{"title":"Investigation of end-stage kidney disease risk prediction in an ethnically diverse cohort of people with type 2 diabetes: use of kidney failure risk equation","authors":"Aicha Goubar, Anastasios Mangelis, Stephen Thomas, Nikolaos Fountoulakis, Julian Collins, Salma Ayis, Janaka Karalliedde","doi":"10.1136/bmjdrc-2024-004282","DOIUrl":"https://doi.org/10.1136/bmjdrc-2024-004282","url":null,"abstract":"Introduction The four variable kidney failure (KF) risk equation (KFRE) is recommended to estimate KF risk (ie, need for dialysis or kidney transplantation). Earlier referral to clinical kidney services for people with high-risk of kidney failure can ensure appropriate care, education and support are in place pre-emptively. There are limited data on investigating the performance of KFRE in estimating risk of end-stage kidney disease (ESKD) in people with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). The primary ESKD endpoint event was defined as estimated glomerular filtration rate (eGFR) <10 mL/min/1.73 m2 and secondary endpoint eGFR <15 mL/min/1.73 m2. Research design and methods We studied 7296 people (30% women, 41% African-Caribbean, 45% Caucasian) with T2DM and CKD (eGFR median (range) 48 (15–59) mL/min/1.73 m2) were included at two hospitals in London (median follow-up 10.2 years). Time to ESKD event was the endpoint and Concordance index (C-index) was used to assess KFRE’s discrimination of those experiencing ESKD from those who did not. Mean (integrated calibration index (ICI)) and 90th percentile (E90) of the difference between observed and predicted risks were used as calibration metrics. Results Of the cohort 746 (10.2%) reached ESKD primary event (135 (1.9%) and 339 (4.5%) over 2 and 5 years, respectively). Similarly, 1130 (15.5%) reached the secondary endpoint (270 (3.7%) and 547 (7.5%) over 2 and 5 years, respectively). The C-index for the primary endpoint was 0.842 (95% CI 0.836 to 0.848) and 0.816 (95% CI 0.812 to 0.820) for 2 and 5 years, respectively. KFRE ‘under-predicted’ ESKD risk overall and by ethnic group. Likewise, the C-index for secondary endpoint was 0.843 (0.839–0.847) and 0.801 (0.798–0.804) for 2 and 5 years, respectively. KFRE performance analysis performed more optimally with the primary endpoint with 50% enhancement of the calibration metrics than with the secondary endpoint. KFRE recalibration improved ICI by 50% and E90 by more than 78%. Conclusions Although derived for predicting KF, KFRE also demonstrated good discrimination for ESKD outcome. Further studies are needed to identify variables/biomarkers that may improve KFRE’s performance/calibration and to aid the development of other predictive models to enable early identification of people at risk of advanced stages of CKD prior to onset of KF. No data are available.","PeriodicalId":9151,"journal":{"name":"BMJ Open Diabetes Research & Care","volume":"49 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142266999","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":"Glucokinase activators and imeglimin: new weaponry in the armamentarium against type 2 diabetes.","authors":"Åke Sjöholm","doi":"10.1136/bmjdrc-2024-004291","DOIUrl":"10.1136/bmjdrc-2024-004291","url":null,"abstract":"<p><p>The prevalence of type 2 diabetes (T2D) is increasing relentlessly all over the world, in parallel with a similar increase in obesity, and is striking ever younger patients. Only a minority of patients with T2D attain glycemic targets, indicating a clear need for novel antidiabetic drugs that not only control glycemia but also halt or slow the progressive loss of β-cells. Two entirely novel classes of antidiabetic agents-glucokinase activators and imeglimin-have recently been approved and will be the subject of this review.Allosteric activators of glucokinase, an enzyme stimulating insulin secretion in β-cells and suppressing hepatic glucose production, are oral low-molecular-weight drugs. One of these, dorzagliatin, is approved in China for use in adult patients with T2D, either as monotherapy or as an add-on to metformin. It remains to be seen whether the drug will produce sustained antidiabetic effects over many years and whether the side effects that led to the discontinuation of early drug candidates will limit the usefulness of dorzagliatin.Imeglimin-which shares structural similarities with metformin-targets mitochondrial dysfunction and was approved in Japan against T2D. In preclinical studies, the drug has also shown promising β-cell protective and preservative effects that may translate into disease-modifying effects.Hopefully, these two newcomers will contribute to filling the great medical need for new treatment modalities, preferably with disease-modifying potential. It remains to be seen where they will fit in contemporary treatment algorithms, which combinations of drugs are effective and which should be avoided. Time will tell to what extent these new antidiabetic agents will add value to the current treatment options against T2D in terms of sustained antidiabetic effect, acceptable safety, utility in combination therapy, and impact on hard end-points such as cardiovascular disease.