Project description:Family history of lung cancer (FHLC) has been widely studied but most prospective cohort studies have primarily been conducted in non-Asian countries. We assessed the association between FHLC with risk of lung cancer (LC) incidence and mortality in a population of East Asian individuals. A total of 478,354 participants from 11 population-based cohorts in the Asia Cohort Consortium were included. A Cox proportional hazards regression model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 7,785 LC incident cases were identified. FHLC (any LC subtype) was associated with an increased risk of LC incidence (HR = 1.45, 95% CI = 1.30-1.63). The positive association was observed in men and women (HR = 1.44, 95% CI = 1.26-1.66 in men; HR = 1.47, 95% CI = 1.22-1.79 in women), and in both never-smokers and ever-smokers (HR = 1.43, 95% CI = 1.18-1.73 in never-smokers; HR = 1.46, 95% CI =1.27-1.67 in ever-smokers). FHLC was associated with an increased risk of lung adenocarcinoma (HR = 1.63, 95% CI: 1.36-1. 94), squamous cell carcinoma (HR = 1.88, 95% CI: 1.46-2.44), and other non-small cell LC (HR = 1.94, 95% CI: 1.02-3.68). However, we found no evidence of significant effect modification by sex, smoking status, and ethnic groups. In conclusion, FHLC was associated with increased risk of LC incidence and mortality, and the associations remained consistent regardless of sex, smoking status and ethnic groups among the East Asian population.
Project description:Aims/hypothesisThis study aimed to investigate whether the effects of sleep duration interacted with the presence of diabetes. We specifically sought to examine the relationship between sleep duration and all-cause and cause-specific mortality in people with type 2 diabetes across sex, age at diagnosis, duration of diabetes and treatment type.MethodsThe sample consisted of 273,029 adults, including 248,817 without diabetes and 24,212 with type 2 diabetes, who participated in the National Health Interview Survey from 2004 to 2013 and whose data were linked to a mortality database up to 31 December 2015. Sleep duration was measured using self-report, whereby participants were asked 'on average how long do you sleep each day (≤5, 6, 7, 8, 9 or ≥10 h/day)?' The relationship between sleep duration and mortality risk was investigated using Cox proportional hazards regression model, with adjustments for demographics, BMI, lifestyle behaviours and clinical variables.ResultsAbsolute mortality rate was higher in adults with diabetes and extremes of sleep duration (≤5 h/day, 215.0 per 10,000 person-years; ≥10 h/day, 363.5 per 10,000 person-years). There was a non-significant interaction between sleep duration and the presence of diabetes (p for interaction = 0.08). A J-shaped relationship existed between sleep duration and all-cause mortality risk in people with type 2 diabetes. Compared with the reference group (7 h/day), both shorter and longer sleep durations were associated with increased risk of all-cause mortality (≤5 h/day, HR 1.24 [95% CI 1.09, 1.40]; 6 h/day, HR 1.13 [1.01, 1.28]; 8 h/day, HR 1.17 [1.06, 1.30]; ≥10 h/day, HR 1.83 [1.61, 2.08]). Similar associations were also observed for mortality risk from CVD, cancer, kidney disease, Alzheimer's disease and chronic lower respiratory diseases. Longer sleep duration in those with a younger age at diabetes onset was associated with greater risks of all-cause and CVD mortality. Shorter sleep duration in individuals treated with both insulin and oral glucose-lowering medication was also associated with higher risks of all-cause and CVD mortality.Conclusions/interpretationThe associations between sleep duration and mortality risk may be different between diabetic and non-diabetic individuals. In people with type 2 diabetes, sleeping less or more than 7 h/day was associated with increased risk of all-cause and condition-specific mortality. The association was more prominent in those with a younger age at diabetes onset and receiving treatment with both oral glucose-lowering medication and insulin. This population may benefit from targeted sleep-related interventions to reduce the risks of adverse health outcomes. Graphical abstract.
