Hepatic fat in early childhood is independently associated with estimated insulin resistance: The Healthy Start Study

Author(s):  
Catherine C Cohen ◽  
Wei Perng ◽  
Shikha S Sundaram ◽  
Ann Scherzinger ◽  
Kartik Shankar ◽  
...  

Abstract Background Fatty liver disease is a common metabolic abnormality in adolescents with obesity, but remains under-studied in early childhood. Objectives To describe hepatic fat deposition in prepubertal children and examine associations with metabolic markers and body composition. Methods Data were from 286 children ages 4-8 years old in the Healthy Start Study, a longitudinal pre-birth cohort in Colorado. Assessments included magnetic resonance imaging to quantify hepatic and abdominal fats, fasting blood draws to measure metabolic markers, and air displacement plethysmography to measure body composition (fat mass and fat-free mass). Results The median (IQR) for hepatic fat was 1.65% (1.24%,2.11%). Log-transformed hepatic fat was higher in Hispanic [Mean (95% CI): 0.63 (0.52,0.74)] vs. non-Hispanic white children [0.46 (0.38,0.53), p=0.01] and children with overweight/obesity [0.64 (0.49,0.79)] vs. normal-weight [0.47 (0.40,0.53), p=0.02]. Higher log-hepatic fat was associated with higher insulin [β(95% CI): 1.47 (0.61,2.33) uIU/mL, p=0.001] and estimated insulin resistance (homeostatic model assessment) [0.40 (0.20,0.60), p<0.001] in the full sample, and glucose [5.53 (2.84,8.21) mg/dL, p<0.001] and triglycerides [10.92 (2.92,18.91) mg/dL, p=0.008] in boys, in models adjusted for sociodemographics, maternal/perinatal confounders, and percent body fat. Log-hepatic fat was also associated with abdominal subcutaneous adipose tissue [7.37 (1.12,13.60) mm 2, p=0.02] in unadjusted models, but this was attenuated and insignificant after adjusting for confounders. Conclusions While hepatic fat was low in children 4-8 years old, it was independently associated with estimated insulin sensitivity and exhibited sex-specific associations with glucose and triglycerides, suggesting hepatic fat may be an early indicator of metabolic dysfunction in youth.

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Lu Xu ◽  
Ming Li ◽  
Jinhua Yin ◽  
Hong Cheng ◽  
Miao Yu ◽  
...  

A transient increase in insulin resistance (IR) is a component of puberty. We investigated the impact of body composition and adipokines on IR during puberty in Chinese children. This study included 3223 schoolchildren aged 6–18 years. IR was calculated using homeostasis model assessment (HOMA-IR). We revealed that body mass index (BMI) and waist circumference increased gradually during puberty in both genders, while fat-mass percentage (FAT%) increased steadily only in girls. Change of leptin showed striking sexual dimorphisms: in girls leptin increased steadily during puberty, whereas in boys, after a transient rise at the beginning of puberty, leptin declined by Tanner staging even in those overweight or obese. Inversely, adiponectin level decreased significantly during puberty. In both genders, HOMA-IR started to increase at the beginning of puberty, peaked in the middle, and revised at late puberty in overweight/obesity boys while it stayed high till the end of puberty in girls and normal weight boys. Multivariate regression analysis revealed that leptin presented a stronger indicator of HOMA-IR than anthropometric measures during puberty. Our results demonstrated that gender-specific FAT% and leptin changed with pubertal development. Leptin emerged as a stronger predictor of IR than traditional anthropometric indices, suggesting a prominent role in the development of pubertal IR.


Author(s):  
Katherine A Sauder ◽  
Wei Perng ◽  
Michaela P Palumbo ◽  
Lizan D Bloemsma ◽  
John Carey ◽  
...  

