Translational Medical Research Commons^™

Retraction Note: Obesity-Induced Adipokine Imbalance Impairs Mouse Pulmonary Vascular Endothelial Function And Primes The Lung For Injury, Dilip Shah, Freddy Romero, Michelle Duong, Nadan Wang, Bishnuhari Paudyal, Benjamin T Suratt, Caleb B Kallen, Jianxin Sun, Ying Zhu, Kenneth Walsh, Ross Summer

Center for Translational Medicine Faculty Papers

The Authors have retracted this Article. Afer publication of this Article, concerns have been raised about irregularities in the western blot data. In particular, the following bands appear to be duplicated: – Fig. 1e HFD/p-Src lane 1 and 3; – Fig. 4c NCD/Ve-cadherin lane 1 and 3 – Fig. 5e HFD+APN/ICAM-1 lane 1 and 2 – Fig. 5f HFD/beta-catenin lane 2 and HFD+APN/beta-catenin lane 1 – Fig. S1d HFD/beta-catenin all lanes – Fig. S4c NCD/beta-catenin lane 1 and 3. Additionally, the beta-catenin subpanel in Fig. 5f was subsequently reused in another study [1] and described as showing GRP87. Te Authors …

European Union Food Law Update, Emilie Majster

Journal of Food Law & Policy

Nutrition is increasingly important in both the European Union (EU) and in global food-related policy making. Governments, which up until recently have focused on regulating food products based on a food safety perspective, are now turning to regulate from a nutritional aspect.

Human Regulatory T Cells Control Inflammation From Effector T Cells In Prediabetes, Rui Liu

Theses and Dissertations--Pharmacy

Type 2 diabetes (T2D) is a chronic low-grade inflammatory disease. A T cell cytokine profile (Th17) from PBMCs can distinguish obese T2D from obese non-diabetes subjects. Individual T cell subsets interact with each other and the diverse subsets jointly determine overall inflammation. Cellular metabolism drives cytokine production of CD4⁺ T cells, and therefore contributes to inflammation in T2D. However, specific changes in metabolism and function of CD4⁺ T cells during the progression from lean healthy to obese and diabetic stages in people have not been clarified.

We hypothesize that human regulatory T cells (Treg) impact metabolism of effector …

Treatment-Associated Improvements In Self-Regulation And Mood As Theory-Based Correlates Of Increased Self-Efficacy For Weight-Management Behaviors, James J. Annesi

Health Behavior Research

Expanded understanding of the psychosocial dynamics of weight-loss treatment processes is required to improve consistently poor results. Women with obesity of ages 40–59 years participated in self-regulation-based (n = 41) and information-based (n = 46) treatments. Improvements in self-regulation and self-efficacy related to exercise and eating, mood, exercise, intake of fruits/vegetables and sweets, and weight were significant, and generally greater in the self-regulation group. Exercise- and eating-behavior changes significantly mediated the prediction of self-efficacy changes by changes in self-regulation, with mood change significantly adding to the prediction strength. Findings suggested the value in supporting exercise for its psychosocial …

Prediction Of Neonatal Birthweight Associated With Maternal Obesity And Diabetes, Laura Gleason, Rebekah Mccurdy, Md, Mph

Phase 1

Introduction: To design a model that will predict neonatal birth weight within obese mothers by diabetic status.

Methods: A secondary data analysis of an RCT (NCT 02909582) was utilized to create a neonatal birth weight prediction model. Women (n=325) with a BMI > 35 kg/m2 from a tertiary academic institution, 2016 – 2019, were included to estimate the risk of large for gestational age (LGA) infants and neonatal birth weight based on maternal prepregnancy BMI and diabetic status. LGA was defined as an infant birth weight > 90th percentile. Analysis included Chi-square, t-test, multivariate logistic and linear regression.

