Diabetes in Cancerland

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Diabetes in Cancerland

• Edwin Gale

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This Meeting

• Thanks to
• The Steno team
• The Danish Cancer Society
• The EASD

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Questions We Want to Answer

• Background
• The Diabetologia papers drew attention to the
  issue of cancer and diabetes
• But also revealed how little we knew
• And drew attention to the pitfalls of reaching
  conclusions about cancer risk

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ADA/ACS Consensus

• Is there a meaningful association between
  diabetes and cancer incidence or prognosis?
• What risk factors are common to both diabetes and
  cancer?
• What are possible biologic risks between diabetes
  and cancer risk?
• Do diabetes treatments influence risk of cancer
  or cancer progression?

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The Consortium

• Arose from the desire of some of the groups to
  establish core methodologies, and (where
  possible) to pool data and work together on major
  unanswered questions.

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• A number of issues relating to diabetes and
  cancer have recently become the focus of
  considerable interest and controversy, and form
  the basis for a recent call for research
  applications from the EASD/EFSD. Three questions
  appear central to this debate
• What is the mechanistic basis for the
  epidemiological association between diabetes and
  cancer?
• Does choice of therapy for diabetes influence
  cancer risk? If so, how and why?
• Why does cancer have a worse prognosis in people
  with diabetes, and could this be overcome?

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Although some pointers can be derived from
controlled clinical trials, much research in this
area will inevitably take the form of descriptive
studies. The limitations of this approach are
well established, but descriptive studies have an
essential role in hypothesis generation, and may
potentially form the basis for future clinical
trials. We believe that collaboration is a key
element of future work in this area, and that
this should bring together those with expertise
in basic science, oncology, diabetes therapy,
epidemiology, and statistical modelling.
Oversight of this activity would be entrusted to
a Steering Committee, whose membership would be
drawn from non-participants in the study groups.
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A central aim of such a consortium would be to
optimise methodology for descriptive studies, to
develop joint work-programmes, and (where
possible) to analyse data derived from different
databases in parallel. Participants in the
consortium are invited to exchange and discuss
protocols, and to meet in regular workshop groups
to discuss methodology and share analysis of
their research findings. Although the EASD
initiative would form the focus for such an
interaction, participation in the collaboration
would potentially be open to other groups with
shared interests and activities. A key criterion
for participation in the consortium is the
contribution and sharing of novel data and/or
methodologies to address the central questions
outlined above.
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Aims

• To meet one another and discuss resources
  available and work in progress
• To provide a workshop for discussion of shared
  methodologies
• To outline some of the major unanswered
  questions
• To explore the feasibility of joint analysis of
  these questions

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So, What are the Questions?
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Obesity
Diabetes
Cancer
Glucose
Insulin
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Diabetes therapy
Obesity
Diabetes
Cancer
Glucose
Insulin
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Diabetes therapy
Obesity
Diabetes
Cancer
Glucose
Insulin
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Hyperglycaemia?
Obesity?
Diabetes therapy?
Insulin/resistance?
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Question One

• To what extent are the excess cancer risks
  associated with diabetes due to non-glycaemic
  risk factors (obesity, insulin resistance, etc)?

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Question Two

• (a) What is the influence of hyperglycaemia upon
  cancer development?
• (b) What is the influence of hyperglycaemia upon
  cancer progression?
• If so, which cancers?

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Question Three

• What is the role of endogenous
  hyperinsulinaemia upon cancer development?
• What is the role of exogenous hyperinsulinaemia
  upon cancer development?
• If so, which cancers?
• Does insulin formulation matter?

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Cancer Risk vs Insulin dose
Adjusted HR
Currie et al submitted
insulin dose
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Question Four

• Can a beneficial effect of metformin upon cancer
  risk be confirmed?
• If so, which cancers?

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Question Five

• What, if any, are the effects of other diabetes
  therapies?
• TZDs
• Sulfonylureas
• GLP-1 agonists
• DPP-4 antagonists

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Question Six

• Do people with diabetes have a higher cancer
  mortality?
• If so, is this tumour specific?

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Six Questions

1. Is the increased cancer risk with diabetes
   secondary to other associated features?
2. What is the role of hyperglycaemia?
3. What is the role of hyperinsulinaemia?
4. Is metformin protective?
5. What other agents should be examined?
6. Does diabetes affect cancer mortality?

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Problems worthy of attack Show their worth by
fighting back
Piet Hein