The DOI matches its Crossref record, with a small difference in title or year; 90 of the 90 references it cites were found in a registry or an index; none of the 32 sources its claims cite is checked for support yet.
Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus: A Systematic Review and Meta-analysis
Open accessAbstract
CONTEXT: Diabetes mellitus appears to be a risk factor for some cancers, but the effect of preexisting diabetes on all-cause mortality in newly diagnosed cancer patients is less clear. OBJECTIVE: To perform a systematic review and meta-analysis comparing overall survival in cancer patients with and without preexisting diabetes. DATA SOURCES: We searched MEDLINE and EMBASE through May 15, 2008, including references of qualifying articles. STUDY SELECTION: English-language, original investigations in humans with at least 3 months of follow-up were included. Titles, abstracts, and articles were reviewed by at least 2 independent readers. Of 7858 titles identified in our original search, 48 articles met our criteria. DATA EXTRACTION: One reviewer performed a full abstraction and other reviewers verified accuracy. We contacted authors and obtained additional information for 3 articles with insufficient reported data. RESULTS: Studies reporting cumulative survival rates were summarized qualitatively. Studies reporting Cox proportional hazard ratios (HRs) or Poisson relative risks were combined in a meta-analysis. A random-effects model meta-analysis of 23 articles showed that diabetes was associated with an increased mortality HR of 1.41 (95% confidence interval [CI], 1.28-1.55) compared with normoglycemic individuals across all cancer types. Subgroup analyses by type of cancer showed increased risk for cancers of the endometrium (HR, 1.76; 95% CI, 1.34-2.31), breast (HR, 1.61; 95% CI, 1.46-1.78), and colorectum (HR, 1.32; 95% CI, 1.24-1.41). CONCLUSIONS: Patients diagnosed with cancer who have preexisting diabetes are at increased risk for long-term, all-cause mortality compared with those without diabetes.
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TL;DR
In cancer patients with preexisting diabetes, pooled long-term all-cause mortality was significantly higher than in normoglycemic patients (HR 1.41; 95% CI, 1.28-1.55) across 23 studies. Significant site-specific increases were found for endometrial, breast, and colorectal cancers.
Key findings
- Meta-analysis of 23 studies found preexisting diabetes associated with increased all-cause mortality after cancer diagnosis: HR 1.41 (95% CI, 1.28-1.55).
- Site-specific pooled estimates were significant for endometrium (HR 1.76; 95% CI, 1.34-2.31), breast (HR 1.61; 95% CI, 1.46-1.78), and colorectum (HR 1.32; 95% CI, 1.24-1.41).
- Nonsignificant increases were reported for prostate (HR 1.51; 95% CI, 0.94-2.43), gastric (HR 1.36; 95% CI, 0.92-2.01), hepatocellular (HR 1.30; 95% CI, 0.99-1.70), lung (HR 1.15; 95% CI, 0.99-1.34), and pancreatic cancer (HR 1.09; 95% CI, 0.70-1.69).
- Sensitivity analyses excluding univariate estimates gave HR 1.40 (95% CI, 1.29-1.52); excluding analyses not adjusting/restricting for age and disease severity gave HR 1.42 (95% CI, 1.28-1.56). No significant publication bias was observed by Begg test (P = .92) or Egger plot (P = .34).
Methods
- Systematic review and meta-analysis searching MEDLINE and EMBASE through May 15, 2008; 7,858 titles identified, 48 articles met criteria for the systematic review of long-term all-cause mortality, and 23 studies met criteria for meta-analysis.
- Included English-language human original investigations with at least 3 months follow-up; meta-analysis required risk estimates (HR/RR) and precision estimates, with authors contacted for additional data.
- Random-effects meta-analysis using DerSimonian-Laird method; heterogeneity assessed with Cochran Q and I²; publication bias assessed with Begg funnel plot and Egger plot; sensitivity analyses and nonparametric sign test performed.
Limitations
- The paper states substantial heterogeneity across studies in demographics, diabetes ascertainment, and confounder adjustment; heterogeneity was significant by Q statistic (205 on 24 df, P < .001) and I² (88.3%, P < .001).
