Exploring Adiponectin in Autosomal Dominant Kidney Disease: Insight and Implications.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a common monogenic disorder characterized by renal cysts and progressive renal failure. In kidney diseases, adipose tissue undergoes functional changes that have been associated with increased inflammation and insulin resistance mediated by release of adipokines. Adiponectin is involved in various cellular processes, such as energy and inflammatory and oxidative processes. However, it remains to be determined whether adiponectin is involved in the concomitant metabolic dysfunctions present in PKD. In this scenario, we aimed to analyze: (a) PPARγ, ADIPOQ, ADIPOR1 and ADIPOR2 gene variations in 92 ADPKD patients through PCR-Sanger sequencing; and (b) adiponectin levels and its oligomerization state by ELISA and Western Blot. Our results indicated that: (a) 14 patients carried the PPARγ SNP, 29 patients carried the ADIPOQ SNP rs1501299, and 25 patients carried the analyzed ADIPOR1 SNPs. Finally, 82 patients carried ADIPOR2 SNPs; and (b) Adiponectin is statistically lower in ADPKD patients compared to controls, and further statistically lower in ESRD than in non-ESRD patients. An inverse relationship between adiponectin and albumin and between adiponectin and creatinine and a direct relationship between adiponectin and eGFR were found. Interestingly, significantly lower levels of adiponectin were found in patients bearing the ADIPOQ rs1501299 SNP and associated with low levels of eGFR. In conclusion, adiponectin levels and the presence of ADIPOQ rs1501299 genotype are significantly associated with a worse ADPKD phenotype, indicating that both could potentially provide important insights into the disease. Further studies are warranted to understand the pathophysiological role of adiponectin in ADPKD patients.

Serum Interleukin 6, Controlling Nutritional Status (CONUT) Score and Phase Angle in Patients with Crohn's Disease.

Crohn's disease (CD) is a chronic inflammatory disorder that may occur in any segment of the gastrointestinal tract. Asymptomatic or untreated inflammation along with malnutrition can often coexist in patients with CD, impairing clinical outcomes, therefore the aim of this study was to assess the relationship between inflammation, malnutrition risk and nutritional status in CD patients. Consecutive adult CD outpatients aged 18-65 years were recruited. Disease activity was clinically defined by the Crohn's Disease Activity Index (CDAI), whilst anthropometry and phase angle (PhA) were measured. The Controlling Nutritional Status (CONUT) score was retrospectively calculated for screening malnutrition risk and blood samples were taken. A total of 140 CD patients with a mean age of 38.8 ± 13.9 years and an average weight of 64.9 ± 12.0 kg were included. Serum interleukin (IL)-6 concentration was increased in active-CD patients, unrelated to medical treatment, which was associated with CDAI and PhA. Based on the CONUT score, the prevalence of patients with moderate/severe malnutrition risk (score ≥ 5) was 10%, showing lower age, body mass index and fat mass, but higher IL-6 and IL-1ß levels than subjects classified as not at risk (score 0-1). Finally, increased IL-6 levels and reduced PhA values were identified as independent predictors of moderate/severe malnutrition risk (p < 0.05). In conclusion, IL-6 increased in active-CD patients, which was inversely correlated with PhA. Although the CONUT score might be helpful for identifying CD patients at moderate/severe risk of malnutrition, larger studies are needed to verify these results in different settings.

Prevalence of Sarcopenia in Women with Breast Cancer.

Sarcopenia is a common finding in patients with cancer and potentially influences the patient's outcome. The aim of this study was to evaluate the prevalence of sarcopenia, according to the European Working Group on Sarcopenia in Older People, in a sample of women with breast cancer (BC) and a BMI lower than 30 kg/m2. This cross-sectional study was conducted in patients with BC, stage 0-III, and receiving therapy for BC; the women were recruited at the Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy. A control group with similar age and BMI was selected from the internal database. Anthropometry, bioimpedance analysis (BIA) and hand grip strength (HGS) were measured to detect sarcopenia. A total of 122 patients (mean age 49.3 ± 11.0 years, BMI 24.6 ± 3.0 kg/m2) and 80 healthy controls were analyzed. Sarcopenia was found in 13.9% patients with BC, while none of the subjects in the control group was sarcopenic. By comparing BC patients with and without sarcopenia and the control group, the fat-free mass of sarcopenic BC patients were significantly lower than those of both non-sarcopenic BC patients and the control (p < 0.05). The phase angle was also significantly lower in sarcopenic patients (−0.5 degrees, p = 0.048) than in the control group. Considering the prevalence of sarcopenia in patients with BC, our findings suggest the usefulness of body composition and HGS evaluation for early screening of sarcopenia to reduce the risk of associated complications.

