scholarly journals Predicting Skeletal Muscle and Whole-Body Insulin Sensitivity Using NMR-Metabolomic Profiling

2020 ◽  
Vol 4 (4) ◽  
Author(s):  
Riku Klén ◽  
Miikka-Juhani Honka ◽  
Jarna C Hannukainen ◽  
Ville Huovinen ◽  
Marco Bucci ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Cross Sectional Study ◽  
Whole Body ◽  
Sensitivity Index ◽  
Model Assessment ◽  
Serum Samples ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Cross Sectional

Abstract Purpose Abnormal lipoprotein and amino acid profiles are associated with insulin resistance and may help to identify this condition. The aim of this study was to create models estimating skeletal muscle and whole-body insulin sensitivity using fasting metabolite profiles and common clinical and laboratory measures. Material and Methods The cross-sectional study population included 259 subjects with normal or impaired fasting glucose or type 2 diabetes in whom skeletal muscle and whole-body insulin sensitivity (M-value) were measured during euglycemic hyperinsulinemic clamp. Muscle glucose uptake (GU) was measured directly using [18F]FDG-PET. Serum metabolites were measured using nuclear magnetic resonance (NMR) spectroscopy. We used linear regression to build the models for the muscle GU (Muscle-insulin sensitivity index [ISI]) and M-value (whole-body [WB]-ISI). The models were created and tested using randomly selected training (n = 173) and test groups (n = 86). The models were compared to common fasting indices of insulin sensitivity, homeostatic model assessment—insulin resistance (HOMA-IR) and the revised quantitative insulin sensitivity check index (QUICKI). Results WB-ISI had higher correlation with actual M-value than HOMA-IR or revised QUICKI (ρ = 0.83 vs −0.67 and 0.66; P < 0.05 for both comparisons), whereas the correlation of Muscle-ISI with the actual skeletal muscle GU was not significantly stronger than HOMA-IR’s or revised QUICKI’s (ρ = 0.67 vs −0.58 and 0.59; both nonsignificant) in the test dataset. Conclusion Muscle-ISI and WB-ISI based on NMR-metabolomics and common laboratory measurements from fasting serum samples and basic anthropometrics are promising rapid and inexpensive tools for determining insulin sensitivity in at-risk individuals.

Analysis of candidate genes in Polish families with obesity

2004 ◽  
Vol 42 (5) ◽  
Author(s):  
Malgorzata Malczewska-Malec ◽  
Iwona Wybranska ◽  
Iwona Leszczynska-Golabek ◽  
Lukasz Partyka ◽  
Jadwiga Hartwich ◽  
...  
Keyword(s):  
Risk Factors ◽  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Body Mass ◽  
Tolerance Test ◽  
Whole Body ◽  
Oral Glucose ◽  
Sensitivity Index ◽  
Model Assessment ◽  
The Metabolic Syndrome

AbstractThis study analyzes the relationship between risk factors related to overweight/obesity, insulin resistance, lipid tolerance, hypertension, endothelial function and genetic polymorphisms associated with: i) appetite regulation (leptin, melanocortin-3-receptor (MCR-3), dopamine receptor 2 (D2R)); ii) adipocyte differentiation and insulin sensitivity (peroxisome proliferator-activated receptor-γThe 122 members of 40 obese Caucasian families from southern Poland participated in the study. The genotypes were analyzed by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) or by direct sequencing. Phenotypes related to obesity (body mass index (BMI), fat/lean body mass composition, waist-to-hip ratio (WHR)), fasting lipids, glucose, leptin and insulin, as well as insulin during oral glucose tolerance test (OGTT) (4 points within 2 hours) and during oral lipid tolerance test (OLTT) (5 points within 8 hours) were assessed. The insulin sensitivity indexes: homeostasis model assessment of insulin resistance, whole body insulin sensitivity index, hepatic insulin sensitivity and early secretory response to an oral glucose load (HOMA-IR, ISI-COMP, ISI-HOMA and DELTA) were calculated.The single gene mutations such as CWe conclude that the polymorphisms we investigated were weakly correlated with obesity but significantly modified the risk factors of the metabolic syndrome.

scholarly journals PSVIII-40 Late-Breaking Abstract: Variability in body composition is associated with insulin sensitivity in growing-finishing pigs

