Incident Type 2 diabetes and the effect of early regression to normoglycaemia in a population with impaired glucose regulation.

AIMS: To report contemporary regression rates from impaired glucose regulation to normal glucose tolerance, identify modifiable factors associated with early regression, and establish whether it affects subsequent diabetes risk in a population-based cohort. METHODS: Participants with impaired glucose regulation (impaired fasting glucose and/or impaired glucose tolerance on a 75-g oral glucose tolerance test) at baseline in the UK-based ADDITION-Leicester study had annual Type 2 diabetes re-screens for 5 years or until diabetes diagnosis. Logistic regression models investigated modifiable risk factors for regression to normal glucose tolerance at 1 year (n = 817). Cox regression models estimated subsequent diabetes risk (n = 630). RESULTS: At 1 year, 54% of participants had regressed to normal glucose tolerance, and 6% had progressed to diabetes. Regression to normal glucose tolerance was associated with weight loss of 0.1-3% [adjusted odds ratio 1.81 (95% CI 1.08, 3.03) compared with maintaining or gaining weight] and a waist circumference reduction of > 3 cm [adjusted odds ratio 1.78 (95% CI 1.03, 3.06) compared with maintaining or increasing waist circumference]. Those with normal glucose tolerance at 1 year subsequently had lower diabetes risk than those who remained with impaired glucose regulation [adjusted hazard ratio 0.19 (95% CI 0.10, 0.37)]. CONCLUSIONS: Early regression to normal glucose tolerance was associated with reduced diabetes incidence, and might be induced by small reductions in weight or waist circumference. If confirmed in experimental research, this could be a clear and achievable target for individuals diagnosed with impaired glucose regulation.

Diagnostic performance of using one- or two-HbA1c cut-point strategies to detect undiagnosed type 2 diabetes and impaired glucose regulation within a multi-ethnic population.

INTRODUCTION: We compared test performance and cost per case for strategies detecting diabetes on the oral glucose tolerance test (OGTT) using either (a) glycated haemoglobin (HbA1c) ≥ 6.5% (48 mmol/mol) or (b) two HbA1c thresholds where the first cut-point 'rules out' and the second 'rules in' diabetes. HbA1c values in between the thresholds require confirmatory glucose testing for diagnosis. MATERIALS AND METHODS: We conducted an analysis of adults aged 40-75 years from the Leicester Ethnic Atherosclerosis and Diabetes Risk (LEADER) cohort (Leicester, UK), from 2002 to 2008, who underwent oral glucose tolerance testing (OGTT) and HbA1c testing. RESULTS: From 8696 individuals (mean age 57.3 years, 73% white Europeans (WE) and 27% South Asians (SA)), HbA1c ≥ 6.5% produced sensitivity of 62.1% for detecting diabetes in WE and 78.9% in SA. Using two selected thresholds, HbA1c ≤ 5.8% (rule-in, 40 mmol/mol) and HbA1c ≥ 6.8% (rule-out, 51 mmol/mol) produced high sensitivity/specificity (> 91.0%) for detecting diabetes, however, 28.8% of the cohort with HbA1c 5.9%-6.7% required a subsequent glucose test. The two cut-point threshold produced a lower cost per case of diabetes detected in WE, compared to HbA1c ≥ 6.5% of £38.53 (1.89 to 86.81) per case, but was more expensive in SA by £84.50 (69.72 to 100.92) per case. Using a risk score to determine HbA1c testing, the same costs per case became £63.33 (23.33 to 113.26) in WE and £69.21 (55.60 to 82.41) in SA. CONCLUSION: Using a two-threshold strategy may have some benefits over a single cut-point; however, 28.8% of individuals required two blood tests.

Detection of impaired glucose regulation and/or type 2 diabetes mellitus, using primary care electronic data, in a multiethnic UK community setting.

