Midlife insulin resistance, APOE genotype, and late-life brain amyloid accumulation

ObjectiveTo examine whether midlife insulin resistance is an independent risk factor for brain amyloid accumulation in vivo after 15 years, and whether this risk is modulated by APOE ε4 genotype.MethodsThis observational study examined 60 elderly volunteers without dementia (mean age at baseline 55.4 and at follow-up 70.9 years, 55.5% women) from the Finnish population-based, nationwide Health2000 study with [11C]Pittsburgh compound B–PET imaging in 2014–2016. The participants were recruited according to their homeostatic model assessment of insulin resistance (HOMA-IR) values in the year 2000, and their APOE ε4 genotype. The exposure group (IR+, n = 30) consisted of individuals with HOMA-IR >2.17 at baseline (highest tertile of the Health2000 study population), and the control group (IR−, n = 30) consisted of individuals with HOMA-IR <1.25 at baseline (lowest tertile). The groups were enriched for APOE ε4 carriers, resulting in 50% (n = 15) APOE ε4 carriers in both groups. Analyses were performed with multivariate logistic and linear regression.ResultsAn amyloid-positive PET scan was found in 33.3% of the IR− group and 60.0% of the IR+ group (odds ratio 3.0, 95% confidence interval 1.1–8.9, p = 0.04). The increased risk was seen in carriers and noncarriers of APOE ε4 genotype. Higher midlife, but not late-life continuous HOMA-IR was associated with a greater brain amyloid burden at follow-up after multivariate adjustments for other cognitive and metabolic risk factors (β = 0.11, 95% confidence interval 0.002–0.22, p = 0.04).ConclusionsThese results indicate that midlife insulin resistance is an independent risk factor for brain amyloid accumulation in elderly individuals without dementia.

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Risk factors for recurrent wheezing after bronchiolitis in infants: 2-year follow up in China

10.21203/rs.3.rs-26354/v2 ◽

2020 ◽

Author(s):

Sainan Chen ◽

Wenjing Gu ◽

Min Wu ◽

Chuangli Hao ◽

Canhong Zhu ◽

...

Keyword(s):

Risk Factor ◽

Independent Risk Factor ◽

Severe Disease ◽

Serum Levels ◽

Control Group ◽

Healthy Children ◽

Recurrent Wheezing ◽

Increased Risk ◽

Tnf Α

Abstract Background: Infants with bronchiolitis have an increased risk of developing recurrent wheezing and asthma. However, the association between bronchiolitis and recurrent wheezing remains controversial.Objective: To investigate the incidence of post-bronchiolitis recurrent wheezing and associated risk factors.Methods: Infants with bronchiolitis were enrolled from November 2016 through March 2017. We also enrolled 24 healthy children with no history of wheezing from the department of children's health prevention as a control group. Nasopharyngeal aspirates were obtained for detection of respiratory viruses which were analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) and direct immunofluorescent assay. Serum cytokines including TSLP, IL2, IL13, TIMP-1, MMP-9, IL33, IL5, IL4, IL25, TNF- α and MIP-1α were measured by flow cytometry. Patients were followed every 3 months for a duration of 2 years by telephone or at outpatient appointments.Results: We enrolled 89 infants, of which 81 patients were successfully followed up. In total, 22.2% of patients experienced recurrent wheezing episodes. The proportion of patients with eczema, systemic glucocorticoid use and patients with moderate-to-severe disease were significantly higher in the recurrent wheezing group than the non-recurrent wheezing group (83.3% vs 52.4%; 66.7% vs 36.5%; 61.1% vs 33.3%, respectively, all P<0.05); The serum level of TNF‑ α was lower in the recurrent wheezing group (P<0.05), and the serum levels of IL-4, IL-5, IL-25, IL-33 were significantly higher among patients without recurrent wheezing (P<0.05). Logistic regression analysis showed that eczema was an independent risk factor for post-bronchiolitis recurrent wheezing (odds ratio [OR]=7.488; 95% confidence interval [CI], 1.447–38.759; P=0.016). Conclusion: The incidence of recurrent wheezing among infants after contracting bronchiolitis was 22.2% during a 2-year follow-up. Eczema was the only independent risk factor identified and no correlation was found between the specific virus and disease severity in children with post-bronchiolitis recurrent wheezing.

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Depression and cardiovascular risk—association among Beck Depression Inventory, PCSK9 levels and insulin resistance

Cardiovascular Diabetology ◽

10.1186/s12933-020-01158-6 ◽

2020 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

C. Macchi ◽

C. Favero ◽

A. Ceresa ◽

L. Vigna ◽

D. M. Conti ◽

...

