BMJ Open Diabetes Research & Care最新文献

{"title":"Investigating the association between incretin-based therapies and thyroid cancer incidence among US Medicare beneficiaries with diabetes.","authors":"Clement O Acheampong, John B Buse, Klara R Klein, Lawrence T Kim, Joshua Evron, Anna R Kahkoska, Caroline A Thompson, Tiansheng Wang, Virginia Pate, Peter Leese, Til Stürmer","doi":"10.1136/bmjdrc-2025-005090","DOIUrl":"10.1136/bmjdrc-2025-005090","url":null,"abstract":"<p><strong>Introduction: </strong>Preclinical studies suggest a potential link between glucagon-like peptide 1 receptor agonists (GLP-1RA) and thyroid cancer (TC), yet it is unclear if this risk translates to humans.</p><p><strong>Research design and methods: </strong>We estimated the comparative effect of incretin-based therapies (GLP-1RA and dipeptidyl-peptidase-4 inhibitors (DPP-4i)) versus sodium-glucose cotransporter-2 inhibitors (SGLT-2i) on TC incidence among US older adults with type 2 diabetes. We defined TC as a thyroidectomy followed by ≥2 separate diagnoses codes for malignant neoplasm of thyroid gland within 90 days. We estimated adjusted 3-year cumulative risk differences of TC (aRDs) with 95% CIs using weighted Kaplan-Meier survival functions, and adjusted HRs using weighted Cox models.</p><p><strong>Results: </strong>We included 73 388 new users in the GLP-1RA versus SGLT-2i cohort (mean age 72.4 years, men: 48.3%) and 106 274 in the DPP-4i versus SGLT-2i cohort (mean age 74.6 years, men: 44.9%). At 3 years and a median duration of treatment of 0.82-1.15 years, the aRD for GLP-1RA versus SGLT-2i for TC was -23 per 10 000 (95% CI: -51 to 4) and the aRD for DPP-4i versus SGLT-2i was -2 per 10 000 (95% CI: -17 to 13). Secondary and sensitivity analyses were consistent.</p><p><strong>Conclusions: </strong>Our study of US Medicare beneficiaries with type 2 diabetes suggests that the initiation of incretin-based therapies may not increase the 3-year risk of TC compared with initiation of SGLT-2i. This finding offers reassurance for short-term use but does not eliminate the possibility of increased long-term or subtype-specific risks.</p>","PeriodicalId":9151,"journal":{"name":"BMJ Open Diabetes Research & Care","volume":"13 5","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12506239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243823","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":"Perinatal and postpartum insulin secretion capacity in women with early-onset and late-onset gestational diabetes.","authors":"Akihiro Katayama, Momoka Hasegawa, Eisaku Morimoto, Mayu Watanabe, Yuichi Matsushita, Masaya Takeda, Kenji Kai, Mizuho Yoshida, Saya Tsukahara, Naoki Okimoto, Katsuhiko Tada, Kazumasa Kumazawa, Kazuyuki Hida","doi":"10.1136/bmjdrc-2025-005114","DOIUrl":"10.1136/bmjdrc-2025-005114","url":null,"abstract":"<p><strong>Introduction: </strong>Gestational diabetes mellitus (GDM) is associated with metabolic risks and adverse maternal and fetal perinatal outcomes. This study aimed to compare pregnancy outcomes, postpartum glucose intolerance and insulin secretion capacity in women with early-onset GDM (EGDM, diagnosed<24 weeks) and late GDM (LGDM, diagnosed≥24 weeks) in Japan.</p><p><strong>Research design and methods: </strong>This single-center, retrospective study included 107 women with EGDM and 109 with LGDM. GDM was diagnosed through the 75 g oral glucose tolerance test. Postpartum glucose tolerance was assessed 4-16 weeks post partum. Maternal and neonatal outcomes, insulin secretion, and postpartum glucose tolerance were analyzed and compared. Subgroup analyses were performed for women with and without obesity.</p><p><strong>Results: </strong>Although gestational weight gain was significantly lower in women with EGDM than in those with LGDM, pregnancy outcomes, including neonatal birth weight, small for gestational age and large for gestational age, were comparable between the two groups. However, postpartum glucose intolerance was more prevalent in women with EGDM, particularly in those without obesity who also had significantly lower initial insulin secretion capacity. Insulin resistance was comparable between the groups, suggesting that reduced insulin secretion, rather than insulin resistance, contributes to postpartum glucose intolerance in EGDM.