Diabetes and Cancer

Bendix Carstensen Steno Diabetes CenterGentofte, Denmarkhttp://BendixCarstensen.com

ASCO, 12th Anuual Meeting

Chicago, June 2012

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Conflicts of interest

I Employee of Steno Diabetes Center, a researchhospital owned by NovoNordisk.

I Stockholder of NovoNordisk.

I NovoNordisk is a major insulin and -analogmanufacturer.

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Conflicts of interest

I Employee of Steno Diabetes Center, a researchhospital owned by NovoNordisk.

I Stockholder of NovoNordisk.

I NovoNordisk is a major insulin and -analogmanufacturer.

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Conflicts of interest

I Employee of Steno Diabetes Center, a researchhospital owned by NovoNordisk.

I Stockholder of NovoNordisk.

I NovoNordisk is a major insulin and -analogmanufacturer.

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Diabetes and Cancer

Two main questions:

I Do diabetes patients get cancer more oftenthan non-diabetics?— cancer incidence studies

I Do cancer patients with diabetes die earlierthan cancer patients without diabetes?— cancer survival studies

I Combination (ignoring the cancer diagnosis):Do diabetes patients die more frequently fromcancer than non-diabetics?— cancer mortality studies

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Diabetes and Cancer

Two main questions:

I Do diabetes patients get cancer more oftenthan non-diabetics?— cancer incidence studies

I Do cancer patients with diabetes die earlierthan cancer patients without diabetes?— cancer survival studies

I Combination (ignoring the cancer diagnosis):Do diabetes patients die more frequently fromcancer than non-diabetics?— cancer mortality studies

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Diabetes and Cancer

Two main questions:

I Do diabetes patients get cancer more oftenthan non-diabetics?— cancer incidence studies

I Do cancer patients with diabetes die earlierthan cancer patients without diabetes?— cancer survival studies

I Combination (ignoring the cancer diagnosis):Do diabetes patients die more frequently fromcancer than non-diabetics?— cancer mortality studies

3/ 16

Diabetes and Cancer

Two main questions:

I Do diabetes patients get cancer more oftenthan non-diabetics?— cancer incidence studies

I Do cancer patients with diabetes die earlierthan cancer patients without diabetes?— cancer survival studies

I Combination (ignoring the cancer diagnosis):Do diabetes patients die more frequently fromcancer than non-diabetics?— cancer mortality studies

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This discussion

I Broader epidemiological / demographic view ofcancer incidence among diabetes patients

I Exemplified by two studies not included in PB’smetaanalysis:

I Johnson et al.:Time-varying incidence of cancer after the onset oftype 2 diabetes: evidence of potential detectionbiasDiabetologia (2011) 54:2263-2271

I Carstensen et al.:Cancer occurrence in Danish diabetic patients:duration and insulin effectsDiabetologia (2012) 55:948-958

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This discussion

I Broader epidemiological / demographic view ofcancer incidence among diabetes patients

I Exemplified by two studies not included in PB’smetaanalysis:

I Johnson et al.:Time-varying incidence of cancer after the onset oftype 2 diabetes: evidence of potential detectionbiasDiabetologia (2011) 54:2263-2271

I Carstensen et al.:Cancer occurrence in Danish diabetic patients:duration and insulin effectsDiabetologia (2012) 55:948-958

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This discussion

I Broader epidemiological / demographic view ofcancer incidence among diabetes patients

I Exemplified by two studies not included in PB’smetaanalysis:

I Johnson et al.:Time-varying incidence of cancer after the onset oftype 2 diabetes: evidence of potential detectionbiasDiabetologia (2011) 54:2263-2271

I Carstensen et al.:Cancer occurrence in Danish diabetic patients:duration and insulin effectsDiabetologia (2012) 55:948-958

4/ 16

This discussion

I Broader epidemiological / demographic view ofcancer incidence among diabetes patients

I Exemplified by two studies not included in PB’smetaanalysis:

I Johnson et al.:Time-varying incidence of cancer after the onset oftype 2 diabetes: evidence of potential detectionbiasDiabetologia (2011) 54:2263-2271

I Carstensen et al.:Cancer occurrence in Danish diabetic patients:duration and insulin effectsDiabetologia (2012) 55:948-958

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Diabetes and Cancer problems

I All studies are observational

I All studies are subject to confounding byindication:

I influenced clinically by diabetes diagnosis.I influenced by decison of diabetes treatment.

