Polymorphisms -374 T/A and -429 T/C of the Receptor for Advanced Glycation End-Products (RAGE) and Serum Levels of RAGE (sRAGE) Are Not Associated with Metabolic Syndrome.

RAGE is a multi-ligand transmembrane glycoprotein that promotes biological signals associated with inflammatory responses and degenerative diseases. sRAGE is a soluble variant, proposed as an inhibitor of RAGE activity. -374 T/A and -429 T/C polymorphisms of the advanced glycation end products receptor AGER gene are associated with the development of some diseases, such as type of cancer, cardiovascular disease, and micro and macrovascular disease in diabetes among others but their role in metabolic syndrome (MS) is still unknown. We studied 80 healthy men without MS, and 80 men with MS according to the harmonized criteria. -374 T/A and -429 T/C polymorphisms were genotyped by RT-PCR, and sRAGE was measured by ELISA. Allelic and genotypic frequencies did not differ between Non-MS and MS groups (-374 T/A p = 0.48, p = 0.57 and -429 T/C p = 0.36, p = 0.59). Significant differences were found in fasting glucose levels and diastolic blood pressure among the genotypes of the -374 T/A polymorphism in the Non-MS group (p < 0.01 and p = 0.008). Glucose levels were different between -429 T/C genotypes in the MS group (p = 0.02). sRAGE levels were similar in both groups, but in the Non-MS group showed a significant difference between individuals with only 1 or 2 components of the metabolic syndrome (p = 0.047). However, no associations of any SNP with MS were found (recessive model p = 0.48, dominant model p = 0.82 for -374 T/A; recessive model p = 0.48, dominant model p = 0.42 for -429 T/C). -374 T/A and -429 T/C polymorphisms are not associated with MS in Mexican population and have no influence on serum sRAGE levels.

Soluble receptor for advanced glycation end products and lipid profile ratio as cardiovascular risk markers in children with obesity.

INTRODUCTION: Obesity has been shown to be associated with low levels of soluble receptor for advanced glycation end products (sRAGE). OBJECTIVE: To evaluate the levels of sRAGE and its association with the lipid index in children with obesity. METHODS: Cross-sectional study of children with obesity aged between six and 11 years. Anthropometric measurements, glucose, lipid profile, insulin and sRAGE were evaluated; body mass index, total cholesterol/high-density cholesterol (TC/HDL-C), triglycerides/glucose (TG/glucose), and triglycerides/HDL-C (TG-HDL-C) ratios and HOMA-IR were also calculated. RESULTS: Eighty children were studied, among which 50% were males and 50% females. Females had higher values for waist circumference, HOMA-IR, and TG/HDL-C and TG/glucose ratios. No significant differences were found for sRAGE. When the variables were compared according to TG/HDL-C ratio tertiles, higher TC/HDL, TG/glucose, and sRAGE values were found at upper tertile. A significant correlation was observed between sRAGE and HOMA-IR (p < 0.03) in males, and between sRAGE and TG/HDL-C (p < 0.01) and TG/glucose ratios (p < 0.008) in females. CONCLUSIONS: The female gender showed more cardiovascular risk factors and higher sRAGE at TG/HDL-C upper tertile. Further studies are required to test the possible predictive effect of higher risk for developing metabolic and cardiovascular complications.

INTRODUCCIÓN: Se ha mostrado que la obesidad está asociada a niveles bajos de la forma soluble del receptor para productos finales de glicación avanzada (sRAGE). OBJETIVO: Evaluar los niveles de sRAGE y su asociación con el índice lipídico en niños con obesidad. MÉTODOS: Estudio transversal de niños de seis a 11 años de edad con obesidad. Se evaluaron medidas antropométricas, glucosa, perfil lipídico, insulina y sRAGE; también se calculó índice de masa corporal, colesterol total/C-HDL, triglicéridos/glucosa, triglicéridos/C-HDL y HOMA-IR. RESULTADOS: Se estudiaron 80 niños, 50 % hombres y 50 % mujeres. Las mujeres presentaron mayor perímetro de cintura, HOMA-IR, triglicéridos/C-HDL y triglicéridos/glucosa. No se encontraron diferencias significativas en sRAGE. Al comparar las variables conforme a los terciles de la relación triglicéridos/C-HDL, en el tercil superior se encontraron mayores valores de colesterol total/HDL, triglicéridos/glucosa y sRAGE. Se observó correlación significativa entre sRAGE y HOMA-IR (p < 0.03) en los hombres y entre sRAGE, triglicéridos/C-HDL (p < 0.01) y triglicéridos/glucosa (p < 0.008) en las mujeres. CONCLUSIONES: El sexo femenino mostró más factores de riesgo cardiovascular y mayor sRAGE en el tercil superior de triglicéridos/C-HDL. Se requieren más estudios para probar el posible efecto predictor de mayor riesgo para desarrollar complicaciones metabólicas y cardiovasculares.