Bioelectrical Phase Angle in Patients with Breast Cancer: A Systematic Review.

Breast cancer (BC) is the most common cancer diagnosed among women worldwide. Phase angle (PhA), a proxy measure of membrane integrity and function, has gained relevance in clinical practice and it has been suggested to be a prognostic and nutritional indicator. This systematic review aimed to explore PhA and its relationship with nutritional status and survival in BC patients. Four databases (PubMed, EMBASE, Web of Science, and CINAHL) were systematically searched until September 2021 for studies evaluating PhA in BC patients. A total of 16 studies met the inclusion criteria, where 11 were observational studies and 5 were interventional studies. Baseline PhA-value varied from 4.9 to 6.30 degrees, showing a great variability and heterogeneity across the selected studies. Available data suggested that PhA decreased by 5-15% after completing chemotherapy, and those effects might persist in the long term. However, the use of tailored nutritional and/or exercise programs during and after therapy could prevent PhA reduction and body derangement. High PhA values were found in women displaying a better nutritional status, while inconsistent data were found on survival. Therefore, further studies are needed to focus on the clinical relevance of PhA in BC patients, evaluating its association with disease outcomes and survival.

Nutritional Screening and Anthropometry in Patients Admitted From the Emergency Department.

BACKGROUND: Due to the high prevalence of malnutrition among hospitalized patients, screening and assessment of nutritional status should be routinely performed upon hospital admission. The main objective of this observational study was to evaluate the prevalence of and the risk for malnutrition, as identified by using three nutritional screening tests, and to observe whether some anthropometric and functional parameters used for nutritional evaluation were related to these test scores. METHODS: This single-center observational study included 207 patients admitted from the emergency department for hospitalization in either the internal medicine or surgery units of our institution from September 2017 to December 2018. The prevalence of malnutrition among this patient sample was evaluated by using the Nutritional Risk Screening (NRS-2002), the Subjective Global Assessment (SGA) and the Global Leadership Initiative on Malnutrition (GLIM) criteria. Body mass index (BMI), bioimpedance analysis (BIA), handgrip strength (HGS) and calf circumference (CC) assessments were also performed. RESULTS: According to the NRS-2002, 93% of the patients were at no risk or at low nutritional risk (NRS score < 3), and 7% were at a high nutritional risk (NRS score ≥ 3). On the other hand, according to the SGA, 46.3% of the patients were well-nourished (SGA-a), 49.8% were moderately malnourished (SGA-b), and 3.9% were severely malnourished (SGA-c). Finally, according to the GLIM criteria, 18% patients were malnourished. Body weight, body mass index (BMI), phase angle (PhA), CC and HGS were significantly lower in the patients with NRS scores ≥ 3, SGA-c and in patients with stage 1 and stage 2 malnutrition, according to the GLIM criteria. CONCLUSION: The NRS-2002, the SGA and the GLIM criteria appear to be valuable tools for the screening and assessment of nutritional status. In particular, the lowest NRS-2002, SGA and GLIM scores were associated with the lowest PhA and CC. Nevertheless, a weekly re-evaluation of patients with better screening and assessment scores is recommended to facilitate early detection of changes in nutritional status.

Bioelectrical impedance (BIA)-derived phase angle in adults with obesity: A systematic review.

