Publications
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Agha-Jaffar R, Oliver NS, Kostoula M, et al., 2020, Hyperglycemia recognised in early pregnancy is phenotypically type 2 diabetes mellitus not gestational diabetes mellitus: a case control study, Journal of Maternal-Fetal and Neonatal Medicine, Vol: 33, Pages: 3977-3983, ISSN: 1476-4954
OBJECTIVE: Gestational diabetes mellitus is defined as "diabetes recognized in the second or third trimester that is not clearly overt diabetes". Evidence relating to women with hyperglycemia early in pregnancy is limited. We aimed to evaluate women diagnosed with hyperglycemia early in pregnancy (eGDM) and compared them to those with pregestational established type 2 diabetes mellitus (T2DM) and gestational diabetes diagnosed routinely at 24-28-week gestation (rtGDM) to determine if the length of exposure to hyperglycemia adversely affected outcomes. METHODS: Forty consecutive women with eGDM who attended a multidisciplinary antenatal clinic were reviewed. Two separate BMI-matched control groups were identified, recognized pregestational T2DM (n = 80) and rtGDM (n = 80). Baseline demographics and outcomes were compared. RESULTS: A higher proportion of women in the eGDM and T2DM group required insulin and the incidence of hypertensive disorders was similarly increased compared with the rtGDM group (88.6, 77.0 versus 8.1%, p < .001 and 42.5%, 37.5 versus 12.5% p < .001, respectively). The proportion of infants born small for gestational age varied (eGDM 11.1%, T2DM 13.0%, and rtGDM 2.5%, p=.049). Postpartum, 7.5% of eGDM women were diagnosed with T2DM versus 1.3% in the rtGDM group (p<.001). CONCLUSIONS: These novel data demonstrate that the length of exposure to glucose adversely affects materno-foetal outcomes independent of maternal adiposity.
Oliver N, Johnston D, Godsland I, et al., 2020, A pragmatic and scalable strategy using mobile technology to promote sustained lifestyle changes to prevent Type 2 diabetes in India and the UK – a randomised controlled trial, Diabetologia, Vol: 63, Pages: 486-496, ISSN: 0012-186X
Aims/hypothesis This randomised controlled trial was performed in India and UK in people with prediabetes to study whether mobile phone short message services can be used to motivate and educate people to follow lifestyle modification, to prevent type 2 diabetes.Methods The study was performed in people with prediabetes (n=2062, control: n=1031; intervention: n=1031) identified by glycosylated haemoglobin A1c42 and 47mmol/mol (6.0% and 6.4%). Participants were recruited from public and private sector organisations in India and by the NHS Health Checks programme in the UK. Allocation to the study groups was performed using a computer generated sequence (1:1) in India and by stratified randomisation in permuted blocks in the UK. Investigators in both countries remained blinded throughout the study period. All participants received advice on healthy lifestyle at baseline. The intervention group in addition received supportive text messages using mobile phone short messaging services2-3 times per week. Participants were assessed at intervals for 2years. The primary outcome was conversion to diabetes and secondary outcomes included anthropometry, biochemistry, dietary and physical activity change, blood pressure and quality of life. Results At 2years follow-up, in the intention-to-treat population the hazard ratio for development of diabetes calculated using a discrete-time proportional hazards model was 0.89,95%CI(0.74-1.07) p=0.22. There were no significant differences in the secondary outcomes.Conclusions/Interpretation This trial in 2 countries with varied ethnic and cultural backgrounds showed no significant reduction in the progression in diabetes in 2 years by lifestyle modification using short messaging services (Hazard Ratio 0.89, 95% CI 0.74 – 1.07, p=0.22)
Bhattarai S, Godsland IF, Misra S, et al., 2019, Metabolic health and vascular complications in type 1 diabetes, Journal of Diabetes and its Complications, Vol: 33, Pages: 634-640, ISSN: 1056-8727
AIMS: Optimal glycaemic control benefits risk of microvascular and macrovascular complications in type 1 diabetes (T1DM) but the importance of other components of metabolic health is less certain, particularly in the context of routine clinical practice. METHODS: Data for this cross-sectional analysis derived from a database covering inner North West London adult diabetes clinics. People with T1DM and with complete information for height, weight, blood pressure and serum high and low-density lipoprotein cholesterol (HDL-c and LDL-c) and triglyceride concentration measurements were included. RESULTS: Among the 920 participants, those with complications were older and had longer duration of diabetes but had similar HbA1c to people without complications. Systolic hypertension and low HDL-c were independently associated with complications. From having 0 risk factors, the prevalence of micro and macrovascular disease increased with increasing number of risk factors. Relative to those with ≥1 risk factor, those with 0 risk factors (n = 179) were at lower risk of retinopathy (OR 0.6 (0.4-0.9), p = 0.01) and nephropathy [OR 0.1 (0.04-0.3), p = 0.002], independent of individual characteristics. CONCLUSIONS: In routine clinical management of T1DM, associations between lipid and blood pressure risk factors and prevalent micro and macrovascular disease remain, implying that more intensive risk factor management may be beneficial.
