Achieving a Preoperative Target HbA1c of < 69 mmol/mol in Elective Vascular and Orthopedic Surgery: A Retrospective Single Center Observational Study

Introduction Diabetes mellitus (DM) is present in 10–15% of the surgical population. It is a known risk factor for adverse postoperative outcomes. UK perioperative guidance recommends optimizing glycemic control preoperatively, aiming for a target glycated hemoglobin (HbA1c) of < 69 mmol/mol. However, real-world compliance with this guidance remains unknown. The aim of our study was to determine how many patients with DM undergoing elective orthopedic and vascular surgery had a preoperative HbA1c of < 69 mmol/mol. We also reviewed the surgical reasons for non-concordance with the recommended preoperative HbA1c target. Methods This was a retrospective observational study of 1000 consecutive patients who had been referred for elective vascular and orthopedic surgery at a large tertiary center. Data were collected on these patients, both those with and without DM, between January 2016 and February 2017. Electronic databases were used to collect information on the patients’ preoperative HbA1c concentration and to determine whether there was a resulting delay in surgery when the preoperative HbA1c target of < 69 mmol/mol was exceeded. Results Of the 1000 patients referred for surgery (500 orthopedic and 500 vascular patients) included in the study, 201 (20%) had diabetes. Among these 201 people with DM, 155 (77%) had a preoperative HbA1c < 69 mmol/mol. Among the 46 people with DM whose HbA1c exceeded the recommended target, 41 were operated on despite the high HbA1c level, and only five had their surgery deferred or canceled due to suboptimal preoperative glycemic control. Conclusions Our data shows that the majority (77% ) of people undergoing elective vascular and orthopedic surgery were able to achieve a target HbA1c of < 69 mmol/mol. The current preoperative guidance is therefore achievable in a real-life setting. However, as is stated in the national guidance, this target should only be used where it is safe to do so and a degree of clinical discretion is necessary

Disease-Related Cardiac Troponins Alter Thin Filament Ca2+ Association and Dissociation Rates

The contractile response of the heart can be altered by disease-related protein modifications to numerous contractile proteins. By utilizing an IAANS labeled fluorescent troponin C, , we examined the effects of ten disease-related troponin modifications on the Ca2+ binding properties of the troponin complex and the reconstituted thin filament. The selected modifications are associated with a broad range of cardiac diseases: three subtypes of familial cardiomyopathies (dilated, hypertrophic and restrictive) and ischemia-reperfusion injury. Consistent with previous studies, the majority of the protein modifications had no effect on the Ca2+ binding properties of the isolated troponin complex. However, when incorporated into the thin filament, dilated cardiomyopathy mutations desensitized (up to 3.3-fold), while hypertrophic and restrictive cardiomyopathy mutations, and ischemia-induced truncation of troponin I, sensitized the thin filament to Ca2+ (up to 6.3-fold). Kinetically, the dilated cardiomyopathy mutations increased the rate of Ca2+ dissociation from the thin filament (up to 2.5-fold), while the hypertrophic and restrictive cardiomyopathy mutations, and the ischemia-induced truncation of troponin I decreased the rate (up to 2-fold). The protein modifications also increased (up to 5.4-fold) or decreased (up to 2.5-fold) the apparent rate of Ca2+ association to the thin filament. Thus, the disease-related protein modifications alter Ca2+ binding by influencing both the association and dissociation rates of thin filament Ca2+ exchange. These alterations in Ca2+ exchange kinetics influenced the response of the thin filament to artificial Ca2+ transients generated in a stopped-flow apparatus. Troponin C may act as a hub, sensing physiological and pathological stimuli to modulate the Ca2+-binding properties of the thin filament and influence the contractile performance of the heart