Prediction and evaluation of resting energy expenditure in a large group of obese outpatients.

BACKGROUND/OBJECTIVES: The aim of this study was to compare resting energy expenditure (REE) measured (MREE) by indirect calorimetry (IC) and REE predicted (PREE) from established predictive equations in a large sample of obese Caucasian adults. SUBJECTS/METHODS: We evaluated 1851 obese patients (body mass index (BMI)>30 kg m-2) aged between 18a and 65 years. Data were obtained by comparing MREE with PREE, derived from different equations, within and between normal weight and obese groups. The mean differences between PREE and MREE as well as the accuracy prediction within ±10% level were investigated in the whole sample and in three subgroups, classified by BMI (Group 1=30-39.9 kg m-2; Group 2=40-49.9 kg m-2; Group 3>50 kg m-2). RESULTS: We observed that FAO, Henry and Muller3 (body composition (BC)) equations provided good mean PREE-MREE (bias -0.7, -0.3 and 0.9%; root mean standard error (RMSE) 273, 263 and 269 kcal per day, respectively); HB and Henry equations were more accurate individually (57 and 56.9%). Only the Muller1 (BC) equation gave the lowest PREE-MREE difference (bias -1.7%; RMSE 228 kcal per day) in females, while Johnstone and De Lorenzo equations were the most accurate (55.1 and 54.8%). When the sample was split into three subgroups according to BMI, no differences were found in males; however, the majority of the equations included in this study failed to estimate REE in severely obese females (BMI>40 kg m-2). Overall, prediction accuracy was low (~55%) for all predictive equations, regardless of BMI. CONCLUSIONS: Different established equations can be used for estimating REE at the population level in both sexes. However, the accuracy was very low for all predictive equations used, particularly among females and when BMI was high, limiting their use in clinical practice. Our findings suggest that the validation of new predictive equations would improve the accuracy of REE prediction, especially for severely obese subjects (BMI>40 kg m-2).

Hematological complications in anorexia nervosa.

BACKGROUND/OBJECTIVES: Anemia, leukopenia and, although less frequently, thrombocytopenia are possible hematological complications of anorexia nervosa considered strictly secondary to chronic malnutrition. This is a retrospective study on the prevalence of these disorders in a large cohort of 318 female patients with AN (20.4±5.6 years, body mass index (BMI) 15.9±1.6 kg/m2), recruited in the Outpatient Unit for Malnutrition secondary to Eating Disorders at the Department of Clinical Medicine and Surgery, Federico II University Hospital, since February 1991 to December 2012. SUBJECTS/METHODS: Patients were studied on an outpatient basis after obtaining medical history, clinical examination, routine hematobiochemical and endocrine tests, electrocardiography, psychiatric interview and bioelectrical impedance analysis and, in particular, phase angle determination. All patients with other comorbidities, in particular with mean corpuscular volume <80 fl, were excluded for suspected genetic alteration in the synthesis of hemoglobin. RESULTS: Hematologic data showed that 16.7% of patients had anemia, 7.9% neutropenia and 8.9% thrombocytopenia. These abnormalities were strictly related to the duration of illness (P=0.028), and to protein energy malnutrition, in particular, BMI and phase angle (P<0.001). CONCLUSIONS: Our study offers description of the incidence of hematologic defects in a selected and large sample of AN female patients, suggesting that its incidence is related to the degree and duration of protein energy malnutrition.

Composition of personalized and standard nutritional mixtures in patients on home parenteral nutrition.