Keyword(s):

Insulin Resistance ◽

Risk Factor ◽

Beck Depression Inventory ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Model Assessment ◽

Cvd Risk ◽

Assessment Index ◽

Increased Risk ◽

Homeostatic Model Assessment

Abstract Background Depression and cardiovascular disease (CVD) are among the most common causes of disability in high-income countries, depression being associated with a 30% increased risk of future CV events. Depression is twice as common in people with diabetes and is associated with a 60% rise in the incidence of type 2 diabetes, an independent CVD risk factor. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of low-density lipoprotein cholesterol, has been related to a large number of CV risk factors, including insulin resistance. Aim of this study was to investigate whether the presence of depression could affect PCSK9 levels in a population of obese subjects susceptible to depressive symptoms and how these changes may mediate a pre-diabetic risk. Results In 389 obese individuals, the Beck Depression Inventory (BDI-II) was significantly associated with PCSK9 levels. For every one-unit increment in BDI-II score, PCSK9 rose by 1.85 ng/mL. Depression was associated also with the HOMA-IR (homeostatic model assessment index of insulin resistance), 11% of this effect operating indirectly via PCSK9. Conclusions This study indicates a possible mechanism linking depression and insulin resistance, a well-known CV risk factor, providing evidence for a significant role of PCSK9.

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Associations of Adiposity from Childhood into Adulthood with Insulin Resistance and the Insulin-Like Growth Factor System: 65-Year Follow-Up of the Boyd Orr Cohort

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2006-0745 ◽

2006 ◽

Vol 91 (9) ◽

pp. 3287-3295 ◽

Cited By ~ 36

Author(s):

Richard M. Martin ◽

Jeff M. P. Holly ◽

George Davey Smith ◽

David Gunnell

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Confidence Interval ◽

Disease Risk ◽

Model Assessment ◽

Homeostasis Model Assessment ◽

Weak Evidence ◽

Igf I ◽

Igf Binding

Abstract Context: One metabolic pathway through which adiposity influences disease risk may be via alterations in insulin and IGF metabolism. Objective: Our objective was to investigate associations of adiposity at different stages of life with insulin and the IGF system. Design, Setting, and Participants: The study was a 65-yr follow-up of 728 Boyd Orr cohort participants (mean age, 71 yr) originally surveyed between 1937 and 1939. Main Outcomes: Outcomes included homeostasis model assessment of insulin resistance, total IGF-I and IGF-II, IGF binding protein (IGFBP)-2, and IGFBP-3 in adulthood. Results: Childhood body mass index (BMI) was weakly inversely related to adult IGF-I (coefficient per BMI sd, −3.4 ng/ml; 95% confidence interval, −7.3 to 0.5; P = 0.09). IGF-II (but not IGF-I) increased with higher current fat mass index (coefficient, 26.1 ng/ml; 95% confidence interval, 4.6 to 47.6; P = 0.02) and waist-hip ratio (30.0 ng/ml; 9.4 to 50.5; P = 0.004). IGFBP-2 decreased by 21.2% (17.2 to 24.9; P < 0.001), and homeostasis model assessment of insulin resistance increased by 38.8% (28.9 to 49.6; P < 0.001) per sd higher adult BMI. Among thin adults (BMI tertiles 1 and 2), IGFBP-2 was positively, and insulin resistance was inversely, associated with childhood BMI. Conclusion: There was only weak evidence that associations of childhood BMI with chronic disease risk may be mediated by adult IGF-I levels. Circulating IGFBP-2 in adulthood, a marker for insulin sensitivity, was inversely associated with current adiposity, but overweight children who became relatively lean adults were more insulin sensitive than thinner children. The findings may indicate programming of later insulin sensitivity and consequently IGFBP-2 levels in response to childhood adiposity. The role of IGF-II in obesity-related chronic diseases warrants additional investigation.

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Risk of Surgery and Anesthesia for Ischemic Stroke

Anesthesiology ◽

10.1097/00000542-200002000-00024 ◽

2000 ◽

Vol 92 (2) ◽

pp. 425-425 ◽

Cited By ~ 46

Author(s):

Gilbert Y. Wong ◽

David O. Warner ◽

Darrell R. Schroeder ◽

Kenneth P. Offord ◽

Mark A. Warner ◽

...

