Association between circulating insulin-like growth factor 1 and risk of all-cause and cause-specific mortality

2021 ◽  
Author(s):  
Yu Xie ◽  
Changzhi Huang ◽  
Xingchen Zhu ◽  
Jiayu Wang ◽  
Xikang Fan ◽  
...  
Keyword(s):  
Growth Factor ◽  
General Population ◽  
Early Death ◽  
Cox Proportional Hazards ◽  
Sensitivity Analyses ◽  
Response Analysis ◽  
Insulin Like Growth Factor ◽  
Increased Risk ◽  
Specific Mortality ◽  
Cvd Mortality

Abstract Background: Insulin-like growth factor 1 (IGF-1) is an important growth factor modulating development, homeostasis, and aging. However, whether and how circulating IGF-1 concentrations influence early death risk in the general population remains largely unknown. Methods: We included 380,997 participants who had serum IGF-1 measurement and no history of cancer, cardiovascular disease (CVD) or diabetes at baseline from UK Biobank, a prospective cohort study initiated in 2006-2010. Restricted cubic splines and Cox proportional hazards regression models were used to assess the association between baseline IGF-1 concentrations and all-cause and cause-specific mortality. Results: Over a median follow-up of 8.8 years, 10,753 of the participants died, including 6110 from cancer and 1949 from CVD. Dose-response analysis showed a U-shaped relationship between IGF-1 levels and mortality. Compared to the fifth decile of IGF-1, the lowest decile was associated with 39% (95% CI: 29%-50%), 20% (95% CI: 8%-34%), and 39% (95% CI: 14%-68%) higher risk of all-cause, cancer, and CVD mortality, respectively, while the highest decile was associated with 17% (95% CI: 7%-28%) and 38% (95% CI: 11%-71%) higher risk of all-cause and CVD mortality, respectively. The results remained stable in detailed stratified and sensitivity analyses. Conclusions: Our findings indicate that both low and high concentrations of serum IGF-1 are associated with increased risk of mortality in the general population. Our study provides a basis for future interrogation of underlying mechanisms of IGF-1 in early death occurrence and possible implications for mitigating the risk.

scholarly journals Urinary excretion of epidermal growth factor and rapid loss of kidney function

2020 ◽  
Author(s):  
Jon Viljar Norvik ◽  
Laura R Harskamp ◽  
Viji Nair ◽  
Kerby Shedden ◽  
Marit D Solbu ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
General Population ◽  
Urinary Excretion ◽  
Assessment System ◽  
Sensitivity Analyses ◽  
Increased Risk ◽  
Gfr Decline ◽  
Epidermal Growth ◽  
End Stage

Abstract Background Lower urinary excretion of the kidney tubule–specific biomarker epidermal growth factor (uEGF) is associated with increased risk of renal function [glomerular filtration rate (GFR)] loss in diabetes and in patients with established chronic kidney disease (CKD). We investigated whether uEGF is associated with rapid GFR decline or incident CKD in the general population. Methods Subjects without CKD or diabetes were recruited from the general population in Tromso, Norway [Renal Iohexol Clearance Survey (RENIS); N = 1249] and Groningen, the Netherlands [Prevention of REnal and Vascular END-stage disease (PREVEND); N = 4534], with a median follow-up of 5.6 and 7.4 years, respectively. GFR was measured by iohexol clearance in the RENIS and estimated using the CKD Epidemiology Collaboration creatinine–cystatin C equation in the PREVEND study. Rapid GFR decline was defined as an annual GFR loss >3.0 mL/min/1.73 m2 and in sensitivity analyses as subjects with the 10% steepest GFR slope within each cohort. Results Lower baseline uEGF excretion was associated with rapid GFR loss in both cohorts {RENIS, odds ratio [OR] per 1 μg/mmol lower uEGF 1.42 [95% confidence interval (CI) 1.06–1.91], P = 0.02; PREVEND, OR 1.29 [95% CI 1.10–1.53], P < 0.01}, adjusted for baseline GFR, albumin:creatinine ratio and conventional CKD risk factors. Similar results were obtained using the outcome of the 10% steepest GFR slope in each cohort. Lower uEGF levels were associated with incident CKD in the combined analysis of both cohorts. Conclusions Lower uEGF levels are associated with increased risk of rapid GFR loss and incident CKD in the general population. This finding, together with previous findings in CKD and high-risk populations, supports that uEGF may serve as a broadly applicable biomarker representing the tubular component of the current glomerulus-centric clinical risk assessment system.