Abstract Context It is unclear how fat mass accretion in early life is related to glucose-insulin homeostasis. Objective Examine associations of fat and fat-free mass accretion from birth to early childhood with glucose-insulin homeostasis in early childhood in a multi-ethnic cohort. Design Observational Healthy Start study with data collection from 2010-2020. Air displacement plethysmography at birth and 4.8 (SD 0.7) years estimated fat mass percent (FMP, %), fat mass index (FMI, kg/m 2), and fat-free mass index (FFMI, kg/m 2). Setting General population recruited from academic obstetrics clinics in Denver, Colorado. Participants 419 mother/offspring dyads Main Outcome Measures Fasting glucose, insulin, homeostasis model assessment-2 insulin resistance (HOMA2-IR), and beta-cell function (HOMA2-B) at 4.8 years. Results Greater fat mass accretion from birth to early childhood was associated with higher fasting glucose (ΔFMP β=0.20 [95% CI 0.06-0.34], ΔFMI β=0.90 [0.30-1.50]) in participants of Hispanic, Black, and Other races/ethnicities, while greater fat-free mass accretion was associated with higher fasting glucose in non-Hispanic White participants (ΔFFMI β=0.76 [0.21-1.32]). Overall, greater fat, but not fat-free, mass accretion was also associated with higher insulin (ΔFMP β=0.14 [0.09-0.18], ΔFMI 0.71 [0.51-0.92]), HOMA2-IR (FMP β=0.02 [0.01-0.02], ΔFMI β=0.09 [0.06-0.12]), and HOMA2-B (ΔFMP β=0.92 [0.18-1.36], ΔFMI β=4.76 [2.79-6.73]). Conclusions Greater fat mass accretion in infancy and childhood is associated with shifts in fasting glucose in children of Hispanic, Black, and Other races/ethnicities at 5 years of age. Body composition beginning in early life is relevant for metabolic health, and precise assessments of adiposity in pediatric research are needed.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 989.3-989
Author(s):  
A. Jitaru ◽  
C. Pomirleanu ◽  
M. M. Leon-Constantin ◽  
F. Mitu ◽  
C. Ancuta

Background:Rheumatoid arthritis (RA) is associated with an increased cardiovascular (CV) risk, due not only to the traditional risk factors (hypertension, insulin resistance/diabetes, obesity, smoking), but to the inflammatory status as well. The blockade of interleukin-6 (IL-6) can regulate the glucose metabolism, reducing the glucose level and insulin resistance (IR). This beneficial effect is seen more in patients with normal values of body mass index (BMI), compared to the obese population.Objectives:Given the mentioned existing data, we aim to demonstrate the positive effect of IL-6 inhibitors in active RA patients with normal or increased BMI.Methods:We recruited 56 consecutive patients with definite and active RA, non-responders/partial responders to conventional synthetic Drug Modifying Anti-Rheumatic Drugs (csDMARDs)/biological therapy. For a period of 52 weeks, patients received subcutaneous Tocilizumab (TCZ) in a dose of 162mg once a week, according to European League Anti Rheumatism (EULAR) recommendation and National Protocol. We assessed demographics, RA-related parameters (clinical, inflammatory and immune) and metabolic markers, as well as the peripheral response to insulin, quantified by Homeostasis Model Assessment for insulin resistance (HOMA-IR) and the Quantitative Insulin Sensitivity Check Index (QUICKI). We did not include in the study the patients known with diabetes mellitus (DM) and those undergoing glucocorticoids.Results:After 52 weeks of treatment, most of the patients showed a statistically significant reduction of HOMA-IR (3.61 ± 1.21 at the onset vs. 2.45 ± 1.46 at the end of the study, p<0.001), while QUICKI registered a slight increase (0.32 ± 0.01 at the onset vs. 0.33 ± 0.01 at the end of the study, p<0.001). Also, the decrease in insulin and glucose levels were more obvious in patients with normal BMI, strictly related to disease activity.Conclusion:Long-term administration of TCZ in active RA is associated with a significant reduction of disease activity and IR, especially in normal weight patients. This confirms that obesity, as a CV risk factor, represents one of the main causes of IR.References:[1]Castañeda S, Remuzgo-Martínez S, López-Mejías R et al. Rapid beneficial effect of the IL-6 receptor blockade on insulin resistance and insulin sensitivity in non-diabetic patients with rheumatoid arthritis.Clin Exp Rheumatol. 2019; 37(3):465-473.[2]Lehrskov LL, Christensen RH. The role of interleukin-6 in glucose homeostasis and lipid metabolism.Semin Immunopathol. 2019; 41(4):491-499.[3]Ursini F, Russo E, Ruscitti P, Giacomelli R, De Sarro G. The effect of non-TNF-targeted biologics and small molecules on insulin resistance in inflammatory arthritis.Autoimmun Rev. 2018 Apr;17(4):399-404.Disclosure of Interests:Alexandra Jitaru: None declared, Cristina Pomirleanu: None declared, Maria-Magdalena Leon-Constantin: None declared, Florin Mitu: None declared, CODRINA ANCUTA Consultant of: AbbVie, Pfizer, Roche, Novartis, UCB, Ewopharma, Merck Sharpe and Dohme, and Eli Lilly, Speakers bureau: AbbVie, Pfizer, Roche, Novartis, UCB, Ewopharma, Merck Sharpe and Dohme, and Eli Lilly


