21 results found
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.
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.
Sivapatham S, Walkey HC, Kaur A, et al., 2019, Changes in beta cell function 6 and 12 months after a diagnosis of type 1 diabetes: insights from the ADDRESS-2 study, 55th Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), Publisher: SPRINGER, Pages: S155-S155, ISSN: 0012-186X
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 HC, Godsl IF, et al., 2019, Predictors of c-peptide in Type 1 diabetes within the first 60 days of diagnosis: Routine laboratory data from the After Diabetes Diagnosis Research Support System (ADDRESS-2) cohort, The Diabetes UK Professional Conference 2019, Publisher: WILEY, Pages: 67-67, ISSN: 0742-3071
Aims: To describe the factors predicting c‐peptide within 60 days of diagnosis, in a multi‐ethnic, incident Type 1 diabetes cohort.Methods: ADDRESS‐2 recruits patients with clinician‐assigned Type 1 diabetes within six months of diagnosis. Clinical, demographic and routine laboratory data are collected. Islet autoantibodies: glutamic acid decarboxylase (GADA), insulinoma‐associated protein 2 (IA‐2A) and zinc transporter‐8 (ZnT8A) are measured in those opting to give a blood sample (52%). We analysed data collected between 01 September 2011 and 30 June 2017.Results: Of the 4,606 participants recruited, 341 (7.4%) had a random c‐peptide measured in clinic within the first 60 days of diagnosis (80% within the first week of diagnosis). The median c‐peptide was 0.23nmol/l (IQR 0.14–0.38nmol/l). C‐peptide was more likely to be lower if participants: were children (0.19 vs 0.26nmol/l, p = 0.01); presented with diabetic ketoacidosis (DKA) (0.19 vs 0.25nmol/l, p < 0.001); and autoantibody positive (0.23 vs 0.32nmol/l, p = 0.004). There were no significant differences in c‐peptide with gender, ethnicity (White vs non‐White), body mass index (BMI) or time from diagnosis to date of c‐peptide measurement. On multiple linear regression of all significant variables (n = 179), autoantibody positivity (coeff. –0.014, p = 0.005) and presenting with DKA (coeff. −0.13, p = 0.002) were strong independent predictors of lower c‐peptide. When excluding antibody status from the regression model (n = 333), presenting with DKA (coeff. −0.16, p = 0.02) remained the only significant independent predictor of lower c‐peptide.Conclusion: Patients with Type 1 diabetes have lower c‐peptide close to diagnosis if they present with DKA and they are autoantibody positive, irrespective of age.Acknowledgement: On behalf of the ADDRESS‐2 Management Committee, Patient Advocate Group and Investigators
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.
Kaur A, Walkey H, Godsland IF, et al., 2017, Characteristics Associated with Diabetic Ketoacidosis in Children and Adults Newly Diagnosed with Type 1 Diabetes: Data from the After Diabetes Diagnosis Research Support System (ADDRESS-2) Cohort, 77th Scientific Sessions of the American-Diabetes-Association, Publisher: AMER DIABETES ASSOC, Pages: A467-A467, ISSN: 0012-1797
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
Misra S, Kaur A, Walkey H, et al., 2017, The extent of diabetes misclassification one year after a diagnosis of Type 1 diabetes: data from the after diabetes diagnosis research support system (ADDRESS-2) cohort, 77th Scientific Sessions of the American-Diabetes-Association, Publisher: AMER DIABETES ASSOC, Pages: A411-A412, ISSN: 0012-1797
Kaur A, Walkey H, Bravis V, et al., 2017, Predictors of glycaemia at the time of diagnosis in people with newly diagnosed Type 1 diabetes: data from the After Diabetes Diagnosis Research Support System (ADDRESS-2) cohort, Diabetes UK Professional Conference 2017, Publisher: Wiley, Pages: 73-73, ISSN: 0742-3071