</p><p><strong>Conclusions: </strong>EGDM in women without obesity is associated with a high risk for postpartum glucose intolerance. This could be related to impaired insulin secretion rather than insulin resistance. These findings highlight the need for close monitoring and tailored interventions for patients with EGDM. More research is required to improve diagnostic and management strategies, considering ethnic variations in insulin secretion and glucose tolerance.</p>","PeriodicalId":9151,"journal":{"name":"BMJ Open Diabetes Research & Care","volume":"13 5","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12506086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238158","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":"Baseline and longitudinal changes of body roundness index and incident type 2 diabetes: evidence from the UK Biobank cohort.","authors":"Xuanli Zhao, Fangyuan Jing, Yanan Ren, Jing Zhu, Xinzhe Jing, Meiqun Lv, Ke Huang, Jing Guo, Jiayu Li, Xiaohui Sun, Yingying Mao, Ding Ye","doi":"10.1136/bmjdrc-2025-005339","DOIUrl":"10.1136/bmjdrc-2025-005339","url":null,"abstract":"<p><strong>Introduction: </strong>Type 2 diabetes (T2D) is closely associated with excess adiposity, particularly visceral fat. The body roundness index (BRI), calculated from height and waist circumference, provides a refined estimate of visceral adiposity. This study aimed to investigate the associations of baseline BRI and longitudinal changes in BRI with the risk of incident T2D.</p><p><strong>Research design and methods: </strong>We used UK Biobank data, a cohort involving adults aged 37-73 years. Both baseline and last follow-up BRI values were classified according to the tertiles of baseline BRI, and long-term BRI changes were categorized by baseline and follow-up grades. The annual average rate of change (AARC) of BRI was also calculated. Cox regression models were employed to evaluate HRs and 95% CIs, while restricted cubic splines explored non-linear relationships.</p><p><strong>Results: </strong>Among 485 509 participants, 32 956 developed T2D during the follow-up period. Elevated baseline BRI was correlated with a greater risk of T2D, with adjusted HRs of 2.39 (95% CI: 2.28 to 2.51) and 6.23 (95% CI: 5.96 to 6.50) for the second and third tertiles of BRI, respectively. In the longitudinal analysis of 65 684 participants (1153 T2D cases), low baseline BRI with grade increase was linked to higher risk of T2D (HR: 1.49, 95% CI: 1.05 to 2.13). Among participants with middle baseline BRI, grade decrease and increase showed HRs of 0.65 (95% CI: 0.45 to 0.93) and 1.66 (95% CI: 1.32 to 2.10) versus stable middle. Grade decrease with high baseline BRI was associated with lower T2D risk (HR: 0.50, 95% CI: 0.40 to 0.62) compared with stable high. Non-linear associations between AARC of BRI and T2D risk were identified (p <0.05).</p><p><strong>Conclusions: </strong>This study shows that both baseline BRI and long-term BRI changes are linked to T2D risk, emphasizing the significance of monitoring BRI trends for T2D prevention and control.</p>","PeriodicalId":9151,"journal":{"name":"BMJ Open Diabetes Research & Care","volume":"13 5","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069137","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":"Slowly progressive type 1 diabetes and female sex as associated factors for pancreatic abnormalities on diagnostic imaging indicating precancerous potential.","authors":"Tomoyasu Fukui, Tetsuro Kobayashi, Takuya Awata, Hiroshi Ikegami, Akihisa Imagawa, Yoichi Oikawa, Haruhiko Osawa, Eiji Kawasaki, Masanari Kuwabara, Kazuhiko Kobayashi, Takeshi Katsuki, Norio Kanatsuna, Junji Kozawa, Noriko Kodani, Akira Shimada, Masayuki Shimoda, Kazuma Takahashi, Daisuke Chujo, Tetsuro Tsujimoto, Kyoichiro Tsuchiya, Jungo Terasaki, Kan Nagasawa, Shinsuke Noso, Ichiro Horie, Kazuki Yasuda, Hisafumi Yasuda, Toshiaki Hanafusa, Hiroshi Kajio","doi":"10.1136/bmjdrc-2025-005229","DOIUrl":"10.1136/bmjdrc-2025-005229","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to identify factors associated with pancreatic abnormal findings on imaging (PAI) suggesting precancerous potential between slowly progressive type 1 diabetes and acute-onset type 1 diabetes.