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Fasting glucose and treatment outcome in breast and colorectal cancer patients treated with targeted agents: results from a historic cohort.

ABSTRACT: We investigated pretreatment fasting glucose as a predictor of patients' important outcomes in breast and colorectal cancers undergoing targeted therapies.In a historic cohort of 202 breast and 218 colorectal cancers treated with targeted agents from 1998 to 2009, we used the Kaplan-Meier method and the log-rank test to estimate survival through tertiles of fasting glucose and the Cox proportional hazards model for multivariate analysis stratified by primary site of cancer and including gender, age and body mass index.The median follow-up was 20 months (1-128). At 60 months, 65% of patients in the lowest tertile of fasting glucose did not experiment disease progression compared with 34% in the highest tertile (P=0.001). Seventy-six percent of females in the lowest tertile showed no progression compared with 49% in the top tertiles (P=0.015). In multivariate analysis, fasting glucose was a significant predictor of time to disease progression only in breast cancer patients in the first tertile compared with the third (P=0.017).We found evidence of a predictive role of pretreatment fasting glucose in the development of resistance in breast cancer patients treated with targeted agents. Prospective studies are warranted to confirm our findings.

SUBMITTER: Barba M

PROVIDER: S-EPMC3387821 | biostudies-other | 2012 Jul

REPOSITORIES: biostudies-other

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Fasting glucose and treatment outcome in breast and colorectal cancer patients treated with targeted agents: results from a historic cohort.

Barba M M Sperati F F Stranges S S Carlomagno C C Nasti G G Iaffaioli V V Caolo G G Mottolese M M Botti G G Terrenato I I Vici P P Serpico D D Giordano A A D'Aiuto G G Crispo A A Montella M M Capurso G G Delle Fave G G Fuhrman B B Botti C C De Placido S S

Annals of oncology : official journal of the European Society for Medical Oncology 20111118 7

<h4>Background</h4>We investigated pretreatment fasting glucose as a predictor of patients' important outcomes in breast and colorectal cancers undergoing targeted therapies.<h4>Patients and methods</h4>In a historic cohort of 202 breast and 218 colorectal cancers treated with targeted agents from 1998 to 2009, we used the Kaplan-Meier method and the log-rank test to estimate survival through tertiles of fasting glucose and the Cox proportional hazards model for multivariate analysis stratified ...[more]

PMID: 22100694

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Project description:IntroductionThe relationship between glucose metabolism and stroke outcome is likely to be complex. We examined whether there is a linear or non-linear relationship between glucose measures in the acute phase of stroke and post-stroke cognition, and whether altered glucose metabolism at different time intervals (long- and short-term before stroke, acute phase) is associated with cognitive outcome.Patients and methodsIn all, 664 consecutively recruited patients with acute ischemic stroke and without pre-stroke dementia were included in this prospective observational study. Blood samples were taken at admission and fasting on the first morning after stroke. Duration of diabetes was assessed by interview. Cognitive outcome was assessed by the Telephone Interview for Cognitive Status 3 months post-stroke. Dose-response analyses were used to investigate non-linearity. Regression analyses were stratified by diabetes status and adjusted for relevant confounders.ResultsCognitive status was testable in 422 patients (81 with diabetes). There was a non-linear relationship between both admission and fasting glucose levels and cognitive outcome. Lower glucose values were significantly associated with lower Telephone Interview for Cognitive Status scores 3 months post-stroke in patients without diabetes with a similar trend in diabetic patients. There was an inverse association between duration of diabetes and Telephone Interview for Cognitive Status scores (linear regression: -0.10 (95% confidence interval: -0.17 to -0.02) per year increase of diabetes duration), whereas HbA1c was not related to cognitive outcome. Results were supported by sensitivity analyses accounting for attrition.ConclusionLower glucose levels in the acute phase of stroke are associated with worse cognitive outcome but the relationship is non-linear. Long-term abnormalities in glucose metabolism are also related to poor outcome but this is not the case for shorter term abnormalities. Altered glucose levels at different stages of stroke may affect stroke outcome through different pathways.

