 levels in DKD were protective for development and progression of albuminuria and associated with fewer renal end points, suggesting plasma ACE2 may be used as a prognosis marker of DKD.</p><p><strong>Trial registration number: </strong>UMIN000011525.</p>","PeriodicalId":9151,"journal":{"name":"BMJ Open Diabetes Research & Care","volume":"12 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11141182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141178934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comparing the effectiveness and cost-effectiveness of sulfonylureas and newer diabetes drugs as second-line therapy for patients with type 2 diabetes.","authors":"Matteo Franchi, Giacomo Pellegrini, Angelo Avogaro, Giuliano Buzzetti, Riccardo Candido, Arturo Cavaliere, Agostino Consoli, Irene Marzona, Francesco Saverio Mennini, Stefano Palcic, Giovanni Corrao","doi":"10.1136/bmjdrc-2023-003991","DOIUrl":"10.1136/bmjdrc-2023-003991","url":null,"abstract":"<p><strong>Introduction: </strong>We aimed to compare the effectiveness and cost-effectiveness profiles of glucagon-like peptide-1 receptor agonist (GLP-1-RA), sodium-glucose cotransporter 2 inhibitor (SGLT2i), and dipeptidyl peptidase-4 inhibitor (DPP-4i) compared with sulfonylureas and glinides (SU).</p><p><strong>Research design and methods: </strong>Population-based retrospective cohort study based on linked regional healthcare utilization databases. The cohort included all residents in Lombardy aged ≥40 years, treated with metformin in 2014, who started a second-line treatment between 2015 and 2018 with SU, GLP-1-RA, SGLT2i, or DPP-4i. For each cohort member who started SU, one patient who began other second-line treatments was randomly selected and matched for sex, age, Multisource Comorbidity Score, and previous duration of metformin treatment. Cohort members were followed up until December 31, 2022. The association between second-line treatment and clinical outcomes was assessed using Cox proportional hazards models. The incremental cost-effectiveness ratios (ICERs) were calculated and compared between newer diabetes drugs and SU.</p><p><strong>Results: </strong>Overall, 22 867 patients with diabetes were included in the cohort, among which 10 577, 8125, 2893 and 1272 started a second-line treatment with SU, DPP-4i, SGLT2i and GLP-1-RA, respectively. Among these, 1208 patients for each group were included in the matched cohort. As compared with SU, those treated with DPP-4i, SGLT2i and GLP-1-RA were associated to a risk reduction for hospitalization for major adverse cardiovascular events (MACE) of 22% (95% CI 3% to 37%), 29% (95% CI 12% to 44%) and 41% (95% CI 26% to 53%), respectively. The ICER values indicated an average gain of €96.2 and €75.7 each month free from MACE for patients on DPP-4i and SGLT2i, respectively.</p><p><strong>Conclusions: </strong>Newer diabetes drugs are more effective and cost-effective second-line options for the treatment of type 2 diabetes than SUs.</p>","PeriodicalId":9151,"journal":{"name":"BMJ Open Diabetes Research & Care","volume":"12 3","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11131106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141157717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Prospective associations between breast feeding, metabolic health, inflammation and bone density in women with prior gestational diabetes mellitus.","authors":"Ines Hebeisen, Elena Gonzalez Rodriguez, Amar Arhab, Justine Gross, Sybille Schenk, Leah Gilbert, Katrien Benhalima, Antje Horsch, Dan Yedu Quansah, Jardena J Puder","doi":"10.1136/bmjdrc-2024-004117","DOIUrl":"10.1136/bmjdrc-2024-004117","url":null,"abstract":"<p><strong>Introduction: </strong>The aim of the study is to investigate prospective associations between breastfeeding and metabolic outcomes, inflammation, and bone density in women with prior gestational diabetes mellitus (GDM).