- The paper states studies spanned many decades (published 1969-2008), follow-up time was not always reported, and differences in follow-up may limit interpretation.
- Evident from the text: 9 studies with regression models had insufficient reporting for meta-analysis, only 3 of 12 contacted authors provided additional information, and many studies did not adjust for age and cancer severity; power was low (<50%) for prostate, gastric, hepatocellular, lung, and pancreatic cancer estimates.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Subgroup analyses by type of cancer showed increased risk for cancers of the endometrium (HR, 1.76; 95% CI, 1.34-2.31), breast (HR, 1.61; 95% CI, 1.46-1.78), and colorectum (HR, 1.32; 95% CI, 1.24-1.41).”
- Also stated in: § Sensitivity Analyses · plain
“Preexisting diabetes was significantly associated with increased long-term, all-cause mortality for cancers of the endometrium (HR, 1.76; 95% CI, 1.34-2.31), breast (HR, 1.61; 95% CI, 1.46-1.78), and colorectum (HR, 1.32; 95% CI, 1.24-1.41).”
§ Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus > Abstract > Results
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We performed a nonparametric sign test and found no association between diabetes and increased cancer-specific mortality (P=.69).”
§ Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus > Results > Cancer-Specific and Noncancer Mortality
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In the paper
“Diabetes was associated with a nonsignificant increase in risk in prostate (HR, 1.51; 95% CI, 0.94-2.43), gastric (HR, 1.36; 95% CI, 0.92-2.01), hepatocellular (HR, 1.30; 95% CI, 0.99-1.70), lung (HR, 1.15; 95% CI, 0.99-1.34), and pancreatic cancer (HR, 1.09; 95% CI, 0.70-1.69).”
§ Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus > Results > Sensitivity Analyses
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In the paper
“In our analysis, however, stage at diagnosis appeared not to be a major explanatory factor.”
§ Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus > Comment
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In the paper
“No study included in this systematic review reported that diabetes was associated with significantly better survival.”
§ Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus > Results > Systematic Review of Evidence
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In the paper
“The large I2 value (88%) indicates that the range of plausible risk estimates is wide”
§ Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus > Comment
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“population-based studies (8 estimates) had a pooled HR of 1.39 (95% CI, 1.27-1.52)”
§ Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus > Results > Sensitivity Analyses
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Diabetes was associated with a nonsignificant increase in risk in prostate (HR, 1.51; 95% CI, 0.94-2.43), gastric (HR, 1.36; 95% CI, 0.92-2.01), hepatocellular (HR, 1.30; 95% CI, 0.99-1.70), lung (HR, 1.15; 95% CI, 0.99-1.34), and pancreatic cancer (HR, 1.09; 95% CI, 0.70-1.69).”
§ Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus > Results > Sensitivity Analyses
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Diabetes was associated with a nonsignificant increase in risk in prostate (HR, 1.51; 95% CI, 0.94-2.43), gastric (HR, 1.36; 95% CI, 0.92-2.01), hepatocellular (HR, 1.30; 95% CI, 0.99-1.70), lung (HR, 1.15; 95% CI, 0.99-1.34), and pancreatic cancer (HR, 1.09; 95% CI, 0.70-1.69).”
§ Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus > Results > Sensitivity Analyses
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We also calculated separate estimates for the 9 studies that considered diabetes as the primary exposure (HR, 1.42; 95% CI, 1.30-1.56)”
§ Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus > Results > Sensitivity Analyses
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- It may state two separate claims as one. 19
- Probably not a substantial claim. 17
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A random-effects model meta-analysis of 23 articles showed that diabetes was associated with an increased mortality HR of 1.41 (95% confidence interval [CI], 1.28-1.55) compared with normoglycemic individuals across all cancer types.”
- Also stated in: § Meta-analysis · plain
“Preexisting diabetes was associated with an increase in all-cause mortality following cancer diagnosis (HR = 1.41; 95% CI, 1.28-1.55).”
