Insulin resistance is a condition of gluco-metabolic sufferance that may hesitate in the further development of type 2 diabetes and cardiovascular disease. The development of insulin resistance is ...mostly associated with the accumulation of excessive fat in the body. The epidemic impact of obesity in the youngest promoted an increase of the prevalence of insulin resistance also in children and adolescents. Increased fat accumulation in the peri-visceral area of the abdomen, occurring preferably at and after puberty, and in the liver, as non-alcoholic fatty liver disease, plays a role in the process. After puberty, males are at higher risk than females to develop insulin resistance. Also ethnicity contributes to sensitivity of children to develop insulin resistance, where Hispanics, South-Asians, and Indians are at higher risk than Whites and Blacks.In spite of the research progress in the field, several questions on the relationship between body composition and insulin resistance are still unanswered. Multiomics approach, combined with nutrition as well as imaging techniques might contribute to unravel the role of body composition on insulin resistance.
Maternal and placental conditions that are unfavourable for the embryo/foetus have long-lasting effects on different tissues and functions of the body, which may persist for life and, potentially, ...also be transmitted to the offspring. This review resumes current evidence on principle maternal and gestational conditions associated with unfavourable metabolic programming of the offspring, along with their mechanisms of action, either supposed or already proved.
Abstract
Context
Nonalcoholic fatty liver disease (NAFLD) is associated with insulin resistance (IR) and predicts type 2 diabetes. Currently, it is uncertain whether NAFLD may directly cause IR or ...vice versa.
Objective
To test the hypothesis that NAFLD is causally related to IR.
Design and Methods
We performed a Mendelian randomization (MR) in 904 obese children/adolescents using an NAFLD-related genetic risk score (GRS) as an instrumental variable. We assessed NAFLD by ultrasonography and IR by homeostasis model assessment (HOMA-IR). We also interrogated the MAGIC Consortium dataset of 46 186 adults to assess the association between PNPLA3 rs738409 (ie, the most robust NAFLD-related polymorphism) and HOMA-IR, and we performed a 2-sample MR with 2 large datasets to test reverse causation (HOMA-IR increasing the risk of NAFLD).
Results
Nonalcoholic fatty liver disease prevalence increased by 20% for every increase in the GRS (β-coefficient = 0.20, P < 0.001), and NAFLD was associated with ln-HOMA-IR (β-coefficient = 0.28, P < 0.001). Thus, the expected increase in ln-HOMA-IR for every increase in the GRS (expected β-coefficient) was 0.056 (0.28*0.20) in the case of complete NAFLD-HOMA-IR causal association, and 0.042 in the case of 75% causality. In our cohort, the GRS did not predict ln-HOMA-IR (β-coefficient = 0.007, P = 0.75). In the MAGIC cohort, the PNPLA3 rs738409 did not associate with ln-HOMA-IR. The 2-sample MR failed to show a causal association between ln-HOMA-IR and NAFLD.
Conclusions
Our study shows that genetically-influenced NAFLD does not increase HOMA-IR, and genetically-influenced HOMA-IR does not increase the risk of NAFLD. Shared pathogenic pathways or NAFLD subtypes not “captured” by our MR design might underpin the association between NAFLD and HOMA-IR.
The aim of this study is to test the hypothesis that the intake of Policaptil Gel Retard
(PGR) is able to affect appetite, metabolic and hormonal postprandial profile in obese children. 46 obese ...children were randomly assigned to treatment with PGR or placebo, in a double blind clinical trial. Two PGR tablets or placebo were given in fasting condition, before the ingestion of a mixed meal (15 kcal/kg lean body mass). Blood samples were taken at baseline and for 4 hours, for measuring blood lipids, glucose, insulin, ghrelin, and glucagon like peptide-1 (GLP-1). Appetite was quantified using a visual analog scale. Children assuming PGR had a significantly lower increase of postprandial triglycerides (area under the curve (AUC): 3021 (2879) vs. 5038 (3738) mg × 240 min/Dl) and appetite (-234 (274) vs. 36 (329)) than children assuming placebo. The AUC of ghrelin was significantly lower after PGR ingestion, than after placebo (-8179 (8073) vs. -2800 (7579) pg × 240 min/mL). Blood glucose, insulin, non-esterified fatty acids (NEFA) and GLP-1 profiles were not significantly different in the two groups. In conclusion, a single intake of two tablets of PGR was associated with a significant reduction of appetite, ghrelin, and triglycerides in the postprandial period in obese children. Further investigation will assess if a chronic intake of PGR may affect body weight and glucose metabolism.
Prevention of obesity should start as early as possible after birth. We aimed to build clinically useful equations estimating the risk of later obesity in newborns, as a first step towards focused ...early prevention against the global obesity epidemic.
We analyzed the lifetime Northern Finland Birth Cohort 1986 (NFBC1986) (N = 4,032) to draw predictive equations for childhood and adolescent obesity from traditional risk factors (parental BMI, birth weight, maternal gestational weight gain, behaviour and social indicators), and a genetic score built from 39 BMI/obesity-associated polymorphisms. We performed validation analyses in a retrospective cohort of 1,503 Italian children and in a prospective cohort of 1,032 U.S. children.
