Diabetes, metabolic comorbidities, and risk of hepatocellular carcinoma: Results from two prospective cohort studies.
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SUBMITTER: Simon TG
PROVIDER: S-EPMC5906170 | biostudies-literature | 2018 May
REPOSITORIES: biostudies-literature
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Diabetes, metabolic comorbidities, and risk of hepatocellular carcinoma: Results from two prospective cohort studies.
Simon Tracey G TG King Lindsay Y LY Chong Dawn Q DQ Nguyen Long H LH Ma Yanan Y VoPham Trang T Giovannucci Edward L EL Fuchs Charles S CS Meyerhardt Jeffrey A JA Corey Kathleen E KE Khalili Hamed H Chung Raymond T RT Zhang Xuehong X Chan Andrew T AT
Hepatology (Baltimore, Md.) 20180326 5
Type 2 diabetes (T2D) is a risk factor for hepatocellular carcinoma (HCC). However, it is unknown whether T2D duration or additional metabolic comorbidities further contribute to HCC risk. From the Nurses' Health Study (NHS), 120,826 women were enrolled in 1980, and from the Health Professionals Follow-up Study (HPFS), 50,284 men were enrolled in 1986 and followed through 2012. Physician-diagnosed T2D was ascertained at baseline and updated biennially. Cox proportional hazards regression models ...[more]
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Project description:BackgroundThe obesity paradigm has been a health concern globally for many years, its meaning is controversial. In this study, we assess the characteristics and causes of obesity paradigm and detail the mediation of obesity and inflammation on survival.MethodsThe original cohort included participants from the US National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018, a prospective cohort of a nationally representative sample of adult participants; the oncology validation cohort included patients from the Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) from 2013 to 2021, a prospective cohort of Chinese patients with cancer. Survival analysis was performed using weighted (NHANES) or unweighted (INSCOC) Cox survival analyses. The normal BMI group was used as a reference for all comparisons. Systemic inflammation was defined as neutrophil-to-lymphocyte ratio (NLR) > 3. Model-based causal mediation analysis was used to identify the mediators.ResultsA total of 52 270 (weighted population: 528506229) participants of the NHANES [mean follow-up times: 10.2 years; mean age (SD): 47 (19.16) years] were included in the original cohort; and a total of 17 418 patients with cancer of INSCOC [mean follow-up times: 2.9 years; mean age (SD): 57.37 (11.66) years] were included in the validation cohort. In the subgroups of all the participants, the obesity paradigm was more apparent in older participants and participants with disease [HR (95% CI): age ≥ 65 years, 0.84 (0.76, 0.93); with cancer, 0.84 (0.71, 0.99); with CVD, 0.74 (0.65, 0.85)]. As aged, the protective effect of a high BMI on survival gradually increased and a high BMI showed the effect of a protective factor on older participants [for obese II, HR (95% CI): young adults, 1.91 (1.40, 2.62); middle age, 1.56 (1.28, 1.91); old adults, 0.85 (0.76, 0.96]). The aged-related obesity paradigm in patients with cancer from the NHANES was verified in the INSCOC cohorts [for obese, HR (95%CI): 0.65 (0.52, 0.81)]. The NLR is an important mediator of the effect of BMI on survival (proportion of mediation = 15.4%).ConclusionsThe obesity paradigm has a strong correlation with age. Relative to normal weight, obese in young people was association with higher all-cause mortality, and obese in elderly people was not association with higher mortality. The protection of obesity is association with systemic inflammation.
| S-EPMC10834317 | biostudies-literature
Project description:The impact of pre-existing diabetes mellitus (DM) on hepatocellular carcinoma (HCC) occurrence and prognosis is complex and unclear. The aim of this meta-analysis is to evaluate the association between pre-existing diabetes mellitus and hepatocellular carcinoma occurrence and prognosis.We searched PubMed, Embase and the Cochrane Library from their inception to January, 2011 for prospective epidemiological studies assessing the effect of pre-existing diabetes mellitus on hepatocellular carcinoma occurrence, mortality outcomes, cancer recurrence, and treatment-related complications. Study-specific risk estimates were combined by using fixed effect or random effect models.The database search generated a total of 28 prospective studies that met the inclusion criteria. Among these studies, 14 reported the risk of HCC incidence and 6 studies reported risk of HCC specific mortality. Six studies provided a total of 8 results for all-cause mortality in HCC patients. Four studies documented HCC recurrence risks and 2 studies reported risks for hepatic decomposition occurrence in HCC patients. Meta-analysis indicated that pre-existing diabetes mellitus (DM) was significantly associated with increased risk of HCC incidence [meta-relative risk (RR)?=?1.87, 95% confidence interval (CI): 1.15-2.27] and HCC-specific mortality (meta-RR?=?1.88, 95%CI: 1.39-2.55) compared with their non-DM counterparts. HCC patients with pre-existing DM had a 38% increased (95% CI: 1.13-1.48) risk of death from all-causes and 91% increased (95%CI: 1.41-2.57) risk of hepatic decomposition occurrence compared to those without DM. In DM patients, the meta-RR for HCC recurrence-free survival was 1.93(95%CI: 1.12-3.33) compared with non-diabetic patients.The findings from the current meta-analysis suggest that DM may be both associated with elevated risks of both HCC incidence and mortality. Furthermore, HCC patients with pre-existing diabetes have a poorer prognosis relative to their non-diabetic counterparts.
