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

BACKGROUND: Diabetes 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. METHODS: We 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. RESULTS: We 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. CONCLUSIONS: Patients 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.

A randomized comparison of the terms estimated average glucose versus hemoglobin A1C.

PURPOSE: The purpose of this study was to evaluate the hypothesis that using estimated average glucose (eAG) while instructing patients yields better knowledge retention than using the term hemoglobin A1C (A1C). METHODS: Patients with diabetes who had poor baseline understanding of A1C (determined by a 4-question survey) were randomized into 1 of 2 groups: A1C or eAG. Depending on randomization, providers discussed patients' current status and personal targets for glycemic control using either the term A1C or estimated average glucose. Patients had a telephone survey 3-4 weeks later, assessing change in knowledge of glycemic control. RESULTS: The 80 participants who completed follow-up had similar baseline characteristics, including poor understanding of A1C and poor recall of previous A1C values. At the 3-4 week follow-up, average score for each survey question improved significantly in both groups, with mean composite score increasing in the A1C group by 32% and in the eAG group by 33%. There was no suggestion of a difference in degree of improvement between groups. CONCLUSIONS: Patients previously unfamiliar with the meaning of A1C, using either term (A1C or eAG) resulted in an equal improvement in knowledge. Within this study, eAG was not a more understandable term, or an easier concept for patients to remember. Further research is needed to test whether use of the term A1C should be replaced by eAG.

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.

Assessing glycemia in diabetes using self-monitoring blood glucose and hemoglobin A1c.

CONTEXT: With the increasing prevalence of diabetes, successful management of blood glucose control is increasingly important. Current approaches to assessing glycemia include the use of self-monitoring of blood glucose (SMBG) and hemoglobin A1c (HbA1c). OBJECTIVES: To assess the evidence underlying the use of these 2 modalities, to evaluate confounders and sources of error in each test, to describe upcoming developments, and to reach evidence-based conclusions on their optimal use. DATA SOURCES, STUDY SELECTION, AND DATA EXTRACTION: Reports identified from MEDLINE searches (1976-2005) using relevant terms were selected for quality and relevance to the stated questions. Particular attention was paid to larger cohort studies, clinical trials, meta-analyses, and established recommendations. DATA SYNTHESIS: If used properly SMBG gives an acceptably accurate reflection of immediate plasma glucose levels. Study results vary, but in general, the evidence supports a positive effect of regular SMBG for improving glycemia, particularly in individuals treated with insulin. The best timing of SMBG and its frequency are controversial issues, but the clinical recommendation is for regular monitoring with frequency depending on the treatment and the instability of glycemia. In the relatively near term, SMBG could gradually be replaced by continuous glucose monitoring. HbA1c measures long-term glycemic control, reflecting a time-weighted mean over the previous 3 to 4 months. There are a number of physiologic and methodologic confounders that can affect HbA1c, but standardization of assays has been well established. The main value of HbA1c is its use as a predictor of diabetic complications and the proven effect of improved control of HbA1c on complication risk. A reasonable target value for HbA1c is less than 7%. A new method for measuring HbA1c may cause significant changes in the recommended levels, the numbers reported, and even the name of the test. CONCLUSION: Assessing glycemia in diabetes can be a challenge, but approaches are available that promote successful management of blood glucose and may thereby lead to a significant reduction in morbidity and mortality related to 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.

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 approximately 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.

Association between hyperglycemia and survival in patients with newly diagnosed glioblastoma.

PURPOSE: Hyperglycemia has been associated with poor outcomes in many disease states. This retrospective study assessed the association between hyperglycemia and survival in patients with newly diagnosed glioblastoma multiforme (GBM). PATIENTS AND METHODS; Between 1999 and 2004, before the standard use of temozolomide, 191 patients were accrued onto New Approaches to Brain Tumor Therapy CNS Consortium trials with similar eligibility criteria. Time-weighted mean glucose and mean glucocorticoid dose were calculated for each patient using all values collected regularly in follow-up. The primary outcome was survival. RESULTS: Mean glucose levels ranged between 65 and 459 mg/dL. These were divided into quartiles: quartile one (< 94 mg/dL), quartile two (94 to 109 mg/dL), quartile three (110 to 137 mg/dL), and quartile four (> 137 mg/dL). Median survival times for patients in quartiles one, two, three, and four were 14.5, 11.6, 11.6, and 9.1 months, respectively. The association between higher mean glucose and shorter survival persisted after adjustment for mean daily glucocorticoid dose, age, and baseline Karnofsky performance score (KPS). Compared with patients in the lowest mean glucose quartile, those in quartile two (adjusted hazard ratio [HR], 1.29; 95% CI, 0.85 to 1.96), quartile three (adjusted HR, 1.35; 95% CI, 0.89 to 2.06), and quartile four (adjusted HR, 1.57; 95% CI, 1.02 to 2.40) were at progressively higher risk of dying (P = .041 for trend). CONCLUSION: In these patients with newly diagnosed GBM and good baseline KPS, hyperglycemia was associated with shorter survival, after controlling for glucocorticoid dose and other confounders. The effect of intensive management of glucocorticoid-related hyperglycemia on survival deserves additional study in patients with GBM.

Antecedent hyperglycemia is associated with an increased risk of neutropenic infections during bone marrow transplantation.

OBJECTIVE: To use bone marrow transplantation (BMT) as a model for testing the association between hyperglycemia and infection. RESEARCH DESIGN AND METHODS: This cohort study included 382 adults (6.5% with diabetes) who had no evidence of infection before neutropenia during BMT. Mean glucose was calculated from central laboratory and bedside measurements taken before neutropenia; the primary outcome was neutropenic infections. RESULTS: Eighty-four patients (22%) developed at least one neutropenic infection, including 51 patients (13%) with bloodstream infections. In patients who did not receive glucocorticoids during neutropenia, each 10 mg/dl increase in mean preneutropenia glucose was associated with an odds ratio of 1.08 (95% CI 0.98-1.19) (P = 0.14) for any infection and 1.15 (1.03-1.28) (P = 0.01) for bloodstream infections, after adjusting for age, sex, race, year, cancer diagnosis, transplant type, and total glucocorticoid dose before neutropenia. In those who received glucocorticoids during neutropenia (n = 71), the adjusted odds ratio associated with a 10 mg/dl increase in mean glucose was 1.21 (1.09-1.34) (P < 0.0001) for any infection and 1.24 (1.11-1.38) (P < 0.0001) for bloodstream infections. There was no association between mean glycemia and long length of hospital stay, critical status designation, or mortality. CONCLUSIONS: In a BMT population highly susceptible to infection, there was a continuous positive association between mean antecedent glycemia and later infection risk, particularly in patients who received glucocorticoids while neutropenic. Tight glycemic control during BMT and glucocorticoid treatment may reduce infections.

Pre-analytic considerations for the proper assessment of hormones of the hypothalamic-pituitary axis in epidemiological research.

There is growing epidemiological interest in hormones as predictors of chronic diseases. The correct handling and analysis of hormones can be cumbersome, and great care must be taken in these processes in order to gain the most information possible. Given differences in sampling, processing, and stability of the various hormonal assays, we sought to provide a comprehensive review to aid future epidemiological research. We have coupled a thorough literature search with our own analytical experience to outline common laboratory problems one must consider in analyzing the hormones of the hypothalamic-pituitary axis. In addition, we describe the benefits and limitations of using alternative media--including urine, saliva, and blood spots on filter paper--to measure endocrine hormones in epidemiological studies.