scholarly journals Total and Cause-Specific Mortality by Moderately and Markedly Increased Ferritin Concentrations: General Population Study and Metaanalysis

2014 ◽  
Vol 60 (11) ◽  
pp. 1419-1428 ◽  
Author(s):  
Christina Ellervik ◽  
Jacob Louis Marott ◽  
Anne Tybjærg-Hansen ◽  
Peter Schnohr ◽  
Børge G Nordestgaard
Keyword(s):  
General Population ◽  
Total Mortality ◽  
Early Death ◽  
Premature Death ◽  
Population Based ◽  
General Population Study ◽  
Ferritin Concentration ◽  
Heart Study ◽  
Increased Risk ◽  
Specific Mortality

Abstract BACKGROUND Previous population-based studies of plasma ferritin concentration have not revealed a relationship with total mortality. We tested the possible association of increased ferritin concentrations with increased risk of total and cause-specific mortality in the general population. METHODS We examined total and cause-specific mortality according to baseline plasma ferritin concentrations in a Danish population–based study (the Copenhagen City Heart Study) of 8988 individuals, 6364 of whom died (median follow-up 23 years). We also included a metaanalysis of total mortality comprising population-based studies according to ferritin quartiles or tertiles. RESULTS Multifactorially adjusted hazard ratios (HRs) for total mortality for individuals with ferritin ≥200 vs <200 μg/L were 1.1 (95% CI 1.1–1.2; P = 0.0008) overall, 1.1 (1.0–1.2; P = 0.02) in men, and 1.2 (1.0–1.3; P = 0.03) in women. Stepwise increasing concentrations of ferritin were associated with a stepwise increased risk of premature death overall (log rank, P = 2 × 10−22), with median survival of 55 years at ferritin concentrations ≥600 μg/L, 72 years at 400–599 μg/L, 76 years at 200–399 μg/L, and 79 years at ferritin <200 μg/L. The corresponding HR for total overall mortality for ferritin ≥600 vs <200 μg/L was 1.5 (1.2–1.8; P = 0.00008). Corresponding adjusted HRs for ferritin ≥600 vs <200 μg/L were 1.6 (1.1–2.3; P = 0.01) for cancer mortality, 2.9 (1.7–5.0; P = 0.0001) for endocrinological mortality, and 1.5 (1.1–2.0; P = 0.01) for cardiovascular mortality. The metaanalysis random effects odds ratio for total mortality for ferritin upper vs reference quartile or tertile was 1.0 (0.9–1.1; P = 0.3) (P heterogeneity = 0.5). CONCLUSIONS Moderately to markedly increased ferritin concentrations represent a biological biomarker predictive of early death in a dose-dependent linear manner in the general population.

scholarly journals Underweight increases the risk of early death in tuberculosis patients

2017 ◽  
Vol 118 (12) ◽  
pp. 1052-1060 ◽  
Author(s):  
Yung-Feng Yen ◽  
Fu-I Tung ◽  
Bo-Lung Ho ◽  
Yun-Ju Lai
Keyword(s):  
Proportional Hazards ◽  
Early Death ◽  
Cox Proportional Hazards ◽  
Tuberculosis Patients ◽  
Proportional Hazards Regression ◽  
Increased Risk ◽  
Specific Mortality ◽  
Joint Consideration ◽  
The Impact ◽  
Timing Of Death