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 350-351
Author(s):  
Hector H Salgado ◽  
Aline Remus ◽  
Marie-Pierre Letourneau-Montminy ◽  
Candido Pomar
Keyword(s):  
Insulin Resistance ◽  
Body Composition ◽  
Insulin Sensitivity ◽  
Growing Pigs ◽  
The Body ◽  
Whole Body ◽  
Oral Glucose ◽  
Sensitivity Index ◽  
Model Assessment ◽  
Glucose Ingestion

Abstract Growing pigs’ body composition variation can be associated with differences in insulin sensitivity given the insulin anabolic effect on protein and lipid synthesis. The objective of this study was to elucidate this association by relating the individual insulin response to the oral glucose tolerance test (OGTT) with the body composition of growing pigs. Thirty 95 kg jugular vein catheterized pigs received an oral dose of 1.75 g of glucose/kg of BW after 18 hours of fasting. Blood samples were collected at -20, -10, 5, 10, 15, 20, 25, 30, 45, 60, 90, 120, 150, 180, 210, 240, 300 and 360 min following glucose ingestion. Insulin sensitivity indexes were calculated and analyzed. Body lipids (LB, %) and protein (PB, %) composition were estimated by dual X-ray densitometry. Association between body composition and insulin sensitivity were studied by using partial least squares and correlations. Average LB and PB were 19.7% (CV = 7.6 %) and 16.2% (CV = 2.2%), respectively. Basal insulin blood concentration and area-under-the-curve (AUC) CV (51.9 % and 26.9 %, respectively) were larger than those for basal glucose and AUC (5.52 and 5.48 %, respectively). Additionally, insulin sensitivity (%S), steady-state beta cell function (%B), and insulin resistance (HOMA-IR) estimated with the Homeostasis Model Assessment (HOMA 2) and whole-body insulin sensitivity index (ISI) were highly variable between pigs which CV ranged from 30.1 % to 54.5 %. These results can indicate an early stage of insulin resistance in an important part of the studied pig population. LB and PB were affected by insulin sensitivity indexes (P < 0.05) which accounted, respectively, for 48% and 44% of the observed variation. In conclusion, lower insulin sensitivity was associated with higher body fat in growing pigs raised under similar conditions.

scholarly journals The PERSonalized Glucose Optimization Through Nutritional Intervention (PERSON) Study: Rationale, Design and Preliminary Screening Results

2021 ◽  
Vol 8 ◽  
Author(s):  
Anouk Gijbels ◽  
Inez Trouwborst ◽  
Kelly M. Jardon ◽  
Gabby B. Hul ◽  
Els Siebelink ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
Dietary Intervention ◽  
Hepatic Insulin Resistance ◽  
Whole Body ◽  
Primary Study ◽  
Sensitivity Index ◽  
Tissue Specific

Background: It is well-established that the etiology of type 2 diabetes differs between individuals. Insulin resistance (IR) may develop in different tissues, but the severity of IR may differ in key metabolic organs such as the liver and skeletal muscle. Recent evidence suggests that these distinct tissue-specific IR phenotypes may also respond differentially to dietary macronutrient composition with respect to improvements in glucose metabolism.Objective: The main objective of the PERSON study is to investigate the effects of an optimal vs. suboptimal dietary macronutrient intervention according to tissue-specific IR phenotype on glucose metabolism and other health outcomes.Methods: In total, 240 overweight/obese (BMI 25 – 40 kg/m2) men and women (age 40 – 75 years) with either skeletal muscle insulin resistance (MIR) or liver insulin resistance (LIR) will participate in a two-center, randomized, double-blind, parallel, 12-week dietary intervention study. At screening, participants undergo a 7-point oral glucose tolerance test (OGTT) to determine the hepatic insulin resistance index (HIRI) and muscle insulin sensitivity index (MISI), classifying each participant as either “No MIR/LIR,” “MIR,” “LIR,” or “combined MIR/LIR.” Individuals with MIR or LIR are randomized to follow one of two isocaloric diets varying in macronutrient content and quality, that is hypothesized to be either an optimal or suboptimal diet, depending on their tissue-specific IR phenotype (MIR/LIR). Extensive measurements in a controlled laboratory setting as well as phenotyping in daily life are performed before and after the intervention. The primary study outcome is the difference in change in disposition index, which is the product of insulin sensitivity and first-phase insulin secretion, between participants who received their hypothesized optimal or suboptimal diet.Discussion: The PERSON study is one of the first randomized clinical trials in the field of precision nutrition to test effects of a more personalized dietary intervention based on IR phenotype. The results of the PERSON study will contribute knowledge on the effectiveness of targeted nutritional strategies to the emerging field of precision nutrition, and improve our understanding of the complex pathophysiology of whole body and tissue-specific IR.Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT03708419, clinicaltrials.gov as NCT03708419.

