BMJ Open Diabetes Research & Care最新文献

{"title":"Genetic risk of type 2 diabetes modifies the association between lifestyle and glycemic health at 5 years postpartum among high-risk women","authors":"Sim Tieu, Saila Koivusalo, Jari Lahti, Elina Engberg, Hannele Laivuori, Emilia Huvinen","doi":"10.1136/bmjdrc-2023-003942","DOIUrl":"https://doi.org/10.1136/bmjdrc-2023-003942","url":null,"abstract":"Introduction Lifestyle interventions are effective in preventing type 2 diabetes, but genetic background may influence the individual response. In the Finnish gestational diabetes prevention study, RADIEL, lifestyle intervention during pregnancy and first postpartum year was effective in preventing gestational diabetes (GDM) and postpartum glycemic abnormalities only among women at highest genetic risk of type 2 diabetes. This study aimed to assess whether still 5 years postpartum the genetic risk modifies the association between lifestyle and glycemic health. Research design and methods The RADIEL study (randomized controlled trial) aimed to prevent GDM with a lifestyle intervention among high-risk women (body mass index ≥30 kg/m2 and/or prior GDM). The follow-up study 5 years postpartum included anthropometric measurements, laboratory assessments, device-measured physical activity (PA), and questionnaires. A Healthy Lifestyle Score (HLS) indicated adherence to lifestyle goals (PA, diet, smoking) and a polygenic risk score (PRS) based on 50 type 2 diabetes risk alleles depicted the genetic risk. Results Altogether 314 women provided genetic and glycemic data 5 years postpartum. The PRS for type 2 diabetes was not associated with glycemic abnormalities, nor was HLS in the total study sample. There was, however, an interaction between HLS and type 2 diabetes PRS on glycemic abnormalities (p=0.03). When assessing the association between HLS and glycemic abnormalities in PRS tertiles, HLS was associated with reduced risk of glycemic abnormalities only among women at the highest genetic risk (p=0.008). Conclusions These results extend our previous findings from pregnancy and first postpartum year demonstrating that still at 5 years postpartum, healthy lifestyle is associated with a lower risk of prediabetes/diabetes only among women at the highest genetic risk of type 2 diabetes. Data are available on reasonable request. Present informed consents do not allow archiving clinical or register data in open repositories. Data described in the manuscript, code book, and analytic code will be made available on reasonable request and requests are subject to further review by the national register authority and by the ethical committees.","PeriodicalId":9151,"journal":{"name":"BMJ Open Diabetes Research & Care","volume":"18 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140613378","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":"Role of kidney function on Nrf2 mRNA levels in type 2 diabetes","authors":"Belinda Spoto, Cristina Politi, Maurizio Postorino, Rosa Maria Parlongo, Alessandra Testa, Giovanni Luigi Tripepi, Francesca Mallamaci, Carmine Zoccali","doi":"10.1136/bmjdrc-2023-003929","DOIUrl":"https://doi.org/10.1136/bmjdrc-2023-003929","url":null,"abstract":"Introduction Diabetic kidney disease (DKD) is a major complication in patients with diabetes and the main contributor to the chronic kidney disease (CKD) global burden. Oxidative stress is a crucial factor in DKD pathogenesis but the role of the antioxidant nuclear factor erythroid 2-related factor 2 (Nrf2) and its molecular regulators has been poorly investigated in man. Research design and methods In this case-control study, we analyzed the roles of Nrf2, a transcription factor shielding cells from oxidative stress, its repressor Kelch-like ECH-associated protein 1 (Keap1) and six microRNAs (miRNAs) that potentially suppress Nrf2. We categorized 99 participants into 3 groups: 33 non-dialysis patients with type 2 diabetes with DKD, 33 patients with type 2 diabetes without DKD and 33 control subjects and quantified the gene expression (messenger RNA (mRNA)) levels of Nrf2, Keap1 and 6 miRNAs. Moreover, we studied the correlation between gene expression levels and clinical indicators of kidney health. Results In patients with diabetes with DKD, Nrf2 mRNA levels were