Introduction: Evidence on the relationship between type 2 diabetes onset age, duration, and mortality risk has been influenced by limited follow-up, inadequate control for confounding, and inability to cover the full range of onset age, duration, and the full spectrum of major causes of death. Moreover, there are scarce data dissecting how type 2 diabetes onset age and duration shape life expectancy. Hypothesis We assessed the hypothesis that early onset of type 2 diabetes and longer disease duration may be associated with higher risk of all-cause and cause-specific mortality and greater loss in life expectancy. Methods: We prospectively followed 270,075 eligible participants in the Nurses’ Health Study, Nurses’ Health Study II, and Health Professionals Follow-up Study longitudinal cohorts for up to 40 years. The exposures include type 2 diabetes onset age (<40, ≥40 to <50, ≥50 to <60, ≥60 to <70, ≥70 to <80, and ≥80 years) and duration (<10, ≥10 to <20, ≥20 to <30, and ≥30 years). Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for age and a wide spectrum of potential confounders. Results: We documented 73,076 deaths during 8,166,216 person-years of follow-up. In fully-adjusted analyses, incident early-onset type 2 diabetes (diagnosed <40 years of age) was associated with significantly higher mortality from all-causes (HR, 95% CI was 3.16, 2.64-3.79; vs. individuals without type 2 diabetes), cardiovascular disease (6.56, 4.27-10.1), respiratory disease (3.43, 1.38-8.51), neurodegenerative disease (5.13, 2.09-12.6), kidney disease (8.55, 1.98-36.9), and suggestively increased mortality from diabetes-related cancer (1.63, 0.94-2.83) and obesity-related cancer (1.63, 0.92-2.88). The relative risk elevations declined dramatically with each higher decade of age at type 2 diabetes diagnosis for deaths from most of these causes, though the absolute risk difference increased continuously. A substantially higher cumulative incidence of mortality and a greater loss in life expectancy were associated with younger age at type 2 diabetes diagnosis. Comparing individuals with early-onset type 2 diabetes to those without type 2 diabetes, their estimated multivariable-adjusted cumulative incidence of all-cause mortality at age 80 was 0.43 vs. 0.20, and the estimated life expectancy loss at age 40 was 2.5 years. Longer disease duration was associated with generally higher relative and absolute risk of mortality. Conclusions: Early onset of type 2 diabetes and longer disease duration are associated with substantially increased risk of all-cause and cause-specific mortality and greater loss in life expectancy. The effect of early-onset type 2 diabetes on mortality risk is stronger than that of later-onset type 2 diabetes.
Loquat (Eriobotrya japonica Lindl.) is an evergreen fruit tree of Chinese origin, and its autumn-winter flowering and fruiting growth habit means that its fruit development is susceptible to low-temperature stress. In a previous study, the triploid loquat (B431 × GZ23) has been identified with high photosynthetic efficiency and strong resistance under low-temperature stress. Analysis of transcriptomic and lipidomic data revealed that the fatty acid desaturase gene EjFAD8 was closely associated with low temperatures. Phenotypic observations and measurements of physiological indicators in Arabidopsis showed that overexpressing-EjFAD8 transgenic plants were significantly more tolerant to low temperatures compared to the wild-type. Heterologous overexpression of EjFAD8 enhanced some lipid metabolism genes in Arabidopsis, and the unsaturation of lipids was increased, especially for SQDG (16:0/18:1; 16:0/18:3), thereby improving the cold tolerance of transgenic lines. The expression of ICE-CBF-COR genes were further analyzed so that the relationship between fatty acid desaturase and the ICE-CBF-COR pathway can be clarified. These results revealed the important role of EjFAD8 under low-temperature stress in triploid loquat, the increase expression of FAD8 in loquat under low temperatures lead to desaturation of fatty acids. On the one hand, overexpression of EjFAD8 in Arabidopsis increased the expression of ICE-CBF-COR genes in response to low temperatures. On the other hand, upregulation of EjFAD8 at low temperatures increased fatty acid desaturation of SQDG to maintain the stability of photosynthesis under low temperatures. This study not only indicates that the EjFAD8 gene plays an important role in loquat under low temperatures, but also provides a theoretical basis for future molecular breeding of loquat for cold resistance.
