Relationship of acanthosis nigricans with metabolic syndrome in obese children.

OBJECTIVES: Acanthosis nigricans is a skin symptom in obesity that helps to identify patients at high risk for dyslipidemia, hypertension, insulin resistance, and diabetes. It is the most important complication of obesity in metabolic syndrome. Studies investigating the relationship between acanthosis nigricans and metabolic syndrome in obese children are insufficient. In our study, the relationship of acanthosis nigricans and metabolic syndrome was evaluated in children. METHODS: Obese children aged between 6 and 18 years old, who were examined in the pediatric endocrinology outpatient clinic, were included. The patients' anthropometric measurements and laboratory results were recorded. Modified IDF (International Diabetes Federation) criteria for children were used in metabolic syndrome classification. RESULTS: A hundred and forty-eight obese children were evaluated. The mean age of the cases was 11.91 ± 2.94 years old. Of the cases, 56.1% were female (n=83) 43.9% (n=65) were male. In 39.9% (n=59) of cases, acanthosis nigricans was determined. Acanthosis nigricans was mostly located in the axillary area (27.1%) and the neck (16.9%). In 55.9% of the cases, it was located in more than one area. The relation of regionally detected acanthosis nigricans and metabolic syndrome was not significant (p=0.291). Metabolic syndrome was detected in 14% of 136 patients according to IDF criteria. Acanthosis nigricans and metabolic syndrome combination was present in 27.7%; however, 6.7% of the metabolic syndrome patients did not have acanthosis nigricans. There was a strong relation between metabolic syndrome and the presence of acanthosis nigricans (p=0.003). CONCLUSIONS: In our study, a correlation between acanthosis nigricans and metabolic syndrome was detected. Acanthosis nigricans is a skin sign that can be easily detected by clinician. It is an important and easy-to-detect dermatosis that helps determine patients at risk of metabolic syndrome in obese children.

Changes in inflammatory markers correlated with increased testosterone after laparoscopic sleeve gastrectomy in obese Chinese men with acanthosis nigricans.

Bariatric surgery is an effective method for severe obesity and its related comorbidities. This study was performed to explore the alterations of sex hormones and inflammatory markers following laparoscopic sleeve gastrectomy (LSG) among obese Chinese men with acanthosis nigricans (AN). Sixty-five obese men who underwent LSG were enrolled, comprising simple obesity without AN (OB group, n = 20) and obesity with AN (AN group, n = 45). There were 31 healthy male controls with normal body mass index (BMI) included. Anthropometry data, inflammatory markers, sex hormones and metabolic parameters were compared preoperatively and 12 months post-operatively. At baseline, patients in the AN group were associated with more severe metabolic abnormalities than the OB and control groups. Twelve months after surgery, AN patients obtained significant improvement in skin condition and reduction in AN score. BMI, fasting insulin (FINS), and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), tumor necrosis factor-α (TNF-α) and total testosterone (TT) were significantly changed in both groups, while interleukin (IL)-6, IL-8 and C-reactive protein were changed significantly only in the AN group. Moreover, FINS, HOMA-IR, TT and IL-6 levels were changed more in the AN group than those in the OB group. Multivariate regression analysis revealed that TT increase correlated significantly with reduction in FINS and HOMA-IR in both groups, but correlated with changes in IL-6 only in the AN group. In conclusion, LSG is effective in improving the skin condition of obese men with AN. The increased TT in AN patients correlated with amelioration of inflammatory state in addition to insulin resistance after LSG.

Luteolin-7-glucoside inhibits IL-22/STAT3 pathway, reducing proliferation, acanthosis, and inflammation in keratinocytes and in mouse psoriatic model.

The epidermis is a dynamic tissue in which keratinocytes proliferate in the basal layer and undergo a tightly controlled differentiation while moving into the suprabasal layers. The balance between keratinocyte proliferation, differentiation, and death is essential, and its perturbation can result in pathological changes. Some common skin diseases, such as psoriasis, are characterized by hyperproliferation accompanied by inflammatory reactions, suggesting that molecules with topical anti-inflammatory and ROS scavenging abilities may be useful for their treatment. Here we investigate the potential of the flavone Luteolin-7-glucoside (LUT-7G) as a treatment for psoriasis. We show that LUT-7G leads to a modification of the cell cycle and the induction of keratinocyte differentiation, with modification of energy, fatty acid, and redox metabolism. LUT-7G treatment also neutralizes the proliferative stimulus induced by the proinflammatory cytokines IL-22 and IL-6 in HEKn. Moreover, in the Imiquimod (IMQ) mouse model of psoriasis, topical administration of LUT-7G leads to a marked reduction of acanthosis and re-expression of epidermal differentiation markers. Dissection of the IL-22 signalling pathway, activated by IMQ treatment, demonstrates that LUT-7G impairs the nuclear translocation of phosphorylated (activated) STAT3, blocking the IL-22 signalling cascade. Thus LUT-7G appears to be a promising compound for the treatment of hyperproliferative and inflammatory skin diseases, such as psoriasis.