| S-EPMC3244388 | biostudies-literature
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Project description:ObjectiveWe aimed to elucidate whether potato consumption is associated with a higher risk of type 2 diabetes (T2D).Research design and methodsWe analyzed data in three cohorts consisting of U.S. male and female health professionals without diabetes, cardiovascular disease, and cancer at baseline: 70,773 women from the Nurses' Health Study (1984-2010), 87,739 women from Nurses' Health Study II (1991-2011), and 40,669 men from the Health Professionals Follow-up Study (1986-2010). Potato consumption was assessed quadrennially using validated food frequency questionnaires (FFQs), and we calculated 4-year change in potato consumption from consecutive FFQs. Self-reported T2D diagnosis was confirmed using a validated supplementary questionnaire.ResultsDuring 3,988,007 person-years of follow-up, 15,362 new cases of T2D were identified. Higher consumption of total potatoes (including baked, boiled, or mashed potatoes and french fries) was significantly associated with an elevated risk for T2D: the pooled hazard ratio (HR) of T2D compared with <1 serving/week was 1.07 (95% CI 0.97-1.18) for 2-4 servings/week and 1.33 (95% CI 1.17-1.52) for ?7 servings/week after adjustment for demographic, lifestyle, and dietary factors. In addition, the pooled HRs of T2D for every 3 servings/week were 1.04 (95% CI 1.01-1.08) for baked, boiled, or mashed potatoes, and 1.19 (95% CI 1.13-1.25) for french fries. We further estimated that the HR of T2D was 0.88 (95% CI 0.84-0.91) for replacing 3 servings/week of total potatoes with the same amount of whole grains. Last, in comparison with stable potato consumption, every 3-servings/week increment of potato consumption in 4 years was associated with a 4% (95% CI 0-8%) higher T2D risk.ConclusionsGreater consumption of potatoes, especially french fries, was associated with a higher T2D risk, independent of BMI and other risk factors. Replacement of potatoes with whole grains was associated with a lower T2D risk.
| S-EPMC4764041 | biostudies-literature
Project description:OBJECTIVES:While emerging evidence supports a possible link between depression and ovarian cancer progression, no prospective studies have explored the association with ovarian cancer risk. METHODS:We prospectively followed 77,451 women from the Nurses' Health Study (1992-2010) and 106,452 women from the Nurses' Health Study II (1993-2011). Depression was defined as having one or more of the following: a 5-item Mental Health Index (MHI-5) score?52, antidepressant use, or physician-diagnosed depression. Multivariable-adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between depression and incident ovarian cancer. RESULTS:We documented 698 incident cases of epithelial ovarian cancer during follow-up. In multivariable analyses, depression assessed 2-4years before cancer diagnosis was associated with a modestly higher incidence of ovarian cancer (HR=1.30, 95% CI 1.05-1.60). Compared to women with persistent negative depression status, the adjusted HRs were 1.34 (95% CI 1.01-1.76) for women with persistent positive depression status and 1.28 (95% CI 0.88-1.85) for women with worsening depression status over follow-up. The association did not appear to vary by ovarian cancer risk factors or tumor characteristics. CONCLUSIONS:Our findings suggest that depression may be associated with a modestly increased risk of ovarian cancer. Given the relatively high prevalence of depression in women, future work in larger prospective human studies is needed to confirm our results.