AbstractEvidence regarding the association between BMI and mortality in tuberculosis (TB) patients is limited and inconsistent. We investigated the impact of BMI on TB-specific and non-TB-specific mortality with respect to different timing of death. All Taiwanese adults with TB in Taipei were included in a retrospective cohort study in 2012–2014. Multinomial Cox proportional hazards regression was used to evaluate the associations between BMI, cause-specific mortality and timing of death. Of 2410 eligible patients, 86·0 % (2061) were successfully treated, and TB-specific and non-TB-specific mortality occurred for 2·2 % (54) and 13·9 % (335), respectively. After controlling for potential confounders, underweight was significantly associated with a higher risk of all-cause mortality (adjusted hazard ratio (AHR) 1·57; 95 % CI 1·26, 1·95), whereas overweight was not. When cause-specific death was considered, underweight was associated with an increased risk of either TB-specific (AHR 1·85; 95 % CI 1·03, 3·33) or non-TB-specific death (AHR 1·52; 95 % CI 1·19, 1·95) during treatment. With joint consideration of cause-specific and timing of death, underweight only significantly increased the risk of TB-specific (AHR 2·23; 95 % CI 1·09, 4·59) and non-TB-specific mortality (AHR 1·81; 95 % CI 1·29, 2·55) within the first 8 weeks of treatment. This study suggests that underweight increases the risk of early death in TB patients during treatment.

Effects of Maternal Diabetes on Fetal Expression of Insulin-Like Growth Factor and Insulin-Like Growth Factor Binding Protein MRNAs in the Rat

1995 ◽  
Vol 147 (2) ◽  
pp. R5-R8 ◽  
Author(s):  
Randal D. Streck ◽  
Veeraramani S. Rajaratnam ◽  
Renata B. Fishman ◽  
Peggy J. Webb
Keyword(s):  
Growth Factor ◽  
Mrna Expression ◽  
Fetal Growth ◽  
Fetal Liver ◽  
Expression Patterns ◽  
Maternal Diabetes ◽  
Limb Bud ◽  
Insulin Like Growth Factor ◽  
Igf Binding Proteins ◽  
Increased Risk

ABSTRACT Matemal diabetes is associated in humans and rats with an increased risk for fetal growth abnormalities and malformations. Therefore, the effect of maternal diabetes on expression of genes that regulate fetal growth and differentiation is of considerable interest. Developmental growth is regulated in part by the expression and availability of insulin-like growth factors (IGFs). Postnatal expression of a subset of the IGFs and IGF binding proteins (IGFBPs) has been demonstrated to be regulated in response to diabetes and other metabolic conditions. We used in situ hybridization to analyze the effect of maternal diabetes, induced by streptozotocin (STZ) prior to mating, upon prenatal rat IGF and IGFBP mRNA expression. At gestational day (GD) 14, the most striking effect of maternal diabetes on fetal IGF/IGFBP gene expression was a marked increase in the abundance of IGFBP-1 mRNA within the liver primordia of fetuses isolated from diabetic dams compared to age-matched controls. This upregulation cannot be entirely due to the approximately one-half-day delay in fetal development (based on limb bud staging) associated with maternal diabetes, as there was no gross difference in the level of IGFBP-1 mRNA between GD13 and GD14 control fetal livers. In contrast, the fetal mRNA expression patterns of IGF-I, IGF-II and IGFBP-2, -3, -4, -5 and -6 were not grossly altered by maternal diabetes. These data are consistent with the hypothesis that IGFBP-1 produced within the fetal liver and secreted into fetal circulation may play a role in regulating rat fetal growth.

Impact of Diabetes Mellitus and Insulin Use on Survival After Colorectal Cancer Diagnosis: The Cancer Prevention Study-II Nutrition Cohort

2012 ◽  
Vol 30 (1) ◽  
pp. 53-59 ◽  
Author(s):  
Ahmed N. Dehal ◽  
Christina C. Newton ◽  
Eric J. Jacobs ◽  
Alpa V. Patel ◽  
Susan M. Gapstur ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Colorectal Cancer ◽  
Cancer Prevention ◽  
Cox Proportional Hazards ◽  
Prevention Study ◽  
Men And Women ◽  
Risk Of Death ◽  
Increased Risk ◽  
Specific Mortality ◽  
Insulin Use