Fibroblast growth factor receptor signaling in kidney and lower urinary tract development.

Fibroblast growth factor receptors (FGFRs) and FGF ligands are highly expressed in the developing kidney and lower urinary tract. Several classic studies showed many effects of exogenous FGF ligands on embryonic renal tissues in vitro and in vivo. Another older landmark publication showed that mice with a dominant negative Fgfr fragment had severe renal dysplasia. Together, these studies revealed the importance of FGFR signaling in kidney and lower urinary tract development. With the advent of modern gene targeting techniques, including conditional knockout approaches, several publications have revealed critical roles for FGFR signaling in many lineages of the kidney and lower urinary tract at different stages of development. FGFR signaling has been shown to be critical for early metanephric mesenchymal patterning, Wolffian duct patterning including induction of the ureteric bud, ureteric bud branching morphogenesis, nephron progenitor survival and nephrogenesis, and bladder mesenchyme patterning. FGFRs pattern these tissues by interacting with many other growth factor signaling pathways. Moreover, the many genetic Fgfr and Fgf animal models have structural defects mimicking numerous congenital anomalies of the kidney and urinary tract seen in humans. Finally, many studies have shown how FGFR signaling is critical for kidney and lower urinary tract patterning in humans.

Case of exogenous insulin-derived acanthosis nigricans caused by insulin injections.

A 73-year-old male with diabetes mellitus had been treated with insulin for six years. He developed a solid mass on his left lateral of the abdomen at the insulin injection site. A firm subcutaneous mass with dark-red erythema was overlaid by dark-brown keratinized plaques. On histological examination of the mass, keratin proliferation and epidermal papilloma were observed. There were four previously reported cases of acanthosis nigricans that were considered to be caused by continuous injections of insulin. Using immunohistochemistry, in our case the findings were positive in the basal epithelial and prickle cell layers when the patient's lesion was dyed with insulin-like growth factor (IGF)-1 antibody. The coexistence of dermal IGF-1 receptor and acanthosis nigricans found in our patient has not been reported previously, to our knowledge.

Serum leptin, adiponectin, and resistin among adult patients with acanthosis nigricans: correlations with insulin resistance and risk factors for cardiovascular disease.

BACKGROUND: Acanthosis nigricans (AN) is linked to obesity and insulin resistance. Major adipokines such as leptin, adiponectin, and resistin are known to be dysregulated in obesity and are key players in the pathogenesis of metabolic syndrome. OBJECTIVES: This study was conducted to assess serum levels of the major adipokines leptin, adiponectin, and resistin, and to study their correlations with the state of insulin resistance and other risk factors for cardiovascular disease (CVD) among AN patients. METHODS: A total of 115 adult subjects were included in the study; 52 of these had benign acquired AN, and 63 (control subjects) were without AN. Thirty-three of the control group were obese, and 30 were healthy subjects of normal weight. Body mass index (BMI), blood pressure, lipid profile, fasting blood glucose, fasting insulin, serum leptin, adiponectin, and resistin were assessed in all subjects. RESULTS: We found significant differences between AN patients and obese controls in serum levels of leptin (30.02 ± 15.14 ng/ml vs. 21.07 ± 7.92 ng/ml; P = 0.002), adiponectin (5.55 ± 2.89 µg/l vs. 9.02 ± 2.33 µg/ml; P = 0.00001), and resistin (20.88 ± 3.97 ng/ml vs. 16.82 ± 4.36 ng/ml; P = 0.00003). Significant positive correlations were found between serum leptin and homeostasis model assessment (HOMA) value, insulin, glucose, BMI, cholesterol, and low-density lipoprotein. There were also significant negative correlations between adiponectin and HOMA value, insulin, BMI, cholesterol, and leptin among AN patients. CONCLUSIONS: Acanthosis nigricans is a likely forerunner of the finding of metabolic syndrome. High serum leptin and resistin and low serum adiponectin may increase the risk for CVD among AN patients.