BACKGROUND & AIMS: Bioimpedance analysis-derived phase angle (PhA), as marker of body cell mass and cell integrity, might be altered in obesity, a condition which is characterized by alterations in muscle structure and function. The aim of this systematic review was to evaluate whether and to which extent PhA varies in individuals/patients with excess body weight focusing on: a) changes in PhA due to obesity; b) changes in PhA after bariatric interventions or training programs. METHODS: According to PRISMA criteria, a systematic literature search until February 2021 using PubMed, Embase, Scopus, and Web of Science was performed. Selection criteria included studies on patients with obesity without comorbidities other than metabolic diseases. RESULTS: A total of 278 articles were first identified. After removing duplicates and excluding studies that did not fulfil the inclusion criteria, the full text of the remaining 80 potentially relevant studies was examined to finally retrieve 11 cross-sectional and 10 longitudinal studies. Few studies have shown that PhA is lower in individuals/patients with obesity than in controls. The only study on the matter showed a decrease with age after the fourth decade of life. Four out of five studies reported consistently greater mean values in men than in women. In two studies PhA was lower in patients with severe obesity; in addition, Patients with low PhA had higher BMI and PhA was inversely correlated with fat mass. Longitudinal studies showed that PhA markedly decreased after bariatric surgery and slightly increased after training programs. CONCLUSIONS: Thus, a relatively low number of studies have evaluated PhA in individuals/patients with obesity with sometimes contradictory and preliminary results. PhA might be useful to evaluate muscle quality in individuals/patients with obesity but further studies are needed to more accurately associate this variable with changes in muscle structure and strength, as well as in metabolic functions.

A proposal for reference values of hand grip strength in women with different body mass indexes.

OBJECTIVE: Hand grip strength (HGS) is frequently used in clinical practice, resulting in a potential marker of nutritional status. This study aimed to develop reference values of HGS in Italian women with different categories of body mass index (BMI). Additionally, the main predictors of HGS were identified. METHODS: A cross-sectional study was conducted in Italian women between ages 16 and 55 y with different categories of BMI at the Department of Clinical Medicine and Surgery, Federico II University Hospital, Naples Italy. The whole sample was divided into tertiles according to BMI: 15 to 17.29 kg/m2 (T1), 17.3 to 19.9 kg/m2 (T2), and 20 to 25 kg/m2 (T3). Anthropometry, bioimpedance analysis, and muscle strength by an HGS test were evaluated. The cut-off values for HGS were developed for all participants and stratified by age group. Finally, a multivariate linear regression analysis was performed to assess the main predictors of HGS. RESULTS: A total of 529 women with a mean age of 23.2 ± 7.0 y and an average BMI of 18.9 ± 2.5 kg/m2 were analyzed. HGS was higher for the dominant hand than for the non-dominant hand in all BMI tertiles. On both sides, according to age groups, HGS increased with increasing age in T1 and T3, whereas it increased in the women between ages 20 and 30 y in T2 only. Multivariate linear regression analysis showed that predictors of HGS varied according to tertiles. Specifically, we found that body weight (R2 = 0.252) was the main predictor in T1, whereas phase angle (PhA) was the main determinant in both T2 (R2 = 0.240) and T3 (R2 = 0.216). CONCLUSION: This study defined the normal reference values of HGS in Italian women with different BMI ranges, stratifying the sample group by age. Additionally, the main predictors of HGS were assessed for each BMI tertile. In primary malnutrition (T1), the main predictor of HGS was body weight, whereas in the other two tertiles (T2, T3), the PhA was the main predictor of HGS.

Bioelectrical impedance analysis (BIA) -derived phase angle in sarcopenia: A systematic review.

BACKGROUND & AIMS: Bioelectrical impedance analysis-derived phase angle (PhA) has been gaining attention in the clinical evaluation of nutritional status because it is thought to be a proxy of water distribution and body cell mass; it is also associated to muscle strength and is an effective predictor of different clinical outcomes. Since an association may be expected between PhA and sarcopenia (defined by low skeletal muscle mass and impaired muscle function), the aim of this systematic review was to evaluate: a) changes in PhA due to sarcopenia; b) prevalence of sarcopenia according to PhA values; c) derivation of phase angle cut-offs for detecting sarcopenia; d) sarcopenia and PhA as predictors of clinical outcomes. METHODS: A systematic research on electronic databases (PubMed, Embase, Scopus and Web of Science) from inception to January 31st, 2020 was performed according to PRISMA checklist. Using PICOS strategy, "P" corresponded to participants of any age, gender or ethnicity, "I" designated diagnosis of sarcopenia, "C" indicated subjects without sarcopenia, "O" corresponded to PhA, and "S" selected all study types. Methodological quality was assessed using the National Institute of Health (NIH) quality assessment tool. RESULTS: Through the initial literature search and after removing duplicates and excluding papers by screening titles and abstracts, 79 potentially relevant studies were examined. Thirteen studies (7668 subjects) met the inclusion criteria. The overall risk of bias was low. Sarcopenia was associated with a significant lower PhA in seven studies out of eight, while five studies out of six reported a high prevalence of sarcopenia was in patients with low PhA. Different cut-off point values from 4.05 to 5.05° have been derived for the identification of sarcopenia. PhA and sarcopenia were independent predictors of survival in cancer patients and geriatric hospitalized patients. CONCLUSIONS: Data from the selected papers demonstrate that PhA is decreased in sarcopenic subjects and the prevalence of sarcopenia is higher in subjects with low PhA. Further studies are needed to determine to what extent PhA may be valuable in detecting low muscle quality and/or identifying sarcopenia.

