Diabetics Not Told of Synthetic Insulin Risk

Report highlighting coma dangers to 15,000 sufferers who were switched to synthetic human substitute deemed alarmist, writes Paul Brown, Guardian Unlimited © Guardian Newspapers Limited 1999 Tuesday March 9, 1999

Evidence that thousands of diabetics in Britain may have suffered a deterioration in their health from synthetic insulin has been withheld by the British Diabetics Association, whose role is to advise patients and to protect their interests. The evidence was contained in a report, commissioned by the association and completed six years ago, which highlighted dangers faced by about 10 per cent of the 150,000 diabetics who had been switched from the traditional animal-derived insulin to synthetic human insulin.

Some of those adversely affected began, without warning, to go into comas, known as hypoglycemic episodes or "hypos". Some suffered severe injuries, a few crashed their cars, and others believed they would have died had they not been rescued as they lay unconscious. An estimated 15,000 people may still suffer because they are injecting themselves twice a day with insulin that may not suit them. Many doctors are unaware of the problem, or have failed to put their patients back on animal insulin because they do not know it is still available.

The association says it did not publish the report because it was "too alarmist". Simon O'Neill, head of diabetes care services, said the association agreed that up to 20 per cent of insulin injectors preferred animal insulin and had experienced difficulties with synthetic insulin. He added that the association had published a report, The Insulin Debate, which dealt with the issues, continued to keep members informed of developments, and campaigned to keep animal insulin available to sufferers.

Synthetic insulin is manufactured by two major drug companies, the Danish Novo Nordisk and US giant Elli Lilly. Neither company accepts that the synthetic version has negative effects. The report was compiled following 3,000 letters of complaint over a period of two years about the new insulin from members of the association.

The letters gave harrowing accounts of how lives had deteriorated after being switched to synthetic human insulin. Eight out of 10 of a sample of the complainants examined by independent researchers said they could no longer control their symptoms and had lost warning signs that they were about to lapse into comas. The main conclusions from the letters were:

• Half the patients had no warning of passing out with hypos once on the new drug.

• A quarter said such episodes were more frequent, and one in five said they were more severe.

• Thirteen per cent said they became unconscious at night and 5 per cent suffered convulsions.

• Ten per cent had memory loss and another 9 per cent were unable to concentrate.

Matthew Kiln a south London GP who is an expert on diabetes, was a member of the committee of inquiry set up by the association that looked into the side-effects of synthetic human insulin.

He told the Guardian: "The association has failed in its duty to protect and represent the interests of diabetics by not publishing the committee's findings in full. I and other doctors who understand this issue have been quietly switching some patients back to animal insulin to avoid the problems but thousands of people are suffering from lack of choice."

Dr. Kiln is himself a diabetic who uses insulin and has experienced the dramatic negative effects on his own health when he switched to the synthetic version. Before synthetic human insulin was introduced in the early 1980s around 150,000 diabetics in Britain injected themselves twice a day with insulin extracted from pigs and cattle in slaughterhouses.

Diabetes is the result of the body's inability to produce insulin which regulates blood sugar levels but it can be successfully managed by injecting animal insulin.

Synthetic human insulin, made from feeding nutrients to E-Coli bacteria, was heralded as a breakthrough because it would avoid an occasional long term problem of antibodies being produced to combat animal insulin.

After the association received a tide of complaints, it commissioned two independent researchers, Hazel Matthews and Natasha Posner, to analyze some of the letters. Their report concluded that many patients were suffering potentially dangerous reactions.

A fuller report ordered from Dr. Posner concluded that doctors and specialists had failed to listen to patients and the very real distress and dangerous symptoms had been largely ignored.

The report was due to be published in the British Medical Journal in 1993 but was withdrawn. The Diabetic Association"s journal, Balance, subsequently produced a supplement, The Insulin Debate, in which some of the problems of synthetic insulin were discussed.

Mr. O'Neill said the BDA continued to educate doctors and health professionals of the need to give diabetics the option of using animal insulin. He said: "The message of the Posner report was right, it was just too alarmist, but it is a message we have disseminated, and it is a message we are still trying to get out. We have campaigned to stop animal insulin being withdrawn. Matt Kiln and we are on the same side."

There was fear of going out alone or driving

The 3,000 letters of complaint written to the British Diabetic Association by patients, their relatives and doctors concerned the deterioration in their condition since being moved from animal insulin to synthetic human insulin.

