scholarly journals Insulin Resistance Is Unrelated to Circulating Retinol Binding Protein and Protein C Inhibitor

2007 ◽  
Vol 92 (11) ◽  
pp. 4306-4312 ◽  
Author(s):  
Miriam Promintzer ◽  
Michael Krebs ◽  
Jelena Todoric ◽  
Anton Luger ◽  
Martin Georg Bischof ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Mass Index ◽  
Insulin Sensitivity ◽  
Body Mass ◽  
Protein C ◽  
Binding Protein ◽  
Retinol Binding Protein ◽  
Insulin Resistant ◽  
Protein C Inhibitor ◽  
Active Antigen

Abstract Context: Recent data suggest that circulating retinol-binding protein (RBP) might be involved in the pathogenesis of insulin resistance. Moreover, protein C inhibitor (PCI), which specifically binds retinoic acid, was found to be increased in myocardial infarction survivors who are also insulin resistant. Objective: The objective of this study was to investigate the association of insulin resistance with RBP factors and PCI active antigen. Design and Setting: This was a clinical study. Patients: Nondiabetic humans with high (IS; n = 20, 14 females, six males, aged 47.2 ± 1.9 yr, body mass index 26 ± 1 kg/m2) and low (IR; n = 20, 14 females, six males, aged 45.5 ± 1.7 yr, body mass index 28 ± 1 kg/m2) insulin-stimulated glucose-disposal (M) participated in this study. Main Outcome Measures: M was measured by 2-h hyperinsulinemic (40 mU·min−1·m−2)-isoglycemic clamp tests. Measurements of RBP were performed using a nephelometric method and validated using quantitative Western blotting. Results: M (80–120 min) was higher in IS (10.9 ± 0.6 mg·min−1·kg−1) than IR (4.0 ± 0.2; P < 10−12). Fasting plasma RBP concentrations were comparable between IS and IR measured by both nephelometry (IS: 4.4 ± 0.3; IR: 4.6 ± 0.3 mg/dl, P = 0.6) and quantitative Western blot (IS 7.9 ± 0.5, IR 8.3 ± 0.6 mg/dl; P = 0.6). Fasting plasma PCI active antigen was similar in both groups. Plasma RBP and PCI were not significantly related to M. RBP was positively correlated with uric acid (r = 0.488, P = 0.003), triglycerides (r = 0.592, P < 0.001), prealbumin (r = 0.63, P < 0.0001), and vitamin A (r = 0.75, P < 10−6). Conclusions: Our data demonstrate that healthy, insulin-resistant humans do not show altered plasma retinol binding factors, such as RBP and PCI. Both do not significantly correlate with insulin sensitivity. Thus, our findings do not support the hypothesis of insulin sensitivity modulation by proteins involved in retinol transport.

scholarly journals Visceral Adipose Tissue was Associated with Increased Risk of Insulin Resistance in Lean Polycystic Ovarian Syndrome, Independent with Retinol Binding Protein-4

2020 ◽  
pp. 168-173
Author(s):  
Vita Silvana ◽  
Andon Hestiantoro ◽  
Muharam Natadisastra ◽  
Kanadi Sumapraja ◽  
Budi Wiweko
Keyword(s):  
Insulin Resistance ◽  
Body Mass Index ◽  
Adipose Tissue ◽  
Body Mass ◽  
Visceral Adipose Tissue ◽  
Binding Protein ◽  
Retinol Binding Protein ◽  
Receiver Operating Curve ◽  
Retinol Binding Protein 4 ◽  
Visceral Adipose

