27 results found
Thomas NJ, Walkey HC, Kaur A, et al., 2022, The relationship between islet autoantibody status and the genetic risk of type 1 diabetes in adult-onset type 1 diabetes, DIABETOLOGIA, Vol: 66, Pages: 310-320, ISSN: 0012-186X
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- Citations: 1
Thomas NJ, Dennis JM, Sharp SA, et al., 2021, DR15-DQ6 remains dominantly protective against type 1 diabetes throughout the first five decades of life (vol 64, pg 2258, 2021), DIABETOLOGIA, Vol: 65, Pages: 258-258, ISSN: 0012-186X
Thomas NJ, Dennis JM, Sharp SA, et al., 2021, DR15-DQ6 remains dominantly protective against type 1 diabetes throughout the first five decades of life, Diabetologia, Vol: 64, Pages: 2258-2265, ISSN: 0012-186X
Aims/hypothesisAmong white European children developing type 1 diabetes, the otherwise common HLA haplotype DR15-DQ6 is rare, and highly protective. Adult-onset type 1 diabetes is now known to represent more overall cases than childhood onset, but it is not known whether DR15-DQ6 is protective in older-adult-onset type 1 diabetes. We sought to quantify DR15-DQ6 protection against type 1 diabetes as age of onset increased.MethodsIn two independent cohorts we assessed the proportion of type 1 diabetes cases presenting through the first 50 years of life with DR15-DQ6, compared with population controls. In the After Diabetes Diagnosis Research Support System-2 (ADDRESS-2) cohort (n = 1458) clinician-diagnosed type 1 diabetes was confirmed by positivity for one or more islet-specific autoantibodies. In UK Biobank (n = 2502), we estimated type 1 diabetes incidence rates relative to baseline HLA risk for each HLA group using Poisson regression. Analyses were restricted to white Europeans and were performed in three groups according to age at type 1 diabetes onset: 0–18 years, 19–30 years and 31–50 years.ResultsDR15-DQ6 was protective against type 1 diabetes through to age 50 years (OR < 1 for each age group, all p < 0.001). The following ORs for type 1 diabetes, relative to a neutral HLA genotype, were observed in ADDRESS-2: age 5–18 years OR 0.16 (95% CI 0.08, 0.31); age 19–30 years OR 0.10 (0.04, 0.23); and age 31–50 years OR 0.37 (0.21, 0.68). DR15-DQ6 also remained highly protective at all ages in UK Biobank. Without DR15-DQ6, the presence of major type 1 diabetes high-risk haplotype (either DR3-DQ2 or DR4-DQ8) was associated with increased risk of type 1 diabetes.Conclusions/interpretationHLA DR15-DQ6 confers dominant protection from type 1 diabetes across the first five decades of life.
Thomas NJ, Walkey HC, Kaur A, et al., 2021, The absence of islet autoantibodies in clinically diagnosed older-adult onset type 1 diabetes suggests an alternative pathology, advocating for routine testing in this age group
<jats:title>Abstract</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>Islet autoantibodies at diagnosis are not well studied in older-adult onset (>30years) type 1 diabetes due to difficulties of accurate diagnosis. We used a type 1 diabetes genetic risk score (T1DGRS) to identify type 1 diabetes aiming to evaluate the prevalence and pattern of autoantibodies in older-adult onset type 1 diabetes.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We used a 30 variant T1DGRS in 1866 white-European individuals to genetically confirm a clinical diagnosis of new onset type 1 diabetes. We then assessed the prevalence and pattern of GADA, IA2A and ZnT8A within genetically consistent type 1 diabetes across three age groups (<18years (n=702), 18-30years (n=524) and >30years (n=588)).</jats:p></jats:sec><jats:sec><jats:title>Findings</jats:title><jats:p>In autoantibody positive cases T1DGRS was consistent with 100% type 1 diabetes in each age group. Conversely in autoantibody negative cases, T1DGRS was consistent with 93%(56/60) of <18years, 55%(37/67) of 18-30years and just 23%(34/151) of >30years having type 1 diabetes. Restricting analysis to genetically consistent type 1 diabetes showed similar proportions of positive autoantibodies across age groups (92% <18years, 92% 18-30years, 93% >30years)[p=0.87]. GADA was the most common autoantibody in older-adult onset type 1 diabetes, identifying 95% of autoantibody positive cases versus 72% in those <18years.</jats:p></jats:sec><jats:sec><jats:title>Interpretation</jats:title><jats:p>Older adult-onset type 1 diabetes has identical rates but different patterns of positive autoantibodies to childhood onset. In clinically suspected type 1 diabetes in older-adults, absence of autoantibodies strongly su
