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Tight glycaemic control - how low should you go?

ESC Congress 2010

Diabetes and the Heart

More than 75% of the seats were filled in the Berlin room during the Clinical Seminar discussing the complicated issue of blood sugar control and the increasing risk for cardiovascular complications in patients with elevated fasting glucose, impaired glucose tolerance and diabetes mellitus. To go too low activates the autonomic nervous system, with a 10-50 fold increase in adrenalin and nor-adrenalin, prolongs QT-interval, induces hypokalemia and platelet activation.

Treatment strategies of the intensive care patient were overviewed by Professor Antonio Ceriello, Barcelona. Recent studies have revealed a significant association between hyperglycaemia and morbidity and mortality rates in adult patients both diabetic and non-diabetic. Conversely, the Nice Sugar Study (2009) randomized patients to intensive blood sugar control or “standard treatment” and could show a higher mortality in the intensive treated group. Glucose variability, especially with deep and frequent hypoglycaemia is associated with mortality in the ICUs, but the definition of blood sugar variability needs to be clarified. High glucose variability together with high mean glucose is associated with the highest mortality rate. Despite conflicting results in studies of intensive care patients, it was concluded that treatment should aim at “cutting the tops” and avoid hypoglycaemias.

Professor Lars Ryden, Stockholm discussed specifically the patients with coronary artery disease and the increasing burden of multiple risk factors in this group. Blood sugar level at admission has important prognostic information and 67% of patients with AMI have impaired glucose tolerance at discharge from the hospital, as showed by Norhammar et al (2002). The DIGAMI I study clearly showed that intensive treatment reduced the absolute risk of death by 11%. Mean blood sugar level at the start of treatment was 15.4 mmol/L compared to that in DIGAMI II, which was 7.1 mmol/l.

This difference may in part explain the neutral result in DIGAMI II. Occasional hypoglycaemia in the CAD-patient is not associated with increased mortality but is related to other co-morbidities. An increase in blood sugar level of 3 mmol/L results in a significant increased risk for mortality with HR 1.20. Blood glucose should be measured in all patients with acute coronary syndrome. Consider intensive treatment in levels > 10 mmol/L, aim towards 5-7.7 mmol/L. Intravenous insulin is currently the most effective method for controlling blood glucose. High dose GIK has no role in the treatment of ST-elevation AMI!

Professor Roden, Dusseldorf focused on the evidence of benefit for low HbA1c targets as elevated HbA1c is an important risk marker for CVD in line with the final speaker, Professor Stefano del Prato, Pisa, who stressed the potential risks of intensive treatment with HbA1c values below 6.5%. The ACCORD, ADVANCE and VADT studies all showed significant numbers of serious hypoglycaemias but HbA1c values below 7% were not associated with any increase in cardiovascular deaths. Overall, an 0.9% reduction in HbA1c was associated with a significant reduction of 17% in non-fatal MI and 15% reduction in CAD.

Long diabetes duration, high BMI and hypoglycaemia increases the risk of CV death with intensive treatment and the higher the HbA1c, the higher the risk of hypoglycaemia! The risk of weight gain should also be considered in patients with intensive treatment and future guidelines for HbA1c levels may be more differentiated with respect to duration of disease, body weight, age etc. Guidelines are valuables tools but should be used with clinical judgement in the treatment of the individual patient.




Tight glycaemic control - how low should you go?
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.