scholarly journals Cardiorespiratory Fitness and Adiposity as Determinants of Metabolic Health—Pooled Analysis of Two Twin Cohorts

2017 ◽  
Vol 102 (5) ◽  
pp. 1520-1528 ◽  
Author(s):  
Sakari Jukarainen ◽  
René Holst ◽  
Christine Dalgård ◽  
Päivi Piirilä ◽  
Jesper Lundbom ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Insulin Sensitivity ◽  
Cardiorespiratory Fitness ◽  
Insulin Response ◽  
Metabolic Health ◽  
Fat Free Mass ◽  
Liver Fat ◽  
Oral Glucose ◽  
Acute Insulin Response ◽  
Metabolic Syndrome Score

Abstract Context: The joint effects of cardiorespiratory fitness (CRF) and body composition on metabolic health are not well known. Objective: To examine the associations of CRF, fat-free mass index (FFMI), and fat mass index (FMI) with metabolic health in individual twins and controlling for genetic and shared environmental effects by studying monozygotic intrapair differences. Design, Setting, and Participants: Two cross-sectional samples of healthy adult monozygotic and dizygotic twins were drawn from population-based Danish and Finnish national twin registries (n = 996 and n = 309). Main Measures: CRF was defined as VO2max divided by fat-free mass. Insulin sensitivity and acute insulin response indices were derived from an oral glucose tolerance test. A continuous metabolic syndrome score was calculated. Visceral and liver fat were measured in the Finnish sample. Associations were analyzed separately in both cohorts with multivariate linear regression and aggregated with meta-analytic methods. Results: Insulin sensitivity, acute insulin response, metabolic syndrome score, visceral, and liver fat amount had strong and statistically significant associations with FMI (|β| 0.53 to 0.79), whereas their associations with CRF and FFMI were at most weak (|β| 0.02 to 0.15). The results of the monozygotic intrapair differences analysis showed the same pattern. Conclusions: Although FMI is strongly associated with worsening of metabolic health traits, even after controlling for genetic and shared environmental factors, there was little evidence for the effects of CRF or FFMI on metabolic health. This suggests that changing FMI rather than CRF or FFMI may affect metabolic health irrespective of genetic or early environmental determinants.

Associations between Liver Enzyme Levels and Parameters of the Metabolic Syndrome in Obese Children

2017 ◽  
Vol 88 (3-4) ◽  
pp. 265-273 ◽  
Author(s):  
Christiane S. Hampe ◽  
Michele L. Shaffer ◽  
Christian L. Roth
Keyword(s):  
Risk Factors ◽  
Metabolic Syndrome ◽  
Insulin Sensitivity ◽  
Liver Enzyme ◽  
Elevated Liver Enzyme ◽  
Insulin Response ◽  
Oral Glucose ◽  
Obese Children ◽  
The Metabolic Syndrome ◽  
Elevated Liver Enzymes

Background: Obesity is strongly associated with insulin resistance, hypertension, dyslipidemia, and therefore risk for metabolic syndrome (MetS), which is an increasing problem in youth. The potential role of elevated liver enzyme levels in this context needs to be further investigated. Methods: This paper provides a post hoc analysis of a cross-sectional study of 77 obese nondiabetic children (51% female; median age 11.7 years; BMI >97th percentile) enrolled at the University of Bonn, Bonn, Germany. Anthropometric parameters, lipid profiles, glycemic control, and liver enzyme levels were evaluated. Glucose and insulin levels were determined during an oral glucose tolerance test (OGTT). Gender- and age-specific cutoff values were used to assess MetS. Results: A high prevalence of hypertension (51%), dyslipidemia (52%), elevated liver enzyme levels (51%), and hyperglycemia (24%) was found. There was considerable overlap between the presence of different MetS risk factors in individuals, and 40% of the participants had ≥3 of a maximum of 5 MetS risk factors. Elevated liver enzyme levels were significantly associated with reduced insulin sensitivity, as the OGTT-insulin response was significantly higher in participants with elevated transaminases (p = 0.01). This association was independent of hyperglycemia and dyslipidemia (p = 0.03). Conclusions: We conclude that liver enzyme levels are related to insulin sensitivity in obese children and could therefore be an indirect indicator for MetS. Testing for disturbed glucose metabolism should be considered for obese children with elevated liver enzymes.