Srivanichakorn W, Godsland IF, Washirasaksiri C, et al., 2019, Cardiometabolic risk factors in Thai individuals with prediabetes treated in a high-risk, prevention clinic - unexpected relationship between HDL cholesterol and glycaemia in men, Journal of Diabetes Investigation, Vol: 10, Pages: 771-779, ISSN: 2040-1124
BACKGROUND: Relationships between cardiometabolic risk and glycaemia have been rarely studied in people under clinical evaluation and treatment for cardiometabolic risk and with prediabetes. We investigated relationships between glycaemia and cardiometabolic risk factors in clinic participants with prediabetes. METHODS: This was a cross-sectional analysis of data collected at a centre in Thailand. Clinic attendees were at high-risk of diabetes or cardiovascular disease, with HbA1c 39-<48 mmol/mol or fasting plasma glucose (FPG) 5.6-<7.0 mmol/L. The relationships between glycaemia and cardiometabolic risk factors were explored. RESULTS: Of 357 participants, two or more insulin resistance-related metabolic disturbances were present in 84%; 61% took a statin and 75% an antihypertensive agent. Independently of age, gender, adiposity, medication use, possible NAFLD and gender-glycaemia interaction, neither FPG nor HbA1c were associated with variation in any other cardiometabolic risk factors. HDL cholesterol decreased with HbA1c in women (female*HbA1c interaction, p=0.03) but, unexpectedly, increased with FPG in men (male*FPG interaction, p=0.02). CONCLUSION: Overall, in Thai people treated for high-cardiometabolic risk and with prediabetes defined by FPG and/or HbA1c, neither FPG nor HbA1c were associated with other cardiometabolic risk factors. However, according to gender, HDL cholesterol showed the expected relationship with glycaemia in women but the reverse in men.
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
Raghavan A, Nanditha A, Snehalatha C, et al., 2018, Incidence of type 2 diabetes is higher among men with persistent impaired glucose tolerance than in transient impaired glucose tolerance – A 5 year follow up study, Journal of Association of Physicians of India, Vol: 66, Pages: 22-26, ISSN: 0004-5772
© 2018, Journal of Association of Physicians of India. All rights reserved. Objective: This was a 5 year comparative analysis of the incidence of type 2 diabetes in men who had persistent impaired glucose tolerance (P-IGT) versus transient impaired glucose tolerance (T-IGT). P-IGT (positive IGT on two oral glucose tolerance tests (OGTT), T-IGT (IGT in first OGTT and normal glucose tolerance (NGT) in the 2 nd OGTT). Methods: The samples were collected from a randomized controlled diabetes prevention study. The prevention study was done using lifestyle modification (LSM) promoted by use of mobile short message services (SMS) for 2 years. The control group of the randomized study who received advice on LSM at only the baseline formed the P-IGT group for the 3 years follow up study (n=236). T-IGT (n=569) were available from those who had NGT on the 2 nd OGTT while screening for the prevention study. The total diabetes incidence at 5 years in the study groups were compared using standard OGTT (WHO criteria). Results: The conversion rate to diabetes in 5 years was significantly lower among T-IGT than among P-IGT, OR=0.202 (95% CI, 0.145-0.296,p<0.0001). P-IGT had higher rate of risk factors for diabetes than T-IGT. Conclusion: The risk of conversion to diabetes was 80 percent lower in T-IGT than in P-IGT. Identification of P-IGT will help in selecting persons who require early intervention for diabetes.