</p>","PeriodicalId":9151,"journal":{"name":"BMJ Open Diabetes Research & Care","volume":"12 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11367400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104235","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}
Sujay Krishna Maity, Avinil Das Sharma, Jit Sarkar, Tamonash Chaudhuri, Om Tantia, Partha Chakrabarti
{"title":"Adipose tissue-derived adipsin marks human aging in non-type 2 diabetes population.","authors":"Sujay Krishna Maity, Avinil Das Sharma, Jit Sarkar, Tamonash Chaudhuri, Om Tantia, Partha Chakrabarti","doi":"10.1136/bmjdrc-2024-004179","DOIUrl":"10.1136/bmjdrc-2024-004179","url":null,"abstract":"<p><strong>Introduction: </strong>Adipsin or complement factor D is an adipokine that augments insulin secretion, is altered in various degrees of obesity, and is involved in alternative complement pathway. However, whether adipsin has any independent association with risk factors and biomarkers in patients with type 2 diabetes (T2D) remains elusive.</p><p><strong>Research design and methods: </strong>We performed an oral glucose tolerance test on a subset of 43 patients with T2D from the community health cohort to access the role of adipsin in insulin secretion. We further cross-sectionally examined the role of adipsin in plasma, adipose tissue (AT), and secretion in a community cohort of 353 subjects and a hospital cohort of 52 subjects.</p><p><strong>Results: </strong>We found that plasma adipsin has no significant correlation with insulin secretion in people with diabetes. Among the risk factors of T2D, adipsin levels were independently associated only with age, and a positive correlation between plasma adipsin and age among subjects without T2D was lost in patients with T2D. Plasma adipsin levels, AT adipsin expression, and secretion were upregulated both in T2D and aging, with a corresponding drop in Homeostatic Model Assessment for assessing β-cell function. Adipsin expression was positively associated with other aging biomarkers, such as β-galactosidase, p21, and p16. These results also corroborated with existing plasma proteomic signatures of aging, including growth, and differentiation factor-15, which strongly correlated with adipsin.</p><p><strong>Conclusions: </strong>Our results demonstrate an increase in circulating adipsin in T2D and aging, and it scores as a candidate plasma marker for aging specifically in non-T2D population.</p>","PeriodicalId":9151,"journal":{"name":"BMJ Open Diabetes Research & Care","volume":"12 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11367331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104232","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":"Combined impact of heat and dust on diabetes hospitalization in Kuwait.","authors":"Barrak Alahmad, Hamad Ali, Yazan Alwadi, Ali Al-Hemoud, Petros Koutrakis, Fahd Al-Mulla","doi":"10.1136/bmjdrc-2024-004320","DOIUrl":"10.1136/bmjdrc-2024-004320","url":null,"abstract":"<p><strong>Introduction: </strong>In Kuwait, a severe diabetes and obesity epidemic coexists with intense dust storms and harsh summer heat. While, theoretically, this interplay between dust, heat, and diabetes presents a serious public health problem, the empirical understanding of the actual risks remains limited. We hypothesized that increased exposure to heat and dust, independently and jointly, exacerbates the risk of hospitalization for diabetes patients.</p><p><strong>Research design and methods: </strong>We placed custom-designed particle samplers in Kuwait to collect daily dust samples for 2 years from 2017 to 2019. Samples were analyzed for elemental concentrations to identify and quantify dust pollution days. Temperature data were collected from meteorological stations. We then collected hospitalization data for unplanned diabetic admissions in all public hospitals in Kuwait. We used a case-crossover study design and conditional quasi-Poisson models to compare hospitalization days to control days within the same subject. Finally, we fitted generalized additive models to explore the smoothed interaction between temperature and dust days on diabetes hospitalization.