Purpose To examine the association between type 2 diabetes mellitus (T2DM) and survival among patients with colorectal cancer (CRC) and to evaluate whether this association varies by sex, insulin treatment, and durations of T2DM and insulin use. Patients and Methods This study was conducted among 2,278 men and women diagnosed with nonmetastatic colon or rectal cancer between 1992 and 2007 in the Cancer Prevention Study-II Nutrition Cohort, a prospective study of cancer incidence. In 1992 to 1993, participants completed a detailed, self-administrated questionnaire. Vital status and cause of death were ascertained through the end of 2008. Multivariable-adjusted relative risks (RRs) and 95% CIs were estimated using Cox proportional hazards regression. Results Among the 2,278 men and women with nonmetastatic CRC, there were 842 deaths by the end of follow-up (including 377 deaths from CRC and 152 deaths from cardiovascular disease [CVD]). Among men and women combined, compared with patients without T2DM, patients with CRC and T2DM were at higher risk of all-cause mortality (RR, 1.53; 95% CI, 1.28 to 1.83), CRC-specific mortality (RR, 1.29; 95% CI, 0.98 to 1.70), and CVD-specific mortality (RR, 2.16; 95% CI, 1.44 to 3.24), with no apparent differences by sex or durations of T2DM or insulin use. Insulin use, compared with no T2DM, was associated with increased risk of death from all causes (RR, 1.68; 95% CI, 1.22 to 2.31) and CVD (RR, 3.87; 95% CI, 2.12 to 7.08) but not from CRC (RR, 0.58; 95% CI, 0.28 to 1.19). Conclusion Patients with CRC and T2DM have a higher risk of mortality than patients with CRC who do not have T2DM, especially a higher risk of death from CVD.

Theoretical substitutions between dairy products and all-cause and cause-specific mortality. Results from the Danish diet, cancer and health cohort

2021 ◽  
pp. 1-10
Author(s):  
Anne Sofie D. Laursen ◽  
Anne L. Thomsen ◽  
Anne Beck ◽  
Kim Overvad ◽  
Marianne U. Jakobsen
Keyword(s):  
Cancer Mortality ◽  
Dairy Products ◽  
Proportional Hazards ◽  
Dairy Product ◽  
Daily Intake ◽  
Cox Proportional Hazards ◽  
Sensitivity Analyses ◽  
Low Fat ◽  
Specific Mortality ◽  
Optimal Health

Abstract A daily intake of dairy products is recommended in many countries in order to maintain optimal health throughout life. However, evidence regarding the association between intake of individual dairy products and mortality is limited. We therfore, explored associations between intake of different dairy products and all-cause and cause-specific mortality using specified theoretical substitution analyses. We analysed data from 55 775 Danish men and women aged 50–64 years between 1993 and 1997. Information about dairy product intake at baseline was collected using a validated food frequency questionnaire. Information about vital status and causes of death was obtained through national registers. Measures of associations were calculated using Cox proportional hazards regression. During a median follow-up of 19·0 years, 11 586 participants died. For all-cause mortality, we observed that the intake of low-fat milk, whole-fat milk or low-fat yogurt products in place of cheese was associated with a higher rate of death (hazard ratios between 1·03 and 1·12 per serving/d substituted). The same pattern was present for CVD mortality. For cancer mortality, whole-fat milk and low-fat yogurt products in place of cheese were also associated with a higher rate of death for men while for women, whole-fat milk in place of buttermilk was associated with a higher cancer mortality rate. The results appeared robust in several sensitivity analyses. Our results suggest that intake of low-fat milk, whole-fat milk or low-fat yogurt products in place of cheese is associated with a higher rate of all-cause and cause-specific mortality.

scholarly journals Effect of Basal Metabolic Rate on Cancer: A Mendelian Randomization Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Jack C. M. Ng ◽  
C. Mary Schooling
Keyword(s):  
Growth Factor ◽  
Cancer Risk ◽  
Confidence Interval ◽  
Metabolic Rate ◽  
Basal Metabolic Rate ◽  
Odds Ratio ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Sensitivity Analyses ◽  
Insulin Like Growth Factor