Results: Mean birthweight did …

Obesity And Obstructive Airways Disease: Clinical Correlates And Therapeutic Considerations, John Magagna, Cali Loblundo, Raymond B. Penn, Deepak A. Deshpande, Ajay P. Nayak

Student Papers, Posters & Projects

Obese patients are more likely to suffer from severe asthma symptoms and less likely to be able to control them. In obese patients, there is evidence that shows decreased efficacy of inhaled corticosteroids and beta-2 adrenergic agonists, the core treatment options for achieving and maintaining asthma control. This may be due to mechanical reasons like decreased ventilation and medication delivery, but there are many more pathologies of obesity that interact with pathways of both asthma pathology and asthma control. This review explores the epidemiological significance of obesity, many physiological changes in patients with obesity, the physiological interactions of asthma and …

Sphk2−/− Mice Are Protected From Obesity And Insulin Resistance, Shwetha Ravichandran, Brian S. Finlin, Philip A. Kern, Sabire Özcan

Clinical and Translational Science Faculty Publications

Sphingosine kinases phosphorylate sphingosine to sphingosine 1‑phosphate (S1P), which functions as a signaling molecule. We have previously shown that sphingosine kinase 2 (Sphk2) is important for insulin secretion. To obtain a better understanding of the role of Sphk2 in glucose and lipid metabolism, we have characterized 20- and 52-week old Sphk2^−/− mice using glucose and insulin tolerance tests and by analyzing metabolic gene expression in adipose tissue. A detailed metabolic characterization of these mice revealed that aging Sphk2^−/− mice are protected from metabolic decline and obesity compared to WT mice. Specifically, we found that 52-week old …

Impact Of Obesity On Mortality In Hospitalized Patients With Pneumonia Due To 2009 H1n1 Influenza A Virus Versus Other Etiologies, Martin A. Espinosa-Ginic, Ryan T. Hurt, Stephen P. Furmanek, Paula Peyrani, Julio A. Ramirez, Timothy Lee Wiemken, The Capo Investigators

The University of Louisville Journal of Respiratory Infections

Background: Reports from the 2009 H1N1 influenza A virus (2009 H1N1) pandemic indicate increased mortality in obese patients hospitalized with pneumonia. However, articles published prior to the pandemic have suggested that obesity may be a protective factor for mortality in these patients. The objective of this study was to compare the impact of obesity on mortality in hospitalized patients with pneumonia due to the 2009 H1N1 versus pneumonia due to other etiologies.

Methods: This was a secondary analysis of the CAPO international cohort study. Study groups were defined as follows: Group One, pneumonia due to 2009 H1N1: Patients hospitalized with …

Obesity-Induced Endoplasmic Reticulum Stress Causes Lung Endothelial Dysfunction And Promotes Acute Lung Injury, Dilip Shah, Freddy Romero, Zhi Guo, Jianxin Sun, Jonathan C. Li, Caleb Kallen, Ulhas P. Naik, Ross Summer

Center for Translational Medicine Faculty Papers

Conclusion

• Lung endothelial dysfunction in DIO mice coincides with increased endoplasmic reticulum (ER) stress.
• Fatty acids in obese serum induce ER stress in the pulmonary endothelium leading to pulmonary endothelial cell dysfunction.
• Reducing protein load in the endoplasmic reticulum of pulmonary endothelial cells might protect against ARDS in obese individuals.

Angiogenic Roles Of Vegfb And Vegfr1 In Vitro And In Vivo, Jacob Cecil

Chancellor’s Honors Program Projects

No abstract provided.

Assessing Feasibility And Readiness To Address Obesity Through Policy In American Indian Reservations, Valarie Blue Bird Jernigan, Gail Boe, Carolyn Noonan, Leslie Carroll, Dedra Buchwald

Journal of Health Disparities Research and Practice

The Institute of Medicine and Centers for Disease Control and Prevention (CDC) have identified policy and environmental strategies as critical to the prevention and control of obesity. However such strategies are rare in American Indian communities despite significant obesity-related disparities. Tribal policymaking processes differ by tribal nation and are often poorly understood by researchers and public health practitioners, hindering the dissemination, implementation, and successful scale-up of evidence-base obesity strategies in tribal communities. To address these gaps in knowledge we surveyed 138 diverse stakeholders in two American Indian reservations to assess the feasibility of and readiness to implement CDC-recommended obesity policy …

The Contributions Of Skeletal Muscle Pkc Theta To Diet-Induced Obesity, Erika Harness, Joseph S. Marino, Phd, Yvette Huet, Phd

Journal of Health Disparities Research and Practice

Protein Kinase C- Theta (PKCθ) is a gene predominantly expressed in hematopoietic cells and skeletal muscle. In skeletal muscle, PKCθ regulates fat metabolism and insulin sensitivity. PKCθ activity increases in response to high levels of diacylglycerol in the cell, a common outcome of chronic high fat diet consumption and obesity. PKCθ is associated with skeletal muscle metabolic dysfunction, which may exacerbate weight gain and metabolic disease. The purpose of this study was to test the hypothesis that the selective deletion of PKCθ from skeletal muscle protects against diet-induced obesity.