Curcumin prevents proteins expression changes of oxidative phosphorylation, cellular stress response, and lipid metabolism proteins in liver of mice fed a high-fructose diet.

Increased fructose consumption has been associated with the development of metabolic diseases due to the modification in protein expression, altering metabolic and signaling pathways. Curcumin is a natural compound with a regulatory effect on genes and metabolic pathways. To identify the fructose-induced protein expression changes and the effect of curcumin on the change of protein expression in the liver of mice fed a standard diet and a high fructose diet, to elucidate the global role of curcumin. Four groups (n = 4/group) of male mice (C57BL6J) of six-weeks-old were formed. One group received a standard diet (C); another received curcumin at 0.75% w/w in the feed (C + C); one more received 30% w/v fructose in drinking water (F); and one group received 30% w/v fructose in drinking water and 0.75% w/w curcumin in food (F + C); for 15 weeks. Proteomic analysis was performed by LC-MS/MS, using the label-free technique with the MaxQuant programs for identification and Perseus for expression change analysis. Differentially expressed proteins (fold change ≥1.5 and p < 0.5) were analyzed by gene ontology and KEGG. A total of 1047 proteins were identified, of which 113 changed their expression in mice fed fructose, compared to the control group, and curcumin modified the expression of 64 proteins in mice fed fructose and curcumin compared to mice that only received fructose. Curcumin prevented the change of expression of 13 proteins involved in oxidative phosphorylation (NDUFB8, NDUFB3, and ATP5L) in the cellular response to stress (PSMA5, HIST1H1D) and lipid metabolism (THRSP, DGAT1, ECI1, and ACOT13). Curcumin in mice fed the standard diet increased the expression of proteins related to oxidative phosphorylation, ribosomes, and PPAR pathways. In addition to fructose, increased expression of proteins involved in oxidative phosphorylation, ribosomes, lipid metabolism, and carbon metabolism. However, curcumin prevented expression change in 13 hepatic proteins of fructose-fed mice involved in oxidative phosphorylation, cellular stress response, and lipid metabolism. SIGNIFICANCE: Curcumin is a natural compound with a regulatory effect on proteins and metabolic pathways. So, curcumin prevents the change of expression in 13 hepatic proteins of fructose-fed mice involved in oxidative phosphorylation, cellular stress response and lipid metabolism, as a supplement with protector activity on fructose-induced toxic effects.

Curcumin Prevents the Glycation of Tricarboxylic Acid Cycle and Cell Respiration Proteins in the Heart of Mice Fed with a High-fructose Diet.

BACKGROUND: A high fructose diet (HFD) induces protein glycation. The latter is related to a higher risk of cardiovascular disease. Curcumin is a natural pleiotropic compound that may possess antiglycant properties. OBJECTIVE: The study aims to analyze the effect of curcumin on the content of glycated proteins in the hearts of 6-week-old mice fed with a HFD for 15 weeks. METHODS: Mice were allocated into four groups (n = 6/group): a control group that received a standard diet (CT); a group that received 30% w/v fructose in water (F); a group that received 0.75% w/w curcumin supplemented in food (C); a group that received 30% w/v fructose in water and 0.75% w/w curcumin supplemented in food (F+C). The content of glycated proteins in the heart was determined by Western Blot (whereas the spots were detected by 2D-PAGE) using anti-AGE and anti-CML antibodies. Densitometric analysis was performed using the ImageLab software. Glycated proteins were identified by MALDI-TOF-MS, and an ontological analysis was performed in terms of biological processes and molecular function based on the STRING and DAVID databases. RESULTS: Fourteen glycated protein spots were detected, two of them with anti-AGE and the other 12 with anti- CML. In total, eleven glycated proteins were identified, out of which three had decreased glycation levels due to curcumin exposure. The identified proteins participate in processes such as cellular respiration, oxidative phosphorylation, lipid metabolism, carbohydrate metabolism, the tricarboxylic acid cycle (TAC), and the organization of intermediate filaments. CONCLUSION: Curcumin decreased the fructose-induced glycation level of the ACO2, NDUFS7, and DLAT proteins.