In the NFBC1986, the cumulative accuracy of traditional risk factors predicting childhood obesity, adolescent obesity, and childhood obesity persistent into adolescence was good: AUROC = 0·780·74-0.82, 0·750·71-0·79 and 0·850·80-0·90 respectively (all p<0·001). Adding the genetic score produced discrimination improvements ≤1%. The NFBC1986 equation for childhood obesity remained acceptably accurate when applied to the Italian and the U.S. cohort (AUROC = 0·700·63-0·77 and 0·730·67-0·80 respectively) and the two additional equations for childhood obesity newly drawn from the Italian and the U.S. datasets showed good accuracy in respective cohorts (AUROC = 0·740·69-0·79 and 0·790·73-0·84) (all p<0·001). The three equations for childhood obesity were converted into simple Excel risk calculators for potential clinical use.
This study provides the first example of handy tools for predicting childhood obesity in newborns by means of easily recorded information, while it shows that currently known genetic variants have very little usefulness for such prediction.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The transition to adult health care (HCT, Health Care Transition), is the purposeful, planned movement of patients from paediatric to adult services. For the adolescent living with obesity (ALwO), ...the HCT represents a crucial window for effective intervention that can help improve body weight, adiposopathy, and metabolic complications. Nevertheless, no transition guidelines, models, and tools have been developed for these patients. The present statement of the Italian Society of Obesity examines the critical transition of ALwO from paediatric to adult healthcare. It synthesises current knowledge and identifies gaps in HCT of ALwO. Drawing on successful practices and evidence-based interventions worldwide, the paper explores challenges, including disparities and barriers, while advocating for patient and family involvement. Additionally, it discusses barriers and perspectives within the Italian health care scenario. The need for specialised training for healthcare providers and the impact of transition on healthcare policies are also addressed. The conclusions underscore the significance of well-managed transitions. The SIO recognises that without proper support during this transition, ALwOs risk facing a gap in healthcare delivery, exacerbating their condition, and increasing the likelihood of complications. Addressing this gap requires concerted efforts to develop effective transition models, enhance healthcare provider awareness, and ensure equitable access to care for all individuals affected by obesity. The document concludes by outlining avenues for future research and improvement.
Background: The minor allele of the single nucleotide polymorphism (SNP) rs2364723 of NFE2L2, a gene encoding a master antioxidant transcription factor, has been associated with poor cardiovascular ...outcomes and with complications of type 2 diabetes. We assessed the association between rs2364723 of NFE2L2 and oxidative stress in children/adolescents with type 1 diabetes (T1D). Methods: In 384 children/adolescents with T1D (age 15.7 ± 3.2 years, 207 males), we assessed the oxidative stress by measuring the concentration of derivatives of reactive oxygen metabolites (d-ROMs) and we genotyped the rs2364723 SNP by real time polymerase chain reaction. Results: The concentration of d-ROMs was 372.8 ± 64.6 Carratelli units. The minor genotype (CC) of rs2364723 at NFE2L2 was associated with higher concentration of derivatives of d-ROMs in the subgroup with HbA1c ≥ 8% (B = 47.85, p for genotype ∗ HbA1c interaction = 0.019). Conclusions: The carriers of the minor genotype of rs2364723 may have increased oxidative stress compared to their counterparts with other genotypes, especially in case of poor glycemic control. This observation needs to be replicated and confirmed in larger independent cohorts of youth with T1D.
Pediatric obesity is closely associated with cardiometabolic comorbidities, but the role of sex in this relationship is less investigated. We aimed to evaluate sex-related differences on ...cardiometabolic risk factors and preclinical signs of target organ damage in adolescents with overweight/obesity (OW/OB).BackgroundPediatric obesity is closely associated with cardiometabolic comorbidities, but the role of sex in this relationship is less investigated. We aimed to evaluate sex-related differences on cardiometabolic risk factors and preclinical signs of target organ damage in adolescents with overweight/obesity (OW/OB).The main cross-sectional study included 988 adolescents (510 boys and 478 girls) with OW/OB aged 10-18 years. In all youths clinical and biochemical variables were evaluated and an abdominal echography was performed. Echocardiographic data for the assessment of left ventricular mass (LVM) and relative wall thickness (RWT) were available in an independent sample of 142 youths (67 boys and 75 girls), while echographic data of carotid intima media thickness (cIMT) were available in 107 youths (59 boys and 48 girls).MethodsThe main cross-sectional study included 988 adolescents (510 boys and 478 girls) with OW/OB aged 10-18 years. In all youths clinical and biochemical variables were evaluated and an abdominal echography was performed. Echocardiographic data for the assessment of left ventricular mass (LVM) and relative wall thickness (RWT) were available in an independent sample of 142 youths (67 boys and 75 girls), while echographic data of carotid intima media thickness (cIMT) were available