HbA1c Variability in Type II Diabetes

Sponsor
Weill Cornell Medical College in Qatar
Study ID
NCT02879409
Status
Active Not Recruiting

Conditions

  • Diabetes Mellitus Type 2

Eligibility Criteria

Sex
ALL
Age
18 Years - 65 Years
Healthy Volunteers
Not accepted

Interventions

  • Metformin — DRUG
    Initial: 500 mg once daily; dosage may be increased by 500 mg weekly; maximum dose: 2,000 mg once daily
  • Gliclazide — DRUG
    There is no fixed-dosage regimen for the management of diabetes mellitus with gliclazide. Dose will be individualized based on frequent determinations of blood glucose during dose titration and throughout maintenance. The 30 mg modified-release tablet equals the 80 mg immediate-release tablet. Immediate-release tablet: Initial: 80 mg twice daily; titrate based on blood glucose levels. Usual dosage range: 80 to 320 mg/day (maximum dose: 320 mg/day); dosage of ≥160 mg should be divided into 2 equal parts for twice-daily administration. Modified-release tablet: Initial: 30 mg once daily; titrate in 30 mg increments every 2 weeks based on blood glucose levels. Maximum dose: 120 mg once daily
  • Sitagliptin — DRUG
    Oral: 100 mg once daily
  • Liraglutide — DRUG
    SubQ: Initial: 0.6 mg once daily for 1 week; then increase to 1.2 mg once daily; may increase further to 1.8 mg once daily if optimal glycemic response not achieved with 1.2 mg daily.
  • Pioglitazone — DRUG
    Oral, Monotherapy or combination therapy: 15-30 mg once daily Patients with heart failure (NYHA Class I or II): Monotherapy or combination therapy: 15 mg once daily
  • Dapagliflozin — DRUG
    5mg once daily increasing to 10mg once daily as required
  • human insulin — DRUG
    insulin dosage and administration according to physician

Study Details

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.

Key Dates

Start date
Nov 30, 2016
Status verified
Jul 2025
Primary completion
Oct 1, 2023
Completion
Oct 1, 2026

Study Design

Enrollment
150 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER

Arms

  • Experimental: Treatment arm 1
    75 Type 2 diabetic patients with a gender balance who will have the intervention if/when their FBG \>140mg/dl Intervention: intensify treatment until their FBG is \<90mg/dl, using whatever treatment is clinically appropriate for them using different interventions (Metformin, Gliclazide, Sitagliptin, Dapagliflozin, Liraglutide, Pioglitazone, human insulin), and only intensify it further if their FPG rises to \>140mg/dl again.
  • Experimental: Treatment arm 2
    75 Type 2 diabetic patients with a gender balance who will have the intervention if/when their FBG \>115mg/dl Intervention: intensify treatment until FBG is \<=115 mg/dl and intensify further if \>115 mg/dl again, using what ever clinical treatment is necessary (Metformin, Gliclazide, Sitagliptin, Dapagliflozin, Liraglutide, Pioglitazone, human insulin).

Primary Outcome Measure

Determination of the variability of HbA1c (by measurement of standard deviation of HbA1c) between the 2 diabetes treatment thresholds [ Time Frame: 24-30 months ]

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