scholarly journals Tyrosine Is Associated with Insulin Resistance in Longitudinal Metabolomic Profiling of Obese Children

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Christian Hellmuth ◽  
Franca Fabiana Kirchberg ◽  
Nina Lass ◽  
Ulrike Harder ◽  
Wolfgang Peissner ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Weight Loss ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Clinical Markers ◽  
Obese Children ◽  
Intervention Programme ◽  
Before And After ◽  
Branched Chain ◽  
One Year

In obese children, hyperinsulinaemia induces adverse metabolic consequences related to the risk of cardiovascular and other disorders. Branched-chain amino acids (BCAA) and acylcarnitines (Carn), involved in amino acid (AA) degradation, were linked to obesity-associated insulin resistance, but these associations yet have not been studied longitudinally in obese children. We studied 80 obese children before and after a one-year lifestyle intervention programme inducing substantial weight loss >0.5 BMI standard deviation scores in 40 children and no weight loss in another 40 children. At baseline and after the 1-year intervention, we assessed insulin resistance (HOMA index), fasting glucose, HbA1c, 2 h glucose in an oral glucose tolerance test, AA, and Carn. BMI adjusted metabolite levels were associated with clinical markers at baseline and after intervention, and changes with the intervention period were evaluated. Only tyrosine was significantly associated with HOMA (p<0.05) at baseline and end and with change during the intervention (p<0.05). In contrast, ratios depicting BCAA metabolism were negatively associated with HOMA at baseline (p<0.05), but not in the longitudinal profiling. Stratified analysis revealed that the children with substantial weight loss drove this association. We conclude that tyrosine alterations in association with insulin resistance precede alteration in BCAA metabolism. This trial is registered with ClinicalTrials.gov IdentifierNCT00435734.

scholarly journals Obese Older Type 2 Diabetes Mellitus Patients with Muscle Insulin Resistance Benefit from an Enriched Protein Drink during Combined Lifestyle Intervention: The PROBE Study

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2979 ◽  
Author(s):  
Wilrike J. Pasman ◽  
Robert G. Memelink ◽  
Johan de Vogel-Van den Bosch ◽  
Mark P. V. Begieneman ◽  
Willem J. van den Brink ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Muscle Mass ◽  
Lifestyle Intervention ◽  
Tolerance Test ◽  
Whole Body ◽  
Physiological Data ◽  
Oral Glucose ◽  
Before And After

(1) Background: Recent research showed that subtypes of patients with type 2 diabetes may differ in response to lifestyle interventions based on their organ-specific insulin resistance (IR). (2) Methods: 123 Subjects with type 2 diabetes were randomized into 13-week lifestyle intervention, receiving either an enriched protein drink (protein+) or an isocaloric control drink (control). Before and after the intervention, anthropometrical and physiological data was collected. An oral glucose tolerance test was used to calculate indices representing organ insulin resistance (muscle, liver, and adipose tissue) and β-cell functioning. In 82 study-compliant subjects (per-protocol), we retrospectively examined the intervention effect in patients with muscle IR (MIR, n = 42) and without MIR (no-MIR, n = 40). (3) Results: Only in patients from the MIR subgroup that received protein+ drink, fasting plasma glucose and insulin, whole body, liver and adipose IR, and appendicular skeletal muscle mass improved versus control. Lifestyle intervention improved body weight and fat mass in both subgroups. Furthermore, for the MIR subgroup decreased systolic blood pressure and increased VO2peak and for the no-MIR subgroup, a decreased 2-h glucose concentration was found. (4) Conclusions: Enriched protein drink during combined lifestyle intervention seems to be especially effective on increasing muscle mass and improving insulin resistance in obese older, type 2 diabetes patients with muscle IR.

scholarly journals Metabolomic Analysis of the Effects of Leptin Replacement Therapy in Patients with Lipodystrophy

2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Shivraj Grewal ◽  
Sriram Gubbi ◽  
Andin Fosam ◽  
Caroline Sedmak ◽  
Shanaz Sikder ◽  
...  
Keyword(s):  
Replacement Therapy ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Metabolomic Analysis ◽  
Metabolomic Profiling ◽  
Branched Chain Amino Acid ◽  
Before And After ◽  
Branched Chain