AIMS/HYPOTHESIS: The aim of this study was to develop and validate a score for detecting the glycaemic categories of impaired glucose regulation (IGR) and type 2 diabetes using the WHO 2011 diagnostic criteria. METHODS: We used data from 6,390 individuals aged 40-75 years from a multiethnic population based screening study. We developed a logistic regression model for predicting IGR and type 2 diabetes (diagnosed using OGTT or HbA(1c) ≥ 6.5% [48 mmol/mol]) from data which are routinely stored in primary care. We developed the score by summing the ß coefficients. We externally validated the score using data from 3,225 participants aged 40-75 years screened as part of another study. RESULTS: The score includes age, ethnicity, sex, family history of diabetes, antihypertensive therapy and BMI. Fifty per cent of a population would need to be invited for testing to detect type 2 diabetes mellitus on OGTT with 80% sensitivity; this is slightly raised to 54% that need to be invited if using HbA(1c). Inviting the top 10% for testing, 9% of these would have type 2 diabetes mellitus using an OGTT (positive predictive value [PPV] 8.9% [95% CI 5.8%,12.8%]), 26% would have IGR (PPV 25.9% [95% CI 20.9%, 31.4%]). Using HbA(1c) increases the PPV to 19% for type 2 diabetes mellitus (PPV 18.6% [95% CI 14.2%, 23.7%]) and 28% for an HbA(1c) between 6.0% and 6.4% (PPV 28.3% [95% CI 23.1%, 34.0%]). CONCLUSIONS: The score can be used to reliably identify those with undiagnosed IGR and type 2 diabetes in multiethnic populations. This is the first score developed taking into account HbA(1c) in the diagnosis of type 2 diabetes.

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

AIMS: To compare the effects of intensive multifactorial cardiovascular risk intervention with standard care in screen-detected Type 2 diabetes. METHODS: Twenty general practices randomly invited 30 950 adults without diagnosed diabetes for screening (World Health Organization, 1999). In a cluster randomized controlled trial, screen-detected cases were assigned by practice allocation to receive intensive protocol-driven cardiovascular risk management (n = 146) or standard care (n = 199) according to local guidelines. Intensive intervention was designed to achieve an HbA(1c) of 48 mmol/mol (6.5%), blood pressure < 130/80 mmHg and total cholesterol < 3.5 mmol/l. Primary outcome was modelled 5-year coronary heart disease risk (UKPDS-CHD). Analysis was via intention to treat. RESULTS: After 1.1 years 339 (98%) individuals were still participating. There were significant reductions in HbA(1c) , blood pressure and total cholesterol from baseline in both groups [mean change for total study population -27.7 mmol/mol (-0.62%), -11.64/10.01 mmHg, -1.11 mmol/l]. After adjustment for baseline and clustering, significant inter-group differences were observed in mean changes from baseline for HbA(1c) {-28.5 mmol/mol [-0.7% (1.4)] vs. -27.5 mmol/mol [-0.6% (1.6)], P = 0.001}, blood pressure [systolic -16.2 (19.6) vs. -8.4 (18.6) mmHg, P < 0.001], total cholesterol [-1.3 (1.3) vs. -1.0 (1.2) mmol/l, P < 0.001] and weight [-3.8 (5.5) vs. -2.2 (5.5) kg, P = 0.01] in favour of intensive treatment. UKPDS 5-year coronary heart disease risk was reduced by 3.2% and 2.3%, respectively (P < 0.0001). Intensive intervention was associated with more lipid-lowering and anti-hypertensive but not hypoglycaemic medication use [odds ratios 2.5 (1.4-4.4), 5.5 (2.4-11.5), 1.6 (0.8-2.3); compared with standard care, P < 0.001, P = 0.003, P = 0.65]. Treatment satisfaction responses were superior with intensive intervention, with no increase in self-reported hypoglycaemia. CONCLUSION: Intensive intervention in patients with diabetes identified through systematic non-risk-factor-based screening significantly reduces modelled coronary heart disease risk. This is achieved predominantly with lipid-lowering and anti-hypertensive treatments with no adverse effect on quality of life or hypoglycaemia.

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

AIMS: Risk assessment scores identify those at high risk of impaired glucose regulation and Type 2 diabetes mellitus. To date no risk assessment scores that can be completed by a lay person have been developed and validated specifically for multiethnic populations in the UK. METHODS: We used data on 6186 subjects aged 40-75 years from a multiethnic UK screening study (73% white European, 22% South Asian). All participants were given a 75 g oral glucose tolerance test. We developed logistic regression models for predicting current impaired glucose regulation (impaired fasting glycaemia/impaired glucose tolerance) or Type 2 diabetes mellitus using data from anthropometric measurements and self-reported questionnaires. Using the best-fitting model, we developed the Leicester Risk Assessment score. We externally validated the score using data from 3171 subjects aged 40-75 years from a separate screening study. RESULTS: The components of the final model are age, ethnicity [white European vs. other (predominantly South Asian)], sex, first degree family history of diabetes, antihypertensive therapy or history of hypertension, waist circumference and body mass index. The score ranges from 0 to 47. Validating this model using the data from the second screening study gave an area under the receiver operator characteristic curve of 72% (95% confidence interval, 69-74%). A cut point of 16 had a sensitivity of 81% and a specificity of 45%. CONCLUSIONS: The Leicester Risk Assessment score can be used to identify those at high risk of impaired glucose regulation and Type 2 diabetes mellitus in UK multiethnic populations. The score is simple (seven questions) and non-invasive.

