Does Glycated Hemoglobin Variability in Type 2 Diabetes Differ Depending on the Diabetes Treatment Threshold Used in the Qatari Population: Implication on Diabetes Complication Risk?

14-00058

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.

2016-11-01

2023-10-01

2024-10-01

Active (not recruiting)

150

Inclusion Criteria: * Qatari subjects only with type 2 diabetes taking any medication. * HbA1c 7.5-9.0%. * Body mass index 26-36. * Age 18 - 65 years of age. * Recruitment of a gender balance reflecting the local eligible diabetes patients until 150 are recruited. Exclusion Criteria: * Patients with anemia or other conditions known to affect the validity of HbA1c measurement e.g. a haemoglobinopathy known to affect the Hamad HbA1c method or renal failure (CKD Stage 5) * Patients with concurrent illness * Patients on medication leading to insulin resistance e.g. corticosteroids * Pregnancy * Active retinopathy * Any clinical exclusion for optimal diabetes control * Hypoglycemic unawareness

{'studyType': 'INTERVENTIONAL', 'phases': ['NA'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'OTHER', 'maskingInfo': {'masking': 'NONE', 'maskingDescription': 'This is an randomized open label clinical trial.'}}, 'enrollmentInfo': {'count': 150, 'type': 'ESTIMATED'}}

2023-12-14