</p><p><strong>Research design and methods: </strong>We prospectively included 171 women with GDM from the MySweetheart trial. Women were followed during pregnancy (from 24 up to 32 weeks' gestational age) up to 1 year postpartum. Outcomes included weight, weight retention, body composition, insulin resistance and secretion indices, C reactive protein (CRP), and bone density. We compared differences in the associations between breastfeeding and health outcomes between women who breast fed <6 months vs ≥6 months. Analyses were adjusted for potential medical and sociodemographic confounders.</p><p><strong>Results: </strong>Breastfeeding initiation was 94.2% (n=161) and mean breastfeeding duration was 6.6 months. Breastfeeding duration was independently associated with lower weight, weight retention, body fat, visceral adipose tissue, lean mass, CRP, insulin resistance (Homeostatic Model Assessment for Insulin Resistance), and insulin secretion (Homeostatic Model Assessment of β-cell index) at 1 year postpartum (all p≤0.04) after adjusting for confounders. Breastfeeding was associated with higher insulin resistance-adjusted insulin secretion (Insulin Secretion-Sensitivity Index-2) in the unadjusted analyses only. There was no association between breastfeeding duration and bone density. Compared with <6 months, breastfeeding duration ≥6 months was associated with lower weight, weight retention, body fat, fat-free mass as well as lower CRP at 1 year postpartum (all p<0.05) after adjusting for confounders.</p><p><strong>Conclusions: </strong>Longer breastfeeding duration among women with prior GDM was associated with lower insulin resistance, weight, weight retention, body fat and inflammation, but not lower bone density at 1 year postpartum. Breastfeeding for ≥6 months after GDM can help to improve cardiometabolic health outcomes 1 year after delivery.</p>","PeriodicalId":9151,"journal":{"name":"BMJ Open Diabetes Research & Care","volume":"12 3","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11110608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141074737","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}
John Pemberton, Louise Collins, Lesley Drummond, Renuka P Dias, Ruth Krone, Melanie Kershaw, Suma Uday
{"title":"Enhancing equity in access to automated insulin delivery systems in an ethnically and socioeconomically diverse group of children with type 1 diabetes.","authors":"John Pemberton, Louise Collins, Lesley Drummond, Renuka P Dias, Ruth Krone, Melanie Kershaw, Suma Uday","doi":"10.1136/bmjdrc-2024-004045","DOIUrl":"10.1136/bmjdrc-2024-004045","url":null,"abstract":"<p><strong>Introduction: </strong>Manufacturer-supported didactic teaching programmes offer effective automated insulin delivery (AID) systems onboarding in children and young people (CYP) with type 1 diabetes (T1D). However, this approach has limited flexibility to accommodate the needs of families requiring additional support.</p><p><strong>Research design and methods: </strong>Evaluate the efficacy of an inperson manufacturer-supported didactic teaching programme (Group A), in comparison to a flexible flipped learning approach delivered virtually or inperson (Group B). Retrospective analysis of CYP with T1D using continuous glucose monitoring (CGM), who were initiated on AID systems between 2021 and 2023. Compare CGM metrics from baseline to 90 days for both groups A and B. Additionally, compare the two groups for change in CGM metrics over the 90-day period (∆), patient demographics and onboarding time.</p><p><strong>Results: </strong>Group A consisted of 74 CYP (53% male) with median age of 13.9 years and Group B 91 CYP (54% male) with median age of 12.7 years. From baseline to 90 days, Group A lowered mean (±SD) time above range (TAR, >10.0 mmol/L) from 47.6% (±15.0) to 33.2% (±15.0) (p<0.001), increased time in range (TIR, 3.9-10.0 mmol/L) from 50.4% (±14.0) to 64.7% (±10.2) (p<0.001). From baseline to 90 days, Group B lowered TAR from 51.3% (±15.1) to 34.5% (±11.3) (p<0.001) and increased TIR from 46.5% (±14.5) to 63.7% (±11.0) (p<0.001). There was no difference from baseline to 90 days for time below range (TBR, <3.9 mmol/L) for Group A and Group B. ∆ TAR, TIR and TBR for both groups were comparable. Group B consisted of CYP with higher socioeconomic deprivation, greater ethnic diversity and lower carer education achievement (p<0.05). The majority of Group B (n=79, 87%) chose virtual flipped learning, halving diabetes educator time and increasing onboarding cadence by fivefold.