2007 Abstracts

 

Pre-type 1 diabetes dysmetabolism: maximal sensitivity achieved with both oral and intravenous glucose tolerance testing

Barker JM, McFann K, Harrison LC, Fourlanos S, Krischer J, Cuthbertson D, Chase HP, Eisenbarth GS; DPT-1 Study Group

J Pediatr 150:31-36 (2007)

OBJECTIVE: To determine the relationship of intravenous (IVGTT) and oral (OGTT) glucose tolerance tests abnormalities to diabetes development in a high-risk pre-diabetic cohort and to identify an optimal testing strategy for detecting preclinical diabetes. STUDY DESIGN: Diabetes Prevention Trial-Type 1 Diabetes (DPT-1) randomized subjects to oral (n = 372) and parenteral (n = 339) insulin prevention trials. Subjects were followed with IVGTTs and OGTTs. Factors associated with progression to diabetes were evaluated. RESULTS: Survival analysis revealed that higher quartiles of 2-hour glucose and lower quartiles of first phase insulin response (FPIR) at baseline were associated with decreased diabetes-free survival. Cox proportional hazards modeling showed that baseline body mass index (BMI), FPIR, and 2-hour glucose levels were significantly associated with an increased hazard for diabetes. On testing performed within 6 months of diabetes diagnosis, 3% (1/32) had normal FPIR and normal 2-hour glucose on OGTT. The sensitivities for impaired glucose tolerance (IGT) and low FPIR performed within 6 months of diabetes diagnosis were equivalent (76% vs 73%). CONCLUSIONS: Most (97%) subjects had abnormal IVGTTs and/or OGTTs before the development of diabetes. The highest sensitivity is achieved using both tests.

[View free full-text article on J Pediatr website]

 

Desirable performance standards for HbA(1c) analysis - precision, accuracy and standardisation: consensus statement of the Australasian Association of Clinical Biochemists (AACB), the Australian Diabetes Society (ADS), the Royal College of Pathologists of Australasia (RCPA), Endocrine Society of Australia (ESA), and the Australian Diabetes Educators Association (ADEA)

Goodall I, Colman PG, Schneider HG, McLean M, Barker G

Clin Chem Lab Med 45:1038-1097 (2007)

BACKGROUND: HbA(1c) (glycohaemoglobin) is universally used in the ongoing monitoring of all patients with diabetes. There are many % HbA(1c) target control rating recommendations by national, regional and international expert bodies for diabetes patients and these are variable around the world. General patient target control ratings are currently most often recommended as either <6.5% or <7.0% HbA(1c), with <6.0% HbA(1c) stated for individual patients where clinically possible. This necessitates very precise HbA(1c) assays and the same patient values, irrespective of HbA(1c) method or area of the world. METHODS: HbA(1c) targets recommended by major expert groups and published HbA(1c) assay precision (coefficient of variation, %CV) levels have been detailed. These have been compared with published biological variation levels and with calculated HbA(1c) error ranges at various HbA(1c) levels and %CV levels. In addition, these have been compared with the analytical precision necessary to differentiate between the upper limit of the normal range for HbA(1c) and targets recommended by expert groups for diabetes control. RESULTS: Intralaboratory analytical CVs of <2% are necessary and are achievable on automated HPLC analysers, and are supported on grounds of both clinical need and biological variation, as well as the need to differentiate the national, regional and international target recommendations from the upper limit of the normal range (<6.0% HbA(1c) level). CONCLUSIONS: Routine methods with tight long-term imprecision with CVs of <2% are recommended. International HbA(1c) targets essentially require that all HbA(1c) methods be precise, and have minimal standardisation bias and minimal methodological interferences in individual patients.

[View article page on Clin Chem Lab Med website]

 

Seasonal changes in preprandial glucose, A1C, and blood pressure in diabetic patients: response to Liang.

Honeyman MC, Elkassaby S, Harrison LC

Diabetes Care 30:e118 (2007)

Liang (1) reported seasonal variations in preprandial glucose, A1C, blood pressure, and LDL cholesterol in Taiwanese Chinese type 2 diabetic patients, which correlated inversely with monthly mean temperature, with higher values in the winter and lower values in the summer. We found that mean monthly temperature strongly correlated (r2 = 0.76, P = 0.0002) with serum 25-hydroxyvitamin D3 [25(OH)D3] measured monthly in 30 healthy subjects (median age 10.5 years, 15 male subjects). We suggest that Liang's observations could, instead, be due to variation in vitamin D nutrition, reflected by the seasonal variation in the serum concentration of 25(OH)D3.