Objective: To determine whether visceral adipose tissue or serum RBP-4 were related with the risk increment of insulin resistance in normal BMI PCOS patients. Methods: This was a cross-sectional study conducted in normal body mass index PCOS patients at Yasmin Clinic, RSCM, Jakarta from July 2014 until March 2015. Diagnosis of PCOS was established using Rotterrdam (2003) criteria. Insulin resistance was confirmed by using ratio of HOMA-IR >1.4. Results: Among 40 subjects, 20 subjects (50%) belong insulin resistance group. Serum RBP-4 level was higher in insulin resistance group (p=0.06). After ROC analysis was conducted, area under curve for of serum RBP-4 was 69.9% (CI 95% -3754.77 - (186.60-7696.14, p=0.061)). Cut-off level of serum RBP-4 was 23814.5 ng/mL yielded sensitivity and specificity to a level of 60% and 60%, respectively. After logistic regression were analyzed, visceral adipose tissue demonstrated substantial association with the risk increment of insulin resistance in normal BMI PCOS patients. Conclusions: Visceral adipose tissue demonstrated substantial association with the risk increment of insulin resistance in normal BMI PCOS patients, independent with serum RBP-4 levels. Key words: body mass index, diagnosis, insulin resistance, PCOS, retinol binding protein-4   Abstrak Tujuan: Untuk menentukan apakah jaringan adiposa viseral atau serum RBP-4 berhubungan dengan peningkatan risiko resistensi insulin pada Sindrom Ovarium Polikistik dengan indeks masa tubuh normal. Metode: Studi potong lintang dilakukan pada subjek SOPK dengan IMT normal di Klinik Yasmin, RSCM, Jakarta sejak Juli 2014 sampai dengan Maret 2015. Penegakan diagnosis SOPK dilakukan dengan kriteria Rotterdam (2003). Resistensi insulin dikonfirmasi dengan pemeriksaan rasio HOMA-IR > 1.4 Hasil: Diantara 40 subjek, sebanyak 20 subjek (50%) mengalami resistensi insulin. Kadar serum RBP-4 lebih tinggi pada kelompok resistensi insulin (p=0.06). Setelah dilakukan analisis Receiver Operating Curve (ROC), serum RBP-4 memiliki Area Under the Curve  (AUC) sebesar 69.9% (IK 95% -3754.77 - (186.60-7696.14, p=0,061)). Titik potong kadar serum RBP-4 adalah 23814.5 ng/mL dengan sensitivitas dan spesifisitas masing-masing 60% dan 60%. Setelah dilakukan analisis regresi logistik, jaringan adiposa viseral menunjukan asosiasi yang kuat dengan terjadinya resistensi insulin pada pasien SOPK dengan IMT normal. Kesimpulan: Jaringan adiposa viseral menunjukan asosiasi yang kuat dengan terjadinya resistensi insulin pada SOPK dengan IMT normal, independen terhadap kadar serum RBP-4. Kata kunci: diagnosis, indeks masa tubuh, resistensi insulin, retinol binding protein-4, SOPK

scholarly journals Retinol-Binding Protein 4 and Its Relation to Insulin Resistance in Obese Children before and after Weight Loss

2008 ◽  
Vol 93 (6) ◽  
pp. 2287-2293 ◽  
Author(s):  
Thomas Reinehr ◽  
Birgit Stoffel-Wagner ◽  
Christian L. Roth
Keyword(s):  
Insulin Resistance ◽  
Body Mass Index ◽  
Weight Loss ◽  
Body Mass ◽  
Weight Status ◽  
Retinol Binding Protein ◽  
Homa Index ◽  
Obese Children ◽  
Retinol Binding Protein 4 ◽  
Lean Children

Abstract Context: There are limited and controversial data concerning the relationships between retinol-binding protein 4 (RBP4), weight status, and insulin resistance in obese humans and especially in children. Objective: Our objective was to study the longitudinal relationships among RBP4, insulin resistance and weight status in obese children. Design, Setting, and Patients: We conducted a 1-yr longitudinal follow-up study in a primary-care setting with 43 obese children (median age 10.8 yr) and 19 lean children of same the age and gender. Intervention: Our outpatient 1-yr intervention program was based on exercise, behavior, and nutrition therapy. Main Outcomes Measures: Changes of weight status (body mass index sd score), RBP4, molar RBP4/serum retinol (SR) ratio, insulin resistance index homeostasis model assessment (HOMA), and quantitative insulin sensitivity check index (QUICKI). Results: Obese children had significantly (P < 0.01) higher RBP4 concentrations and a higher RBP4/SR ratio compared with lean children. In multiple linear regression analyses adjusted to age, gender, and pubertal stage, RBP4 was significantly correlated to insulin and body mass index. Pubertal children demonstrated significantly decreased QUICKI and significantly increased HOMA index, insulin, and RBP4 concentrations compared with prepubertal children. Changes of RBP4 correlated significantly to changes of insulin (r = 0.29), HOMA index (r = 0.29), QUICKI (r = 0.22), and weight status (r = 0.31). Substantial weight loss in 25 children led to a significant (P < 0.001) decrease of RBP4, RBP4/SR, blood pressure, triglycerides, insulin, and HOMA index and an increase in QUICKI in contrast to the 18 children without substantial weight loss. Conclusion: RBP4 levels were related to weight status and insulin resistance in both cross-sectional and longitudinal analyses, suggesting a relationship between RBP4, obesity, and insulin resistance in children.