scholarly journals Modification and Validation of the Triglyceride-to–HDL Cholesterol Ratio as a Surrogate of Insulin Sensitivity in White Juveniles and Adults without Diabetes Mellitus: The Single Point Insulin Sensitivity Estimator (SPISE)

2016 ◽  
Vol 62 (9) ◽  
pp. 1211-1219 ◽  
Author(s):  
Katharina Paulmichl ◽  
Mensud Hatunic ◽  
Kurt Højlund ◽  
Aleksandra Jotic ◽  
Michael Krebs ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Single Point ◽  
Hdl Cholesterol ◽  
Whole Body ◽  
Oral Glucose ◽  
Sensitivity Index ◽  
Model Assessment ◽  
Blood Draw ◽  
Sensitivity Indices

Abstract BACKGROUND The triglyceride-to–HDL cholesterol (TG/HDL-C) ratio was introduced as a tool to estimate insulin resistance, because circulating lipid measurements are available in routine settings. Insulin, C-peptide, and free fatty acids are components of other insulin-sensitivity indices but their measurement is expensive. Easier and more affordable tools are of interest for both pediatric and adult patients. METHODS Study participants from the Relationship Between Insulin Sensitivity and Cardiovascular Disease [43.9 (8.3) years, n = 1260] as well as the Beta-Cell Function in Juvenile Diabetes and Obesity study cohorts [15 (1.9) years, n = 29] underwent oral-glucose-tolerance tests and euglycemic clamp tests for estimation of whole-body insulin sensitivity and calculation of insulin sensitivity indices. To refine the TG/HDL ratio, mathematical modeling was applied including body mass index (BMI), fasting TG, and HDL cholesterol and compared to the clamp-derived M-value as an estimate of insulin sensitivity. Each modeling result was scored by identifying insulin resistance and correlation coefficient. The Single Point Insulin Sensitivity Estimator (SPISE) was compared to traditional insulin sensitivity indices using area under the ROC curve (aROC) analysis and χ2 test. RESULTS The novel formula for SPISE was computed as follows: SPISE = 600 × HDL-C0.185/(TG0.2 × BMI1.338), with fasting HDL-C (mg/dL), fasting TG concentrations (mg/dL), and BMI (kg/m2). A cutoff value of 6.61 corresponds to an M-value smaller than 4.7 mg · kg−1 · min−1 (aROC, M:0.797). SPISE showed a significantly better aROC than the TG/HDL-C ratio. SPISE aROC was comparable to the Matsuda ISI (insulin sensitivity index) and equal to the QUICKI (quantitative insulin sensitivity check index) and HOMA-IR (homeostasis model assessment–insulin resistance) when calculated with M-values. CONCLUSIONS The SPISE seems well suited to surrogate whole-body insulin sensitivity from inexpensive fasting single-point blood draw and BMI in white adolescents and adults.

scholarly journals Circulating vaspin is unrelated to insulin sensitivity in a cohort of nondiabetic humans

2010 ◽  
Vol 162 (3) ◽  
pp. 507-513 ◽  
Author(s):  
Christian von Loeffelholz ◽  
Matthias Möhlig ◽  
Ayman M Arafat ◽  
Frank Isken ◽  
Joachim Spranger ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Sexual Dimorphism ◽  
Insulin Sensitivity ◽  
Intervention Study ◽  
Cross Sectional Study ◽  
Model Assessment ◽  
Homeostasis Model Assessment ◽  
Short Term ◽  
Cross Sectional ◽  
Glucose Tolerance Status