Project description:BackgroundMetformin and aspirin are commonly co-prescribed to people with diabetes. Metformin may prevent cancer, but in older people (over 70 years), aspirin has been found to increase cancer mortality. This study examined whether metformin reduces cancer mortality and incidence in older people with diabetes; it used randomization to 100 mg aspirin or placebo in the ASPirin in Reducing Events in the Elderly (ASPREE) trial to quantify aspirin's impact on metformin users.MethodsAnalysis included community-dwelling ASPREE participants (aged ≥70 years, or ≥65 years for members of US minority populations) with diabetes. Diabetes was defined as a fasting blood glucose level greater than 125 mg/dL, self-report of diabetes, or antidiabetic medication use. Cox proportional hazards regression models were used to analyze the association of metformin and a metformin-aspirin interaction with cancer incidence and mortality, with adjustment for confounders.ResultsOf 2045 participants with diabetes at enrollment, 965 were concurrently using metformin. Metformin was associated with a reduced cancer incidence risk (adjusted hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.51 to 0.90), but no conclusive benefit for cancer mortality (adjusted HR = 0.72, 95% CI = 0.43 to 1.19). Metformin users randomized to aspirin had greater risk of cancer mortality compared with placebo (HR = 2.53, 95% CI = 1.18 to 5.43), but no effect was seen for cancer incidence (HR = 1.11, 95% CI = 0.75 to 1.64). The possible effect modification of aspirin on cancer mortality, however, was not statistically significant (interaction P = .11).ConclusionsIn community-dwelling older adults with diabetes, metformin use was associated with reduced cancer incidence. Increased cancer mortality risk in metformin users randomized to aspirin warrants further investigation.Aspree trial registrationClinicalTrials.gov ID NCT01038583.
Project description:BackgroundThe antitumor effect of statins has been highlighted, but clinical study results remain inconclusive. While patients with diabetes are at high risk of cancer, it is uncertain whether statins are effective for cancer chemoprevention in this population.ObjectiveThis study evaluated the association between statins and cancer incidence/mortality in patients with type 2 diabetes.DesignThis study was a follow-up observational study of the Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial, which was a randomized controlled trial of low-dose aspirin in Japanese patients with type 2 diabetes.ParticipantsThis study enrolled 2536 patients with type 2 diabetes, age 30-85 years, and no history of atherosclerotic cardiovascular disease, from December 2002 until May 2005. All participants recruited in the JPAD trial were followed until the day of any fatal event or July 2015. We defined participants taking any statin at enrollment as the statin group (n = 650) and the remainder as the no-statin group (n = 1886).Main measuresThe primary end point was the first occurrence of any cancer (cancer incidence). The secondary end point was death from any cancer (cancer mortality).Key resultsDuring follow-up (median, 10.7 years), 318 participants developed a new cancer and 123 died as a result. Cancer incidence and mortality were 10.5 and 3.7 per 1000 person-years in the statin group, and 16.8 and 6.3 per 1000 person-years in the no-statin group, respectively. Statin use was associated with significantly reduced cancer incidence and mortality after adjustment for confounding factors (cancer incidence: adjusted hazard ratio [HR], 0.67; 95% CI, 0.49-0.90, P = 0.007; cancer mortality: adjusted HR, 0.60; 95% CI, 0.36-0.98, P = 0.04).ConclusionsStatin use was associated with a reduced incidence and mortality of cancer in Japanese patients with type 2 diabetes.
