Publications
342 results found
Loh WJ, Stevenson JC, Godsland IF, 2019, Independent relationships between bone mineral density, regional body fat and insulin sensitivity in white males, Clinical Endocrinology, Vol: 91, Pages: 63-71, ISSN: 1365-2265
BACKGROUND: Adiposity and insulin sensitivity may affect bone mineral density (BMD) but the confounding effect of weight hinders discrimination of independent associations. We explored whether regional fat masses and insulin sensitivity are independently related to BMD. MATERIALS AND METHODS: Relationships between total and regional body fat, insulin sensitivity and measures of BMD in 8 different regions were evaluated in a cross-section of 590 generally healthy, white males, 274 of whom received measurement of insulin sensitivity (Si) using the intravenous glucose tolerance test. Measurements included total, android and gynoid fat and lean body mass and regional BMDs by dual-energy X-ray absorptiometry. Linear regression analyses were combined in a mediation analysis to explore associations with each regional BMD. RESULTS: Weight correlated positively with total fat mass (R2 =0.67, p<0.001) and negatively with Si (R2 =0.14, p<0.001). Body composition measures were consistently positively related to BMD in all regions except lumbar and thoracic spine. Accounting for body weight rendered negative the majority of associations between total and regional fat masses and BMDs. An independent association between android fat and spine BMD was particularly apparent. Si was positively associated with total and limb BMD (p<0.01) specifically among exercisers. Accounting for Si diminished the associations of total fat (negative) and lean body mass (positive) with total and limb BMD. CONCLUSION: Android fat is independently negatively associated with spine BMD. Among those taking exercise, increased insulin sensitivity is associated with higher limb BMD and may underlie positive associations between lean body mass and BMD.
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
Godsland IF, 2019, Stats: abuse by researchers' lust for certainty, Nature, Vol: 569, Pages: 192-192, ISSN: 0028-0836
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.
Izzi-Engbeaya CN, Comninos AN, Clarke S, et al., 2018, The effects of kisspeptin on β-cell function, serum metabolites and appetite in humans, Diabetes, Obesity and Metabolism, Vol: 20, Pages: 2800-2810, ISSN: 1462-8902
AimsTo investigate the effect of kisspeptin on glucose‐stimulated insulin secretion and appetite in humans.Materials and methodsIn 15 healthy men (age: 25.2 ± 1.1 years; BMI: 22.3 ± 0.5 kg m−2), we compared the effects of 1 nmol kg−1 h−1 kisspeptin versus vehicle administration on glucose‐stimulated insulin secretion, metabolites, gut hormones, appetite and food intake. In addition, we assessed the effect of kisspeptin on glucose‐stimulated insulin secretion in vitro in human pancreatic islets and a human β‐cell line (EndoC‐βH1 cells).ResultsKisspeptin administration to healthy men enhanced insulin secretion following an intravenous glucose load, and modulated serum metabolites. In keeping with this, kisspeptin increased glucose‐stimulated insulin secretion from human islets and a human pancreatic cell line in vitro. In addition, kisspeptin administration did not alter gut hormones, appetite or food intake in healthy men.ConclusionsCollectively, these data demonstrate for the first time a beneficial role for kisspeptin in insulin secretion in humans in vivo. This has important implications for our understanding of the links between reproduction and metabolism in humans, as well as for the ongoing translational development of kisspeptin‐based therapies for reproductive and potentially metabolic conditions.
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.
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., J Assoc Physicians India, Vol: 66, Pages: 22-26, ISSN: 0004-5772
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 2nd 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 2nd 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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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
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.
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.
Misra S, Godsland I, Lupak L, et al., 2017, Predictors of C-Peptide in a Young-Onset Diabetes UK Multiethnic Cohort: Results from the MY DIABETES Study, 77th Scientific Sessions of the American-Diabetes-Association, Publisher: AMER DIABETES ASSOC, Pages: A421-A421, 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
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
Anagnostis P, Galanis P, Chatzistergiou V, et al., 2017, The effect of hormone replacement therapy and tibolone on lipoprotein (a) concentrations in postmenopausal women: A systematic review and meta-analysis, MATURITAS, Vol: 99, Pages: 27-36, ISSN: 0378-5122
Objective:Data on the effect of hormone replacement therapy (HRT) and tibolone on lipoprotein (a) [Lp(a)], an independent risk factor for cardiovascular disease, are heterogeneous and conflicting. Studies of the effect of HRT and tibolone on Lp(a) concentrations in post-menopausal women are reviewed in this meta-analysis.Design and methods:MEDLINE, Scopus, EMBASE and Cochrane databases were searched (up to February 10, 2017). Two researchers identified randomized controlled studies and extracted data. Potential controversies were resolved by a third reviewer.Results:In 24 eligible studies, HRT caused a significant reduction in Lp(a) concentrations compared with placebo or no treatment [mean relative difference: −20.35%, 95% Confidence Interval (CI): −25.33% to −15.37%, p < 0.0001], with significant heterogeneity between studies (I2 = 98.5%), but without evidence of publication bias. No significant effect was found for tibolone (n = 7) (mean relative difference: −23.84%, 95% CI: −63.43% to 15.74%, p = 0.238) (I2 = 98.7%, but without publication bias). Oral estrogen caused a greater reduction in Lp(a) concentrations than transdermal estrogen (n = 10) (mean relative difference: 37.66%, 95% CI: 16.84% to 58.48%, p < 0.0001), with significant heterogeneity between studies (I2 = 99%), but no evidence of publication bias. No difference was observed when continuous was compared with cyclical HRT, conventional with low-dose estrogen, and estrogen monotherapy with estrogen combined with progestogen. No difference was observed between HRT and tibolone regarding their effect on Lp(a).Conclusions:HRT significantly decreases Lp(a) concentrations, with oral being more effective than transdermal estradiol. The type of HRT, dose of estrogen and addition of progestogen do not seem to modify the Lp(a)-lowering effect of HRT.