Hyperinsulinemia associated with acanthosis nigricans, finger pebbles, acrochordons, and the sign of Leser-Trélat.

OBJECTIVE: To review common skin manifestations associated with type 2 diabetes mellitus (DM), and to discuss a potential underlying mechanism for these manifestations. METHODS: A PubMed literature search was conducted for articles describing the skin manifestations associated with hyperinsulinemia and type 2 DM. A case presentation describes a morbidly obese patient with type 2 DM treated with metformin who developed acanthosis nigricans, finger pebbles, scores of skin tags (acrochordons), and the sign of Leser-Trélat (sudden onset shower of seborrheic keratoses) in the absence of internal malignancy. RESULTS: Acanthosis nigricans, acrochordons, and finger pebbles have been associated with type 2 DM and obesity. While the Leser-Trélat sign is classically associated with internal malignancy, it can also be idiopathic. To our knowledge, this the first report of the occurrence of the Leser-Trélat sign in a patient with DM absent internal malignancy. CONCLUSION: Several skin manifestations can be seen in this patient with DM because of underlying insulin resistance and subsequent stimulation of insulin-like growth factor receptors. Management strategies could include weight loss, diet, and insulin-sensitizing pharmacologic therapy.

Associations of acanthosis nigricans with metabolic abnormalities in polycystic ovary syndrome women with normal body mass index.

Acanthosis nigricans (AN) usually correlates to insulin resistance (IR) or obesity in obese populations, but adequate studies on the significance of AN in people with normal body mass index (BMI) have not been performed and discussed. Three hundred and thirty-nine polycystic ovary syndrome (PCOS) patients with normal BMI (<23 kg/m(2) ) were recruited. The anthropometric and biochemical parameters of these patients were measured. In these patients with normal BMI, 33 (9.7%) women had AN, and six (1.77%) women were diagnosed with metabolic syndrome. Most of the anthropometric and biochemical variables associated with metabolic status were more unfavorable in the AN-positive group compared with the AN-negative groups. The prevalence of central obesity, IR and reduced high-density lipoprotein cholesterol (HDL-C) level were also significantly higher in the AN-positive group (P < 0.05). In multiple regression analysis, presence of AN was still significantly associated with IR (odds ratio [OR] = 2.952, 95% confidence intervals [CI] = 1.367-6.376] and reduced HDL-C level (OR = 2.668, 95% CI = 1.160-6.135) after adjustments for age and BMI. Sensitivity, specificity, and positive and negative predictive values for AN to detect IR were 18.6%, 92.6%, 39.4% and 81.4%, respectively. In conclusion, presence of AN correlated with IR and reduced HDL-C level in PCOS women with normal BMI. AN status had high specificity to detect IR, but lack of sensitivity.

Quantitative skin color measurements in acanthosis nigricans patients: colorimetry and diffuse reflectance spectroscopy.

Tristimulus colorimetry and diffuse reflectance spectroscopy (DRS) are white-light skin reflectance techniques used to measure the intensity of skin pigmentation. The tristimulus colorimeter is an instrument that measures a perceived color and the DRS instrument measures biological chromophores of the skin, including oxy- and deoxyhemoglobin, melanin and scattering. Data gathered from these tools can be used to understand morphological changes induced in skin chromophores due to conditions of the skin or their treatments. The purpose of this study was to evaluate the use of these two instruments in color measurements of acanthosis nigricans (AN) lesions. Eight patients with hyperinsulinemia and clinically diagnosable AN were seen monthly. Skin pigmentation was measured at three sites: the inner forearm, the medial aspect of the posterior neck, and anterior neck unaffected by AN. Of the three, measured tristimulus L*a*b* color parameters, the luminosity parameter L* was found to most reliably distinguish lesion from normally pigmented skin. The DRS instrument was able to characterize a lesion on the basis of the calculated melanin concentration, though melanin is a weak indicator of skin change and not a reliable measure to be used independently. Calculated oxyhemoglobin and deoxyhemoglobin concentrations were not found to be reliable indicators of AN. Tristimulus colorimetry may provide reliable methods for respectively quantifying and characterizing the objective color change in AN, while DRS may be useful in characterizing changes in skin melanin content associated with this skin condition.