<p>Table S5. Hazard ratio of cancer-specific mortality by plasma 25-hydroxyvitamin D levels in plasma biomarker companion study and by predicted vitamin D scores in diet and lifestyle companion study</p>
We thank Zhang and Lv for their comments [1] on our recently published large prospective cohort study investigating the associations between genetic risk, health-associated lifestyle, and risk of early-onset total cancer and breast cancer.We appreciate the opportunity to clarify and respond to their concerns regarding participation bias, the generalizability of the UK Biobank data, and death as a competing risk.
Abstract Background: Weight loss is a common symptom in patients with cancer. However, little is known about how much weight loss and over what time period weight loss precedes cancer diagnosis. Herein, we evaluate the association between weight loss and subsequent 2-year cancer diagnosis using repeatedly measured weight data in two large prospective cohorts. Methods: The analysis included 111,891 US women from the Nurses’ Health Study and 45,498 US men from the Health Professional Follow-up Study, who were enrolled in 1978 and 1988, respectively, and followed through 2012, and who were cancer-free and ≥40 years old at study entry. Current weight and lifestyle information were assessed every 2 years by questionnaire, and weight change in the previous 2 years was calculated by comparing two consecutive questionnaires. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for subsequent risk of cancer diagnosis according to weight change percentage. We also examined 20-year trajectories of body mass index (BMI) before cancer diagnosis. Results: During 4.1 million person-years of follow-up, we documented 30,441 incident cancers. Participants with recent weight loss were at increased risk for cancer diagnosis in the subsequent 2 years (Ptrend <0.0001). Compared with participants without weight loss, those who had a weight loss of 5-10% or >10% had a multivariable-adjusted HR for total cancer of 1.09 (95% CI, 1.04-1.13) and 1.17 (95% CI, 1.10-1.24), respectively. For individual cancer types, increased weight loss was associated with a subsequent cancer diagnosis of esophagus, liver, pancreas, leukemia, stomach, myeloma, lung, colorectal, and non-Hodgkin lymphoma (all Ptrend <0.005). Comparing participants with weight loss of >10% to those without weight loss, multivariable-adjusted HRs were 4.22 (95% CI, 2.50-7.13) for esophageal cancer, 3.30 (95% CI, 1.65-6.61) for liver cancer, 2.46 (95% CI, 1.84-3.30) for pancreatic cancer, 2.40 (95% CI, 1.59-3.61) for leukemia, 2.26 (95% CI, 1.32-3.87) for stomach cancer, 1.80 (95% CI, 1.14-2.83) for myeloma, 1.45 (95% CI, 1.22-1.73) for lung cancer, 1.38 (95% CI, 1.14-1.66) for colorectal cancer, and 1.35 (95% CI, 1.06-1.72) for non-Hodgkin lymphoma. The 20-year trajectory of BMI indicated that most weight loss occurred in the 2 years before cancer diagnosis, with the magnitude of weight loss increasing closer to the time of subsequent cancer diagnosis. Conclusion: Recent weight loss of >10% predicts elevated risk of cancer diagnosis in the forthcoming 2 years, particularly for cancers of the upper gastrointestinal tract, hematological system, colorectum, and lung. Citation Format: Qiao-Li Wang, Ana Babic, Michael H. Rosenthal, Alice A. Lee, Yin Zhang, Xuehong Zhang, Mingyang Song, Leandro F. Rezende, Dong Hoon Lee, Leah Biller, Kimmie Ng, Andrew T. Chan, Meir J. Stampfer, Edward L. Giovannucci, Peter Kraft, Chen Yuan, Brian M. Wolpin. Weight loss and subsequent cancer diagnosis: A prospective cohort study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5934.
