Bethany B Barone

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

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.

Diabetes Mellitus and Breast Cancer Outcomes: A Systematic Review and Meta-Analysis

PURPOSE The goal of this study was to perform a systematic review and meta-analysis to examine the effect of pre-existing diabetes on breast cancer-related outcomes. METHODS We searched EMBASE and MEDLINE databases from inception through July 1, 2009, using search terms related to diabetes mellitus, cancer, and prognostic outcome. Studies were included if they reported a prognostic outcome by diabetes status, evaluated a cancer population, and contained original data published in the English language. We performed a meta-analysis of pre-existing diabetes and its effect on all-cause mortality in patients with breast cancer and qualitatively summarized other prognostic outcomes. RESULTS Of 8,828 titles identified, eight articles met inclusion/exclusion criteria and described outcomes in patients with breast cancer and diabetes. Pre-existing diabetes was significantly associated with all-cause mortality in six of seven studies. In a meta-analysis, patients with breast cancer and diabetes had a significantly higher all-cause mortality risk (pooled hazard ratio [HR], 1.49; 95% CI, 1.35 to 1.65) compared with their nondiabetic counterparts. Three of four studies found pre-existing diabetes to be associated with more advanced stage at presentation. Diabetes was also associated with altered regimens for breast cancer treatment and increased toxicity from chemotherapy. CONCLUSION Compared with their nondiabetic counterparts, patients with breast cancer and pre-existing diabetes have a greater risk of death and tend to present at later stages and receive altered treatment regimens. Studies are needed to investigate pathophysiologic interactions between diabetes and breast cancer and determine whether improvements in diabetes care can reduce mortality in patients with breast cancer.

Risk Factors for Type 2 Diabetes Among Women with Gestational Diabetes: A Systematic Review

We conducted a systematic review of studies examining risk factors for the development of type 2 diabetes among women with previous gestational diabetes. Our search strategy yielded 14 articles that evaluated 9 categories of risk factors of type 2 diabetes in women with gestational diabetes: anthropometry, pregnancy-related factors, postpartum factors, parity, family history of type 2 diabetes, maternal lifestyle factors, sociodemographics, oral contraceptive use, and physiologic factors. The studies provided evidence that the risk of type 2 diabetes was significantly higher in women having increased anthropometric characteristics with relative measures of association ranging from 0.8 to 8.7 and women who used insulin during pregnancy with relative measures of association ranging between 2.8 and 4.7. A later gestational age at diagnosis of gestational diabetes, >24 weeks gestation on average, was associated with a reduction in risk of development of type 2 diabetes with relative measures of association ranging between 0.35 and 0.99. We concluded that there is substantial evidence for 3 risk factors associated with the risk of type 2 diabetes in women having gestational diabetes.

Postoperative Mortality in Cancer Patients With Preexisting Diabetes Systematic review and meta-analysis

OBJECTIVE Diabetes appears to increase risk for some cancers, but the association between preexisting diabetes and postoperative mortality in cancer patients is less clear. Our objective was to systematically review postoperative mortality in cancer patients with and without preexisting diabetes and summarize results using meta-analysis. RSEARCH DESIGN AND METHODS We searched the Medical Literature Analysis and Retrieval System Online (MEDLINE) and Excerpta Medica Database (EMBASE) for articles published on or before 1 July 2009, including references of qualifying articles. We included English language investigations of short-term postoperative mortality after initial cancer treatment. Titles, abstracts, and articles were reviewed by at least two independent readers. Study population and design, results, and quality components were abstracted with standard protocols by one reviewer and checked for accuracy by additional reviewers. RESULTS Of 8,828 titles identified in our original search, 20 articles met inclusion criteria for qualitative systematic review. Of these, 15 reported sufficient information to be combined in meta-analysis. Preexisting diabetes was associated with increased odds of postoperative mortality across all cancer types (OR = 1.85 [95% CI 1.40–2.45]). The risk associated with preexisting diabetes was attenuated but remained significant when we restricted the meta-analysis to models that controlled for confounders (1.51 [1.13–2.02]) or when we accounted for publication bias using the trim and fill method (1.52 [1.13–2.04]). CONCLUSIONS Compared with their nondiabetic counterparts, cancer patients with preexisting diabetes are ∼50% more likely to die after surgery. Future research should investigate physiologic pathways to mortality risk and determine whether improvements in perioperative diabetes care can reduce postoperative mortality.

