U shaped association between glycaemic control and mortality in type 2 diabetes

The association between diabetic control and mortality seems to be U shaped in people with type 2 diabetes⇑. In a large observational analysis from the UK, people with mean glycated haemoglobin (HbA1c) concentrations around 7.5% had the lowest mortality. Risk of death rose significantly on both sides of this reference group, reaching a hazard ratio of 1.52 (1.32 to 1.76) for patients in the bottom 10th of HbA1c concentration (median 6.4%), and 1.79 (1.56 to 2.06) for patients in the top 10th (median 10.5%). Researchers analysed data from nearly 48 000 primary care patients who had stepped up their hypoglycaemic treatment. The U shape persisted after multiple adjustments and sensitivity analyses, and it looked most convincing for patients who had switched from oral drugs to regimens that included insulin.

But we can’t draw firm causal inferences from retrospective observations, however statistically powerful they are, says a linked comment (doi:10.1016/S0140-6736(09)62192-9). It is tempting to speculate that hypoglycaemia might be behind some of the excess deaths in people with the tightest control though, particularly those taking insulin.

These authors also report a U shaped association between glycaemic control and risk of cardiovascular disease, which was harder to explain. Again, an HbA1c of 7.5% was associated with the lowest risk.

Uncertainty prevails over glucose control for adults with septic shock

Despite years of research, doctors still have little hard evidence to go on when trying to decide how much insulin, if any, to give critically ill patients with hyperglycaemia. The latest trial—in patients with septic shock treated with hydrocortisone—failed to settle the controversy, and at least one expert says mega trials that recruit many thousands of patients may be the only remaining option (p 365).

The new trial looked at 509 patients given hydrocortisone and one of four treatment options: tight glucose control with insulin, plus or minus fludrocortisone; or conventional …