</p><p><strong>Research design and methods: </strong>The study was designed to identify factors associated with PAI using data from a nationwide cohort, the Japanese Type 1 Diabetes Database. Clinical factors, including sex, age, type of diabetes onset, diabetes duration, body mass index, and human leucocyte antigen genotypes associated with type 1 diabetes, were evaluated.</p><p><strong>Results: </strong>Among 279 patients with type 1 diabetes, 95 patients who had not undergone imaging evaluations, two patients with pancreatic lipomatosis, and 15 patients with missing data were excluded. Finally, a total of 167 patients with type 1 diabetes were analyzed. Among 13 patients who were identified as PAI positive, female sex (92.3% vs 53.2%, p=0.007), slowly progressive type 1 diabetes (69.2% vs 36.4%, p=0.034), and older age were more common compared with PAI-negative cases. The multivariable logistic regression analysis revealed that female sex (OR 13.87; 95% CI 1.6 to 120.1; p=0.017), slowly progressive type 1 diabetes (OR 5.70; 95% CI 1.46 to 22.19; p=0.012), and age (OR 1.05; 95% CI 1.002 to 1.103; p=0.043) were independently associated with PAI positivity.</p><p><strong>Conclusions: </strong>The findings indicate that slowly progressive type 1 diabetes and female sex are closely associated with PAI, along with age. These results suggest the need for increased clinical vigilance for pancreatic pathology in patients with slowly progressive type 1 diabetes.</p>","PeriodicalId":9151,"journal":{"name":"BMJ Open Diabetes Research & Care","volume":"13 5","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069187","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":"Skeletal health in adolescents with poorly controlled type 1 diabetes: results from a randomized controlled trial.","authors":"Mari-Anne Pulkkinen, Tero Varimo, Sanna Toiviainen-Salo, Taina H Härkönen, Saila Laakso, Anna-Kaisa Tuomaala, Matti Hero","doi":"10.1136/bmjdrc-2025-005134","DOIUrl":"10.1136/bmjdrc-2025-005134","url":null,"abstract":"<p><strong>Introduction: </strong>Poorly controlled type 1 diabetes (T1D) has been associated with impaired bone health, but the mechanisms remain unclear. We aimed to investigate whether changes in glycemic control and glucose variability are associated with skeletal health and to evaluate the roles of insulin-like growth factor I (IGF-I) and advanced glycation end-products (AGEs) in bone mineral accrual.</p><p><strong>Research design and methods: </strong>This longitudinal study included adolescents with poorly controlled T1D (HbA1c >9%/75 mmol/mol), who underwent dual-energy X-ray absorptiometry (DXA) at baseline and after 12 months. Glycemic control was assessed using glycohemoglobin (HbA1c), continuous glucose monitoring (CGM) parameters, and glycemic load. Serum IGF-I and AGEs, specifically methyl-glyoxal-hydro-imidazolone (MG-HI), were measured. Correlation analyses and linear regression models were used to evaluate the associations between glycemic markers, IGF-I, AGEs and bone parameters.</p><p><strong>Results: </strong>Altogether, 37 adolescents (48.6 % female) with T1D, with mean HbA1c 9.9% (85 mmol/mol), were followed up from mean age of 14.3 for 12 months. DXA-derived bone mineral density (BMD) z-scores at lumbar spine, proximal femur, and total body less head were approximately 0.5 SDS lower than reference values (p=0.005-0.04). The only significant change in BMD z-scores during the 12-month follow-up was an increase in proximal femur in girls. In the whole group, an increase in IGF-1 was associated with BMD accrual, while changes in HbA1c, time in range, or MG-HI were not. No vertebral fractures were detected.</p><p><strong>Conclusions: </strong>Despite lower BMD in adolescents with poorly controlled T1D, neither changes in glycemic control nor MG-HI levels correlated significantly with bone health measures, while increase of IGF-1 was associated with BMD accrual. Future studies should explore alternative AGEs and use advanced bone imaging techniques to better understand skeletal fragility in T1D.