Federica Coccia

Lack of effect of apolipoprotein C3 polymorphisms on indices of liver steatosis, lipid profile and insulin resistance in obese Southern Europeans.

BackgroundApolipoprotein C3 (APOC3) is a component of triglyceride-rich lipoproteins, and APOC3 rs2854116 and rs2854117 polymorphisms have been associated with non-alcoholic fatty liver disease, hypertriglyceridaemia, and insulin-resistance.ObjectiveTo determine if the APOC3 variants alter the susceptibility of obese subjects to develop liver damage, hypertrigliceridaemia, and insulin-resistance.MethodsThe study was carried out on 585 unrelated obese Italians (median body mass index BMI = 41 kg/m2) who were genotyped for the rs2854116 and rs2854117 variants. All participants underwent oral glucose tolerance tests (OGTT), with measurement of glucose, insulin, lipid parameters. Indices of insulin-resistance (HOMA and ISI) were calculated. Alanine transaminase (ALT) and aspartate transaminase (AST) were used as markers of liver injury.ResultsThe study subjects were divided into two groups: those homozygous for the wild-type alleles at both SNPs (-482C and -455T alleles) and those who were carriers of at least one variant allele or both (-482T, -455C or both). Also each SNP was analysed independently. No significant differences were found in ALT and AST levels and in the lipid profile between the two groups. Insulin concentrations, glucose tolerance and insulin sensitivity were similar in the two groups.ConclusionWe did not identify any significant association between APOC3 polymorphisms and fatty liver disease, lipids, and insulin-resistance in obese subjects, thus not confirming the suggested role of these APOC3 gene sequence variants.

Laparoscopic gastric sleeve and micronutrients supplementation: Our experience

Background. Laparoscopic gastric sleeve (LGS) has been recently introduced as a stand-alone, restrictive bariatric surgery. Theoretically, LGS attenuates micronutrients deficiencies and associated complications that were typically observed following malabsorptive procedures. The aim of this study was to assess some micronutrients and mineral deficiencies in patients undergoing LGS. Methods. In the period between July 2008 and April 2010, 138 obese patients (110 females and 28 males) with mean BMI 44.4 kg/m2 ± 6.5, mean age 43.9 ± 10.9 years were enrolled and underwent LGS. Patients were followed up with routine laboratory tests and anthropometric measurements and assessed for nutritional status, as regards vitamin B12, folic acid, iron, hemoglobin, calcium, and vitamin D, every three months throughout 12 months. Results. 12 months after sleeve, patients did not show iron deficiency and/or anemia; plasma calcium levels were in the normal range without supplementation from the sixth month after the operation. Vitamin B12 and folic acid were adequately supplemented for all the follow-up period. Vitamin D was in suboptimal levels, despite daily multivitamin supplementation. Conclusion. In this study, we showed that LGS is an effective surgery for the management of morbid obesity. An adequate supplementation is important to avoid micronutrients deficiencies and greater weight loss does not require higher dosage of multivitamins.

Association of FTO Polymorphisms with Early Age of Obesity in Obese Italian Subjects

Obesity is recognized as a major health problem worldwide. Genetic factors play a major role in obesity, and genomewide association studies have provided evidence that several common variants within the fat mass- and obesity-associated (FTO) gene are significantly associated with obesity. Very limited data is available on FTO in the Italian population. Aims of our study are to investigate: (1) the association of FTO gene SNPs rs9939609 and rs9930506 with body mass index (BMI) and obesity-related parameters in a large cohort (n = 752) of Italian obese subjects; (2) the association between the two FTO SNPs and age of onset of obesity. Our results demonstrate a strong association between FTO SNPs rs9939609 (P < 0.043) and rs9930506 (P < 0.029) with BMI in the Italian population. FTO rs9930506 was significantly associated with higher BMI in a G allele dose-dependent manner (BMI + 1.4 kg/m2 per G allele). We also observed that the association with BMI of the two FTO variants varied with age, with the carriers of the risk alleles developing an increase in body weight earlier in life. In conclusion, our study further demonstrates a role of the genetic variability in FTO on BMI in a large Italian population.