scholarly journals Mitochondrial mutation m.3243A>G associates with insulin resistance in non-diabetic carriers

2019 ◽  
Vol 8 (7) ◽  
pp. 829-837 ◽  
Author(s):  
Jakob Høgild Langdahl ◽  
Anja Lisbeth Frederiksen ◽  
John Vissing ◽  
Morten Frost ◽  
Knud Bonnet Yderstræde ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
Fat Body ◽  
Insulin Response ◽  
Oral Glucose ◽  
Sensitivity Index ◽  
Acute Insulin Response ◽  
Insulin Sensitivity Index ◽  
Mitochondrial Mutation ◽  
Mutation Carriers

Aim This case–control study aimed to examine impairments in glucose metabolism in non-diabetic carriers of the mitochondrial mutation m.3243A>G by evaluating insulin secretion capacity and sensitivity. Methods Glucose metabolism was investigated in 23 non-diabetic m.3243A>G carriers and age-, sex- and BMI-matched healthy controls with an extended 4-h oral glucose tolerance test (OGTT). Insulin sensitivity index and acute insulin response were estimated on the basis of the OGTT. This was accompanied by examination of body composition by dual-energy X-ray absorptiometry (DXA), maximum aerobic capacity and a Recent Physical Activity Questionnaire (RPAQ). Results Fasting p-glucose, s-insulin and s-c-peptide levels did not differ between m.3243A>G carriers and controls. Insulin sensitivity index (BIGTT-S1) was significantly lower in the m.3243A>G carriers, but there was no difference in the acute insulin response between groups. P-lactate levels were higher in carriers throughout the OGTT. VO2max, but not BMI, waist and hip circumferences, lean and fat body mass%, MET or grip strength, was lower in mutation carriers. BIGTT-S1 remained lower in mutation carriers after adjustment for multiple confounding factors including VO2max in regression analyses. Conclusions Glucose metabolism in m.3243A>G carriers was characterized by reduced insulin sensitivity, which could represent the earliest phase in the pathogenesis of m.3243A>G-associated diabetes.

scholarly journals Beneficial Effect of Diazoxide in Obese Hyperinsulinemic Adults1

1998 ◽  
Vol 83 (6) ◽  
pp. 1911-1915 ◽  
Author(s):  
Ramin Alemzadeh ◽  
Gina Langley ◽  
Lori Upchurch ◽  
Pam Smith ◽  
Alfred E. Slonim
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Body Fat ◽  
Therapeutic Potential ◽  
Controlled Trial ◽  
Insulin Response ◽  
Tolerance Test ◽  
Fat Free Mass ◽  
Zucker Rats ◽  
Significant Difference