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Project description:Although many case-control studies suggested that garlic intake may reduce gastric cancer risk, evidence from prospective cohort studies has been lacking. We examined the association between garlic intake and subsequent risk of gastric cancer among 77,086 women in the Nurses' Health Study (1984-2014) and 46,398 men in the Health Professionals Follow-Up Study (1986-2014). Relative risks (RRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards models. We additionally examined garlic intake in relation to Helicobacter pylori (H. pylori) infection among 613 participants using logistic regression. During up to 30 years of follow-up, 292 participants were diagnosed with gastric cancer. The pooled multivariable RR of gastric cancer among participants who ate garlic, as compared to those who did not, were 1.11 (95% CI?=?0.81-1.51) for the intake of garlic less than once per week, 0.98 (95% CI?=?0.71-1.36) for one to four times per week and 1.39 (95% CI?=?0.89-2.17) for five or more times per week (p for trend?=?0.23). Similarly, no statistically significant association was observed cross-sectionally between garlic intake and H. pylori infection (comparing five or more times per week to never, pooled multivariable odds ratio?=?1.66, 95% CI?=?0.89-3.09; p for trend?=?0.11). The findings from this large prospective study do not support the hypothesis that high garlic intake reduces risk of gastric cancer.
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Project description:BackgroundUnderstanding the association between diet and colorectal cancer (CRC) risk is essential to curbing the epidemic of this cancer. This study prospectively evaluated adherence to the Chinese Food Pagoda (CHFP), and two American Dietary Guidelines: the Alternative Healthy Eating Index (AHEI-2010) and the Dietary Approaches to Stop Hypertension (DASH) in association with CRC risk among Chinese adults living in urban Shanghai, China.MethodsParticipants included 60 161 men and 72 445 women aged 40-74, from two ongoing population-based prospective cohort studies. Associations between dietary guideline compliance scores and CRC risk were evaluated by Cox proportional hazard regression analyses, with age as time metric, and potential confounders were adjusted.ResultsWe identified 1670 CRC incidence cases (691 males and 979 females) during an average 8.1?years of follow-up for men and 13.4 years for women. CHFP score was inversely associated with risk of CRC, with hazard ratios (HRs) (95% confidence intervals) of 0.88 (0.77, 1.00), 0.86 (0.75, 0.98) and 0.84 (0.73, 0.96) for the 2nd, 3rd and 4th quartiles versus 1st quartile, respectively (Ptrend= 0.01). The inverse association appeared stronger for rectal cancer, individuals at younger age (< 50?years), with a lower BMI (<25?kg/m2) or without any metabolic conditions at baseline, although no multiplicative interactions were noted. No consistent association pattern was observed for the modified DASH score and the modified AHEI-2010.ConclusionsCompliance with the Dietary Guidelines for Chinese was associated with reduced risk of CRC among Chinese adults. To maximize health impacts, dietary recommendations need to be tailored for specific populations.
| S-EPMC7124505 | biostudies-literature
Project description:BackgroundParacetamol overdose is common but patient stratification is suboptimal. We investigated the usefulness of new biomarkers that have either enhanced liver specificity (microRNA-122 [miR-122]) or provide mechanistic insights (keratin-18 [K18], high mobility group box-1 [HMGB1], and glutamate dehydrogenase [GLDH]). The use of these biomarkers could help stratify patients for their risk of liver injury at hospital presentation.MethodsUsing data from two prospective cohort studies, we assessed the potential for biomarkers to stratify patients who overdose with paracetamol. We completed two independent prospective studies: a derivation study (MAPP) in eight UK hospitals and a validation study (BIOPAR) in ten UK hospitals. Patients in both cohorts were adults (≥18 years in England, ≥16 years in Scotland), were diagnosed with paracetamol overdose, and gave written informed consent. Patients who needed intravenous acetylcysteine treatment for paracetamol overdose had circulating biomarkers measured at hospital presentation. The primary endpoint was acute liver injury indicating need for continued acetylcysteine treatment beyond the standard course (alanine aminotransferase [ALT] activity >100 U/L). Receiver operating characteristic (ROC) curves, category-free net reclassification index (cfNRI), and integrated discrimination index (IDI) were applied to assess endpoint prediction.FindingsBetween June 2, 2010, and May 29, 2014, 1187 patients who required acetylcysteine treatment for paracetamol overdose were recruited (985 in the MAPP cohort; 202 in the BIOPAR cohort). In the derivation and validation cohorts, acute liver injury was predicted at hospital presentation by miR-122 (derivation cohort ROC-area under the curve [AUC] 0·97 [95% CI 0·95-0·98]), HMGB1 (0·95 [0·93-0·98]), and full-length K18 (0·95 [0·92-0·97]). Results were similar in the validation cohort (miR-122 AUC 0·97 [95% CI 0·95-0·99], HMGB1 0·98 [0·96-0·99], and full-length K18 0·93 [0·86-0·99]). A combined model of miR-122, HMGB1, and K18 predicted acute liver injury better than ALT alone (cfNRI 1·95 [95% CI 1·87-2·03], p<0·0001 in the MAPP cohort; 1·54 [1·08-2·00], p<0·0001 in the BIOPAR cohort).InterpretationPersonalised treatment pathways could be developed by use of miR-122, HMGB1, and full-length K18 at hospital presentation for patient stratification. This prospective study supports their use for hepatic safety assessment of new medicines.FundingEdinburgh and Lothians Health Foundation, UK Medical Research Council.