Axis II disorders, body image and childhood abuse in bariatric surgery candidates

BACKGROUND AND AIMS Psychiatric disorders are common in obese patients and they are often considered contraindications for bariatric surgery. In this patients Axis I profile has been widely investigated, while only few studies on Axis II profile are reported. Aim of the study was to examine the prevalence of Axis II psychopathology, to describe the typical body image and to evaluate the prevalence of childhood abuse in bariatric surgery candidates. MATERIALS AND METHODS A total of 102 consecutive obese patients (77 females) were evaluated by the Structured Clinical Interview for DSM IV which assessed Axis I Disorders. After the exclusion of Axis I Disorders, 50 patients (36 females, BMI: 44.68 ± 9.48 Kg/m2, age: 44.5 ± 11.7 years) were enrolled. All 50 patients received a psychiatric assessment including the Structured Clinical Interview for DSM-IV Axis II Disorders (SCID-II); the Body Uneasiness Test, part a (BUT-A), which assesses body image disorders; the Childhood Trauma Questionnaire (CTQ) as a screening test of childhood maltreatment histories. RESULTS Nineteen patients (38%) were affected by Axis II disorders. Cluster C disorders, including avoidant, dependent and obsessive-compulsive personality disorders, represented the most common diagnosis (24%). Moreover, 34 patients (68%) showed body image disorders (BID), with a GSI score ≥1.2 and 24 (48%) referred an abuse during childhood. Patients with Axis II disorder or a body image uneasiness or a history of maltreatment during childhood, showed higher BMI in adulthood. CONCLUSIONS Psychiatric comorbidities in obese patients were not only represented by depression or anxiety (Axis I disorders), but also by personality disorders (Axis II), body image disorders and childhood abuse. The identification of these conditions could improve outcomes of bariatric surgery and represent an indication for a most important psychiatric support before, during and after surgery.

Search for Genetic Variant in the Apelin Gene by Resequencing and Association Study in European Subjects

AIMS Apelin is a peptide produced and secreted by white adipose tissue. It is synthesized as preproapelin, a protein containing 77 aminoacids which is then cleaved to shorter active fragments. As an adipokine, apelin plays a role in the regulation of many biological functions, including body energy homeostasis and glucose metabolism, water balance, and immunity. We have recently demonstrated that subjects with type 2 diabetes (T2D) have significantly higher serum apelin levels compared with controls, and that these levels associate with fasting glucose, basal disposition index, age, and diagnosis of T2D. The first aim of this study was to search for sequence variants in the apelin gene (APLN), located on chromosome Xq25-q26.1 that may associate with serum levels of apelin. The second aim was to analyze the possible association between diabetes and diabetes-related traits and APLN variants. METHODS We designed a two-step genetic association study. Step one consisted of an initial screen of 100 individuals selected from the extremes of the apelin distribution levels wherein we sequenced the APLN gene to identify common variants. In step two, the rs181301686 with a minor allele frequency >0.2 was genotyped in 917 individuals to explore its association with T2D and diabetes-related traits. RESULTS Five sequence variations were found across the APLN gene. To test for association with apelin levels, the rs181301686 and rs2281069 single-nucleotide polymorphisms were genotyped in 256 subjects for whom serum apelin levels were available. No significant differences were observed in apelin levels between genotypes. Association analysis in 917 individuals did not show significant differences between APLN genotypes and diabetes and diabetes-related traits. CONCLUSIONS Resequencing of the apelin gene in subjects stratified by low or high apelin levels identified five APLN variants in an European population. No association was found between the most frequent variant, diabetes, and metabolic parameters.