[View free full-text article on Diabetes Care website]

 

Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial

Keech AC, Mitchell P, Summanen PA, O'Day J, Davis TM, Moffitt MS, Taskinen MR, Simes RJ, Tse D, Williamson E, Merrifield A, Laatikainen LT, d'Emden MC, Crimet DC, O'Connell RL, Colman PG; FIELD study investigators

Lancet 370:1689-1697 (2007)

BACKGROUND: Laser treatment for diabetic retinopathy is often associated with visual field reduction and other ocular side-effects. Our aim was to assess whether long-term lipid-lowering therapy with fenofibrate could reduce the progression of retinopathy and the need for laser treatment in patients with type 2 diabetes mellitus. METHODS: The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study was a multinational randomised trial of 9795 patients aged 50-75 years with type 2 diabetes mellitus. Eligible patients were randomly assigned to receive fenofibrate 200 mg/day (n=4895) or matching placebo (n=4900). At each clinic visit, information concerning laser treatment for diabetic retinopathy-a prespecified tertiary endpoint of the main study-was gathered. Adjudication by ophthalmologists masked to treatment allocation defined instances of laser treatment for macular oedema, proliferative retinopathy, or other eye conditions. In a substudy of 1012 patients, standardised retinal photography was done and photographs graded with Early Treatment Diabetic Retinopathy Study (ETDRS) criteria to determine the cumulative incidence of diabetic retinopathy and its component lesions. Analyses were by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN64783481. FINDINGS: Laser treatment was needed more frequently in participants with poorer glycaemic or blood pressure control than in those with good control of these factors, and in those with a greater burden of clinical microvascular disease, but the need for such treatment was not affected by plasma lipid concentrations. The requirement for first laser treatment for all retinopathy was significantly lower in the fenofibrate group than in the placebo group (164 [3.4%] patients on fenofibrate vs 238 [4.9%] on placebo; hazard ratio [HR] 0.69, 95% CI 0.56-0.84; p=0.0002; absolute risk reduction 1.5% [0.7-2.3]). In the ophthalmology substudy, the primary endpoint of 2-step progression of retinopathy grade did not differ significantly between the two groups overall (46 [9.6%] patients on fenofibrate vs 57 [12.3%] on placebo; p=0.19) or in the subset of patients without pre-existing retinopathy (43 [11.4%] vs 43 [11.7%]; p=0.87). By contrast, in patients with pre-existing retinopathy, significantly fewer patients on fenofibrate had a 2-step progression than did those on placebo (three [3.1%] patients vs 14 [14.6%]; p=0.004). An exploratory composite endpoint of 2-step progression of retinopathy grade, macular oedema, or laser treatments was significantly lower in the fenofibrate group than in the placebo group (HR 0.66, 95% CI 0.47-0.94; p=0.022). INTERPRETATION: Treatment with fenofibrate in individuals with type 2 diabetes mellitus reduces the need for laser treatment for diabetic retinopathy, although the mechanism of this effect does not seem to be related to plasma concentrations of lipids.

[View article page on Lancet website]

 

New haemoglobin A1c: the way it is reported is about to change...

Schneider HG, Goodall I, Colman PG, McLean M, Barker G; Australian Working Party for HbA1c standardization.

Intern Med J 37:213-215 (2007)

While the world struggles to provide care for increasing numbers of persons with diabetes, there is ongoing discussion behind the doors of an international committee about the name and unit in which the most commonly used measurement of diabetic glycaemic control – haemoglobin A1c (HbA1c) – is to be reported in the future.
Glycated haemoglobins are formed when glucose in the blood spontaneously reacts with the amino groups of the haemoglobin protein. Haemoglobin consists of two α and two β chains. The amino acids that undergo nonenzymatic glycation are the N-terminal valine group and free ε-amino groups of lysine residues. Approximately 60% of the glycation happens at the N-terminal valine. Such glycated proteins are quite stable and the amount formed correlates to the exposure to different concentrations of glucose over the previous 2–3 month.

[View article page on Intern Med J website]

 

Does insulin resistance need resistin?

Wentworth JM, Harrison LC

J Clin Endocrinol Metab 92:2036-2037 (2007)

It has long been recognized that sepsis, a potent activator of the innate immune system, is associated with insulin resistance in critical illness and increases insulin requirements in people with type 2 diabetes (T2D). More recently, circulating markers of innate immune activation such as C-reactive protein, IL-6, TNF-{alpha}, and monocyte chemoattractant protein-1 have been associated with obesity-T2D and vascular disease (1) and have been shown to predict the risk of T2D in at-risk populations (1, 2). These findings support the view that even low-grade activation of the innate immune system leads to insulin resistance.

[View free full-text article on J Clin Endocrinol Metab website]

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