Cardiometabolic Risks Among Survivors of Childhood Hematologic Malignancies.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4113-4113
Author(s):  
Daniel A. Mulrooney ◽  
Aaron Kelly ◽  
K. Scott Baker ◽  
Lyn Steffen ◽  
Jill Lunsford-Lee ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Mass Index ◽  
Carotid Artery ◽  
Body Mass ◽  
Visceral Fat ◽  
Fasting Glucose ◽  
Lymphoblastic Leukemia ◽  
Pubertal Development ◽  
Hematologic Malignancies ◽  
Increased Risk

Abstract Abstract 4113 Survival rates for childhood hematologic malignancies continue to improve. Research suggests these individuals are at increased risk for late adverse cardiovascular outcomes. This analysis includes children (n=101) who survived ≥ 5-yrs following diagnosis of acute lymphoblastic leukemia (ALL) (n=78), acute myeloid leukemia (AML) (n=5), and non-Hodgkin lymphoma (NHL) (n=18), compared to their frequency matched healthy siblings (n=123). Anthropometric measurements, blood pressure (BP), fasting glucose, insulin, and lipids were collected; insulin resistance was assessed by euglycemic hyperinsulinemic clamp, adjusted for lean body mass (low Mlbm represents insulin resistance); carotid artery stiffness (distensibility and compliance – low levels represent increased stiffness), adjusted for lumen diameter, was assessed by ultrasound. Least squares means and standard errors, adjusted for age, gender, pubertal development, and body mass index (BMI) were compared. Survivors (63.4% male) mean age at diagnosis was 10.3 yrs (5.7-15.8) and 15.0 yrs (9.9-17.9) at evaluation; siblings (56.1% male) were 13.6 yrs (9.0-18.0) at evaluation. Among survivors, 88 (87.1%) received chemotherapy only and 13 (12.9%) chemotherapy and cranial radiation. Metabolic syndrome (MS) (modified criteria for children) was present in 8 (7.9%) survivors vs. 6 (4.9%) siblings (p=0.35). Nevertheless, 25 (24.8 %) survivors had two or more MS components compared to 17 (13.8 %) siblings (p=0.04). There were no differences between cases and siblings on measures of adiposity (BMI, waist circumference, % body fat, visceral fat), BP, fasting glucose, insulin, and lipids. However, survivors were significantly more insulin resistant and had stiffer carotid arteries compared to controls (Table). Despite similar levels of adiposity, survivors of childhood hematologic malignancies demonstrate signs of insulin resistance and increased vascular stiffness at a young age compared to healthy controls. These findings highlight: 1) the heightened cardiovascular risk profile among children who survived hematologic malignancies and 2) that the typical components of the MS may not be sufficiently sensitive measures of risk in this young population. Survivors (n = 101) Siblings (n = 123) (p) LS means (SE) LS means (SE) Body mass index (BMI) (kg/m2) 21.3 (0.5) 21.2 (0.5) 0.8 Visceral fat (cm3) 22.8 (1.0) 22.3 (1.0) 0.7 Insulin resistance [Mlbm (mg/kg/min)] 12.6 (0.5) 14.2 (0.5) 0.007 Carotid artery distensibility (%) 13.5 (0.4) 14.9 (0.4) 0.004 Carotid artery compliance (mm2/mmHg) 0.16 (0.004) 0.17 (0.004) 0.008 Disclosures: No relevant conflicts of interest to declare.

Total Body Irradiation (TBI) Increases Cardio-Metabolic Risk and Induces Carotid Vascular Stiffness in Survivors After Hematopoietic Cell Transplant (HCT) for Childhood Hematologic Malignancies.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3329-3329
Author(s):  
K. Scott Baker ◽  
Lyn Steffen ◽  
Xia Zhou ◽  
Aaron Kelly ◽  
Jill Lee ◽  
...  
Keyword(s):  
Risk Factors ◽  
Insulin Resistance ◽  
Carotid Artery ◽  
Body Mass ◽  
Hematologic Malignancies ◽  
Cell Transplant ◽  
Cranial Radiation ◽  
Cardiovascular Morbidity And Mortality ◽  
Increased Risk ◽  
Significant Difference

