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Fasting Hyperglycaemia Study



Background

Type 2 diabetes (non-insulin dependent diabetes mellitus) often has an insidious onset with dysglycaemia frequently being present for many years until health checks reveal raised plasma glucose levels or diabetic symptoms develop. By the time the diagnosis is made around half of all subjects have diabetes related tissue damage as shown by the UK Prospective Diabetes Study (UKPDS). Even after diagnosis, management of type 2 diabetes is not easy as near normal glucose levels are difficult to achieve, can rarely be maintained and long-term complications pose particular problems.Coronary heart disease has been shown to be more prevalent in people with impaired glucose tolerance (IGT) than in those with normal glucose tolerance. It is unclear if this increased risk is a direct result of hyperglycaemia or whether some underlying defect is responsible for both the hyperglycaemia and the cardiovascular disease.

Earlier identification of those at risk of type 2 diabetes may be advisable as it is likely that there is a phase where intervention, prior to the onset of overt diabetes, may prevent or delay its development and possibly may also diminish the risk of cardiovascular complications. Preventing diabetes by detecting and treating at risk individuals is an attractive possibility although previous attempts to do this have been largely unsuccessful.The primary aim of the FHS study is to determine whether deterioration in glycaemic tolerance towards diabetes can be delayed or prevented using an insulin secretagogue (glicalazide) or a reinforced healthy living advice.

Subjects

174 self referred subjects, male or female, thought to be at risk of developing diabetes,aged 30 to 70 years inclusive and with two consecutive fasting plasma glucose levels in the range 5.5 to 7.7 mmol/L have been randomised.

Two-by-Two Factorial Randomisation

Subjects were randomised to double-blind, fixed-dose therapy with:gliclazide (160 mg twice a day) or matching placebo and, simultaneously, to:reinforced or basic healthy living advice.

Gliclazide
Arm

Healthy
Living
Advice
Arm
47
gliclazide
reinforced
46
placebo
reinforced
93
reinforced
advice
48
gliclazide
basic
47
placebo
basic
95
basic
advice

95
gliclazide
93
placebo
188
subjects
in total

The factorial design makes for a more efficient study and allows for separate assessment of the gliclazide and healthy living interventions, with minimal effects on non-drug study costs and sample size requirements. In addition, the possible additional benefits or risks of combined therapy can be investigated. The main analyses for the gliclazide arm will be performed comparing the 316 subjects allocated gliclazide with the 315 allocated matching placebo, irrespective of their healthy living allocation. Similarly, the metformin arm analyses will compare reinforced with basic healthy living, irrespective of gliclazide allocation.

Six Year Followup

Three year follow up data on the rate of progression of fasting glycaemia is now available. Publication of the final results concerning progression to type 2 diabetes is scheduled for 2002 with secondary analyses examining the effects on beta cell function, insulin sensitivity, lipid profiles, biochemical risk factors, body weight, microalbuminuria, retinopathy, digital electrocardiography and quality of life.

Study Management

The Fasting Hyperglycaemia Study is an academic, investigator led trial designed, run and analysed by the University of Oxford Diabetes Trials Unit.

Funding

The trial was funded by the MRC and an educational grant from Servier.