BACKGROUND/OBJECTIVES: The compounding of personalized parenteral nutrition mixtures (PPNMs) for home parenteral nutrition (HPN) gives the possibility to better satisfy nutritional requirements for patients in selected clinical conditions. The objective of this study was to compare the composition of PPNMs prescribed in selected cases, by a practitioner nutritionist, with that of industrially manufactured standard parenteral nutrition mixtures (SPNMs). SUBJECTS/METHODS: Two hundred and ninety-eight patients (151 men, 147 women, aged 17-87 years) on HPN, followed up in 2011 at our Center, were retrospectively recruited. RESULTS: Industrially manufactured SPNMs were prescribed in 230 (77.2%) patients, whereas compounded PPNMs were prescribed in 68 (22.8%). Formulation of PPNMs, adjusted for body weight, did not significantly differ from SPNMs as regards total daily calorie amount, but was significantly different as far as nutrient composition is concerned (P<0.01). Analysis on the daily amount of nutrients per kg of body weight and per patient disease showed that 16/34 (47%) benign chronic intestinal failure (CIF) patients, 47/233 (20%) cancer patients and 5/31 (16%) patients grouped as 'having other diseases' needed personalized mixtures (in PPNMs 4-9 nutrients were significantly different from those in SPNMs). Moreover, in CIF patients receiving PPNMs, frequent changes in the formulation (mean 6 times per year, range 1-28) were necessary. CONCLUSIONS: Our data suggest that, presently, PPNMs cannot be completely replaced by SPNMs owing to special needs in macro and/or micronutrients of some patients and/or the necessity of frequent changes in the nutritional mixture composition, at least until stabilization of clinical and metabolic conditions.

Iron absorption following a single oral dose of ferrous sulfate or ferric gluconate in patients with gastrectomy.

BACKGROUND: Iron deficiency anemia frequently occurs in gastrectomized patients. METHODS: Serum iron levels following the ingestion of a single oral dose of 105 mg elemental iron, taken as ferrous sulfate (FeS) or ferric gluconate (FeG), have been evaluated in 20 gastrectomized patients (and 20 controls). All subjects participated on 2 different test days, 1 month apart: they took a single dose of 105 mg elemental iron as FeS or FeG after a night of fasting. Serum iron concentrations at baseline, 30, 60, 120 and 180 min after the oral dose administration were measured. RESULTS: In patients and controls receiving FeG, serum iron levels did not significantly change. After oral ingestion of FeS, patients' serum iron levels gradually increased. The increase in serum iron levels was 148 and 168% at 120 and 180 min in patients (p < 0.0001 for both evaluations), whilst in controls, it was 216% at 120 min and 234% at 180 min, i.e. significantly higher than in gastrectomized patients (p < 0.001 for both evaluations). CONCLUSIONS: In gastrectomized patients, a single oral dose of FeS shows a significant increase in iron serum concentration, albeit lower than in controls. Further studies on a larger sample of patients will be necessary to confirm these results.

The absence of polymorphisms in ADRB3, UCP1, PPARγ, and ADIPOQ genes protects morbid obese patients toward insulin resistance.

BACKGROUND AND AIMS: The insulin resistance (IR) is a major metabolic impairment in severe obesity, a multifactorial disease in which the importance of the effect of single nucleotide polymorphisms (SNP) associations in different rather than individual genes was established. The aim of this study was to test the predictive value of presence/absence of polymorphisms/ variants in ß3-adrenergic receptor (ADRB3), uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor γ (PPARγ), and adiponectin (ADIPOQ) genes in diagnosing the IR in obesity. SUBJECTS AND METHODS: We studied 112 (40 males, 72 females) severely obese (body mass index: 48.5±7.5 kg/m2) subjects recruited from the outpatient obesity clinic of Federico II University Hospital in Naples. Genomic DNA was extracted from peripheral leukocytes with a commercial kit. The gene polymorphisms Trp64Arg in ADRB3, -3826 A>G in UCP1, Pro12Ala in PPARγ, and c.268G>A, c.331T>C, and c.334C>T in ADIPOQ were characterized by TaqMan assay or by direct sequencing (ADIPOQ). RESULTS AND CONCLUSION: Our results demonstrate that -3826A>G UCP1 polymorphism is associated with IR in morbid obesity. Further, the lack of any polymorphisms, Trp64Arg in ADRB3 and/or -3826 A>G in UCP1 and/or Pro12Ala in PPARγ and/or c.268G>A, c.331T>C and c.334C>T in ADIPOQ, appears a useful prognostic factor (NPV=100%) toward the IR onset in these obese patients representing a further parameter for an earlier and appropriate therapy.