Abstract Abstract 3329 Poster Board III-217 Background Cardiovascular disease, hypertension and diabetes all contribute to the increased risk of late non-relapse mortality after HCT and lead to diminished life expectancy compared to the general population. An association between TBI exposure and cardio-metabolic (C-M) risk factors in adult HCT survivors has been described but this association has not been well characterized in children. Methods Measures of insulin resistance (euglycemic hyperinsulinemic clamp adjusted for lean body mass [Mlbm], low Mlbm represents insulin resistance), fasting glucose, insulin, lipids, anthropometry, blood pressure (BP), and carotid artery compliance and distensibility (lower values represent arterial stiffness) were determined in 106 children and young adults (current age 26.6 yr, 60.4% male) who had received HCT for hematologic malignancy during childhood (mean age at HCT 9.9 yr) and 72 healthy sibling controls (current age 23.7 yr, 51.4% male). Subjects were compared in 3 radiation exposure groups, all received myeloablative preparative regimens; 79 received allogeneic HCT and 27 received autologous HCT. Diagnoses included AML (n=50), ALL (n=30), myelodysplastic syndrome, n=8, Hodgkin's (n=10) and non-Hodgkin's lymphoma (n=8). Sixty two (58.5%) received TBI, 20 (18.9%) received cranial radiation (CRT) prior to TBI (TBI+CRT), and 24 (22.6%) received no TBI or cranial radiation (noXRT) before or during HCT. Linear regression models were used to evaluate risk factors between groups after adjusting for age, gender, pubertal stage, body mass index (BMI), and carotid lumen diameter (stiffness measures only). Results Metabolic syndrome (MS) (ATP III criteria for adults, modified criteria for children) was present in 15 (15.6%) HCT survivors and 4 (5.6%) controls (OR 2.3, 95% CI 0.7-7.7, p=0.16). Two or more components of the MS were present in 39 (37.1%) survivors and 10 (14.5%) controls (OR, 2.7, 95% CI 1.2-5.9, p=0.015). Compared to siblings, there were no differences between groups for glucose, BMI, waist circumference, percent body fat, or BP. However, HCT survivors who had TBI or TBI+CRT all had significantly higher cholesterol, LDL cholesterol, triglycerides and insulin. Those who received TBI+CRT had significantly lower HDL cholesterol and were also more insulin resistant (Table). However, for the noXRT group there were no differences in any of the C-M risk factors compared to controls. Carotid artery distensibility was decreased in survivors who received TBI compared to controls with even greater negative impact in those who received TBI+CRT. There was not a significant difference in distensibility in the noXRT group compared to controls. Only the TBI+CRT group had lower compliance compared to controls. Conclusions Even at a relatively young age, and independent of obesity, HCT survivors of childhood hematologic malignancies have increased C-M risk factors present as well as adverse vascular changes, which are associated with exposure to TBI +/- CRT. These abnormalities may ultimately contribute to a higher risk of early cardiovascular morbidity and mortality thus early screening and management of modifiable C-M risk factors should be considered in HCT survivors. Disclosures No relevant conflicts of interest to declare.

scholarly journals Monitoring of the Metabolic Syndrome in Psychiatric Inpatients

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
J. Cordes ◽  
G. Regenbrecht ◽  
M.W. Agelink ◽  
J. Zielasek ◽  
K.G. Kahl
Keyword(s):  
Metabolic Syndrome ◽  
Body Mass Index ◽  
Waist Circumference ◽  
Body Mass ◽  
Visceral Fat ◽  
Inpatient Treatment ◽  
Fasting Glucose ◽  
The Body ◽  
The Metabolic Syndrome ◽  
Increased Risk

