Stephen Colagiuri

International Expert Committee Report on the Role of the A1C Assay in the Diagnosis of Diabetes

Members of the International Expert Committee have recommended that diabetes should be diagnosed if A1C is ≤6.5%, without need to measure the plasma glucose concentration (1). We are concerned that practical limitations will lead to false positives and negatives with this approach. A given A1C instrument may identify some but not other abnormal hemoglobins (http://www.ngsp.org/prog/index2.html). How, therefore, can we be sure whether a hemoglobinopathy is causing (or preventing) diagnosis? Before diagnosis, should we not also exclude iron deficiency anemia, which may increase A1C by 1–1.5%, as well as hemolytic anemia and renal failure or chronic infections, which also lower …

Chronic kidney disease and measurement of albuminuria or proteinuria: a position statement.

Optimal detection and subsequent risk stratification of people with chronic kidney disease (CKD) requires simultaneous consideration of both kidney function (glomerular filtration rate [GFR]) and kidney damage (as indicated by albuminuria or proteinuria). Measurement of urinary albuminuria and proteinuria is hindered by a lack of standardisation regarding requesting, sample collection, reporting and interpretation of tests. A multidisciplinary working group was convened with the goal of developing and promoting recommendations that achieve consensus on these issues. The working group recommended that the preferred method for assessment of albuminuria in both diabetic and non‐diabetic patients is urinary albumin‐to‐creatinine ratio (UACR) measurement in a first‐void spot urine specimen. Where a first‐void specimen is not possible or practical, a random spot urine specimen for UACR is acceptable. The working group recommended that adults with one or more risk factors for CKD should be assessed using UACR and estimated GFR every 1–2 years, depending on their risk‐factor profile. Recommended testing algorithms and sex‐specific cut‐points for microalbuminuria and macroalbuminuria are provided. The working group recommended that all pathology laboratories in Australia should implement the relevant recommendations as a vital component of an integrated national approach to detection of CKD.

Priority actions for the non-communicable disease crisis

The UN High-Level Meeting on Non-Communicable Diseases (NCDs) in September, 2011, is an unprecedented opportunity to create a sustained global movement against premature death and preventable morbidity and disability from NCDs, mainly heart disease, stroke, cancer, diabetes, and chronic respiratory disease. The increasing global crisis in NCDs is a barrier to development goals including poverty reduction, health equity, economic stability, and human security. The Lancet NCD Action Group and the NCD Alliance propose five overarching priority actions for the response to the crisis--leadership, prevention, treatment, international cooperation, and monitoring and accountability--and the delivery of five priority interventions--tobacco control, salt reduction, improved diets and physical activity, reduction in hazardous alcohol intake, and essential drugs and technologies. The priority interventions were chosen for their health effects, cost-effectiveness, low costs of implementation, and political and financial feasibility. The most urgent and immediate priority is tobacco control. We propose as a goal for 2040, a world essentially free from tobacco where less than 5% of people use tobacco. Implementation of the priority interventions, at an estimated global commitment of about US

Liraglutide, a once‐daily human GLP‐1 analogue, added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with Type 2 diabetes (LEAD‐1 SU)

9 billion per year, will bring enormous benefits to social and economic development and to the health sector. If widely adopted, these interventions will achieve the global goal of reducing NCD death rates by 2% per year, averting tens of millions of premature deaths in this decade.

The metabolic syndrome: useful concept or clinical tool? Report of a WHO Expert Consultation

Aim  To compare the effects of combining liraglutide (0.6, 1.2 or 1.8 mg/day) or rosiglitazone 4 mg/day (all n ≥ 228) or placebo (n = 114) with glimepiride (2–4 mg/day) on glycaemic control, body weight and safety in Type 2 diabetes.

