Transcript No Slide Title

Diabetes in Cancerland
Edwin Gale
This Meeting
Thanks to:
The Steno team
The Danish Cancer Society
The EASD
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
ADA/ACS Consensus
1. Is there a meaningful association between
diabetes and cancer incidence or prognosis?
2. What risk factors are common to both
diabetes and cancer?
3. What are possible biologic risks between
diabetes and cancer risk?
4. Do diabetes treatments influence risk of
cancer or cancer progression?
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.
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?
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.
A central aim of such a consortium would be to optimise
methodology for descriptive studies, to develop joint workprogrammes, 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.
1.
Aims
To meet one another and discuss
resources available and work in progress
2.
To provide a workshop for discussion of
shared methodologies
3.
To outline some of the major
unanswered questions
4.
To explore the feasibility of joint
analysis of these questions
So, What are the Questions?
Obesity
Diabetes
Glucose
Insulin
Cancer
Diabetes
Obesity
Diabetes
therapy
Glucose
Cancer
Insulin
Diabetes
Obesity
Diabetes
therapy
Glucose
Cancer
Insulin
Hyperglycaemia?
Obesity?
Diabetes
therapy?
Insulin/resistance?
Question One
To what extent are the excess cancer risks
associated with diabetes due to non-glycaemic
risk factors (obesity, insulin resistance, etc)?
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?
Question Three
(a)
What is the role of endogenous
hyperinsulinaemia upon cancer development?
(b)
What is the role of exogenous
hyperinsulinaemia upon cancer development?
If so, which cancers?
& Does insulin formulation matter?
Adjusted HR
Cancer Risk vs Insulin dose
insulin dose
Currie et al
submitted
Question Four
Can a beneficial effect of metformin upon
cancer risk be confirmed?
If so, which cancers?
Question Five
What, if any, are the effects of other
diabetes therapies?
TZDs
Sulfonylureas
GLP-1 agonists
DPP-4 antagonists
Question Six
Do people with diabetes have a higher cancer
mortality?
If so, is this tumour specific?
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?
Problems worthy of attack
Show their worth by fighting back
Piet Hein