Mice lacking PKCθ in skeletal muscle were created using Cre-Lox recombination. …

An Intervention To Promote Navajo Gardening, Nutrition, And Community Wellness, Sonia Avitia, Mark C. Bauer, Phd, Linda Garcia

Journal of Health Disparities Research and Practice

The rates of diabetes and obesity in Navajo communities are higher than national rates. A healthy diet of fresh fruits and vegetables will help to prevent and reduce such rates. So the project focuses on promoting gardening to make vegetables and fruits more accessible at the comfort of one’s own home. Previous research in this area shows that gardeners consume 2 more servings of fruits and vegetables than nongardeners. Thirty participants were recruited by flyer distribution at chapter houses, senior centers, and community centers, from four Navajo targeted areas: Shiprock, NM; Tsaile, AZ; Lukachukai, AZ, and Hogback, NM. With the …

Leptin Induces Proliferation And Notch Expression In Pancreatic Cancer, Felice Watson, Ruben Gonzalez-Perez, Phd

Journal of Health Disparities Research and Practice

Pancreatic adenocarcinoma (PA) is an aggressive cancer. It develops in a way that causes almost no detectable symptoms, which leads to a rapid progression and a short survival rate.

Researchers have discovered a link between pancreatic cancer (and other cancer types) and obesity. High levels of leptin, an appetite hormone secreted by adipocytes, have been found in obese people. Studies have shown that the absence of leptin in the body or severe leptin resistance can lead to uncontrolled eating and weight gain, hence, its connection to obesity. Consequently, our lab is analyzing the relationship between obesity and leptin and what …

Exploration Of Antagonist Efficacy For Lpra2 Like Peptide, Ayobami Loye, Ruben R. Gonzalez-Perez, Phd

Journal of Health Disparities Research and Practice

Leptin is a small protein hormone that controls satiety and is produced by adipocytes. Obese people have increased levels of circulating leptin. Excessive leptin levels cause a break down in the control of leptin signaling pathways leading to increased angiogenesis, proliferation, cell migration, invasion, and anti-apoptotic events. Obesity and leptin signaling have been linked to cancer progression. Literature shows that LPrA2 is an effective leptin antagonist as it decreases proliferation of breast cancer cells in vitro.

This project compares the effectiveness of LPrA2 like compounds in breast cancer cell-line MDA-MB-468 (M-468 BCs). We hypothesize that the new peptide antagonists have …

Targeting Iκb Kinase Β In Adipocyte Lineage Cells For Treatment Of Obesity And Metabolic Dysfunctions, Robert N. Helsley, Yipeng Sui, Se-Hyung Park, Zun Liu, Richard G. Lee, Beibei Zhu, Philip A. Kern, Changcheng Zhou

Clinical and Translational Science Faculty Publications

IκB kinase β (IKKβ), a central coordinator of inflammation through activation of nuclear factor-κB, has been identified as a potential therapeutic target for the treatment of obesity-associated metabolic dysfunctions. In this study, we evaluated an antisense oligonucleotide (ASO) inhibitor of IKKβ and found that IKKβ ASO ameliorated diet-induced metabolic dysfunctions in mice. Interestingly, IKKβ ASO also inhibited adipocyte differentiation and reduced adiposity in high-fat (HF)-fed mice, indicating an important role of IKKβ signaling in the regulation of adipocyte differentiation. Indeed, CRISPR/Cas9-mediated genomic deletion of IKKβ in 3T3-L1 preadipocytes blocked these cells differentiating into adipocytes. To further elucidate the role of …

The Role Of Fat Grafting And Adipose-Derived Stem Cells In Breast Reconstruction, Krishna S. Vyas

Theses and Dissertations--Clinical and Translational Science

Fat grafting is a common surgical procedure that involves the transfer of fat from one area of the body to another in order to improve contour deformities, such as in breast reconstruction. Advantages of the technique include using autologous tissue rather than a foreign body and the added benefit of having liposuction to remove fat from an undesirable location. Although adipose tissue could be the ideal soft tissue filler, fat grafting is plagued by tremendous variability in long-term retention, with volume survival rates of 20-80%, resulting in suboptimal outcomes and repetitive procedures.

