5 results on '"Peakman, M"'
Search Results
2. Immunological pathways to β-cell damage in Type 1 diabetes.
- Author
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Peakman, M.
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AUTOIMMUNE disease diagnosis , *T cells , *ISLANDS of Langerhans , *CELL physiology , *CELL surface antigens , *IMMUNITY , *IMMUNODIAGNOSIS , *INFLAMMATION , *INTERLEUKIN-1 , *TYPE 1 diabetes , *CD4 antigen , *DISEASE complications , *ANATOMY , *DIAGNOSIS , *PHYSIOLOGY - Abstract
Following almost 30 years of intensive research, initiated by the observation that Type 1 diabetes development is associated with a characteristic pancreatic immune cell infiltrate, a picture is emerging of which of the diverse effector arms of the immune system are involved in β-cell destruction. Like any chronic pathology, there is considerable complexity, and our ability to model the disease is hampered by a lack of ready access to the target organ and limited longitudinal analyses. However, it seems that putative pathways can start to be ruled in and out, in part as a result of focused mechanistic studies that make use of new technologies, and in part through analysis of the outcomes of clinical trials of new agents aimed at halting the disease process. The picture that emerges suggests a pathway to prevention that may require combinations of therapeutic agents that target different aspects of the immune system and will need to be used with due attention to their risk-benefit profiles. [ABSTRACT FROM AUTHOR]
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- 2013
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3. β-cell specific T-lymphocyte response has a distinct inflammatory phenotype in children with Type 1 diabetes compared with adults.
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Arif, S., Gibson, V. B., Nguyen, V., Bingley, P. J., Todd, J. A., Guy, C., Dunger, D. B., Dayan, C. M., Powrie, J., Lorenc, A., and Peakman, M.
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ANTIGENS , *B cells , *CYTOKINES , *INSULIN , *TYPE 1 diabetes , *PROINSULIN , *RESEARCH funding , *T cells , *PHENOTYPES - Abstract
Aim To examine the hypothesis that the quality, magnitude and breadth of helper T-lymphocyte responses to β cells differ in Type 1 diabetes according to diagnosis in childhood or adulthood. Methods We studied helper T-lymphocyte reactivity against β-cell autoantigens by measuring production of the pro-inflammatory cytokine interferon-γ and the anti-inflammatory cytokine interleukin-10, using enzyme-linked immunospot assays in 61 people with Type 1 diabetes (within 3 months of diagnosis, positive for HLA DRB1*0301 and/or *0401), of whom 33 were children/adolescents, and a further 91 were unaffected siblings. Results Interferon-γ responses were significantly more frequent in children with Type 1 diabetes compared with adults (85 vs 61%; P = 0.04). Insulin and proinsulin peptides were preferentially targeted in children ( P = 0.0001 and P = 0.04, respectively) and the breadth of the interferon-γ response was also greater, with 70% of children having an interferon-γ response to three or more peptides compared with 14% of adults ( P < 0.0001). Islet β-cell antigen-specific interleukin-10 responses were similar in children and adults in terms of frequency, breadth and magnitude, with the exception of responses to glutamic acid decarboxylase 65, which were significantly less frequent in adults. Conclusions At diagnosis of Type 1 diabetes, pro-inflammatory autoreactivity is significantly more prevalent, focuses on a wider range of targets, and is more focused on insulin/proinsulin in children than adults. We interpret this as indicating a more aggressive immunological response in the younger age group that is especially characterized by loss of tolerance to proinsulin. These findings highlight the existence of age-related heterogeneity in Type 1 diabetes pathogenesis that could have relevance to the development of immune-based therapies. [ABSTRACT FROM AUTHOR]
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- 2017
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4. Stimulated urine C-peptide creatinine ratio vs serum C-peptide level for monitoring of β-cell function in the first year after diagnosis of Type 1 diabetes.