I There is no remedy for this.

I Description of cancer occurrence in diabetespatients.

I Causal interpretations are pure speculation.

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Diabetes and Cancer problems

I All studies are observational

I All studies are subject to confounding byindication:

I influenced clinically by diabetes diagnosis.I influenced by decison of diabetes treatment.

I There is no remedy for this.

I Description of cancer occurrence in diabetespatients.

I Causal interpretations are pure speculation.

5/ 16

Diabetes and Cancer problems

I All studies are observational

I All studies are subject to confounding byindication:

I influenced clinically by diabetes diagnosis.I influenced by decison of diabetes treatment.

I There is no remedy for this.

I Description of cancer occurrence in diabetespatients.

I Causal interpretations are pure speculation.

5/ 16

Diabetes and Cancer problems

I All studies are observational

I All studies are subject to confounding byindication:

I influenced clinically by diabetes diagnosis.I influenced by decison of diabetes treatment.

I There is no remedy for this.

I Description of cancer occurrence in diabetespatients.

I Causal interpretations are pure speculation.

5/ 16

Diabetes and Cancer problems

I All studies are observational

I All studies are subject to confounding byindication:

I influenced clinically by diabetes diagnosis.I influenced by decison of diabetes treatment.

I There is no remedy for this.

I Description of cancer occurrence in diabetespatients.

I Causal interpretations are pure speculation.

5/ 16

Diabetes and Cancer problems

I All studies are observational

I All studies are subject to confounding byindication:

I influenced clinically by diabetes diagnosis.I influenced by decison of diabetes treatment.

I There is no remedy for this.

I Description of cancer occurrence in diabetespatients.

I Causal interpretations are pure speculation.

5/ 16

The Danish & British Columbia studiesCarstensen et al., Diabetologia, 2012

Johnson et al., Diabetologia, 2011

I Cancer incidence study in the total population.

I Comparing diabetes patients with non-diabetespatients.

I Outcome: Rate-ratio of cancer occurrencebetween DM-patients and non-DM persons inthe entire population.

I Cancers in DM ptt: Denmark 22,826B.C. 12,438

— by far the largest studies to date.

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The Danish & British Columbia studiesCarstensen et al., Diabetologia, 2012

Johnson et al., Diabetologia, 2011

I Cancer incidence study in the total population.

I Comparing diabetes patients with non-diabetespatients.

I Outcome: Rate-ratio of cancer occurrencebetween DM-patients and non-DM persons inthe entire population.

I Cancers in DM ptt: Denmark 22,826B.C. 12,438

— by far the largest studies to date.

6/ 16

The Danish & British Columbia studiesCarstensen et al., Diabetologia, 2012

Johnson et al., Diabetologia, 2011

I Cancer incidence study in the total population.

I Comparing diabetes patients with non-diabetespatients.

I Outcome: Rate-ratio of cancer occurrencebetween DM-patients and non-DM persons inthe entire population.

I Cancers in DM ptt: Denmark 22,826B.C. 12,438

— by far the largest studies to date.

6/ 16

The Danish & British Columbia studiesCarstensen et al., Diabetologia, 2012

Johnson et al., Diabetologia, 2011

I Cancer incidence study in the total population.

I Comparing diabetes patients with non-diabetespatients.

I Outcome: Rate-ratio of cancer occurrencebetween DM-patients and non-DM persons inthe entire population.

I Cancers in DM ptt: Denmark 22,826B.C. 12,438

— by far the largest studies to date.

