Impact of haemoglobin variants on the use of haemoglobin A1c for the diagnosis and monitoring of diabetes: a contextualised review.

HbA1c is the established test for monitoring glycaemic control in diabetes, and intervention trials studying the impact of treatment on glycaemic control and risk of complications focus predominantly on this parameter in terms of evaluating the glycaemic outcomes. It is also the main parameter used when targets for control are being individualised, and more recently, it has been used for the diagnosis of type 2 diabetes. For laboratories performing this test and clinicians utilising it in their decision-making process, a thorough understanding of factors that can impact on the accuracy, and appropriate interpretation of the test is essential. The changing demographic in the Irish population over the last two decades has brought this issue sharply into focus. It is therefore timely to review the utility, performance and interpretation of the HbA1c test to highlight factors impacting on the results, specifically the impact of haemoglobin variants, and the impact of these factors on its utilisation in clinical practice.

ortho-Phenylene oligomers with terminal push-pull substitution.

ortho-Phenylenes are an emerging class of helical oligomers and polymers. We have synthesized a series of push-pull-substituted o-phenylene oligomers (dimethylamino/nitro) up to the octamer. Conformational analysis of the hexamer using a combination of low-temperature NMR spectroscopy and ab initio predictions of (1)H NMR chemical shifts indicates that, like other o-phenylenes, they exist as compact helices in solution. However, the substituents are found to have a significant effect on their conformational behavior: the nitro-functionalized terminus is 3-fold more likely to twist out of the helix. Protonation of the dimethylamino group favors the helical conformer. UV/vis spectroscopy indicates that the direct charge-transfer interaction between the push-pull substituents attenuates quickly compared to other conjugated systems, with no significant charge-transfer band for oligomers longer than the trimer. On protonation of the dimethylamino group, significant bathochromic shifts with increasing oligomer length are observed: the effective conjugation length is 9 repeat units, more than twice that of the parent oligomer. This behavior may be rationalized through examination of the frontier molecular orbitals of these compounds, which exhibit greater delocalization after protonation, as shown by DFT calculations.