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Primary Prevention of Cardio-Vascular Disease

NOTES From ASEANZ Meeting 2009

Diabetes complications- a lot more to it than just HbA1c

Analysis of the DCCT trial suggested that the improvement of HbA1c only explained less than 25% of the reduction of risk of developing retinopathy.

In the DCCT trial, there was more diabetic retinopathy in the control group when matched with similar subjects with the same HbA1c level in the more intensively treated group- raising the possiblity that simply relying on HbA1C measurments is not appropriate..

Some of the possible reasons why the same HbA1c might be obtained in two individuals with varying degree of control include:

  • the spikes of high and troughs of low glucose levels can vary between subjects and still lead to the same HbA1c level.
  • individuals with the same mean glucose level can have different HbA1c levels because glycation rates are not the same between individuals. A high percentage of the variability of glycation rates is genetically determined.
  • deglycation rates may also vary between individuals- an enzyme that promotes dyglycation has been indentified and the activity of this may vary between individuals and account for some of the differences.

Other reasons for differences observed include:

  • lab studies have shown that oscillating glucose spikes affect adversely flow medicated vasodilation and other measues of inflammation.
  • transient high glucose levels cause epigenetic changes that persist during normoglycaemia.
  • a month after intensive therapy with insulin some diabetics develop a distal sensory polyneuropathy. Could similar abnormalities occur in the autonomic nervous system and might these changes increase risk of sudden death?

Residual pancreatic function as measured by levels of C-peptide, in DCCT, was asscociated with fewer complications.