Serum Fatty Acid-Binding Protein 4 Levels in Adolescents: Effect of Insulin Resistance.

Background: Fatty acid-binding protein 4 (FABP4) is an adipokine that plays a causative role in obesity and diabetes. In a stratified cross-sectional study with adolescents, we explored whether changes in FABP4 are already present in lean adolescents, provided they display elements of insulin resistance (IR). Methods: Adolescents were divided in four groups according to body mass index and homeostasis model assessment-IR. Results: In metabolically unhealthy lean (MUL) adolescents (MUL, lean with IR), FABP4 was 33% higher than in healthy counterparts (metabolically healthy lean [MHL]). Obese adolescents without IR (metabolically healthy obesity [MHO]) had 50% higher levels of FABP4 than their lean counterparts (MHL), while levels of FABP4 in obese adolescents with IR (metabolically unhealthy obese [MUO]) were 220% higher than those of MUL adolescents. The differences were significant at least with P < 0.005. MUO > MHO > MUL. Our data demonstrate that the known FABP4 defect in adults with obesity also occurs in youth and even in lean adolescents, suggesting an early association between impaired glucose metabolism and FABP4 irrespective of body weight. FABP4 was more sensitive in discerning each of our 4 subgroups than either adiponectin or leptin. Moreover, evidence for a putative early adiponectin resistance in MUL suggests a combined defect in these adolescents that call for early detection and prevention of the metabolic disturbance that should stay away from concentrating only in subjects with obesity. Conclusions: Our data may serve to draw the considerable attention that is currently paid to FABP4 to the adolescent population, irrespective of the presence of obesity. Further studies with larger cohorts and analyses of visceral and liver fat are warranted.

Lean adolescents with insulin resistance display higher angiopoietin like protein 3, ApoC-III and chylomicron remnant dyslipidemia.

BACKGROUND: Triglyceride-rich lipoproteins (TRL: chylomicrons and VLDL) are a key component of diabetes dyslipoproteinemia and cardiovascular risk. We have shown that it is already prevalent in obese adolescents in association with lipoprotein lipase (LPL) dysregulation. Insulin resistance (IR) suffices to produce TRL dyslipoproteinemia and LPL dysfunction even in the absence of obesity. METHODS: This cross-sectional study included euglycemic adolescents between 15 and 19 y, classified in 4 groups according to BMI, HOMA-IR and fasting lipid as: metabolically healthy lean (MHL, n = 30), metabolically unhealthy lean (MUL, n = 25), metabolically healthy obese (MHO, = 30), and metabolically unhealthy obese (MUO, n = 42). RESULTS: As compared to MHL, MUL participants showed 73% higher concentrations of ApoB-48; 84% of ApoC-III; 24% ANGPTL-3; 200% of TG; 218% of VLDL-C and 238% of TG/HDL-C c, No changes were found in LPL mass. Interestingly, the differences in these parameters between MUL and MHO were not significant. CONCLUSION: Euglycemic lean adolescents with IR display TRL dyslipoproteinemia with increased inhibition of LPL as highlighted by higher concentrations of ANGPTL-3, ApoC-III and fasting chylomicron remnants (ApoB-48).

The Relationship Between Psychosocial Factors and Adherence to Treatment in Men, Premenopausal and Menopausal Women with Type 2 Diabetes Mellitus.

INTRODUCTION: Type 2 Diabetes Mellitus (T2DM) is a chronic disease that begins in adulthood, and is caused by multiple factors. The onset of menopause involves changes that predispose women to the development of T2DM, which can worsen if the adherence to treatment is inadequate due to psychosocial factors or medications. The present study aims to describe the psychosocial factors that may affect adherence to treatment among men and premenopausal and menopausal women with T2DM. METHODS: This was a cross-sectional study of 96 patients with T2DM, who were divided into three groups: 1) men (n=32); 2) premenopausal women (n=32); and 3) menopausal women (n=32). Somatometric and metabolic control data were obtained. Adherence to treatment and psychosocial factors were evaluated: social support, belief in conventional medicine, disease denial, and depressive symptoms. RESULTS: Adherence to medication had a negative correlation with depressive symptoms in men (p <0.001) and menopausal women (p <0.021). Dietary adherence had a positive correlation with belief in conventional medicine in men (p <0.037) and premenopausal women (p <0.029). CONCLUSION: Medication adherence in men and menopausal women was correlated with fewer depressive symptoms. Adherence to diet in men and premenopausal women was correlated with greater belief in conventional medicine. The results show the diversity of psychosocial factors among the groups that must be addressed in order to improve adherence.