</p><p><strong>Conclusions: </strong>A flexible virtual flipped learning programme increases onboarding cadence and capacity to offer equitable AID system onboarding.</p>","PeriodicalId":9151,"journal":{"name":"BMJ Open Diabetes Research & Care","volume":"12 3","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11097826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140944002","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}
Anders L Carlson, Roy W Beck, Zoey Li, Elizabeth Norton, Richard M Bergenstal, Mary Johnson, Sean Dunnigan, Matthew Banfield, Katie J Krumwiede, Judy R Sibayan, Peter Calhoun, Celeste Durnwald
{"title":"Glucose levels measured with continuous glucose monitoring in uncomplicated pregnancies.","authors":"Anders L Carlson, Roy W Beck, Zoey Li, Elizabeth Norton, Richard M Bergenstal, Mary Johnson, Sean Dunnigan, Matthew Banfield, Katie J Krumwiede, Judy R Sibayan, Peter Calhoun, Celeste Durnwald","doi":"10.1136/bmjdrc-2023-003989","DOIUrl":"10.1136/bmjdrc-2023-003989","url":null,"abstract":"<p><strong>Introduction: </strong>To characterize glucose levels during uncomplicated pregnancies, defined as pregnancy with a hemoglobin A1c <5.7% (<39 mmol/mol) in early pregnancy, and without a large-for-gestational-age birth, hypertensive disorders of pregnancy, or gestational diabetes mellitus (ie, abnormal oral glucose tolerance test).</p><p><strong>Research design and methods: </strong>Two sites enrolled 937 pregnant individuals aged 18 years and older prior to reaching 17 gestational weeks; 413 had an uncomplicated pregnancy (mean±SD body mass index (BMI) of 25.3±5.0 kg/m<sup>2</sup>) and wore Dexcom G6 continuous glucose monitoring (CGM) devices throughout the observed gestational period. Mealtimes were voluntarily recorded. Glycemic levels during gestation were characterized using CGM-measured glycemic metrics.</p><p><strong>Results: </strong>Participants wore CGM for a median of 123 days each. Glucose levels were nearly stable throughout all three trimesters in uncomplicated pregnancies. Overall mean±SD glucose during gestation was 98±7 mg/dL (5.4±0.4 mmol/L), median per cent time 63-120 mg/dL (3.5-6.7 mmol/L) was 86% (IQR: 82-89%), median per cent time <63 mg/dL (3.5 mmol/L) was 1.8%, median per cent time >120 mg/dL (6.7 mmol/L) was 11%, and median per cent time >140 mg/dL (7.8 mmol/L) was 2.5%. Mean post-prandial peak glucose was 126±22 mg/dL (7.0±1.2 mmol/L), and mean post-prandial glycemic excursion was 36±22 mg/dL (2.0±1.2 mmol/L). Higher mean glucose levels were low to moderately associated with pregnant individuals with higher BMIs (103±6 mg/dL (5.7±0.3 mmol/L) for BMI ≥30.0 kg/m<sup>2</sup> vs 96±7 mg/dL (5.3±0.4 mmol/L) for BMI 18.5-<25 kg/m<sup>2</sup>, r=0.35).</p><p><strong>Conclusions: </strong>Mean glucose levels and time 63-120 mg/dL (3.5-6.7 mmol/L) remained nearly stable throughout pregnancy and values above 140 mg/dL (7.8 mmol/L) were rare. Mean glucose levels in pregnancy trend higher as BMI increases into the overweight/obesity range. The glycemic metrics reported during uncomplicated pregnancies represent treatment targets for pregnant individuals.</p>","PeriodicalId":9151,"journal":{"name":"BMJ Open Diabetes Research & Care","volume":"12 3","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11097821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140903905","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}
Kun Chen, Tian Tian, Peng Gao, Xiaoxiang Fang, Wang Jiang, Zongchao Li, Kexing Tang, Pan Ouyang, Liangjun Li