The mechanisms contributing to long-term fat graft survival …

Impact Of Sleep And Circadian Disruption On Energy Balance And Diabetes: A Summary Of Workshop Discussions, Deanna M. Arble, Joseph Bass, Cecilia Diniz Behn, Matthew P. Butler, Etienne Challet, Charles Czeisler, Christopher M. Depner, Joel Elmquist, Paul Franken, Michael A. Grandner, Erin C. Hanlon, Alex C. Keene, Michael J. Joyner, Ilia Karatsoreos, Philip A. Kern, Samuel Klein, Christopher J. Morris, Allan I. Pack, Satchidananda Panda, Louis J. Ptacek, Naresh M. Punjabi, Paolo Sassone-Corsi, Frank A. Scheer, Richa Saxena, Elizabeth R. Seaquest, Matthew S. Thimgan, Eve Van Cauter, Kenneth P. Wright

Clinical and Translational Science Faculty Publications

A workshop was held at the National Institute for Diabetes and Digestive and Kidney Diseases with a focus on the impact of sleep and circadian disruption on energy balance and diabetes. The workshop identified a number of key principles for research in this area and a number of specific opportunities. Studies in this area would be facilitated by active collaboration between investigators in sleep/circadian research and investigators in metabolism/diabetes. There is a need to translate the elegant findings from basic research into improving the metabolic health of the American public. There is also a need for investigators studying the impact …

Receptor Of Advanced Glycation Endproducts (Rage) Is Positively Correlated With Tumor Necrosis Factor-Α In Adolescents With Obesity, Tasnim Rahman, Daniel H. Conrad, Anshu Gupta

Undergraduate Research Posters

Introduction: Obesity in childhood is associated with an increased prevalence of diabetes and other traditional cardiometabolic risk factors, suggesting an epidemic of premature cardiovascular disease among today’s youth. Glycotoxins, known as advanced glycationend products (AGE’s), activating via the membrane-bound receptors (mRAGE), have been implicated in the pathophysiology of inflammation, (increased tumor necrosis factor-α [TNF-α ]), insulin resistance and vascular dysfunction in adults, but the role of RAGE in the early stages of metabolic disorders is unknown. In this study, we assessed relationship of cardiometabolicrisk factors, mRNA expression of TNF-α and RAGE in peripheral monocytes in adolescents with obesity.

Methods: Thirty …

History Of Fructose Use In Food Products, Jody L. Vogelzang Phd, Rdn, Fand, Ches

Jody L Vogelzang PhD, RDN, FAND, CHES

Food can be classified in ways other than by the nutrients they contain. In today’s fast moving culture, foods are characterized as having “magical” qualities that can turn consumers “superstars”, or reduce them to a less than optimal state of health and wellness. Sugars appear to be one of those vulnerable foodstuffs that can be enjoyed in moderation, but also contribute to the development of Type 2 Diabetes, metabolic syndrome, impaired cognitive function, obesity, and tooth decay .

Obesity And Cancer Screening According To Race And Gender., Heather Bittner Fagan, Richard Wender, Ronald E Myers, Nicholas Petrelli

Department of Family & Community Medicine Faculty Papers

The relationship between obesity and cancer screening varies by screening test, race, and gender. Most studies on cervical cancer screening found a negative association between increasing weight and screening, and this negative association was most consistent in white women. Recent literature on mammography reports no association with weight. However, some studies show a negative association in white, but not black, women. In contrast, obese/overweight men reported higher rates of prostate-specific antigen (PSA) testing. Comparison of prostate cancer screening, mammography, and Pap smears implies a gender difference in the relationship between screening behavior and weight. In colorectal cancer (CRC) screening, the …

Matrix Metalloproteinase-9 Is Increased In Obese Subjects And Decreases In Response To Pioglitazone, Resat Unal, Aiwei Yao-Borengasser, Vijayalakshmi Varma, Neda Rasouli, Craig Labbate, Philip A. Kern, Gouri Ranganathan

Clinical and Translational Science Faculty Publications

Context: The study investigated the regulation of matrix metalloproteinases (MMP)-9 in obesity-associated insulin resistance in humans.

Objectives: The objectives of the investigation were to study MMP-9 regulation by insulin resistance and pioglitazone treatment in impaired glucose tolerant subjects using adipose tissue biopsies and study the mechanism of MMP-9 regulation by pioglitazone in adipocyte cultures.

