General Practice and Primary Care - Research Publications
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ItemRationale and design of the ADDITION-Leicester study, a systematic screening programme and Randomised Controlled Trial of multi-factorial cardiovascular risk intervention in people with Type 2 Diabetes Mellitus detected by screening(BMC, 2010-02-19)BACKGROUND: Earlier diagnosis followed by multi-factorial cardiovascular risk intervention may improve outcomes in type 2 diabetes mellitus (T2DM). Latent phase identification through screening requires structured, appropriately targeted population-based approaches. Providers responsible for implementing screening policy await evidence of clinical and cost effectiveness from randomised intervention trials in screen-detected T2DM cases. UK South Asians are at particularly high risk of abnormal glucose tolerance and T2DM. To be effective national screening programmes must achieve good coverage across the population by identifying barriers to the detection of disease and adapting to the delivery of earlier care. Here we describe the rationale and methods of a systematic community screening programme and randomised controlled trial of cardiovascular risk management within a UK multiethnic setting (ADDITION-Leicester). DESIGN: A single-blind cluster randomised, parallel group trial among people with screen-detected T2DM comparing a protocol driven intensive multi-factorial treatment with conventional care. METHODS: ADDITION-Leicester consists of community-based screening and intervention phases within 20 general practices coordinated from a single academic research centre. Screening adopts a universal diagnostic approach via repeated 75g-oral glucose tolerance tests within an eligible non-diabetic population of 66,320 individuals aged 40-75 years (25-75 years South Asian). Volunteers also provide detailed medical and family histories; complete health questionnaires, undergo anthropometric measures, lipid profiling and a proteinuria assessment. Primary outcome is reduction in modelled Coronary Heart Disease (UKPDS CHD) risk at five years. Seven thousand (30% of South Asian ethnic origin) volunteers over three years will be recruited to identify a screen-detected T2DM cohort (n = 285) powered to detected a 6% relative difference (80% power, alpha 0.05) between treatment groups at one year. Randomisation will occur at practice-level with newly diagnosed T2DM cases receiving either conventional (according to current national guidelines) or intensive (algorithmic target-driven multi-factorial cardiovascular risk intervention) treatments. DISCUSSION: ADDITION-Leicester is the largest multiethnic (targeting >30% South Asian recruitment) community T2DM and vascular risk screening programme in the UK. By assessing feasibility and efficacy of T2DM screening, it will inform national disease prevention policy and contribute significantly to our understanding of the health care needs of UK South Asians. TRIAL REGISTRATION: Clinicaltrial.gov (NCT00318032).
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ItemDefining Obesity Cut-Off Points for Migrant South Asians(PUBLIC LIBRARY SCIENCE, 2011-10-19)BACKGROUND: Body mass index (BMI) and waist circumference (WC) are used to define cardiovascular and type 2 diabetes risk. We aimed to derive appropriate BMI and WC obesity cut-off points in a migrant South Asian population. METHODS: 4688 White Europeans and 1333 South Asians resident in the UK aged 40-75 years inclusive were screened for type 2 diabetes. Principal components analysis was used to derive a glycaemia, lipid, and a blood pressure factor. Regression models for each factor, adjusted for age and stratified by sex, were used to identify BMI and WC cut-off points in South Asians that correspond to those defined for White Europeans. FINDINGS: For South Asian males, derived BMI obesity cut-off points equivalent to 30.0 kg/m(2) in White Europeans were 22.6 kg/m(2) (95% Confidence Interval (95% CI) 20.7 kg/m(2) to 24.5 kg/m(2)) for the glycaemia factor, 26.0 kg/m(2) (95% CI 24.7 kg/m(2) to 27.3 kg/m(2)) for the lipid factor, and 28.4 kg/m(2) (95% CI 26.5 kg/m(2) to 30.4 kg/m(2)) for the blood pressure factor. For WC, derived cut-off points for South Asian males equivalent to 102 cm in White Europeans were 83.8 cm (95% CI 79.3 cm to 88.2 cm) for the glycaemia factor, 91.4 cm (95% CI 86.9 cm to 95.8 cm) for the lipid factor, and 99.3 cm (95% CI 93.3 cm to 105.2 cm) for the blood pressure factor. Lower ethnicity cut-off points were seen for females for both BMI and WC. CONCLUSIONS: Substantially lower obesity cut-off points are needed in South Asians to detect an equivalent level of dysglycemia and dyslipidemia as observed in White Europeans. South Asian ethnicity could be considered as a similar level of risk as obesity (in White Europeans) for the development of type 2 diabetes.