- Also stated in: § Comment · plain
“Preexisting diabetes in cancer patients at the time of diagnosis was associated with an HR of 1.41 for the risk of all-cause mortality compared with individuals without diabetes when pooled across 23 studies of various types of cancer.”
§ Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus > Abstract > Results
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § Meta-analysis · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Of 9 estimates from 8 articles reporting the association of diabetes with cancer-specific mortality, 2 estimates found significantly higher risk,48,78 2 estimates found a nonsignificantly higher risk,36,77 2 estimates found a nonsignificantly lower risk,42,77 and 3 articles did not report a direction of effect.47,68,76”
§ Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus > Results > Cancer-Specific and Noncancer Mortality
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The sign test rejected the null hypothesis of equal mortality in patients with and without preexisting diabetes whether we excluded studies that did not report a direction of effect (P = .001) or assumed studies that did not report a direction of effect fell evenly in either category (5 each side, P=.005).”
§ Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus > Results > Systematic Review of Evidence
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- The authors state this as an assumption: In the sign test, studies that did not report a direction of effect fell evenly in either category.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The omission of any one study did not appreciably change the pooled HR, and the estimates in each case were well within the confidence limits of the overall estimate.”
§ Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus > Results > Sensitivity Analyses
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Heterogeneity was significant by the Q statistic (205 on 24 df, P < .001) and by I2 (88.3%, P < .001).”
§ Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus > Results > Meta-analysis
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
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In the paper
“Our subsidiary analysis of studies that distinguished between cancer and noncancer mortality was inconclusive, so this possibility cannot be excluded.”
§ Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus > Comment
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None of the sources cited for this claim have been checked yet.
In the paper
“Of the 3 studies evaluating noncancer mortality, 2 found a significant association with increased risk among patients with preexisting diabetes36,79 and 1 article reported a nonsignificant association with no direction of effect.67”
§ Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus > Results > Cancer-Specific and Noncancer Mortality
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Overall, 32 study estimates found diabetes was associated with increased risk of mortality, 7 found diabetes was associated with decreased risk of mortality, 1 found a null effect, and 10 did not report a direction of effect.”
§ Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus > Results > Systematic Review of Evidence
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“It is possible that high insulin or insulin-like growth factor levels may promote cancer cell and tumor growth.10”
§ Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus > Comment
What the sources say
- Not checked yetcites [10] Richardson LC Pollack LA Therapy insight: influence of type 2 diabetes on the development, treatment and outcomes of cancer Nat Clin Pract Oncol 2005 2 1 48 53 16264856
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Because some cancers—including cancers of the breast,2 colorectum,3 endometrium,4 liver,5 and pancreas6—occur more commonly in individuals with diabetes”
§ Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus > Abstract > Conclusions
What the sources say
- Not checked yetcites [2] Larsson SC Mantzoros CS Wolk A Diabetes mellitus and risk of breast cancer: a meta-analysis Int J Cancer 2007 121 4 856 862 17397032
- Not checked yetcites [3] Larsson SC Orsini N Wolk A Diabetes mellitus and risk of colorectal cancer: a meta-analysis J Natl Cancer Inst 2005 97 22 1679 1687 16288121
- Not checked yetcites [4] Friberg E Orsini N Mantzoros CS Wolk A Diabetes mellitus and risk of endometrial cancer: a meta-analysis Diabetologia 2007 50 7 1365 1374 17476474
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Using the method described by Cohn and Becker,27 post hoc power calculations based on the overall and site-specific pooled HRs revealed excellent power (≥95%) for overall, endometrial, breast, and colorectal cancer estimates and low power (<50%) for prostate, gastric, hepatocellular, lung, and pancreatic cancer estimates.”
§ Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus > Methods > Data Synthesis and Statistical Analysis
What the sources say
- Not checked yetcites Cohn and Becker,27
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In the paper
“Diabetes is a well-established risk factor for cardiovascular mortality in adults without cancer,86”
§ Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus > Comment
What the sources say
- Not checked yetcites [86] Morrish NJ Wang SL Stevens LK Fuller JH Keen H Mortality and causes of death in the WHO Multinational Study of Vascular Disease in Diabetes Diabetologia 2001 44 suppl 2 S14 S21 11587045
Strength:boosted· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Third, patients with preexisting diabetes may have poorer response to cancer treatment, including increased infection risk and intraoperative mortality.39,81”
§ Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus > Comment
What the sources say
- Not checked yetcites [39] Meyerhardt JA Catalano PJ Haller DG Impact of diabetes mellitus on outcomes in patients with colon cancer J Clin Oncol 2003 21 3 433 440 12560431
- Not checked yetcites [81] Weiser MA Cabanillas ME Konopleva M Relation between the duration of remission and hyperglycemia during induction chemotherapy for acute lymphocytic leukemia with a hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone/methotrexatecytarabine regimen Cancer 2004 100 6 1179 1185 15022284
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Of the 12 authors contacted, 3 were able to provide additional information, 4 were unable to furnish the necessary information, and 5 did not respond to our request.”
§ Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus > Methods > Data Synthesis and Statistical Analysis
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In the paper
“Cancer patients with diabetes may receive less aggressive cancer treatment or less aggressive diabetes care, both of which could compromise survival.10”
§ Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus > Abstract > Conclusions
What the sources say
- Not checked yetcites [10] Richardson LC Pollack LA Therapy insight: influence of type 2 diabetes on the development, treatment and outcomes of cancer Nat Clin Pract Oncol 2005 2 1 48 53 16264856
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
In the paper
“Fleming et al83 found that women older than 67 years with preexisting diabetes had a 17% greater risk of being diagnosed with late vs early stage breast cancer in the SEER database compared with normoglycemic women.”
§ Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus > Comment
What the sources say
- Not checked yetcites Fleming et al83
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Fourth, patients with preexisting diabetes may present with later-stage disease because of suboptimal cancer screening practices.82”
§ Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus > Comment
What the sources say
- Not checked yetcites [82] Beckman TJ Cuddihy RM Scheitel SM Naessens JM Killian JM Pankratz VS Screening mammogram utilization in women with diabetes Diabetes Care 2001 24 12 2049 2053 11723081
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Adults with diabetes experienced increased cancer mortality in the American Cancer Society Cancer Prevention Study II,8 but not in the Second National Health and Nutrition Examination Survey Mortality Follow-Up.9”
§ Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus > Abstract > Conclusions
What the sources say
- Not checked yetcites [8] Coughlin SS Calle EE Teras LR Petrelli J Thun MJ Diabetes mellitus as a predictor of cancer mortality in a large cohort of US adults Am J Epidemiol 2004 159 12 1160 1167 15191933
- Not checked yetcites [9] Saydah SH Loria CM Eberhardt MS Brancati FL Abnormal glucose tolerance and the risk of cancer death in the United States Am J Epidemiol 2003 157 12 1092 1100 12796045
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Quality was assessed using elements of the STROBE checklist for cohort studies considered important for quality in these studies.11”
§ Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus > Methods > Data Extraction and Quality Assessment
What the sources say
- Not checked yetcites [11] von Elm E Altman DG Egger M Pocock SJ Gøtzsche PC Vandenbroucke JP STROBE initiative: the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies J Clin Epidemiol 2008 61 4 344 349 18313558
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“While the association of diabetes and site-specific mortality risk reached statistical significance only for cancers of the endometrium, breast, and colorectum, diabetes appeared to be associated with some additional mortality risk for all types of cancer.”
§ Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus > Comment
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The majority of the studies included in the review evaluated multiple prognostic variables, which likely decreased the risk of publication bias with respect to the relationship between diabetes and mortality in this patient population”
§ Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus > Comment
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Finally, differences in follow-up time, which was not always reported, may also limit interpretation of the results.”
§ Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus > Comment
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“One reviewer performed a full abstraction and other reviewers verified accuracy.”
§ Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus > Abstract > Data Extraction
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None of the sources cited for this claim have been checked yet.