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Ischemic Stroke ◽

High Risk ◽

Confidence Interval ◽

Odds Ratio ◽

Independent Risk Factor ◽

Index Date ◽

Stroke Index ◽

Increased Risk

Background The goal of this study was to determine if the combination of surgery and anesthesia is an independent risk factor for the development of incident (first-time) ischemic stroke. Methods All residents of Rochester, MN, with incident ischemic stroke from 1960 through 1984 (1,455 cases and 1,455 age- and gender-matched controls) were used to identify risk factors associated with ischemic stroke. Cases and controls undergoing surgery involving general anesthesia or central neuroaxis blockade before their stroke/index date of diagnosis were identified. A conditional logistic regression model was used to estimate the odds ratio of surgery and anesthesia for ischemic stroke while adjusting for other known risk factors. Results There were 59 cases and 17 controls having surgery within 30 days before their stroke/index date. After adjusting for previously identified risk factors, surgery within 30 days before the stroke/index date (perioperative period) was found to be an independent risk factor for stroke (P<0.001; odds ratio, 3.9; 95% confidence interval, 2.1-7.4). In an analysis that excluded matched pairs where the case and/or control underwent surgery considered "high risk" for stroke (cardiac, neurologic, or vascular procedures), "non-high-risk surgery" was also found to be an independent risk factor for perioperative stroke (P = 0.002; odds ratio, 2.9; 95% confidence interval, 1.5-5.7). Conclusion Our results suggest that there is an increased risk of ischemic stroke in the 30 days after surgery and anesthesia. This risk remains elevated even after excluding surgeries (cardiac, neurologic, and vascular surgeries) considered to be high risk for ischemic stroke.

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Liver Transplant Patients with High Preoperative Serum Bilirubin Levels Are at Increased Risk of Postoperative Delirium: A Retrospective Study

Journal of Clinical Medicine ◽

10.3390/jcm9051591 ◽

2020 ◽

Vol 9 (5) ◽

pp. 1591

Author(s):

Kyu Hee Park ◽

Hyo Jung Son ◽

Yoon Ji Choi ◽

Gene Hyun Park ◽

Yoon Sook Lee ◽

...

Keyword(s):

Risk Factor ◽

Bilirubin Level ◽

Independent Risk Factor ◽

Postoperative Delirium ◽

Serum Bilirubin ◽

Meld Score ◽

Risk Indicators ◽

Control Group ◽

Preoperative Serum ◽

Increased Risk

Postoperative delirium is a common complication after liver transplantation (LT). A high model for end-stage liver disease (MELD) score is an independent risk factor for postoperative delirium, but it is unclear which of the components of this score are risk indicators. The aim of this study was to analyze the incidence of postoperative delirium according to the preoperative serum bilirubin level, a component of the MELD score, in patients who underwent LT. The medical records of 325 patients who underwent LT from January 2010 to February 2019 at a single university hospital were retrospectively reviewed. The patients were divided into two groups: those who experienced postoperative delirium (Delirium group, n = 69) and those who did not (Control group, n = 256). Data on the patients’ demographic characteristics, perioperative management, and postoperative complications were collected. Mean preoperative bilirubin level was higher in the Delirium group than in the Control group (p < 0.0001). In the Delirium group, 54 (78.26%) patients had preoperative bilirubin levels above 3.5 mg/dL. In the multivariate analysis, preoperative bilirubin above 3.5 mg/dL was associated with postoperative delirium (p = 0.002). Therefore, preoperative hyperbilirubinemia is an independent risk factor for postoperative delirium.

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ATL

International Journal of Gynecological Cancer ◽

10.1097/igc.0b013e3182a80b14 ◽

2013 ◽

Vol 23 (9) ◽

pp. 1663-1669 ◽

Cited By ~ 20

Author(s):

Stefania Cortecchia ◽

Giuseppe Galanti ◽

Cecilia Sgadari ◽

Silvano Costa ◽

Margherita De Lillo ◽

...

Keyword(s):