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ItemIndependent Effect of Ethnicity on Glycemia in South Asians and White Europeans(AMER DIABETES ASSOC, 2012-08)OBJECTIVE: HbA(1c) levels are higher in most ethnic groups compared with white Europeans (WEs) independent of glycemic control. This comparison has not been performed between South Asians (SAs) and WEs. We analyzed the independent effect of ethnicity on HbA(1c) and fasting and 2-h plasma glucose (FPG and 2 hrPG, respectively) between these groups. RESEARCH DESIGN AND METHODS: Analysis of the ADDITION-Leicester study, in which 4,688 WEs and 1,352 SAs underwent oral glucose tolerance testing, HbA(1c), and other risk factor measurements. RESULTS: Significant associations with HbA(1c) included ethnicity, FPG, 2 hrPG, and homeostasis model assessment of β-cell function (P < 0.001); age and sex (P < 0.01); and fasting insulin and potassium (P < 0.05). After adjusting for these and other risk factors, SAs demonstrated higher HbA(1c) (6.22 and 6.02%, mean difference 0.20%, 0.10-0.30, P < 0.001), FPG (5.15 and 5.30 mmol/L, mean difference 0.15 mmol/L, 0.09-0.21, P < 0.001), and 2 hrPG (5.82 and 6.57 mmol/L, mean difference 0.75 mmol/L, 0.59-0.92, P < 0.001) compared with WEs, respectively. CONCLUSIONS: HbA(1c), FPG, and 2 hrPG levels were higher in SAs independent of factors affecting glycemic control.
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ItemThe Association of the Triglyceride-to-HDL Cholesterol Ratio with Insulin Resistance in White European and South Asian Men and Women(PUBLIC LIBRARY SCIENCE, 2012-12-10)INTRODUCTION: There is recent interest surrounding the use of the triglyceride-to-HDL cholesterol ratio as a surrogate marker of insulin resistance in clinical practice, as it may identify people at high risk of developing diabetes or its complications. However, it has been suggested using this lipid ratio may not be appropriate for measuring insulin resistance in African-Americans, particularly women. We investigated if this inconsistency extended to South Asian women in a UK multi-ethnic cohort of White Europeans and South Asians. METHODS: Cross-sectional analysis was done of 729 participants from the ADDITION-Leicester study from 2005 to 2009. The association between tertiles of triglyceride-to-HDL cholesterol ratio to fasting insulin, homeostatic model of assessment for insulin resistance (HOMA1-IR), quantitative insulin sensitivity check index (QUICKI) and glucose: insulin ratio was examined with adjustment for confounding variables. RESULTS: Incremental tertiles of the triglyceride-to-HDL cholesterol ratio demonstrated a significant positive association with levels of fasting insulin, HOMA1-IR, glucose: insulin ratio and a negative association with QUICKI in White European men (n = 255) and women (n = 250) and South Asian men (n = 124) (all p<0.05), but not South Asian women (n = 100). A significant interaction was demonstrated between sex and triglyceride-to-HDL cholesterol ratio tertiles in South Asians only (p<0.05). The area under the receiver operating characteristic curve for triglyceride-to-HDL cholesterol ratio to detect insulin resistance, defined as the cohort HOMA1-IR ≥ 75(th) percentile (3.08), was 0.74 (0.67 to 0.81), 0.72 (0.65 to 0.79), 0.75 (0.66 to 0.85) and 0.67 (0.56 to 0.78) in White European men and women, South Asian men and women respectively. The optimal cut-points for detecting insulin resistance were 0.9-1.7 in mmol/l (2.0-3.8 in mg/dl) for the triglyceride-to-HDL ratio. CONCLUSION: In South Asian women the triglyceride-to-HDL cholesterol ratio was not associated with insulin resistance; therefore there may be limitations in its use as a surrogate marker in this group.
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ItemAdipocytokine Associations with Insulin Resistance in British South Asians(HINDAWI LTD, 2013)Aims. Adipocytokines are implicated in the pathogenesis of type 2 diabetes and may represent identifiable precursors of metabolic disease within high-risk groups. We investigated adiponectin, leptin, and TNF- α and assessed the contribution of these molecules to insulin resistance in south Asians. Hypothesis. South Asians have adverse adipocytokine profiles which associate with an HOMA-derived insulin resistance phenotype. Methods. We measured adipocytokine concentrations in south Asians with newly diagnosed impaired glucose tolerance or Type 2 Diabetes Mellitus in a case-control study. 158 (48.5% males) volunteers aged 25-75 years with risk factors for diabetes but no known vascular or metabolic disease provided serum samples for ELISA and bioplex assays. Results. Total adiponectin concentration progressively decreased across the glucose spectrum in both sexes. A reciprocal trend in leptin concentration was observed only in south Asian men. Adiponectin but not leptin independently associated with HOMA-derived insulin resistance after logistic multivariate regression. Conclusion. Diasporic south Asian populations have an adverse adipocytokine profile which deteriorates further with glucose dysregulation. Insulin resistance is inversely associated with adiponectin independent of BMI and waist circumference in south Asians, implying that adipocytokine interplay contributes to the pathogenesis of metabolic disease in this group.
