Search

AIMS: To prospectively determine the change in prevalence of microalbuminuria in relation to changes in glycaemic control in children diagnosed with type 1 diabetes between 1986 and 1996. DESIGN: Prospective observational study of an inception cohort. SETTING: The geographically defined region of Oxfordshire, UK. PATIENTS: 527 children diagnosed with type 1 diabetes under 16 years of age, were divided into three groups based on year of diagnosis of diabetes: group A (1986–1989, n = 165), group B (1990–1993, n = 179) and group C (1994–1996, n = 183). Each group was followed prospectively for 10 years. MAIN OUTCOME MEASURES: Cumulative prevalence of microalbuminuria. RESULTS: After 4052 patient years of follow-up, in groups C versus B versus A, the cumulative prevalence of microalbuminuria was 31.7% (95% CI 20.9 to 42.5), 24.8% (17.8 to 31.8) and 23.2% (15.4 to 30.0) (log rank p = 0.22), and risk for development of microalbuminuria was not associated with year of onset of diabetes (hazard ratio 1.05 (0.99 to 1.12), p = 0.11). In groups C versus B versus A, glycaemic control improved after 10 years of diabetes (mean HbA1c 8.9% (1.5%) vs 9.4% (1.5%) vs 10.1% (1.7%), p value for ANOVA <0.001) and more children achieved an HbA1c level <7.5% (15.6% vs 5.9% vs 6.1%, p value for ANOVA = 0.032). CONCLUSION: In this UK based inception cohort of children diagnosed with type 1 diabetes, the adjusted prevalence of microalbuminuria was unchanged since 1986, despite some improvements in glycaemic control. This observation highlights the need for more proactive intervention with drugs such as angiotensin converting enzyme (ACE) inhibitors. [ABSTRACT FROM AUTHOR]

