scholarly journals Steroid Metabolism in Children and Adolescents With Obesity and Insulin Resistance: Altered SRD5A and 20α/20βHSD Activity

2021 ◽  
Vol 12 ◽  
Author(s):  
Marta Sumińska ◽  
Rafał Podgórski ◽  
Piotr Fichna ◽  
Marta Fichna
Keyword(s):  
Insulin Resistance ◽  
Children And Adolescents ◽  
Hydroxysteroid Dehydrogenase ◽  
Steroid Metabolism ◽  
Gas Chromatography Mass Spectrometry ◽  
Compensatory Mechanism ◽  
Obese Children ◽  
The Difference ◽  
Steroid Excretion ◽  
Glucocorticoid Metabolism

Alterations in glucocorticoid metabolism may contribute to the development of obesity and insulin resistance (IR). Obesity in turn affects the androgen balance. The peripheral metabolism of steroids is equally an important determinant of their bioavailability and activity. The aim of this study was to evaluate steroid metabolism in obese children and to define which enzyme alterations are associated with IR. Clinical characteristics and anthropometric measurements were determined in 122 obese children and adolescents (72 girls, 50 boys) aged 8 – 18 years. 26 of them (21.3%) were diagnosed with IR (13 boys, 13 girls). Routine laboratory tests were performed and 24h urinary steroid excretion profiles were analyzed by gas chromatography/mass spectrometry. Positive relationship between 5α-reductase (SRD5A) activity and IR was found. According to the androsterone to etiocholanolone (An/Et) ratio the activity of SRD5A was significantly increased in obese children with IR, but the difference remained insignificant once the 5α-dihydrotestosterone to testosterone (5αDHT/T) ratio was considered. Furthermore, this relationship persisted in boys but was not observed in girls. The activity of 20α-hydroxysteroid dehydrogenase (20αHSD) and 20β-hydroxysteroid dehydrogenase (20βHSD) was reduced only in obese girls with IR. Conclude, in the context of obese children and adolescents with IR, we surmise that increased SRD5A represents a compensatory mechanism to reduce local glucocorticoid availability. This phenomenon is probably different in the liver (restriction) and in the adipose tissue (expected increase in activity). We show significant changes in 20αHSD and 20βHSD activity in obese girls with IR, but it is difficult to clearly determine whether the activity of these enzymes is an indicator of the function in their ovaries or adrenal glands.

Abstract P088: Obesity, Hypertension and Insulin Resistance in a Primary Pediatric Setting in Southern Italy

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Giampaolo De Filippo ◽  
Domenico Rendina ◽  
Domenico Viggiano ◽  
Antonio Fasolino ◽  
Paola Sabatini ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Body Weight ◽  
Children And Adolescents ◽  
Diagnostic Criteria ◽  
Southern Italy ◽  
Serum Insulin ◽  
High Density Lipoproteins ◽  
Obese Children ◽  
Campania Region

Background: Obesity is the main risk factor for essential hypertension (EH) in childhood. The O.Si.Me. study (Obesity and Metabolic Syndrome in children and adolescents) evaluated the prevalence of metabolic syndrome (MetS) and its constitutive traits in a sample of obese children and adolescents living in Campania, southern Italy. Patients and methods: Four hundred and fifteen children and adolescents consecutively referred to the National Health Service participating Outpatient Clinics for minor health problems and found to have a Body Mass Index (BMI) Z-score > 2.0 were enrolled in the study. The entire sample was screened for MetS, which was defined as the presence of at least 2 of the following alterations in addition to obesity: fasting hyperglycemia, low levels of high-density lipoproteins cholesterol, hypertriglyceridemia, and EH. The present analysis evaluated the clinical characteristics of the O.Si.Me subgroup of EH participants (systolic and/or diastolic BP ≥ 95 th percentile for age, gender and height) as compared with normotensive participants. Results: The prevalence of EH in the O.Si.Me population was 23.6 % (98/415, 48M and 50F.) and two-thirds of the EH participants met the MetS diagnostic criteria. The EH participants featured serum insulin and HOMA-IR levels significantly higher compared with normotensive ones (11.6±0.6 vs. 9.5±0.4 μIU/ml, p = 0.014; 2.6±0.1 vs. 2.2±0.1, p = 0.028 for insulin and HOMA-IR, respectively). These differences were common to boys and girls and remained significant after correction for age, pubertal stage, body weight, length, BMI, gestational age at birth, duration of breastfeeding and anthropometric parental parameters. Accordingly, children and adolescents with EH had a a relative risk of being insulin resistant (defined as a HOMA-IR ≥2.5) significantly greater compared to those without. Moreover, they exhibited higher serum creatinine levels (53.8±7.1 vs. 35.4±6.8 μmol/l, p=0.025) accounting for gender and body weight. Conclusions: More than a quarter of obese children and adolescents meet the diagnostic criteria for EH in the Campania region in southern Italy. These obese boys and girls have an increased prevalence of insulin resistance and apparently an initial reduction in renal function compared with obese children and adolescents with normal BP.