</p><p><strong>Results: </strong>There were 11 155 unplanned diabetes hospitalizations over the study period. We found that each year, there was an excess of 282 diabetic admissions attributed to hot days (95% CI: -14 to 473). Additionally, for every 10 µg/m<sup>3</sup> increase in dust levels, there were about 114 excess diabetic admissions annually (95% CI: 11 to 219). Compared with mild non-dusty days (33°C (0 µg/m<sup>3</sup>)), hot-dusty days jointly increased the relative risk of diabetic admissions from 1.11 at 42°C (85 µg/m<sup>3</sup>) to 1.36 at 42°C (150 µg/m<sup>3</sup>).</p><p><strong>Conclusions: </strong>Both heat and dust seem to contribute to the increased diabetes morbidity, with combined hot-dusty conditions exacerbating these risks even further.</p>","PeriodicalId":9151,"journal":{"name":"BMJ Open Diabetes Research & Care","volume":"12 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11367401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104233","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}
Davis Kibirige, Jean-Claude Katte, Anita V Hill, Isaac Sekitoleko, William Lumu, Julieanne Knupp, Steven Squires, Andrew T Hattersley, Liam Smeeth, Angus G Jones, Moffat J Nyirenda
{"title":"Ethnic differences in the manifestation of early-onset type 2 diabetes.","authors":"Davis Kibirige, Jean-Claude Katte, Anita V Hill, Isaac Sekitoleko, William Lumu, Julieanne Knupp, Steven Squires, Andrew T Hattersley, Liam Smeeth, Angus G Jones, Moffat J Nyirenda","doi":"10.1136/bmjdrc-2024-004174","DOIUrl":"10.1136/bmjdrc-2024-004174","url":null,"abstract":"<p><strong>Introduction: </strong>We undertook phenotypic characterization of early-onset and late-onset type 2 diabetes (T2D) in adult black African and white European populations with recently diagnosed T2D to explore ethnic differences in the manifestation of early-onset T2D.</p><p><strong>Research design and methods: </strong>Using the Uganda Diabetes Phenotype study cohort of 500 adult Ugandans and the UK StartRight study cohort of 714 white Europeans with recently diagnosed islet autoantibody-negative T2D, we compared the phenotypic characteristics of participants with early-onset T2D (diagnosed at <40 years) and late-onset T2D (diagnosed at ≥40 years).</p><p><strong>Results: </strong>One hundred and thirty-four adult Ugandans and 113 white Europeans had early-onset T2D. Compared with late-onset T2D, early-onset T2D in white Europeans was significantly associated with a female predominance (52.2% vs 39.1%, p=0.01), increased body mass index (mean (95% CI) 36.7 (35.2-38.1) kg/m<sup>2</sup> vs 33.0 (32.4-33.6) kg/m<sup>2</sup>, p<0.001), waist circumference (112.4 (109.1-115.6) cm vs 108.8 (107.6-110.1) cm, p=0.06), and a higher frequency of obesity (82.3% vs 63.4%, p<0.001). No difference was seen with the post-meal C-peptide levels as a marker of beta-cell function (mean (95% CI) 2130.94 (1905.12-2356.76) pmol/L vs 2039.72 (1956.52-2122.92), p=0.62).In contrast, early-onset T2D in Ugandans was associated with less adiposity (mean (95% CI) waist circumference 93.1 (89.9-96.3) cm vs 97.4 (95.9-98.8) cm, p=0.006) and a greater degree of beta-cell dysfunction (120 min post-glucose load C-peptide mean (95% CI) level 896.08 (780.91-1011.24) pmol/L vs 1310.10 (1179.24-1440.95) pmol/L, p<0.001), without female predominance (53.0% vs 57.9%, p=0.32) and differences in the body mass index (mean (95% CI) 27.3 (26.2-28.4) kg/m<sup>2</sup> vs 27.9 (27.3-28.5) kg/m<sup>2</sup>, p=0.29).</p><p><strong>Conclusions: </strong>These differences in the manifestation of early-onset T2D underscore the need for ethnic-specific and population-specific therapeutic and preventive approaches for the condition.</p>","PeriodicalId":9151,"journal":{"name":"BMJ Open Diabetes Research & Care","volume":"12 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11409382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142104234","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}
Kavita Singh, Dimple Kondal, Ram Jagannathan, Mohammed K Ali, Dorairaj Prabhakaran, K M Venkat Narayan, Shuchi Anand, Nikhil Tandon