Effects of L-Citrulline Supplementation and Aerobic Training on Vascular Function in Individuals with Obesity across the Lifespan.

Children with obesity are at higher risk for developing cardiometabolic diseases that once were considered health conditions of adults. Obesity is commonly associated with cardiometabolic risk factors such as dyslipidemia, hyperglycemia, hyperinsulinemia and hypertension that contribute to the development of endothelial dysfunction. Endothelial dysfunction, characterized by reduced nitric oxide (NO) production, precedes vascular abnormalities including atherosclerosis and arterial stiffness. Thus, early detection and treatment of cardiometabolic risk factors are necessary to prevent deleterious vascular consequences of obesity at an early age. Non-pharmacological interventions including L-Citrulline (L-Cit) supplementation and aerobic training stimulate endothelial NO mediated vasodilation, leading to improvements in organ perfusion, blood pressure, arterial stiffness, atherosclerosis and metabolic health (glucose control and lipid profile). Few studies suggest that the combination of L-Cit supplementation and exercise training can be an effective strategy to counteract the adverse effects of obesity on vascular function in older adults. Therefore, this review examined the efficacy of L-Cit supplementation and aerobic training interventions on vascular and metabolic parameters in obese individuals.

Dietary AGEs as Exogenous Boosters of Inflammation.

Most chronic modern non-transmissible diseases seem to begin as the result of low-grade inflammation extending over prolonged periods of time. The importance of diet as a source of many pro-inflammatory compounds that could create and sustain such a low-grade inflammatory state cannot be ignored, particularly since we are constantly exposed to them during the day. The focus of this review is on specific components of the diet associated with inflammation, specifically advanced glycation end products (AGEs) that form during thermal processing of food. AGEs are also generated in the body in normal physiology and are widely recognized as increased in diabetes, but many people are unaware of the potential importance of exogenous AGEs ingested in food. We review experimental models, epidemiologic data, and small clinical trials that suggest an important association between dietary intake of these compounds and development of an inflammatory and pro-oxidative state that is conducive to chronic diseases. We compare dietary intake of AGEs with other widely known dietary patterns, such as the Mediterranean and the Dietary Approaches to Stop Hypertension (DASH) diets, as well as the Dietary Inflammation Index (DII). Finally, we delineate in detail the pathophysiological mechanisms induced by dietary AGEs, both direct (i.e., non-receptor-mediated) and indirect (receptor-mediated).

Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes.

Hundreds of thousands of genetic variants have been reported to cause severe monogenic diseases, but the probability that a variant carrier develops the disease (termed penetrance) is unknown for virtually all of them. Additionally, the clinical utility of common polygenetic variation remains uncertain. Using exome sequencing from 77,184 adult individuals (38,618 multi-ancestral individuals from a type 2 diabetes case-control study and 38,566 participants from the UK Biobank, for whom genotype array data were also available), we apply clinical standard-of-care gene variant curation for eight monogenic metabolic conditions. Rare variants causing monogenic diabetes and dyslipidemias display effect sizes significantly larger than the top 1% of the corresponding polygenic scores. Nevertheless, penetrance estimates for monogenic variant carriers average 60% or lower for most conditions. We assess epidemiologic and genetic factors contributing to risk prediction in monogenic variant carriers, demonstrating that inclusion of polygenic variation significantly improves biomarker estimation for two monogenic dyslipidemias.

Reduction of small dense LDL and Il-6 after intervention with Plantago psyllium in adolescents with obesity: a parallel, double blind, randomized clinical trial.