significantly lower than in patients without DKD (p=0.01) and controls (p=0.02), whereas no difference in Nrf2 expression levels existed between patients without DKD and controls. Conversely, in patients with and without DKD, Keap1 expression levels were significantly higher than in controls. Of the six miRNAs studied, miRNA 30e-5p showed differential expression, being markedly reduced in patients with DKD (p=0.007). Nrf2 mRNA levels directly correlated with estimated glomerular filtration rate (eGFR) in patients with DKD (r=0.34, p=0.05) and in a formal mediation analysis the eGFR emerged as the first factor in rank for explaining the difference in Nrf2 mRNA levels between patients with and without DKD. Conclusions The observed dysregulation in the Nrf2-Keap1 axis and the unique expression pattern of miRNA30e-5p in DKD underscore the need for more focused research in this domain that can help identify novel intervention strategies for DKD in patients with type 2 diabetes. Data are available on reasonable request. Not applicable.","PeriodicalId":9151,"journal":{"name":"BMJ Open Diabetes Research & Care","volume":"238 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140572069","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":"The case for a ketogenic diet in the management of kidney disease","authors":"Shaminie J Athinarayanan, Caroline G P Roberts, Chandan Vangala, Greeshma K Shetty, Amy L McKenzie, Thomas Weimbs, Jeff S Volek","doi":"10.1136/bmjdrc-2024-004101","DOIUrl":"https://doi.org/10.1136/bmjdrc-2024-004101","url":null,"abstract":"Ketogenic diets have been widely used for weight loss and are increasingly used in the management of type 2 diabetes. Despite evidence that ketones have multiple positive effects on kidney function, common misconceptions about ketogenic diets, such as high protein content and acid load, have prevented their widespread use in individuals with impaired kidney function. Clinical trial evidence focusing on major adverse kidney events is sparse. The aim of this review is to explore the effects of a ketogenic diet, with an emphasis on the pleiotropic actions of ketones, on kidney health. Given the minimal concerns in relation to the potential renoprotective effects of a ketogenic diet, future studies should evaluate the safety and efficacy of ketogenic interventions in kidney disease. No data are available.","PeriodicalId":9151,"journal":{"name":"BMJ Open Diabetes Research & Care","volume":"89 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140798367","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":"Child Opportunity Index and clinical characteristics at diabetes diagnosis in youth: type 1 diabetes versus type 2 diabetes","authors":"Kim Hoyek, Ingrid Libman, Nkeiruka Mkparu, Yong Hee Hong, Silva Arslanian, Mary Ellen Vajravelu","doi":"10.1136/bmjdrc-2023-003968","DOIUrl":"https://doi.org/10.1136/bmjdrc-2023-003968","url":null,"abstract":"Introduction Among youth with type 1 diabetes (T1D), longitudinal poor glycemic control is associated with adverse socioeconomic conditions at the neighborhood level. Child Opportunity Index (COI), which encompasses measures of education, health, environment, social, and economic factors, is associated with obesity in youth but has not been evaluated in youth with new-onset T1D or type 2 diabetes (T2D). We hypothesized that lower COI would be associated with adverse clinical outcomes at diabetes diagnosis, and due to differing risk factors and pathophysiology, that youth with new-onset T2D would have lower COI than youth with T1D. Research design and methods Retrospective cohort of youth with new-onset diabetes admitted to a large academic pediatric hospital. COI was compared by diabetes type using t-tests and Χ2 tests. Multivariable linear and logistic regression analyses were used to evaluate associations between COI and clinical characteristics, stratified by diabetes type and adjusted for age and sex. Results The cohort (n=484) differed in race and age by diabetes type (T1D: n=389; 10.0% black, 81.2% white; age 9.6±0.2 years; T2D: n=95; 44.2% black, 48.4% white; age 14.8±0.3 years). Youth with T2D had lower COI (p<0.001). Low COI was associated with diabetic ketoacidosis in T1D and T2D. Black youth with low COI had the highest hemoglobin