</p>","PeriodicalId":9151,"journal":{"name":"BMJ Open Diabetes Research & Care","volume":"13 5","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12434736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069126","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":"Low parental stress and positive well-being in Finnish children and adolescents with type 1 diabetes.","authors":"Riina Pironetti, Marja-Terttu Saha, Tiina Luukkaala, Nina Vuorela, Kirsi Kakko, Paivi Keskinen","doi":"10.1136/bmjdrc-2025-005248","DOIUrl":"10.1136/bmjdrc-2025-005248","url":null,"abstract":"<p><strong>Introduction: </strong>Given the limited knowledge about family dynamics and well-being among pediatric patients with type 1 diabetes (T1D) in Finland, this study aimed to assess parental stress, patient well-being, and their potential associations with glycemic control at a Finnish diabetes clinic.</p><p><strong>Research design and methods: </strong>A cross-sectional survey was conducted with 199 children (aged 1-16 years) using a background information questionnaire, the Parenting Stress Index Short Form (PSI-4-SF), and the WHO-5 Well-Being Index (WHO-5) questionnaire.</p><p><strong>Results: </strong>The mean glycated hemoglobin (HbA1c) level was 7.7% (61 mmol/mol), and the time in range (TIR) was 55.4%. Parents reported low stress levels (PSI total stress: median=31, IQR=12-55, n=133), with no significant correlation between parental stress and children's glycemic control. However, parents of children aged <7 years reported higher stress levels, which correlated with better metabolic control in children (HbA1c: rho=-0.86; TIR: rho=0.78; n=9). The mean WHO-5 score for all children was good (70; IQR=64-80, n=180). Their WHO-5 did not correlate with HbA1c (rho=-0.08, n=180) but correlated positively with TIR (rho=0.17, p=0.038, n=156).</p><p><strong>Conclusions: </strong>Better glycemic stability in children, as measured by TIR, correlated with well-being. Additionally, higher parental stress in young children was linked to better metabolic control in their children. These findings emphasize the importance of integrating psychosocial aspects into the care of pediatric patients with T1D.</p>","PeriodicalId":9151,"journal":{"name":"BMJ Open Diabetes Research & Care","volume":"13 5","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039160","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":"Latent class growth mixture modeling of HbA1C trajectories identifies individuals at high risk of developing complications of type 2 diabetes mellitus in the UK Biobank.","authors":"Dale Handley, Alexandra C Gillett, Renu Bala, Jessica Tyrrell, Cathryn M Lewis","doi":"10.1136/bmjdrc-2024-004826","DOIUrl":"10.1136/bmjdrc-2024-004826","url":null,"abstract":"<p><strong>Introduction: </strong>Frequent glycated hemoglobin A1c (HbA1c) monitoring is recommended in individuals with type 2 diabetes mellitus (T2D). We aimed to identify distinct, long-term HbA1c trajectories following a T2D diagnosis and investigate how these glycemic control trajectories were associated with health-related traits and T2D complications.</p><p><strong>Research design and methods: </strong>A cohort of 12,435 unrelated individuals of European ancestry with T2D was extracted from the UK Biobank data linked to primary care records. Latent class growth mixture modeling was applied to identify classes with similar HbA1c trajectories over the 10 years following T2D diagnosis. Associations between HbA1c class membership and sociodemographic factors, biomarkers, polygenic scores, and T2D-related outcomes, were tested using logistic regression and Cox proportional hazards models.</p><p><strong>Results: </strong>Six HbA1c trajectory classes were identified. The largest class (76.8%) maintained low and stable HbA1c levels over time. Five additional smaller classes with distinct, but more variable, trajectories were found and were associated with younger age at T2D diagnosis, higher fasting glucose levels, higher random glucose levels, higher body mass index polygenic score and increased healthcare use before T2D diagnosis. Relative to the low and stable class, these five showed increased risks of T2D complications, including stroke (HR=1.55 (1.31-1.84)), kidney disease (HR=1.39 (1.27-1.53)), all-cause mortality (HR=1.36 (1.23-1.51)), and progression to combination therapy (HR=3.22 (3.04-3.41)) or insulin (HR=3.21 (2.89-3.55)).