in 107 youths (59 boys and 48 girls).The three samples did not differ for age, body mass index, and sex distribution. In the main sample, boys showed higher waist-to-height ratio (WHtR) values (p < 0.0001) and fasting glucose levels (p = 0.002) than girls. Lower levels of estimates glomerular filtration rate (eGFR) were found in girls vs boys (p < 0.0001). No sex-related differences for prediabetes and hyperlipidemia were observed. A higher prevalence of WHtR ≥ 0.60 (57.3% vs 49.6%, p = 0.016) and fatty liver disease (FLD) (54.5% vs 38.3%, p < 0.0001) as well as a trend for high prevalence of hypertension (40.4 vs 34.7%, p = 0.06) were observed in boys vs girls. More, a higher prevalence of mild reduced eGFR (MReGFR) ( < 90 mL/min/1.73 m 2 ) was observed in girls vs boys (14.6% vs 9.6 %, p < 0.0001). In the sample with echocardiographic evaluation, boys showed higher levels of LVM (p = 0.046), and RWT (p = 0.003) than girls. Again, in the sample with carotid echography, boys showed higher levels of cIMT as compared to girls (p = 0.011).ResultsThe three samples did not differ for age, body mass index, and sex distribution. In the main sample, boys showed higher waist-to-height ratio (WHtR) values (p < 0.0001) and fasting glucose levels (p = 0.002) than girls. Lower levels of estimates glomerular filtration rate (eGFR) were found in girls vs boys (p < 0.0001). No sex-related differences for prediabetes and hyperlipidemia were observed. A higher prevalence of WHtR ≥ 0.60 (57.3% vs 49.6%, p = 0.016) and fatty liver disease (FLD) (54.5% vs 38.3%, p < 0.0001) as well as a trend for high prevalence of hypertension (40.4 vs 34.7%, p = 0.06) were observed in boys vs girls. More, a higher prevalence of mild reduced eGFR (MReGFR) ( < 90 mL/min/1.73 m 2 ) was observed in girls vs boys (14.6% vs 9.6 %, p < 0.0001). In the sample with echocardiographic evaluation, boys showed higher levels of LVM (p = 0.046), and RWT (p = 0.003) than girls. Again, in the sample with carotid echography, boys showed higher levels of cIMT as compared to girls (p = 0.011).Adolescent boys with OW/OB showed higher risk of abdominal adiposity, FLD, and increased cardiac and vascular impairment than girls, whereas the latter had a higher risk of MReGFR. Risk stratification by sex for cardiometabolic risk factors or preclinical signs of target organ damage should be considered in youths with OW/OB.ConclusionsAdolescent boys with OW/OB showed higher risk of abdominal adiposity, FLD, and increased cardiac and vascular impairment than girls, whereas the latter had a higher risk of MReGFR. Risk stratification by sex for cardiometabolic risk factors or preclinical signs of target organ damage should be considered in youths with OW/OB.
Objective To assess the accuracy of body mass index (BMI), Z score of the BMI, waist circumference, and waist-to-height ratio in selecting obese children with fasting metabolic impairments or ...impaired glucose tolerance. Study design In a cohort of 883 obese children and adolescents (age 8-18 years), we assessed the associations of anthropometric indices with traditional metabolic complications of obesity (impaired fasting glucose, impaired glucose tolerance, hypertension, high triglycerides, low high-density lipoprotein-cholesterol). The accuracy of anthropometric indices as markers of metabolic impairment was assessed by receiver operating characteristic analysis and the areas under the receiver operating characteristics curves (AUROCs) of anthropometric indices were compared with each other by the DeLong test. Results BMI, Z score of the BMI, waist circumference, and waist-to-height ratio were associated with metabolic impairments but showed low to moderate accuracy in discriminating both single and clustered metabolic impairments. The AUROCs ranged from 0.55-0.70. The 4 anthropometric indices did not show significantly different AUROCs as predictors of clustered metabolic risk factors (all P values of DeLong tests: >.05). Conclusions Commonly used anthropometric indices are not satisfactory markers of metabolic comorbidity among obese children and adolescents and should not be adopted as screening tools for the metabolic assessment of this category of patients.
Urogenital complications of obesity Morandi, Anita, MD, PhD; Maffeis, Claudio, MD, PhD
Baillière's best practice & research. Clinical endocrinology & metabolism,
04/2013, Letnik:
27, Številka:
2
Journal Article
Recenzirano
We performed a critical review focused on the main non-oncologic disorders that have a strong, direct association with obesity: chronic kidney disease, kidney stones and female and male lower urinary ...tract symptoms/disorders. We discuss the epidemiology, pathogenesis and therapeutic aspects regarding the association between obesity and non-diabetic and non-hypertensive forms of chronic kidney disease directly caused or worsened by weight excess, with particular attention on obesity-related glomerulopathy (ORG), which is typical of severe obesity, and the consequences of intentional weight loss on proteinuria and glomerular filtration rate. The associations of obesity with kidney stones and lower urinary tract conditions are also discussed from the epidemiological, physiopathological and therapeutical points of view, with emphasis on the principal concerns raised by the heterogeneity of study designs and outcome definitions typical of research in these fields. We also call attention to important clinical and scientific questions that should be addressed by future research.
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