Circulating levels of cytochrome C, gamma-glutamyl transferase, triglycerides and unconjugated bilirubin in overweight/obese patients with non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease, characterized by hepatocyte apoptosis, is distinct in fatty liver and non-alcoholic steatohepatitis, the more severe form. Apoptotic cell death is caspase-dependent and associated with mitochondrial membrane depolarization and cytochrome c release. Adhering to the hypothesis that the exposure of hepatocytes to free fatty acids, resulting in increased ROS production and mitochondrial damage, is balanced by the presence of antioxidant substances, circulating levels of gamma-glutamyl transferase, cytochrome c, triglycerides and unconjugated bilirubin were explored in patients suffering from non-alcoholic fatty liver disease with different severity. One hundred and eighty-six consecutive patients who presented recent ultrasound feature of bright liver without any liver disease of known origin were enrolled, eighty-nine of whom underwent liver biopsy. Forty-five subjects were allocated on the basis of histology in fatty liver group while 44 patients formed the group with non-alcoholic steatohepatitis. A cohort of 27 young, lean, apparently healthy individuals was selected as control group. The levels of gamma-glutamyl transferase were normal or slightly increased, while unconjugated bilirubin concentrations were elevated in all the spectra of non-alcoholic fatty liver disease. Comparing the present results with relevant findings from other studies dealing with diseases characterized by apoptosis, we did not find high circulating levels of cytochrome c in non-alcoholic fatty liver disease. What is more, our patients, categorized as suffering from simple fatty liver or from the more severe non-alcoholic steatohepatitis, had similar levels of cytochrome c and gamma-glutamyl transferase, p=0.19 and 0.11. Serum triglycerides were higher in patients with non-alcoholic fatty liver disease than in the healthy group, p=0.001. These findings likely reflect a balance between oxidative stress and anti-oxidant response rather than a lack of reliability of cytochrome c as a reliable biomarker of mitochondrial damage.

[Obesity and Eating Disorders. Indications for the different levels of care. An Italian Expert Consensus Document]. / Documento di Consensus. Obesità e Disturbi dell'Alimentazione Indicazioni per i diversi livelli di trattamento.

This paper is an Italian Expert Consensus Document on multidimensional treatment of obesity and eating disorders. The Document is based on a wide survey of expert opinion. It presents, in particular, considerations regarding how clinicians go about choosing the most appropriate site of treatment for a given patient suffering from obesity and/or eating disorders: outpatient, partial hospitalization, residential rehabilitation centre, inpatient hospitalization. In a majority of instances obesity and eating disorders are long-term diseases and require a multiprofessional team-approach. In determining an initial level of care or a change to a different level of care, it is essential to consider together the overall physical condition, medical complications, disabilities, psychiatric comorbidity, psychology, behaviour, family, social resources, environment, and available services. We first created a review manuscript, a skeleton algorithm and two rating scales, based on the published guidelines and the existing research literature. As the second point we highlighted a number of clinical questions that had to be addressed in the specific context of our National Health Service and available specialized care units. Then we submitted eleven progressive revisions of the Document to the experts up to the final synthesis that was approved by the group. Of course, from point to point, some of the individual experts would differ with the consensus view. The document can be viewed as an expert consultation and the clinical judgement must always be tailored to the particular needs of each clinical situation. We will continue to revise the Document periodically based on new research information and on reassessment of expert opinion to keep it up-to-date. The Document was not financially sponsored.

UCP1 -3826 AG+GG genotypes, adiponectin, and leptin/adiponectin ratio in severe obesity.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS) are well-recognized complications of obesity. This study was designed to evaluate the role of the UCP1 -3826 A>G polymorphism, adiponectin levels, leptin/adiponectin ratio (L/A), and main biochemical parameters in 102 unrelated severely obese adults [61 females and 41 males, median body mass index (BMI) = 47.8 kg/m2] with NAFLD, with (MS+) or without MS (MS-) from Southern Italy. SUBJECT AND METHODS: The UCP1 polymorphism was tested by the TaqMan method, main biochemical parameters by routinary methods, adiponectin, and leptin serum levels by enzyme-linked immunosorbent assay. MS was diagnosed according to the American Heart Association criteria, liver steatosis was detected by ultrasound. RESULTS: MS was present in 53% male and 66% female obese patients. Only total cholesterol (p=0.04 males and p=0.002 females) and L/A ratio (p=0.03 males) differed between MS+ and MS- obese patients. At multivariate analysis, severe liver steatosis was significantly associated with: UCP1 (AG+GG) genotypes [odds ratio-confidence interval (OR-CI): 4.25; 1.12-16.13], MS (OR-CI: 8.47; 1.78-40.25), low adiponectin levels (OR-CI: 0.92; 0.87-0.98), high alanine aminotransferase levels (OR-CI: 1.03; 1.00-1.06), age (ORCI: 1.08; 1.00-1.15), and male gender (OR-CI: 10.78; 1.61- 71.96). CONCLUSION: In addition to traditional factors, total cholesterol and L/A ratio appear to contribute to MS characterization in severe obesity. Furthermore, the UCP1 (AG+GG) genotypes and low adiponectin levels could predispose to a more severe liver steatosis independently of MS presence. Based on our data, polymorphic UCP1 (AG+GG) obese patients with low adiponectin levels appear to be high-risk subjects for worsening of liver steatosis, a NAFLD, possibly requiring a second-step evaluation by liver biopsy.