Bilio-pancreatic diversion: report of a case involving bone metabolism complications.

Prolonged vitamin D deficiency may result in lower calcium absorption and osteoporosis, leading to pathologic fractures. We report the case of a young woman with severe, complicated osteoporosis, which developed several years after biliopancreatic diversion that was performed to treat morbid obesity. Chronic low vitamin D levels provided a continuous stimulus for parathormone secretion, which resulted in parathyroid hyperplasia/adenoma and autonomous production of the hormone.

Association between Health-Related Quality of Life and Nutritional Status in Adult Patients with Crohn's Disease.

This study aimed to assess health related quality of life (HRQoL) in adult patients with Crohn's disease (CD), considering disease severity and gender differences, and also its relationship with nutritional status. Consecutive adult patients aged 18-65 years with CD were recruited. Disease activity was clinically defined by the Crohn's Disease Activity Index (CDAI) in active and quiescent phases. HRQoL was evaluated using the validated short form (SF)-36 questionnaire for the Italian population. Additionally, anthropometry, bioimpedance analysis, and handgrip-strength (HGS) were performed. Findings showed that 135 patients (79 men and 56 women) were included, having a mean age of 38.8 ± 14 years and a BMI of 23.2 ± 3.7 kg/m2. Overall, active CD patients had a lower perception of their QoL compared to those clinically quiescent, while gender differences emerged mostly in the quiescent group. Interestingly, HRQoL was significantly associated with many nutritional variables, and muscle strength was the main predictor. Therefore, HRQoL is perceived lower in active compared to quiescent patients, but women experienced poorer QoL than men, especially in the quiescent phase. Finally, higher QoL scores were found in subjects being in clinical remission phase with a preserved muscle function. However, further studies are still required to verify these findings.

Evaluation of nutritional adequacy in adult patients with Crohn's disease: a cross-sectional study.

PURPOSE: Inadequate oral intake may play an important role in the onset of malnutrition in patients with Crohn's disease (CD). The aims of this cross-sectional study were: (1) to compare dietary intake in clinically active and quiescent CD patients, and (2) to assess patients' nutritional adequacy relative to the dietary reference values (DRVs) for the Italian population using LARN (Livelli di Assunzione di Riferimento di Nutrienti ed energia per la popolazione italiana). METHODS: Patients aged between 18 and 65 years with a diagnosis of CD were recruited. All participants underwent anthropometry and were instructed to fill in a 3-day food record. Disease activity was clinically defined using the Crohn's disease activity index (CDAI). RESULTS: Overall, 117 patients, 71 males and 46 females, with a mean age of 39.6 ± 13.8 years and a mean body weight of 65.4 ± 11.8 kg, were ultimately included. Our findings showed that the amount of nutrients was similar between patients with active and quiescent disease. The mean intake of macronutrients was adequate, except for fiber, while dietary micronutrients were insufficient. Median intakes of sodium, phosphorus, and fluorine met LARN recommendations in both sexes, and the DRVs were accomplished by many patients (53/117; 104/117 and 98/117, respectively). Interestingly, dietary amounts of iron and zinc were barely acceptable in males but not in females. However, a few of the patients (< 15) met the LARN for potassium, calcium, and magnesium, regardless of sex and CDAI. With respect to vitamins, no relevant difference was found between the active and quiescent groups, and none of them met recommended values in both sexes. CONCLUSIONS: This study showed that the assessment of dietary intake can be crucial for optimizing dietary intervention with focused nutrition counseling, to improve nutritional status in CD patients.