In the paper
“However, experts in cancer epidemiology recognize that attribution of cause of death is often problematic and that undue reliance on attributed cause can bias estimates of risk related to cancer treatment.87-90”
§ Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus > Comment
What the sources say
- Not checked yetcites [87] Begg CB Schrag D Attribution of deaths following cancer treatment J Natl Cancer Inst 2002 94 14 1044 1045 12122090
- Not checked yetcites [88] Ederer F Geisser MS Mongin SJ Church TR Mendel JS Colorectal cancer deaths as determined by expert committee and from death certification: a comparison J Clin Epidemiol 1999 52 5 447 452 10360340
- Not checked yetcites [89] Welch HG Black WC Are deaths within 1 month of cancer-directed surgery attributed to cancer? J Natl Cancer Inst 2002 94 14 1066 1070 12122097
- Not checked yetcites [90] Lu TH Shih TP Lee MC Chou MC Lin CK Diversity in death certification: a case vignette approach J Clin Epidemiol 2001 54 11 1086 1093 11675159
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Fifth, the diagnosis and treatment of cancer may distract both the patient and the health care team from appropriate management of glycemia, blood pressure, and lipids, proven to reduce morbidity and mortality in diabetic adults.”
§ Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus > Comment
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✗ Checkable: fails✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Titles, abstracts, and articles were reviewed by at least 2 independent readers.”
§ Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus > Abstract > Study Selection
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and the microvascular and macrovascular damage it causes likely accumulates to some extent regardless of cancer status.”
§ Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus > Comment
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✗ Checkable: fails✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
In the paper
“First, cancer patients with diabetes may have increased tumor cell proliferation and metastases in a physiologic environment of hyperinsulinemia and hyperglycemia.10”
§ Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus > Comment
What the sources say
- Not checked yetcites [10] Richardson LC Pollack LA Therapy insight: influence of type 2 diabetes on the development, treatment and outcomes of cancer Nat Clin Pract Oncol 2005 2 1 48 53 16264856
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“If several estimates were reported in the same article, we chose the most fully adjusted estimate (ie, multivariate regression was selected over univariate regression, which was selected over unadjusted Kaplan-Meier analysis).”
§ Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus > Methods > Data Synthesis and Statistical Analysis
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
In the paper
“Another potential pathway is that acute exposure to hyperglycemia may increase endothelial cell permeability due to increased generation of reactive oxidative species and structural changes in the basement membrane, increasing the likelihood of metastasis.80”
§ Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus > Comment
What the sources say
- Not checked yetcites [80] Morss AS Edel ER Glucose modulates basement membrane fibroblast growth factor-2 via alterations in endothelial cell permeability J Biol Chem 2007 282 19 14635 14644 17327226
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“To avoid overlapping patient populations, we compared data on recruitment years, data source, and geographic location. If a patient population was found to overlap, we included the article with the most comprehensive population or most adjusted estimate of risk associated with preexisting diabetes. This resulted in the exclusion of 12 articles from our systematic review.12-23”
§ Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus > Methods > Data Synthesis and Statistical Analysis
What the sources say
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- Not checked yetcites [16] Huo TI Wu JC Lui WY Diabetes mellitus is a recurrence-independent risk factor in patients with hepatitis B virus-related hepatocellular carcinoma undergoing resection Eur J Gastroenterol Hepatol 2003 15 11 1203 1208 14560154
- Not checked yetcites [17] Hanbali A Al-Khasawneh K Cole-Johnson C Divine G Ali H Protective effect of diabetes against metastasis in patients with non-small cell lung cancer Arch Intern Med 2007 167 5 513 17353502
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- Not checked yetcites [20] Janssen-Heijnen ML Lemmens VE van den Borne BE Biesma B Oei SB Coebergh JW Negligible influence of comorbidity on prognosis of patients with small cell lung cancer: a population-based study in the Netherlands Crit Rev Oncol Hematol 2007 62 2 172 178 17197191
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Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper relies on this without support.
The association of preexisting diabetes in newly diagnosed cancer patients with long-term, all-cause mortality has not been systematically assessed.
“However, the association of preexisting diabetes in newly diagnosed cancer patients with long-term, all-cause mortality has not been systematically assessed.”