2020 ◽  
Vol 36 (8) ◽  
Author(s):  
Maria de Fátima Haueisen Sander Diniz ◽  
Alline Maria Rezende Beleigoli ◽  
Maria Inês Schmidt ◽  
Bruce B. Duncan ◽  
Antônio Luiz P. Ribeiro ◽  
...  

Abstract: Homeostasis model assessment of insulin resistance (HOMA-IR) is a method to measure insulin resistance. HOMA-IR cut-offs for identifying metabolic syndrome might vary across populations and body mass index (BMI) levels. We aimed to investigate HOMA-insulin resistance cut-offs that best discriminate individuals with insulin resistance and with metabolic syndrome for each BMI category in a large sample of adults without diabetes in the baseline of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Among the 12,313 participants with mean age of 51.2 (SD 8.9) years, the prevalence of metabolic syndrome was 34.6%, and 60.1% had overweight or obesity. The prevalence of metabolic syndrome among normal weight, overweight and obesity categories were, respectively, 13%, 43.2% and 60.7%. The point of maximum combined sensitivity and specificity of HOMA-IR to discriminate the metabolic syndrome was 2.35 in the whole sample, with increasing values at higher BMI categories. This investigation contributes to better understanding HOMA-IR values associated with insulin resistance and metabolic syndrome in a large Brazilian adult sample, and that use of cut-off points according to ROC curve may be the better strategy. It also suggests that different values might be appropriate across BMI categories.


2003 ◽  
Vol 62 (2) ◽  
pp. 521-528 ◽  
Author(s):  
J. C. K. Wells

Body composition in children is of increasing interest within the contexts of childhood obesity, clinical management of patients and nutritional programming as a pathway to adult disease. Energy imbalance appears to be common in many disease states; however, body composition is not routinely measured in patients. Traditionally, clinical interest has focused on growth or nutritional status, whereas more recent studies have quantified fat mass and lean mass. The human body changes in proportions and chemical composition during childhood and adolescence. Most of the weight gain comprises lean mass rather than fat. In general, interest has focused on percentage fat, and less attention has been paid to the way in which lean mass varies within and between individuals. In the general population secular trends in BMI have been widely reported, indicating increasing levels of childhood obesity, which have been linked to reduced physical activity. However, lower activity levels may potentially lead not only to increased fatness, but also to reduced lean mass. This issue merits further investigation. Diseases have multiple effects on body composition and may influence fat-free mass and/or fat mass. In some diseases both components change in the same direction, whereas in other diseases, the changes are contradictory and may be concealed by relatively normal weight. Improved techniques are required for clinical evaluations. Both higher fatness and reduced lean mass may represent pathways to an increased risk of adult disease.