scholarly journals Ghrelin- and GH-induced insulin resistance: no association with retinol-binding protein-4

2013 ◽  
Vol 2 (2) ◽  
pp. 96-103 ◽  
Author(s):  
Esben Thyssen Vestergaard ◽  
Morten B Krag ◽  
Morten M Poulsen ◽  
Steen B Pedersen ◽  
Niels Moller ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Binding Protein ◽  
Human Subjects ◽  
Retinol Binding Protein ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Retinol Binding Protein 4 ◽  
Euglycemic Clamp ◽  
Hyperinsulinemic Euglycemic Clamp

ObjectiveSupraphysiological levels of ghrelin and GH induce insulin resistance. Serum levels of retinol-binding protein-4 (RBP4) correlate inversely with insulin sensitivity in patients with type 2 diabetes. We aimed to determine whether ghrelin and GH affect RBP4 levels in human subjects.Materials and methodsTo study GH-independent effects of ghrelin, seven hypopituitary men undergoing replacement therapy with GH and hydrocortisone were given ghrelin (5 pmol/kg per min) and saline infusions for 300 min in a randomized, double-blind, placebo-controlled, crossover design. Circulating RBP4 levels were measured at baseline and during a hyperinsulinemic–euglycemic clamp on both study days. To study the direct effects of GH, nine healthy men were treated with GH (2 mg at 2200 h) and placebo for 8 days in a randomized, double-blind, placebo-controlled, crossover study. Serum RBP4 levels were measured before and after treatment, and insulin sensitivity was measured by the hyperinsulinemic–euglycemic clamp technique.ResultsGhrelin acutely decreased peripheral insulin sensitivity. Serum RBP4 concentrations decreased in response to insulin infusion during the saline experiment (mg/l): 43.2±4.3 (baseline) vs 40.4±4.2 (clamp), P<0.001, but this effect was abrogated during ghrelin infusion (mg/l): 42.4±4.5 (baseline) vs 42.9±4.7 (clamp), P=0.73. In healthy subjects, serum RBP4 levels were not affected by GH administration (mg/l): 41.7±4.1 (GH) vs 43.8±4.6 (saline), P=0.09, although GH induced insulin resistance.Conclusionsi) Serum RBP4 concentrations decrease in response to hyperinsulinemia, ii) ghrelin abrogates the inhibitory effect of insulin on circulating RBP4 concentrations, and iii) ghrelin as well as GH acutely induces insulin resistance in skeletal muscle without significant changes in circulating RBP4 levels.

scholarly journals Responses of Serum Androgen and Insulin Resistance to Metformin and Pioglitazone in Obese, Insulin-Resistant Women with Polycystic Ovary Syndrome

2005 ◽  
Vol 90 (3) ◽  
pp. 1360-1365 ◽  
Author(s):  
C. Ortega-González ◽  
S. Luna ◽  
L. Hernández ◽  
G. Crespo ◽  
P. Aguayo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Mass Index ◽  
Body Weight ◽  
Insulin Sensitivity ◽  
Polycystic Ovary Syndrome ◽  
Body Mass ◽  
Polycystic Ovary ◽  
Obese Women ◽  
Ovary Syndrome ◽  
Waist To Hip Ratio

Severe insulin resistance is a key abnormality in obese women with polycystic ovary syndrome (PCOS). The purpose of this study was to evaluate whether pioglitazone decreases insulin resistance (IR) and hyperandrogenism to the same extent as metformin in obese women with PCOS who have not received any previous treatment. Fifty-two women with PCOS were randomly allocated to receive either pioglitazone (30 mg/d, n = 25) or metformin (850 mg three times daily, n = 27) and were assessed before and after 6 months. Body weight, body mass index, and waist to hip ratio increased significantly (P ≤ 0.05) after pioglitazone treatment but not after metformin treatment. Fasting serum insulin concentration (P &lt; 0.001 for both drugs) and the area under the insulin curve during a 2-h oral glucose tolerance test decreased after pioglitazone (P &lt; 0.002) or metformin (P &lt; 0.05) treatment. IR (homeostasis model of assessment-IR index) decreased and insulin sensitivity (elevation of the quantitative insulin sensitivity check index and the fasting glucose to insulin ratio) increased (P ≤ 0.008) after treatment with either drug. Hirsutism (P &lt; 0.05) and serum concentrations of free testosterone (P &lt; 0.02) and androstenedione (P &lt; 0.01) declined to a similar extent after treatment with the drugs. Treatment with pioglitazone or metformin was associated with the occurrence of pregnancy (n = 5 and n = 3, respectively). These results suggest that pioglitazone is as effective as metformin in improving insulin sensitivity and hyperandrogenism, despite an increase in body weight, body mass index, and the waist to hip ratio associated with pioglitazone.