The authors state this as an assumption.
Age and disease severity at cancer diagnosis are particularly important potential confounders.
“because we believe these are particularly important potential confounders.”
The authors state this as an assumption.
In the sign test, studies that did not report a direction of effect fell evenly in either category.
“assumed studies that did not report a direction of effect fell evenly in either category (5 each side, P=.005)”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Results of some, but not all, epidemiological studies suggest that diabetes may significantly increase mortality in patients with cancer (8).”
From Diabetes and Cancer (2010) · cites this paper as [8]
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The Role for Insulin and Insulin-like Growth Factors in the Increased Risk of Cancer in Diabetes
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Crawley, D., Chamberlain, F., Garmo, H., Rudman, S. M., Zethelius, B., Holmberg, L., Adolfsson, J., Stattin, P. E., Carroll, P., & Hemelrijck, M. V. (2018) · ecancermedicalscience · doi:10.3332/ecancer.2018.802 · Cited by 32
“Impact of pre-existing T2DM on prostate cancer outcomes and mortality Introduction In 2008, a systematic review and meta-analysis examining all-cause mortality in cancer patients reported worse outcomes in cancer patients who had pre-existing diabetes mellitus (DM) [40].”
BackgroundAhn, H. R., Kang, S. Y., Youn, H. J., & Jung, S. H. (2020) · Journal of Breast Cancer · doi:10.4048/jbc.2020.23.e44 · Cited by 32
“In particular, in patients with pancreatic, colorectal, and bladder cancer, hyperglycemia has been reported to increase short and long-term mortality and prevalence [4,5].”
BackgroundAn integrative theory for cancer (Review)
Luo, G., & Liu, N. (2018) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2018.4004 · Cited by 33
“Importantly, diabetes is associated with the poorer worse survival of cancer patients (25,38-41).”
Type 2 diabetes and colorectal cancer survival: The multiethnic cohort
Amshoff, Y., Maskarinec, G., Shvetsov, Y. B., Raquinio, P., Grandinetti, A., Setiawan, V. W., Haiman, C. A., & Marchand, L. L. (2018) · International Journal of Cancer · doi:10.1002/ijc.31311 · Cited by 31
“J. Cancer: 143, 263–268 (2018) VC 2018 UICC analysis.10 For all-cause mortality, the majority of studies reported a 20–30% higher mortality for CRC patients with T2D than without T2D.9 Whereas one study detected higher overall mortality for patients with T2D compared to those without for colon (HR5 1.28; 95% CI5 1.14–…”
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“Most studies that have explored outcomes in cancer patients with diabetes have either been retrospective or prospective cohort studies using medical records or claims data([2,3,9,14]) or cross‐sectional.”
BackgroundImpact of diabetes on colorectal cancer stage and mortality risk: a population-based cohort study
Qiang, J. K., Sutradhar, R., Giannakeas, V., Bhatia, D., Singh, S., & Lipscombe, L. L. (2020) · Diabetologia · doi:10.1007/s00125-020-05094-8 · Cited by 31
“Diabetes has also been associated with increased all-cause mortality after cancer diagnosis, with the strongest relationship seen for colorectal, breast and endometrial cancers [12].”
BackgroundIncidence of New-Onset Type 2 Diabetes After Cancer: A Danish Cohort Study
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Inhibition of tumor energy pathways for targeted esophagus cancer therapy
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Type of Diabetes Mellitus and the Odds of Gleason Score 8 to 10 Prostate Cancer
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“Explanations for worse outcome include increased proliferation of tumor cells triggered by higher concentration of insulin-like growth factors and hyperglycemia(4).”
BackgroundCancer and diabetes co-occurrence: A national study with 44 million person-years of follow-up
Gurney, J., Stanley, J., Teng, A. M., Krebs, J. D., Koea, J., Lao, C., Lawrenson, R. A., Meredith, I., Sika‐Paotonu, D., & Sarfati, D. (2022) · PLoS ONE · doi:10.1371/journal.pone.0276913 · Cited by 30
“People with diabetes have poorer survival from cancer [19, 20] (including women with breast cancer [15, 21]), with a large meta-analysis finding that cancer patients with diabetes were 41% more likely to die than cancer patients without diabetes [22].”