Bioelectrical impedance phase angle in constitutionally lean females, ballet dancers and patients with anorexia nervosa.

BACKGROUND/OBJECTIVE: Several articles have described body composition in anorexia nervosa, whereas little is known about this issue in underweight ballet dancers and constitutionally lean females. The main aim of this study was to assess whether phase angle (a bioimpedance variable related to body cell mass) differs according to the type of underweight in female adolescents and young women. SUBJECTS/METHODS: Skinfold thicknesses and bioimpedance analysis (whole body and limbs) were evaluated in three groups of underweight patients (30 patients with anorexia nervosa, 10 constitutionally lean individuals and 15 classical dancers) and 30 normal weight controls. RESULTS: There were no differences between the three groups of underweight patients with respect to anthropometric and bioelectrical impedance analysis (BIA) variables with the exception of phase angle. The latter was significantly higher in dancers, lower in anorectic patients and not different in constitutionally lean patients, as compared with controls. CONCLUSIONS: Phase angle (assessed by single-frequency BIA) appears to discriminate between different forms of underweight, being an effective marker of qualitative changes in body composition.

Molecular analysis of the adiponectin gene in severely obese patients from southern Italy.

BACKGROUND: Severe obesity is a major worldwide public health concern affecting 0.5-5% of the adult population. Adiponectin (Acpr30), an adipokine secreted from adipocytes, shows pleiotropic beneficial effects on obesity and related disorders. In this study, sequence analysis of Acpr30 gene (ACDC) was performed in a highly selected population of severely obese young adult patients from Southern Italy to investigate the associations between polymorphisms in the ACDC gene and the development of severe obesity concomitantly with other features of the metabolic syndrome. METHODS: The ACDC gene was analyzed by direct sequencing in the severely obese patients (n=220) and compared to healthy controls (n=116). The associations between the ACDC gene single-nucleotide polymorphisms (SNPs) and the levels of serum Acpr30 as well as the correlation with the presence of severe obesity jointly associated with other features of the metabolic syndrome were also investigated. Total serum Acpr30 concentrations were measured by the ELISA method. RESULTS: ACDC gene molecular screening revealed the presence of previously described SNPs and a new nucleotide alteration, c.355T>G, leading to a protein variant, p.L119V. Measurement of serum concentration of Acpr30 demonstrated lower levels of Acpr30 in the obese population compared to controls (30.5+/-28.3 vs. 43.9+/-35.7 microg/ml, p<0.01); in particular, significantly lower Acpr30 concentrations were observed in obese patients bearing c.-11377C>G SNP CG+GG genotypes than in those with CC genotype (22.9+/-20.5 vs. 33.1+/-29.4 microg/ml, p<0.05). CONCLUSIONS: Our results confirmed that low serum levels of Acpr30 are related to severe obesity and a difference in protein expression is associated with variants in ACDC gene promoter region.

Clinical outcome of long-term home parenteral nutrition in non-oncological patients: a report from two specialised centres.