Hyperinsulinemia, insulin resistance, and increased adipose tissue are hallmarks of the obesity state in both humans and experimental animals. The role of hyperinsulinemia as a possible preceding event in the development of obesity has been proposed. We previously demonstrated that administration of diazoxide (DZ), an inhibitor of insulin secretion, to obese hyperinsulinemic Zucker rats resulted in less weight gain, enhanced insulin sensitivity, and improved glucose tolerance. Assuming that hyperinsulinemia plays a major role in the development of human obesity, then its reversal should have therapeutic potential. To test this hypothesis, we conducted a randomized placebo-controlled trial in 24 hyperinsulinemic adults [body mass index (BMI) > 30 kg/m2]. All subjects were placed on a low-calorie (1260 for females and 1570 for males) Optifast (Sandoz, Minneapolis, MN) diet. After an initial 1-week lead-in period, 12 subjects (mean ± se for age and BMI, 31 ± 1 and 40 ± 2, respectively) received DZ (2 mg/kg BW·day; maximum, 200 mg/day, divided into 3 doses) for 8 weeks; and 12 subjects (mean± se for age and BMI, 28 ± 1 and 43 ± 1, respectively) received placebo. Compared with the placebo group, DZ subjects had greater weight loss (9.5 ± 0.69% vs. 4.6 ± 0.61%, P < 0.001), greater decrease in body fat (P < 0.01), greater increase in fat-free mass to body fat ratio (P < 0.01), and greater attenuation of acute insulin response to glucose (P < 0.01). However, there was no significant difference in insulin sensitivity and glucose effectiveness, as determined by the insulin-modified iv glucose tolerance test (Bergman’s minimal model) and no significant difference in glycohemoglobin values. Conclusion: 8 weeks treatment with DZ had a significant antiobesity effect in hyperinsulinemic obese adults without inducing hyperglycemia.

HDL Containing Apolipoprotein C-III is Associated with Insulin Sensitivity: a Multi-Center Cohort Study

2021 ◽  
Author(s):  
Rain Yamamoto ◽  
Majken K Jensen ◽  
Sarah Aroner ◽  
Jeremy D Furtado ◽  
Bernard Rosner ◽  
...  
Keyword(s):  
Cohort Study ◽  
Insulin Sensitivity ◽  
Clinical Investigation ◽  
Biological Effects ◽  
Sandwich Elisa ◽  
Insulin Response ◽  
Protein Composition ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Euglycemic Hyperinsulinemic Clamp

Abstract Context HDL in humans is composed of a heterogeneous group of particles varying in protein composition as well as biological effects. Objective We investigated the prospective associations between HDL subspecies containing and lacking apoC-III at baseline and insulin sensitivity at year 3. Design, Setting, and Participants A prospective cohort study of 864 healthy volunteers drawn from the RISC study, a multi-center European clinical investigation, whose recruitment initiated in 2002 with a follow-up of 3 years. Main Measures Insulin sensitivity was estimated from an oral glucose tolerance test (OGTT) at baseline and year 3, and by euglycemic-hyperinsulinemic clamp at baseline only. The apolipoprotein concentrations were measured at baseline by a sandwich ELISA-based method. Results The two HDL subspecies demonstrated significantly opposite associations with insulin sensitivity at year 3 (p-heterogeneity=0.004). The highest quintile of HDL containing apoC-III was associated with a 1.2% reduction in insulin sensitivity (p-trend=0.02), while the highest quintile of HDL lacking apoC-III was associated with a 1.3% increase (p-trend=0.01), compared to the lowest quintile. No significant association was observed for total HDL, and VLDL and LDL containing apoC-III. ApoC-III contained in HDL was associated with a decrease in insulin sensitivity even more strongly than plasma total apoC-III. Conclusion Both HDL containing apoC-III and apoC-III in HDL adversely affect the beneficial properties of HDL on insulin response to glucose. Our results support the potential of HDL-associated apoC-III as a promising target for diabetes prevention and treatment.

scholarly journals No Independent Association of Circulating Fetuin-A with Insulin Sensitivity in Young Women

2020 ◽  
Vol 52 (11) ◽  
pp. 809-814
Author(s):  
Sabrina Reif ◽  
Sarah Moschko ◽  
Christina Gar ◽  
Uta Ferrari ◽  
Nina Hesse ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Metabolic Syndrome ◽  
Insulin Sensitivity ◽  
Young Women ◽  
Fat Content ◽  
Liver Fat ◽  
Liver Fat Content ◽  
Fetuin A ◽  
The Metabolic Syndrome ◽  
Independent Association

