HbA1c: chasing numbers or considering context?

Glycated haemoglobin (HbA<sub>1c</sub>) reflects the average blood glucose level in the three months preceding the test. Changes in consecutive HbA<sub>1c</sub> tests indicate deteriorating, or improved, glycaemic control. HbA<sub>1c</sub> is considered to be the "gold standard" measure of blood glucose control and is often used as the basis for prescribing choices and other care decisions. A number of factors can affect the accuracy of the HbA<sub>1c</sub> result, for example, the life span of red blood cells, assay methods and clinicians\u27 awareness of possible interfering factors. The aim of this article is to outline how HbA<sub>1c</sub> is used as a diagnostic test, how it is used to monitor glycaemic control and how it can guide management decisions. It is also important to emphasise the importance of considering HbA<sub>1c</sub> in the context of the individual rather than as an isolated number

Obesity and type 2 diabetes have additive effects on left ventricular remodelling in normotensive patients-a cross sectional study

BackgroundIt is unclear whether obesity and type 2 diabetes (T2D), either alone or in combination, induce left ventricular hypertrophy (LVH) independent of hypertension. In the current study, we provide clarity on this issue by rigorously analysing patient left ventricular (LV) structure via clinical indices and via LV geometric patterns (more commonly used in research settings). Importantly, our sample consisted of hypertensive patients that are routinely screened for LVH via echocardiography and normotensive patients that would normally be deemed low risk with no further action required.MethodsThis cross sectional study comprised a total of 353 Caucasian patients, grouped based on diagnosis of obesity, T2D and hypertension, with normotensive obese patients further separated based on metabolic health. Basic metabolic parameters were collected and LV structure and function were assessed via transthoracic echocardiography. Multivariable logistic and linear regression analyses were used to identify predictors of LVH and diastolic dysfunction.ResultsMetabolically healthy normotensive obese patients exhibited relatively low risk of LVH. However, normotensive metabolically non-healthy obese, T2D and obese/T2D patients all presented with reduced normal LV geometry that coincided with increased LV concentric remodelling. Furthermore, normotensive patients presenting with both obesity and T2D had a higher incidence of concentric hypertrophy and grade 3 diastolic dysfunction than normotensive patients with either condition alone, indicating an additive effect of obesity and T2D. Alarmingly these alterations were at a comparable prevalence to that observed in hypertensive patients. Interestingly, assessment of LVPWd, a traditional index of LVH, underestimated the presence of LV concentric remodelling. The implications for which were demonstrated by concentric remodelling and concentric hypertrophy strongly associating with grade 1 and 3 diastolic dysfunction respectively, independent of sex, age and BMI. Finally, pulse pressure was identified as a strong predictor of LV remodelling within normotensive patients.ConclusionsThese findings show that metabolically non-healthy obese, T2D and obese/T2D patients can develop LVH independent of hypertension. Furthermore, that LVPWd may underestimate LV remodelling in these patient groups and that pulse pressure can be used as convenient predictor of hypertrophy status.<br /

Temporal HbA1c patterns amongst patients with type 2 diabetes referred for specialist care : data from the S4S-DINGO-Diabetes Informatics Group

Aims: To evaluate the achievement of HbA1c targets in patients with type 2 diabetes mellitus in specialist practice. Methods: This audit was undertaken by members of the S4S Diabetes Informatics Group (DINGO), a consortium of Australian endocrinologists in private practice who contribute de-identified data from their electronic medical record, Audit 4 (Software 4 Specialists, S4S, Australia & New Zealand) for audit purposes. Data from patients with type 2 diabetes was extracted. Inclusion criteria were: initial age 7% (53 mmol/mol), with at least another HbA1c recorded in the next 2 years, and a minimum of 2 years follow-up. Data was analysed using a linear mixed effects model. Results: Of the 4796 patients in the dataset with type 2 diabetes mellitus, 1379 patients fulfilled inclusion criteria. The median age at initial consultation was 57 (49-64) years. The median baseline HbA1c was 8.7 (7.8-9.8)% (72 mmol/mol). There was a 1.0% reduction in HbA1c to 7.7 (7.1-8.6)% (61 mmol/mol) (p < 0.0001) in the first 3-6 months following referral, after which there were no further changes. The initial reduction was maintained with minimal loss of control at 4 years. By 3-6 months, 24% of patients achieved the target HbA1c. Conclusions: Referral of patients with type 2 diabetes to an endocrinologist reduces HbA1c, and the effect is sustained over the medium term; however only a minority of patients reach targets

Developing and applying the adverse outcome pathway concept for understanding and predicting neurotoxicity

The Adverse Outcome Pathway (AOP) concept has recently been proposed to support a paradigm shift in regulatory toxicology testing and risk assessment. This concept is similar to the Mode of Action (MOA), in that it describes a sequence of measurable key events triggered by a molecular initiating event in which a stressor interacts with a biological target. The resulting cascade of key events includes molecular, cellular, structural and functional changes in biological systems, resulting in a measurable adverse outcome. Thereby, an AOP ideally provides information relevant to chemical structure-activity relationships as a basis for predicting effects of structurally similar compounds. AOPs could potentially also form the basis for qualitative and quantitative predictive modeling of the human adverse outcome resulting from molecular initiating or other key events for which higher-throughput testing methods are available or can be developed. A variety of cellular and molecular processes are known to be critical for normal function of the central (CNS) and peripheral nervous systems (PNS). Because of the biological and functional complexity of the CNS and PNS, it has been challenging to establish causative links and quantitative relationships between key events that comprise the pathways leading from chemical exposure to an adverse outcome in the nervous system. Following introduction of the principles of MOA and AOPs, examples of potential or putative adverse outcome pathways specific for developmental or adult neurotoxicity are summarized and aspects of their assessment considered. Their possible application in developing mechanistically informed Integrated Approaches to Testing and Assessment (IATA) is also discussed