{"title":"Unveiling potential therapeutic targets for diabetes-induced frozen shoulder through Mendelian randomization analysis of the human plasma proteome","authors":"Kun Chen, Tian Tian, Peng Gao, Xiaoxiang Fang, Wang Jiang, Zongchao Li, Kexing Tang, Pan Ouyang, Liangjun Li","doi":"10.1136/bmjdrc-2023-003966","DOIUrl":"https://doi.org/10.1136/bmjdrc-2023-003966","url":null,"abstract":"Introduction This study aimed to assess the causal relationship between diabetes and frozen shoulder by investigating the target proteins associated with diabetes and frozen shoulder in the human plasma proteome through Mendelian randomization (MR) and to reveal the corresponding pathological mechanisms. Research design and methods We employed the MR approach for the purposes of establishing: (1) the causal link between diabetes and frozen shoulder; (2) the plasma causal proteins associated with frozen shoulder; (3) the plasma target proteins associated with diabetes; and (4) the causal relationship between diabetes target proteins and frozen shoulder causal proteins. The MR results were validated and consolidated through colocalization analysis and protein–protein interaction network. Results Our MR analysis demonstrated a significant causal relationship between diabetes and frozen shoulder. We found that the plasma levels of four proteins were correlated with frozen shoulder at the Bonferroni significance level (p<3.03E-5). According to colocalization analysis, parathyroid hormone-related protein (PTHLH) was moderately correlated with the genetic variance of frozen shoulder (posterior probability=0.68), while secreted frizzled-related protein 4 was highly correlated with the genetic variance of frozen shoulder (posterior probability=0.97). Additionally, nine plasma proteins were activated during diabetes-associated pathologies. Subsequent MR analysis of nine diabetic target proteins with four frozen shoulder causal proteins indicated that insulin receptor subunit alpha, interleukin-6 receptor subunit alpha, interleukin-1 receptor accessory protein, glutathione peroxidase 7, and PTHLH might contribute to the onset and progression of frozen shoulder induced by diabetes. Conclusions Our study identified a causal relationship between diabetes and frozen shoulder, highlighting the pathological pathways through which diabetes influences frozen shoulder. Data are available in a public, open access repository. All data relevant to the study are included in the article or uploaded as supplementary information.","PeriodicalId":9151,"journal":{"name":"BMJ Open Diabetes Research & Care","volume":"22 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140884944","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}
{"title":"Multidisciplinary proactive e-consults to improve guideline-directed medical therapies for patients with diabetes and chronic kidney disease: an implementation study","authors":"Sharon Rikin, Laurie Bauman, Ivelina Arnaoudova, Katherine DiPalo, Nisha Suda, Sonali Gupta, Yuting Deng, Ladan Golestaneh","doi":"10.1136/bmjdrc-2024-004155","DOIUrl":"https://doi.org/10.1136/bmjdrc-2024-004155","url":null,"abstract":"Introduction We hypothesized that multidisciplinary, proactive electronic consultation (MPE) could overcome barriers to prescribing guideline-directed medical therapies (GDMTs) for patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). Research design and methods We conducted an efficacy-implementation pilot study of MPE for T2D and CKD for primary care provider (PCP)–patient dyads at an academic health system. MPE included (1) a dashboard to identify patients without a prescription for sodium-glucose cotransporter-2 inhibitors (SGLT2i) and without a maximum dose prescription for renin–angiotensin–aldosterone system inhibitors (RAASi), (2) a multidisciplinary team of specialists to provide recommendations using e-consult templates, and (3) a workflow to deliver timely e-consult recommendations to PCPs. In-depth interviews were conducted with PCPs and specialists to assess feasibility, acceptability, and appropriateness of MPE and were analyzed using an iterative qualitative analysis approach to identify major themes. Prescription data were extracted from the electronic health record to assess preliminary effectiveness to increase GDMT. Results 20 PCPs agreed to participate, 18 PCPs received MPEs for one of their patients with T2D and CKD, and 16 PCPs and 2 specialists were