Humphreys A, Bravis V, Kaur A, et al., 2019, Individual and diabetes presentation characteristics associated with partial remission status in children and adults evaluated up to 12 months following diagnosis of type 1 diabetes: An ADDRESS-2 (After Diagnosis Diabetes Research Support System-2) study analysis, Diabetes Research and Clinical Practice, Vol: 155, ISSN: 0168-8227
AIMS: People with recently-diagnosed type 1 diabetes mellitus (T1D) may undergo a transient period of glycaemic control with less exogenous insulin. Identification of predictors of this 'remission' could inform a better understanding of glycaemic control. METHODS: Participants in the ADDRESS-2 study were included who had 1 or 2 assessments of remission status (coincident insulin dose and HbA1c measurement, with remission defined by ≤0.4 units insulin/kg-body-weight/day with HbA1c < 53 mmol/mol). Demographic and clinical presentation characteristics were compared according to remission status and predictors of remission were explored by logistic regression analysis. RESULTS: 1470 first and 469 second assessments of remission status were recorded within 12 months of diagnosis of T1D. Step increases in the probability of remission were identified at age-at-diagnosis 20 years and 3 months after diagnosis (both p < 0.001). Among those aged < 20 years, remission was associated with male gender (p = 0.02), no ketoacidosis (p = 0.02) and fewer than 2 symptoms at presentation (p = 0.004). None of these characteristics predicted remission in those aged ≥ 20 years. In the subgroup with two assessments, transition to remission was independently associated with first remission assessment in months 1-2 post-diagnosis (p = 0.01), with age-at-diagnosis ≥ 20 years (p = 0.01) and, in those aged < 20 years, with an early HbA1c of <57 mmol/mol. Adiposity, ethnicity, autoantibody status and other autoimmune disease were unrelated to remission. CONCLUSIONS: For those diagnosed before 20 years of age, males, ketoacidosis-free, with fewer symptoms and low early HbA1c were more likely to experience remission, but remission was most likely in anyone aged ≥ 20 at diagnosis.
Patel KA, Thomas N, Weedon MN, et al., 2019, Analysis of Type 1 Diabetes Genetic Risk Score Shows 1 in 8 People with Clinically Diagnosed Adult-Onset T1D Are Misdiagnosed, and Presenting Features at Diagnosis Do Not Identify Those Misdiagnosed, 79th Scientific Sessions of the American-Diabetes-Association (ADA), Publisher: AMER DIABETES ASSOC, ISSN: 0012-1797
Walkey HC, Kaur A, Godsland IF, et al., 2019, The impact of ethnicity on clinical characteristics and autoantibody status at clinical onset of Type 1 diabetes-from the ADDRESS-2 study, 79th Scientific Sessions of the American-Diabetes-Association (ADA), Publisher: AMER DIABETES ASSOC, Pages: 1-2, ISSN: 0012-1797
Introduction: The phenotype of type 1 diabetes (T1D) has been explored mainly in white populations. People of non-white ethnicity are reportedly less likely to be antibody positive, but phenotypic differences are not well characterised. We investigated ethnic group differences in the clinical characteristics and antibody (Ab) status at clinical onset of T1D.Methods: We studied people of white European (WE), Asian (A) and black African/Caribbean (AC) ethnicity with clinically-assigned T1D, age ≥5 years, recruited ≤ 6 months after diagnosis, and with Abs (GADA, IA-2A and ZnT8A) measured by radioimmunoassay.Results: Ethnic breakdown: WE n=1,997, A n=50, AC n=41. Median (IQR) ages were: WE 23(14-24), A 18(12-29), AC 26 (15-41) years p=0.007. Presentation with DKA was more common in AC (65%) than WE (42%) or A (53%) p=0.006; otherwise clinical presentation (polyuria/dipsia, weight loss, fatigue, symptom duration) was similar. Proportions with 0, 1 and ≥2 Abs differed by ethnicity: WE (15%, 24%, 61%); A (28%, 26%, 46%); AC (36%, 32%, 32%) p<0.001. For Ab negative (0 Abs), ethnic groups differed in BMI (p=0.001) and presentation with DKA (<0.001), but other characteristics, including daily insulin dose, were similar. For Ab positive (≥1 Ab), there were differences in parental history of diabetes p=0.02; otherwise ethnicity had no impact. Also, differences were seen in the frequency of IA-2A: WE (67%), A (53%), AC (50%) p=0.03 and ZnT8A: WE (60%), A (39%), AC (42%) p=0.01, but not GADA: WE (83%), A (94%) AC (92%) p=0.09.Conclusion: Although clinical presentation of T1D was remarkably similar across ethnic groups, variations were found in the proportions with Ab positivity and frequencies of individual Abs. Antibody negativity was more common in non-white ethnic groups and the presence of >1 Ab most common in white ethnicity. Practitioners should be alert to differences in phenotype according to antibody status that may impact classification in some ethn