Author(s):  
Ilanit Bomer ◽  
Carola Saure ◽  
Carolina Caminiti ◽  
Javier Gonzales Ramos ◽  
Graciela Zuccaro ◽  
...  

AbstractCraniopharyngioma is a histologically benign brain malformation with a fundamental role in satiety modulation, causing obesity in up to 52% of patients.To evaluate cardiovascular risk factors, body composition, resting energy expenditure (REE), and energy intake in craniopharyngioma patients and to compare the data with those from children with multifactorial obesity.All obese children and adolescents who underwent craniopharyngioma resection and a control group of children with multifactorial obesity in follow-up between May 2012 and April 2013.Anthropometric measurements, bioelectrical impedance, indirect calorimetry, energy intake, homeostatic model assessment insulin resistance (HOMA-IR), and dyslipidemia were evaluated.Twenty-three patients with craniopharyngioma and 43 controls were included. Children with craniopharyngioma-related obesity had a lower fat-free mass percentage (62.4 vs. 67.5; p=0.01) and a higher fat mass percentage (37.5 vs. 32.5; p=0.01) compared to those with multifactorial obesity. A positive association was found between %REE and %fat-free mass in subjects with multifactorial obesity (68±1% in normal REE vs. 62.6±1% in low REE; p=0.04), but not in craniopharyngioma patients (62±2.7 in normal REE vs. 61.2±1.8% in low REE; p=0.8). No differences were found in metabolic involvement or energy intake.REE was lower in craniopharyngioma patients compared to children with multifactorial obesity regardless of the amount of fat-free mass, suggesting that other factors may be responsible for the lower REE.


2010 ◽  
Vol 10 (3) ◽  
pp. 303-311
Author(s):  
Gregory Killough ◽  
Danielle Battram ◽  
Joanne Kurtz ◽  
Gillian Mandich ◽  
Laura Francis ◽  
...  

OBJECTIVES: "Pause-2-Play" is an obesity prevention program targeting screen-related sedentary behaviours and increasing physical activity among elementary school students. The program consisted of a Behavioural Modification Curriculum and a Health Promoting Afterschool Program. This pilot study reports program feasibility, practicability, and impact. METHODS: the 12-week pilot program was implemented with 32 grade five and six students. Program feasibility and practicability were assessed using a qualitative approach. Intervention effects were assessed by comparing pre-post changes in BMI, body composition, fitness scores, screen time, and cognitive variables related to screening viewing behaviours. RESULTS: "Pause-2-Play" was perceived as a useful, fun program with numerous benefits including: children trying new snacks, feeling fitter and better about one's own body shape, and becoming more aware of a healthy lifestyle. The intervention resulted in a statistically significant reduction in percent body fat and an increase in fat-free mass index in overweight children; a decrease in waist circumference and an increase in fat-free mass index were observed in normal weight children. The intervention also statistically improved fitness scores in both normal weight and overweight children. CONCLUSIONS: "Pause-2-Play" was feasible, practical, and favourably changed body composition and fitness level.


Endocrine ◽  
2021 ◽  
Author(s):  
Mariangela Rondanelli ◽  
Simone Perna ◽  
Zahra Ilyas ◽  
Gabriella Peroni ◽  
Philip Bazire ◽  
...  

Abstract Purpose This study aims to evaluate the effects of a VLCKD combined with omega-3 supplementation (VLCKD diet only lasted for some weeks, and it was followed by a non-ketogenic LCD for the rest of the study period) on body composition, visceral fat, satiety hormones, inflammatory and metabolic markers. Methods It has been performed a pilot open label study lasted 90 days, in a cohort of 12 women with class I obesity aged 18 to 65 years. Data on body composition (evaluated by Dual X-Ray Absorptiometry—DXA), visceral fat, satiety hormones, inflammatory and metabolic markers were recorded. Results This study showed a body weight reduction mean difference over time of −13.7 kg and the waist circumference mean difference decrease of −13.3 cm. Also, the fat mass (FM) decreased—9.1 kg and visceral adipose tissue (VAT)—0.41 kg. No effects on fat-free mass (FFM) have been reported. Improvements were observed in the satiety hormones, with increased ghrelin and decreased leptin, and also in the metabolic profiles. Conclusions A VLCKD combined with omega-3 supplementation appears to be an effective strategy for promoting an high loss of FM with preservation of FFM in patients with class I obesity.