AbstractAnimal data link high circulating fetuin-A to low insulin sensitivity and observational studies identify the hepatokine as a marker of future incident type 2 diabetes mellitus in humans. However, a recent, well-powered Mendelian randomization study finds no causal role. We therefore tested in a deeply-phenotyped human cohort if circulating fetuin-A correlates independently with insulin sensitivity and how it relates to the metabolic syndrome and ectopic fat deposition. We analyzed data from 290 young women with and without recent gestational diabetes mellitus. We found that circulating fetuin-A correlates inversely with insulin sensitivity in univariate analyses, but that this correlation is lost after adjustment for markers of the metabolic syndrome and of fatty liver. Additionally, we investigated which fat compartment associates most strongly with circulating fetuin-A. In whole body MRI data from a subcohort of 152 women, this was liver fat content. We conclude that high circulating fetuin-A occurs as part of the metabolic syndrome in young women and associates most strongly with liver fat content. Its close link to the metabolic syndrome may also cause the inverse correlation of circulating fetuin-A with insulin sensitivity as we found no independent association.

The effect of high multivitamin diet during pregnancy on food intake and glucose metabolism in Wistar rat offspring fed low-vitamin diets post weaning

2011 ◽  
Vol 2 (5) ◽  
pp. 302-310 ◽  
Author(s):  
I. M. Y. Szeto ◽  
P. S. P. Huot ◽  
S. A. Reza-López ◽  
A. Jahan-mihan ◽  
G. H. Anderson
Keyword(s):  
Metabolic Syndrome ◽  
Food Intake ◽  
Insulin Response ◽  
Fold Increase ◽  
Wistar Rat ◽  
Oral Glucose ◽  
Glucose Response ◽  
Rat Offspring ◽  
Vitamin Content ◽  
The Metabolic Syndrome

Rat offspring born to dams fed a high multivitamin diet (HV) are shown to have increased risks of obesity and metabolic syndrome. We hypothesized that a low-vitamin postweaning diet would enhance these characteristics in offspring born to HV dams. During pregnancy, Wistar rats were fed the AIN-93G diet with or without a 10-fold increase in vitamin content. In Experiment 1, at weaning, males were fed the recommended diet (RV) or a diet with 1/3 the vitamin content (1/3 RV) for 12 weeks. In Experiment 2, males and females were fed the RV diet or 1/6 RV diet for 35 weeks. Body weight was measured on a weekly basis, food intake on a daily basis, and for 1 h after an overnight fast following glucose gavage at 6, 12 and 24 weeks. Blood glucose and insulin responses to an oral glucose load were measured at 30 weeks. Males from HV dams, compared with those from RV dams, gained more weight in Experiment 1 (+7%,P< 0.05) and Experiment 2 (+11%,P< 0.0001), along with higher glucose response (+33%,P< 0.05). The 1/6 RV pup diet led to lower weight gain in males (−16%,P< 0.0001) and females (−13%,P< 0.0005), and lower food intake in males (−9%,P< 0.01) independent of the gestational diet. Females on the 1/6 RV diet and from HV dams had higher 1 h food intake (+36%,P< 0.05) and lower insulin response (−25%,P< 0.05) compared with those from RV dams. Exposure of the offspring to low-vitamin diets did not amplify the expression of the metabolic syndrome observed in those born to dams fed an HV diet.

scholarly journals Different metabolic responses induced by long-term interdisciplinary therapy in obese adolescents related to ACE I/D polymorphism

2017 ◽  
Vol 18 (2) ◽  
pp. 147032031770345 ◽  
Author(s):  
Sandro S Almeida ◽  
Flavia C Corgosinho ◽  
Carlos EN Amorim ◽  
Marcos F Gregnani ◽  
Raquel MS Campos ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Low Density Lipoprotein ◽  
Insulin Response ◽  
Density Lipoprotein ◽  
Fat Free Mass ◽  
Interdisciplinary Therapy ◽  
Obese Adolescents ◽  
Cholesterol Levels ◽  
The Metabolic Syndrome