Kaur A, Walkey H, Godsland I, et al., 2018, Ethnic variation in phenotype and autoantibody number in newonset Type 1 diabetes (T1D) in a UK cohort: (ADDRESS-2), Immunology of Diabetes Society Congress 2018
Misra S, Kaur A, Godsland IF, et al., 2018, Overweight individuals with Type 1 diabetes are less likely to present with diabetic ketoacidosis-data from the after diabetes diagnosis research support system (ADDRESS-2) cohort, 78th Scientific Sessions of the American-Diabetes-Association, Publisher: AMER DIABETES ASSOC, Pages: 1-2, ISSN: 0012-1797
Introduction: Insulin resistance has been proposed to accelerate progression to type 1 diabetes (T1D) in antibody positive relatives of affected individuals. We hypothesised that overweight individuals with confirmed T1D would be less likely to present with diabetic ketoacidosis (DKA), signifying an earlier onset of T1D, due to concomitant insulin resistance.Methods: The ADDRESS-2 study recruits incident clinician-assigned T1D cases within 6-months of diagnosis and systematically assesses pancreatic autoimmunity by GAD-65, IA-2 and ZnT8 antibodies. People with at least two positive antibodies were selected to confirm diagnosis of T1D and categorised for adiposity according to BMI (adults) or Z-scores (children). Odds ratios (OR) for presentation with DKA were compared, adjusted for potential confounders and sub-analysed by whether adult or child at recruitment.Results: 31% (969/ 3132) were positive for two or more pancreatic antibodies. Of these 44% (424/969) presented with DKA. The proportions with DKA varied significantly by adiposity: 59% underweight (16/27), 47% normal (280/601), 39% overweight (103/263), 30% obese (19/63) and 40% severely obese (6/15) (p=0.02). When adjusted for age, being overweight or obese was associated with lower risk of DKA in adults (OR 0.58, p=0.006; 0.44, p=0.03, respectively) not children (OR 0.9, p=0.81; 0.51, p=0.12, respectively). Higher adiposity category was associated with higher daily insulin-requirements independent of age, with obesity associated with a 4 unit/day increase (p=0.03) and severe obesity, 11 units/day increase (p=0.008).Conclusion: Adults with T1D are less likely to present with DKA if overweight or obese. Despite smaller proportions of DKA, insulin requirements are higher. These data suggest that, in adults, T1D presentation is unmasked by the insulin resistance of obesity prior to absolute insulin deficiency and ketoacidosis.
Walkey HC, Bravis V, Akaal K, et al., 2018, The relationship between islet autoantibody status and the clinical characteristics of children and adults with incident type 1 diabetes in a UK cohort, BMJ Open, Vol: 8, ISSN: 2044-6055
Walkey HC, Kaur A, Bravis V, et al., 2017, Rationale and protocol for the After Diabetes Diagnosis REsearch Support System (ADDRESS): an incident and high risk type 1 diabetes UK cohort study., BMJ Open, Vol: 7, ISSN: 2044-6055
INTRODUCTION: Type 1 diabetes is heterogeneous in its presentation and progression. Variations in clinical presentation between children and adults, and with ethnic group warrant further study in the UK to improve understanding of this heterogeneity. Early interventions to limit beta cell damage in type 1 diabetes are undergoing evaluation, but recruitment is challenging. The protocol presented describes recruitment of people with clinician-assigned, new-onset type 1 diabetes to understand the variation in their manner of clinical presentation, to facilitate recruitment into intervention studies and to create an open-access resource of data and biological samples for future type 1 diabetes research. METHODS AND ANALYSIS: Using the National Institute for Health Research Clinical Research Network, patients >5 years of age diagnosed clinically with type 1 diabetes (and their siblings) are recruited within 6 months of diagnosis. Participants agree to have their clinical, laboratory and demographic data stored on a secure database, for their clinical progress to be monitored using information held by NHS Digital, and to be contacted about additional research, in particular immunotherapy and other interventions. An optional blood sample is taken for islet autoantibody measurement and storage of blood and DNA for future analyses. Data will be analysed statistically to describe the presentation of incident type 1 diabetes in a contemporary UK population. ETHICS AND DISSEMINATION: Ethical approval was obtained from the independent NHS Research Ethics Service. Results will be presented at national and international meetings and submitted for publication to peer-reviewed journals.