ObjectiveTo study the association of vaspin with glucose metabolism.DesignCross-sectional and intervention study.Subjects and methodsThe association of serum vaspin with metabolic and anthropometric characteristics was investigated in 108 volunteers. Euglycemic–hyperinsulinemic clamps (EHC) were performed in 83 of the participants. Changes of circulating vaspin levels were additionally studied in a crossover study using 300 min EHC with lipid versus saline infusion (n=10).ResultsNeither glucose tolerance status nor insulin sensitivity, both as measured using EHCs and using homeostasis model assessment for insulin resistance (HOMA-IR), was significantly associated with serum vaspin in the cross-sectional study. Furthermore, there was no effect of short-term lipid-induced insulin resistance due to a 300 min intravenous lipid challenge on circulating vaspin. However, circulating vaspin levels were significantly elevated in women using oral contraceptives (OC), both compared to women without OC intake (1.17±0.26 vs 0.52±0.09 ng/ml, P=0.02) and males (1.17±0.26 vs 0.29±0.04 ng/ml, P=0.01). After exclusion of OC using females and stratification according to body mass index (BMI), a significant sexual dimorphism in subjects with a BMI <25 kg/m2 was observed (males 0.21±0.04 ng/ml versus females 0.70±0.16 ng/ml, P=0.009).ConclusionOur results support the existence of a sexual dimorphism regarding circulating vaspin. The lack of an association of serum vaspin with HOMA-IR and M value indicates, however, no major role for vaspin concerning insulin sensitivity in nondiabetic humans.

scholarly journals Insulin Resistance is Associated with Central Pain in Patients with Fibromyalgia

2021 ◽  
pp. 175-184
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Hemoglobin A1c ◽  
Laboratory Data ◽  
Cross Sectional Study ◽  
Central Pain ◽  
Model Assessment ◽  
Sectional Study ◽  
Cross Sectional ◽  
Hba1c Levels

BACKGROUND: Insulin resistance (IR) is a pathological condition in which cells fail to respond normally to insulin. IR has been associated with multiple conditions, including chronic pain. Fibromyalgia (FM) is one of the common generalized chronic painful conditions with an incidence rate affecting 3% to 6% of the population. Substantial interest and investigation into FM continue to generate many hypotheses. The relationship between IR and FM has not been explored. IR is known to cause abnormalities in the cerebral microvasculature, leading to focal hypoperfusion. IR also has been shown to cause cognitive impairment in FM patients, as in parkinsonism. As demonstrated by advanced imaging methods, similar brain perfusion abnormalities occur in the brain of patients with FM as with IR. OBJECTIVES: To determine the potential association between FM and IR. SETTING: Subspecialty pain medicine clinics. STUDY DESIGN: Observational cross-sectional study. METHODS: Laboratory data was extracted through a retrospective review of medical records from patients who had met the American College of Rheumatology (ACR) criteria for FM. The Hemoglobin A1c (HbA1c) values from 33 patients with FM were compared with the means of the glycated HbA1c levels of 2 control populations. In addition, established indices of IR [Quantitative Insulin Sensitivity Check Index (QUICKI) and the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)] were calculated in a subgroup of patients in whom the analytes necessary for these calculations were available. To assess for confounding factors, the associations between HbA1c, QUICKI, HOMA-IR, fasting insulin levels, and glucose, after controlling for age, were explored by multiple analyses of variance with relation to gender and ethnicity. RESULTS: We found an association between IR and FM that was independent of age, gender, and ethnicity. We found that patients with FM belong to a distinct population that can be segregated from the control groups by their HbA1c levels, a surrogate marker of IR. This was demonstrated by analyzing the data after introducing an age correction into a linear regression model. This strategy showed significant differences between patients with FM and control subjects (P < 0.0001 and P = 0.0002, for 2 separate control populations, respectively). A subgroup analysis using the QUICKI and HOMA-IR showed that all patients with FM in this subgroup (100%) exhibited laboratory abnormalities pointing to IR. LIMITATIONS: Small observational cross-sectional study. There are also intrinsic limitations that are attributed to cross-sectional studies. CONCLUSION: The association demonstrated in this study warrant further investigation, including the pursuit of randomized, double-blind clinical trials to determine the effect of improving insulin sensitivity in FM related pain scores. Such studies could unveil a potential pathogenetic relationship between FM, central pain, and IR. Based on these initial findings, we present the hypothesis that IR may underlie pathological mechanisms leading to central pain. If confirmed, this may lead to a paradigm shift in the management of central pain. KEY WORDS: Fibromyalgia, insulin resistance, chronic widespread pain, hemoglobin A1c