A1c among youth with T2D and the highest obesity prevalence among youth with T1D. Conclusions COI is associated with differing characteristics at diagnosis in youth-onset T1D and T2D but is worse among youth with T2D overall. These findings underscore the need to address socioeconomic adversity when designing interventions to reduce T2D risk and to improve outcomes at diabetes diagnosis in youth. Data are available upon reasonable request. De-identified data are available upon reasonable request.","PeriodicalId":9151,"journal":{"name":"BMJ Open Diabetes Research & Care","volume":"303 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140613341","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":"A static glucose-stimulated insulin secretion (sGSIS) assay that is significantly predictive of time to diabetes reversal in the human islet bioassay.","authors":"Ruth Damaris Molano, Antonello Pileggi, Hubert M Tse, Cherie L Stabler, Christopher A Fraker","doi":"10.1136/bmjdrc-2023-003897","DOIUrl":"10.1136/bmjdrc-2023-003897","url":null,"abstract":"<p><strong>Introduction: </strong>Static incubation (static glucose-stimulated insulin secretion, sGSIS) is a measure of islet secretory function. The Stimulation Index (SI; insulin produced in high glucose/insulin produced in low glucose) is currently used as a product release criterion of islet transplant potency.</p><p><strong>Research design and methods: </strong>Our hypothesis was that the Delta, insulin secreted in high glucose minus insulin secreted in low glucose, would be more predictive. To evaluate this hypothesis, sGSIS was performed on 32 consecutive human islet preparations, immobilizing the islets in a slurry of Sepharose beads to minimize mechanical perturbation. Simultaneous full-mass subrenal capsular transplants were performed in chemically induced diabetic immunodeficient mice. Logistic regression analysis was used to determine optimal cut-points for diabetes reversal time and the Fisher Exact Test was used to assess the ability of the Delta and the SI to accurately classify transplant outcomes. Receiver operating characteristic curve analysis was performed on cut-point grouped data, assessing the predictive power and optimal cut-point for each sGSIS potency metric. Finally, standard Kaplan-Meier-type survival analysis was conducted.</p><p><strong>Results: </strong>In the case of the sGSIS the Delta provided a superior islet potency metric relative to the SI.<b>Conclusions</b>The sGSIS Delta value is predicitive of time to diabetes reversal in the full mass human islet transplant bioassay.</p>","PeriodicalId":9151,"journal":{"name":"BMJ Open Diabetes Research & Care","volume":"12 2","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10941118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140130667","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":"Cost-effectiveness analysis of two interventions to promote physical activity in a multiethnic population at high risk of diabetes: an economic evaluation of the 48-month PROPELS randomized controlled trial.","authors":"Laura Ellen Heathcote, Daniel J Pollard, Alan Brennan, Melanie J Davies, Helen Eborall, Charlotte L Edwardson, Michael Gillett, Laura J Gray, Simon J Griffin, Wendy Hardeman, Joseph Henson, Kamlesh Khunti, Stephen Sharp, Stephen Sutton, Thomas Yates","doi":"10.1136/bmjdrc-2023-003516","DOIUrl":"10.1136/bmjdrc-2023-003516","url":null,"abstract":"<p><strong>Introduction: </strong>Physical activity (PA) is protective against type 2 diabetes (T2D). However, data on pragmatic long-term interventions to reduce the risk of developing T2D via increased PA are lacking. This study investigated the cost-effectiveness of a pragmatic PA intervention in a multiethnic population at high risk of T2D.</p><p><strong>Materials and methods: </strong>We adapted the School for Public Health Research diabetes prevention model, using the PROPELS trial data and analyses of the NAVIGATOR trial. Lifetime costs, lifetime quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated for each intervention (Walking Away (WA) and Walking Away Plus (WA+)) versus usual care and compared with National Institute for Health and Care Excellence's willingness-to-pay of £20 000-£30 000 per QALY gained. We conducted scenario analyses on the outcomes of the PROPELS trial data and a threshold analysis to determine the change in step count that would be needed for the interventions to be cost-effective.