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Hypo risk may outweigh benefit of lower HbA1C

Aggressively lowering blood glucose in patients with type 2 diabetes only slightly reduces the risk of developing neuropathy, but greatly increases the risk of hypoglycaemia, says a gold-standard analysis of data.

The researchers found type 2 diabetes patients had less than a 1% reduction in the risk of neuropathy when their HbA1c levels were lowered below 9.6 mmol/l (7%), but they had a three-fold increase in hypoglycaemic events.

 The authors of the analysis by the Cochrane Collaboration said their study indicated GPs have a delicate balance to maintain when deciding to use intensive blood glucose control to control complications in type 2 diabetes.

The systematic review looked at 17 trials – that ran for 12 months or more - involving patients with type 1 and type 2 diabetes, where the presence of peripheral neuropathy had been measured.

They found a risk reduction of 1.84% for neuropathy in all patients with diabetes whose blood glucose was lowered below 9.6 mmol/l (7%), compared with those who had standard treatment (moderate control was defined as a HbA1c of 9.6 to 13.5 mmol/l.

In patients with type 1 diabetes, this translated to a 53% risk reduction for developing a neuropathy after five years in those with aggressive treatment, compared with those receiving standard care.

But the outcomes for type 2 diabetes patients were less impressive – with an annual risk reduction of 0.58% in patients treated aggressively, compared with conventional control patients.

For aggressively treated patients with type 1 diabetes three of the seven studies reported a threefold increase in hypoglycaemic events, while another found 3.9% of glucose measurements were in the hypoglycaemic range in intensively controlled patients, compared with 2.2% in the standard group.

Similar rates of hypoglycaemia were seen were present in patients with type 2 diabetes, with the three largest studies also showing three-fold increases in risks.

The authors said their data left GPs with a dilemma over the aggressive control of glucose in patients with type 2 diabetes, although the benefits were clearer in type 1 patients.

Study lead Dr Brian Callaghan, neurologist at the University of Michigan, USA,  said: ‘While these results show clear improvement in the prevention of neuropathy in those with type 1 diabetes and potential benefits to those with type 2 diabetes, the precise glucose control target remains to be defined and potential adverse events must be weighed in the decision.'

Dr Rubin Minhas, clinical director of the BMJ Clinical Evidence Centre and a GP in Hoo, Kent, said the study showed good benefits for type 1 patients with peripheral neuropathy, but that the risk of adverse events was too high.

He said: ‘This adds to the increasing evidence that lowering glucose too far can be detrimental.'

‘Treatment should never be aggressive, but measured and optimised on an individual patient basis. Counterintuitive to the tight control concept, its patients with poorest control stand to gain more from improvements.'

Cochrane Database of Systematic Reviews 2012, online 12 Jun

Difference in risk of developing clinical neuropathy for aggressive treatment

Type 1 diabetes

Type 2 diabetes

-1.53%

-0.58%


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