Abstract 17025: Myeloid Rage Protects From Insulin Resistance in Mice Fed High Fat Diet

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Lakshmi Arivazhagan ◽  
Henry Ruiz ◽  
Robin Wilson ◽  
Laura Frye ◽  
Ravichandran Ramasamy ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Body Mass ◽  
High Fat Diet ◽  
Whole Body ◽  
High Fat ◽  
Double Knockout ◽  
Euglycemic Clamp ◽  
Insulin Resistant ◽  
Hyperinsulinemic Euglycemic Clamp

Introduction: Obesity is a major global health problem, with over one third of adults in the US classified as obese. Obesity often leads to a state of insulin resistance (IR), type 2 diabetes (T2D) and its complications. We previously showed that the receptor for advanced glycation end products (RAGE) and its ligands contribute to the pathogenesis of obesity and IR, as whole body and adipocyte-specific Ager (gene encoding RAGE) deleted mice fed a high fat diet (HFD) were significantly protected from weight gain and IR. Here, we hypothesize that myeloid RAGE contributed to IR upon HFD feeding. Methods: We generated mice with myeloid-specific (MDR) LyzMCre(+/+).Ager flox/flox and adipocyte and myeloid-specific (Double Knockouts) AdipoQCre(-/+)LyzMCre(+/+).Ager flox/flox deletion of Ager and LysMCre mice were used as control. Mice were fed either standard chow (LFD) or HFD (60% kcal/fat) for 3 months starting at age 6 weeks. Mice were assessed for body mass and composition, glucose and insulin sensitivity and whole body glucose metabolism by hyperinsulinemic-euglycemic clamp studies. Results: After 3 months HFD, there were no significant differences in body mass, body composition, food intake, energy expenditure and physical activity of the MDR mice vs. controls. Similar findings were observed in mice fed LFD. However, surprisingly, in HFD-fed mice, insulin tolerance tests and hyperinsulinemic-euglycemic clamp studies showed decreased insulin sensitivity and insulin action in the MDR vs. control mice, indicating that the MDR mice were more insulin resistant. The Double Knockout (myeloid/adipocyte) Cre (+) mice were more glucose tolerant and insulin sensitive compared to MDR mice, showing that deletion of Ager in the adipocytes rescued the adverse effects of Ager deletion in myeloid cells. Conclusions: Myeloid Ager protects from IR in mice fed HFD. Furthermore, in MDR mice, concomitant adipocyte-specific deletion of Ager rescues these mice from IR and, at the same time, reduces HFD-induced adiposity. The mechanisms underlying these findings are under active investigation.

scholarly journals Modulation of Adiponectin and Leptin during Refeeding of Female Anorexia Nervosa Patients

2007 ◽  
Vol 92 (5) ◽  
pp. 1843-1847 ◽  
Author(s):  
Dalit Modan-Moses ◽  
Daniel Stein ◽  
Clara Pariente ◽  
Amit Yaroslavsky ◽  
Anka Ram ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Mass Index ◽  
Anorexia Nervosa ◽  
Insulin Sensitivity ◽  
Body Mass ◽  
Female Adolescent ◽  
Model Assessment ◽  
Homeostasis Model Assessment ◽  
Hmw Adiponectin ◽  
Total Adiponectin

Abstract Context: Several studies assessed adiponectin levels in anorexia nervosa (AN) patients, however, data regarding the dynamics of changes in adiponectin levels during refeeding of these patients is limited and contradicting. Objective: Our objective was to assess adiponectin levels and the distribution of its different isoforms in AN patients before and after long-term refeeding, and to relate them to alterations in body mass index, leptin, insulin sensitivity, and additional endocrine parameters. Design, Setting, and Participants: We conducted a longitudinal controlled study of 38 female adolescent malnourished AN inpatients, with 13 young, lean, healthy women serving as controls. Blood samples were obtained upon admission and thereafter at 1, 3, and 5 months (at target weight). Main Outcome Measures: Changes in body mass index, leptin, adiponectin, insulin sensitivity, and adiponectin multimeric forms were measured. Results: At admission, leptin levels of AN patients were significantly lower, whereas insulin sensitivity (assessed by homeostasis model assessment-insulin resistance), adiponectin levels, and the ratio of high molecular weight (HMW) adiponectin to total adiponectin were significantly higher compared with controls. During weight recovery, leptin levels and homeostasis model assessment-insulin resistance increased significantly, whereas adiponectin and HMW adiponectin/total adiponectin ratio decreased significantly, to levels similar to controls. An initial increase in adiponectin levels was observed after 1 month of refeeding. There was no correlation between adiponectin and either T4 or cortisol levels. Conclusions: Our study demonstrates hyperadiponectinemia, increased adiponectin HMW isoform, and increased insulin sensitivity in adolescent AN female patients and reversal of these findings with weight rehabilitation. We hypothesize that increased adiponectin levels may have a protective role in maintaining energy homeostasis during extreme malnourishment.

