NOTES From ASEANZ Meeting 2009
Diabetes- controversies
Control of symptoms of hyperglycamia
The renal threshold for osmotic diuresis is approximately 10mmol/l and this equates to a HbA1C level of 8%.
Usually, the symptoms of polyuria and polydipsia can be controlled if the HbA1C is reduced below 8%. Some individuals have a higher renal threshold for osmotic diuresis and may not have symptoms despite even higher mean glucose levels.
Macrovascular complications- the story before 2008
The UKPDS studied relatively younger diabetics and found more intensive therapy reduced complications, particularly
it reduced the risk of microvascular complications. These findings lead to changes in guidelines for treatment.
Macrovascular complications- the story in 2008
ACCORD, ADVANCE and VADT were published. The three trials did have notable similarities and differences. The ADVANCE study included
more Asians and only 2% of the intensive therapy group were on insulin, in contrast to approximately a third of the more
intensively treated group in the other studies. In ADVANCE the baseline HbA1c was 7.8%, in ACCORD the baseline HbA1c was higher at 8.3%
The ACCORD study found no significant reduction in macrovascular complications but a suggestion of harm with more
intensive therapy.
The experts debate why these newer trials did not find any benefit. Some of the possible reasons include:
- the newer trials recruited older patients with established atherosclerosis- intervention in this stage with more intensive
glycaemic control does not reduce risk of macrovascular complications. More intensive control could reduce the counter-regulatory
mechanisms to deal with hypoglycaemia and this may have been responsible for some of increased mortality seen in the intensively
treated groups.
- in the statin era the rates of macrovascular complications are lower and it is more difficult to show a benefit from
more intensive control. In other words, if diabetics are not treated with statins then there may be benefits in this endpoint with
treatment of macrovascular complications.
- the best possible explanation may be that these newer trials were not of long enough duration. A longer period of
more intensive control is needed to overcome the effects of poor diabetic control, including the expression of proinflammatory genes and
to reverse the glycalated products of poor control (poor control including spikes in glucose levels causes expession of certain
deleterious proinflammatory genes and leads to glycalation of various proteins).
Microvascular complications in ADVANCE
There were fewer microvascular complications in the UKPDS with more intensive control. Surprisingly, in ADVANCE there was no
difference in diabetic retinopathy complications and paradoxically there was evidence for reduction of worsening microalbuminuria.
Conclusions
Intensive therapy for all diabetics has not been proven to be beneficial. The target HbA1c will need to be set for individual diabetics taking into account factors such as their age; duration of diabetes;
the presence of complications; and the risk of weight gain with insulin therapy (see Diabetes- New Targets for Therapy).
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