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Cited by 882Metabolism, Diabetes, and CancerCancer Risks and FactorsDiabetes Management and Research

Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus: A Systematic Review and Meta-analysis

Open access
Barone, Bethany B.·2008·JAMA
DOI 10.1001/jama.2008.824PMC PMC3093051
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Abstract

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.

AI snapshot

Written from the paper’s full text.

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.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1001/jama.2008.824

Cites

90 of 90 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 32 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Preexisting diabetes is associated with increased long-term all-cause mortality in patients with breast cancer, with a pooled hazard ratio of 1.61 (95% CI, 1.46-1.78).

    “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).”
    Quote in the paperSubstantial claim
  • Findingown data

    A nonparametric sign test found no association between diabetes and increased cancer-specific mortality (P = .69).

    “We performed a nonparametric sign test and found no association between diabetes and increased cancer-specific mortality (P=.69).”
    Quote in the paperNot a substantial claim
  • Findingown data

    Preexisting diabetes is associated with a nonsignificant increase in long-term all-cause mortality in patients with pancreatic cancer, with a pooled hazard ratio of 1.09 (95% CI, 0.70-1.69).

    “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).”
    Quote in the paperNot a substantial claim
  • Findingown data

    In the meta-analysis, stage at diagnosis appeared not to be a major explanatory factor.

    “In our analysis, however, stage at diagnosis appeared not to be a major explanatory factor.”
    Quote in the paperNot a substantial claim
  • Findingown data

    No study included in the systematic review reported that diabetes was associated with significantly better survival.

    “No study included in this systematic review reported that diabetes was associated with significantly better survival.”
    Quote in the paperSubstantial claim
  • May combine two claims. 19
  • Classified as probably not a substantial claim. 17

  • May combine two claims.

    Findingown data

    Preexisting diabetes in cancer patients is associated with increased long-term all-cause mortality compared with patients without diabetes, with a pooled hazard ratio of 1.41 (95% CI, 1.28-1.55) across all cancer types.

    “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.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Of 9 estimates from 8 articles on cancer-specific mortality, 2 found significantly higher risk, 2 nonsignificantly higher risk, 2 nonsignificantly lower risk, and 3 did not report a direction of effect.

    “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”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The sign test rejected the null hypothesis of equal mortality in patients with and without preexisting diabetes, whether excluding studies without a direction of effect (P = .001) or assuming those studies fell evenly in either category (P = .005).

    “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).”
    Quote in the paperSubstantial claim
    • 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.

  • May combine two claims.

    Findingown data

    Omission of any one study did not appreciably change the pooled hazard ratio, and each estimate remained within the confidence limits of the overall estimate.

    “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.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Between-study heterogeneity was significant by the Q statistic (205 on 24 df, P < .001) and by I2 (88.3%, P < .001).

    “Heterogeneity was significant by the Q statistic (205 on 24 df, P < .001) and by I2 (88.3%, P < .001).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The subsidiary analysis of studies that distinguished between cancer and noncancer mortality was inconclusive, so the possibility that excess mortality risk related to diabetes is independent of cancer cannot be excluded.

    “Our subsidiary analysis of studies that distinguished between cancer and noncancer mortality was inconclusive, so this possibility cannot be excluded.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    Of 3 studies evaluating noncancer mortality, 2 found a significant association with increased risk among patients with preexisting diabetes and 1 reported a nonsignificant association with no direction of effect.

    “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”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Across study estimates, 32 found diabetes associated with increased mortality risk, 7 found decreased risk, 1 found a null effect, and 10 did not report a direction of effect.

    “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.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    High insulin or insulin-like growth factor levels may promote cancer cell and tumor growth.

    “It is possible that high insulin or insulin-like growth factor levels may promote cancer cell and tumor growth.10”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [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

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Some cancers, including breast, colorectal, endometrial, liver, and pancreatic cancers, occur more commonly in individuals with diabetes.

    “Because some cancers—including cancers of the breast,2 colorectum,3 endometrium,4 liver,5 and pancreas6—occur more commonly in individuals with diabetes”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [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 in the free run.

    • cites [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 in the free run.

    • cites [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

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    Post hoc power calculations based on the overall and site-specific pooled hazard ratios 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.

    “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.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Cohn and Becker,27

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Diabetes is a well-established risk factor for cardiovascular mortality in adults without cancer.

    “Diabetes is a well-established risk factor for cardiovascular mortality in adults without cancer,86”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [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

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Patients with preexisting diabetes may have poorer response to cancer treatment, including increased infection risk and intraoperative mortality.

    “Third, patients with preexisting diabetes may have poorer response to cancer treatment, including increased infection risk and intraoperative mortality.39,81”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [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 in the free run.

    • cites [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

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Of 12 authors contacted, 3 provided additional information, 4 were unable to furnish the necessary information, and 5 did not respond.

    “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.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Cancer patients with diabetes may receive less aggressive cancer treatment or less aggressive diabetes care, both of which could compromise survival.

    “Cancer patients with diabetes may receive less aggressive cancer treatment or less aggressive diabetes care, both of which could compromise survival.10”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [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

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    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.