Confidence Interval ◽

Rate Ratio ◽

Intraepithelial Neoplasia ◽

Control Group ◽

First Year ◽

Progression Rate ◽

Low Grade ◽

Increased Risk ◽

P16 Expression

ObjectiveThe p16Ink4a (p16) tumor-suppressor protein is a biomarker for activated expression of human papillomavirus oncogenes. However, data are insufficient to determine whether p16 overexpression predicts the risk for progression of low-grade cervical intraepithelial neoplasia (CIN). This study was aimed at evaluating the risk for progression to CIN2 or worse during a 3-year follow-up of an unselected series of 739 patients with CIN1 biopsy specimens tested for p16 expression.MethodsPositivity of p16 was defined as a diffuse overexpression in the basal/parabasal cell layers. Selection biases were ruled out using a control group of 523 patients with CIN1 biopsies not tested for p16 expression. Analysis was based on the ratio of progression rates.ResultsIn the first year of follow-up, the 216 patients (29%) with p16-positive CIN1 had a higher progression rate (12.3%) than did the 523 patients with p16-negative CIN1 (2.2%) (rate ratio, 5.5; 95% confidence interval [CI], 2.59–11.71). In the second and third years, differences were smaller (rate ratio, 1.32 and 1.14, respectively) and not significant. The patients with p16-positive CIN1 also had a lower risk for regression to normal in the first year of follow-up (rate ratio, 0.55; 95% confidence interval, 0.42–0.71) and nonsignificant changes in the second and third years (rate ratio, 0.81 and 0.84, respectively).ConclusionsThe patients with p16-positive CIN1 had an increased risk for progression that was concentrated in the first year of follow-up. Immunostaining of p16 could have a role in short-term surveillance of patients with CIN1. Further research should focus on midterm/long-term outcomes of p16-positive CIN1.

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Risk factors for recurrent wheezing after bronchiolitis in infants: 2-year follow up in China

BMC Infectious Diseases ◽

10.1186/s12879-021-05937-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Sainan Chen ◽

Wenjing Gu ◽

Min Wu ◽

Chuangli Hao ◽

Canhong Zhu ◽

...

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Independent Risk Factor ◽

Severe Disease ◽

Recurrent Wheezing ◽

Increased Risk ◽

Tnf Α ◽

History Of ◽

Outpatient Appointments

Abstract Background Infants with bronchiolitis have an increased risk of developing recurrent wheezing and asthma. However, the risk factors for the development of recurrent wheezing after bronchiolitis remains controversial. Our study was to investigate risk factors of post-bronchiolitis recurrent wheezing. Methods Infants with bronchiolitis were enrolled from November 2016 through March 2017. Nasopharyngeal aspirates were obtained for detection of respiratory viruses which were analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) and direct immunofluorescent assay. Serum cytokines including TSLP, IL2, IL13, TIMP-1, MMP-9, IL33, IL5, IL4, IL25, TNF- α and MIP-1α were measured by flow cytometry. Patients were followed up every 3 months for a duration of 2 years by telephone or at outpatient appointments. Results We enrolled 89 infants, of which 81 patients were successfully followed up. In total, 22.2% of patients experienced recurrent wheezing episodes. The proportion of patients with history of eczema, systemic glucocorticoid use and patients with moderate-to-severe disease were significantly higher in the recurrent wheezing group than the non-recurrent wheezing group (83.3% vs 52.4%; 66.7% vs 36.5%; 61.1% vs 33.3%, respectively, all P < 0.05); There were no significant differences between patients with and without recurrent wheezing episodes in the levels of TSLP, IL2, IL13, TIMP-1, MMP-9, IL33, IL5, IL4, IL25, TNF- α and MIP-1α (P > 0.05). Logistic regression analysis showed that history of eczema was an independent risk factor for post-bronchiolitis recurrent wheezing (odds ratio [OR] = 5.622; 95% confidence interval [CI], 1.3–24.9; P = 0.023). Conclusion The incidence of recurrent wheezing among infants after contracting bronchiolitis was 22.2% during a 2-year follow-up. History of eczema was the only independent risk factor identified and no correlation was found between the specific virus and disease severity in children with post-bronchiolitis recurrent wheezing.

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Depression and Cardiovascular Risk - Association Among Beck Depression Inventory, PCSK9 Levels and Insulin Resistance

10.21203/rs.3.rs-56070/v2 ◽

2020 ◽

Author(s):

Chiara Macchi ◽

Chiara Favero ◽

Alessandro Ceresa ◽

Luisella Vigna ◽

Diana Misaela Conti ◽

...

Keyword(s):

Insulin Resistance ◽

Risk Factor ◽

Beck Depression Inventory ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Model Assessment ◽

Cvd Risk ◽

Assessment Index ◽

Increased Risk ◽

Homeostatic Model Assessment

Abstract Background. Depression and cardiovascular disease (CVD) are among the most common causes of disability in high-income countries, depression being associated with a 30% increased risk of future CV events. Depression is twice as common in people with diabetes and is associated with a 60% rise in the incidence of type 2 diabetes, an independent CVD risk factor. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of low-density lipoprotein cholesterol, has been related to a large number of CV risk factors, including insulin resistance. Aim of this study was to investigate whether in a population of obese subjects, more susceptible to depressive symptoms, the presence of depression could affect PCSK9 levels and how these changes may mediate a pre-diabetic risk. Results. In 389 obese individuals, the Beck Depression Inventory (BDI-II) was significantly associated with PCSK9 levels. For every one-unit increment in BDI-II score, PCSK9 rose by 1.85 ng/mL. Depression was associated also with the HOMA-IR (homeostatic model assessment index of insulin resistance), 11% of this effect operating indirectly via PCSK9. Conclusions. This study indicates a possible mechanism linking depression and insulin resistance, a well-known CV risk factor, providing evidence for a significant role of PCSK9.