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The Danish study — main sitesRate ratios

All cancers 1.2Digestive system ≈ 1.2Liver M: 4.0 F: 1.8Pancreas 2.8Lung 1.2Breast 1.04 (1.00; 1.09)Endometrium 1.6Kidney 1.7Bladder M: 1.2 F: 1.0Prostate 0.95Brain, lymphomas 1.2

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The Danish study — main sitesRate ratios

All cancers 1.2Digestive system ≈ 1.2Liver M: 4.0 F: 1.8Pancreas 2.8Lung 1.2Breast 1.04 (1.00; 1.09)Endometrium 1.6Kidney 1.7Bladder M: 1.2 F: 1.0Prostate 0.95Brain, lymphomas 1.2

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Danish study

Well

Ca (W) Dead (Ca)

Dead (O)

DM

Ca (DM) Dead (Ca)

Dead (O)

DM+Ins

Ca (Ins) Dead (Ca)

Dead (O)

Well

Ca (W) Dead (Ca)

Dead (O)

DM

Ca (DM) Dead (Ca)

Dead (O)

DM+Ins

Ca (Ins) Dead (Ca)

Dead (O)

Well

Ca (W) Dead (Ca)

Dead (O)

DM

Ca (DM) Dead (Ca)

Dead (O)

DM+Ins

Ca (Ins) Dead (Ca)

Dead (O)

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0 3 6 9 120.5

1.0

2.0

5.0

●

●

M

0 3 6 9 12

●

●

F

Diabetes duration (years)

Rat

e ra

tio D

M, D

M+

Ins

vs N

o D

M

All malignant neoplasms

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0 3 6 9 120.5

1.0

2.0

5.0

●

M

0 3 6 9 12

●

F

Insulin duration (years)

Rat

e ra

tio D

M+

Ins

vs D

M

All malignant neoplasms

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0 3 6 9 12

0.5

1.0

2.0

●

●

0 3 6 9 12

●●

Diabetes duration (years)

Rat

e ra

tio D

M, D

M+

Ins

vs N

o D

M

Prostate Breast

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Johnson et

al, Diabetolo-

gia, 2011

Breastcancer

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Johnson et

al, Diabetolo-

gia, 2011

Prostatecancer

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0 3 6 9 120.5

1.0

2.0

5.0

●

●

M

0 3 6 9 12

●

●

F

Diabetes duration (years)

Rat

e ra

tio D

M, D

M+

Ins

vs N

o D

M

Lung, bronchus and pleura

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Cumulative risk of cancer

No DM DM DM+InsM F M F M F

0

20

40

60

80

10010

yea

r cu

mul

ativ

e ris

ks o

f can

cer

and

deat

hAge at start: 60 years Age at start: 65 years Age at start: 70 years

No DM DM DM+InsM F M F M F

Age at start: 60 years Age at start: 65 years Age at start: 70 years

No DM DM DM+InsM F M F M F

Age at start: 60 years Age at start: 65 years Age at start: 70 years

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Conclusions

1. Detection “bias” (shortly after diagnosis ofdiabetes) ⇒ overall effects on incidence mustevaluated in the long term

2. Short term-studies (e.g. Glargine) studies likelybiased.

3. Colorectal, liver, pancreas, corpus uteri, kidneyhave elevated long-term rates.

4. Insulin treated generally have higher cancerrates than non-insulin treated.

5. Lung cancer elevated only for insulin treated.6. No exess risk of breast cancer for DM patients,

regardless of treatment.7. Smaller incidence rates for prostate.

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Conclusions

1. Detection “bias” (shortly after diagnosis ofdiabetes) ⇒ overall effects on incidence mustevaluated in the long term

2. Short term-studies (e.g. Glargine) studies likelybiased.

3. Colorectal, liver, pancreas, corpus uteri, kidneyhave elevated long-term rates.

4. Insulin treated generally have higher cancerrates than non-insulin treated.

5. Lung cancer elevated only for insulin treated.6. No exess risk of breast cancer for DM patients,

regardless of treatment.7. Smaller incidence rates for prostate.