OBJECTIVE AND METHODS: Forty-one (20 m, 21 f) non-oncological home parenteral nutrition (HPN) patients (52.0+/-16.6 years, BMI 20.2+/-4.0 kg/m(2)), enrolled from 1995 to 2005, underwent a clinical and biochemical follow-up at 3 months, 1 and 3 years. RESULTS: At admittance the Karnofsky Index ranged between 40 and 50 in 13 (31.7%) and 60 and 80 in 28 (68.3%) patients; the most frequent underlying disease was mesenteric infarction (11 patients, 27%). All had a central venous access. Mean catheterization days were 864+/-992, while mean HPN days were 630+/-668. At the 3-month follow-up, all patients were on HPN, at 1 year 24 (58.5%) and at 3 years 11 (27%). At 3 months, 1 and 3 years there was a significant increase in BMI (p=0.001), body weight (p=0.001) and Karnofsky Index (p=0.001), as well as an improvement of several biochemical parameters. Survival rate of HPN patients was 90.2% at 1 year, 87.8% at 3 years and 82.9% at 5 years. As to HPN-related complications, there was a central venous catheter (CVC) obstruction in 8 patients (19.5%) and 47 CVC infections in 24 (58.5%) patients. The infection rate was 1.32/(00) days of catheterization (1.8/(00) from 1995 to 1998 and 1.0/(00) from 1999 to 2005). Hospitalisation was necessary in over 50% of patients, and death occurred in 8, always as a consequence of the primary disease. CONCLUSIONS: The experience of the nutritional team and careful patient and caregiver training reduce CVC infection rate and the overall risk of complications possibly due to HPN.

Metabolic syndrome and ADRB3 gene polymorphism in severely obese patients from South Italy.

OBJECTIVE: To evaluate the prevalence of beta(3)-adrenergic receptor (ADRB3) Trp64Arg polymorphism and its relationship with the metabolic syndrome in severe obesity. DESIGN: Cross-sectional outpatients study. PATIENTS AND METHODS: In 265 (100 men) severely obese non-diabetic subjects and 78 (25 men) healthy volunteers, genomic DNA was isolated from peripheral leukocytes. In obese patients, plasma concentrations of leptin, lipids, glucose and insulin, the homeostasis model assessment index and blood pressure have been measured. The Trp64Arg mutation was identified with the real-time TaqMan method. RESULTS: Neither genotype distribution nor allele frequency differed between the two groups. The metabolic syndrome prevalence was 59% in obese subjects, and was higher in men than in women (65 vs 55%: P=0.03). The body mass index (BMI) was related to age tertiles (beta=0.08; P<0.001; multiple linear regression) in Trp64Arg-positive obese subjects. CONCLUSION: We confirm the high prevalence of the metabolic syndrome among severely obese subjects. ADRB3 polymorphism was significantly related to insulin resistance only in obese male subjects. Moreover, increased BMI was related to age in obese subjects with the ADRB3 polymorphism.

Prevalence of home artificial nutrition in Italy in 2005: a survey by the Italian Society for Parenteral and Enteral Nutrition (SINPE).

AIM: To determine the prevalence (cases per million inhabitants) of home artificial nutrition (HAN), enteral (HEN) and parenteral (HPN), in Italy, grouped according to administrative regions, patient age and primary disease, and to analyze the impact both of the presence of an HAN regional regulation and of demographic characteristics. METHODS: In April 2005, the Regional Coordinators of the Italian Society for Parenteral and Enteral Nutrition (SINPE) recorded all the ongoing cases of HAN using a structured questionnaire and were asked to estimate the representativeness of the collected sample with respect to the total expected HAN. RESULTS: A total of 6955 cases of HAN (93.5% adults, 6.5% pediatric patients < or = 18 years) were recorded in 16 of the 20 Italian regions (80% of the Italian population; sample representativeness 78%). HAN prevalence 152.6 (83.9% HEN, 16.1% HPN); the HAN range among the regions was: prevalence 28.1-519.8; oncological disease 13.8-75.7%, neurological disease 15.5-79.9%, intestinal failure 1.3-14.0%. An HAN regulation was present in 11 regions. A positive association (P=0.012) was found between the number of years since the regulation was issued and the HAN prevalence, and also between the % neurological patients and the population density (P=0.130) and the % inhabitants > or = 75 years (P=0.040). CONCLUSIONS: The need for HAN regards a great number of patients throughout the country; there are substantial differences between the regions with respect to both the prevalence and the use of HAN in various disease categories. A specific regulation may favor the development of HAN.

Long-term mortality in anorexia nervosa: a report after an 8-year follow-up and a review of the most recent literature.