{"title":"Rate and risk factors of kidney function decline among South Asians with type 2 diabetes: analysis of the CARRS Trial.","authors":"Kavita Singh, Dimple Kondal, Ram Jagannathan, Mohammed K Ali, Dorairaj Prabhakaran, K M Venkat Narayan, Shuchi Anand, Nikhil Tandon","doi":"10.1136/bmjdrc-2024-004218","DOIUrl":"10.1136/bmjdrc-2024-004218","url":null,"abstract":"<p><strong>Introduction: </strong>People with diabetes are at risk of developing chronic kidney disease. However, limited data are available to quantify their risk of kidney function decline in South Asia. This study evaluates the rate and predictors of kidney function decline among people with type 2 diabetes in South Asia.</p><p><strong>Research design and methods: </strong>We analyzed data from the Centre for Cardiometabolic Risk Reduction in South Asia (CARRS) Trial to quantify the rate of decline in estimated glomerular filtration rate (eGFR) in people with type 2 diabetes (n=1146) over 2.5 years of follow-up. The CARRS Trial evaluated a multicomponent intervention of decision-supported electronic health records and non-physician care coordinator to improve diabetes management at 10 diabetes clinics in India and Pakistan. We used linear mixed models to estimate eGFR slope among all participants and tested the association of eGFR slope with demographic, disease-related, and self-care parameters, accounting for randomization and site.</p><p><strong>Results: </strong>The mean age of participants was 54.2 years, with a median duration of diabetes of 7.0 years (IQR: 3.0 - 12.0) and median CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) eGFR of 83.6 (IQR: 67.7 to 97.9) mL/min/1.73 m<sup>2</sup>. The overall mean eGFR slope was -1.33/mL/min/1.73 m<sup>2</sup>/year. There were no differences in the eGFR slope by treatment assignment to intervention versus usual care. In the adjusted regression model, pre-existing diabetic retinopathy (slope difference: -2.11; 95% CI: -3.45 to -0.77), previous cardiovascular disease (-1.93; 95% CI: -3.45 to -0.40), and statins use (-0.87; 95% CI: -1.65 to -0.10) were associated with faster eGFR decline.</p><p><strong>Conclusions: </strong>People with diabetes receiving care at urban diabetes clinics in South Asia experienced annual eGFR decline at two times higher rate than that reported from other contemporary international diabetes cohorts. Risk factors for faster decline were similar to those previously established, and thus care delivery models must put an additional emphasis on kidney protective therapies among subgroups with microvascular and macrovascular diabetes complications.</p><p><strong>Trial registration number: </strong>NCT01212328.</p>","PeriodicalId":9151,"journal":{"name":"BMJ Open Diabetes Research & Care","volume":"12 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11409274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995249","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}
Rakesh Dattani, Zia Ul-Haq, Moulesh Shah, Tahereh Kamalati, Benjamin Pierce, Amanda Lucas, Ahmed Baruwa, Livi Bickford-Smith, Jack Chilcott, Thomas Griffiths, Andrew Howard Frankel, Tony Willis, Frederick Wai Keung Tam
{"title":"Real-world study of the multimorbidity and health service utilisation among individuals with non-diabetic hyperglycemia and type 2 diabetes mellitus in North West London.","authors":"Rakesh Dattani, Zia Ul-Haq, Moulesh Shah, Tahereh Kamalati, Benjamin Pierce, Amanda Lucas, Ahmed Baruwa, Livi Bickford-Smith, Jack Chilcott, Thomas Griffiths, Andrew Howard Frankel, Tony Willis, Frederick Wai Keung Tam","doi":"10.1136/bmjdrc-2023-003873","DOIUrl":"10.1136/bmjdrc-2023-003873","url":null,"abstract":"<p><strong>Introduction: </strong>The prevalence of non-diabetic hyperglycemia (NDH) and type 2 diabetes mellitus (T2DM) is increasing. While T2DM is recognised to be associated with multimorbidity and early mortality, people with NDH are frequently thought to be devoid of such complications, potentially exposing individuals with NDH to suboptimal care. We therefore used the Discover London Secure Data Environment (SDE) dataset to appreciate the relationship of NDH/T2DM with multimorbidity, healthcare usage, and clinical outcomes.</p><p><strong>Research design and methods: </strong>The dataset was retrospectively analysed between January 1, 2015 and December 31, 2020 to understand the relationship between NDH/T2DM and multimorbidity primary/secondary healthcare usage and clinical outcomes. This was compared with a cohort of individuals with thyroid disease but no NDH/T2DM.</p><p><strong>Results: </strong>The dataset identified 152,384 and 124,190 adults with NDH and T2DM compared with 11,626 individuals with thyroid disease (control group). Individuals with NDH and individuals with T2DM had a high burden of disease, with only 13.1% of individuals with either NDH or T2DM not found to be suffering from at least one of the disease states of interest. The three most common comorbidities experienced by individuals with NDH were hypertension (41.4%), hypercholesterolemia (37.5%), and obesity (29.8%) compared with retinopathy (68.7%), hypertension (59.4%), and obesity (45.8%) in individuals with T2DM. Comparatively, the most common comorbidities in the control group were depression (30.8%), hypercholesterolemia (24.4%), and hypertension (17.1%). 