Normal-weight 14-year-old girl with acanthosis nigricans and markedly increased hepatic steatosis: evidence for the important role of ectopic fat deposition in the pathogenesis of insulin resistance in childhood and adolescence.

BACKGROUND: A major factor in the development of insulin resistance is obesity. While the contribution of intrahepatic lipids to insulin resistance is well established in adults, there are only few reports in childhood and adolescence. AIM: To investigate the correlation between ectopic fat deposition and insulin sensitivity in a normal-weight girl with acanthosis nigricans before and after lifestyle intervention. METHODS: Variations in body fat composition and intrahepatic lipids were monitored by means of anthropometric measures and by means of methods based on magnetic resonance imaging and magnetic resonance spectroscopy. RESULTS: We present the case of a normal-weight 14-year-old Caucasian girl with pronounced hepatic steatosis together with acanthosis nigricans, increased waist-circumference and increased visceral fat. During a 7-month period of lifestyle intervention, the girl lost 7.1 kg in weight. Acanthosis nigricans, whole-body insulin sensitivity index (WBISI) and homeostasis model assessment (HOMA) improved significantly (before intervention: WBISI 0.42, HOMA 22.2; after intervention: WBISI 1.35, HOMA 6.9). Even though all lipid compartments were decreased in size, the intrahepatic lipids showed an extraordinarily great reduction. CONCLUSION: This case presentation of a normal-weight girl with acanthosis nigricans and markedly increased hepatic steatosis provides support for the association between intrahepatic fat deposition and insulin resistance in adolescence.

Molecular mechanism of kallikrein-related peptidase 8/neuropsin-induced hyperkeratosis in inflamed skin.

BACKGROUND: Hyperkeratosis and acanthosis occur in inflamed skin. Proliferation and differentiation of keratinocytes are important processes during epidermal repair after inflammation. Neuropsin and its human homologue kallikrein-related peptidase 8 (KLK8) have been reported to be involved in epidermal proliferation and differentiation, but the involved molecular mechanisms are obscure. OBJECTIVES: To explore the molecular mechanism of KLK8/neuropsin-induced hyperkeratosis and acanthosis in inflamed skin. METHODS: The molecular mechanism involved in KLK8/neuropsin-induced hyperkeratosis and acanthosis in inflamed skin was investigated both in vivo and in vitro using neuropsin knockout mice and KLK8 knockdown human keratinocytes. Neuropsin-related genes were identified by differential gene display. The localization and functional relationship of the molecules affected downstream of KLK8/neuropsin in normal and inflamed skin were analysed by in situ hybridization and immunohistochemistry. RESULTS: Hyperkeratosis and acanthosis in sodium lauryl sulphate-stimulated skin were markedly inhibited in neuropsin knockout mice. Knockdown of KLK8/neuropsin increased transcription factor activator protein-2α (AP-2α) expression and decreased keratin 10 expression in human keratinocytes and mouse skin, respectively. AP-2α has been reported to inhibit epidermal proliferation and keratin 10 expression. Distributional analysis showed that KLK8/neuropsin was expressed in the stratum spinosum, AP-2α was expressed in the stratum basale and the lower part of the stratum spinosum, and keratin 10 was expressed throughout the stratum spinosum. CONCLUSIONS: The above findings suggest the following mechanism of events underlying KLK8/neuropsin-induced hyperkeratosis: (i) skin inflammation increases KLK8/neuropsin expression in the stratum spinosum; (ii) the released KLK8/neuropsin inhibits AP-2α expression in the cells of the stratum basale and stratum spinosum; (iii) the decrease in AP-2α results in cell proliferation in the stratum basale and cell differentiation in the stratum spinosum, with an increase in keratin 10 expression.

Acanthosis nigricans identifies youth at high risk for metabolic abnormalities.