Sa1403 Upper Gastrointestinal Symptoms After Laparoscopic Sleeve Gastrectomy

occur at a higher frequency in ileal segments of refed guinea pigs (p=0.028). Ca2+-imaging in longitudinal muscle myenteric plexus preparations (N=3-4) revealed elevated responses to orexigenic ghrelin in fasted animals (p=0.013), but the percentage of responders to anorexigenic CCK-8 was higher in refed animals (p<0.001). High K+-evoked Ca2+-peaks were consistently higher in refed animals (p<0.001), suggestive of a hyperexcitable state. We investigated whether a humoral factor was involved by exposing cultured myenteric neurons (N=3-6) to fasted or refed guinea pig serum and found that the cells acutely exposed to refed serum displayed a higher Ca2+-peak (p<0.001) and more neurons became spontaneously active (p<0.001). Interestingly, we found that ghrelin-responses were higher in cells incubated with fasted serum (p=0.023), whereas serotonin-responses proved to be higher in cells incubated with refed serum (p=0.005). Centrifugal ultrafiltration (MW cutoff 3K) removed a feeding state-independent along with a feeding state-dependent factor from the serum, the latter reverting amplitudes of refed serumto fasted serum-responses (N=3). Since glycemia in refed guinea pigs was almost 3 times as high as in fasted guinea pigs, we tested whether these glucose-levels play a role in the fasted-refed differences in neuronal Ca2+-signaling (N=3). We found that ghrelin evoked higher amplitudes in cells incubated with fasted glucose-levels (p<0.001), whereas CCK-8 (p=0.005), serotonin (p= 0.006) and high K+ (p<0.001) evoked higher responses in cells incubated with refed glucoselevels. These observations indicate that the feeding status of an animal remains imprinted ex-vivo and humoral feeding state-related factors are implicated. Although the molecular link with hyperactivity is not entirely elucidated yet, we found that a glucose-dependent pathway is involved, probably in combination with other factors. Although responses in the refed state are generally increased, the reduced neuronal responses to ghrelin prove that the effect is signaling pathway-specific and suggests feeding state-related differential tuning of excitability.

Le ipoglicemie funzionali

RiassuntoLe ipoglicemie funzionali possono costituire un primo passo verso la malattia diabetica oppure essere una conseguenza di un intervento chirurgico sul tratto gastrointestinale superiore. Nell’ambito di quest’ultima categoria, accanto agli interventi di gastrectomia che in passato venivano fatti, spesso in urgenza, per la presenza di una patologia ulcerosa, si sta delineando una forma di ipoglicemia associata ad alcuni interventi di chirurgia bariatrica, effettuati per favorire la perdita di peso in pazienti obesi. Al di là di queste condizioni rimangono le forme cosiddette “reattive idiopatiche” che costituiscono un’alterazione del ricambio glucidico controversa. Alcuni studiosi, infatti, arrivano addirittura a negarne l’esistenza, quando è noto che nella comune pratica clinica spesso i pazienti ci riferiscono una sintomatologia suggestiva per la presenza di ipoglicemia in particolare a metà mattina, più o meno a distanza di 3–4 ore dalla prima colazione. Tuttavia, l’ipoglicemia è spesso un’autodiagnosi, intendendo con questo che spesso il paziente si reca dal medico accusando una mancanza di zuccheri e di sentirsi immediatamente meglio assumendo qualcosa di dolce. Addirittura si possono trovare articoli sulle riviste non mediche che confortano le persone e aiutano a fortificare la convinzione di andare spesso in ipoglicemia. Va da sé che il rimedio a questa autodiagnosi è normalmente molto ben accetto dalle persone che si sentono “costrette” ad assumere quando stanno male bibite zuccherate se non proprio caramelle, cioccolatini e altri dolci. Questo atteggiamento contrasta totalmente con le prescrizioni del medico che, laddove ravvisi veramente la presenza di una sindrome ipoglicemica funzionale, dovrà prescrivere proprio l’abolizione di carboidrati raffinati nella dieta e in questo articolo cercheremo di capirne il perché.