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The effect of baseline serum uric acid on chronic kidney disease in normotensive, normoglycemic, and non-obese individuals: A health checkup cohort study

PLoS ONE ◽

10.1371/journal.pone.0244106 ◽

2021 ◽

Vol 16 (1) ◽

pp. e0244106

Author(s):

Young-Bin Son ◽

Ji Hyun Yang ◽

Myung-Gyu Kim ◽

Sang Kyung Jo ◽

Won Yong Cho ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Uric Acid ◽

Risk Factor ◽

Kidney Disease ◽

Serum Uric Acid ◽

Independent Risk Factor ◽

Baseline Serum ◽

Increased Risk ◽

Egfr Decline

Introduction The independent role of serum uric acid (SUA) on kidney disease is controversial due to its association with metabolic syndrome. The objective of this study was to investigate the association of baseline SUA with development of chronic kidney disease and eGFR decline in normotensive, normoglycemic and non-obese individuals during follow up period. Materials and methods We included non-hypertensitive, non-diabetic, and non-obese 13,133 adults with estimated glomerular filtration rate (eGFR) ≥ 60ml/min/1.73m2 who had a voluntary health check-up during 2004–2017. Results SUA was positively related to adjusted means of systolic blood pressure (SBP), triglyceride, body mass index, and body fat percent. SUA was inversely associated with high density lipoprotein HDL (P for trend ≤0.001). SUA was an independent risk factor for the development of diabetes, hypertension, and obesity. During 45.0 [24.0–76.0] months of median follow up, the highest quartiles of SUA showed significant risks of 30% eGFR decline compared than the lowest quartile (RR:3.701; 95% CI: 1.504–9.108). The highest quartile had a 2.2 fold (95% CI: 1.182–4.177) increase in risk for incident chronic kidney disease (CKD). Conclusions SUA is an independent risk factor for the development of diabetes, hypertension, and obesity in the healthy population. High SUA is associated with increased risk of CKD development and eGFR decline in participants with intact renal function.

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Associations Between Sex Steroids and the Development of Metabolic Syndrome: A Longitudinal Study in European Men

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2014-4184 ◽

2015 ◽

Vol 100 (4) ◽

pp. 1396-1404 ◽

Cited By ~ 59

Author(s):

Leen Antonio ◽

Frederick C. W. Wu ◽

Terence W. O'Neill ◽

Stephen R. Pye ◽

Emma L. Carter ◽

...

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Sex Steroids ◽

Community Dwelling ◽

Sex Hormone Binding Globulin ◽

Gas Chromatography Mass Spectrometry ◽

Model Assessment ◽

Lower Baseline ◽

Increased Risk

Context: Low testosterone (T) has been associated with incident metabolic syndrome (MetS), but it remains unclear if this association is independent of sex hormone binding globulin (SHBG). Estradiol (E2) may also be associated with MetS, but few studies have investigated this. Objective: To study the association between baseline sex steroids and the development of incident MetS and to investigate the influence of SHBG, body mass index (BMI) and insulin resistance on this risk. Methods: Three thousand three hundred sixty nine community-dwelling men aged 40–79 years were recruited for participation in EMAS. MetS was defined by the updated NCEP ATP III criteria. Testosterone and E2 levels were measured by liquid and gas chromatography/mass spectrometry, respectively. Logistic regression was used to assess the association between sex steroids and incident MetS. Results: One thousand six hundred fifty one men without MetS at baseline were identified. During follow-up, 289 men developed incident MetS, while 1362 men did not develop MetS. Men with lower baseline total T levels were at higher risk for developing MetS [odds ratio (OR) = 1.72, P < .001), even after adjustment for SHBG (OR = 1.43, P = .001), BMI (OR = 1.44, P < .001) or homeostasis model assessment of insulin resistance (HOMA-IR) (OR = 1.64, P < .001). E2 was not associated with development of MetS (OR = 1.04; P = .56). However, a lower E2/T ratio was associated with a lower risk of incident MetS (OR = 0.38; P < .001), even after adjustment for SHBG (OR = 0.48; P < .001), BMI (OR = 0.60; P = .001) or HOMA-IR (OR = 0.41; P < .001). Conclusions: In men, lower T levels, but not E2, are linked with an increased risk of developing MetS, independent of SHBG, BMI or insulin resistance. A lower E2/T ratio may be protective against developing MetS.

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