</p><p><strong>Conclusion: </strong>Individuals with T2D who show higher and more variable HbA1c trajectories are at increased risk of developing T2D-related complications. Early identification of patients at risk, based on factors such as age at diagnosis and previous healthcare utilization could improve patient outcomes.</p>","PeriodicalId":9151,"journal":{"name":"BMJ Open Diabetes Research & Care","volume":"13 5","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12421182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022901","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":"Association between multifactorial control and excess risk of liver diseases in type 2 diabetes: a prospective cohort study.","authors":"Rui Chen, Ying Zhou, Minzhi Xu, Yanhong Gong, Wenfei Xia, Xiaoxv Yin","doi":"10.1136/bmjdrc-2025-005336","DOIUrl":"10.1136/bmjdrc-2025-005336","url":null,"abstract":"<p><strong>Introduction: </strong>To examine the association of the number of controlled risk factors with the excess risk of severe metabolic dysfunction-associated steatotic liver disease (MASLD) and major adverse liver outcomes (MALO) among patients with type 2 diabetes.</p><p><strong>Research design and methods: </strong>In this cohort study, a total of 307,688 participants from the UK Biobank were included. Participants with baseline type 2 diabetes were categorized according to the number of risk factors within the guideline-recommended ranges (diet, smoking, drinking, exercise, sedentary behavior, body mass index, glycated hemoglobin, blood pressure, and low-density lipoprotein cholesterol).</p><p><strong>Results: </strong>During a median (IQR) of 12.5 (11.8-13.2) years of follow-up, 519 (3.9%) participants with type 2 diabetes and 2718 (0.9%) participants without diabetes developed severe MASLD. Patients with type 2 diabetes had an increased risk of severe MASLD compared with participants without diabetes (HR 3.93, 95% CI 3.56 to 4.33), but the excess risk decreased stepwise with an increasing number of risk factors on target (HR (95% CI) for zero to two controlled risk factors: 5.44 (4.09 to 7.25); three controlled risk factors: 4.47 (3.59 to 5.57); four controlled risk factors: 4.16 (3.49 to 4.96); five controlled risk factors: 3.91 (3.28 to 4.66); six controlled risk factors: 3.50 (2.80 to 4.38); seven to nine controlled risk factors: 2.61 (1.92 to 3.56)). Similar patterns were observed in the analysis of MALO.</p><p><strong>Conclusions: </strong>Patients with type 2 diabetes who had more controlled risk factors showed progressively lower excess risk of severe MASLD and MALO. Comprehensive interventions targeting multiple risk factors may be associated with reduced liver lesions in patients with type 2 diabetes.</p>","PeriodicalId":9151,"journal":{"name":"BMJ Open Diabetes Research & Care","volume":"13 5","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12421187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022883","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":"TLR5 influences the development of type 1 diabetes.","authors":"Karsten Buschard, Lars Krogvold, Flemming Pociot, Ivan Gerling, Rikke Thea, Knut Dahl-Jørgensen, Camilla Hartmann Friis Hansen","doi":"10.1136/bmjdrc-2025-005111","DOIUrl":"10.1136/bmjdrc-2025-005111","url":null,"abstract":"<p><p>In mammalian and human life, it is important that the immune system defends against microorganisms. Although there is a huge overlap, innate cells are good against bacteria, whereas T cells are good against viruses, mainly because of antibody production via T helper and B lymphocytes. Toll-like receptor 5 (TLR5) is a regulator; when it is highly expressed, T cells are inhibited, and innate cells are favored. In glucose-activated pancreatic islets, <i>TLR5</i> gene expression has been found to be highly upregulated, and the islets may therefore be protected from T cell destruction resulting in autoimmune type 1 diabetes (T1D).