Walkey HC, Kaur A, Godsland IF, et al., 2017, Clinical presentation and islet autoantibody status in a UK multi-ethnic cohort of children and adults with new-onset Type 1 diabetes-the after diabetes diagnosis research support system-2 (ADDRESS-2), 77th Scientific Sessions of the American-Diabetes-Association, Publisher: American Diabetes Association, Pages: A467-A468, ISSN: 0012-1797
Freiding A, Eloholma M, Ketomaki J, et al., 2007, Mesopic visual efficiency I: detection threshold measurements, LIGHTING RESEARCH & TECHNOLOGY, Vol: 39, Pages: 319-334, ISSN: 1477-1535
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- Citations: 30
Goodman T, Forbes A, Walkey H, et al., 2007, Mesopic visual efficiency IV: a model with relevance to nighttime driving and other applications, LIGHTING RESEARCH & TECHNOLOGY, Vol: 39, Pages: 365-388, ISSN: 1477-1535
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- Citations: 59
Varady G, Freiding A, Eloholma M, et al., 2007, Mesopic visual efficiency III: discrimination threshold measurements, LIGHTING RESEARCH & TECHNOLOGY, Vol: 39, Pages: 355-364, ISSN: 1477-1535
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- Citations: 28
Walkey H, Orrevetelainen P, Barbur J, et al., 2007, Mesopic visual efficiency II: reaction time experiments, LIGHTING RESEARCH & TECHNOLOGY, Vol: 39, Pages: 335-354, ISSN: 1477-1535
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- Citations: 32
Goodman T, Forbes A, Walkey H, 2006, A practical model for mesopic photometry, Pages: 1855-1860
This article reports the results of a multinational research project investigating visual performance in halflight (mesopic) conditions. From the experimental investigations using reaction time, detection threshold and recognition contrast threshold techniques, the results were used to develop a system for practical mesopic photometry, which provides an acceptably good fit to the experimental data and is also suitable for practical implementation by the lighting industry. A major feature of the model is that it can be implemented in terms of photopic and scotopic luminance measurements, measurements that can easily be made in practice. Copyright© (2006) by the International Measurement Federation (IMEKO).
Walkey HC, Harlow JA, Barbur JL, 2006, Characterising mesopic spectral sensitivity from reaction times, VISION RESEARCH, Vol: 46, Pages: 4232-4243, ISSN: 0042-6989
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- Citations: 15
Walkey HC, Barbur JL, 2006, Guest Editorial: Shedding new light on the twilight zone, OPHTHALMIC AND PHYSIOLOGICAL OPTICS, Vol: 26, Pages: 223-224, ISSN: 0275-5408
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- Citations: 3
Walkey HC, Harlow JA, Barbur JL, 2006, Changes in reaction time and search time with background luminance in the mesopic range, OPHTHALMIC AND PHYSIOLOGICAL OPTICS, Vol: 26, Pages: 288-299, ISSN: 0275-5408
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- Citations: 18
Eloholma M, Viikari M, Halonen L, et al., 2005, Mesopic models—from brightness matching to visual performance in night-time driving: A review, Lighting Research & Technology, Vol: 37, Pages: 155-173, ISSN: 1477-1535
At present, suitable methods to evaluate the visual effectiveness of lighting products in the mesopic region are not available. The majority of spectral luminous efficiency functions obtained to date in the mesopic range have been acquired by heterochromatic brightness matching. However, the most recent studies in the mesopic field have adopted a task performance-based approach. This paper summarizes the major mesopic models proposed so far, presenting in detail the experimental conditions of these studies. The authors represent a research consortium which has adopted the task performance-based approach for night-time driving in which mesopic visual performance has been divided into three subtasks. Data for each sub-task will be generated by using a set of common parameter values and 120 observers. The approach and methods used by the consortium are presented. © 2006, Sage Publications. All rights reserved.