</p><p><strong>Results: </strong>Estimated lifetime costs for usual care, WA, and WA+ were £22 598, £23 018, and £22 945, respectively. Estimated QALYs were 9.323, 9.312, and 9.330, respectively. WA+ was estimated to be more effective and cheaper than WA. WA+ had an ICER of £49 273 per QALY gained versus usual care. In none of our scenario analyses did either WA or WA+ have an ICER below £20 000 per QALY gained. Our threshold analysis suggested that a PA intervention costing the same as WA+ would have an ICER below £20 000/QALY if it were to achieve an increase in step count of 500 steps per day which was 100% maintained at 4 years.</p><p><strong>Conclusions: </strong>We found that neither WA nor WA+ was cost-effective at a limit of £20 000 per QALY gained. Our threshold analysis showed that interventions to increase step count can be cost-effective at this limit if they achieve greater long-term maintenance of effect.</p><p><strong>Trial registration number: </strong>ISRCTN registration: ISRCTN83465245: The PRomotion Of Physical activity through structuredEducation with differing Levels of ongoing Support for those with pre-diabetes (PROPELS)https://doi.org/10.1186/ISRCTN83465245.</p>","PeriodicalId":9151,"journal":{"name":"BMJ Open Diabetes Research & Care","volume":"12 2","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10936471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140109143","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":"Landscape of pharmacogenetic variants associated with non-insulin antidiabetic drugs in the Indian population.","authors":"Ambily Sivadas, S Sahana, Bani Jolly, Rahul C Bhoyar, Abhinav Jain, Disha Sharma, Mohamed Imran, Vigneshwar Senthivel, Mohit Kumar Divakar, Anushree Mishra, Arpita Mukhopadhyay, Greg Gibson, Km Venkat Narayan, Sridhar Sivasubbu, Vinod Scaria, Anura V Kurpad","doi":"10.1136/bmjdrc-2023-003769","DOIUrl":"10.1136/bmjdrc-2023-003769","url":null,"abstract":"<p><strong>Introduction: </strong>Genetic variants contribute to differential responses to non-insulin antidiabetic drugs (NIADs), and consequently to variable plasma glucose control. Optimal control of plasma glucose is paramount to minimizing type 2 diabetes-related long-term complications. India's distinct genetic architecture and its exploding burden of type 2 diabetes warrants a population-specific survey of NIAD-associated pharmacogenetic (PGx) variants. The recent availability of large-scale whole genomes from the Indian population provides a unique opportunity to generate a population-specific map of NIAD-associated PGx variants.</p><p><strong>Research design and methods: </strong>We mined 1029 Indian whole genomes for PGx variants, drug-drug interaction (DDI) and drug-drug-gene interactions (DDGI) associated with 44 NIADs. Population-wise allele frequencies were estimated and compared using Fisher's exact test.</p><p><strong>Results: </strong>Overall, we found 76 known and 52 predicted deleterious common PGx variants associated with response to type 2 diabetes therapy among Indians. We report remarkable interethnic differences in the relative cumulative counts of decreased and increased response-associated alleles across NIAD classes. Indians and South Asians showed a significant excess of decreased metformin response-associated alleles compared with other global populations. Network analysis of shared PGx genes predicts high DDI risk during coadministration of NIADs with other metabolic disease drugs. We also predict an increased CYP2C19-mediated DDGI risk for CYP3A4/3A5-metabolized NIADs, saxagliptin, linagliptin and glyburide when coadministered with proton-pump inhibitors (PPIs).</p><p><strong>Conclusions: </strong>Indians and South Asians have a distinct PGx profile for antidiabetes drugs, marked by an excess of poor treatment response-associated alleles for various NIAD classes. This suggests the possibility of a population-specific reduced drug response in atleast some NIADs. In addition, our findings provide an actionable resource for accelerating future diabetes PGx studies in Indians and South Asians and reconsidering NIAD dosing guidelines to ensure maximum efficacy and safety in the population.