Abstract Context and Objective Leptin treatment has dramatic clinical effects on glucose and lipid metabolism in leptin-deficient patients with lipodystrophy. Further elucidation of metabolic effects of exogenous leptin therapy will shed light on understanding leptin physiology in humans. Our objective was to utilize metabolomic profiling to examine the changes associated with administration of short-term metreleptin therapy in patients with lipodystrophy. Study Design We conducted a pre-post-treatment study in 19 patients (75% female) with varying forms of lipodystrophy (congenital generalized lipodystrophy, n = 10; acquired generalized lipodystrophy, n = 1; familial partial lipodystrophy, n = 8) who received daily subcutaneous metreleptin injections for a period of 16 to 23 weeks. A 3-hour oral glucose tolerance test and body composition measurements were conducted before and after the treatment period, and fasting blood samples were used for metabolomic profiling. The study outcome aimed at measuring changes in physiologically relevant metabolites before and after leptin therapy. Results Metabolomic analysis revealed changes in pathways involving branched-chain amino acid metabolism, fatty acid oxidation, protein degradation, urea cycle, tryptophan metabolism, nucleotide catabolism, vitamin E, and steroid metabolism. Fold changes in pre- to post-treatment metabolite levels indicated increased breakdown of fatty acids, branched chain amino acids proteins, and nucleic acids. Conclusions Leptin replacement therapy has significant effects on important metabolic pathways implicated in patients with lipodystrophy. Continued metabolomic studies may provide further insight into the mechanisms of action of leptin replacement therapy and provide novel biomarkers of lipodystrophy. Abbreviations: 1,5-AG, 1,5-anhydroglucitol; 11βHSD1, 11-β hydroxysteroid dehydrogenase 1; BCAA, branched-chain amino acid; FFA, free fatty acid; GC-MS, gas chromatography mass spectrometry; IDO, indoleamine 2,3-dioxygenase; IFN-γ, interferon-γ; m/z, mass to charge ratio; OGTT, oral glucose tolerance test; TDO, tryptophan 2,3-dioxygenase; TNF-α, tumor necrosis factor-α; UPLC-MS/MS, ultra-performance liquid chromatography-tandem mass spectrometry.

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.

Relationship between insulin resistance and puberty in children with increased cardiometabolic risk

2011 ◽  
Vol 152 (27) ◽  
pp. 1068-1074 ◽  
Author(s):  
Borbála Tobisch ◽  
László Blatniczky ◽  
László Barkai
Keyword(s):  
Insulin Resistance ◽  
Glucose Tolerance ◽  
Oral Glucose Tolerance Test ◽  
Cardiometabolic Risk ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
Obese Children ◽  
T1 Stage

Epidemiologic data provide evidence that the frequency of obesity and cardiometabolic risk factors shows an increasing tendency in childhood. Insulin resistance plays a central role in the pathogenesis of cardiovascular and metabolic consequences of obesity. Transient decrease in the insulin sensitivity during puberty is a well-known physiological process; however, the feature of this phenomenon is not clear in obese children with increased cardiometabolic risk. Aim: The aim of the present study was to assess the effect of puberty on insulin resistance and metabolic parameters in obese children with and without increased cardiometabolic risk. Materials and methods: Anthropometric data, insulin levels during oral glucose tolerance test and lipid status were analyzed of 161 obese children aged 4-18 years. Σinsulin/Σglucose ratio was obtained during glucose load and HOMA index was used to assess insulin resistance. Children were sorted into prepubertal (T1), pubertal (T2-4) and postpubertal (T5) cohorts according to Tanner staging criteria and metabolic and insulin resistance parameters were evaluated. Increased cardiometabolic risk was defined as the presence of any two risk factors (elevated fasting plasma glucose, blood pressure, triglyceride or decreased HDL-cholesterol) in addition to obesity. Results: Out of 161 obese subjects, 43 (26.7%) had increased cardiometabolic risk. Decreased HDL-cholesterol and/or elevated triglyceride was observed in 101 (56.5%) cases. Impaired glucose tolerance and/or impaired fasting glucose was found in 23 (14.4%) cases. In subjects without increased cardiometabolic risk, the Σinsulin/Σglucose ratio in T1 stage was significantly lower than in T2-4 and T5 stages (p = 0.01). In children with increased cardiometabolic risk, the insulin/glucose ratio was similar in T1, T2-4 and T5 stages, however, it was significantly higher in T1 stage as compared to subjects without increased cardiometabolic risk (p = 0.04). In T2-4 and T5 stages, Σinsulin/Σglucose ratio did not differ between children with and without increased cardiometabolic risk. No difference was found in HOMA index between groups with and without increased cardiometabolic risk in T1 stage, however significantly higher levels were observed in subjects with increased cardiometabolic risk at T2-4 stages (p = 0.01), indicating the presence of fasting hyperinsulinemia in this cohort. Elevated HbA1c (≥6.0%) was found in 13 (16%) out of the 81 children investigated, of whom only two cases had abnormal oral glucose tolerance test. In cases having normal HbA1c, oral glucose tolerance test showed impaired glucose tolerance in 5 cases, impaired fasting glucose in 2 cases, both impaired glucose tolerance and impaired fasting glucose in 2 cases, and type 2 diabetes in 2 cases. Conclusion: Increased insulin resistance can be observed in obese children without increased cardiometabolic risk. In obese children with increased cardiometabolic risk, substantial insulin resistance occurs in prepuberty and it is present at similar level throughout puberty. Fasting insulin levels are elevated in obese subjects with increased cardiometabolic risk as compared to those without increased cardiometabolic risk. To reveal type 2 diabetes cases, HbA1c and oral glucose tolerance test results should be assessed parallel. Orv. Hetil., 2011, 152, 1068–1074.