New Predictive Equations for Estimating Resting Energy Expenditure in Adults With Crohn's Disease.

BACKGROUND: Increased resting energy expenditure (REE) has been hypothesized to be a potential cause of weight loss in individuals with Crohn's disease (CD). This study aimed to develop and validate new predictive equations for estimating REE in adults with CD. METHODS: Adults, ages 18-65 years, with CD were recruited. Anthropometry, indirect calorimetry, and bioimpedance analysis were performed in all patients. Disease activity was assessed by Crohn's Disease Activity Index. The new predictive equations were generated using different regression models. Prediction accuracy of the new equations was assessed and compared with the most commonly used equations. RESULTS: A total of 270 CD patients (159 males, 111 females) were included and randomly assigned to the calibration (n = 180) and validation groups (n = 90). REE was directly correlated with weight and bioimpedance index, whereas the relation with both age and disease activity was inverse. The new equations were suitable for estimating REE at population level (bias: -0.2 and -0.3, respectively). Individual accuracy was good in both models (≥80%, respectively), especially in females; and similar results were shown by some of the selected equations. But, when accuracy was set within ±5%, the new equations gave the highest prediction. CONCLUSION: The new, disease-specific, equations for predicting REE in individuals with CD give a good prediction accuracy as far as those proposed in the literature for the general population. However, the new ones performed better at the individual level. Further studies are needed to verify the reliability and usefulness of these new equations.

Assessment of bioelectrical phase angle as a predictor of nutritional status in patients with Crohn's disease: A cross sectional study.

BACKGROUND & AIMS: The assessment of body composition (BC) can be used to identify malnutrition in patients with Crohn's disease (CD). The aim of this study was to evaluate the nutritional status of CD patients by assessing BC, phase angle (PhA) and muscle strength. Differences in disease duration and medications were also considered. METHODS: Consecutive adult CD patients aged 18-65 years were enrolled in this cross-sectional study. Disease activity was clinically defined by the Crohn's Disease Activity Index (CDAI) in the active and quiescent phases. All participants underwent anthropometry, BC and handgrip-strength (HGS) measurements; additionally, blood samples were taken. Data from CD patients were also compared with age-, sex- and BMI-matched healthy people. RESULTS: A total of 140 CD patients with a mean age of 38.8 ± 13.9 years and a mean body weight of 64.9 ± 12 kg were recruited and compared to controls. The findings showed that all nutritional parameters, especially PhA and HGS, were lower in CD patients than in controls, and these parameters were substantially impaired as disease activity increased. Active CD patients had a lower body weight and fat mass than both the quiescent and control groups. PhA was negatively correlated with age (r = -0.362; p = 0.000) and CDAI (r = -0.135; p = 0.001) but was positively associated with fat free mass (FFM) (r = 0.443; p = 0.000) and HGS (r = 0.539; p = 0.000). Similarly, serum protein markers were lower in the active CD group than in the quiescent group (p < 0.05). Disease duration and medications did not significantly affect nutritional status. CONCLUSIONS: BIA-derived PhA is a valid indicator of nutritional status in CD patients, and its values decreased with increasing disease activity. Additionally, small alterations in BC, such as low FFM, and reduced HGS values can be considered markers of nutritional deficiency. Therefore, the assessment of BC should be recommended in clinical practice for screening and monitoring the nutritional status of CD patients.

Resting energy expenditure in adult patients with Crohn's disease.