Objective: Spinal muscular atrophy (SMA) is a neuromuscular disorder that manifests with motor deterioration and respiratory complications. The paradigm of care is shifting as disease-modifying therapies including nusinersen, onasemnogene abeparvovec and risdiplam alter the disease trajectory of SMA. The objective of this study was to explore caregivers' experiences with disease-modifying therapies for SMA., Design: Qualitative study including semistructured interviews with caregivers of children with SMA who received disease-modifying therapies. Interviews were audio recorded, transcribed verbatim, coded and analysed using content analysis., Setting: The Hospital for Sick Children (Toronto, Canada)., Results: Fifteen family caregivers of children with SMA type 1 (n=5), type 2 (n=5) and type 3 (n=5) participated. There were two emerging themes and several subthemes (in parentheses): (1) inequities in access to disease-modifying therapies (variable regulatory approvals, prohibitively expensive therapies and insufficient infrastructure) and (2) patient and family experience with disease-modifying therapies (decision making, hope, fear and uncertainty)., Conclusion: The caregiver experience with SMA has been transformed by the advent of disease-modifying therapies. Consistent and predictable access to disease-modifying therapies is a major concern for caregivers of children with SMA but is influenced by regulatory approvals, funding and eligibility criteria that are heterogenous across jurisdictions. Many caregivers described going to great lengths to access therapies, highlighting issues related to justice, such as equity and access. This diverse population reflects contemporary patients and families with SMA; their broad experiences may inform the healthcare delivery of other emerging orphan drugs., Competing Interests: Competing interests: RA is a committee member of the American College of Chest Physicians and a paediatrics committee member of the American Thoracic Society, and holds research grants from Canadian Institutes of Health Research, Cure SMA Canada, Muscular Dystrophy Canada, VHA Home Healthcare, Boehringer-Ingelheim, Medigas, ProResp, Baxter Corporation Endowment Fund for Home Care, and Ontario Ministry of Health and Long-term Care. LX reported receiving research funding from The Hospital for Sick Children Clinician-Scientist Training Program, American Thoracic Society ASPIRE fellowship, Baxter Corporation Endowment Fund for Home Care, International Pediatric Sleep Association, and the Sleep Research Society Foundation during the conduct of the study., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To evaluate the course of sleep disordered breathing (SDB) in infants with Prader-Willi syndrome (PWS)., Design: Retrospective longitudinal observational study., Setting: Sleep laboratory at The Hospital for Sick Children, Toronto, Canada., Patients: Infants with PWS., Main Outcome Measures: The natural history of SDB in infants with PWS within 2 years from baseline assessment., Results: We identified 28 (12 male) infants with PWS who had a baseline polysomnography (PSG) at a median age (interquartile (IQR)) of 0.9 (0.5, 1.1) years. The median central apnoea index (CAI) at baseline was 6.6 events/hour (IQR 2.6, 12.1). Of these, 15/28 (53%) infants with PWS were diagnosed with significant central sleep apnoea (CSA) (CAI≥5 events/hour). Median age (IQR) at follow-up PSG was 2.1 (1.5, 2.6) years. The median CAI improved from 6.6 to 2.3 events/hour (p<0.0001). Only four infants with PWS had persistent CSA at the time of the follow-up PSG. Furthermore, three infants with PWS were diagnosed with mild-to-moderate obstructive sleep apnoea (OSA) that has improved at follow-up studies whereas two patients with PWS with no evidence of OSA at baseline were diagnosed with severe OSA on the follow-up PSG requiring adenotonsillectomy. The overall median obstructive apnoea-hypopnoea index was similar between baseline and follow-up studies (0.6 and 0.8, respectively, p=0.91)., Conclusions: CSA is prevalent in infants with PWS but usually improves with age. However, these patients continue to require ongoing PSG surveillance because some infants will have persistent CSA and others are at risk of developing OSA., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Objective: We prospectively determined islet autoantibody status in children presenting with diabetes to a single UK region in relation to ethnicity., Design: 316 (68.0% non-white) children presenting with diabetes between 2006 and 2013 were tested centrally for islet cell autoantibodies (ICA) and glutamic acid decarboxylase autoantibodies (GAD-65) at diagnosis, and if negative for both, tested for insulin autoantibodies (IAA). The assay used to measure GAD-65 autoantibodies changed from an in-house to a standardised ELISA method during the study., Results: Even with use of the standardised ELISA method, 25.8% of children assigned a diagnosis of type 1 diabetes still tested negative for all three autoantibodies. 30% of children assigned a diagnosis of type 2 diabetes were autoantibody positive, and these had the highest glycated haemoglobin (HbA1c) levels at 12 months follow-up compared with other groups (p value for analysis of variance <0.001), although the sample size was small. Autoantibody positivity was similar between non-white and white children regardless of assay used (60.0% (n=129) vs 56.4% (n=57), χ(2)=0.9, p=0.35), as was mean GAD-65 autoantibody levels, but fewer non-white children had two or more autoantibodies detectable (13% (n=28) vs 27.7% (n=28), χ(2)=12.1, p=0.001)., Conclusions: Islet autoantibody positivity was associated with a more severe phenotype, as demonstrated by poorer glycaemic control, regardless of assigned diabetes subtype. Positivity did not differ by ethnic group., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objectives: To perform a cross-sectional comparison of endogenous markers of glomerular filtration rate (GFR) (plasma symmetric dimethylarginine (SDMA) and estimated GFR (eGFR)) with a direct measure of GFR (using the plasma clearance of Inutest (In-GFR)), and a longitudinal evaluation of these markers in relation to the development of microalbuminuria, in young people with type 1 diabetes (T1D)., Methods: Longitudinal stored blood samples (n=1105) were available from 417 young people from the Oxford Regional Prospective Study (an inception cohort of 527 children followed for a median of 10.3 (interquartile range 7.1-12.3) years), for measurement of SDMA and creatinine. Additional annually collected data on anthropometric parameters, HbA1c, insulin dose and three early morning albumin:creatinine ratios were available. In-GFR was measured in a representative subgroup of 183 subjects., Main Outcome Measures: SDMA and eGFR., Results: SDMA and eGFR were significantly and similarly associated with In-GFR (r=-0.38 and r=0.36, p<0.001). Overall SDMA levels were lower in microalbuminuric (n=116) than normoalbuminuric subjects (n=301) (0.385 + or - 0.063 vs 0.412 + or - 0.059 micromol/l, p<0.001), probably reflecting hyperfiltration. The pattern of change in SDMA levels with age differed between microalbuminuric and normoalbuminuric subjects. Whereas SDMA levels declined in both groups until the age of 16 years, thereafter they tended to rise only in microalbuminuric subjects, probably reflecting a decline in renal function., Conclusions: In this longitudinal study of young people with T1D, measurement of SDMA, in contrast to eGFR, proved to be a reliable marker in identifying changes in filtration rates associated with the development of microalbuminuria (MA).

Aims: To determine risk factors for development of microalbuminuria (MA) in relation to detection of limited joint mobility (LJM+) of the interphalangeal joints in a longitudinal cohort of type 1 diabetic (T1DM) subjects., Methods: A total of 479 T1DM subjects diagnosed <16 years were followed from diagnosis of diabetes with annual assessments consisting of assessment of LJM, measurement of HbA1c and insulin-like growth factor 1 (IGF-1), and three urine samples for albumin:creatinine ratio (ACR)., Results: After a median follow up of 10.9 years, 162 subjects (35.1%) developed LJM at median age 13.0 years and duration 5.2 years. More subjects developed LJM after compared to before puberty (67.6 v 32.4%). In LJM+ compared to LJM- subjects, HbA1c (mean 10.1 (SD 1.6) v 9.6 (1.4) %)) and ACR levels (median 1.1 (range 0.2-242.9) v 0.9 (0.4-70.7) mg/mmol) were higher, and in a Cox model probability of developing LJM was related to puberty and higher HbA1c levels. ACR levels were higher after detection of LJM compared to before (median 1.2 (range 0.4-102.6) v 0.8 (0.2-181.9) mg/mmol). Probability of developing MA was related to puberty, HbA1c, female sex, and presence of LJM (a 1.9-fold increased risk). Both LJM and MA were associated with lower height SDS (LJM: mean 0.0 (SD 1.0) v 0.2 (1.1); MA: 0.0 (1.0) v 0.2 (SD 1.0)) and lower IGF-1 levels., Conclusion: The development of LJM was associated with an increased risk of microalbuminuria, independent of glycaemic control. Risk for both microalbuminuria and LJM was associated with puberty, reduced growth, and reduced IGF-1 levels, and may indicate underlying shared pathogenic mechanisms.