In this naturalistic observational study carried out in an inpatient treatment setting we as yet surveyed the parameters of the metabolic syndrome. A weekly monitoring procedure was implemented. The analysis included data of 350 patients over a time of 12 weeks. The last observation carried forward method was applied. Additionally we are evaluating the informative value of visceral body fat percentage as measured by a body composition analyzer. The patients showed a weight increase over the first 12 weeks (mean increase: 0.87 kg, p < .001) as well as an increase of the body mass index (mean increase: 0.45 kg/m2, p < .001). Accordingly, waist circumference (mean increase: 1.06 cm, p = .007) and visceral fat index (mean increase: 0.19, p = .007) increased. No worsening of fasting glucose and blood lipid concentrations was detected. Spearmens coefficient indicated correlations between visceral fat index and body mass index (ρ = .77; p < .001), waist circumference (ρ = .70; p < .001), and triglyceride concentrations (ρ = .39; p < .001). Correlations between visceral fat index and fasting glucose (ρ = .18; p = .019), and visceral fat index and total cholesterol (ρ = .16; p = .049) were weak but also significant. In contrast, the HDL cholesterol showed a negative relation with ρ < -.39 at each point in time (p < .001).We conclude that psychiatric patients are at increased risk for the development of metabolic alterations during inpatient treatment. The possible underlying mechanisms of this interaction are discussed.

scholarly journals Circulating Irisin in Relation to Insulin Resistance and the Metabolic Syndrome

2013 ◽  
Vol 98 (12) ◽  
pp. 4899-4907 ◽  
Author(s):  
Kyung Hee Park ◽  
Lesya Zaichenko ◽  
Mary Brinkoetter ◽  
Bindiya Thakkar ◽  
Ayse Sahin-Efe ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Body Mass Index ◽  
Body Mass ◽  
Model Assessment ◽  
Homeostasis Model Assessment ◽  
Cvd Risk ◽  
Baseline Serum ◽  
The Metabolic Syndrome ◽  
Increased Risk

Context: Irisin, a recently identified hormone, has been proposed to regulate energy homeostasis and obesity in mice. Whether irisin levels are associated with risk of the metabolic syndrome (MetS), cardiometabolic variables, and cardiovascular disease (CVD) risk in humans remains unknown. Objective: Our objective was to assess the associations between baseline serum irisin levels and MetS, cardiometabolic variables, and CVD risk. Design, Setting, and Subjects: We conducted a comparative cross-sectional evaluation of baseline circulating levels of the novel hormone irisin and the established adipokine adiponectin with MetS, cardiometabolic variables, and CVD risk in a sample of 151 subjects. Results: Baseline irisin levels were significantly higher in subjects with MetS than in subjects without MetS. Irisin was associated negatively with adiponectin (r = −0.4, P &lt; .001) and positively with body mass index (r = 0.22, P = .008), systolic (r = 0.17, P = .04) and diastolic (r = 0.27, P = .001) blood pressure, fasting glucose (r = 0.25, P = .002), triglycerides (r = 0.25, P = .003), and homeostasis model assessment for insulin resistance (r = 0.33, P &lt; .001). After adjustment for potential confounders, including body mass index, subjects in the highest tertile of irisin levels were more likely to have MetS (odds ratio [OR] = 9.44, 95% confidence interval [CI] = 2.66–33.44), elevated fasting blood glucose (OR = 5.80, 95% CI = 1.72–19.60), high triglycerides (OR = 3.89, 95% CI = 1.16–13.03), and low high-density lipoprotein cholesterol (OR = 3.30, 95% CI = 1.18–9.20). Irisin was independently associated with homeostasis model assessment for insulin resistance and general Framingham risk profile in multiple linear regression analyses after adjustment for confounders. Adiponectin demonstrated the expected associations with outcomes. Conclusions: Irisin is associated with increased risk of MetS, cardiometabolic variables, and CVD in humans, indicating either increased secretion by adipose/muscle tissue and/or a compensatory increase of irisin to overcome an underlying irisin resistance in these subjects.

scholarly journals The effect of combination therapy of insulin glargine, metformin, and sitagliptin on insulin secretion, insulin resistance, and metabolic parameters in obese subjects with type 2 diabetes