BackgroundMicrobial signatures and continuum in endometrial cancer and benign patients
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“Several other factors may link diabetes to breast cancer outcomes: presentation with later-stage cancer due to suboptimal breast cancer screening practices [19,20] or other health-seeking behavior [21-23]; interactions in the management of the two conditions, including less aggressive breast cancer treatment due to di…”
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“…can increase reactive oxidative stress, resulting in structural changes to the endothelial cells and increasing the likelihood of metastasis (Barone et al., 2008), and that high levels of glucose may aid malignant cells in resistance to apoptosis (normal programmed cell death) (Zeng et al.,…”
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“Nutrient overload in obesity leads to increased insulin secretion and consequent hyperinsulinemia [5], a symptom of T2D, and this high level of circulating insulin has been implicated in promoting more aggressive cancer phenotypes, often with poor prognosis [6].”
BackgroundPivotal role of oxidative stress in tumor metastasis under diabetic conditions in mice
Ikemura, M., Nishikawa, M., Kusamori, K., Fukuoka, M., Yamashita, F., & Hashida, M. (2013) · Journal of Controlled Release · doi:10.1016/j.jconrel.2013.05.028 · Cited by 28
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“It has been shown that patients with preexisting diabetes have poorer responses to cancer treatments, and may be more likely to have increased chemotherapy-related toxicities compared with non-diabetic patients who are receiving chemotherapy [ 11 ].”
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Diabetology and oncology meet in a network model: union is strength
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“Additionally, both the risk of several tumors and cancer mortality are moderately increased in people with diabetes [5, 6].”
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Higher risk of mortality from lung cancer in Taiwanese people with diabetes
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“34) [5].”
BackgroundMethodInfluentialAntihyperglycaemic therapies and cancer risk
Lutz, S. Z., Staiger, H., Fritsche, A., & Häring, H. (2014) · Diabetes and Vascular Disease Research · doi:10.1177/1479164114549553 · Cited by 28
“Effects of glucagon and glucagon-like peptide-1-(7-36) amide on C cells from rat thyroid and medullary thyroid carcinoma CA-77 cell line.”
BackgroundChallenges in the management of people with diabetes and cancer
Chowdhury, T. A., & Jacob, P. (2019) · Diabetic Medicine · doi:10.1111/dme.13919 · Cited by 27
Association between diabetes, obesity, aging, and cancer: review of recent literature
Qiang, J. K., Lipscombe, L. L., & Lega, I. C. (2020) · Translational Cancer Research · doi:10.21037/tcr.2020.03.14 · Cited by 28
A Novel Metabolic Reprogramming Strategy for the Treatment of Diabetes‐Associated Breast Cancer
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“Diabetes has been reported to increase the risk of all-cause death not only in cancer patients [31], but also in the general population [32].”
BackgroundIrizarry, L., Li, Q. E., Duncan, I. G., Thurston, A. L., Fitzner, K. A., Edwards, B. J.-A., McKoy-Bent, J. M., Tulas, K. M., & McKoy, J. M. (2012) · Population Health Management · doi:10.1089/pop.2012.0028 · Cited by 27
“Furthermore, this increased risk could be related to problems managing the comorbidity; for example, these patients could experience a delayed cancer diagnosis because preventive screening is deferred when more focus is placed on the antecedent diabetes diagnosis.(12) Given this striking association between diabetes a…”
BackgroundKwon, M., Roh, J., Song, J., Lee, S.-W., Kim, S., Choi, S., & Nam, S. Y. (2015) · The Oncologist · doi:10.1634/theoncologist.2014-0426 · Cited by 27
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Zhang, D., Zhao, Y., Wang, T., Xi, Y., Li, N., & Huang, H. (2016) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.2868 · Cited by 27
Diabetes and its Potential Impact on Head and Neck Oncogenesis
Wang, X., Wang, H., Zhang, T., Cai, L., Dai, E., & He, J. (2019) · Journal of Cancer · doi:10.7150/jca.35607 · Cited by 26
“Candida infection is highly prevalent in DM patients, and can induce squamous epithelial metaplasia and epithelial cell proliferation [89].”