    “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.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Fleming et al83

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    Patients with preexisting diabetes may present with later-stage disease because of suboptimal cancer screening practices.

    “Fourth, patients with preexisting diabetes may present with later-stage disease because of suboptimal cancer screening practices.82”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [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

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Adults with diabetes experienced increased cancer mortality in the American Cancer Society Cancer Prevention Study II but not in the Second National Health and Nutrition Examination Survey Mortality Follow-Up.

    “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”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [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 in the free run.

    • cites [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

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    Quality was assessed using elements of the STROBE checklist for cohort studies considered important for quality in these studies.

    “Quality was assessed using elements of the STROBE checklist for cohort studies considered important for quality in these studies.11”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [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

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Although site-specific mortality risk reached statistical significance only for endometrial, breast, and colorectal cancers, diabetes appeared to be associated with some additional mortality risk for all types of cancer.

    “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.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    The majority of included studies 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.

    “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”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Differences in follow-up time, which was not always reported, may limit interpretation of the results.

    “Finally, differences in follow-up time, which was not always reported, may also limit interpretation of the results.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    One reviewer performed a full abstraction and other reviewers verified accuracy.

    “One reviewer performed a full abstraction and other reviewers verified accuracy.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    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.

    “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”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [87] Begg CB Schrag D Attribution of deaths following cancer treatment J Natl Cancer Inst 2002 94 14 1044 1045 12122090

      Not checked in the free run.

    • cites [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 in the free run.

    • cites [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 in the free run.

    • cites [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

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based).

    Interpretationnone given

    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.

    “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.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Titles, abstracts, and articles were reviewed by at least 2 independent readers.

    “Titles, abstracts, and articles were reviewed by at least 2 independent readers.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Interpretationreasoning

    The microvascular and macrovascular damage caused by diabetes likely accumulates to some extent regardless of cancer status.

    “and the microvascular and macrovascular damage it causes likely accumulates to some extent regardless of cancer status.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    Cancer patients with diabetes may have increased tumor cell proliferation and metastases in a physiologic environment of hyperinsulinemia and hyperglycemia.

    “First, cancer patients with diabetes may have increased tumor cell proliferation and metastases in a physiologic environment of hyperinsulinemia and hyperglycemia.10”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [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

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    When several estimates were reported in the same article, the most fully adjusted estimate was chosen.

    “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).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationcitation

    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.

    “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”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [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

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    To avoid overlapping patient populations, the authors compared recruitment years, data source, and geographic location, and excluded 12 articles from the systematic review.

    “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”
    Quote in the paperSubstantial claim0 of 10 sources checked
    • cites [12] Janssen-Heijnen ML Maas HA Houterman S Lemmens VE Rutten HJ Coebergh JW Comorbidity in older surgical cancer patients: influence on patient care and outcome Eur J Cancer 2007 43 15 2179 2193 17681780

      Not checked in the free run.

    • cites [13] Lemmens VE Janssen-Heijnen ML Verheij CD Houterman S Repelaer van Driel OJ Coebergh JW Co-morbidity leads to altered treatment and worse survival of elderly patients with colorectal cancer Br J Surg 2005 92 5 615 623 15779071

      Not checked in the free run.

    • cites [14] Tanisada K Teshima T Ikeda H Prognostic factors for patients with esophageal cancer treated with radiation therapy in PCS: a preliminary study Radiat Med 1998 16 6 461 468 9929147

      Not checked in the free run.

    • cites [15] Nagasue N Kohno H Tachibana M Yamanoi A Ohmori H El-Assal ON Prognostic factors after hepatic resection for hepatocellular carcinoma associated with Child-Turcotte class B and C cirrhosis Ann Surg 1999 229 1 84 90 9923804 PMC1191612

      Not checked in the free run.

    • cites [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 in the free run.

    • cites [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

      Not checked in the free run.

    • cites [18] Merrick GS Butler WM Wallner KE Galbreath RW Allen ZA Adamovich E Androgen-deprivation therapy does not impact cause-specific or overall survival after permanent prostate brachytherapy Int J Radiat Oncol Biol Phys 2006 65 3 669 677 16682149

      Not checked in the free run.

    • cites [19] Kouvaris J Kouloulias V Loghis C Sykiotis C Balafouta M Vlahos L Prognostic factors for survival in invasive squamous cell vulvar carcinoma: a univariate analysis Gynecol Obstet Invest 2001 51 4 262 265 11408738

      Not checked in the free run.

    • cites [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

      Not checked in the free run.

    • cites [21] Maas HA Kruitwagen RF Lemmens VE Goey SH Janssen-Heijnen ML The influence of age and co-morbidity on treatment and prognosis of ovarian cancer: a population-based study Gynecol Oncol 2005 97 1 104 109 15790445

      Not checked in the free run.

31 of 31

  • 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)”
3 of 3

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?

  • Results of some, but not all, epidemiological studies suggest that diabetes may significantly increase mortality in patients with cancer.

    “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]

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. [24]Rosner B Fundamentals of Biostatistics Sixth Belmont, CA Duxbury Press 2006 361 366

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Related

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
DOI
10.1001/jama.2008.824
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
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.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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