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

AIMS: There are calls to simplify the diagnosis of Type 2 diabetes mellitus (T2DM) to reduce the burden of undiagnosed disease. Glycated haemoglobin (HbA(1c)) is therefore being considered as a preferred diagnostic tool to replace the need for an oral glucose tolerance test (OGTT), considered by many as cumbersome and inconvenient. The aim of this study was to examine the potential impact of the preferred use of HbA(1c) as a diagnostic tool on the prevalence and phenotype of T2DM. METHODS: Analysis of the Leicester Ethnic Atherosclerosis and Diabetes Risk (LEADER) cohort for previously undiagnosed individuals between 40 and 75 years of age who had OGTT, repeated if within the diabetes range, and HbA(1c) results. We compared the prevalence and phenotype of subjects with T2DM based on either HbA(1c)> or =6.5% or OGTT using 1999 World Health Organization criteria. RESULTS: From the total population of 8696, we detected 291 (3.3%) with T2DM from using an OGTT, and 502 (5.8%) had HbA(1c)> or =6.5%. Of those diagnosed with T2DM by OGTT, 93 (1.2%) had HbA(1c) <6.5% and therefore would not have been classified as having T2DM using proposed criteria. Using HbA(1c) criteria resulted in 304 (3.5%) additional cases of T2DM, approximately doubling the prevalence. Of these 304 additional people, 172 (56.7%) had impaired glucose tolerance/impaired fasting glycaemia according to 1999 World Health Organization criteria. Using HbA(1c) criteria there was an increase of 2.2- and 1.4-fold in south Asians and white Europeans detected, respectively. CONCLUSIONS: Within this multi-ethnic cohort, we found that introducing HbA(1c)> or =6.5% as the preferred diagnostic test to diagnose T2DM significantly increased numbers detected with T2DM; however, some people were no longer detected as having T2DM.

Effect of insulin glargine on glycaemic control and weight in obese and non-obese people with type 2 diabetes: data from the AT.LANTUS trial.

AIMS: To explore glucose lowering response to insulin initiation or switch to insulin glargine in obese and non-obese individuals with type 2 diabetes mellitus (T2DM) and to examine weight gain and hypoglycaemic episodes in this group. METHODS: Post hoc subgroup analysis using data of obese and non-obese participants from a large multi-centre (4555 participants with T2DM), multi-national 24-week randomized controlled trial of investigator titrated insulin glargine versus patient self-managed titrated insulin glargine. This analysis was carried out to compare two subgroups: obese (> or =30 kg/m2) and non-obese (<30 kg/m2) participants. RESULTS: The mean body mass index (BMI) values were 33.7 kg/m2(n = 1833) and 25.9 kg/m(2)(n = 2755) in obese and non-obese subjects, respectively. There was a significant reduction in glycated haemoglobin (HbA1c) from baseline in both subgroups but no significant difference between subgroups (1.15 vs. 1.15%, p = 0.50). Overall, there was a 1.21 kg (s.d. 3.3) increase in weight in individuals who were non-obese and a 1.08 kg (s.d. 3.9) increase in obese individuals (p = 0.67). There was no significant difference in the proportion of participants achieving an HbA1c of <7.0% at 6 months in both the subgroups (28.8 vs. 27.1%, p = 0.20). In multiple logistic regression, BMI was not a prognostic factor in achieving a target of HbA1c < or = 7.0%. There was no significant difference in severe hypoglycaemic episodes between obese and non-obese subgroups (1.3 vs. 1.0%); however, significantly more non-obese individuals experienced nocturnal hypoglycaemic episodes(4.5 vs. 2.4%, p < 0.05). CONCLUSIONS: In this study, treatment with insulin glargine in people with T2DM was associated with a significant reduction in HbA1c without differential increase in weight gain in obese and non-obese subgroups. Rates of severe hypoglycaemia were not different between obese and non-obese subgroups.

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 beta 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.