After analyzing nearly 400 of the letters, Natasha Posner, an independent researchers commissioned by the DBA, said: "Many correspondents reported that a diabetic condition which had been stable and controlled over many years and allowed a full and normal life, suddenly changed and became problematic and life disrupting. For people experiencing these difficulties, the cost in terms of immediate negative effects far out-weighed any possible long term benefits of this new insulin."

The report says that in many cases where the patient had complained, the relationship between the diabetic and doctor was breaking down and there was a potential for conflict because the patient felt his fears had been ignored.

• The single most important complaint was the sudden onset of comas.

• A second problem was personality changes, mostly noticed by partners and colleagues.

• A third, and of great concern to the association, was a breakdown in relationship between the diabetics who manage their illness, and the professionals who advise them and prescribe their insulin.

• There was also strong evidence that the problems were reversible.

• One fifth of the patients in the survey switched back to animal insulin. Of these only 1 per cent said there was no improvement when they returned to animal insulin. Many doctors refused to change them back or told them erroneously there was no longer an animal alternative.

• "Correspondents reported the consequences of loss of control of the diabetes, deterioration in general health or accidents meant increased dependence on others and loss of confidence about controlling the diabetes so that there was fear of going out alone, going to bed or driving. "

• Some people had lost their job, been made redundant or found that they were unable to work. A few had been refused renewal of their driving licenses.

• There were several reports of people who had been prosecuted by police after being involved in accidents while having a hypo," the report said.

The report concludes: "The letters examined constitute a source of data which amount to very much more than mere anecdotes."

Patients' comments were directly quoted in the report:

• "While I was on human insulin, my life was absolute hell. There was absolutely no warning of my blood sugar going low, and I have been in several comas because of this. My clinic put me back on to animal insulin in July, and I have felt a different person since."

• "It was only when I went on to human insulin that I thought I was not in control of my diabetes, I went into hypos almost daily with no warning whatsoever (thanks to paramedics and good neighbors plus the casualty department at the local hospital I am still here to tell the tale)."

• One patient reported that his family noticed: "The complete change of character. I was becoming moody, critical, confused, forgetful and seemed to lack concentration. But more and more I seemed to have unnoticed hypos."

• From a wife: "There is no doubt in my mind that had be been living alone he would now be dead, Many of the hypos occur during the night for no reason."

• From a mother: "The clinic argues that the human insulin is better for him in the long run than animal insulin - that is if he can survive."

"Guinea pig" doctor became aggressive and forgot things

Matthew Kiln unwittingly used himself as a human guinea pig to test the effects of human insulin. At first he was delighted that modern science had produced a synthetic human version which could replace the bovine and pork varieties which had been in use for 50 years. As a diabetic himself he had chosen to specialize in the illness and in his job as registrar at Torbay hospital ran a diabetic clinic. Diabetics, unable to produce insulin, keep their blood sugar levels at the correct level by twice daily injections, and can correct any problems by eating glucose tablets or other sweet foods.

If they fail to act when they begin to feel unwell or dizzy they may lapse into a coma known as a hypoglycemic episode. But Dr. Kiln found that, in a few cases with human insulin, patients complained that these episodes were more frequent and occurred while cooking, or driving, without any of the normal signs of stress.

Dr. Kiln went on to human insulin as soon as it was available. "I kept passing out, I had low blood sugars. I had arguments with consultants. My father noticed all this and he urged me to change back. He just said I was more obstinate and more difficult. I changed back and my condition improved.

"I tried going on to the human variety again in 1986. My wife demanded I change back: I had become unreliable, was forgetting things, and had become more aggressive."

Dr. Kiln said his experiences were mirrored by patients and their carers who had written to the Diabetic Association "an extraordinary number who could not be ignored".

He said: "It needs a big scientific study to investigate the problems of synthetic insulin properly."

In his south London practice he has 110 diabetics who have to inject themselves twice daily. He believes that about 10 per cent have had a bad reaction to human insulin.

How ironic that Dr. Kiln's experience is identical to mine save that he had to try human twice and managed not to have any auto-accidents or career destroying iatrogenic insulin reactions (come on, folks let's go back to calling a spade a spade) on the job or on the road. How ironic that I started using human (it is not the fact that it is made from E. Coli bacteria by synthetic rDNA processes, in my opinion) about the time of Dr. Kiln's second try with it. DGG