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ItemJoint Prevalence of Diabetes, Impaired Glucose Regulation, Cardiovascular Disease Risk and Chronic Kidney Disease in South Asians and White Europeans(PUBLIC LIBRARY SCIENCE, 2013-01-30)BACKGROUND: Multiple vascular risk factors may confer very high risk, but the degree of commonality between risk factors is unclear, particularly among ethnic minorities. Furthermore, it is unknown what impact this commonality will have on the UK-based NHS Health Check Programme; a vascular disease prevention programme that screens individuals aged 40-74 years. We estimated the joint prevalence of diabetes, impaired glucose regulation (IGR), high cardiovascular disease (CVD) risk and chronic kidney disease (CKD) among White Europeans and South Asians who would be eligible for the Programme. METHODS: Cross-sectional data were analysed for 3707 participants (23.6% South Asian) in a screening study set in Leicestershire, UK. Diabetes and IGR were screen-detected. CKD may have been diagnosed previously. IGR was defined as impaired fasting glucose and/or impaired glucose tolerance, and high CVD risk as 10 year risk greater than 20%. RESULTS: Among males, South Asians had higher prevalence than White Europeans of diabetes (9.0% vs. 3.9%, respectively, p<0.001), IGR (12.5% vs. 9.2%, p = 0.06), and high CVD risk (39.1% vs. 33.1%, p = 0.03), but lower prevalence of CKD (1.5% vs. 4.6%, p<0.01). Among females, South Asians had higher prevalence than White Europeans of diabetes (7.4% vs. 3.3%, p<0.001), but lower prevalence of CKD (3.7% vs. 13.0%, p <0.001) and CVD risk (2.4% vs. 4.6%, p = 0.03), and a non-significant difference in IGR prevalence. At least one risk factor was diagnosed in 34% of participants, and all of them in 0.4%, suggesting that 723,589-734,589 more individuals each year will require monitoring following implementation of the Health Check Programme. CONCLUSIONS: The collective prevalence of risk factors for vascular disease in this population was high, but there was little overlap between the risk factors, and prevalence differed by ethnicity. This has implications for service delivery and resources, and should be considered when planning screening and intervention programmes.
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ItemInvestigating Endothelial Activation and Oxidative Stress in relation to Glycaemic Control in a Multiethnic Population(HINDAWI LTD, 2012)AIM: An exploration of ethnic differences in measures of oxidative stress and endothelial activation in relation to known cardiovascular risk factors within South Asians (SA) and White Europeans (WE) residing in the UK. METHODS: 202 participants within a UK multiethnic population provided biomedical and anthropometric data. Human urinary 2,3-dinor-8-iso-prostaglandin-F1α and plasma ICAM-1 were quantified as measures of oxidative stress and endothelial activation, respectively. RESULTS: 2,3-Dinor-8-iso-prostaglandin-F1α levels were significantly higher in the SA group compared to WE group (10.36 (95% CI: 9.09, 11.79) versus 8.46 (7.71, 9.29), P = 0.021) after adjustment for age, gender, smoking status, body weight, HbA1c, and medication. Oxidative stress was positively associated with HbA1c (β = 1.08, 95% CI:1.02, 1.14, P = 0.009), fasting (β = 1.06, 95% CI: 1.02, 1.10, P = 0.002), and 2 hr glucose (β = 1.02, 95% CI: 1.00, 1.04, P = 0.052). In each adjusted model, SA continued to have elevated levels of oxidative stress compared to WE. ICAM-1 levels were significantly higher in the composite IGR group compared to the normoglycaemic group (P < 0.001). No ethnic differences in ICAM-1 were observed. CONCLUSION: These results suggest that SA are more susceptible to the detrimental effects of hyperglycaemia-induced oxidative stress at lower blood glucose thresholds than WE. Further research into the potential mechanisms involved is warranted.
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ItemBody Mass Index and Waist Circumference Cut-Points in Multi-Ethnic Populations from the UK and India: The ADDITION-Leicester, Jaipur Heart Watch and New Delhi Cross-Sectional Studies(PUBLIC LIBRARY SCIENCE, 2014-03-05)AIMS: To derive cut-points for body mass index (BMI) and waist circumference (WC) for minority ethnic groups that are risk equivalent based on endogenous glucose levels to cut-points for white Europeans (BMI 30 kg/m2; WC men 102 cm; WC women 88 cm). MATERIALS AND METHODS: Cross-sectional data from participants aged 40-75 years: 4,672 white and 1,348 migrant South Asian participants from ADDITION-Leicester (UK) and 985 indigenous South Asians from Jaipur Heart Watch/New Delhi studies (India). Cut-points were derived using fractional polynomial models with fasting and 2-hour glucose as outcomes, and ethnicity, objectively-measured BMI/WC, their interaction and age as covariates. RESULTS: Based on fasting glucose, obesity cut-points were 25 kg/m2 (95% Confidence Interval: 24, 26) for migrant South Asian, and 18 kg/m2 (16, 20) for indigenous South Asian populations. For men, WC cut-points were 90 cm (85, 95) for migrant South Asian, and 87 cm (82, 91) for indigenous South Asian populations. For women, WC cut-points were 77 cm (71, 82) for migrant South Asian, and 54 cm (20, 63) for indigenous South Asian populations. Cut-points based on 2-hour glucose were lower than these. CONCLUSIONS: These findings strengthen evidence that health interventions are required at a lower BMI and WC for South Asian individuals. Based on our data and the existing literature, we suggest an obesity threshold of 25 kg/m2 for South Asian individuals, and a very high WC threshold of 90 cm for South Asian men and 77 cm for South Asian women. Further work is required to determine whether lower cut-points are required for indigenous, than migrant, South Asians.