Samiul A. Mostafa

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.

A comparison of cost per case detected of screening strategies for Type 2 diabetes and impaired glucose regulation: modelling study.

BACKGROUND To determine a cost per case detected for different screening strategies for both Type 2 diabetes alone and in combination with impaired glucose regulation. METHODS Bayesian framework modelling study using data from the ADDITION-Leicester screening study in UK multi-ethnic primary care setting. There were 5794 people aged 40-75 years (77.4% white European; 22.6% south Asian) without previously known diabetes. We compared 212 screening strategies including blood tests, a computer practice data score and a risk score, as part of a multi-stage process that all used an oral glucose tolerance test as the diagnostic test. Simulation models were created using sensitivity estimates for the expected cost per case. RESULTS The estimated costs per case identified for the 18 most sensitive strategies varied from £457 to £1639 (€526-1886, for £1=€1.15) for diabetes and £148-913 (€170-1050) for both diabetes and impaired glucose regulation. The lowest costing diabetes strategies ranged from £457 to £523 (€526-601) involving a two-stage screening strategy, a non-invasive risk stratifying tool followed by a blood test, producing sensitivities ranging from 67.1 to 82.4%. CONCLUSION Screening a population using a non-invasive risk stratification tool followed by a screening blood test is the most cost-effective method of screening for diabetes and abnormal glucose tolerance.

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.

The Association of the Triglyceride-to-HDL Cholesterol Ratio with Insulin Resistance in White European and South Asian Men and Women

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≥75th 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.

Conduit vessel stiffness in British south Asians of Indian descent relates to 25-hydroxyvitamin D status.

Background: South Asians migrating to Northern latitudes are more susceptible to premature cardiovascular disease (CVD) than expected for given levels of blood pressure. Vitamin D deficiency is common in this group and may play an important role mediating vascular wall senescence in response to central pressure effects. Methods: A cross-sectional association study. South Asian and White European participants were randomly recruited from a population-based diabetes-screening programme. Carotid–femoral pulse wave velocity (cfPWV), biochemistry (25-hydroxyvitamin D, fasting glucose), anthropometrics, resting blood pressure and a physical activity measure (International Physical Activity Questionnaire) were measured under controlled conditions. Participants: One hundred and thirty-two and 125 age-matched South Asians and White Europeans not taking vitamin D supplementation with a risk factor for diabetes but no overt CVD. Results: Age (mean south Asian: 55.7 vs. White European: 56.0 years), mean arterial pressure (MAP) and calculated CVD risk were similar in both groups. Unadjusted cfPWV (m/s) was higher (9.32 vs. 8.68 P = 0.001) and 25-hydroxyvitamin D (nmol/l) lower in (21.29 vs. 52.5 P < 0.001) south Asians. 25-Hydroxyvitamin D independently associated with cfPWV in multivariate modelling adjusted for age, MAP, sex, glucose, heart rate, vasoactive medication and south Asian ethnicity (R2 = 0.73, P = 0.004). 25-Hydroxyvitamin D but not physical activity was negatively correlated with cfPWV independent of south Asian ethnicity. Conclusion: Aortic stiffness is increased in British Indo-Asians without vascular disease despite conventional risk profiles, which are comparable to age-matched white Europeans. This effect may be mediated by a greater pressure-dependent increase in stiffness in individuals with vitamin D insufficiency.

The cost-effectiveness of testing strategies for type 2 diabetes: a modelling study.

