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Insulin use and cancer – no direct link

The potential link between insulin use and cancer appears to have gained a more 'MMR–autism' feel

With speculation rife in recent days and weeks over the surprise, potential link between insulin use for diabetes and the development of cancer, from many angles the affair seems now to have gained a more 'MMR–autism' feel.

It was finally agreed between experts this week, at the International Federation of Diabetes 2009 meeting in Montreal, that there is no evidence to suggest a heightened risk of cancer directly related to insulin analogues, such as sanofi-aventis' Lantus (insulin glargine).

Just a handful of weeks before, exasperated international medical journalists had collectively demanded clarity from scientific experts on any potential cancer danger for insulin-treated diabetics, at September's European Association for the Study of Diabetes in Vienna.

The world's leading authorities on the topic could offer no conclusive answers, which they stated with apologetic sincerity.

In fact, the story broke in August, when editor of Diabetologia Edwin Gale published (against the counsel of several peers) a German study by Hemkens L G et al – acknowledged retrospectively at IDF this week to be fundamentally flawed in several aspects.

Industry leaders in diabetes, including sanofi-aventis (s-a) and Novo Nordisk (NN), had moved swiftly to protect the hard-won reputation of their insulin analogues; Lantus and Levemir, respectively.

However, at a packed symposium at Montreal's Palais de Congrès, a panel of experts asserted in unison that the evidence available does not suggest any increased risk of cancer for patients taking insulin analogues to control diabetes.

Under closer scrutiny
Professor John Lachin, from the George Washington University, Washington DC, discussed the weaknesses and limitations of the Hemken study, citing selection bias and the omission of potentially confounding co-variates as vital flaws.

Indeed, close scrutiny of the study revealed that, contrary to the author's original claims, in fact insulin glargine may even confer a lowering of cancer risk in some patients, although firm conclusions cannot be derived from the existing data.

"In conclusion, there is no replicated evidence that insulin glargine at any dose is a cause of, or associated with an increase in the risk of cancer," Professor Lachin told delegates.

Diabetologia's Edwin Gale added: "When we press the button to lower blood glucose, we're actually doing something much more profound," going on to describe potential effects on cell lines, gene expression, nutrient flux and other metabolic changes.

"This controversy will be solved by [new] data, not by further analysis of what we know," he added. "Overall, glargine users are not at risk of solid tumours."

More research needed
Professor Hannele Yki-Jarvinen, from the University of Helsinki, Finland, said she felt s-a had been unfortunate in being the focus as this story had emerged. "We need more data – not a witch-hunt", she noted.

A series of respected diabetologists present at the meeting agreed too that they could not and would not change clinical practice – as regards continuing and initiating Lantus therapy – on the basis of existing data.

Professor Hertzel Gerstein, a renowned diabetologist from McMaster University & Hamilton Health Sciences, Onatario, said it was clear from the recent controversies that "we still have much to learn about insulin despite nearly 100 years of clinical experience with it".

"We know that obesity and diabetes are both associated with risk of cancer, and we need more data on insulin binding and metabolism, as current epidemiological data shows conflicting outcomes. All we can say for sure is that we have a lot to think about."

Avenues for future exploration
Several theories as to why diabetes is a risk factor for cancer, and what potential solutions may exist were discussed freely at the meeting this week. Distilled down by diabetologists, future research priorities included:

  • Adding metformin (known to negate certain increases in cancer risk) to insulin therapy
  • Understanding the link between insulin resistance and cancer
  • Targeted screening of high-risk groups
  • Understanding why diabetics have higher cancer-related mortality.

  • 21st October 2009

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