Thomson HH, Srivanichakorn W, Oliver N, et al., 2018, Protocol for a clinical trial of text messaging in addition to standard care versus standard care alone in prevention of type 2 diabetes through lifestyle modification in India and the UK, BMC Endocrine Disorders, Vol: 18, ISSN: 1472-6823
BackgroundType 2 diabetes is a serious clinical problem in both India and the UK. Adoption of a healthy lifestyle through dietary and physical activity modification can help prevent type 2 diabetes. However, implementing lifestyle modification programmes to high risk groups is expensive and alternative cheaper methods are needed. We are using a short messaging service (SMS) programme in our study as a tool to provide healthy lifestyle advice and an aid to motivation. The aim of the study is to assess the efficacy and user acceptability of text messaging employed in this way for people with pre-diabetes (HbA1c 6.0% to ≤6.4%; 42–47 mmol/mol) in the UK and India.Methods/designThis is a randomised, controlled trial with participants followed up for 2 years. After being screened and receiving a structured education programme for prediabetes, participants are randomised to a control or intervention group. In the intervention group, text messages are delivered 2–3 times weekly and contain educational, motivational and supportive content on diet, physical activity, lifestyle and smoking. The control group undergoes monitoring only. In India, the trial involves 5 visits after screening (0, 6, 12, 18 and 24 months). In the UK there are 4 visits after screening (0, 6, 12 and 24 months). Questionnaires (EQ-5D, RPAQ, Transtheoretical Model of Behavioural Change, and food frequency (UK)/24 h dietary recall (India)) and physical activity monitors (Actigraph GT3X+ accelerometers) are assessed at baseline and all follow-up visits. The SMS acceptability questionnaires are evaluated in all follow-up visits. The primary outcome is progression to type 2 diabetes as defined by an HbA1c of 6.5% or over(India) and by any WHO criterion(UK). Secondary outcomes are the changes in body weight, body mass index, waist circumference, blood pressure, fasting plasma glucose; lipids; proportion of participants achieving HbA1c ≤6.0%; HOMA-IR; HOMA-β; acceptability of SMS; dieta
Nanditha A, Snehalatha C, Raghavan A, et al., 2018, The post-trial analysis of the Indian SMS diabetes prevention study shows persistent beneficial effects of lifestyle intervention, DIABETES RESEARCH AND CLINICAL PRACTICE, Vol: 142, Pages: 213-221, ISSN: 0168-8227
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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.
Sharma S, El-Laboudi A, Reddy M, et al., 2018, A pilot study in humans of microneedle sensor arrays for continuous glucose monitoring, Analytical Methods, Vol: 10, Pages: 2088-2095, ISSN: 1759-9660
Although subcutaneously implanted continuous glucose monitoring (CGM) devices have been shown to support diabetes self-management, their uptake remains low due to a combination of high manufacturing cost and limited accuracy and precision arising from their invasiveness. To address these points, minimally invasive, a solid microneedle array-based sensor for continuous glucose monitoring is reported here. These intradermal solid microneedle CGM sensors are designed for low cost manufacturing. The tolerability and performance of these devices is demonstrated through clinical studies, both in healthy volunteers and participants with type 1 diabetes (T1D). The geometry of these solid microneedles allows them to penetrate dermal tissue without the need for an applicator. The outer surface of these solid microneedles are modified as glucose biosensors. The microneedles sit in the interstitial fluid of the skin compartment and monitor real-time changes in glucose concentration. Optical coherence tomography measurements revealed no major axial movement of the microneedles in the tissue. No significant adverse events were observed and low pain scores were reported when compared to catheter insertion, deeming it safe for clinical studies in T1D. These amperometric sensors also yielded currents that tracked venous blood glucose concentrations, showing a clinically acceptable correlation. Studies in people with T1D gave a mean absolute relative difference (MARD) of 9% (with respect to venous blood glucose) with over 94% of the data points in the A and B zones of the Clarke error grid. These findings provide baseline data for further device development and a larger clinical efficacy and acceptability study of this microneedle intradermal glucose sensor in T1D.