scholarly journals A Chinese Herbal Decoction, Dang Gui Bu Xue Tang, Prepared from Radix Astragali and RadixAngelicae sinensis, Ameliorates Insulin Resistance Induced by A High-Fructose Diet in Rats

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
I-Min Liu ◽  
Thing-Fong Tzeng ◽  
Shorong-Shii Liou
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Oral Administration ◽  
Glucose Transporter ◽  
Plasma Lipid ◽  
Whole Body ◽  
Oral Glucose ◽  
Sensitivity Index ◽  
Model Assessment ◽  
Radix Astragali

Dang Gui Bu Xue Tang (DBT), a Chinese medicinal decoction contains RadixAngelicae sinensis(Danggui) and Radix Astragali (Huangqi) at a ratio of 1 : 5, is used commonly for treating women's ailments. This study was conducted to explore the effects of this preparation on insulin resistance in rats fed with 6-week diet containing 60% fructose. Similar to the action of rosiglitazone (4 mg kg-1per day by an oral administration), repeated oral administration of DBT (2.5 g kg-1per day) for 14 days was found to significantly alleviate the hyperglycemia but made no influence on plasma lipid profiles nor weight gain in fructose chow-fed rats. Also, the higher degree of insulin resistance as measured by homeostasis model assessment of basal insulin resistance in fructose chow-fed rats was significantly decreased by repeated DBT treatment. DBT displays the characteristic of rosiglitazone by increasing the whole-body insulin sensitivity in fructose chow-fed rats after 2-week treatment, as evidenced by the marked elevation of composite whole-body insulin sensitivity index during the oral glucose tolerance test. DBT improves insulin sensitivity through increased post-receptor insulin signaling mediated by enhancements in insulin receptor substrate-1-associated phosphatidylinositol 3-kinase step and glucose transporter subtype 4 translocation in soleus muscles of animals exhibiting insulin resistance. DBT is therefore proposed as potentially useful adjuvant therapy for patients with insulin resistance and/or the patients who wish to increase insulin sensitivity.

Investigating the relationship between insulin resistance and adipose tissue in a randomized Tehrani population

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Jalaledin Mirzay Razzaz ◽  
Hossein Moameri ◽  
Zahra Akbarzadeh ◽  
Mohammad Ariya ◽  
Seyed ali Hosseini ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Body Fat ◽  
Odds Ratio ◽  
Cross Sectional Study ◽  
Model Assessment ◽  
Fasting Insulin ◽  
Cross Sectional ◽  
Body Fat Percent ◽  
The Relationship

Abstract Objectives Insulin resistance is the most common metabolic change associated with obesity. The present study aimed to investigate the relationship between insulin resistance and body composition especially adipose tissue in a randomized Tehrani population. Methods This study used data of 2,160 individuals registered in a cross-sectional study on were randomly selected from among subjects who were referred to nutrition counseling clinic in Tehran, from April 2016 to September 2017. Insulin resistance was calculated by homeostasis model assessment formula. The odds ratio (95% CI) was calculated using logistic regression models. Results The mean age of the men was 39 (±10) and women were 41 (±11) (the age ranged from 20 to 50 years). The risk of increased HOMA-IR was 1.03 (95% CI: 1.01–1.04) for an increase in one percent of Body fat, and 1.03 (95% CI: 1.00–1.05) for an increase in one percent of Trunk fat. Moreover, the odds ratio of FBS for an increase in one unit of Body fat percent and Trunk fat percent increased by 1.05 (adjusted odds ratio [95% CI: 1.03, 1.06]) and 1.05 (95% CI: 1.02, 1.08). Also, the risk of increased Fasting Insulin was 1.05 (95% CI: 1.03–1.07) for an increase in one unit of Body fat percent, and 1.05 (95% CI: 1.02–1.08) for an increase in one unit of Trunk fat percent. Conclusions The findings of the present study showed that there was a significant relationship between HOMA-IR, Fasting blood sugar, Fasting Insulin, and 2 h Insulin with percent of Body fat, percent of Trunk fat.