Colorectal cancer outcomes, recurrence, and complications in persons with and without diabetes mellitus: a systematic review and meta-analysis.

BackgroundDiabetes mellitus increases the risk of incident colorectal cancer, but it is less clear if pre-existing diabetes mellitus influences mortality outcomes, recurrence risk, and/or treatment-related complications in persons with colorectal cancer.MethodsWe performed a systematic review and meta-analysis comparing colorectal cancer mortality outcomes, cancer recurrence, and treatment-related complications in persons with and without diabetes mellitus. We searched MEDLINE and EMBASE through October 1, 2008, including hand-searching references of qualifying articles. We included studies in English that evaluated diabetes mellitus and cancer treatment outcomes, prognosis, and/or mortality. The initial search identified 8,208 titles, of which 15 articles met inclusion criteria. Each article was abstracted by one author using a standardized form and re-reviewed by another author for accuracy. Authors graded quality based on pre-determined criteria.ResultsWe found significantly increased short-term perioperative mortality in persons with diabetes mellitus. In the meta-analysis of long-term mortality, persons with diabetes mellitus had a 32% increase in all-cause mortality compared to those without diabetes mellitus (95% CI: 1.24, 1.41). Although data on other outcomes are limited, available studies suggest that pre-existing diabetes mellitus predicts increased risk of some post-operative complications as well as 5-year cancer recurrence. In contrast, there is little evidence that diabetes confers increased risk for long-term cancer-specific mortality.ConclusionsPatients with colorectal cancer and pre-existing diabetes mellitus have an increased risk of short- and long-term mortality. Future research should determine whether improvements in prevention and treatment of diabetes mellitus will improve outcomes for colorectal cancer patients.

Does pre-existing diabetes affect prostate cancer prognosis? A systematic review.

To summarize the influence of pre-existing diabetes on mortality and morbidity in men with prostate cancer. We searched MEDLINE and EMBASE from inception through 1 October 2008. Search terms were related to diabetes, cancer and prognosis. Studies were included if they reported an original data analysis of prostate cancer prognosis, compared outcomes between men with and without diabetes and were in English. Titles, abstracts and articles were reviewed independently by two authors. Conflicts were settled by consensus or third review. We abstracted data on study design, analytic methods, outcomes and quality. We summarized mortality and morbidity outcomes qualitatively and conducted a preliminary meta-analysis to quantify the risk of long-term (>3 months), overall mortality. In total, 11 articles were included in the review. Overall, one of four studies found increased prostate cancer mortality, one of two studies found increased nonprostate cancer mortality and one study found increased 30-day mortality. Data from four studies could be included in a preliminary meta-analysis for long-term, overall mortality and produced a pooled hazard ratio of 1.57 (95% CI: 1.12–2.20). Diabetes was also associated with receiving radiation therapy, complication rates, recurrence and treatment failure. Our analysis suggests that pre-existing diabetes affects the treatment and outcomes of men with prostate cancer.

Antepartum Glucose Tolerance Test Results as Predictors of Type 2 Diabetes Mellitus in Women With a History of Gestational Diabetes Mellitus : A Systematic Review

BACKGROUND Women with a history of gestational diabetes mellitus (GDM) are at high risk for type 2 diabetes mellitus (T2DM). OBJECTIVE We reviewed prospective studies of antepartum glucose tolerance test results as risk factors for development of T2DM among women with a history of GDM. METHODS We searched 4 electronic databases and hand-searched 13 journals for literature published through January 2007. The search strategy consisted of medical subject headings and text words for GDM, T2DM, and other relevant terms. Articles were excluded for the following reasons: (1) not written in English; (2) no human data; (3) no original data; (4) <90% of sample was diagnosed with GDM without a separate analysis for women with GDM; (5) case report or series; (6) diagnosis of GDM not based on 3-hour 100-g oral glucose tolerance test (OGTT) or 2-hour 75-g OGTT; (7) T2DM not evaluated as outcome; (8) no relative measure of association or incidence reported; or (9) design did not address antepartum OGTT as a predictor of T2DM. Two investigators independently reviewed citations, performed serial data abstraction on full articles, and assessed the quality of each article. Data were abstracted for study participants and characteristics, T2DM diagnosis, length of follow-up, regression model covariates, and measures of association and variability. RESULTS Of 11,400 unique citations, we identified 11 articles that evaluated antepartum glucose testing and risk of T2DM in women with a history of GDM. Five studies found that the fasting blood glucose (FBG) on the antepartum diagnostic OGTT was a significant predictor of T2DM (odds ratio [OR] range: 11.1-21.0; relative risk [RR] range: 1.37-1.5; relative hazard [RH] = 2.47). Risk of incident T2DM was predicted by the antepartum 2-hour OGTT plasma glucose in 3 studies (OR range: 1.02-1.03; RR = 1.3) and by the antepartum OGTT glucose AUC in 3 other studies (OR range: 3.64-15; RH = 2.13). Overall, study quality was limited by high losses to follow-up (>20% in 6 studies) and short duration. Few studies adjusted for adiposity, an established diabetes risk factor. CONCLUSION FBG, OGTT 2-hour blood glucose, and OGTT glucose AUC appeared to be strong and consistent predictors of subsequent T2DM among women who met diagnostic criteria for GDM using the OGTT.

