OLDER patients with type 2 diabetes who experience severe hypoglycaemia should be closely monitored for increased risk of adverse clinical outcomes, according to leading diabetes specialist Associate Professor Jonathan Shaw.

Professor Shaw, Associate Director of the Baker IDI Heart and Diabetes Institute in Melbourne, said new Australian research indicated that hypoglycaemia might be a marker of the frailty of a patient, requiring careful and cautious ongoing care.

He was commenting on a study published in the New England Journal of Medicine last week that showed severe hypoglycaemia is strongly associated with increased risks of a broad range of adverse clinical outcomes in patients with long-standing type 2 diabetes.(1)

The study examined the relationship between severe hypoglycaemia and the subsequent risks of vascular complications and death among 11 140 patients from 20 countries with type 2 diabetes who participated in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) study.

The patients were followed for a median 5-year period.

The international study team included Australian researchers from the George Institute for International Health in Sydney and the Monash University School of Public Health in Melbourne.

“Although our findings cannot exclude the possibility that severe hypoglycaemia has a direct causal link with these outcomes, they suggest that it is as likely to be a marker of vulnerability to a wide range of adverse clinical outcomes,” the researchers said.

They said the presence of severe hypoglycaemia should raise clinical suspicion of the patient’s susceptibility to adverse outcomes and prompt action to address this possibility.

Professor Shaw said practitioners should encourage older patients to report all “hypos”, although many older people did not consider a hypo to be a serious event or did not recognise hypos when they had “a funny turn”.

“Patients should recognise that a hypo is not just a nuisance and practitioners should see it as a signal of frailty,” he said.

“The balance of evidence is that a less aggressive approach to blood glucose control is needed for older patients and patients with established cardiovascular disease, and that avoidance of hypoglycaemia is likely to be important in these patients.”

Professor Shaw said the benefits of tight HbA1c control were limited in older patients as they can take many years to become apparent, whereas the risks with severe hypoglycaemia were more immediate.

Hypoglycaemia was defined as a blood glucose level of less than 2.8 mmol in the presence of typical symptoms and signs of hypoglycaemia without other apparent cause.

Patients who were unable to treat themselves were considered to have severe hypoglycaemia.

The research showed that among patients who reported severe hypoglycaemia, 16.8% (35 of 208) had a subsequent major macrovascular event, 11.5% (24 of 209) a subsequent microvascular event and 19.5% (45 of 231) died.

The respective rates for those who did not report severe hypoglycaemia were 10.2% (1112 of 10 932), 10.1% (1107 of 10 931) and 9.0% (986 of 10 909).

Those who experienced severe hypoglycaemia had a risk of cardiovascular death 3.78 times greater than those without severe hypoglycaemia, and a 2.86 times greater risk of death from a non-cardiovascular cause.

The proportions of patients reporting severe hypoglycaemia who died from cardiovascular and non-cardiovascular causes were similar (49% and 51%, respectively) to those not reporting severe hypoglycaemia (53% and 47%).

Average time from onset of severe hypoglycaemia to the first major macrovascular event was 1.56 years; to the first major microvascular event, 0.99 years; and 1.05 years for death.

However, the researchers found no relationship between repeated episodes of severe hypoglycaemia and vascular outcomes or death.

1. N Engl J Med 2010; 363: 1410-1418.


Posted 11 October 2010

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