BACKGROUND & AIMS: Crohn's disease (CD) is a chronic intestinal disorder of unknown etiology involving any section of the gastrointestinal tract often associated with protein-energy malnutrition (PEM). Increased resting energy expenditure (REE) unmatched by adequate dietary intake is amongst the pathogenetic mechanisms proposed for PEM. Aim of this study was to evaluate REE in CD patients receiving or not immuno-suppressive therapy as compared to controls. METHODS: 36 CD patients (22 M and 14 F, age range 18-55 years) clinically stable and without complications since at least 6 month were studied. REE was evaluated by indirect calorimetry and body composition by BIA. Full biochemistry was performed. Patients were divided into two groups: Group 1 (G1 = 12 patients) without and Group 2 (G2 = 24 patients) with immuno-suppressive therapy. RESULTS: The two groups were similar for age, height and BMI whereas significantly differed for weight (G1 vs G2: 56.9 ± 7.44 vs 62.3 ± 8.34 kg), fat free mass (FFM: 40.4 ± 5.73 vs 48.2 ± 7.06 kg), fat mass (FM: 17.0 ± 3.55 vs 13.9 ± 5.54 kg) and phase angle (PA: 5.6 ± 1.4 vs 6.5 ± 1.0°). Serum inflammation parameters were significantly higher in G1 than in G2: hs-PCR: 7.76 ± 14.2 vs 7.16 ± 13.4 mg/dl; alfa 2-protein: 11.7 ± 3.69 vs 9.74 ± 2.08 mg/dl; fibrinogen: 424 ± 174 vs 334 ± 118 mg/dl (p < 0.05). REE was higher in G2 vs G1: 1383 ± 267 vs 1582 ± 253kcal/die (p < 0.05) both in men: 1579 ± 314 vs 1640 ± 203 and women: 1267 ± 140 vs 1380 ± 132. Nevertheless, when corrected for FFM, REE resulted higher in G1 than G2 (34.8 ± 4.89 vs 33.0 ± 4.35 kcal/kg, p < 0.05) group, also higher compared to our, age and sex matched, control population (REE/FFM: 30.9 ± 4.5 kcal/kg). CONCLUSIONS: Our preliminary results show that REE when adjusted for FFM is increased in clinically stable CD patients and mildly reduced by immunosuppressive therapy possibly through a direct action on inflammation and on body composition characteristics.

Serum levels of adipocytokines in psoriasis patients receiving tumor necrosis factor-α inhibitors: results of a retrospective analysis.

BACKGROUND: Adipocytokines are bioactive molecules that are deeply involved in the occurrence of atherosclerosis, obesity, and autoimmune inflammatory diseases. OBJECTIVES: This study was conducted to evaluate the effects of tumor necrosis factor-α (TNF-α) inhibitors on serum levels of adipocytokines in patients with chronic plaque psoriasis. METHODS: Serum levels of adiponectin, resistin, visfatin, leptin, TNF-α, and interleukin-6 (IL-6) were evaluated in sera obtained from 47 patients with psoriasis, both at baseline and after they had received TNF-α inhibitors for 24 weeks. Equivalent data were obtained for 39 control subjects matched by age, sex, body mass index, waist : hip ratio, geographical origin, Mediterranean dietary habits, and smoking habits. RESULTS: At baseline, mean serum levels of TNF-α, IL-6, leptin, resistin, and visfatin were higher in the psoriasis group than in healthy controls; these differences were statistically significant (P < 0.05). Conversely, mean serum levels of adiponectin were significantly lower in patients with psoriasis than in controls (P < 0.0001). Serum levels of adipocytokines did not linearly correlate with anthropometric indices in psoriasis patients (P > 0.05), except in the case of leptin, for which serum levels were related to waist : hip ratio in both men and women (P < 0.05). After 24 weeks of treatment, although serum levels of proinflammatory adipocytokines were decreased, only that of leptin showed a statistically significant reduction (P = 0.0003). Serum levels of adiponectin, an anti-inflammatory adipocytokine, were only mildly increased and persisted at a significantly lower level than in healthy controls (P > 0.005). CONCLUSIONS: Patients with psoriasis show an imbalance between pro- and anti-inflammatory adipocytokines, which is reduced but not normalized after administration of TNF-α inhibitors for 24 weeks. This partial rebalancing seems to be mainly related to a reduction in proinflammatory adipocytokines, rather than an increase in anti-inflammatory adipocytokines.

The p53 codon 72 (Arg72Pro) polymorphism is associated with the degree of insulin resistance in type 2 diabetic subjects: a cross-sectional study.