2016 ◽  
Vol 144 (9-10) ◽  
pp. 497-502
Author(s):  
Teodora Beljic-Zivkovic ◽  
Milica Marjanovic-Petkovic ◽  
Miljanka Vuksanovic ◽  
Ivan Soldatovic ◽  
Dobrila Kanlic ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Body Mass Index ◽  
Waist Circumference ◽  
Insulin Glargine ◽  
Body Mass ◽  
Fasting Glucose ◽  
C Peptide ◽  
Obese Subjects

Introduction. A combination of drugs is required for treatment of obese subjects with diabetes, due to multiple pathogenic mechanisms implicated in the development of both diabetes and obesity. Objective. Assessment of the effect of sitagliptin added to insulin glargine and metformin, in obese subjects with type 2 diabetes. Methods. A total of 23 obese subjects on metformin and insulin glargine participated in the study. Titration of insulin glargine during a one-month period preceded the addition of 100 mg of sitagliptin daily. Body mass index, waist circumference, fasting, and prandial glucose were measured monthly, lipids and hemoglobin A1c (HbA1c) every three months, insulin, c-peptide and glucagon at the start and after six months of treatment. Homeostatic models for insulin secretion (HOMA B) and insulin resistance (HOMA IR) were calculated. Results. Participants were 58.65 ?} 7.62 years of age with a body mass index of 35.06 ?} 5.15 kg/m2, waist circumference of 115.04 ?} 15.5 cm, and the duration of diabetes of 4.11 ?} 2.57 years. With the titration of insulin glargine, target fasting glucose levels were not achieved. Waist circumference and body mass index decreased during three months of sitagliptin treatment, thereafter remaining stable. HbA1c decreased significantly after three and six months of therapy. C-peptide increased significantly, while glucagon level fell. HOMA indexes were unchanged. Conclusion. Sitagliptin can improve diabetes control and induce modest weight loss in obese subjects poorly controlled on insulin glargine and metformin. Titration of insulin glargine to optimal fasting glucose values is a prerequisite of success of this combination therapy.

scholarly journals Childhood Body Mass Index and Fasting Glucose and Insulin Predict Adult Type-2 Diabetes: The International Childhood Cardiovascular Cohort (i3C) Consortium

2020 ◽  
Author(s):  
Tian Hu ◽  
David R. Jacobs Jr. ◽  
Alan R. Sinaiko ◽  
Lydia A. Bazzano ◽  
Trudy L. Burns ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Mass Index ◽  
Body Mass ◽  
Fasting Glucose ◽  
Self Report ◽  
Adult Type ◽  
Childhood Body Mass Index ◽  
Increased Risk ◽  
Design And Methods

Objective: To examine childhood body mass index (BMI), fasting glucose and insulin in relation to incident adult type-2 diabetes mellitus (T2DM). <p>Research Design and Methods: We used data from The International Childhood Cardiovascular Cohort Consortium. Data included childhood measurements (age 3-19) obtained during the 1970s-90s, a health questionnaire including self-report of adult T2DM (occurrence age, medication use) obtained at mean age 40 years, and a medical diagnosis registry (Finland). </p> <p>Results: The sample included 6,738 participants. Of these, 436 (6.5%) reported onset of T2DM between ages 20-59 (mean 40.8) years, and 86% of them reported use of a confirmed anti-diabetic medication. BMI and glucose (age- and sex-standardized) were associated with incident T2DM after adjustment for cohort, country, sex, race, age and calendar year of measurement. Increasing levels of childhood BMI and glucose were related to incrementally increased risk of T2DM beginning at age 30, beginning at cut points below the 95<sup>th</sup> percentile for BMI and below 100 mg/dL for glucose. Insulin was positively associated with adult T2DM after adjustment for BMI and glucose and added to T2DM discrimination. </p> <p>Conclusions: Childhood BMI and glucose are predictors of adult T2DM at levels previously considered to be within the normal range. These easy to apply measurements are appealing from a clinical perspective. Fasting insulin has the potential to be an additional predictor.</p>

scholarly journals Childhood Body Mass Index and Fasting Glucose and Insulin Predict Adult Type-2 Diabetes: The International Childhood Cardiovascular Cohort (i3C) Consortium