Kaur A, Johnston DG, Godsland IF, 2016, Does metabolic health in overweight and obesity persist? - Individual variation and cardiovascular mortality over two decades, European Journal of Endocrinology, Vol: 175, Pages: 133-143, ISSN: 1479-683X
Objective: Overweight and obese individuals may be metabolically healthy but attention needs to be given to long-term persistence of this trait and any associated variation in cardiovascular risk.Design: Cross-sectional and longitudinal variation in metabolic health and associated cardiovascular mortality were analysed in 1099 white European-origin normal weight and overweight or obese males followed for 20 years.Methods: Definitions of metabolic health were based on LDL and HDL cholesterol, triglycerides, blood pressure, fasting glucose and cardiovascular risk. Insulin resistance (e.g. HOMA-IR) and subclinical inflammation (ESR and white blood cell count) were explored. Cardiovascular mortality risks and persistence of metabolic health status were evaluated.Results: There were 87 cardiovascular deaths. Insulin resistance was increased in metabolically healthy overweight or obese participants (median HOMA-IR 2.63, 95%ci 1.79-3.65, p<0.001) relative to normal weight (median HOMA-IR 1.67, 95%ci 1.08-2.67, p<0.001) as was subclinical inflammation but metabolically healthy overweight or obese individuals were not at increased risk of cardiovascular mortality compared with the metabolically healthy normal-weight (hazard ratio 1.13, 95% ci 0.34-3.72, p=0.8). The proportions of initially metabolically healthy overweight or obese who remained metabolically healthy for visits 2, 3 and 4 were 54, 48 and 39%, respectively, and for initially normal-weight individuals, 68, 51 and 41%. A lower proportion of metabolically healthy overweight or obese individuals remained metabolically healthy at visit 2 compared with normal weight individuals (p=0.007) but proportions converged thereafter..Conclusions: Despite being insulin resistant and having greater subclinical inflammation, and despite instability in metabolic health status, metabolically healthy overweight or obese individuals were at no greater risk of cardiovascular mortality than their normal-weight equivalents.
Humphreys A, Bravis V, Godsland IF, et al., 2016, Influences on clinical remission after presentation with Type 1 diabetes: an ADDRESS-2 (After Diagnosis Diabetes Research Support System 2) study analysis, Publisher: Wiley, Pages: 24-24, ISSN: 0742-3071
Bravis V, Kaur A, Walkey H, et al., 2016, The effect of ethnicity on the clinical presentation of people with Type 1 diabetes and on humoral autoimmunity of the cohort within ADDRESS-2 (After Diagnosis Diabetes Research Support System 2), Publisher: Wiley, Pages: 25-25, ISSN: 0742-3071
Misra S, Kaur A, Walkey H, et al., 2016, Reclassification of diabetes subtype following a diagnosis of Type 1 diabetes: data from the After Diabetes Diagnosis Research Support System (ADDRESS-2) cohort, Publisher: Wiley, Pages: 186-186, ISSN: 0742-3071
Bravis V, Kaur A, Walkey H, et al., 2015, An incident and high risk Type 1 diabetes cohort, After Diagnosis Diabetes Research Support System (ADDRESS-2): description and comparison of clinical characteristics and presentation of patients with and without evidence of humoral autoimmunity, Publisher: WILEY-BLACKWELL, Pages: 86-86, ISSN: 0742-3071
Bravis V, Kaur A, Walkey H, et al., 2014, Ater diagnosis diabetes research support system-2 (ADDRESS-2): clinical presentation of type 1 diabetes in the beginning of the 21st century in a multi-ethnic UK cohort, European Association for the Study of Diabetes, Publisher: SPRINGER, Pages: S127-S128, ISSN: 0012-186X
Bravis V, Kaur A, Walkey H, et al., 2014, An Incident and High-Risk Type 1 Diabetes Cohort-After Diagnosis Diabetes Research Support System-2 (ADDRESS-2): Key Initial Findings, Publisher: AMER DIABETES ASSOC, Pages: A645-A645, ISSN: 0012-1797
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