Tumor suppressor protein p53 has been demonstrated to regulate genes involved in energy generating metabolic pathways and apoptosis. To date, a new field of research is the involvement of TP53 codon 72 (Arg72Pro) polymorphism in the diabetic disease. The aim of this study was to evaluate whether the genotype and the related genetic models of Arg72Pro polymorphism of TP53 (rs1042522) are associated with insulin resistance and its metabolic parameters in diabetic and non-diabetic subjects. We examined 335 type 2 diabetic patients (65.5 ± 8.4 years) and 367 non-diabetic subjects (60.5 ± 11.7 years). The results were validated in a validation sample consisting of 199 type 2 diabetic (66.2 ± 8.5 years) and 224 non-diabetic subjects (61.2 ± 12.7 years). In the study sample, the analysis of covariance, adjusted for the effects of age, gender and BMI, showed a significant genotype-diabetes effect on insulin resistance evaluated by HOMA-IR (p = 0.038). This result was mediated by variations in fasting plasma insulin (p = 0.027), as no TP53 genotype-diabetes effects were detected for fasting plasma glucose. In particular, in the diabetic subjects, Pro/Pro genotype was associated with lower values of HOMA-IR with respect to Arg/Arg (p = 0.013) and Arg/Pro (p = 0.006) carriers. No difference in HOMA-IR between diabetic and non-diabetic Pro/Pro carriers was found. Significant recessive model-diabetes interaction effects on fasting insulin and HOMA-IR adjusted for age, sex and BMI were found (p = 0.007 and p = 0.029, respectively). Linear regression analyses, based on the assumption of an additive genetic model adjusted for age, sex and BMI, highlight p53 gene-diabetes interaction effects on fasting insulin (ß = -1.27; p = 0.001) and HOMA-IR (ß = -0.22; p = 0.006). The results of statistical analyses on fasting insulin and HOMA-IR were all confirmed in the validation sample. Furthermore, the logistic regression models confirmed that the effect of HOMA-IR levels on diabetes was moderated by Pro/Pro genotype in both study and validation samples (OR = 0.29, p = 0.034, 95 % CI = 0.09-0.91, OR = 0.37, p = 0.035, 95 % CI = 0.15-0.93, respectively). Our findings suggest that p53 codon 72 (Arg72Pro) polymorphism influences insulin resistance in type 2 diabetic patients independently of body mass.

Mass spectrometry measurement of plasma hepcidin for the prediction of iron overload.

BACKGROUND: Hepcidin has emerged as the primary regulator of iron homeostasis. Previous studies on assessing urinary hepcidin are limited. We developed a method for quantifying hepcidin-25 (Hep-25) in plasma using surface-enhanced laser-desorption-ionization time-of-flight mass spectrometry (SELDI-TOF/MS) and a 25-AA peptide as reference standard. The aims of the study were 1) to assess the performance of this method in different conditions of iron metabolism disorders; 2) to assess the diagnostic validity of non-invasive serum biomarkers in the identification of iron overload. METHODS: Validation of the method was performed in 10 patients with type I hemochromatosis (HE) and in 177 subjects previously enrolled in a general population epidemiological study. Among the latter group, 17 had non-alcoholic fatty liver disease, 10 had chronic hepatitis C, and 150 subjects had normal ultrasound, normal liver function tests (LFTs), an alcohol intake < 20 g ethanol/day and were negative for the C282Y mutation. The following biomarkers were assayed in each case: plasma Hep-25, C282Y and H63D mutations of the HFE gene; serum iron, ferritin (SF), transferrin saturation, transaminases, γ-glutamyltransferase (GGT), glucose, insulin, total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol and triglycerides. RESULTS: Plasma Hep-25 concentrations were higher in HCV+ patients (26.3 ± 7.2 nmol/L) than in controls, and correlated positively with SF (p < 0.001). H63D heterozygous subjects revealed a pattern of iron overload that was significantly higher than H63D wild type subjects. Analyzing the data with the Biomarker Pattern 5.0.2. software to identify the most significant biomarkers for discriminating between HE cases and controls allowed us to produce an algorithm with four terminal nodes, which included glucose > 4.8 mmol/L and Hep-25/SF ratio ≤ 6.6 as the main splitters. These variables enabled the correct diagnosis of HE with 100% sensitivity, 93% specificity and an area under the receiver operating characteristic (ROC) curve of 0.993. CONCLUSIONS: Our plasma Hep-25 mass spectrometry method yields measurements that reflect pathological and genetic influences; simple non-invasive biomarkers (Hep-25/SF ratio and glucose) can predict the presence of HE.