OBJECTIVE: To determine the prevalence of abnormal glucose homeostasis and cardiovascular risk factors in youth with acanthosis nigricans (AN). STUDY DESIGN: Youth (8-14 years) were recruited from community pediatric offices. Each subject underwent a questionnaire, a targeted physical examination, and an oral glucose tolerance test. RESULTS: Subjects (n = 236) with AN of the neck (AN+) (60% Hispanic, 30% African American, 54% female, body mass index [BMI] z-score 2.3 kg/m(2)) and 51 youth without AN (65% Hispanic, 22% African American, 37% female, BMI z-score 2.1 kg/m(2)) completed the study. Twenty-nine percent of the AN+ group had abnormal glucose homeostasis, 27% had systolic blood pressure > 95th percentile, and 50% had high-density lipoprotein-cholesterol < or =5th percentile. Once corrected for sex, puberty, maternal education, and BMI z-score, AN remained significantly associated with insulin resistance and abnormal glucose homeostasis. For youth in the AN+ group, homeostasis model assessment of insulin resistance, female sex, and positive glutamic acid decarboxylase antibodies remained significantly and independently associated with impaired glucose tolerance. CONCLUSIONS: Youth in the AN+ group had severe insulin resistance, and more than 1 in 4 already had abnormal glucose homeostasis. AN identified a high-risk population, for whom appropriate interventions have the potential to attenuate or even prevent the development of diabetes and further metabolic abnormalities.

Evaluation of insulin resistance in obese women with and without acanthosis nigricans.

Acanthosis nigricans is characterized by hyperpigmented velvety plaques of body folds and neck. Insulin could be a responsible factor in the pathogenesis of this condition and hyperinsulinemia: a consequence of insulin resistance stimulates the formation of these characteristic plaques. In this study, insulin resistance was compared in obese women with and without acanthosis nigricans. This was a cross-sectional study. Sixty-six obese women (32 patients with acanthosis nigricans and 34 patients without acanthosis nigricans) were selected randomly. Levels of fasting serum insulin and fasting blood glucose were measured in both groups and insulin resistance was determined using homeostasis model assessment. Glucose tolerance test also was performed for all of participants. Five (15.6%) patients with acanthosis nigricans and no (0%) patient without acanthosis nigricans had insulin resistance (P < 0.05). Six (18.7%) patients with acanthosis nigricans and one (2.9%) patient without acanthosis nigricans had impaired glucose tolerance test (P < 0.05). The mean levels of fasting serum insulin were 15.7 +/- 8.7 and 12.2 +/- 4.1 microm/mL (P < 0.05) and the mean values of insulin resistance index were 3.5 +/- 1.9 and 2.6 +/- 0.9 microm/mL between patients with and without acanthosis nigricans, respectively (P < 0.05). In Iranian obese women, acanthosis nigricans is a marker of insulin resistance.

Alterations of carbohydrate and lipoprotein metabolism in childhood obesity--impact of insulin resistance and acanthosis nigricans.

AIM: To study the prevalence of alterations of glucose and lipoprotein metabolism and the impact of acanthosis nigricans (AN) in childhood obesity. PATIENTS AND METHODS: 113 obese children, 57 with simple obesity (SO) and 58 with obesity and AN (OAN). Oral glucose tolerance test was performed, serum glucose, insulin and lipoprotein parameters were determined, and insulin resistance/sensitivity indices were calculated. RESULTS: Insulin resistance, basal and reactive hyperinsulinemia, impaired glucose tolerance (IGT) and dyslipidemia were found to be frequent conditions in children with OS as well as OAN. Reactive insulinemia was more pronounced in OAN than in SO, and insulin resistance was more frequent when AN was more prominent. Triglycerides were higher and HDL-C was lower, and atherogenic dyslipidemia was more frequent in OAN compared to SO. CONCLUSION: Children with obesity form a risk population. AN is a factor which can be used in metabolic risk factor clustering estimation in childhood obesity.

Diabetes mellitus in Asian Indian children and adolescents.

AIM: To study the clinical and metabolic profile of type 1 and type 2 diabetes mellitus in children and adolescents in a South Asian population. RESEARCH DESIGN AND METHODS: Sixty children were recruited. They were divided into three groups: Group I--type 2 diabetes mellitus (DM2), Group II--type 1 diabetes mellitus (DM1), and Group III--healthy controls. The clinical history and biochemical parameters (HbA1c, serum insulin, C-peptide, triglycerides, total cholesterol and HDL-cholesterol) were recorded. Homeostasis model assessment for insulin resistance (HOMAIR) and quantitative insulin sensitivity check index (QUICKI) were calculated. RESULTS AND CONCLUSIONS: Children and adolescents with DM2 had a significant family history of DM and clinical features of insulin resistance, including increased body mass index, waist:hip ratio and acanthosis nigricans. They also had decreased insulin sensitivity together with dyslipidemia of metabolic syndrome, i.e. high triglyceride, high total cholesterol and low HDL-cholesterol. The presence of these predictors of cardiovascular disorders is known to contribute to morbidity and mortality. Hence, DM2 needs to be recognized early in Asian Indian children.