Project description:PurposeDiabetes has been associated with increased risk of Parkinson's disease (PD). Diabetes medications have been suggested as a possible explanation, but findings have been inconsistent. More information on the role of exposure in different time windows is needed because PD has long onset. We assessed the association between use of different diabetes medication categories and risk of PD in different exposure periods.MethodsA case-control study restricted to people with diabetes was performed as part of nationwide register-based Finnish study on PD (FINPARK). We included 2017 cases (diagnosed 1999-2015) with PD and 7934 controls without PD. Diabetes medication use was identified from Prescription Register (1995-2015) and categorized to insulins, biguanides, sulfonylureas, thiazolidinediones (TZDs), dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) analogues and glinide. Exposure for each medication class was determined as none, at least 3 years before outcome and only within the three-year lag time before PD outcome.ResultsThe use of insulins, biguanides, sulfonylureas, DPP-4 inhibitors, GLP-1 analogues or glinides was not associated with PD. Use of TZDs before lag time compared to non-use of TZDs (adjusted odds ratio (OR) 0.78; 95% Confidence interval (CI) 0.64-0.95) was associated with decreased risk of PD.ConclusionsOur nationwide case-control study of people with diabetes found no robust evidence on the association between specific diabetes medication classes and risk of PD. Consistent with earlier studies, TZD use was associated with slightly decreased risk of PD. The mechanism for this should be verified in further studies.
Project description:Numerous studies have reported that antibiotics could lead to diabetes, even after adjusting for confounding variables. This study aimed to determine the causal relationship between antibiotics use and diabetes in a nationally representative cohort. This retrospective cohort study included adults aged 40 years or older who were enrolled in the Korean National Health Insurance Service-Health Screening Cohort. Antibiotic exposure was assessed from 2002 to 2005 and newly diagnosed diabetes mellitus was determined based on diagnostic codes and history of antidiabetic medication use from 2006 to 2015. Multivariate Cox proportional hazards model was used to assess the association between antibiotic use and diabetes incidence. The mean age of the 201,459 study subjects was 53.2 years. People who used antibiotics for 90 or more days had a higher risk of diabetes (adjusted hazard ratio [aHR] 1.16, 95% confidence interval [CI] 1.07-1.26) compared to non-users. Those who used five or more classes of antibiotics had a higher risk of diabetes than those who used one antibiotic class (aHR 1.14; 95% CI 1.06-1.23). The clear dose-dependent association between antibiotics and diabetes incidence supports the judicious use of antibiotics in the future.
Project description:The genomic region at 9p21 chromosome near the CDKN2A/CDKN2B genes is associated with type 2 diabetes(T2D) and cardiovascular disease(CVD). The effect of the 9p21 locus on long-term mortality in patients with T2D has yet to be determined.We examined three single nucleotide polymorphisms (SNPs) on 9p21, consistently and independently associated with T2D (rs10811661) or CVD (rs10757278, rs2383206), in relation to the risk of total and cardiovascular mortality in diabetic patients. We also aimed to replicate the previously observed interaction between rs2383206 and glycemic control on mortality.Genotypes for three SNPs were determined in 914 individuals from a prospective cohort of T2D patients of Dutch origin. Associations with mortality were assessed using Cox proportional hazard analyses.After a median follow-up of 9.5 years, 358 out of 914 patients had died. The hazard ratio (HR) for total mortality among individuals homozygous for the T2D-risk allele of rs10811661 compared to non-homozygous individuals was 0.74(95%CI 0.59-0.93). For the carriers of both CVD-risk alleles of rs10757278, the HR for total mortality was 1.31(95%CI 1.01-1.70). We found a significant interaction between rs2383206 and HbA1c on mortality, which was higher among patients with two CVD-risk alleles in the two lowest HbA1c tertiles (HR 1.68(95%CI 1.08-2.63); HR 1.48(95%CI 1.01-2.18).In conclusion, common variants on 9p21 were associated with mortality in patients with T2D in a Dutch population. The T2D SNP was inversely associated with mortality, while the CVD SNP increased the risk for mortality. We confirmed a possible, although different, synergistic relationship between HbA1c and rs2383206 on total mortality.