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.
Petropoulou K, Chambers ES, Morrison DJ, et al., 2016, Identifying crop variants with high resistant starch content to maintain healthy glucose homeostasis, Nutrition Bulletin, Vol: 41, Pages: 372-377, ISSN: 1467-3010
Identifying dietary tools that prevent disordered insulin secretion from pancreatic β-cells is an attractive strategy to combat the increasing prevalence of type 2 diabetes. Dietary resistant starch has been linked to improvements in the function of β-cells, possibly via increased colonic fermentation and production of short-chain fatty acids (SCFAs). Increasing the resistant starch content of commonly consumed foods could therefore maintain glucose homeostasis at the population level. As part of Biotechnology and Biological Sciences Research Council (BBSRC) Diet and Health Research Industry Club (DRINC) initiative, variants of Pisum sativum L. (pea) are being investigated to identify the features of pea starch that make it resistant to digestion and available for colonic fermentation and SCFA production. Parallel in vitro and in vivo studies are being conducted using both whole pea seeds and pea flour to facilitate a better understanding of how cells in the pea cotyledons are affected by processing and, in turn, how this influences starch digestibility. Trials in human volunteers are being used to monitor a full spectrum of short- and long-term physiological responses relevant to pancreatic β-cell function and glucose homeostasis. This project is providing new insights into variants of crops that are associated with the specific types of resistant starch that provide the best protection against defects in insulin secretion and function.
Hill NE, Campbell C, Buchanan P, et al., 2016, Biochemical, physiological and psychological changes during endurance exercise in people with type 1 diabetes., Journal of Diabetes Science and Technology, Vol: 11, Pages: 529-536, ISSN: 1932-2968
BACKGROUND: Increasing numbers of people with diabetes are adopting exercise programs. Fear of hypoglycemia, hypoglycemia itself, and injuries are major issues for many people with diabetes undertaking physical activity. The purpose of this study was to investigate the effects of type 1 diabetes mellitus on the risk of hypoglycemia, glycemic variability, exercise performance, changes in body composition, changes in insulin dosage, and psychosocial well-being during a multiday endurance exercise event. METHODS: Eleven participants (7 with type 1 diabetes, 4 with normal glucose tolerance) undertook a 15-day, 2300 km cycling tour from Barcelona to Vienna. Data were prospectively collected using bike computers, continuous glucose monitors, body composition analyzers, and mood questionnaires. RESULTS: Mean blood glucose in riders with and without diabetes significantly reduced as the event progressed. Glycemic variability and time spent in hypoglycemia did not change throughout the ride for either set of riders. Riders with diabetes in the lowest quartile of sensor glucose values had significantly reduced power output. Percentage body fat also significantly fell. Hypo- and hyperglycemia provoked feelings of anxiety and worry. CONCLUSIONS: This is the first study to describe a real-time endurance event in type 1 diabetes, and provides important new data that cannot be studied in laboratory conditions. Hypoglycemia continues to occurs in spite of peer support and large reductions in insulin dose. Glycemic variability is shown as a potential barrier to participation in physical activity through effects on mood and psychological well-being.
Agha-Jaffar R, Misra S, Oliver N, et al., 2016, Ethnic variations in glucose and the interaction with fetal growth in a multi-ethnic inner city antenatal cohort, 52nd Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), Publisher: Springer Verlag, Pages: S447-S448, 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.
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.
Meienberg F, Yee M, Johnston D, et al., 2016, Liver fat in adults with GH deficiency: comparison to matched controls and the effect of GH replacement, Clinical Endocrinology, Vol: 85, Pages: 76-84, ISSN: 1365-2265
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
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
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