Diabetes is a chronic disease which affected 140 million people in the world in 1995 and has grown to 175 million people affected by the year 2000 and will likely affect 240 million by the year 2010.

There were an estimated 15 million IDDM patients in the world in 1997 which rose to an estimated 18 million by the year 2000 and 23 million by 2010.

Insulin requirement ( based on 15,000 IU per patient per annum) is likely to grow to a requirement for 350 million IU by year 2010.

It has been estimated that there are around 15 million diabetics in Europe of which over over 2.0 million are insulin-dependent. In the UK there are an estimated 450,000 insulin-dependent diabetic patients.

It is estimated that around 8% of the NHS annual budget and possibly up to 10% is required to manage UK diabetic patients. Possibly one in ten hospital beds in the UK are occupied by diabetic patients. Side effects of insulin treatment regimes are being reported at alarming rates and are very worrying for diabetics and carers.

Large trials conducted during recent years have clearly demonstrated that many of the complications of diabetes can be prevented by more intensive and more appropriate therapy which includes education and adequate use of treatment options. Studies to date suggest that more money has to flow into direct metabolic treatment of diabetes, where the large potential for reducing complications, and reducing costs of complications, could be exploited.

Many insulin-dependent diabetic patients have reported adverse effects to insulin treatment, especially treatment with human insulin, and in many instances these adverse effects minimise upon reverting to animal insulin.

Typical adverse reactions from a typical sample of 100 respondents include:

Loss of warnings of hypoglycaemia - 41%, Extreme tiredness / lethargy -34%, Weight increase of over 1.5 stones - 32%, Feeling unwell all the time - 28%, Memory loss, confusion - 24%, Depression - 24%, Mood changes, not the same person, difficult to live with -13%, Blood sugar levels dip and peak erratically - 9%, Loss of employment-5%, Marriage break up - 4%, Road traffic / other accident- 5%

These adverse reactions have a serious effect on everyday life for an insulin-dependent diabetic patient and their carers. Many adverse reactions have been reported to diabetic organisations. It is estimated that probably 50% of diabetic subjects are doing reasonably well but what of the other 50%? Are many suffering quietly?

An insulin-dependent diabetic patient requires to manage a lifestyle and aima to achieve normal glycaemia based upon type of insulin, insulin dose, diet and exercise. The patient requires to minimise the risk of hyperglycaemia and hypoglycaemia, and the long term complications of diabetes such as neuropathy; nephropathy; diabetic retinopathy; cardiac and macro vascular disease. Fast acting insulin's act in 1-2 hours and slow acting insulin's in 12-18 hours and sometimes longer.

Hypoglycaemia is the major fear of insulin-dependent diabetic patients. It has been reported that multiple episodes of hypoglycaemia and impaired awareness of hypoglycaemia can lead to cerebral dysfunction. This is a worrying concern for diabetic patients and their carers.

Present insulin's are not good enough to enable the achievement of normal glycaemia. A need exists to provide an insulin which will achieve normal glycaemia and be guaranteed to be available well into this millennium.

The DCCT trial in the USA studied 1,422 patients over a 6.5 year period. The trial demonstrated that complications such as diabetic retinopathy, nephropathy and cardiac and muscular events were reduced significantly, but hypoglycaemia increased by a factor of 3 in patients who aimed to keep tight control. It is believed that patients in the DCCT trial were treated with human insulin as the trial started when human insulin was first introduced to the market. It is estimated that worldwide, today, over 85% of insulin-dependent diabetic patients are treated with human insulin.

The Bellagio Report released on 20 June 1996 advised of the concerns of some patients treated with human insulin and the side effects encountered. This was supported by the Rockefeller Foundation, New York, USA, and others. Some patients have suffered serious side effects from treatment with human insulin and the consequences make disturbing reading, especially the onset of hypoglycaemia unawareness. In 1989 - 1992 the British Diabetic Association (BDA) received at least 3,000 letters of complaint about human insulin.

Clearly there is a need for new insulin development to minimise hypoglycaemia. Phosphorylated insulin's which can be prepared from chemically extracted pharmacological insulin by gentle treatment with phosphorus oxychloride, have been shown to have reduced bioactivity by mouse convulsion assay, but such phosphorylated insulin's reduce hyperglycaemia when administered to diabetic subjects without inducing hypoglycaemia.

In 1921 Banting and Best reported one water solubilized extract which normalised blood sugar in a diabetic dog, but did not produce hypoglycaemia, and which was subsequently abandoned in favour of more vigorous chemical extractions with a more potent hypoglycaemic action. Early workers attempting to phosphorylate insulin reported a product with 38% of the biological activity of the original, using mouse convulsion assay, but apparently did not test it in diabetic animals.

U S Patent Number 5,242,900 (dated 7 September 1993) entitled 'Treatment of Diabetes Using Phosphorylated Insulin' describes the inventions of Dr A Michael Albisser, Toronto, Canada. The Patent gives a detailed description of preferred embodiments; a method for making phosphorylated insulin; animal studies; intravenous studies and subcutaneous studies using dogs. The inventor makes eight claims as detailed in the patent including substantially pure phosphorylated insulin for use in the treatment of diabetes, which reduces hyperglycaemia without inducing hypoglycaemia when administered to a diabetic subject, and a method for producing such a phosphorylated insulin. Perhaps future insulin's might be phosphorylated by gentle treatment with phosphorus oxychloride to produce an insulin which can be administered to diabetic subjects to reduce hyperglycaemia without inducing hypoglycaemia?