Noninvasive evaluation of abdominal fat and liver changes following progressive weight loss in severely obese patients treated with laparoscopic gastric bypass.

BACKGROUND: Obesity is a chronic complex disease, consequence of an unbalance between energy intake and expenditure and of the interaction between predisposing genotype and facilitating environmental factors. The aim of the study was to evaluate body composition, abdominal fat, and metabolic changes in a group of severely obese patients before and after laparoscopic gastric bypass (LGBP) at standardized (10% and 25%) total weight loss. METHODS: Twenty-eight patients (14 M, 14 F; age 41.71 +/- 6.9 years; body mass index (BMI) 49.76 +/- 5.8 kg/m(2)) were treated with laparoscopic gastric bypass. All evaluations before surgery and after achieving ~10% and ~25% weight loss (WL). Body composition was assessed by bioimpedance analysis; resting metabolic rate (RMR) was measured by indirect calorimetry. RESULTS: Body weight, BMI, and waist circumference significantly decreased at 10% and 25% WL. We observed a significant reduction of both RMR (2,492 +/- 388 at entry vs. 2,098 +/- 346.6 at 10% WL vs. 2,035 +/- 312 kcal per 24 h at 25% WL, p = 0.001 vs. baseline) as well as of RMR corrected for fat-free mass (FFM; 35.7 +/- 6.7 vs. 34.9 +/- 9.0 at 10% WL vs. 33.5 +/- 5.4 at 25% WL kilocalorie per kilogram FFM x 24 h, p = 0.041 vs. baseline). Body composition analysis showed a relative increase in FFM and a reduction of fat mass at 25% WL. A significant reduction in blood glucose, insulin, homeostasis model assessment index was observed. Ultrasonography showed a marked decrease in the signs of hepatic steatosis. CONCLUSION: In conclusion, our study confirms that LGBP is a safe procedure in well-selected severely obese patients and has early favorable effects on both metabolic parameters and body composition. Longer-term observations are required for in-depth evaluation of body composition changes.

The Pro/Pro genotype of the p53 codon 72 polymorphism modulates PAI-1 plasma levels in ageing.

Plasminogen activator inhibitor 1 (PAI-1) is over-expressed during ageing and it has been linked to cellular senescence. Recently, PAI-1 has been also identified in vitro as a critical downstream target of p53. TP53, the p53 gene, has a common functional polymorphism at codon 72 which influences the capability to modulate both apoptosis and cell senescence. In the attempt to demonstrate an in vivo role of p53 in the relationship between PAI-1 and age, we studied PAI-1 on 570 healthy subjects (aged from 18 to 92yrs.). PAI-1 showed significant relationship with age (r=0.12, p=0.02). Stratifying by genotype, it became evident that the association between PAI-1 and age was mainly due to Pro/Pro subjects (partial r=0.75, p<0.01). These results have been confirmed by a validation study on an independent sample population of 496 subjects (aged from 18 to 94yrs.). This is the first demonstration of an in vivo role of TP53 polymorphism in PAI-1 regulation, supporting the hypothesis that the effects of this polymorphism are age-dependent. In particular, our results indicate that Pro/Pro genotype plays a pivotal role in determining PAI-1 levels in aged subjects, while in Arg carriers PAI-1 levels are associated to the known insulin related determinants.

Prognostic significance of bioelectrical impedance phase angle in advanced cancer: preliminary observations.

Bioelectrical impedance-derived phase angle is a potentially sensible indicator of protein-energy malnutrition and of fat-free mass loss, frequent in patients with advanced cancer. We evaluated in 13 patients with advanced cancer some biochemical (serum albumin, lymphocyte count, cholesterol, cholinesterase) and clinical (Karnofsky index, Subjective Global Assessment, dietary inquiry) parameters and bioelectrical impedance analysis was performed. In addition to albumin, cholinesterase, and the Karnofsky index, phase angle (R(2)=0.384, P=0.024) was found to be strictly related to survival time and can be therefore considered a prognostic tool in patients with advanced cancer.