</p>","PeriodicalId":9151,"journal":{"name":"BMJ Open Diabetes Research & Care","volume":"12 2","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10936492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140109144","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":"MicroRNA-5010-5p ameliorates high-glucose induced inflammation in renal tubular epithelial cells by modulating the expression of PPP2R2D","authors":"Sunghee Choi, Mithun Kumer Sarker, Mi Ra Yu, Haekyung Lee, Soon Hyo Kwon, Jin Seok Jeon, Hyunjin Noh, Hyoungnae Kim","doi":"10.1136/bmjdrc-2023-003784","DOIUrl":"https://doi.org/10.1136/bmjdrc-2023-003784","url":null,"abstract":"Introduction We previously reported the significant upregulation of eight circulating exosomal microRNAs (miRNAs) in patients with diabetic kidney disease (DKD). However, their specific roles and molecular mechanisms in the kidney remain unknown. Among the eight miRNAs, we evaluated the effects of miR-5010-5p on renal tubular epithelial cells under diabetic conditions in this study. Research design and methods We transfected the renal tubular epithelial cell line, HK-2, with an miR-5010-5p mimic using recombinant plasmids. The target gene of hsa-miR-5010-5p was identified using a dual-luciferase assay. Cell viability was assessed via the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. Moreover, mRNA and protein expression levels were determined via real-time PCR and western blotting, respectively. Results High glucose levels did not significantly affect the intracellular expression of miR-5010-5p in HK-2 cells. Transfection of the miR-5010-5p mimic caused no change in cell viability. However, miR-5010-5p-transfected HK-2 cells exhibited significantly decreased expression levels of inflammatory cytokines, such as the monocyte chemoattractant protein-1, interleukin-1β, and tumor necrosis factor-ɑ, under high-glucose conditions. These changes were accompanied by the restored expression of phosphorylated AMP-activated protein kinase (AMPK) and decreased phosphorylation of nuclear factor-kappa B. Dual-luciferase assay revealed that miR-5010-5p targeted the gene, protein phosphatase 2 regulatory subunit B delta (PPP2R2D), a subunit of protein phosphatase 2A, which modulates AMPK phosphorylation. Conclusions Our findings suggest that increased miR-5010-5p expression reduces high glucose-induced inflammatory responses in renal tubular epithelial cells via the regulation of the target gene, PPP2R2D, which modulates AMPK phosphorylation. Therefore, miR-5010-5p may be a promising therapeutic target for DKD. Data are available upon reasonable request.","PeriodicalId":9151,"journal":{"name":"BMJ Open Diabetes Research & Care","volume":"69 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140033481","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":"Pilot feasibility and efficacy of a strategy to sustain A1C improvement among diverse adults with type 2 diabetes completing a diabetes care management program","authors":"Alex Renato Montero, Carine M Nassar, Saba Ahmed, Michelle Magee","doi":"10.1136/bmjdrc-2023-003788","DOIUrl":"https://doi.org/10.1136/bmjdrc-2023-003788","url":null,"abstract":"Introduction Evidence-based strategies are needed to sustain improvements in outcomes following diabetes care management (DCM) programs. We examined the impact of Boot Camp-Plus (BC-Plus), an innovative sustaining strategy, on A1C among adults with type 2 diabetes completing a 3-month Diabetes Boot Camp (DBC). This health system sponsored program consisted of diabetes self-management education and support, medical nutrition therapy and antihyperglycemic medications management. Research design and methods From March 2019 to July 2021, adult DBC completers with Medicare or a health system Medicaid or employee commercial plan were enrolled in BC-Plus for 9 months. DBC completers not meeting insurance eligibility or who declined to participate in BC-Plus acted as controls. During the first 3 months, BC-Plus participants received ongoing daily remote blood glucose (BG) monitoring; and during all 9 months, they received monthly check-in calls with BG review by a medical assistant who addressed needs