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
Objectives:Todescribethecharacteristicsofchildrenandadultswithincidenttype1diabetesincontemporary,multi-ethnicUK,focusingondifferencesbetweentheisletautoantibodynegativeandpositive.Design:Observationalcohortstudy.Setting:146mainlysecondarycarecentresacrossEnglandandWales.Participants:3,312peopleaged≥5yearswererecruitedwithin6monthsofaclinicaldiagnosisoftype1diabetesviatheNationalInstituteforHealthResearchClinicalResearchNetwork.3,021wereofwhiteEuropeanethnicityand291(9%)werenon-white.Therewasasmallmalepredominance(57%).Youngpeople<17yearscomprised59%.Mainoutcomemeasures:Autoantibodystatusandcharacteristicsatpresentation.Results:Themajoritypresentedwithclassicalosmoticsymptoms,weightloss,andfatigue.Ketoacidosiswascommon(42%),especiallyinadults,andirrespectiveofethnicity.35%wereoverweightorobese.Ofthe1,778participantswhodonatedabloodsample,85%werepositiveforoneormoreautoantibodiesagainstglutamatedecarboxylase,isletantigen-2,andzinctransporter8.Presentingsymptomsweresimilarintheautoantibodypositiveandnegativeparticipants,aswasthefrequencyofketoacidosis(43%vs40%,p=0·3).Autoantibodypositivitywaslesscommonwithincreasingage(p=0·0001),inmalescomparedwithfemales(82%vs90%,p<0·0001)andinpeopleofnon-whitecomparedwithwhiteethnicity(73%vs86%,p<0·0001).Bodymassindexwashigherinautoantibodynegativethanpositiveadults(median,IQR25·5,23·1-29·2vs23·9,21·4-26·7kg/m2;p=0·0001).Autoantibodynegativeparticipants weremorelikelytohaveaparentwithdiabetes(28%vs16%,p<0·0001)andlesslikelytohaveanotherautoimmunedisease(4%vs8%,p=0.01).Conclusions:Mostpeopleassignedadiagnosisoftype1diabetespresentedwithclassicalclinicalfeaturesandisletautoantibodies.Althoughindistinguishableatanindividuallevel,autoantibodynegativeparticipantsasagroupdemonstratedfeaturesmoretypicallyassociatedwithotherdiabetessubtypes.
Groom O, Sebastian A, Liu X, et al., 2018, The utility of family history in classifying diabetes subtype: Insights from the MY DIABETES Study, Publisher: WILEY, Pages: 136-136, ISSN: 0742-3071
Misra S, Sebastian A, Groom O, et al., 2018, Systematic screening for monogenic diabetes in people of South Asian and African Caribbean ethnicity: Preliminary results from the My Diabetes study, Publisher: WILEY, Pages: 160-160, ISSN: 0742-3071
Loh WJ, Oliver NS, Johnston DG, et al., 2018, Skinfold thickness measurements and mortality in white males during 27.7 years of follow-up, International Journal of Obesity, Vol: 42, Pages: 1939-1945, ISSN: 0307-0565
IntroductionObesity is a major risk factor for mortality from a range of causes. We investigated whether skinfold measurements were associated with mortality independently of variation in body mass index (BMI).MethodsA prospective analysis of mortality in 870 apparently healthy adult Caucasian men participating in an occupational health cohort was undertaken. At baseline, skinfold measurements were taken at biceps, triceps, iliac and subscapular sites. Derived measurements included the sum of all four skinfolds and subscapular to triceps, subscapular to iliac and BMI to iliac ratios. All-cause mortality was analysed by Cox proportional hazards modelling and death in specific mortality subcategories by competing risks analysis.ResultsDuring a mean of 27.7 years follow up, there were 303 deaths (119 cancer, 101 arteriovascular, 40 infection, 43 other). In univariable analysis, BMI was associated with all-cause, cancer, arteriovascular and other mortality and subscapular skinfold with all-cause and arteriovascular mortality. On bivariable analysis, with inclusion of BMI, subscapular skinfold ceased to be a associated with mortality but iliac skinfold emerged as strongly, negatively associated with all-cause and arteriovascular mortality. In multivariable analysis, with inclusion of age, BMI, smoking, alcohol and exercise, iliac skinfold was negatively associated with all-cause (Hazard ratio HR 0.77, 95% confidence interval CI 0.66–0.90, p = 0.002), arteriovascular (HR 0.75, 95%CI 0.58,0.97, p = 0.02) and infection (HR 0.63, 95%CI 0.42,0.94, p = 0.02) death. Among obese participants (BMI ≥ 30 kg/m2), iliac skinfold of ≤9.7 mm was associated with a six-fold increase in all-cause mortality risk.ConclusionLow iliac skinfold thickness is an independent risk factor for all-cause mortality in adult white males with risk apparently concentrated among people who are obese.