Usefulness of Cystatin C and Prognosis Following Admission for Acute Heart Failure

Cystatin C is a novel marker of renal function that has been found to predict adverse cardiovascular outcomes in ambulatory patients. The aim of this study was to investigate whether this biomarker predicts the length of hospitalization and adverse outcomes in patients hospitalized for heart failure. Two hundred forty consecutive patients aged > or =25 admitted to Johns Hopkins Hospital with exacerbations of heart failure were prospectively enrolled. Cystatin C levels were measured on admission. Patients were followed for 1 year. The primary outcome measure was the length of hospitalization. Secondary outcomes included all-cause mortality and readmission for heart failure. Cystatin C showed no significant association with the length of hospitalization. Patients in the highest quartile (quartile 4) of cystatin C level were at increased risk for death (hazard ratio 2.07 for quartile 4 vs quartiles 1 to 3, p = 0.01) and death or rehospitalization (hazard ratio 1.61 for quartile 4 vs quartiles 1 to 3, p = 0.01). The association between cystatin C and the combined end point of death or rehospitalization during 1-year follow-up remained significant after adjusting for age, race, gender, co-morbidities, and creatinine. Cystatin C was more predictive of these end points than creatinine, and the combination of cystatin C and creatinine was more predictive than either variable alone. In conclusion, cystatin C may be useful in addition to creatinine for predicting outcomes after admission for acute heart failure exacerbations.

Decreased exercise blood pressure in older adults after exercise training: contributions of increased fitness and decreased fatness

Objective: To describe the contribution of changes in fitness and fatness resulting from exercise training on changes in submaximal exercise blood pressure (BP) during treadmill testing. Design and setting: Prospective, randomised, controlled trial. Participants: Sedentary older adults (n = 115) with untreated prehypertension or mild hypertension. Intervention: Six-month supervised aerobic and strength training. Main outcome measurement: Systolic BP (SBP) was assessed at rest and during each stage of a maximal graded exercise test (GXT) that determined Vo2peak. General and regional fatness was assessed by anthropometry, dual-energy x-ray absorptiometry and MRI. BP changes were calculated for each GXT stage, and multivariate regression models were used to describe the association of changes in exercise BP with changes in fitness and fatness. Results: After training, exercisers versus controls had significantly increased Vo2peak and significantly lower measures of general and regional fatness. Also, stage-specific SBP was significantly lower at stage 3 (−9.4 vs −1.6 mm Hg, p = 0.03) and stage 4 (−7.9 vs −1.2 mm Hg, p = 0.03). Pooled regression analysis across all stages showed that exercisers had a 7.1 mm Hg reduction in SBP, but this reduction fell short of statistical significance (p = 0.12) compared with controls. A 1.0 ml/kg/min increase in Vo2peak and a 1.0 cm decrease in waist circumference independently predicted a 1.0 mm Hg decrease in exercise SBP (p = 0.04 and p = 0.001, respectively). Conclusions: Decreased exercise SBP was independently associated with decreased waist circumference, a marker of abdominal obesity and increased fitness. These findings suggest that exercise training improves multiple factors that have an independent influence on SBP.

Lifetime weight patterns in male physicians: The effects of cohort and selective survival

Objective: The natural history of lifetime weight change is not well understood because of conflicting evidence from cross‐sectional and longitudinal studies. Cross‐sectional analyses find that adult weight is highest at ∼60 years of age and lower thereafter. Longitudinal analyses have not found this pattern. Our objective was to test whether cohort effects and selective survival may explain the differences observed between cross‐sectional and longitudinal studies.