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Tatovic, D., Luzio, S., Dunseath, G., Liu, Y., Alhadj Ali, M., Peakman, M., Dayan, C. M., O'Keefe, A., Stenson, R., Pell, J., Howell, A., Arif, S., Bayly, G., Thorogood, N., Green, K., Andrews, R. C., McLintock, N., Leech, N., Kyne, D., and Joseph, F.
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BLOOD testing , *C-peptide , *CONFIDENCE intervals , *CREATININE , *PEOPLE with diabetes , *GLYCOSYLATED hemoglobin , *TYPE 1 diabetes , *LONGITUDINAL method , *NONPARAMETRIC statistics , *RESEARCH funding , *STATISTICS , *URINALYSIS , *DATA analysis , *RANDOMIZED controlled trials , *REPEATED measures design , *BLIND experiment - Abstract
Aims To determine if urine C-peptide/creatinine ratio is a useful tool for monitoring β-cell function in new-onset Type 1 diabetes. Methods Data were obtained from a prospective immunomodulation study in people with Type 1 diabetes ≤ 3 months from diagnosis, with a standard mixed-meal tolerance test and measurement of urine C-peptide/creatinine ratio carried out at 0, 3, 6, 9 and 12 months. The change in the insulin-dose-adjusted HbA1c level was also correlated with the change in serum/urine C-peptide level during the 12-month follow-up period. Results A significant reduction in urine C-peptide/creatinine ratio, measured after a mixed-meal, was reached at 9 months (−45.4%), whilst the reduction in stimulated serum C-peptide level reached significance after 3 months (−54.7%) in placebo-treated participants. Neither change in stimulated serum C-peptide nor change in urine C-peptide level correlated with each other, and nor did change in insulin-dose-adjusted HbA1c level in the first 6 months, but all measures correlated significantly in the second half of the 12-month follow-up period. Conclusion Mixed-meal-stimulated urine C-peptide/creatinine ratio was similar to, although less sensitive than, stimulated serum C-peptide level in monitoring β-cell function during the first year after diagnosis. Because the former is significantly less invasive, it warrants inclusion in further studies in Type 1 diabetes and may represent an attractive alternative outcome measure in cohort studies and in children. [ABSTRACT FROM AUTHOR]
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- 2016
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5. Prevalence of autoantibodies to autonomic nervous tissue structures in Type 1 diabetes mellitus.
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Ejskjaer, N., Arif, S., Dodds, W., Zanone, M. M., Vergani, D., Watkins, P. J., and Peakman, M.
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DIABETES , *AUTOANTIBODIES , *AUTONOMIC nervous system physiology , *IMMUNOLOGY - Abstract
SummaryAims The pathogenesis of diabetic autonomic neuropathy is multifactorial, but recent studies have suggested a link between the presence of autoantibodies to nervous tissue structures and severe, symptomatic autonomic neuropathy. The present study was designed to examine the true prevalence of these autoantibodies in a large clinic-based population of Type 1 diabetic patients compared to nondiabetic controls. Methods The presence of complement fixing autoantibodies to vagus nerve (CF-VN), sympathetic ganglion (CF-SG) and adrenal medulla (CF-ADM) was assessed by immunofluorescence in a large cohort of patients (n = 394) of varying duration of Type 1 DM (median 28 years, range 6 months to 73 years) and 160 age and sex-matched nondiabetic control subjects. Results All three autoantibodies were frequently detected in Type 1 DM (CF-VN, 22.1%; CF-SG, 30.7%; CF-ADM, 13.2%) but only rarely in healthy control subjects (4.4%, 4.4% and 3.1%, respectively; P < 0.0005 for all). There was no association between any of the autoantibodies and retinopathy (fundoscopy), peripheral somatic neuropathy (biothesiometry) or nephropathy (urinary albumin–creatinine ratio). Conclusions Our results on this large cohort establish the extensive presence of autonomic nervous tissue autoantibodies in Type 1 DM. Their role in reflecting, causing or predicting autonomic neuropathy remains to be determined. [ABSTRACT FROM AUTHOR]
- Published
- 1999
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