Type 2 Diabetes Mellitus: New focus on individualising Glycaemic targets

In the field of Type 2 Diabetes management, there is a recent trend towards individualising the HbA1c targets by taking into account several patient and disease factors. Adequate glucose control reduces the risk of development and progression of diabetes-related complications, however aiming to achieve a normal blood glucose level is not necessarily beneficial for everyone diagnosed with Type 2 Diabetes. The positive effects on micro- and macro-vascular events from intensive glycaemic control need to be weighed up against the potential of severe hypoglycaemia which, in some cases, results in death.

This finding is substantiated by a number of large clinical trials. The target range generally can be divided into 3 categories based on different population groups as summarised in Table 1.

Table 1. Recommended HbA1c targets for people with Type 2 Diabetes.

A lower HbA1c target (48mmol/mol, 6.5%) should be aimed at for people in the early phase of diabetes disease who do not have cardiovascular co-morbidity and who are not using insulin. If this group of people only requires lifestyle modification +/- metformin, achieving an even tighter HbA1c of 42mmol/mol (6%) should be encouraged.

The United Kingdom Prospective Diabetes Study has confirmed the importance of maintaining good glucose control in reducing the incidence of diabetes complications. The subjects who received intensive treatment regimen (median HbA1c 53mmol/mol [7%] achieved) with sulphonylureas or insulin at the time of diagnosis of Type 2 Diabetes have shown a greater reduction in microvascular complications and all-cause mortality, compared with those receiving standard treatment (median HbA1c 63mmol/mol [7.9%] achieved).

In patients with long-standing diabetes, and/or on multiple anti-diabetic medications, or with cardiovascular disease; attaining an HbA1c < 42mmol/mol (6%) may not be appropriate as this increases the risk of severe hypoglycaemia while the clinical benefit of preventing macrovascular events is limited. Long standing diabetes might be regarded as 10 to 20 years in an older adult, but much longer in those with an early onset.

In the Action to Control Cardiovascular Risk in Diabetes study these people were randomised to intensive control (target HbA1c <42mmol/mol [6%]) or standard control (target HbA1c 53-63mmol/mol [7-7.9%]). After 3.5 years the intensive control group showed such a concerning increase in all-cause mortality and incidence of hypoglycaemia, it led to early discontinuation of the trial. Therefore a HbA1c target of 53mmol/mol (7%) is more appropriate in this population.

A higher HbA1c target of 64mmol/mol (8%) should be used for patients prone to hypoglycaemia (e.g. elderly), with a history of recurrent severe hypoglycaemia, or hypoglycaemia unawareness. There is strong evidence of severe hypoglycaemia being associated with increased risk of death.

No one size fits all. Although the National Health and Medical Research Council recommends a general HbA1c target of <53mmol/mol (7%) for the majority of patients with
Type 2 Diabetes, the optimal glucose level should be tailored for individuals based on the duration of disease, medications being taken, presence of co-morbidities, and risk of developing hypoglycaemia.