28 (control group), 12 (NDH), and 16 (T2DM) primary care contacts per individual per year were identified, with 27,881, 282,371, and 314,880 inpatient admissions for the control, NDH, and T2DM cohorts, respectively. Prescription of drugs used to treat T2DM in individuals with NDH and T2DM was 27,772 (18.2%) and 109,361 (88.1%), respectively, accounting for approximately one in five individuals with NDH developing T2DM.</p><p><strong>Conclusion: </strong>Both NDH and T2DM were associated with significant multimorbidity alongside primary and secondary care utilisation. Given the morbidity highlighted with NDH, we highlight the need for earlier detection of NDH, recognition of multimorbidity associated with both NDH and T2DM, as well as the need for the further implementation of interventions to prevent progression to T2DM/multimorbidity.</p>","PeriodicalId":9151,"journal":{"name":"BMJ Open Diabetes Research & Care","volume":"12 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11409243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141911746","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}
Jorge Andrés Cázares-Preciado, Alejandra López-Arredondo, José Antonio Cruz-Cardenas, Luis Alberto Luévano-Martínez, Gerardo García-Rivas, Heriberto Prado-Garcia, Marion E G Brunck
{"title":"Metabolic features of neutrophilic differentiation of HL-60 cells in hyperglycemic environments.","authors":"Jorge Andrés Cázares-Preciado, Alejandra López-Arredondo, José Antonio Cruz-Cardenas, Luis Alberto Luévano-Martínez, Gerardo García-Rivas, Heriberto Prado-Garcia, Marion E G Brunck","doi":"10.1136/bmjdrc-2024-004181","DOIUrl":"10.1136/bmjdrc-2024-004181","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic hyperglycemia affects neutrophil functions, leading to reduced pathogen killing and increased morbidity. This impairment has been directly linked to increased glycemia, however, how this specifically affects neutrophils metabolism and their differentiation in the bone marrow is unclear and difficult to study.</p><p><strong>Research design and methods: </strong>We used high-resolution respirometry to investigate the metabolism of resting and activated donor neutrophils, and flow cytometry to measure surface CD15 and CD11b expression. We then used HL-60 cells differentiated towards neutrophil-like cells in standard media and investigated the effect of doubling glucose concentration on differentiation metabolism. We measured the oxygen consumption rate (OCR), and the enzymatic activity of carnitine palmitoyl transferase 1 (CPT1) and citrate synthase during neutrophil-like differentiation. We compared the surface phenotype, functions, and OCR of neutrophil-like cells differentiated under both glucose concentrations.</p><p><strong>Results: </strong>Donor neutrophils showed significant instability of CD11b and OCR after phorbol 12-myristate 13-acetate stimulation at 3 hours post-enrichment. During HL-60 neutrophil-like cell differentiation, there was a significant increase in surface CD15 and CD11b expression together with the loss of mitochondrial mass. Differentiated neutrophil-like cells also exhibited higher CD11b expression and were significantly more phagocytic. In higher glucose media, we measured a decrease in citrate synthase and CPT1 activities during neutrophil-like differentiation.</p><p><strong>Conclusions: </strong>HL-60 neutrophil-like differentiation recapitulated known molecular and metabolic features of human neutrophil differentiation. Increased glucose concentrations correlated with features described in hyperglycemic donor neutrophils including increased CD11b and phagocytosis. We used this model to describe metabolic features of neutrophil-like cell differentiation in hyperglycemia and show for the first time the downregulation of CPT1 and citrate synthase activity, independently of mitochondrial mass.</p>","PeriodicalId":9151,"journal":{"name":"BMJ Open Diabetes Research & Care","volume":"12 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11409339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141911745","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}
Ronald Horswell, San Chu, Addison E Stone, Daniel Fort, Gabriel Uwaifo, Vivian A Fonseca, Elizabeth B Norton