scholarly journals Inverse association between soya food consumption and insulin resistance in Japanese adults

2014 ◽  
Vol 18 (11) ◽  
pp. 2031-2040 ◽  
Author(s):  
Mariko Nakamoto ◽  
Hirokazu Uemura ◽  
Tohru Sakai ◽  
Sakurako Katsuura-Kamano ◽  
Miwa Yamaguchi ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Rural Communities ◽  
Food Consumption ◽  
Dose Response ◽  
Cross Sectional Study ◽  
Soya Protein ◽  
Model Assessment ◽  
Inverse Association ◽  
Cross Sectional ◽  
Soya Product

AbstractObjectiveThe purpose of the present study was to examine the association between soya food consumption and insulin resistance using baseline data of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study in Tokushima, Japan.DesignThis cross-sectional study included 1274 subjects, aged 34–70 years at baseline, living in Tokushima Prefecture between 2008 and 2013. Fasting blood samples were collected and information on lifestyle characteristics including soya food intake and medical history were obtained using a structured self-administered questionnaire. The homeostasis model assessment of insulin resistance (HOMA-IR) was measured and those with HOMA-IR≥2·5 were defined as having insulin resistance. Multiple logistic regression models were used to analyse the association between soya product intake and the prevalence of insulin resistance.SettingRural communities located in Tokushima Prefecture, Japan, between 2008 and 2013.SubjectsA total of 1148 adults (565 men and 583 women), aged 34–70 years.ResultsThe frequency of intake of miso soup, total non-fried soya products and total soya products showed significant inverse dose–response relationships with insulin resistance, after adjustments for potential confounders. When soya product intake was calculated as soya protein and isoflavone, the odds ratios of insulin resistance decreased significantly as the estimated intake of soya protein increased. Furthermore, significant inverse dose–response relationships were observed for total non-fried soya products and total soya products, after adjustment for total vegetable or total fibre consumption.ConclusionsThe present results indicate that the intake of soya products and non-fried soya products is associated with reduced insulin resistance in the Japanese population.

scholarly journals Reduced Oxygenation in Human Obese Adipose Tissue Is Associated with Impaired Insulin Suppression of Lipolysis

2010 ◽  
Vol 95 (8) ◽  
pp. 4052-4055 ◽  
Author(s):  
Magdalena Pasarica ◽  
Jennifer Rood ◽  
Eric Ravussin ◽  
Jean-Marc Schwarz ◽  
Steven R. Smith ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Capillary Density ◽  
Cross Sectional Study ◽  
Fat Cell ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Cross Sectional ◽  
Clinical Research Center ◽  
Endothelial Growth Factor

Context: Adipose tissue in obese individuals is characterized by reduced capillary density and reduced oxygenation. Objective: Our objective was to test whether hypoxia is associated with reduced antilipolytic effect of insulin. Participants, Design, and Setting: Twenty-one lean and obese individuals participated in this cross-sectional study at a university-based clinical research center. Intervention: In all subjects, in situ adipose tissue (AT) oxygenation [AT oxygen partial pressure (ATpO2)] was measured with a Clark electrode, insulin sensitivity as well as basal and insulin-suppressed lipolysis (continuous infusion of (2H5)glycerol) were measured during a euglycemic-hyperinsulinemic clamp, and abdominal sc AT biopsies were collected to assess fat cell size (Coulter counting of osmium-fixed cells), capillary density (by staining of histological sections), and gene expression (by quantitative RT-PCR). Main Outcome Measure: In situ ATpO2 was evaluated. Results: The ability of insulin to suppress lipolysis (percent) was positively correlated with insulin sensitivity (r = 0.43; P &lt; 0.05), ATpO2 (r = 0.44; P &lt; 0.05), vascular endothelial growth factor mRNA (r = 0.73; P &lt; 0.01), and capillary density (r = 0.75; P &lt; 0.01). Conclusion: These results indicate that low capillary density and ATpO2 in AT are potentially upstream causes of AT dysfunction.

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