scholarly journals Relation among Left Ventricular Mass, Insulin Resistance, and Blood Pressure in Nonobese Subjects1

1998 ◽  
Vol 83 (12) ◽  
pp. 4284-4288
Author(s):  
Robert A. Phillips ◽  
Lawrence R. Krakoff ◽  
Andrea Dunaif ◽  
Diane T. Finegood ◽  
Richard Gorlin ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Body Mass Index ◽  
Insulin Sensitivity ◽  
Body Mass ◽  
Tolerance Test ◽  
Left Ventricular ◽  
Sensitivity Index ◽  
Consecutive Series ◽  
Arterial Blood

Because left ventricular (LV) mass (LVM) is a powerful predictor of future cardiovascular events, it is important to identify hemodynamic and nonhemodynamic factors that increase LVM. We studied the separate contribution to LVM of daily arterial blood pressure (BP) and insulin resistance in a consecutive series of 29 (mean ± sd age, 43 ± 13 yr) nonobese (body mass index, 24 ± 1.8 kg/m2), nondiabetic, glucose-tolerant subjects with untreated borderline or mild hypertension. The insulin sensitivity index (SI) was quantitatively determined from the frequently sampled iv glucose tolerance test. BP was characterized by ambulatory 24-h BP monitoring, and LVM index (LVMI) was determined by two-dimensional directed M-mode echocardiography. LVMI was directly related to 24-h mean BP (r = 0.47; P = 0.01). LMVI was also significantly related to SI (r = −0.43; P = 0.02). In this nonobese group, neither LVMI nor SI was related to body mass index or age. After adjustment for the influence of BP on LVMI, a significant relation remained between LVMI and SI (P &lt; 0.05). We conclude that in nonobese subjects with high normal BP, insulin sensitivity is related to LVM independently of BP and may be an important modulator of LV growth. In addition to a reduction of arterial BP, optimal prevention of LV hypertrophy in hypertensives may require improved insulin sensitivity.

scholarly journals The Effects of Reduction Mammaplasty on Serum Leptin Levels and Insulin Resistance

2015 ◽  
Vol 2015 ◽  
pp. 1-5
Author(s):  
Hakan Uzun ◽  
Ozan Bitik ◽  
Yahya Baltu ◽  
Çiğdem Sönmez ◽  
Ayşegül Öztürk Kaymak
Keyword(s):  
Insulin Resistance ◽  
Body Mass Index ◽  
Insulin Sensitivity ◽  
Body Mass ◽  
Reduction Mammaplasty ◽  
The Body ◽  
Fatty Tissue ◽  
Model Assessment ◽  
Homeostasis Model Assessment ◽  
Serum Leptin

Background.The reduction mammaplasty has been a well-executed and known procedure in which considerable amount of fatty tissue is removed from the body. The authors aimed to show the effects of the reduction mammaplasty on serum leptin levels and insulin resistance.Methods.42 obese female patients who had gigantomastia were operated on. We recorded patients’ demographic and preoperative data, including age, weight, height, and body mass index. Fasting serum leptin, glucose, and insulin levels were noted. Homeostasis model assessment scores were calculated. At the postoperative 8th week, patients were reevaluated in terms of above parameters assessing the presence of any difference.Results.Serum leptin levels were decreased postoperatively and the decrease was statistically significant. We were able to show a decrease in homeostasis model assessment score, which indicated an increase in insulin sensitivity, and this change was statistically significant. A significant correlation between body mass index and leptin change was found postoperatively.Conclusion.Reduction mammaplasty is not solely an aesthetic procedure but it decreases serum leptin levels and increases insulin sensitivity, which may help obese women to reduce their cardiovascular risk.

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