</p><p><strong>Research design and methods: </strong>We investigated mRNA from the islets of Langerhans in patients with newly diagnosed T1D for <i>TLR5</i> gene expression, as well as <i>Tlr5</i> and <i>Cd3</i> expression in the whole pancreatic tissue of female diabetic non-obese diabetic (NOD) mice. Also, we examined for polymorphisms between <i>TLR5</i>, immunological parameters, and T1D.</p><p><strong>Results: </strong>Islet mRNA for <i>TLR5</i> was downregulated by one-third of patients with newly diagnosed T1D, compared with controls, and correlated inversely with T cell infiltration in the islets. Moreover, the association between TLR5 and T cells was supported by a corresponding correlation of <i>Tlr5</i> and <i>Cd3</i> expression in the pancreatic tissue of diabetic NOD mice. Regarding polymorphisms, two associations were found between <i>TLR5</i> and monocytes. Also, a significant polymorphism was seen concerning <i>TLR5</i> and T1D.</p><p><strong>Conclusions: </strong>In the present study, we find a low expression of mRNA for <i>TLR5</i> in patients with newly diagnosed T1D associated with enhanced T cell infiltration. T cells are important for autoimmune diseases, including T1D. We hope that the present findings may be influential for the understanding of how T1D develops.</p>","PeriodicalId":9151,"journal":{"name":"BMJ Open Diabetes Research & Care","volume":"13 5","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12414181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145005865","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":"The impact of learning disabilities on control, management, and outcomes of type 2 diabetes mellitus in the UK: an observational cohort study using the Clinical Practice Research Datalink.","authors":"Archie Wing, Rohini Mathur","doi":"10.1136/bmjdrc-2024-004879","DOIUrl":"10.1136/bmjdrc-2024-004879","url":null,"abstract":"<p><strong>Introduction: </strong>Adults with learning disabilities in the UK have a substantially higher risk of developing type 2 diabetes mellitus (T2DM) than the general population. This study aimed to assess the impact of living with learning disabilities on T2DM control, therapeutic management, vascular outcomes, and mortality in UK primary care.</p><p><strong>Research design and methods: </strong>We conducted an observational cohort study using primary care electronic health records from the UK Clinical Practice Research Datalink. The study included adults newly diagnosed with T2DM from 2004 to 2021. The exposure was learning disability status at the time of diagnosis. Multivariable logistic regression was used to compare glycemic control at 5 years post-diagnosis between people with and without learning disabilities. Multivariable Cox regression was used to compare time to insulin initiation, macrovascular and microvascular complications, and mortality between people with and without learning disabilities.</p><p><strong>Results: </strong>Of 280 300 adults with T2DM included in the study, 2074 (0.74%) had a learning disability at T2DM diagnosis. After adjustment, people with learning disabilities had lower odds of poor glycemic control than those without learning disabilities 5 years after diagnosis (OR=0.81, 95% CI 0.70 to 0.94) and faster insulin initiation (HR=1.20, 95% CI 1.00 to 1.45) than those without learning disabilities. The risks of all-cause and diabetes-related mortality were doubled in those with learning disabilities (all-cause HR=2.15, 95% CI 1.82 to 2.54; diabetes-related HR=1.93, 95% CI 1.32 to 2.80). We found no difference in the risk of vascular complications.</p><p><strong>Conclusions: </strong>Individuals with learning disabilities had better glycemic control but shorter time to insulin initiation. This may be related to more frequent diabetes monitoring, or faster advancing T2DM requiring quicker treatment intensification. Despite having similar risks of vascular complications, people with learning disabilities were at higher risk of death. Future research into the mechanisms behind this could help reduce health disparities for people with T2DM and learning disabilities.</p>","PeriodicalId":9151,"journal":{"name":"BMJ Open Diabetes Research & Care","volume":"13 5","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144942937","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}