Project description:OBJECTIVE: We recently showed that RNA oxidation, estimated by urinary excretion of 8-oxo-7,8-dihydroguanosine (8-oxoGuo), independently predicted mortality in a cohort of 1,381 treatment-naive patients with newly diagnosed type 2 diabetes. In the present investigation, we analyzed urine collected 6 years after the diagnosis to assess the association between urinary markers of nucleic acid oxidation and mortality in patients with established and treated diabetes. RESEARCH DESIGN AND METHODS: We used data from the 970 patients who attended the screening for diabetes complications 6 years after the diagnosis. Cox proportional hazards regression was used to examine the relationship between urinary markers of DNA oxidation (8-oxo-7,8-dihydro-2'-deoxyguanosine [8-oxodG] [n = 938]) and RNA oxidation (8-oxoGuo [n = 936]) and mortality. RESULTS: During a median of 9.8 years of follow-up, 654 patients died. Urinary 8-oxoGuo assessed 6 years after the diagnosis was significantly associated with mortality. The multivariate-adjusted hazard ratios for all-cause and diabetes-related mortality of patients with 8-oxoGuo levels in the highest quartile compared with those in the lowest quartile were 1.86 (95% CI 1.34-2.58) and 1.72 (1.11-2.66), respectively. Conversely, 8-oxodG was not associated with mortality. In addition, we found an association between changes in 8-oxoGuo from diagnosis to 6-year follow-up and mortality, with increased risk in patients with an increase and decreased risk in patients with a decrease in 8-oxoGuo. CONCLUSIONS: The RNA oxidation marker 8-oxoGuo is an independent predictor of mortality in patients with established and treated type 2 diabetes, and changes in 8-oxoGuo during the first 6 years after diagnosis are associated with mortality.
Project description:BackgroundParenting style is associated with offspring health, but whether it is associated with offspring mortality at older ages remains unknown.AimsWe examined whether childhood experiences of suboptimal parenting style are associated with increased risk of death at older ages.MethodLongitudinal cohort study of 1964 community-dwelling adults aged 65-79 years.ResultsThe association between parenting style and mortality was inverse and graded. Participants in the poorest parenting style score quartile had increased risk of death (hazard ratio (HR) = 1.72, 95% CI 1.20-2.48) compared with those in the optimal parenting style score quartile after adjustment for age and gender. Full adjustment for covariates partially explained this association (HR = 1.49, 95% CI 1.02-2.18). Parenting style was inversely associated with cancer and other mortality, but not cardiovascular mortality. Maternal and paternal parenting styles were individually associated with mortality.ConclusionsExperiences of suboptimal parenting in childhood are associated with increased risk of death at older ages.
Project description:A growing body of evidence suggests that diabetes is a risk factor for endometrial cancer incidence. However, most of these studies used case-control study designs and did not adjust for obesity, an established risk factor for endometrial cancer. In addition, few epidemiological studies have examined the association between diabetes treatment and endometrial cancer risk. The objective of this study was to assess the relationships among diabetes, diabetes treatment and endometrial cancer risk in postmenopausal women participating in the Women's Health Initiative (WHI).A total of 88 107 postmenopausal women aged 50-79 years who were free of cancer and had no hysterectomy at baseline were followed until date of endometrial cancer diagnosis, death, hysterectomy or loss to follow-up, whichever came first. Endometrial cancers were confirmed by central medical record and pathology report review. Multivariate Cox proportional hazards regression models were used to estimate hazard ratios (HRs) (95% confidence interval (CI)) for diagnosis of diabetes and metformin treatment as risk factors for endometrial cancer.Over a mean of 11 years of follow-up, 1241 endometrial cancers developed. In the primary analysis that focused on prevalent diabetes at enrolment, compared with women without diabetes, women with self-reported diabetes, and the subset of women with treated diabetes, had significantly higher risk of endometrial cancer without adjusting for BMI (HR=1.44, 95% CI: 1.13-1.85 for diabetes, HR=1.57, 95% CI: 1.19-2.07 for treated diabetes). However after adjusting for BMI, the associations between diabetes, diabetes treatment, diabetes duration and the risk of endometrial cancer became non-significant. Elevated risk was noted when considering combining diabetes diagnosed at baseline and during follow-up as time-dependent exposure (HR=1.31, 95% CI: 1.08-1.59) even after adjusting for BMI. No significant association was observed between metformin use and endometrial cancer risk.Our results suggest that the relationship observed in previous research between diabetes and endometrial cancer incidence may be largely confounded by body weight, although some modest independent elevated risk remains.