Obesity can lead children and adolescents to an increased cardiovascular disease (CVD) risk. A diet supplemented with Plantago psyllium has been shown to be effective in reducing LDL-C and IL-6 in adolescents. However, there are no studies that have explored small-dense LDL (sdLDL) or HDL subclasses. The aim of this study was to evaluate the impact of a fiber dietary intervention on LDL and HDL subclasses in adolescents with obesity. In this parallel, double blind, randomized clinical trial, the participants were assigned to Plantago psyllium or placebo (10g/day for 7 weeks). We randomized 113 participants, and evaluated and analyzed 100 adolescents (50 in each group), 15 to 19 years with a body mass index of 29-34. We measured biochemical markers LDL and HDL subclasses using the Lipoprint system (Quantimetrix) and IL-6 by ELISA. Post-treatment there was a decrease in sdLDL between the groups 2.0 (0-5.0) vs 1 (0-3.0) mg/dl (p = 0.004), IL-6 median 3.32 (1.24-5.96) vs 1.76 (0.54-3.28) pg/ml, p <0.0001. There were no differences in HDL subclasses and no adverse effects were reported in either group.Conclusions: Small dense LDL and IL-6 reduced in adolescents with obesity when consuming Plantago psyllium. This may be an early good strategy for the reduction of cardiovascular disease risk in this vulnerable population.Trial registration: ISRCTN # 14180431. Date assigned 24/08/2020 What is Known: • Supplementing the diet with Plantago psyllium lowers LDL-C levels. What is New: • First evidence that soluble fiber supplementation like Plantago psyllium decreases small dense LDL particles in association with lowered IL-6, reducing the risk of cardiovascular disease in obese adolescents.

Contribution of RAGE axis activation to the association between metabolic syndrome and cancer.

Far beyond the compelling proofs supporting that the metabolic syndrome represents a risk factor for diabetes and cardiovascular diseases, a growing body of evidence suggests that it is also a risk factor for different types of cancer. However, the involved molecular mechanisms underlying this association are not fully understood, and they have been mainly focused on the individual contributions of each component of the metabolic syndrome such as obesity, hyperglycemia, and high blood pressure to the development of cancer. The Receptor for Advanced Glycation End-products (RAGE) axis activation has emerged as an important contributor to the pathophysiology of many clinical entities, by fueling a chronic inflammatory milieu, and thus supporting an optimal microenvironment to promote tumor growth and progression. In the present review, we intend to highlight that RAGE axis activation is a crosswise element on the potential mechanistic contributions of some relevant components of metabolic syndrome into the association with cancer.

Validation of an instrument to measure adherence to type 2 diabetes management.

Background Adherence to type 2 diabetes management is defined as the extent to which the behaviour of a person matches the one recommended by health care professionals. Control of this disease depends on adherence to diabetes management, which includes monitoring blood glucose levels, adopting a healthy diet, exercising, taking medication, quitting smoking, and undergoing psychosocial care and periodic check-ups. This can also prevent health complications and reduce medical costs. Objective The objective of this study is to validate a culturally appropriate instrument directed towards the Mexican population that measures a patient's level of adherence to their type 2 diabetes mellitus management. Method The study design was cross-sectional. The instrument was applied individually (face to face researcher-assisted survey) by a member of the team. The study sample included 200 participants, which were attended at an outpatient clinic. To evaluate the psychometric validity of the scale we calculated response frequencies, the discrimination of items for extreme groups, the validity, and the internal reliability. The scale of adherence for complete management in patients with type 2 diabetes includes disease monitoring, complication prevention, and social support using questions and answers based on the Likert scale, corresponding to the 5 stages of the transtheoretical model. Main outcome measure The validity and internal reliability of the instrument to measure adherence to type 2 diabetes management, which proved to be justifiable and reliable with a Cronbach's alpha of 0.92 and a total explained variance of 65.03%. Results The instrument was composed of 29 items and 6 factors: adherence to medical Cronbach's alpha = 0.92 and dietary treatment Cronbach's alpha = 0.88, change in dietary habits Cronbach's alpha = 0.89, adherence to physical activity and exercise Cronbach's alpha = 0.84, social support Cronbach's alpha = 0.79, and prevention of complications Cronbach's alpha = 0.70. The instrument obtained a content validity index (I-CVI) of 0.9. Conclusion The proposed instrument, which includes factors that measure adherence in type 2 diabetes mellitus patient's management, using the transtheoretical model of behaviour change to simultaneously identify patient motivation to change their lifestyle, is valid and reliable.