Eloholma M, Viikari M, Halonen L, et al., 2005, Authors’ response to SA Fotios, Lighting Research & Technology, Vol: 37, Pages: 174-175, ISSN: 1477-1535
Walkey HC, Barbur JL, Harlow JA, et al., 2005, Effective contrast of colored stimuli in the mesopic range: a metric for perceived contrast based on achromatic luminance contrast, JOURNAL OF THE OPTICAL SOCIETY OF AMERICA A-OPTICS IMAGE SCIENCE AND VISION, Vol: 22, Pages: 17-28, ISSN: 1084-7529
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- Citations: 21
Eloholma M, Viikari M, Halonen L, et al., 2005, Mesopic models - From brightness matching to visual performance in night-time driving: A review, Lighting Research and Technology, Vol: 37, Pages: 155-173, ISSN: 1477-1535
At present, suitable methods to evaluate the visual effectiveness of lighting products in the mesopic region are not available. The majority of spectral luminous efficiency functions obtained to date in the mesopic range have been acquired by heterochromatic brightness matching. However, the most recent studies in the mesopic field have adopted a task performance-based approach. This paper summarizes the major mesopic models proposed so far, presenting in detail the experimental conditions of these studies. The authors represent a research consortium which has adopted the task performance-based approach for night-time driving in which mesopic visual performance has been divided into three subtasks. Data for each sub-task will be generated by using a set of common parameter values and 120 observers. The approach and methods used by the consortium are presented. © The Chartered Institution of Building Services Engineers 2005.
Fotios SA, Eloholma M, Viikari M, et al., 2005, Comment on 'Mesopic models - From brightness matching to visual performance in night-time driving: A review' by M Eloholma, M Viikari, L Halonen, H Walkey, T Goodman, J Alferdinck, A Frieding, P Bodrogi and G Várady, Lighting Research and Technology, Vol: 37, Pages: 173-175, ISSN: 1477-1535
A previous work summarized the history of the measurement of visual sensitivity to identify the problems inherent in mesopic photometry. The authors stated that in practical lighting applicatons, the detection and recognition of visual objects at or near visual threshold, and the reaction time needed to perceive objects in the visual field, are more relevant than the visual assessment of brightness. In this paper, Fotios comments on the study's results particularly on differences in spectral sensitivity between people of different nationalities. He emphasizes that brightness should not be relegated as it is a fundamental visual perception that is related to the amount of light present, and that in turn related to how well one can see. For their part, the authors of the previous study emphasize that visual task perception is not based on brightness itself but contrast.
Walkey HC, Barbur JL, Harlow JA, et al., 2001, Measurements of chromatic sensitivity in the mesopic range, Color Research and Application, Vol: 26, ISSN: 0361-2317
We measured chromatic threshold sensitivity in the mesopic range using a combination of techniques that mask the detection of photopic and scotopic luminance contrast signals. The measurements were carried out at a number of light levels in the range 45-0.004 cd/m2, both foveally and with the stimulus centered 3.5° in the periphery. In order to investigate the effect of rod signals on chromatic detection thresholds in the near periphery of the visual field, we measured chromatic threshold ellipses when fully dark-adapted and during the cone plateau region of the dark-adaptation curve. The results confirm a number of previous observations and reveal new findings: • A reduction in background adaptation causes a loss of chromatic sensitivity that becomes more rapid as one enters the mesopic range. This loss is observed both foveally and in the near periphery and cannot, therefore, be attributed entirely to rod intrusion. A small increase in chromatic thresholds is observed in the near periphery when compared with foveal measurements. Comparison of foveal and peripheral measurements also reveals a tilt in the orientation of the major axis of the chromatic threshold ellipse away from the tritanopic towards the deuteranopic colour confusion line: • The loss of chromatic sensitivity is not uniform, with the tritan axis being most affected. The ellipticity (i.e., the ratio of major to minor axis of the ellipse plotted on the CIE 1976, UCS diagram) can increase by as much as a factor of two, as the light level decreases from 10-0.056 cd/m2. • At lower light levels, some subjects show an asymmetry in chromatic thresholds along the tritan axis. This asymmetry is consistent with greater sensitivity to increases than decreases in S-cone excitation. • Measurements of chromatic sensitivity following either complete dark-adaptation or during the cone plateau phase of the dark-adaptation curve yield essentially the same results. These findings, therefore, sug
Walkey HC, Barbur JL, Harlow JA, et al., 2001, Measurements of chromatic sensitivity in the mesopic range, XVth Meeting of the International-Color-Vision-Society, Publisher: JOHN WILEY & SONS INC, Pages: S36-S42, ISSN: 0361-2317
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- Citations: 29
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