Background: Basal metabolic rate is associated with cancer, but these observations are open to confounding. Limited evidence from Mendelian randomization studies exists, with inconclusive results. Moreover, whether basal metabolic rate has a similar role in cancer for men and women independent of insulin-like growth factor 1 increasing cancer risk has not been investigated.Methods: We conducted a two-sample Mendelian randomization study using summary data from the UK Biobank to estimate the causal effect of basal metabolic rate on cancer. Overall and sex-specific analysis and multiple sensitivity analyses were performed including multivariable Mendelian randomization to control for insulin-like growth factor 1.Results: We obtained 782 genetic variants strongly (p-value < 5 × 10–8) and independently (r2 < 0.01) predicting basal metabolic rate. Genetically predicted higher basal metabolic rate was associated with an increase in cancer risk overall (odds ratio, 1.06; 95% confidence interval, 1.02–1.10) with similar estimates by sex (odds ratio for men, 1.07; 95% confidence interval, 1.002–1.14; odds ratio for women, 1.06; 95% confidence interval, 0.995–1.12). Sensitivity analyses including adjustment for insulin-like growth factor 1 showed directionally consistent results.Conclusion: Higher basal metabolic rate might increase cancer risk. Basal metabolic rate as a potential modifiable target of cancer prevention warrants further study.

Abstract 25: Six-year Change in C-reactive Protein Levels and Risk of Incident Diabetes, Cardiovascular Events and Mortality

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Christina M Parrinello ◽  
Pamela L Lutsey ◽  
Christie M Ballantyne ◽  
Aaron R Folsom ◽  
James S Pankow ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Proportional Hazards ◽  
Cohort Analysis ◽  
Cox Proportional Hazards ◽  
Sensitivity Analyses ◽  
C Reactive Protein ◽  
Baseline Measure ◽  
Reactive Protein ◽  
Inflammatory Status ◽  
Increased Risk

Background: High levels of C-reactive protein (CRP) are associated with cardiovascular disease, diabetes and mortality. It is unclear whether changes in CRP or persistently high CRP are associated with these outcomes beyond the baseline measure. Methods: We conducted a prospective cohort analysis of 10,229 participants from the ARIC Study with two measurements of CRP six years apart (at visits 2 and 4, 1990-92 and 1996-98, respectively). CRP was categorized into two groups using a standard cut-point for defining high levels (≥3 vs. <3 mg/L). Six-year change in CRP was categorized as: persistently not high (<3 mg/L), decreasing (≥3 to <3 mg/L), increasing (<3 to ≥3 mg/L), and persistently high (≥3 mg/L). Cox proportional hazards models were used to assess the association between visit 2 CRP, visit 4 CRP and six-year change in CRP and each of the following outcomes from visit 4 through 2010: diabetes, coronary heart disease, ischemic stroke, heart failure and all-cause mortality. Models were adjusted for traditional risk factors at visit 2. Sensitivity analyses additionally adjusted for visit 4 covariates. Results: Persons with CRP ≥3 mg/L at visit 2 or 4 had higher risk of each outcome compared to those with CRP <3 mg/L ( Table ). We observed higher risk of all outcomes in persons with persistently high CRP, and of all outcomes except stroke in persons with increasing CRP, compared to those with CRP <3 mg/L at both visits ( Table ). Persons whose CRP decreased from high to <3 mg/L did not have significantly increased risk of cardiovascular outcomes or diabetes compared to those with CRP persistently <3 mg/L. Results were similar after adjusting for visit 4 covariates. Conclusions: Persons with sustained high levels of CRP or whose CRP increased to high levels had higher risk of diabetes, cardiovascular disease, and death, while those whose levels decreased from high to moderate or low were at lower risk. Multiple measures of CRP may better characterize inflammatory status and provide more comprehensive information regarding long-term risk.

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