scholarly journals Metabolic Profiles in Obese Children and Adolescents with Insulin Resistance

2018 ◽  
Vol 6 (3) ◽  
pp. 511-518 ◽  
Author(s):  
Marko Kostovski ◽  
Viktor Simeonovski ◽  
Kristina Mironska ◽  
Velibor Tasic ◽  
Zoran Gucev
Keyword(s):  
Insulin Resistance ◽  
Children And Adolescents ◽  
Plasma Glucose ◽  
Metabolic Profile ◽  
Total Serum ◽  
Model Assessment ◽  
Fasting Insulin ◽  
Obese Children ◽  
Insulin Resistant ◽  
Study Results

BACKGROUND: In the past several decades, the increasing frequency of overweight and obese children and adolescents in the world has become a public health problem. It has contributed significantly to the already high tide of diabetes, cardiovascular and cerebrovascular diseases.AIM: To investigate the frequency of insulin resistance and to evaluate the metabolic profile of insulin resistant and non-insulin resistant obese children and adolescents.SUBJECTS AND METHODS: The study included 96 (45 boys, 51 girls) obese children and adolescents aged     4-17 years old (10.50 ± 2.87 years). Only participants with Body Mass Index ≥ 95 percentile were included.  We analysed sera for fasting insulin levels (FI), fasting serum triglycerides (TG), total serum cholesterol (TC), fasting plasma glucose (FPG) and plasma glucose 2 hours after the performance of the oral glucose tolerance test        (2-h G). Homeostatic model assessment for insulin resistance (HOMA-IR) index was calculated as fasting insulin concentration (microunits per millilitre) x fasting glucose concentration (millimolar)/22.5. The value of HOMA-IR above 3.16 was used as a cut-off value for both genders.RESULTS: Insulin resistance was determined in 58.33% of study participants. Insulin resistant participants had significantly higher level of 2-h G (p = 0.02), FI level (p = 0.000) as well as TG levels (p = 0.01), compared to non-insulin resistant group. Strikingly, 70.73% of the pubertal adolescents were insulin resistant in comparison to 49.09% of the preadolescents (p = 0.03). Significantly higher percentage of insulin-resistant participants were girls (p = 0.009). Moreover, a higher percentage of the girls (70.59%) than boys (44.44%) had HOMA-IR above 3.16 and had elevated FI levels (70.59% vs 48.89%). The difference in the frequency of insulin resistance among obese versus severely obese children and adolescents was not significant (p = 0.73, p > 0.05). Our study results also showed positive, but weak, correlation of HOMA-IR with age, FPG, TG and BMI of the participants (p < 0.05).CONCLUSION: Higher percentage of insulin-resistant participants was of female gender and was adolescents. In general, insulin resistant obese children and adolescents tend to have a worse metabolic profile in comparison to individuals without insulin resistance. It is of note that the highest insulin resistance was also linked with the highest concentrations of triglycerides.

scholarly journals Longitudinal changes in glucocorticoid metabolism are associated with later development of adverse metabolic phenotype

2014 ◽  
Vol 171 (4) ◽  
pp. 433-442 ◽  
Author(s):  
Rachel K Crowley ◽  
Beverly Hughes ◽  
Joanna Gray ◽  
Theresa McCarthy ◽  
Susan Hughes ◽  
...  
Keyword(s):  
Metabolic Disease ◽  
Insulin Resistance ◽  
Glucose Tolerance ◽  
Hydroxysteroid Dehydrogenase ◽  
Metabolic Phenotype ◽  
Model Assessment ◽  
Observation Study ◽  
Longitudinal Changes ◽  
Glucocorticoid Metabolism ◽  
Prospective Longitudinal