Srivanichakorn W, Godsland IF, Thomson H, et al., 2017, Fasting plasma glucose and variation in cardiometabolic risk factors in people with high-risk HbA1c-defined prediabetes: a cross-sectional multiethnic study., Diabetes Research and Clinical Practice, Vol: 134, Pages: 183-190, ISSN: 0168-8227
AIMS: Variation in cardiometabolic risk in prediabetes and any impacts of ethnicity on such variation have been little studied. In an ethnically diverse dataset, selected according to a high-risk HbA1c-based definition of prediabetes, we have investigated relationships between glycaemia and cardiometabolic risk factors and the influence of ethnicity on these relationships. METHODS: We undertook a cross-sectional analysis of baseline data from a diabetes prevention study in the UK and a chronic care clinic in Thailand, selected for people without diabetes (fasting plasma glucose <7.0 mmol/l) with HbA1c 6.0% - 6.4% (42-47 mmol/mol). Thai (n=158) and UK White (n=600), South Asian (n=112), Black (n=70) and other/mixed (n=103) groups were distinguished and measurements included fasting plasma glucose (FPG), blood pressure (BP), lipids and insulin resistance-related risk factors (IRFs). RESULTS: Independently of individual characteristics including ethnicity, only systolic BP was weakly associated with FPG (beta coefficient 1.76 (95%CI 0.10 to 3.42), p=0.03), and only LDL-c with IFG (FPG 5.6-<7) (adjusted -0.14 (-0.27, -0.003) p 0.04). There were no significant independent associations with cardiometabolic risk factors when categories of impaired fasting glucose (FPG ≥ 6.1 to <7.0 mmol/L) were considered. Relative to White, South Asian ethnicity was independently associated with lower systolic and diastolic BP, Black with lower triglycerides, cholesterol/HDL-c ratio and having 2 or more IRFs, and Thai with lower cholesterol/HDL-c ratio and all three non-white ethnicities with lower total and LDL cholesterol. CONCLUSION: In high-risk HbA1c-defined prediabetes additional measurement of FPG will add little to evaluation of cardiometabolic risk. Additionally, UK Whites tend to have the most adverse cardiometabolic profile of any ethnic group.
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
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
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
Misra S, Colclough K, Lupak L, et al., 2017, Clinical and biochemical definitions of Type 1 diabetes do not agree in a multi-ethnic young-onset diabetes cohort: results from the MY DIABETES study, Publisher: WILEY, Pages: 7-7, ISSN: 0742-3071
Pesl P, Herrero P, Reddy M, et al., 2017, Case-Based Reasoning for Insulin Bolus Advice., J Diabetes Sci Technol, Vol: 11, Pages: 37-42
BACKGROUND: Insulin bolus calculators assist people with Type 1 diabetes (T1D) to calculate the amount of insulin required for meals to achieve optimal glucose levels but lack adaptability and personalization. We have proposed enhancing bolus calculators by the means of case-based reasoning (CBR), an established problem-solving methodology, by individualizing and optimizing insulin therapy for various meal situations. CBR learns from experiences of past similar meals, which are described in cases through a set of parameters (eg, time of meal, alcohol, exercise). This work discusses the selection, representation and effect of case parameters used for a CBR-based Advanced Bolus Calculator for Diabetes (ABC4D). METHODS: We analyzed the usage and effect of selected parameters during a pilot study (n = 10), where participants used ABC4D for 6 weeks. Retrospectively, we evaluated the effect of glucose rate of change before the meal on the glycemic excursion. Feedback from study participants about the choice of parameters was obtained through a nonvalidated questionnaire. RESULTS: Exercise and alcohol were the most frequently used parameters, which was congruent with the feedback from study participants, who found these parameters most useful. Furthermore, cases including either exercise or alcohol as parameter showed a trend in reduction of insulin at the end of the study. A significant difference ( P < .01) was found in glycemic outcomes for meals where glucose rate of change was rising compared to stable rate of change. CONCLUSIONS: Results from the 6-week study indicate the potential benefit of including parameters exercise, alcohol and glucose-rate of change for insulin dosing decision support.