scholarly journals Insulin resistance in obese children: debate on assessment

2009 ◽  
Vol 55 (3) ◽  
pp. 8-12 ◽  
Author(s):  
Olga V. Vasyukova ◽  
A V Vitebskaya
Keyword(s):  
Insulin Resistance ◽  
Children And Adolescents ◽  
Diagnostic Error ◽  
Diagnostic Value ◽  
Tolerance Test ◽  
Immunoreactive Insulin ◽  
Oral Glucose ◽  
Obese Children ◽  
Matsuda Index ◽  
And Gender

No age- and gender-adjusted criteria remain to be a main problem the investigators face when studying insulin resistance in children. This paper compares insulin resistance (IR) indices in 63 children and adolescents with simple (constitutionally exogenous) obesity. The authors demonstrated a low reproducibility of individual baseline values of insulin (not more than 26% as shown by Pearsons correlation analysis). Estimation of IR by means of the design indices calculated from the fasting concentration of immunoreactive insulin and glucose: 40% of obese children and adolescents had no fit of baseline IR indices with the results of an oral glucose tolerance test (OGTT), which may result in a diagnostic error - both hyperdiagnosis (in 12% of patients) and hypodiagnosis (18% of children). According to the results of this study, the values of stimulated insulin release and the Matsuda index, which were determined from the OGTT data, are of the highest diagnostic value in the assessment of insulin resistance in obesity in children and adolescents.

scholarly journals CORRELATION BETWEEN PRE AND POSTOPERATIVE LEVELS OF GLP-1/GLP-2 AND WEIGHT LOSS AFTER ROUX-EN-Y GASTRIC BYPASS: A PROSPECTIVE STUDY

2016 ◽  
Vol 29 (4) ◽  
pp. 257-259 ◽  
Author(s):  
Everton CAZZO ◽  
◽  
Martinho Antonio GESTIC ◽  
Murillo Pimentel UTRINI ◽  
José Carlos PAREJA ◽  
...  
Keyword(s):  
Weight Loss ◽  
Gastric Bypass ◽  
Prospective Study ◽  
Gut Hormones ◽  
Tolerance Test ◽  
Beneficial Effects ◽  
Excess Loss ◽  
Before And After ◽  
One Year ◽  
A Prospective Study

ABSTRACT Background: The role of gut hormones in glucose homeostasis and weight loss achievement and maintenance after bariatric surgery appears to be a key point in the understanding of the beneficial effects observed following these procedures. Aim: To determine whether there is a correlation between the pre and postoperative levels of both GLP-1 and GLP-2 and the excess weight loss after Roux-en-Y gastric bypass (RYGB). Methods: An exploratory prospective study which enrolled 11 individuals who underwent RYGB and were followed-up for 12 months. GLP-1 and GLP-2 after standard meal tolerance test (MTT) were determined before and after surgery and then correlated with the percentage of excess loss (%EWL). Results: GLP-2 AUC presented a significant postoperative increase (945.3±449.1 vs.1787.9±602.7; p=0.0037); GLP-1 AUC presented a non-significant trend towards increase after RYGB (709.6±320.4 vs. 1026.5±714.3; p=0.3808). Mean %EWL was 66.7±12.2%. There was not any significant correlation between both the pre and postoperative GLP-1 AUCs and GLP-2 AUCs and the %EWL achieved after one year. Conclusion: There was no significant correlation between the pre and postoperative levels of the areas under the GLP-1 and GLP-2 curves with the percentage of weight loss reached after one year.

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