for supplies/drugs, whether participants were checking BGs, and self-care encouragement. Escalation to a nurse practitioner occurred if the monthly BG trend was >200 mg/dL and/or several BG <80 mg/dL and/or new A1C >9.0% were identified. A1C was followed for an additional 9 months post-BC-Plus. A longitudinal mixed effects analysis was used to assess change in A1C from month 0 to month 21 of follow-up between BC-Plus participants versus controls. Results A total of 838 DCM completers were identified, among whom 281 joined the BC-Plus intervention and 557 acted as controls. Mean age was 55.9 years; 58.2% were women; 66.2% were black; and 30.6% insured by Medicare. BC-Plus participants experienced significantly lower A1C compared with controls and remained below 8.0% to month 18. Conclusions Among completers of a 3-month DCM program, a low intensity 9-month sustaining strategy maintained A1C under 8.0% (HEDIS (Healthcare Effectiveness Data and Information Set) threshold for diabetes control) compared with controls for 15 months after completion of the initial DCM intervention. Data are available upon reasonable request.","PeriodicalId":9151,"journal":{"name":"BMJ Open Diabetes Research & Care","volume":"84 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140106945","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":"Colonic epithelial hypoxia remains constant during the progression of diabetes in male UC Davis type 2 diabetes mellitus rats","authors":"Brian D Piccolo, James L Graham, Leslie Tabor-Simecka, Christopher E Randolph, Becky Moody, Michael S Robeson, Ping Kang, Renee Fox, Renny Lan, Lindsay Pack, Noah Woford, Laxmi Yeruva, Tanya LeRoith, Kimber L Stanhope, Peter J Havel","doi":"10.1136/bmjdrc-2023-003813","DOIUrl":"https://doi.org/10.1136/bmjdrc-2023-003813","url":null,"abstract":"Introduction Colonocyte oxidation of bacterial-derived butyrate has been reported to maintain synergistic obligate anaerobe populations by reducing colonocyte oxygen levels; however, it is not known whether this process is disrupted during the progression of type 2 diabetes. Our aim was to determine whether diabetes influences colonocyte oxygen levels in the University of California Davis type 2 diabetes mellitus (UCD-T2DM) rat model. Research design and methods Age-matched male UCD-T2DM rats (174±4 days) prior to the onset of diabetes (PD, n=15), within 1 month post-onset (RD, n=12), and 3 months post-onset (D3M, n=12) were included in this study. Rats were administered an intraperitoneal injection of pimonidazole (60 mg/kg body weight) 1 hour prior to euthanasia and tissue collection to estimate colonic oxygen levels. Colon tissue was fixed in 10% formalin, embedded in paraffin, and processed for immunohistochemical detection of pimonidazole. The colonic microbiome was assessed by 16S gene rRNA amplicon sequencing and content of short-chain fatty acids was measured by liquid chromatography-mass spectrometry. Results HbA1c % increased linearly across the PD (5.9±0.1), RD (7.6±0.4), and D3M (11.5±0.6) groups, confirming the progression of diabetes in this cohort. D3M rats had a 2.5% increase in known facultative anaerobes, Escherichia–Shigella , and Streptococcus (false discovery rate <0.05) genera in colon contents. The intensity of pimonidazole staining of colonic epithelia did not differ across groups (p=0.37). Colon content concentrations of acetate and propionate also did not differ across UCD-T2DM groups; however, colonic butyric acid levels were higher in D3M rats relative to PD rats (p<0.01). Conclusions The advancement of diabetes in UCD-T2DM rats was associated with an increase in facultative anaerobes; however, this was not explained by changes in colonocyte oxygen levels. The mechanisms underlying shifts in gut microbe populations associated with the progression of diabetes in the UCD-T2DM rat model remain to be identified. Data are available in a public, open access repository. Data are available upon reasonable request. Data and coding will be made available upon reasonable request to the corresponding author.","PeriodicalId":9151,"journal":{"name":"BMJ Open Diabetes Research & Care","volume":"7 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140056442","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}