Follow-up of Blood-Pressure Lowering and Glucose Control in Type 2 Diabetes

This article presents the conclusions of a WHO Expert Consultation that evaluated the utility of the ‘metabolic syndrome’ concept in relation to four key areas: pathophysiology, epidemiology, clinical work and public health. The metabolic syndrome is a concept that focuses attention on complex multifactorial health problems. While it may be considered useful as an educational concept, it has limited practical utility as a diagnostic or management tool. Further efforts to redefine it are inappropriate in the light of current knowledge and understanding, and there is limited utility in epidemiological studies in which different definitions of the metabolic syndrome are compared. Metabolic syndrome is a pre-morbid condition rather than a clinical diagnosis, and should thus exclude individuals with established diabetes or known cardiovascular disease (CVD). Future research should focus on: (1) further elucidation of common metabolic pathways underlying the development of diabetes and CVD, including those clustering within the metabolic syndrome; (2) early-life determinants of metabolic risk; (3) developing and evaluating context-specific strategies for identifying and reducing CVD and diabetes risk, based on available resources; and (4) developing and evaluating population-based prevention strategies.

Glucose indices, health behaviors, and incidence of diabetes in Australia: The Australian diabetes, obesity and lifestyle study

BACKGROUND In the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) factorial trial, the combination of perindopril and indapamide reduced mortality among patients with type 2 diabetes, but intensive glucose control, targeting a glycated hemoglobin level of less than 6.5%, did not. We now report results of the 6-year post-trial follow-up. METHODS We invited surviving participants, who had previously been assigned to perindopril-indapamide or placebo and to intensive or standard glucose control (with the glucose-control comparison extending for an additional 6 months), to participate in a post-trial follow-up evaluation. The primary end points were death from any cause and major macrovascular events. RESULTS The baseline characteristics were similar among the 11,140 patients who originally underwent randomization and the 8494 patients who participated in the post-trial follow-up for a median of 5.9 years (blood-pressure-lowering comparison) or 5.4 years (glucose-control comparison). Between-group differences in blood pressure and glycated hemoglobin levels during the trial were no longer evident by the first post-trial visit. The reductions in the risk of death from any cause and of death from cardiovascular causes that had been observed in the group receiving active blood-pressure-lowering treatment during the trial were attenuated but significant at the end of the post-trial follow-up; the hazard ratios were 0.91 (95% confidence interval [CI], 0.84 to 0.99; P=0.03) and 0.88 (95% CI, 0.77 to 0.99; P=0.04), respectively. No differences were observed during follow-up in the risk of death from any cause or major macrovascular events between the intensive-glucose-control group and the standard-glucose-control group; the hazard ratios were 1.00 (95% CI, 0.92 to 1.08) and 1.00 (95% CI, 0.92 to 1.08), respectively. CONCLUSIONS The benefits with respect to mortality that had been observed among patients originally assigned to blood-pressure-lowering therapy were attenuated but still evident at the end of follow-up. There was no evidence that intensive glucose control during the trial led to long-term benefits with respect to mortality or macrovascular events. (Funded by the National Health and Medical Research Council of Australia and others; ADVANCE-ON ClinicalTrials.gov number, NCT00949286.).

Association of HbA1c levels with vascular complications and death in patients with type 2 diabetes: evidence of glycaemic thresholds