{"title":"Risk of healthcare visits from influenza in subjects with diabetes and impacts of early vaccination.","authors":"Ronald Horswell, San Chu, Addison E Stone, Daniel Fort, Gabriel Uwaifo, Vivian A Fonseca, Elizabeth B Norton","doi":"10.1136/bmjdrc-2023-003841","DOIUrl":"10.1136/bmjdrc-2023-003841","url":null,"abstract":"<p><strong>Introduction: </strong>The objective of this study was to determine the burden of influenza disease in patients with or without diabetes in a population of American adults to understand the benefits of seasonal vaccination.</p><p><strong>Research design and methods: </strong>We performed a retrospective cohort study using electronic medical records totaling 1,117,263 from two Louisiana healthcare providers spanning January 2012 through December 2017. Adults 18 years or older with two or more records within the study period were included. The primary outcome quantified was influenza-related diagnosis during inpatient (IP) or emergency room (ER) visits and risk reduction with the timing of immunization.</p><p><strong>Results: </strong>Influenza-related IP or ER visits totaled 0.0122-0.0169 events per person within the 2013-2016 influenza seasons. Subjects with diabetes had a 5.6-fold more frequent influenza diagnosis for IP or ER visits than in subjects without diabetes or 3.7-fold more frequent when adjusted for demographics. Early immunization reduced the risk of influenza healthcare utilization by 66% for subjects with diabetes or 67% for subjects without diabetes when compared with later vaccination for the 2013-2016 influenza seasons. Older age and female sex were associated with a higher incidence of influenza, but not a significant change in risk reduction from vaccination.</p><p><strong>Conclusions: </strong>The risk for influenza-related healthcare utilization was 3.7-fold higher if patients had diabetes during 2013-2016 influenza seasons. Early immunization provides a significant benefit to adults irrespective of a diabetes diagnosis. All adults, but particularly patients with diabetes, should be encouraged to get the influenza vaccine at the start of the influenza season.</p>","PeriodicalId":9151,"journal":{"name":"BMJ Open Diabetes Research & Care","volume":"12 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11308876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141896782","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":"Early screening for foot problems in people with diabetes is the need of the hour: 'Save the Feet and Keep Walking Campaign' in India.","authors":"Vijay Viswanathan, Amit Gupta, Arutselvi Devarajan, Satyavani Kumpatla, Sharvari Shukla, Sanjay Agarwal, Brij Mohan Makkar, Banshi Saboo, Vasanth Kumar, Rakesh Kumar Sahay","doi":"10.1136/bmjdrc-2024-004064","DOIUrl":"10.1136/bmjdrc-2024-004064","url":null,"abstract":"<p><strong>Introduction: </strong>Evidence on the prevalence of foot problems among people with diabetes in India at a national level is lacking. Hence, this study was aimed to assess the burden of high-risk (HR) feet in people with diabetes across India.</p><p><strong>Research design and methods: </strong>A cross-sectional national-level project 'Save the Feet and Keep Walking' campaign was conducted by the Research Society for the Study of Diabetes in India (RSSDI) from July 10, 2022 to August 10, 2022. A modified version of 3 min foot examination was used to assess the foot problems. Around 10 000 doctors with RSSDI membership were trained online to conduct foot screening and provided a standardised monofilament for detection of loss of protective sensation. People with diabetes aged >18 years who visited the clinics during the study period were examined for foot problems. Data were collected online using the semi-structured questionnaire. A total of 33 259 participants with complete information were included for the final analysis. The foot at risk was categorised based on International Working Group on the Diabetic Foot guidelines 2023.</p><p><strong>Results: </strong>Nearly 75% of the participants were aged above 45 years. Around 49% had diabetes duration >5 years and uncontrolled diabetes (hemoglobin A1c >8%). Presence of history of foot ulcer (20%), lower limb amputation (15.3%), foot deformities (24.5%) and absence of diminished dorsal pedis and posterior tibial pulses (26.4%) was noted in the study participants. Around 25.2% of them had HR feet and highly prevalent among males. Diabetic kidney and retinal complications were present in 70% and 75.5% of people with HR feet. Presence of heel fissures (OR (95% CI) 4.6 (4.2 to 5.1)) and callus or corns (OR (95% CI) 3.6 (3.3 to 4.0)) were significantly associated with HR feet.</p><p><strong>Conclusions: </strong>One-fourth of people with diabetes were found to have HR feet in India. The findings are suggestive of regular screening of people with diabetes for foot problems and strengthening of primary healthcare.</p>","PeriodicalId":9151,"journal":{"name":"BMJ Open Diabetes Research & Care","volume":"12 4","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11298753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888401","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}