The effects of IL-20 subfamily cytokines on reconstituted human epidermis suggest potential roles in cutaneous innate defense and pathogenic adaptive immunity in psoriasis.

IL-19, IL-20, IL-22, IL-24, and IL-26 are members of the IL-10 family of cytokines that have been shown to be up-regulated in psoriatic skin. Contrary to IL-10, these cytokines signal using receptor complex R1 subunits that are preferentially expressed on cells of epithelial origin; thus, we henceforth refer to them as the IL-20 subfamily cytokines. In this study, we show that primary human keratinocytes (KCs) express receptors for these cytokines and that IL-19, IL-20, IL-22, and IL-24 induce acanthosis in reconstituted human epidermis (RHE) in a dose-dependent manner. These cytokines also induce expression of the psoriasis-associated protein S100A7 and keratin 16 in RHE and cause persistent activation of Stat3 with nuclear localization. IL-22 had the most pronounced effects on KC proliferation and on the differentiation of KCs in RHE, inducing a decrease in the granular cell layer (hypogranulosis). Furthermore, gene expression analysis performed on cultured RHE treated with these cytokines showed that IL-19, IL-20, IL-22, and IL-24 regulate many of these same genes to variable degrees, inducing a gene expression profile consistent with inflammatory responses, wound healing re-epithelialization, and altered differentiation. Many of these genes have also been found to be up-regulated in psoriatic skin, including several chemokines, beta-defensins, S100 family proteins, and kallikreins. These results confirm that IL-20 subfamily cytokines are important regulators of epidermal KC biology with potentially pivotal roles in the immunopathology of psoriasis.

Adipose tissue, hepatic, and skeletal muscle insulin sensitivity in extremely obese subjects with acanthosis nigricans.

We evaluated insulin action in skeletal muscle (glucose disposal), liver (glucose production), and adipose tissue (lipolysis) in 5 extremely obese women with acanthosis nigricans (AN), who had normal oral glucose tolerance, and 5 healthy lean subjects, by using a 5-stage pancreatic clamp and stable isotopically labeled tracer infusion. Basal plasma insulin concentration was much greater in obese subjects with AN than lean subjects (54.8 +/- 4.5 vs 8.0 +/- 1.3 microU/mL, P < .001), but basal glucose and free fatty acid concentrations were similar in both groups. During stage 1 of the clamp, glucose rate of appearance (R(a)) (2.6 +/- 0.3 vs 3.7 +/- 0.3 micromol x kg FFM(-1) x min(-1), P = .02) and palmitate R(a) (2.4 +/- 0.6 vs 7.0 +/- 1.5 micromol x kg FFM(-1) x min(-1), P < .05) were greater in obese subjects with AN than lean subjects despite slightly greater plasma insulin concentration in subjects with AN (3.0 +/- 0.7 vs 1.1 +/- 0.4 microU/mL, P < .05). The area under the curve for palmitate R(a) (1867 +/- 501 vs 663 +/- 75 micromol x kg FFM(-1) x 600 min(-1), P = .03) and glucose R(a) (1920 +/- 374 vs 1032 +/- 88 micromol x kg FFM(-1) x 600 min(-1), P = .02) during the entire clamp procedure was greater in subjects with AN than lean subjects. During intermediate insulin conditions (plasma insulin, approximately 35 microU/mL), palmitate R(a) was 5-fold greater in subjects with AN than in lean subjects (2.6 +/- 1.1 vs 0.5 +/- 0.2 micromol x kg FFM(-1) x min(-1), P = .05). Maximal glucose disposal was markedly lower in obese subjects with AN than in lean subjects (13.0 +/- 0.8 vs 23.4 +/- 1.8 mg x kg FFM(-1) x min(-1), P = .01) despite greater peak plasma insulin concentration (1842 +/- 254 vs 598 +/- 38 microU/mL, P < .05). These data demonstrate obese young adults with AN have marked insulin resistance in multiple tissues. However, marked insulin hypersecretion can compensate for impaired insulin action, resulting in normal glucose and fatty acid metabolism during basal conditions.