Research Design: 86 nondiabetic, weight-stable subjects between 21 and 66 yr of age were recruited in a university hospital research center setting. All subjects underwent a sc adipose tissue incisional biopsy from the lower abdominal wall and insulin sensitivity testing using a frequently sampled iv glucose …

The Impact Of Exercise Training Compared To Caloric Restriction On Hepatic And Peripheral Insulin Resistance In Obesity, Robert H. Coker, Rick H. Williams, Sophie E. Yeo, Patrick M. Kortebein, Don L. Bodenner, Philip A. Kern, William J. Evans

Clinical and Translational Science Faculty Publications

Context: It has been difficult to distinguish the independent effects of caloric restriction versus exercise training on insulin resistance.

Objective: Utilizing metabolic feeding and supervised exercise training, we examined the influence of caloric restriction vs. exercise training with and without weight loss on hepatic and peripheral insulin resistance.

Design, Participants, and Intervention: Thirty-four obese, older subjects were randomized to: caloric restriction with weight loss (CR), exercise training with weight loss (EWL), exercise training without weight loss (EX), or controls. Based on an equivalent caloric deficit in EWL and CR, we induced matched weight loss. Subjects in the EX group received …

Obesity And Cancer, Rickie Brawer, Phd, Mph, Nancy Brisbon, Md, James Plumb, Md

Department of Family & Community Medicine Faculty Papers

Obesity has become the second leading preventable cause of disease and death in the United States, trailing only tobacco use. Weight control, dietary choices, and levels of physical activity are important modifiable determinants of cancer risk. If multi-factorial approaches to prevention and management are not implemented, obesity will likely become the leading modifiable cause of death in the coming years. Physicians have a key role in integrating these approaches into clinical care and advocating for systemic prevention efforts. This article provides: 1) an introduction to the epidemiology and magnitude of childhood and adult obesity; 2) the relationship of overweight/obesity to …

Endoplasmic Reticulum Stress Markers Are Associated With Obesity In Nondiabetic Subjects, Neeraj K. Sharma, Swapan K. Das, Ashis K. Mondal, Oksana Hackney, Winston S. Chu, Philip A. Kern, Neda Rasouli, Horace J. Spencer, Aiwei Yao-Borengasser, Steven C. Elbein

Clinical and Translational Science Faculty Publications

Objective: Adipocyte and hepatocyte endoplasmic reticulum (ER) stress response is activated in dietary and genetic models of obesity in mice. We hypothesized that ER stress was also activated and associated with reduced insulin sensitivity (S_I) in human obesity.

Research Design and Methods: We recruited 78 healthy, nondiabetic individuals over a spectrum of body mass index (BMI) who underwent oral and iv glucose tolerance tests, and fasting sc adipose and muscle biopsies. We tested expression of 18 genes and levels of total and phosphorylated eukaryotic initiation factor 2α, c-jun, and c-Jun N-terminal kinase 1 in adipose tissue. We compared …

Stearoyl-Coenzyme A Desaturase 1 Gene Expression Increases After Pioglitazone Treatment And Is Associated With Peroxisomal Proliferator-Activated Receptor-Γ Responsiveness, Aiwei Yao-Borengasser, Negah Rassouli, Vijayalakshmi Varma, Angela M. Bodles, Neda Rasouli, Resat Unal, Bounleut Phanavanh, Gouri Ranganathan, Robert E. Mcgehee Jr., Philip A. Kern

Clinical and Translational Science Faculty Publications

Context and Objective: Stearoyl-coenzyme A desaturase (SCD1) is the rate-limiting enzyme that converts palmitoyl- and stearoyl-coenzyme A to palmitoleoyl- and oleoyl-cownzyme A, respectively. SCD-deficient mice are protected from obesity, and the ob/ob mouse has high levels of SCD. This study was designed to better characterize SCD1 gene and protein expression in humans with varying insulin sensitivity.

