Diabetes and Cancer: A Consensus Report

Giovannucci, Edward; Harlan, David M.; Archer, Michael C.; Bergenstal, Richard M.; Gapstur, Susan M.; Habel, Laurel A.; Pollak, Michael; Regensteiner, Judith G.; Yee, Douglas

doi:10.3322/caac.20078

Cited by 1,100 publications

(1,126 citation statements)

References 117 publications

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“…A Danish study utilising a populationbased register (26) found that men and women with diabetes were at 10% increased risk but only hospitalised patients were included and diabetes status was ascertained using inpatient coding alone. Because of differences in apparent relationships between diabetes and the various types of malignancy, analyses of associations with all-cause cancers have been discouraged (8). However, the consistency of the results of this and other studies (22,23,24,26,27) suggests that there is a moderate diabetes-specific increase in overall cancer risk.…”

Section: Discussionmentioning

confidence: 81%

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Incidence and predictors of all-cause and site-specific cancer in type 2 diabetes: the Fremantle Diabetes Study

Magliano

Davis

Shaw

et al. 2012

European Journal of Endocrinology

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Objective: To explore the relationship between diabetes and cancer. Design: The Fremantle Diabetes Study (FDS) was a community-based longitudinal observational study of 1426 subjects, 1294 of which had type 2 diabetes. Methods: The FDS type 2 cohort and four age-, sex-and postcode-matched controls per case were followed for cancer events from 1993 until mid-2010 and incidence rate ratios (IRRs) were calculated. Competing risks proportional hazards models generated risk factors for incident cancers in the diabetic group. Results: There were 309 first cancers over 13 051 patient-years, or 2368 (95% confidence interval (95% CI) 2111-2647)/100 000 patient-years in the diabetes patients vs 1131 over 60 324 patient-years (1875 (1769-1987)/100 000 patient-years) in the controls. For those aged R45 years, the risk of all-cause cancer was elevated in type 2 diabetic men (IRRs 1.23, 95% CI 1.04-1.45) and women (1.30, 1.06-1.59). The incidence of colorectal cancer was increased (1.36, 1.01-1.82), especially in diabetic men aged 75-84 years (2.14, 1.22-3.64). Age at diabetes diagnosis (sub-hazard ratio 1.05, 1.02-1.09), calcium channel blocker therapy (2.37, 1.39-4.06), recent exercise (2.11, 1.06-4.20) and serum total cholesterol (0.68, 0.52-0.88) increased colorectal cancer risk. Pancreatic cancer was also more frequent in the diabetic patients (IRR 2.26,. Diabetic men and women had similar risks of prostate and breast cancer to those of controls (0.83, 0.59-1.14 and 0.86, 0.52-1.36). Conclusions: Type 2 diabetes is associated with a moderately increased cancer risk in well-characterised community-based patients, especially pancreatic cancer and colorectal cancer in older men. Recommended cancer screening should be considered as part of routine diabetes management.

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Section: Discussionmentioning

confidence: 81%

“…Associations between diabetes and cancer may, however, be confounded by co-incident risk factors including ageing, obesity and insulin resistance, an imprudent diet and lack of physical activity (8). In addition, some diabetes treatments may increase (9,10,11) or decrease (12) cancer risk.…”

Section: Introductionmentioning

confidence: 99%

Incidence and predictors of all-cause and site-specific cancer in type 2 diabetes: the Fremantle Diabetes Study

Magliano

Davis

Shaw

et al. 2012

European Journal of Endocrinology

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“…Diabetes is an important risk factor for cardiovascular disease. Increasing evidence also relates diabetes to a higher risk of cancer, including cancers of the pancreas, endometrium, liver, colorectum, and breast, possibly by mechanisms related to hyperinsulinema, hyperglycemia, and chronic inflammation 46. Furthermore, some studies found that diabetes may increase mortality in patients with cancer 47.…”

Section: Discussionmentioning

confidence: 99%

Trajectory of body shape in early and middle life and all cause and cause specific mortality: results from two prospective US cohort studies