Background: Prior studies have reported controversial conclusions regarding the risk of adverse cardiovascular events in patients using proton-pump inhibitors (PPIs) combined with clopidogrel therapy, causing much uncertainty in clinical practice. We sought to evaluate the safety of PPIs use among high-risk cardiovascular patients who underwent percutaneous coronary intervention (PCI) in a long-term follow-up study. Methods: A total of 7868 consecutive patients who had undergone PCI and received dual antiplatelet therapy (DAPT) at a single center from January 2013 to December 2013 were enrolled. Adenosine diphosphate (ADP)-induced platelet aggregation inhibition was measured by modified thromboelastography (mTEG) in 5042 patients. Propensity score matching (PSM) was applied to control differing baseline factors. Cox proportional hazards regression was used to evaluate the 2-year major adverse cardiovascular and cerebrovascular events (MACCEs), as well as individual events, including all-cause death, myocardial infarction, unplanned target vessel revascularization, stent thrombosis, and stroke. Results: Among the whole cohort, 27.2% were prescribed PPIs. The ADP-induced platelet aggregation inhibition by mTEG was significantly lower in PPI users than that in non-PPI users (42.0 ± 30.9% vs. 46.4 ± 31.4%, t = 4.435, P < 0.001). Concomitant PPI use was not associated with increased MACCE through 2-year follow-up (12.7% vs. 12.5%, χ2 = 0.086, P = 0.769). Other endpoints showed no significant differences after multivariate adjustment, regardless of PSM. Conclusion: In this large cohort of real-world patients, the combination of PPIs with DAPT was not associated with increased risk of MACCE in patients who underwent PCI at up to 2 years of follow-up.
Importance Weight loss is common in primary care. Among individuals with recent weight loss, the rates of cancer during the subsequent 12 months are unclear compared with those without recent weight loss. Objective To determine the rates of subsequent cancer diagnoses over 12 months among health professionals with weight loss during the prior 2 years compared with those without recent weight loss. Design, Setting, and Participants Prospective cohort analysis of females aged 40 years or older from the Nurses’ Health Study who were followed up from June 1978 until June 30, 2016, and males aged 40 years or older from the Health Professionals Follow-Up Study who were followed up from January 1988 until January 31, 2016. Exposure Recent weight change was calculated from the participant weights that were reported biennially. The intentionality of weight loss was categorized as high if both physical activity and diet quality increased, medium if only 1 increased, and low if neither increased. Main Outcome and Measures Rates of cancer diagnosis during the 12 months after weight loss. Results Among 157 474 participants (median age, 62 years [IQR, 54-70 years]; 111 912 were female [71.1%]; there were 2631 participants [1.7%] who self-identified as Asian, Native American, or Native Hawaiian; 2678 Black participants [1.7%]; and 149 903 White participants [95.2%]) and during 1.64 million person-years of follow-up, 15 809 incident cancer cases were identified (incident rate, 964 cases/100 000 person-years). During the 12 months after reported weight change, there were 1362 cancer cases/100 000 person-years among all participants with recent weight loss of greater than 10.0% of body weight compared with 869 cancer cases/100 000 person-years among those without recent weight loss (between-group difference, 493 cases/100 000 person-years [95% CI, 391-594 cases/100 000 person-years]; P &lt; .001). Among participants categorized with low intentionality for weight loss, there were 2687 cancer cases/100 000 person-years for those with weight loss of greater than 10.0% of body weight compared with 1220 cancer cases/100 000 person-years for those without recent weight loss (between-group difference, 1467 cases/100 000 person-years [95% CI, 799-2135 cases/100 000 person-years]; P &lt; .001). Cancer of the upper gastrointestinal tract (cancer of the esophagus, stomach, liver, biliary tract, or pancreas) was particularly common among participants with recent weight loss; there were 173 cancer cases/100 000 person-years for those with weight loss of greater than 10.0% of body weight compared with 36 cancer cases/100 000 person-years for those without recent weight loss (between-group difference, 137 cases/100 000 person-years [95% CI, 101-172 cases/100 000 person-years]; P &lt; .001). Conclusions and Relevance Health professionals with weight loss within the prior 2 years had a significantly higher risk of cancer during the subsequent 12 months compared with those without recent weight loss. Cancer of the upper gastrointestinal tract was particularly common among participants with recent weight loss compared with those without recent weight loss.
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