interviewed. Major themes were as follows: appropriateness of prioritization of GDMT for T2D and CKD, acceptability of the content of the recommendations, PCP characteristics impact experience with MPE, acceptability and appropriateness of multidisciplinary collaboration, feasibility of MPE to overcome patient-specific barriers to GDMT, and appropriateness of workflow. At 6 months postbaseline, 7/18 (39%) patients were newly prescribed an SGLT2i, and 7/18 (39%) patients were either newly prescribed or had increased dose of RAASi. Conclusions MPE was an acceptable and appropriate health system strategy to identify and address gaps in GDMT among patients with T2D and CKD. Adopting MPE could enhance GDMT, though PCPs raised feasibility concerns which could be improved with program enhancements, including follow-up e-consults for reinforcement, and administrative support for navigating system-level barriers. Data are available upon reasonable request. Deidentified participant data are available upon request from the corresponding author.","PeriodicalId":9151,"journal":{"name":"BMJ Open Diabetes Research & Care","volume":"31 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140889819","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}
Thomas A McCormick, Jason Kramer, Elizabeth G Liles, Qiana Amos, John P Martin, John L Adams
{"title":"Cardiovascular and mortality benefits of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide 1 receptor agonists as third-step glucose-lowering medicine in patients with type 2 diabetes: a retrospective cohort analysis","authors":"Thomas A McCormick, Jason Kramer, Elizabeth G Liles, Qiana Amos, John P Martin, John L Adams","doi":"10.1136/bmjdrc-2023-003792","DOIUrl":"https://doi.org/10.1136/bmjdrc-2023-003792","url":null,"abstract":"Introduction Studies have found that sodium-glucose cotransporter 2 inhibitors (SGLT2) and glucagon-like peptide 1 receptor agonists (GLP1) have cardiovascular benefits for patients with type 2 diabetes (DM2) and atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD), or heart failure (HF). The literature does not provide evidence specifically for patients with these conditions who are adding one of these medicines to two glucose-lowering medications (ie, as “third-step” therapy). We explored the effects of different third-step medications on cardiovascular outcomes in patients with diabetes and these comorbid conditions. Specifically, we compared third-step SGLT2 or GLP1 to third-step dipeptidyl peptidase-4 inhibitors (DPP4), insulin, or thiazolidinediones (TZD). Research design and methods We assembled a retrospective cohort of adults at five Kaiser Permanente sites with DM2 and ASCVD, CKD, or HF, initiating third-step treatment between 2016 and 2020. Propensity score weighted Poisson models were used to calculate adjusted rate ratios (ARRs) for all-cause mortality, incident major adverse cardiovascular event (MACE), and incident HF hospitalization in patients initiating SGLT2 or GLP1 compared with DPP4, insulin, or TZD. Results We identified 27 542 patients initiating third-step treatment with one or more of these conditions (19 958 with ASCVD, 14 577 with CKD, and 3919 with HF). ARRs for GLP1 and SGLT2 versus DPP4, insulin, and TZD in the patient subgroups ranged between 0.22 and 0.55 for all-cause mortality, 0.38 and 0.81 for MACE, and 0.46 and 1.05 for HF hospitalization. Many ARRs were statistically significant, and all significant ARRs showed a benefit (ARR <1) for GLP1 or SGLT2 when compared with DPP4, insulin, or TZD. Conclusions Third-step SGLT2 and GLP1 are generally associated with a benefit for these outcomes in these patient groups when compared with third-step DPP4, insulin, or TZD. Our results add to evidence of a cardiovascular benefit of SGLT2 and GLP1 and could inform clinical guidelines for choosing third-step diabetes treatment. No data are available.","PeriodicalId":9151,"journal":{"name":"BMJ Open Diabetes Research & Care","volume":"50 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140885081","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}