A new UK study has suggested that both very low and very high blood sugar levels in type 2 diabetes are associated with increased all-cause mortality and cardiac events.
For UK healthcare professionals only
These findings are in line with those of the US ACCORD trial which was stopped early because of an increased risk of death in type 2 diabetes patients who underwent intensive blood glucose lowering compared with conventional therapy.
In the new UK study, published recently in The Lancet (Lancet 2010;375:481–9), the lowest death and event rates were seen at an HbA1c level of 7.5%.
The new data come from studying around 48,000 type 2 diabetes patients aged 50 or over who are included in the UK General Practice Research Database. These patients had either had their treatment intensified from oral monotherapy to combination therapy with oral blood glucose lowering agents, or had changed to regimens that included insulin.
Results showed that compared with the HbA1c decile with the lowest hazard (median HbA1c 7.5%), the adjusted hazard ratio for all-cause mortality in the lowest HbA1c decile (median 6.4%) was 1.52 and in the highest HbA1c decile (median 10.5%) was 1.79.
The 10% of patients with lowest HbA1c values (<6.7%) had a higher death rate than all but those in the top 10%, who had an HbA1c of 9.9% or higher. Cardiovascular disease was also more frequent in this low-HbA1c group than in any other decile.
Mortality was three times higher in patients who had severe hypoglycemia than in those who did not have severe hypoglycemia, suggesting that the increase in mortality in the low sugar decile could have been related to hypoglycemia, the researchers suggest.
In addition, mortality was higher in patients treated with insulin versus those given combination oral agents. “These data imply for oral combination therapy that a wide HbA1c range is safe with respect to all-cause mortality and large-vessel events, but for insulin-based therapy, a more narrow range might be desirable,” the authors write.
An accompanying editorial, says that individualisation of therapy is key, requiring differing recommendations according to the patient. It adds that 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.