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Increase In Mortality Risk When Intensive Glucose Control For Diabetes Lowers Blood Glucose Too Far Hypoglycaemia

An article Online First and in an upcoming edition of The Lancet reports that new research indicates that intensive treatment to control blood glucose can lower it too far and cause hypoglycaemia. This can increase mortality. Uncontrolled high blood glucose (hyperglycaemia) in patients with diabetes is known to also increase mortality. Therefore in order to lower the risk to patients, blood glucose level targets should have lower as well as upper limits. In addition, it is reported that patients with type 2 diabetes given insulin-based regimens have a 50 percent increased mortality risk compared to those given combination oral therapy. The article is the work of Dr Craig Currie, School of Medicine, Cardiff University, UK, and colleagues.
When controlling blood sugar, the objective is to maintain glycated haemoglobin (HbA1c) to a normal range. Glycated haemoglobin is a form of haemoglobin used to identify the average plasma glucose concentration over prolonged periods of time. The HbA1c level is proportional to average blood glucose concentration over the previous four weeks to three months. Good blood sugar (glycaemic) control helps to reduce risk of long-term small blood vessel complications in both type 1 and type 2 diabetes. With information of potentially raised mortality rates associated with intensive glycaemic control, there has been growing debate about recommendations for treatment of type 2 diabetes. Discussions specifically relate to the optimum target for HbA1c. There is indication that hypoglycaemia contributes to an augmented risk of mortality in patients with diabetes. Intensive glycaemic control increases risk of hypoglycaemia with some drugs more than with others. For that reason, the evaluation of risks associated with the different blood glucose-lowering regimens is essential. The authors in this study looked at the association between all-cause mortality and HbA1c in patients with type 2 diabetes, in a primary-care setting. They then established whether any evident association was independent of the diabetes treatment regimen.
From November 1986 to November 2008, two cohorts of patients aged 50 years and older with type 2 diabetes were generated from the UK General Practice Research Database. The researchers identified two groups. In the first group of 27,965 patients, treatment had been intensified from oral monotherapy to combination therapy with oral blood-glucose lowering agents (metformin plus sulphonylurea). In the second group of 20,005, patients had changed to regimens that included insulin. Those with diabetes secondary to other causes were excluded. All-cause mortality was the primary outcome. Data were subsequently adjusted for these important confounding factors: age, sex, smoking status, cholesterol, cardiovascular risk, and general morbidity.
The glycated haemoglobin (HbA1c) level with the lowest mortality risk (7.5 percent) was used as a reference point. Researchers found that for the two combined cohorts, mortality risk in the lowest HbA1c decile (6‚ 4 percent) was 52 percent higher. In the highest HbA1c decile (10‚ 6 percent) was 79 percent higher. The typical HbA1c target for diabetes treatment is 7.0 percent. Findings suggested a similar U-shaped curve for both oral combination therapy and insulin therapy. However, all-cause mortality in people given insulin-based regimens (2,834 deaths) was 49 percent higher than those give combination oral agents (2,035 deaths).
Data suggest that insulin could increase the risk of death in type 2 diabetes. But, the authors explain that differences in the baseline characteristics of the insulin treated patients could be one reason behind this risk. Patients could be older, have more comorbidities and longer duration of diabetes. In addition, they also draw attention to a potential link between use of insulin and cancer progression that has been reported in an earlier study. However, the authors wish to clarify they are not recommending diabetes patients who are prescribed insulin to stop taking their medication. They explain: "Whether intensification of glucose control with insulin therapy alone further heightens risk of death in patients with diabetes needs further investigation and assessment of the overall risk balance."
They write in conclusion: "Low and high mean HbA1c values were associated with increased all-cause mortality and cardiac events. If confirmed, diabetes guidelines might need revision to include a minimum HbA1c value."
In an associated note, Dr Beverley Balkau and Dr Dominique Simon, CESP Centre for Research in Epidemiology and Population Health, Inserm, Villejuif, France, comment: "In patients with type 2 diabetes, when using insulin secretagogues or insulin itself, today's study does provide a rationale for an HbA1c threshold of 7‚ 5%, corresponding to the lowest death rate and lowest event rate for large-vessel disease. Priority should be given to insulin sensitisers for as long as possible in patients with type 2 diabetes, because these drugs allow a low HbA1c to be targeted without any risk of hypoglycaemia. More research is needed to establish HbA1c thresholds and the combination of drugs to be recommended for intensive treatment, with perhaps differing recommendations according to the patient - intensive treatment seems to be more beneficial for cardiovascular outcomes for those who are younger than 60 years, with a short duration of diabetes, and absence of microvascular and macrovascular disease."
"Survival as a function of HbA1c in people with type 2 diabetes: a retrospective cohort study"
Craig J Currie, John R Peters, Aod√ n Tynan, Marc Evans, Robert J Heine, Oswaldo L Bracco, Tony Zagar, Chris D Poole
DOI: 10.1016/S0140-6736(09)61969-3
The Lancet
Written by Stephanie Brunner (B.A.)
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today


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