ObjectiveDysregulation of enzymes that control local tissue steroid metabolism has been implicated in the pathogenesis of obesity and insulin resistance; however, longitudinal changes in glucocorticoid metabolism have not been investigated. This study was performed to evaluate the role of glucocorticoid metabolism in the development of insulin resistance and obesity and to identify biomarkers for future development of metabolic disease.DesignThis was a prospective longitudinal observation study conducted over 5 years.MethodsA 24-h collection was used to serially analyze urinary glucocorticoid and mineralocorticoid metabolites in 57 obese and overweight patients with no prior diagnosis of diabetes mellitus, recruited from the community.ResultsBaseline higher 5α-reductase (5αR) activity, but not 11β-hydroxysteroid dehydrogenase type 1 activity, was predictive of increased fasting insulin at final visit (11.4 compared with 7.4 mU/l in subjects with lower 5αR activity, P<0.05), area under the curve insulin response to oral glucose tolerance test (176.7 compared with 89.1 mU/l.h, P<0.01), and homeostasis model assessment (HOMA2-IR; 1.3 compared with 0.8, P<0.01). Higher total glucocorticoid production was associated with abnormal glucose tolerance and increased BMI. During this study, systolic blood pressure increased (equivalent to ∼1 mmHg/year), as did plasma sodium levels; this evidence of increased mineralocorticoid activity was associated with increased aldosterone metabolites and decreased 11β-hydroxysteroid dehydrogenase type 2 activity.ConclusionsIncreased 5αR activity and glucocorticoid secretion rate over time are linked with the development of metabolic disease, and may represent targets for therapeutic intervention, which merits further study.

scholarly journals Novel genetic variant in FTO influences insulin levels and insulin resistance in severely obese children and adolescents

2008 ◽  
Vol 32 (11) ◽  
pp. 1730-1735 ◽  
Author(s):  
J A Jacobsson ◽  
J Klovins ◽  
I Kapa ◽  
P Danielsson ◽  
V Svensson ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Children And Adolescents ◽  
Genetic Variant ◽  
Obese Children ◽  
Insulin Levels ◽  
Severely Obese

Deep breathing improves blunted baroreflex sensitivity in obese children and adolescents with insulin resistance

2013 ◽  
Vol 168 (2) ◽  
pp. 1614-1615 ◽  
Author(s):  
V. Calcaterra ◽  
M. Vandoni ◽  
G. Debarbieri ◽  
D. Larizza ◽  
R. Albertini ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Children And Adolescents ◽  
Baroreflex Sensitivity ◽  
Deep Breathing ◽  
Obese Children

Metabolic syndrome in obese children and adolescents in Serbia: prevalence and risk factors

2015 ◽  
Vol 28 (7-8) ◽  
Author(s):  
Rade Vukovic ◽  
Dragan Zdravkovic ◽  
Katarina Mitrovic ◽  
Tatjana Milenkovic ◽  
Sladjana Todorovic ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Children And Adolescents ◽  
Strong Predictor ◽  
Pubertal Development ◽  
International Diabetes Federation ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Obese Children ◽  
Diet Induced Obesity

AbstractTo assess the prevalence of metabolic syndrome (MS) in obese children and adolescents in Serbia.The study group consisted of 254 subjects (148 female and 106 male), aged 4.6–18.9 years with diet-induced obesity (body mass index ≥95th percentile). Presence of MS using the International Diabetes Federation definition was assessed in all subjects, as well as oral glucose tolerance test and insulin resistance indices.Overall prevalence of MS in all subjects aged ≥10 years was 31.2%, namely, 28.7% in children aged 10 to <16 years and 40.5% in adolescents ≥16 years. When adjusted for age, gender and pubertal development, higher degree of obesity was a strong predictor of MS. Multivariate analysis showed that taller subjects and those with higher degree of insulin resistance were at significantly higher risk of MS, independent of the degree of obesity.High prevalence of MS emphasizes the need for prevention and treatment of childhood obesity.

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