Author(s):  
Daniel A Dumesic ◽  
Ayli Tulberg ◽  
Megan McNamara ◽  
Tristan R Grogan ◽  
David H Abbott ◽  
...  

Abstract Context Increased aldo-keto reductase 1C3 (AKR1C3)-mediated conversion of androstenedione (A4) to testosterone (T) promotes lipid storage in subcutaneous (SC) abdominal adipose in overweight/obese polycystic ovary syndrome (PCOS) women. Objective To examine whether an elevated serum T/A4 ratio, as a marker of enhanced AKR1C3 activity in SC abdominal adipose, predicts metabolic function in normal-weight PCOS women. Design Prospective cohort study. Setting Academic center. Patients Nineteen normal-weight PCOS women; 21 age- and body mass index-matched controls. Intervention(s) Circulating hormone/metabolic determinations, intravenous glucose tolerance testing, total body dual-energy x-ray absorptiometry, SC abdominal fat biopsy. Main Outcome Measure(s) Serum T/A4 ratios, hormone/metabolic measures and AKR1C3 expression of adipocytes matured in vitro were compared between female types; serum T/A4 ratios were correlated with serum lipids, adipose insulin resistance (adipose-IR), homeostatic model assessment of insulin resistance (HOMA-IR) and insulin sensitivity (Si). Results Increased serum T/A4 ratios (P=0.040) and log adipose-IR values (P=0.002) in PCOS women versus controls were accompanied by AKR1C3 mRNA overexpression of PCOS adipocytes matured in vitro (P=0.016). Serum T/A4 ratios in PCOS women, but not controls, negatively correlated with log triglycerides (TG: R=-0.65, P=0.002) and the TG index (R=-0.57, P=0.011). Adjusting for serum free T, serum T/A4 ratios in PCOS women remained negatively correlated with log TG (R=-0.57, P=0.013) and TG index (R=-0.50, P=0.036), respectively, without significant relationships with other metabolic measures. Conclusion An elevated serum T/A4 ratio, as a marker of enhanced AKR1C3 activity in SC abdominal adipose, predicts healthy metabolic function in normal-weight PCOS women.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Leila Setayesh ◽  
Krista Casazza ◽  
Nariman Moradi ◽  
Sanaz Mehranfar ◽  
Habib Yarizadeh ◽  
...  

Abstract Objective Equivocal association the contribution of 25-hydroxyvitamin D (25(OH)D) and the well-accepted role of vitamin D-binding protein (VDBP) on bioavailability of 25(OH)D or its independent roles, has led to possible association of the VDBP in glucose metabolism. This study was conducted to evaluate the relationships among 25(OH)D, VDBP, glucose/insulin metabolism and homeostatic model assessment (HOMA-IR). Blood samples were collected from 236 obese and overweight women. VDBP and 25(OH)D levels, and biochemical parameters were measured using an enzyme-linked immunosorbent assay (ELISA). An impedance fat analyzer was utilized to acquire the body composition. Results Using the multivariate linear regression, a reverse relationship was observed between VDBP and (HOMA-IR), such that women with higher VDBP displayed lower insulin resistance. The relationship was independent of age, body mass index, standardized energy intake and physical activity (p = 0.00). No significant relationship between 25(OH)D levels, FBS, body composition or insulin resistance were observed (p > 0.2). Current study observed that higher level of VDBP may be associated with lower levels of insulin and HOMA-IR, thus the evaluation of VDBP in diverse population groups seems to have significant clinical value in evaluating the prevalence of DM or early stage of glucose intolerance.


Sign in / Sign up

Export Citation Format

Share Document