| S-EPMC5777094 | biostudies-literature
Project description:ObjectiveTo determine whether individual fruits are differentially associated with risk of type 2 diabetes.DesignProspective longitudinal cohort study.SettingHealth professionals in the United States.Participants66,105 women from the Nurses' Health Study (1984-2008), 85,104 women from the Nurses' Health Study II (1991-2009), and 36,173 men from the Health Professionals Follow-up Study (1986-2008) who were free of major chronic diseases at baseline in these studies.Main outcome measureIncident cases of type 2 diabetes, identified through self report and confirmed by supplementary questionnaires.ResultsDuring 3,464,641 person years of follow-up, 12,198 participants developed type 2 diabetes. After adjustment for personal, lifestyle, and dietary risk factors of diabetes, the pooled hazard ratio of type 2 diabetes for every three servings/week of total whole fruit consumption was 0.98 (95% confidence interval 0.97 [corrected] to 0.99). With mutual adjustment of individual fruits, the pooled hazard ratios of type 2 diabetes for every three servings/week were 0.74 (0.66 to 0.83) for blueberries, 0.88 (0.83 to 0.93) for grapes and raisins, 0.89 (0.79 to 1.01) for prunes, 0.93 (0.90 to 0.96) for apples and pears, 0.95 (0.91 to 0.98) for bananas, 0.95 (0.91 to 0.99) for grapefruit, 0.97 (0.92 to 1.02) for peaches, plums, and apricots, 0.99 (0.95 to 1.03) for oranges, 1.03 (0.96 to 1.10) for strawberries, and 1.10 (1.02 to 1.18) for cantaloupe. The pooled hazard ratio for the same increment in fruit juice consumption was 1.08 (1.05 to 1.11). The associations with risk of type 2 diabetes differed significantly among individual fruits (P<0.001 in all cohorts).ConclusionOur findings suggest the presence of heterogeneity in the associations between individual fruit consumption and risk of type 2 diabetes. Greater consumption of specific whole fruits, particularly blueberries, grapes, and apples, is significantly associated with a lower risk of type 2 diabetes, whereas greater consumption of fruit juice is associated with a higher risk.
| S-EPMC3978819 | biostudies-literature
Project description:Aims/hypothesisStudies suggest a potential link between low-grade metabolic acidosis and type 2 diabetes. A western dietary pattern increases daily acid load but the association between diet-dependent acid load and type 2 diabetes is still unclear. This study aimed to assess whether diet-dependent acid load is associated with the risk of type 2 diabetes.MethodsWe examined the association between energy-adjusted net endogenous acid production (NEAP), potential renal acid load (PRAL) and animal protein-to-potassium ratio (A:P) on incident type 2 diabetes in 67,433 women from the Nurses' Health Study, 84,310 women from the Nurses' Health Study II and 35,743 men from the Health Professionals' Follow-up Study who were free from type 2 diabetes, cardiovascular disease and cancer at baseline. Study-specific HRs were estimated using Cox proportional hazards models with time-varying covariates and were pooled using a random effects meta-analysis.ResultsWe documented 15,305 cases of type 2 diabetes during 4,025,131 person-years of follow-up. After adjustment for diabetes risk factors, dietary NEAP, PRAL and A:P were positively associated with type 2 diabetes (pooled HR [95% CI] for highest (Q5) vs lowest quintile (Q1): 1.29 [1.22, 1.37], p trend <0.0001; 1.29 [1.22, 1.36], p trend <0.0001 and 1.32 [1.24, 1.40], p trend <0.0001 for NEAP, PRAL and A:P, respectively). These results were not fully explained by other dietary factors including glycaemic load and dietary quality (HR [95% CI] for Q5 vs Q1: 1.21 [1.09, 1.33], p trend <0.0001; 1.19 [1.08, 1.30] and 1.26 [1.17, 1.36], p trend <0.0001 for NEAP, PRAL and A:P, respectively).Conclusions/interpretationThis study suggests that higher diet-dependent acid load is associated with an increased risk of type 2 diabetes. This association is not fully explained by diabetes risk factors and overall diet quality.
| S-EPMC5831375 | biostudies-literature