OBJECTIVE: To evaluate long-term mortality rate of anorexia nervosa (AN) patients in a southern Italy population compared to the most recent literature. DESIGN: Retrospective and review setting. PATIENTS AND INTERVENTIONS: One hundred and forty-seven female AN patients, consecutively admitted from 1994 to 1997 to the Outpatient Unit, were re-examined between June and November 2003. Our data are compared with 10 other studies published since 1988. RESULTS: One hundred and twenty-three deaths in 2240 patients, amounting to a total mortality rate of 5.25% were reported in the literature. Deaths due to suicide, AN-related and AN-unrelated diseases were 1.20, 3.07 and 0.98%, respectively. After correcting for unrelated deaths, mortality rate was 4.27%. In our 8-year follow-up, we found a mortality rate of 2.72% (1.82% after correcting for unrelated deaths). Standardized mortality ratio was 9.7. CONCLUSION: We interpret our favourable findings as a consequence of an integrated, clinical-nutritional and psychiatric approach. Finally, considering AN demographic characteristics, that is young female subjects in Westernized societies, mortality rate is confirmed to be dramatically high.

Adult home parenteral nutrition: a clinical evaluation after a 3-year experience in a Southern European centre.

AIM: To evaluate the current use of Home Parenteral Nutrition (HPN) in a Southern European region. SUBJECTS AND METHODS: A total of 159 (86 m, 73 f) HPN patients, mean age 60.1 +/- 14.2 years, BMI 18.8 +/- 3.3kg/m2, consecutively referred to the Artificial Nutrition outpatient Unit of the Federico II University Hospital in Naples (Italy), from January 2000 to December 2002 and treated for at least 4 weeks. Retrospective evaluation of baseline disease, indications and duration of HPN treatment, type of venous access, complications. RESULTS: In all, 140 (88%) were cancer and 19 (12%) noncancer patients. Main indications were carcinosis in 68 for total, and hypophagia/dysphagia in 62 patients for partial/integrative (to oral-enteral nutrition) HPN; mean duration of HPN was 81.45 +/- 110.86 days of treatment and infection rate 2.89% in the whole population and 2.66% in the 36 patients treated for more than 3 months. No other major complications have been observed. CONCLUSION: HPN is confirmed to be a safe and effective treatment when prescribed and administered by a trained team.

Non-alcoholic fatty liver disease in young adult severely obese non-diabetic patients in South Italy.

BACKGROUND/AIMS: In the absence of other causes, obesity increases the risk of liver disease. We evaluated the prevalence and degree of metabolic and hepatic abnormalities associated with non-alcoholic fatty liver disease (NAFLD) in type II-III obesity in a metropolitan area of South Italy. METHODS: 187 (81 M, 106 F) young adult non-diabetic obese patients, age range 18-50 years (mean 31.9 +/- 8.8), body mass index (BMI) > or =30 (mean 47.5 +/- 9.6), consecutively admitted from January 2000 to April 2003 to the Obesity Outpatients Clinic entered into the study. Patients were divided into two groups: (1) BMI 30.0-39.9, and (2) BMI> or =40. Ultrasound detected liver steatosis was classified as: (I) mild; (II) moderate, and (III) severe. RESULTS: All patients, except 4, showed a variable degree of steatosis: mild was more frequent among females, severe steatosis present only in grade III obesity, with higher prevalence in males than in females (p < 0.001). Mean serum transaminases, in particular alanine aminotransferase (ALT), increased according to BMI and degree of steatosis. Homeostasis Model Assessment (HOMA) index, ferritin and fibrinogen levels increased with BMI, particularly in severe steatosis. In group 2, patients with BMI> or =40 showed a positive correlation between ferritin, aspartate aminotransferase (AST) (r = 0.46, p < 0.018), ALT (r = 0.41, p < 0.036) and gamma-glutamyltransferase (gammaGT) (r = 0.51, p < 0.007), between serum triglycerides (TG) and AST (r = 0.28, p < 0.036), ALT (r = 0.30, p < 0.02) and between HOMA and ALT (r = 0.30, p < 0.03) and gammaGT (r = 0.35, p < 0.012). In group 2 patients with severe steatosis the prevalence of metabolic syndrome according to Adult Treatment Panel III (ATP III) was 40%. CONCLUSION: These data suggest that, in young adult non-diabetic grade III obese patients, fatty liver is always present and strictly related to insulin resistance which, in the presence of severe liver steatosis, is also related to serum ferritin.