Liquid chromatography-mass spectrometry untargeted metabolomics reveals increased levels of tryptophan indole metabolites in urine of metabolic syndrome patients.

Metabolic syndrome (MetS) is a multifactor condition predisposing for diabetes, cardiovascular diseases and other degenerative disorders. Although several diagnostic criteria have been established, none of them is specific and there is a call for better pathophysiological explanation of MetS and for the discovery of molecular biomarkers. Phenotype characterization at metabolome level might be useful for both purposes. To this end, our aim was to perform comparative untargeted metabolomics of urines from MetS patients and from the control group. The study participants included 52 diagnosticated and 50 healthy individuals from Leon city in central Mexico; 23 anthropometric and clinical parameters were measured and submitted to Principal Component Analysis (PCA). The obtained PCA model allowed us for selection of 11 MetS patients and 13 control subjects, correspondingly representative for each of the two groups (clearly separated in PCA). The first morning urines from these subjects were ambulatory collected and, after methanol extraction and acidification, were submitted to capillary liquid chromatography-high resolution mass spectrometry (LC-HRMS). The obtained data were analyzed on MetaboScape® platform (Bruker Daltonics). Specifically, t-test applied to LC-HRMS data revealed several ions presenting at least 3-fold higher intensities in MetS with respect to the control samples (p < 0.05). Data analysis and complementary experiments yielded the identification of the following metabolites: indole-3-acetic acid, indole-3-acetic acid-O-glucuronide, N-(indol-3-ylacetyl) glutamine, indole-3-carbaldehyde and hydroxyhexanoycarnitine. Additionally, indole-3-carboxylic acid was annotated with 2.13-fold higher abundance in MetS patients. To assess the contribution of individual metabolites in the difference between two groups of subjects, partial least square discriminant analysis was performed for LC-HRMS data and the obtained values of variable importance in projection (VIP), confirmed the association of six above mentioned compounds with MetS. Overall, this study provides direct evidence on the disturbed catabolism of tryptophan in metabolic syndrome.

Higher ANGPTL3, apoC-III, and apoB48 dyslipidemia, and lower lipoprotein lipase concentrations are associated with dysfunctional visceral fat in adolescents with obesity.

BACKGROUND: We hypothesized that adolescents with obesity have higher remnant B48 concentrations associated with lipoprotein lipase dysregulation. METHODS: Cross-sectional study of 32 adolescents with obesity and 27 control subjects. RESULTS: As compared to lean controls, obese participants showed 35% higher concentrations of apoB48: 3.60 (2.93-4.30) vs 2.65 (1.64-3.68) ng/ml; 28% of apoC-III: (72.7 (58.6-89.7) vs 56.9 (44.8-79.8 ug/ml and 17% ANGPTL 3: (72.2 ± 20.2 vs 61.2 ± 19.2 ng/ml). This was accompanied by a 33% reduction in LPL: 13.1 ± 5.1 vs 18.9 ± 4.7 ng/ml. Obese participants had 25% lower adiponectin 2.9 (1.9-3.8) vs 4.4 (3.2.-5.2) µg/ml; 260% higher leptin 25.7 (11.2-44.8) vs 9.3 (2.8-20.7) ng/ml c and 83% higher Il-6: 2.2 (1.3-5.4) vs 1.2 (0.8-1.4) pg/ml. ApoC-III and ANGPTL3 correlated positively with VAI; ANGPTL3 negatively with HDL-C; LDL size and VLDL-C. ApoB48 correlated negatively with LDL-C. CONCLUSIONS: Adolescents with obesity show higher ANGPTL3 compounded with increased apoC-III associated with increased CR and lower LPL mass. This is associated with inflammation and visceral fat. The significance of these findings resides in that they shed light on a mechanism for TRL dyslipidemia in adolescents: increased LPL inhibition impairs VLDL and chylomicron catabolism leading to atherogenic remnants.

INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN-1, NON-ALCOHOLIC FATTY LIVER DISEASE, AND ITS RELATIONSHIP WITH FRUCTOSE CONSUMPTION IN CHILDREN WITH OBESITY.