2020 ◽  
Author(s):  
Tian Hu ◽  
David R. Jacobs Jr. ◽  
Alan R. Sinaiko ◽  
Lydia A. Bazzano ◽  
Trudy L. Burns ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Mass Index ◽  
Body Mass ◽  
Fasting Glucose ◽  
Self Report ◽  
Adult Type ◽  
Childhood Body Mass Index ◽  
Increased Risk ◽  
Design And Methods

Objective: To examine childhood body mass index (BMI), fasting glucose and insulin in relation to incident adult type-2 diabetes mellitus (T2DM). <p>Research Design and Methods: We used data from The International Childhood Cardiovascular Cohort Consortium. Data included childhood measurements (age 3-19) obtained during the 1970s-90s, a health questionnaire including self-report of adult T2DM (occurrence age, medication use) obtained at mean age 40 years, and a medical diagnosis registry (Finland). </p> <p>Results: The sample included 6,738 participants. Of these, 436 (6.5%) reported onset of T2DM between ages 20-59 (mean 40.8) years, and 86% of them reported use of a confirmed anti-diabetic medication. BMI and glucose (age- and sex-standardized) were associated with incident T2DM after adjustment for cohort, country, sex, race, age and calendar year of measurement. Increasing levels of childhood BMI and glucose were related to incrementally increased risk of T2DM beginning at age 30, beginning at cut points below the 95<sup>th</sup> percentile for BMI and below 100 mg/dL for glucose. Insulin was positively associated with adult T2DM after adjustment for BMI and glucose and added to T2DM discrimination. </p> <p>Conclusions: Childhood BMI and glucose are predictors of adult T2DM at levels previously considered to be within the normal range. These easy to apply measurements are appealing from a clinical perspective. Fasting insulin has the potential to be an additional predictor.</p>

Associations of Body Mass Index and Waist Circumference in Young Adulthood with Later Life Incident Diabetes

2021 ◽  
Author(s):  
Nandini Nair ◽  
Eric Vittinghoff ◽  
Mark J Pletcher ◽  
Elizabeth C Oelsner ◽  
Norrina B Allen ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Mass Index ◽  
Young Adult ◽  
Waist Circumference ◽  
Body Mass ◽  
Young Adulthood ◽  
Fasting Glucose ◽  
Later Life ◽  
Overweight And Obesity ◽  
Incident Diabetes

Abstract Context The independent contribution of young adult exposure to overweight and obesity to later life incident diabetes is not well studied. Objective To assess the associations of exposures to elevated body mass index (BMI) and waist circumference (WC) in young adulthood (ages 18 to 39 years) with incident diabetes later in life (≥40 years). Design Pooled data from six US prospective cohorts (ARIC, CARDIA, CHS, Framingham Offspring, Health ABC, MESA). Setting Population-based cohort studies. Participants 30,780 participants (56.1% female, 69.8% non-Hispanic White) without a diagnosis of diabetes by age 40. Interventions We imputed BMI and WC trajectories from age 18 for every participant and estimated time-weighted average exposures to BMI or WC during young adulthood and later life. Main Outcome Measure(s) Incident diabetes defined as fasting glucose ≥126 mg/dL, non-fasting glucose ≥200 mg/dL, or use of diabetes medications. Results During a 9-year median follow-up, 4,323 participants developed incident diabetes. Young adult BMI and WC were associated with later life incident diabetes after controlling for later life exposures (hazard ratios [HR] 1.99 for BMI ≥30 kg/m 2 and 2.13 for WC &gt;88cm [women]/&gt;102cm [men] compared to normal ranges). Young adult homeostatic model of insulin resistance (HOMA-IR) mediated 49% and 44% of the association between BMI and WC with later life incident diabetes. HDL and triglycerides mediated a smaller proportion of these associations. Conclusions Elevated BMI and WC during young adulthood were independently associated with later life incident diabetes. Insulin resistance appears to be a key mediator.

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