BackgroundZhang, F., de Haan-Du, J., Sidorenkov, G. A., Landman, G. W. D., Jalving, M., Zhang, Q., & de Bock, G. H. (2021) · Cancers · doi:10.3390/cancers13194992 · Cited by 27
Roderburg, C., Loosen, S. H., Hoyer, L., Luedde, T., & Kostev, K. (2021) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-021-03861-7 · Cited by 26
Korean Type 2 Diabetes Patients have Multiple Adenomatous Polyps Compared to Non-diabetic Controls
Suh, S., Kang, M., Kim, M. Y., Chung, H. S., Kim, S. K., Hur, K. Y., Kim, J. H., Lee, M., Lee, M. K., & Kim, K. (2011) · Journal of Korean Medical Science · doi:10.3346/jkms.2011.26.9.1196 · Cited by 26
“Several studies show that diabetes increases risk for cancer mortality (5, 6).”
BackgroundFransgaard, T., Thygesen, L. C., & Gögenür, I. (2018) · International Journal of Cancer · doi:10.1002/ijc.31305 · Cited by 26
Cause-of-Death Trends for Diabetes Mellitus over 10 Years
Park, S. K., Park, M.-K., Suk, J. H., Kim, M.-K., Kim, Y. K., Kim, I. J., Kang, Y. H., Lee, K. J., Lee, H. S., Lee, C. W., et al. (2009) · Korean Diabetes Journal · doi:10.4093/kdj.2009.33.1.65 · Cited by 26
Hyperglycemia-driven signaling bridges between diabetes and cancer
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Do we have enough data to confirm the link between antidiabetic drug use and cancer development?
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Dynamic cellular and molecular modulations of diabetes mediated head and neck carcinogenesis
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Pre‐existing diabetes mellitus in patients with multiple myeloma
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“There is also some evidence to suggest that diabetic breast cancer patients are treated less aggressively and suffer more treatment related complications, particularly with respect to chemotherapy [1], compared to non-diabetic patients [14].”
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“Patients with cancer and preexisting diabetes have an increased risk for all-cause mortality (hazard ratio = 1.41, 95% confidence interval [1.28, 1.55]) compared to individuals who had cancer without diabetes (Barone et al., 2008).”
BackgroundInfluentialGlucose Metabolism Disorders and the Risk of Cancer
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BackgroundInfluentialThe impact of diabetes and other metabolic disorders on prostate cancer prognosis
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Metadata
- Authors
- Barone, B. B.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Barone, Bethany B.
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2008-12-17
- Volume
- 300
- Issue
- 23
- Pages
- 2754
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC3093051
- OpenAlex
- W1968234252
- Cited by
- 881
- References
- 89
- Citations by year
- 2026: 22 · 2025: 35 · 2024: 67 · 2023: 42 · 2022: 53 · 2021: 52 · 2020: 62 · 2019: 53 · 2018: 50 · 2017: 53 · 2016: 46 · 2015: 47 · 2014: 53 · 2013: 60 · 2012: 57
- FWCI
- 17.57
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5p60dk079637-02)
- U.S. Public Health Service (T32HP10025-14)
- National Institute of Diabetes and Digestive and Kidney Diseases (P60 DK-079637, K24-DK62222, K24DK062222, P30DK079637, T32DK062707)
- National Center for Research Resources (UL1RR025005)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Oncology › Cancer Risks and Factors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- diabetes mellitus, cancer, all-cause mortality, overall survival, endometrial cancer, breast cancer, colorectal cancer, comorbidities, cancer risk factors
- MeSH terms
- Cause of Death, Diabetes Mellitus, Humans, Neoplasms, Risk Factors, Comorbidity, Survival Analysis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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