El-Laboudi AH, Godsland I, Johnston D, et al., 2016, Measures of Glycemic Variability In Type 1 Diabetes and the Effect of Real-Time Continuous Glucose Monitoring, Diabetes Technology & Therapeutics, Vol: 18, Pages: 806-812, ISSN: 1557-8593
Objective: To report the impact of continuous glucose monitoring (CGM) onglycemic variability (GV) indices, factors predictive of change and to correlatevariability with conventional markers of glycaemia.Methods: Data from the JDRF study of CGM in participants with type 1 diabeteswere used. Participants were randomised to CGM or self-monitored blood glucose(SMBG). GV indices at baseline, at 26 weeks in both groups, and at 52 weeks in thecontrol group were analysed. The associations of demographic and clinical factorswith change in GV indices from baseline to 26 weeks were evaluated.Results: Baseline data were available for 448 subjects. GV indices were all outsidenormative ranges (P<0.001). Inter-correlation between GV indices was common and,apart from coefficient of variation (CV), low blood glucose index (LBGI) andpercentage of glycemic risk assessment diabetes equation score attributable tohypoglycaemia (%GRADEhypoglycaemia), all indices correlate positively with HbA1c.There was strong correlation between time spent in hypoglycaemia, and CV, LBGIand %GRADEhypoglycaemia, but not with HbA1c. A significant reduction in all GVindices, except lability index and mean absolute glucose change per unit time (MAG),was demonstrated in the intervention group at 26 weeks compared with the controlgroup. Baseline factors predicting a change in GV with CGM include baselineHbA1c, baseline GV, frequency of daily SMBG and insulin pump use.Conclusions: CGM reduces most GV indices compared with SMBG in people withtype 1 diabetes. The strong correlation between time spent in hypoglycaemia and CV,LBGI and %GRADEhypoglycaemia highlights the value of these metrics in assessinghypoglycaemia as an adjunct to HbA1c in overall assessment of glycaemia.
Chamukuttan S, Ram J, Nanditha A, et al., 2016, Baseline level of 30-min plasma glucose is an independent predictor of incident diabetes among Asian Indians: analysis of two diabetes prevention programmes, DIABETES-METABOLISM RESEARCH AND REVIEWS, Vol: 32, Pages: 762-767, ISSN: 1520-7560
Misra S, Shields B, Colclough K, et al., 2016, South Asian individuals with diabetes who are referred for MODY testing in the UK have a lower mutation pick-up rate than white European people, Diabetologia, Vol: 59, Pages: 2262-2265, ISSN: 0012-186X
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.
CHANG C, LEE T, VAMOS E, et al., 2016, Impact of NHS Health Check on cardiovascular disease risk: difference-in-differences matching analysis, Canadian Medical Association Journal, ISSN: 1488-2329
Anagnostis P, Stevenson JC, Crook D, et al., 2016, Effects of gender, age and menopausal status on serum apolipoprotein concentrations, Clinical Endocrinology, Vol: 85, Pages: 733-740, ISSN: 1365-2265
ObjectiveTo undertake a comprehensive evaluation of apolipoprotein risk markers for cardiovascular disease (CVD) according to gender, age and menopausal status.DesignCross-sectional analysis of independent associations of gender, age and menopause with serum apolipoproteins.ParticipantsApparently healthy Caucasian premenopausal (n = 109) and postmenopausal (n = 252) women not taking oral contraceptives or hormone replacement, and Caucasian men (n = 307).MeasurementsSerum apolipoprotein (apo) B, A-I and A-II concentrations were measured, plus serum total cholesterol, low-density and high-density lipoprotein cholesterol (LDL-C and HDL-C, respectively), triglycerides, cholesterol in HDL subfractions and the apoB/apoA-I, LDL-C/apoB, HDL-C/apoA-I and HDL-C/apoA-II ratios. Analyses were undertaken with and without standardization for confounding characteristics and in 5-year age ranges.ResultsOverall, apoB concentrations were highest in men but in women rose with age and menopause to converge, in the age range of 50–55 years, with concentrations in men. The LDL-C/apoB ratio was generally higher in women than in men. ApoA-I concentrations were highest in postmenopausal women and lowest in men (standardized median (IQR) 144 (130, 158) vs 119 (108, 132) g/l, respectively, P < 0·001). ApoA-II concentrations were also highest in postmenopausal women but were lowest in premenopausal women (40·3 (37·5, 44·5) vs 32·9 (30·5, 35·7) g/l, respectively, P < 0·001). Nevertheless, postmenopausal women had HDL-C/apoA-I and HDL-C/apoA-II ratios approaching the lowest ratios, which were seen in men.ConclusionsConsistent with adverse effects on CVD risk, male gender, ageing in women and menopause were associated with increased apoB concentrations, and menopause and male gender were associated with a decreased cholesterol content of HDL particles.
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
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
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