Balasubramanian Thiagarajan Srinivasan

The Leicester Risk Assessment score for detecting undiagnosed Type 2 diabetes and impaired glucose regulation for use in a multiethnic UK setting

Diabet. Med. 27, 887–895 (2010)

Rationale 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

BackgroundEarlier 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).DesignA single-blind cluster randomised, parallel group trial among people with screen-detected T2DM comparing a protocol driven intensive multi-factorial treatment with conventional care.MethodsADDITION-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.DiscussionADDITION-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 registrationClinicaltrial.gov (NCT00318032).

The potential impact of using glycated haemoglobin as the preferred diagnostic tool for detecting Type 2 diabetes mellitus

Diabet. Med. 27, 762–769 (2010)

The potential impact and optimal cut-points of using glycated haemoglobin, HbA1c, to detect people with impaired glucose regulation in a UK multi-ethnic cohort

INTRODUCTION Recommended diagnostic cut-points to detect impaired glucose regulation (IGR, also termed prediabetes: impaired fasting glucose and/or impaired glucose tolerance based on WHO 1999 criteria) are HbA1c 6.0-6.4% and 5.7-6.4% from an International Expert Committee and American Diabetes Association, respectively. We investigated the impact on prevalence/phenotype from using these criteria compared to IGR detected on oral glucose tolerance testing (OGTT) and determined optimal HbA1c cut-points for IGR in a multi-ethnic cohort. METHODS Analysis of 8696 participants in the LEADER study of primary care individuals aged 40-75 years without diabetes, in Leicestershire (UK) who underwent OGTT and had HbA1c measured. RESULTS Use of OGTT detected less people with IGR (n=1407, 16.2%) compared to HbA1c 6.0-6.4% (n=1610, 18.5%) and HbA1c 5.7-6.4%(n=3904, 44.9%), a 1.1- and 2.8-fold increase in prevalence, respectively. There were 930 (10.7%) and 534 (6.1%) people with IGR on OGTT not detected using HbA1c 6.0-6.4% and 5.7-6.4%, respectively. From ROC curve analysis, the optimal cut-point for detecting IGR in white Europeans was HbA1c>or=5.8%, sensitivity/specificity 61.5%/67.9%, but in south Asians HbA1c>or=6.0%, sensitivity/specificity 63.8%/69.4%. CONCLUSION Recommended HbA1c cut-points to detect IGR significantly increase numbers detected, however introduce a change in people identified. Using HbA1c 6.0-6.4% lacks sensitivity in white Europeans, but is a reasonable option in south Asians.

Recent advances in the management of type 2 diabetes mellitus: a review

Type 2 diabetes mellitus (T2DM) is a progressive disorder caused by a combination of insulin resistance and β cell dysfunction. It is associated with an increased and premature risk of cardiovascular disease as well as specific microvascular complications such as retinopathy, nephropathy and neuropathy. In the last 5 years new glucose lowering drugs acting on novel pathways have been developed, licensed and launched, such as the glucagon-like peptide (GLP-1) agonists (exenatide) and dipeptidyl peptidase (DPP-IV) inhibitors such as sitagliptin and vildagliptin. This review looks at these new agents in terms of their mode of action, pharmacokinetics and use in clinical practice. This review also includes new agents in the area of weight loss that may have a positive effect for glucose management—for example, rimonabant.

The potential impact of using glycated haemoglobin as the preferred diagnostic tool for detecting Type 2 diabetes mellitus.

Diabet. Med. 27, 762–769 (2010)

Independent Effect of Ethnicity on Glycemia in South Asians and White Europeans

OBJECTIVE HbA1c 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 HbA1c and fasting and 2-h plasma glucose (FPG and 2hrPG, 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, HbA1c, and other risk factor measurements. RESULTS Significant associations with HbA1c included ethnicity, FPG, 2hrPG, 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 HbA1c (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 2hrPG (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 HbA1c, FPG, and 2hrPG levels were higher in SAs independent of factors affecting glycemic control.

Should glycated haemoglobin (HbA1c) be used to detect people with type 2 diabetes mellitus and impaired glucose regulation

There is a need to simplify screening tests for type 2 diabetes mellitus (T2DM) so patients can be identified earlier and more efficiently. Glycated haemoglobin (HbA1c) has been recommended by some international organisations as a diagnostic tool for detecting T2DM and impaired glucose regulation (IGR, also termed prediabetes and includes impaired fasting glucose and/or impaired glucose tolerance). The HbA1c cut-point of ≥6.5% (48 mmol/mol) has been selected as diagnostic for T2DM, while the cut-points for IGR are debated by the different international organisations: an International Expert Committee has suggested using HbA1c 6.0–6.4% (42–46 mmol/mol); however, the American Diabetes Association has recommended using HbA1c 5.7–6.4% (39–46 mmol/mol). Some countries will adopt a new method of reporting HbA1c values in millimoles per mole (mmol/mol). Use of HbA1c has some logistical advantages over using an oral glucose tolerance test (OGTT). As patients do not need to fast, appointments do not need to be limited to the morning. The HbA1c result reflects longer term glycaemia and is less affected by recent physical/emotional stress. However, there is some debate as to whether HbA1c should replace fasting plasma glucose or the OGTT. As the two tests detect different people, some individuals with diabetes detected on OGTT will no longer be classified as having T2DM using HbA1c ≥6.5% criteria. Furthermore, some medical conditions can result in HbA1c assay measurements not reflecting glycaemic control over the last 2–3 months; these include haematological disorders, renal failure, and chronic excess alcohol consumption.

Intensive multifactorial intervention improves modelled coronary heart disease risk in screen‐detected Type 2 diabetes mellitus: a cluster randomized controlled trial

Diabet. Med. 29, 531–540 (2012)

Intensive multifactorial intervention improves modelled coronary heart disease risk in screen-detected Type2 diabetes mellitus: A cluster randomized controlled trial

Diabet. Med. 29, 531–540 (2012)