There are numerous possible reasons why it could be speculated that HbA1c variability may
affect complication risk. Of interest are the concepts that both laboratory and clinic
evidence suggests that periods of sustained hyperglycemia are 'remembered' (metabolic
memory), this in turn is recognized to place patients at greater long-term risk of
complications. As such it can be speculated that the detrimental effect of variability in
HbA1c may be mediated via the same mechanism as 'metabolic memory' phenomenon.
Aims: To determine whether treatment to one of 2 threshold levels will result in one group of
type 2 diabetes patients having the same mean HbA1c but with differing HbA1c variability to
that of another and related to markers of oxidative stress, inflammation and microvascular
complications. To determine whether a difference in HbA1c variability between the 2 groups
will reflect in changes in small nerve fibers assessed with the sensitive method of corneal
confocal microscopy and cardiac autonomic function testing. To assess the reproducibility of
HbA1c measurement from a whole blood samples initially analyzed and then stored at -80C until
the end of the study (2-3 years), as well as storing an aliquot of haemolysate, for
reanalysis at the end of the study.
In one arm the investigators will intensify treatment in those with FPG>140mg/dl until their
FPG is <90mg/dl, using whatever treatment is clinically appropriate for them, and only
intensify it further if their FPG rises to >140mg/dl again. In the other group the
investigators will intensify if their FPG is >115 mg/dl until it is <=115 mg/dl and intensify
further if >115 mg/dl again. A total of 20 visits within a time frame of 2 and half years
will be performed. Visits procedures will include routine biochemistry, eGFR, lipids, fasting
glucose, insulin and full blood count, HbA1c, SHBG, hsCRP. EPIC and G-PAQ questionnaires will
be collected. Autonomic function testing using deep breathing heart rate variability, and a
sensitive measure of small fiber neuropathy using corneal confocal microscopy and a 24 hour
urine collection for urinary isoprostanes to measure oxidative stress will be performed, at
baseline, 12 and 24 months.
Phase:
N/A
Details
Lead Sponsor:
Weill Cornell Medical College in Qatar
Collaborators:
Hamad Medical Corporation Sidra Medical and Research Center University of Hull