Introduction: The main purpose of the present study was to investigate whether I/D polymorphism of the ACE gene might affect metabolic changes related to the metabolic syndrome through a long-term interdisciplinary therapy in obese adolescents. Methods: In total, 125 obese adolescents who entered the interdisciplinary obesity programme were assigned to the following two subgroups: metabolic syndrome or non-metabolic syndrome. They were evaluated at baseline and after 1 year. Genomic DNA was extracted from circulating leukocytes. Results: Subjects with the II genotype in the non-metabolic syndrome group were only to increase their fat-free mass after therapy. Regarding lipid profile, subjects with ID and DD genotypes from both groups reduced their low-density lipoprotein cholesterol levels significantly. The metabolic parameters from the ID and DD genotypes of the non-metabolic syndrome group showed a significantly improved insulin response. Conclusion: In the present study, we showed that the ACE polymorphism was able to influence the fat-free mass in the I-carry allele in the non-metabolic syndrome group positively. In addition, the I-carry allele was able to improve the insulin resistance of the metabolic syndrome group significantly. These results suggest that the ACE I/D genotypes can influence, in different ways, the specific parameters of metabolism among obese adolescents submitted for long-term interdisciplinary therapy.

The Relation of Proinsulin, Insulin, and Proinsulin-to-Insulin Ratio to Insulin Sensitivity and Acute Insulin Response in Normoglycemic Subjects

Diabetes ◽  
1997 ◽  
Vol 46 (12) ◽  
pp. 1990-1995 ◽  
Author(s):  
Leena Mykkänen ◽  
Steven M Haffner ◽  
C Nick Hales ◽  
Tapani Rönnemaa ◽  
Markku Laakso
Keyword(s):  
Insulin Sensitivity ◽  
Insulin Response ◽  
Acute Insulin Response

scholarly journals Sucralose decreases insulin sensitivity in healthy subjects: a randomized controlled trial

2018 ◽  
Vol 108 (3) ◽  
pp. 485-491 ◽  
Author(s):  
Alonso Romo-Romo ◽  
Carlos A Aguilar-Salinas ◽  
Griselda X Brito-Córdova ◽  
Rita A Gómez-Díaz ◽  
Paloma Almeda-Valdes
Keyword(s):  
Randomized Controlled Trial ◽  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
Healthy Subjects ◽  
Controlled Trial ◽  
Insulin Response ◽  
Control Group ◽  
Acute Insulin Response ◽  
Randomized Controlled ◽  
Insulin Response To Glucose

ABSTRACT Background Recently, the absence of metabolic effects from nonnutritive sweeteners has been questioned. Objective The aim of this study was to evaluate the effects of sucralose consumption on glucose metabolism variables. Design We performed a randomized controlled trial involving healthy subjects without comorbidities and with a low habitual consumption of nonnutritive sweeteners (n = 33/group). Methods The intervention consisted of sucralose consumption as 15% of Acceptable Daily Intake every day for 14 d using commercial sachets. The control group followed the same procedures without any intervention. The glucose metabolism variables (insulin sensitivity, acute insulin response to glucose, disposition index, and glucose effectiveness) were evaluated by using a 3-h modified intravenous-glucose-tolerance test before and after the intervention period. Results Individuals assigned to sucralose consumption showed a significant decrease in insulin sensitivity with a median (IQR) percentage change of −17.7% (−29.3% to −1.0%) in comparison to −2.8% (−30.7% to 40.6%) in the control group (P= 0.04). An increased acute insulin response to glucose from 577 mU · L-1· min (350–1040 mU · L-1· min) to 671 mU · L-1· min (376–1010 mU · L-1· min) (P = 0.04) was observed in the sucralose group for participants with adequate adherence. Conclusions Sucralose may have effects on glucose metabolism, and our study complements findings previously reported in other trials. Further studies are needed to confirm the decrease in insulin sensitivity and to explore the mechanisms for these metabolic alterations. This trial was registered at www.clinicaltrials.gov as NCT02589002.

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