Design, Participants, and Setting: In a university hospital clinical research center setting, SCD1 gene expression was measured in sc adipose and vastus lateralis muscle of 86 nondiabetic subjects; 10 wk of pioglitazone (45 mg daily) and metformin (1000 mg twice daily) treatment were assessed …

Retinol Binding Protein 4 Expression In Humans: Relationship To Insulin Resistance, Inflammation, And Response To Pioglitazone, Aiwei Yao-Borengasser, Vijayalakshmi Varma, Angela M. Bodles, Neda Rasouli, Bounleut Phanavanh, Mi-Jeong Lee, Tasha Starks, Leslie M. Kern, Horace J. Spencer Iii, Amir Adel Rashidi, Robert E. Mcgehee Jr., Susan K. Fried, Philip A. Kern

Clinical and Translational Science Faculty Publications

Context: Retinol binding protein 4 (RBP4) was recently found to be expressed and secreted by adipose tissue, and was strongly associated with insulin resistance.

Objective: The aim was to determine the relationship between RBP4 and obesity, insulin resistance, and other markers of insulin resistance in humans.

Design and Patients: RBP4 mRNA levels in adipose tissue and muscle of nondiabetic human subjects with either normal or impaired glucose tolerance (IGT) were studied, along with plasma RBP4. RBP4 gene expression was also measured in adipose tissue fractions, and from visceral and sc adipose tissue (SAT) from surgical patients.

Setting: The study was …

The Interplay Of Obesity And Asthma, James Plumb, Rickie Brawer, Nancy Brisbon

Department of Family & Community Medicine Faculty Papers

The relationships, interactions, and association between obesity and asthma are complex, and are active sources of hypotheses and research. An association between obesity and asthma has been reported in many studies, although considerable debate about the existence of the association and its meaning still exists. Potential associative relationships may result from genetics, immune system modifications, and mechanical mechanisms. The rising prevalence of asthma and obesity in children and adults, and the significant morbidity from both, makes it imperative that clinicians recognize the importance of weight management in patients with and without asthma.

Oxpat/Pat-1 Is A Ppar-Induced Lipid Droplet Protein That Promotes Fatty Acid Utilization, Nathan E. Wolins, Benjamin K. Quaynor, James R. Skinner, Anatoly Tzekov, Michelle A. Croce, Matthew C. Gropler, Vijayalakshmi Varma, Aiwei Yao-Borengasser, Neda Rasouli, Philip A. Kern, Brian N. Finck, Perry E. Bickel

Clinical and Translational Science Faculty Publications

Lipid droplet proteins of the PAT (perilipin, adipophilin, and TIP47) family regulate cellular neutral lipid stores. We have studied a new member of this family, PAT-1, and found that it is expressed in highly oxidative tissues. We refer to this protein as "OXPAT." Physiologic lipid loading of mouse liver by fasting enriches OXPAT in the lipid droplet tissue fraction. OXPAT resides on lipid droplets with the PAT protein adipophilin in primary cardiomyocytes. Ectopic expression of OXPAT promotes fatty acid-induced triacylglycerol accumulation, long-chain fatty acid oxidation, and mRNAs associated with oxidative metabolism. Consistent with these observations, OXPAT is induced in mouse …

Adiponectin Expression From Human Adipose Tissue: Relation To Obesity, Insulin Resistance, And Tumor Necrosis Factor-Α Expression, Philip A. Kern, Gina B. Di Gregorio, Tong Lu, Negah Rassouli, Gouri Ranganathan

Clinical and Translational Science Faculty Publications

Adiponectin is a 29-kDa adipocyte protein that has been linked to the insulin resistance of obesity and lipodystrophy. To better understand the regulation of adiponectin expression, we measured plasma adiponectin and adipose tissue adiponectin mRNA levels in nondiabetic subjects with varying degrees of obesity and insulin resistance. Plasma adiponectin and adiponectin mRNA levels were highly correlated with each other (r = 0.80, P < 0.001), and obese subjects expressed significantly lower levels of adiponectin. However, a significant sex difference in adiponectin expression was observed, especially in relatively lean subjects. When men and women with a BMI2were compared, women had a twofold higher percent body fat, yet their plasma adiponectin levels were 65% higher (8.6 ± 1.1 and 14.2 ± 1.6 μg/ml in men and women, respectively; P < 0.02). Plasma adiponectin had a strong association with insulin sensitivity index (S_I) (r = 0.67, P < 0.0001, n = 51) that was not affected by sex, but no relation with insulin secretion. To separate the effects of obesity (BMI) from S_I, subjects who were discordant for S_I were matched for BMI, age, and sex. Using this approach, insulin-sensitive subjects demonstrated a twofold higher plasma level of …