Song

et al. 2016

BMJ

103

101

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Objective To assess body shape trajectories in early and middle life in relation to risk of mortality.Design Prospective cohort study.Setting Nurses’ Health Study and Health Professionals Follow-up Study.Population 80 266 women and 36 622 men who recalled their body shape at ages 5, 10, 20, 30, and 40 years and provided body mass index at age 50, followed from age 60 over a median of 15-16 years for death.Main outcome measures All cause and cause specific mortality.Results Using a group based modeling approach, five distinct trajectories of body shape from age 5 to 50 were identified: lean-stable, lean-moderate increase, lean-marked increase, medium-stable/increase, and heavy-stable/increase. The lean-stable group was used as the reference. Among never smokers, the multivariable adjusted hazard ratio for death from any cause was 1.08 (95% confidence interval 1.02 to 1.14) for women and 0.95 (0.88 to 1.03) for men in the lean-moderate increase group, 1.43 (1.33 to 1.54) for women and 1.11 (1.02 to 1.20) for men in the lean-marked increase group, 1.04 (0.97 to 1.12) for women and 1.01 (0.94 to 1.09) for men in the medium-stable/increase group, and 1.64 (1.49 to 1.81) for women and 1.19 (1.08 to 1.32) for men in the heavy-stable/increase group. For cause specific mortality, participants in the heavy-stable/increase group had the highest risk, with a hazard ratio among never smokers of 2.30 (1.88 to 2.81) in women and 1.45 (1.23 to 1.72) in men for cardiovascular disease, 1.37 (1.14 to 1.65) in women and 1.07 (0.89 to 1.30) in men for cancer, and 1.59 (1.38 to 1.82) in women and 1.10 (0.95 to 1.29) in men for other causes. The trajectory-mortality association was generally weaker among ever smokers than among never smokers (for all cause mortality: P for interaction <0.001 in women and 0.06 in men). When participants were classified jointly according to trajectories and history of type 2 diabetes, the increased risk of death associated with heavier body shape trajectories was more pronounced among participants with type 2 diabetes than those without diabetes, and those in the heavy-stable/increase trajectory and with a history of diabetes had the highest risk of death.Conclusions Using the trajectory approach, we found that heavy body shape from age 5 up to 50, especially the increase in middle life, was associated with higher mortality. In contrast, people who maintained a stably lean body shape had the lowest mortality. These results indicate the importance of weight management across the lifespan.

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“…Carstensen et al (2012) recently analyzed the effect of diabetes and diabetic therapy on cancer incidence in the Danish health system over a 27-year period and noted that the adverse effects of insulin treatment were quite modest. Therefore, caution has been advised in the acceptance of a cancer-promoting effect of insulin until further data are available (Gerstein 2010, Giovannucci et al 2010, Hernandez-Diaz & Adami 2010. Insulin therapy has also been associated with a greater than expected incidence of breast cancer and other malignancies (Home & Lagarenne 2009, Jonasson et al 2009), however, and insulin secretagogues have similarly been implicated in an increased incidence of PC.…”

Section: Proposed Mechanisms Of Diabetes-related Pancreatic Carcinogementioning

confidence: 99%

Diabetes and pancreatic cancer

Cui¹,

Andersen²

2012

Endocrine-Related Cancer

131

102

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Epidemiological studies clearly indicate that the risk of pancreatic cancer (PC) is increased in diabetic patients, but most studies focus on overall diabetes or type 2 diabetes mellitus (T2DM), and there are few studies on the risks of type 1 and type 3c (secondary) diabetes. Possible mechanisms for increased cancer risk in diabetes include cellular proliferative effects of hyperglycemia, hyperinsulinemia, and abnormalities in insulin/IGF receptor pathways. Recently, insulin and insulin secretagogues have been observed to increase the PC risk, while metformin treatment reduces the cancer risk in diabetic subjects. In addition, anticancer drugs used to treat PC may either cause diabetes or worsen coexisting diabetes. T3cDM has emerged as a major subset of diabetes and may have the highest risk of pancreatic carcinoma especially in patients with chronic pancreatitis. T3cDM is also a consequence of PC in at least 30% of patients. Distinguishing T3cDM from the more prevalent T2DM among new-onset diabetic patients can be aided by an assessment of clinical features and confirmed by finding a deficiency in postprandial pancreatic polypeptide release. In conclusion, diabetes and PC have a complex relationship that requires more clinical attention. The risk of developing PC can be reduced by aggressive prevention and treatment of T2DM and obesity and the prompt diagnosis of T3cDM may allow detection of a tumor at a potentially curable stage.

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Diabetes and Cancer: A Consensus Report

Cited by 1,100 publications

References 117 publications

Incidence and predictors of all-cause and site-specific cancer in type 2 diabetes: the Fremantle Diabetes Study

Incidence and predictors of all-cause and site-specific cancer in type 2 diabetes: the Fremantle Diabetes Study

Trajectory of body shape in early and middle life and all cause and cause specific mortality: results from two prospective US cohort studies

Diabetes and pancreatic cancer

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