BACKGROUND An estimated 850,000 people have diabetes without knowing it and as many as 7 million more are at high risk of developing it. Within the NHS Health Checks programme, blood glucose testing can be undertaken using a fasting plasma glucose (FPG) or a glycated haemoglobin (HbA1c) test but the relative cost-effectiveness of these is unknown. OBJECTIVES To estimate and compare the cost-effectiveness of screening for type 2 diabetes using a HbA1c test versus a FPG test. In addition, to compare the use of a random capillary glucose (RCG) test versus a non-invasive risk score to prioritise individuals who should undertake a HbA1c or FPG test. DESIGN Cost-effectiveness analysis using the Sheffield Type 2 Diabetes Model to model lifetime incidence of complications, costs and health benefits of screening. SETTING England; population in the 40-74-years age range eligible for a NHS health check. DATA SOURCES The Leicester Ethnic Atherosclerosis and Diabetes Risk (LEADER) data set was used to analyse prevalence and screening outcomes for a multiethnic population. Alternative prevalence rates were obtained from the literature or through personal communication. METHODS (1) Modelling of screening pathways to determine the cost per case detected followed by long-term modelling of glucose progression and complications associated with hyperglycaemia; and (2) calculation of the costs and health-related quality of life arising from complications and calculation of overall cost per quality-adjusted life-year (QALY), net monetary benefit and the likelihood of cost-effectiveness. RESULTS Based on the LEADER data set from a multiethnic population, the results indicate that screening using a HbA1c test is more cost-effective than using a FPG. For National Institute for Health and Care Excellence (NICE)-recommended screening strategies, HbA1c leads to a cost saving of £12 and a QALY gain of 0.0220 per person when a risk score is used as a prescreen. With no prescreen, the cost saving is £30 with a QALY gain of 0.0224. Probabilistic sensitivity analysis indicates that the likelihood of HbA1c being more cost-effective than FPG is 98% and 95% with and without a risk score, respectively. One-way sensitivity analyses indicate that the results based on prevalence in the LEADER data set are insensitive to a variety of alternative assumptions. However, where a region of the country has a very different joint HbA1c and FPG distribution from the LEADER data set such that a FPG test yields a much higher prevalence of high-risk cases relative to HbA1c, FPG may be more cost-effective. The degree to which the FPG-based prevalence would have to be higher depends very much on the uncertain relative uptake rates of the two tests. Using a risk score such as the Leicester Practice Database Score (LPDS) appears to be more cost-effective than using a RCG test to identify individuals with the highest risk of diabetes who should undergo blood testing. LIMITATIONS We did not include rescreening because there was an absence of required relevant evidence. CONCLUSIONS Based on the multiethnic LEADER population, among individuals currently attending NHS Health Checks, it is more cost-effective to screen for diabetes using a HbA1c test than using a FPG test. However, in some localities, the prevalence of diabetes and high risk of diabetes may be higher for FPG relative to HbA1c than in the LEADER cohort. In such cases, whether or not it still holds that HbA1c is likely to be more cost-effective than FPG depends on the relative uptake rates for HbA1c and FPG. Use of the LPDS appears to be more cost-effective than a RCG test for prescreening. FUNDING The National Institute for Health Research Health Technology Assessment programme.

Diagnosing type 2 diabetes and identifying high-risk individuals using the new glycated haemoglobin (HbA1c) criteria

Up to 30% of people with type 2 diabetes remain undiagnosed in the UK on average for 7 years, and complications are already present at diagnosis in about 50% of people.1,2 Furthermore, impaired glucose regulation or ‘high risk of diabetes’ (prediabetes, impaired glucose tolerance, and.or impaired fasting glucose)1,2 is highly prevalent, at around 15% in adults, and carries an increased risk of progression to type 2 diabetes and vascular complications. Early initiation of lifestyle and therapeutic measures significantly reduces long-term complications of diabetes. Furthermore, intensive lifestyle intervention and/or pharmacotherapy reduce progression to diabetes by 40.60% in individuals at high risk of diabetes. Accurate diagnosis of diabetes and routine screening to identify high-risk individuals is important to improve outcomes. Availability of a simple, accessible, and reliable diagnostic test is crucial. Diagnosis of diabetes has been traditionally based on plasma glucose measurements.3 The fasting plasma glucose (FPG) test is more commonly used on pragmatic grounds but still involves overnight fasting and has modest sensitivity for detecting diabetes compared to the oral glucose tolerance test (OGTT).4 In contrast, the OGTT is sometimes considered as the ‘gold standard’ test but has poor test reproducibility and is inconvenient and costly.4 Furthermore glucose measurement can …

A simple strategy for screening for glucose intolerance, using glycated haemoglobin, in individuals admitted with acute coronary syndrome

Diabet. Med. 29, 838–843 (2012)