BACKGROUND: Over consumption of added sugar is associated with obesity, non-alcoholic fatty liver disease (NAFLD), and insulin resistance (IR). OBJECTIVE: The objective of the study was to study the insulin-like growth factor binding protein-1 (IGFBP-1) and NAFLD and their relationship with fructose consumption in children with obesity. METHODS: A cross-sectional study was carried out in children 6-11 years old with obesity. Anthropometric measurements, fructose consumption, glucose, lipid profile, insulin, and IGFBP-1 levels were evaluated; the homeostatic model assessment of IR (HOMA-IR) was used. NAFLD was evaluated by ultrasound. RESULTS: We studied 83 children with a mean age of 9.2 ± 1.3 years. About 93% of the girls presented IR and lower levels of IGFBP-1 (p = 0.0001). The group with the lower levels of IGFBP-1 had higher HOMA-IR (p = 0.000002); IGFBP-1 was associated with fructose consumption (r = -0.25; p = 0.03), body mass index (BMI) (r=-0.42; p = 0.02), and HOMA-IR (r=-0.61; p = 0.002). About 81% of the children were classified as having mild or moderate/severe NAFLD, and these groups had higher HOMA-IR (p = 0.036) and fructose consumption (p = 0.0014). CONCLUSIONS: The girls had more metabolic alterations. The group with lower levels of IGFBP-1 (hepatic IR) was associated with higher BMI, HOMA-IR, and fructose consumption; the group with higher severity of NAFLD showed higher HOMA-IR and fructose consumption.

Insulin-like growth factor binding protein-1, non-alcoholic fatty liver disease, and its relationship with fructose consumption in children with obesity

Background Over consumption of added sugar is associated with obesity, non-alcoholic fatty liver disease (NAFLD), and insulin resistance (IR). Objective The objective of the study was to study the insulin-like growth factor binding protein-1 (IGFBP-1) and NAFLD and their relationship with fructose consumption in children with obesity. Methods A cross-sectional study was carried out in children 6-11 years old with obesity. Anthropometric measurements, fructose consumption, glucose, lipid profile, insulin, and IGFBP-1 levels were evaluated; the homeostatic model assessment of IR (HOMA-IR) was used. NAFLD was evaluated by ultrasound. Results We studied 83 children with a mean age of 9.2 ± 1.3 years. About 93% of the girls presented IR and lower levels of IGFBP-1 (p = 0.0001). The group with the lower levels of IGFBP-1 had higher HOMA-IR (p = 0.000002); IGFBP-1 was associated with fructose consumption (r = −0.25; p = 0.03), body mass index (BMI) (r=−0.42; p = 0.02), and HOMA-IR (r=−0.61; p = 0.002). About 81% of the children were classified as having mild or moderate/severe NAFLD, and these groups had higher HOMA-IR (p = 0.036) and fructose consumption (p = 0.0014). Conclusions The girls had more metabolic alterations. The group with lower levels of IGFBP-1 (hepatic IR) was associated with higher BMI, HOMA-IR, and fructose consumption; the group with higher severity of NAFLD showed higher HOMA-IR and fructose consumption.

Soluble Receptor for Advanced Glycation End Products and Its Correlation with Vascular Damage in Adolescents with Obesity.

OBJECTIVE: The aim of this study was to evaluate soluble receptor for advanced glycation end products (sRAGE) and advanced glycation end products (AGEs) in adolescents with and without obesity (OB) and their correlation with vascular damage. METHODS: This is a cross-sectional study with 15-19 years old adolescents: 33 with OB and 33 with normal weight (NW), each group included 17 male and 16 female. Lipid profile, insulin, carboxymethylysine (CML), sRAGE, total AGEs, and dietary AGEs intake (dAGEs) were evaluated. Vascular damage was measured by flow-mediated vasodilation (FMD) and arterial stiffness index (Iß). Homeostatic model assessment-insulin (HOMA-IR) and atherogenic index (AI) were calculated. RESULTS: The group with OB had higher triglycerides (TG; p < 0.0001), AI (p < 0.001), HOMA-IR (p < 0.0001), dAGEs intake (p < 0.0001), lower CML (p = 0.05), total AGEs (p < 0.01), sRAGE (p < 0.001), and FMD (p < 0.002). In the total group, sRAGE correlated with AI (r = -0.26 p = 0.037); in the NW group, CML correlated with Iß (r = -0.36; p = 0.037); and in the group of adolescents with OB, sRAGE correlated with FMD (r = -0.37; p = 0.037) and Iß (r = 0.47; p = 0.006), while CML and total AGEs correlated with AI, p = 0.007 and p < 0.01, respectively). CONCLUSIONS: The group of adolescents with OB showed higher cardiometabolic risk as shown by higher TG, AI, HOMA-IR, and lower sRAGE and FMD. sRAGE correlated negatively with FMD and positively with Iß, so it could be suggested as a biochemical marker of impaired endothelial function.