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Conclusions

1. Detection “bias” (shortly after diagnosis ofdiabetes) ⇒ overall effects on incidence mustevaluated in the long term

2. Short term-studies (e.g. Glargine) studies likelybiased.

3. Colorectal, liver, pancreas, corpus uteri, kidneyhave elevated long-term rates.

4. Insulin treated generally have higher cancerrates than non-insulin treated.

5. Lung cancer elevated only for insulin treated.6. No exess risk of breast cancer for DM patients,

regardless of treatment.7. Smaller incidence rates for prostate.

16/ 16

Conclusions

1. Detection “bias” (shortly after diagnosis ofdiabetes) ⇒ overall effects on incidence mustevaluated in the long term

2. Short term-studies (e.g. Glargine) studies likelybiased.

3. Colorectal, liver, pancreas, corpus uteri, kidneyhave elevated long-term rates.

4. Insulin treated generally have higher cancerrates than non-insulin treated.

5. Lung cancer elevated only for insulin treated.6. No exess risk of breast cancer for DM patients,

regardless of treatment.7. Smaller incidence rates for prostate.

16/ 16

Conclusions

1. Detection “bias” (shortly after diagnosis ofdiabetes) ⇒ overall effects on incidence mustevaluated in the long term

2. Short term-studies (e.g. Glargine) studies likelybiased.

3. Colorectal, liver, pancreas, corpus uteri, kidneyhave elevated long-term rates.

4. Insulin treated generally have higher cancerrates than non-insulin treated.

5. Lung cancer elevated only for insulin treated.6. No exess risk of breast cancer for DM patients,

regardless of treatment.7. Smaller incidence rates for prostate.

16/ 16

Conclusions

1. Detection “bias” (shortly after diagnosis ofdiabetes) ⇒ overall effects on incidence mustevaluated in the long term

2. Short term-studies (e.g. Glargine) studies likelybiased.

3. Colorectal, liver, pancreas, corpus uteri, kidneyhave elevated long-term rates.

4. Insulin treated generally have higher cancerrates than non-insulin treated.

5. Lung cancer elevated only for insulin treated.6. No exess risk of breast cancer for DM patients,

regardless of treatment.7. Smaller incidence rates for prostate.

16/ 16

Conclusions

1. Detection “bias” (shortly after diagnosis ofdiabetes) ⇒ overall effects on incidence mustevaluated in the long term

2. Short term-studies (e.g. Glargine) studies likelybiased.

3. Colorectal, liver, pancreas, corpus uteri, kidneyhave elevated long-term rates.

4. Insulin treated generally have higher cancerrates than non-insulin treated.

5. Lung cancer elevated only for insulin treated.6. No exess risk of breast cancer for DM patients,

regardless of treatment.7. Smaller incidence rates for prostate.

16/ 16

Conclusions

1. Detection “bias” (shortly after diagnosis ofdiabetes) ⇒ overall effects on incidence mustevaluated in the long term

2. Short term-studies (e.g. Glargine) studies likelybiased.

3. Colorectal, liver, pancreas, corpus uteri, kidneyhave elevated long-term rates.

4. Insulin treated generally have higher cancerrates than non-insulin treated.

5. Lung cancer elevated only for insulin treated.6. No exess risk of breast cancer for DM patients,

regardless of treatment.7. Smaller incidence rates for prostate.

16/ 16

Conclusions

1. Detection “bias” (shortly after diagnosis ofdiabetes) ⇒ overall effects on incidence mustevaluated in the long term

2. Short term-studies (e.g. Glargine) studies likelybiased.

3. Colorectal, liver, pancreas, corpus uteri, kidneyhave elevated long-term rates.

4. Insulin treated generally have higher cancerrates than non-insulin treated.

5. Lung cancer elevated only for insulin treated.6. No exess risk of breast cancer for DM patients,

regardless of treatment.7. Smaller incidence rates for prostate.

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