Brief Summary

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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

150

participants targeted

Target at P50-P75 for not_applicable diabetes-mellitus-type-2

Timeline

5mo left

Started Nov 2016

Longer than P75 for not_applicable diabetes-mellitus-type-2

Geographic Reach

1 country

1 active site

Status

active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

9.9 years study duration

Study Progress96%

Nov 2016Oct 2026

First Submitted

Initial submission to the registry

July 13, 2016

Completed

1 month until next milestone

First Posted

Study publicly available on registry

August 25, 2016

Completed

2 months until next milestone

Study Start

First participant enrolled

November 1, 2016

Completed

6.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2023

Completed

3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2026

Expected

Last Updated

July 20, 2025

Status Verified

July 1, 2025

Enrollment Period

6.9 years

First QC Date

July 13, 2016

Last Update Submit

July 16, 2025

Conditions

Diabetes Mellitus Type 2

Keywords

HbA1c variabilityDiabetes Mellitus Type 2Diabetes microvascular complicationsDiabetes macrovascular complications

Outcome Measures

Primary Outcomes (1)

Determination of the variability of HbA1c (by measurement of standard deviation of HbA1c) between the 2 diabetes treatment thresholds
The primary objective of this study is 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.
24-30 months

Secondary Outcomes (3)

Association of the variability of HbA1c (by measurement of standard deviation of HbA1c) to microvascular changes in heart rate variability, corneal nerve fiber density, albumin/creatinine ratio and estimated glomerular filtration rate.
24-30 months
Association of the variability of HbA1c (by measurement of standard deviation of HbA1c) to oxidative stress markers measured by urinary isoprostanes and inflammation measured by highly sensitive C-reactive protein.
24-30 months
Comparison of HbA1c (percent) for each subject at baseline and following sample storage of 2 years to assess HbA1c measurement stability.
2-3 years.

Study Arms (2)

Treatment arm 1

EXPERIMENTAL

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.

Drug: MetforminDrug: GliclazideDrug: SitagliptinDrug: LiraglutideDrug: PioglitazoneDrug: DapagliflozinDrug: human insulin

Treatment arm 2

EXPERIMENTAL

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).

Drug: MetforminDrug: GliclazideDrug: SitagliptinDrug: LiraglutideDrug: PioglitazoneDrug: DapagliflozinDrug: human insulin

Interventions

MetforminDRUG

Initial: 500 mg once daily; dosage may be increased by 500 mg weekly; maximum dose: 2,000 mg once daily

Also known as: Glucophage