OBJECTIVE—This national, population-based study reports diabetes incidence based on oral glucose tolerance tests (OGTTs) and identifies risk factors for diabetes in Australians. RESEARCH DESIGN AND METHODS—The Australian Diabetes, Obesity and Lifestyle Study followed-up 5,842 participants over 5 years. Normal glycemia, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetes were defined using World Health Organization criteria. RESULTS—Age-standardized annual incidence of diabetes for men and women was 0.8% (95% CI 0.6–0.9) and 0.7% (0.5–0.8), respectively. The annual incidence was 0.2% (0.2–0.3), 2.6% (1.8–3.4), and 3.5% (2.9–4.2) among those with normal glycemia, IFG, and IGT, respectively, at baseline. Among those with IFG, the incidence was significantly higher in women (4.0 vs. 2.0%), while among those with IGT, it was significantly higher in men (4.4 vs. 2.9%). Using multivariate logistic regression, hypertension (odds ratio 1.64 [95% CI 1.17–2.28]), hypertriglyceridemia (1.46 [1.05–2.02]), log fasting plasma glucose (odds ratio per 1 SD 5.25 [95% CI 3.98–6.92]), waist circumference (1.26 [1.08–1.48]), smoking (1.70 [96% CI 1.11–2.63]), physical inactivity (1.56 [1.12–2.16]), family history of diabetes (1.82 [1.30–2.52]), and low education level (1.85 [1.04–3.31]) were associated with incident diabetes. In age- and sex-adjusted models, A1C was a predictor of diabetes in the whole population, in those with normal glycemia, and in those with IGT or IFG. CONCLUSIONS—Diabetes incidence is 10–20 times greater in those with IGT or IFG than those with normal glycemia. Measures of glycemia, A1C, metabolic syndrome components, education level, smoking, and physical inactivity are risk factors for diabetes.

Guideline for management of postmeal glucose.

Aims/hypothesisThere is conflicting evidence regarding appropriate glycaemic targets for patients with type 2 diabetes. Here, we investigate the relationship between HbA1c and the risks of vascular complications and death in such patients.MethodsEleven thousand one hundred and forty patients were randomised to intensive or standard glucose control in the Action in Diabetes and Vascular disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. Glycaemic exposure was assessed as the mean of HbA1c measurements during follow-up and prior to the first event. Adjusted risks for each HbA1c decile were estimated using Cox models. Possible differences in the association between HbA1c and risks at different levels of HbA1c were explored using linear spline models.ResultsThere was a non-linear relationship between mean HbA1c during follow-up and the risks of macrovascular events, microvascular events and death. Within the range of HbA1c studied (5.5–10.5%), there was evidence of ‘thresholds’, such that below HbA1c levels of 7.0% for macrovascular events and death, and 6.5% for microvascular events, there was no significant change in risks (all p > 0.8). Above these thresholds, the risks increased significantly: every 1% higher HbA1c level was associated with a 38% higher risk of a macrovascular event, a 40% higher risk of a microvascular event and a 38% higher risk of death (all p < 0.0001).Conclusions/interpretationIn patients with type 2 diabetes, HbA1c levels were associated with lower risks of macrovascular events and death down to a threshold of 7.0% and microvascular events down to a threshold of 6.5%. There was no evidence of lower risks below these levels but neither was there clear evidence of harm.Trial Registration:ClinicalTrial.gov NCT00145925Funding:Servier and the National Health and Medical Research Council of Australia (project grant ID 211086 and programme grant IDs 358395 and 571281)

Glycemic Thresholds for Diabetes-Specific Retinopathy: Implications for Diagnostic Criteria for Diabetes

An estimated 246 million people worldwide have diabetes. Diabetes is a leading cause of death in most developed countries, and is reaching epidemic proportions in many developing and newly industrialized nations. Poorly controlled diabetes is associated with the development of renal failure, vision loss, macrovascular diseases and amputations. Large controlled clinical trials have demonstrated that intensive treatment of diabetes can significantly decrease the development and/or progression of microvascular complications of diabetes. There appears to be no glycaemic threshold for reduction of diabetes complications; the lower the glycated haemoglobin (HbA1c), the lower the risk. The progressive relationship between plasma glucose levels and cardiovascular risk extends well below the diabetic threshold. Until recently, the predominant focus of therapy has been on lowering HbA1c levels, with a strong emphasis on fasting plasma glucose. Although control of fasting hyperglycaemia is necessary, it is usually insufficient to obtain optimal glycaemic control. A growing body of evidence suggests that reducing postmeal plasma glucose excursions is as important, or perhaps more important for achieving HbA1c goals. This guideline reviews the evidence on the harmful effects of elevated postmeal glucose and makes recommendations on its treatment, assessment and targets.