Prediction of incident hypertension and arterial stiffness using the non-insulin-based metabolic score for insulin resistance (METS-IR) index.

Hypertension is associated with insulin resistance (IR), metabolic syndrome (MS), and arterial stiffness. Non-insulin-based IR indexes were developed as tools for metabolic screening. Here, we aimed to evaluate the novel non-insulin-based Metabolic Score for IR (METS-IR) index for the prediction of incident hypertension and arterial stiffness evaluated using pulse wave velocity (PWV) analysis, compared with other non-insulin-based IR indexes. We evaluated two populations, a cross-sectional evaluation of high-risk individuals (n = 305) with a wide range of metabolic comorbidities and dyslipidemia in whom PWV measurement was performed and a 3-year prospective cohort of normotensive individuals (N = 6850). We observed a positive correlation between METS-IR and PWV in the cross-sectional cohort, which was higher compared with other non-insulin-based fasting IR indexes; furthermore, PWV values >75th percentile were associated with the upper tercile of METS-IR values. In the prospective cohort, we observed an increased risk for incident hypertension for the upper METS-IR tercile (METS-IR ≥ 46.42; HR: 1.81, 95% CI: 1.41-2.34), adjusted for known cardiovascular risk factors, and observed that METS-IR had greater increases in the predictive capacity for hypertension along with SBP and the Framingham Hypertension Risk Prediction Model compared with other non-insulin-based IR indexes. Therefore, METS-IR is a novel non-insulin-based IR index which correlates with arterial stiffness and is a predictor of incident hypertension, complementary to previously validated risk prediction models.

Changes in circulating levels of carboxymethyllysine, soluble receptor for advanced glycation end products (sRAGE), and inflammation markers in women during normal pregnancy.

Objective: To determine the circulating levels of insulin, Nε-carboxymethyllysine (CML), soluble receptor for advanced glycation end products (sRAGE), and markers of inflammation and oxidative stress (OS) in maternal and umbilical cord blood in a cohort of healthy women with normal pregnancy.Methods: We conducted an observational longitudinal study in a group of women (n = 31; age range 18-39 years) with healthy pregnancy starting at 30 weeks of gestation and finishing at the time of delivery. We collected weight and height in the participants and their neonates and calculated body mass index (BMI). Blood from each patient was collected at 30th week of pregnancy and at delivery when a sample of cord blood was also obtained. Glucose, lipid profile, CML, sRAGE, malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), highly sensitivity C-reactive protein (hsPCR), and insulin were determined. The study was approved by the University of Guanajuato Institutional Ethics Committee.Results: All pregnancies reached term (mean gestational time 38.9 ± 0.83 weeks) and there were no maternal complications. Mean age was 27.6 years. Lipid profile values were higher in the group compared with our values in nonpregnant women. During pregnancy, levels of insulin increased (p < .0006), CML (p < .0001) and sRAGE (p < .01) decreased, levels of MDA did not change, while those of TNF-α and hsPCR tended to increase. In the neonates, we found lower levels of CML (p < .003), hsPCR (p < .004), and insulin (p < .004) and higher levels of sRAGE (p < .013) and TNF-α (p < .022) compared to their mothers at delivery. In the total group, we found association of CML of the mother at baseline with the CML (p < .0006) and MDA (p < .002) in neonates, while maternal sRAGE at the end of pregnancy was associated with CML (p < .004) of their neonates.Conclusions: Our study confirms that normal pregnancy is accompanied by insulin resistance (IR) and significant increase in lipid profile, and demonstrates that circulating levels of CML and sRAGE decreased significantly at the end of pregnancy. The lack of association between the course of insulin levels and those of CML probably results from the predominant role of placental factors in the pathogenesis of IR in pregnancy. sRAGE levels in the neonates are markedly increased compared to their mothers suggesting a placental origin of this compound which may have a protective effect on the fetus since sRAGE restricts Advanced glycation end product (AGE) effects and may exert anti-inflammatory effects.