Project description:BackgroundPrevious studies have shown that type II diabetes mellitus (T2DM) has a significant effect on the occurrence and development of colorectal cancer (CRC). The associations between fasting plasma glucose (FPG) and overall survival (OS) of CRC patients with T2DM are still controversial. The present study sought to examine the association between FPG control and OS in advanced CRC patients with T2DM.MethodsThe data of advanced CRC patients with T2DM who were admitted to Harbin Medical University Cancer Hospital from May 2010 to May 2019 were retrospectively collected and examined. Record patient clinical data including age, sex, blood pressure, body mass index (BMI), primary tumor site, T stage, N stage, histological grade, number of metastatic sites, primary tumor surgery, etc. The baseline FPG which was measured before the first-line treatment and the FPG measured before each admission treatment during advanced chemotherapy were collected. OS was determined as the end point of the study. All the patients were followed-up for at least 3 years. The Kaplan-Meier log-rank method and the Cox proportional hazards regression analyses were used for the analysis of OS and hazard factors.ResultsA total of 210 patients met the inclusion criteria for the study, who had a median age of 66.5 years; 94 patients had baseline FPG levels ≤7 mmol/L, and 116 patients had baseline FPG levels >7 mmol/L. Compared to the baseline FPG >7 mmol/L group, the OS of patients in the baseline FPG ≤7 mmol/L group was not significantly prolonged (P=0.88). There were 52 patients in the FPG-A group and 61 in the FPG-B group. Similarly, there was no significant difference in OS between the FPG-A and FPG-B groups (P=0.96). The N0 stage subgroup analysis showed that glycemic control ≤7 mmol/L resulted in longer OS.ConclusionsThe results of the present study showed that FPG levels may not affect the survival of advanced CRC patients with T2DM. However, this needs multicenter prospective studies to confirm.

Project description:Prediabetes is a metabolic condition associated with gut microbiome composition, although mechanisms remain elusive. We searched for fecal metabolites, a readout of gut microbiome function, associated with impaired fasting glucose (IFG) in 142 individuals with IFG and 1,105 healthy individuals from the UK Adult Twin Registry (TwinsUK). We used the Cooperative Health Research in the Region of Augsburg (KORA) cohort (318 IFG individuals, 689 healthy individuals) to replicate our findings. We linearly combined eight IFG-positively associated metabolites (1-methylxantine, nicotinate, glucuronate, uridine, cholesterol, serine, caffeine, and protoporphyrin IX) into an IFG-metabolite score, which was significantly associated with higher odds ratios (ORs) for IFG (TwinsUK: OR 3.9 [95% CI 3.02-5.02], P < 0.0001, KORA: OR 1.3 [95% CI 1.16-1.52], P < 0.0001) and incident type 2 diabetes (T2D; TwinsUK: hazard ratio 4 [95% CI 1.97-8], P = 0.0002). Although these are host-produced metabolites, we found that the gut microbiome is strongly associated with their fecal levels (area under the curve >70%). Abundances of Faecalibacillus intestinalis, Dorea formicigenerans, Ruminococcus torques, and Dorea sp. AF24-7LB were positively associated with IFG, and such associations were partially mediated by 1-methylxanthine and nicotinate (variance accounted for mean 14.4% [SD 5.1], P < 0.05). Our results suggest that the gut microbiome is linked to prediabetes not only via the production of microbial metabolites but also by affecting intestinal absorption/excretion of host-produced metabolites and xenobiotics, which are correlated with the risk of IFG. Fecal metabolites enable modeling of another mechanism of gut microbiome effect on prediabetes and T2D onset.Article highlightsPrediabetes is a metabolic condition associated with gut microbiome composition, although mechanisms remain elusive. We investigated whether there is a fecal metabolite signature of impaired fasting glucose (IFG) and the possible underlying mechanisms of action. We identified a fecal metabolite signature of IFG associated with prevalent IFG in two independent cohorts and incident type 2 diabetes in a subanalysis. Although the signature consists of metabolites of nonmicrobial origin, it is strongly correlated with gut microbiome composition. Fecal metabolites enable modeling of another mechanism of gut microbiome effect on prediabetes by affecting intestinal absorption or excretion of host compounds and xenobiotics.

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Fasting glucose and treatment outcome in breast and colorectal cancer patients treated with targeted agents: results from a historic cohort.

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Fasting glucose and treatment outcome in breast and colorectal cancer patients treated with targeted agents: results from a historic cohort.

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