The rs45454496 (E1813K) variant in the adiposity gene ANK2 doesn't associate with obesity in Southern European subjects

Recently ANK2, encoding ankyrin-B (AnkB), has been proposed as an obesity susceptibility gene. AnKB negatively regulates the expression of glucose transporter 4 (GLUT4) in adipocytes, and it has been hypothesized that functional alterations of AnkB may determine the persistence of GLUT4 on the cell surface, increasing glucose transport in adipocytes. Adipose tissue-specific AnkB-KO mice develop obesity and progressive pancreatic islet dysfunction with age or high-fat diet. AnkB-deficient adipocytes exhibit increased lipid accumulation associated with increased glucose uptake and impaired endocytosis of GLUT4. Functional alterations have been observed in ANK2 gene in European Americans and African Americans and have been proposed as candidates to contribute to obesity susceptibility in humans. Considering that variants of ANK2 gene were previously observed in subjects of American and African American ethnicity, and that these variants were never studied in association with obesity, we performed a genetic association analysis with obesity in a cohort of Southern European subjects. For this study 1900 Italian subjects with body mass index (BMI) between 16 and 91 were selected. All subjects underwent clinical examination, anthropometric measurements and routine laboratory tests. The SNPs rs45454496 (E1813K) and rs35530544 (L1622I) have been studied in DNAs by Eco TM Real-Time PCR System by Illumina. Among the 1900 subjects we identified 15 (frequency 0.7%) heterozygous subjects for the rs45454496 variant and no homozygous subject. The observed frequency in our population is more than double that observed in other populations of European origin (0.7% vs 0.3%, p = 0.3). We then analysed the association between this polymorphism and clinical and biochemical characteristics. Carriers of the mutation showed no significantly differences compared to wild-type subjects in any of the parameters examined. Population stratification by BMI showed a random distribution of the rs45454496 variant according to weight. Also, population stratification based on glycaemic alterations showed no association of the rs45454496 variant with categories of glucose metabolism. Finally, we analysed the study cohort for the rs35530544, but we did not observe any subject carrying the variant in an initial sample of 840 patients. In conclusion, we observed that the rs45454496 (E1813K) variant of ANK2 gene, although showing a higher frequency in our Southern European population (0.7%) than the frequencies reported in other populations of European origin, in the analysed sample does not seem to have effects on clinical and metabolic alterations

Circulating miRNA-375 levels are increased in autoantibodies-positive first-degree relatives of type 1 diabetes patients

Growing evidence suggests that microRNAs (miRNAs) play a key role in beta-cell metabolism, proliferation and apoptosis, and in immune system functions, all processes involved in the pathogenesis of type 1 diabetes. In the context of diabetes, particular attention has been focused on miR-375, which has been studied most extensively as a putative biomarker of beta cell death. Although dysregulated miRNA profiles have been identified in type 1 diabetes patients, results are inconclusive. The aim of our study was to evaluate miR-375 levels in a very large and carefully selected cohort of 142 Sardinian subjects, which included 49 type 1 diabetes subjects, 46 autoantibodies (Aabs) positive first-degree relatives (FDR) of type 1 diabetes patients and 48 healthy controls. We observed that Aabs-positive FDR subjects showed significantly (p=1x10-6) increased levels of miR-375 compared to type 1 diabetes patients and healthy controls. Also, we observed that increased circulating miR-375 associated with later onset of diabetes, and a direct correlation between C-peptide levels and miR-375 levels, reflecting a longer β-cell residual function. However, ROC analysis to assess the possible predictive role of miR-375 levels on the diagnosis of type 1 diabetes in the FDR that were followed longitudinally did not show any predictive role (AUC 0.50). Hence, our results confirm the role of miR-375 in the autoimmune process of type 1 diabetes, but its utility as a single biomarker does not emerge as clinically applicable

The single-point insulin sensitivity estimator (SPISE) index is a strong predictor of abnormal glucose metabolism in overweight/obese children: a long-term follow-up study

Purpose: To investigate the relationship between the single-point insulin sensitivity estimator (SPISE) index, an insulin sensitivity indicator validated in adolescents and adults, and metabolic profile in overweight/obese children, and to evaluate whether basal SPISE is predictive of impaired glucose regulation (IGR) development later in life. Methods: The SPISE index (= 600 × HDL0.185/Triglycerides0.2 × BMI1.338) was calculated in 909 overweight/obese children undergoing metabolic evaluations at University of Cagliari, Italy, and in 99 normal-weight, age-, sex-comparable children, selected as a reference group, together with other insulin-derived indicators of insulin sensitivity/resistance. 200 overweight/obese children were followed-up for 6.5 [3.5–10] years, data were used for longitudinal retrospective investigations. Results: At baseline, 96/909 (11%) overweight/obese children had IGR; in this subgroup, SPISE was significantly lower than in normo-glycaemic youths (6.3 ± 1.7 vs. 7 ± 1.6, p < 0.001). The SPISE index correlated positively with the insulin sensitivity index (ISI) and the disposition index (DI), negatively with age, blood pressure, HOMA-IR, basal and 120 min blood glucose and insulin (all p values < 0.001). A correlation between SPISE, HOMA-IR and ISI was also reported in normal-weight children. At the 6.5-year follow-up, lower basal SPISE—but not ISI or HOMA-IR—was an independent predictor of IGR development (OR = 3.89(1.65–9.13), p = 0.002; AUROC: 0.82(0.72–0.92), p < 0.001). Conclusion: In children, low SPISE index is significantly associated with metabolic abnormalities and predicts the development of IGR in life

Circulating pro-neurotensin levels predict bodyweight gain and metabolic alterations in children

Background and aims: Neurotensin (NT) is an intestinal peptide released after fat ingestion, which regulates appetite and facilitates lipid absorption. Elevated plasma levels of its stable precursor pro-neurotensin (pro-NT) are associated with type 2 diabetes, obesity and cardiovascular mortality in adult populations; no data on pro-NT and metabolic disease are available in children. Aim of the study was to evaluate plasma pro-NT in relation to the presence of obesity in children, and to test if high pro-NT associates with the development of metabolic impairment later in life. Methods and results: For this longitudinal retrospective study, we studied 151 overweight/obese children undergoing metabolic evaluations at University of Cagliari, Italy. Pro-NT was also assessed in 46 normal-weight, age-, sex-comparable normal-weight children, selected as a reference group. At the baseline, pro-NT was comparable between overweight/obese and normal-weight children and correlated positively with age (p < 0.001), triglycerides (p < 0.001) and inversely with HDL levels (p = 0.008). Plasma pro-NT associated with high triglycerides with OR = 5.9 (95%CI: 1.24–28.1; p = 0.026) after adjustment for multiple confounders. At the 6.5-year follow-up, high basal pro-NT associated with impaired β-cell function to compensate for insulin-resistance (disposition index: r = −0.19, p = 0.035) and predicted bodyweight increase, as indicated by percentage change of standard deviation score BMI (median(95%CI) = +20.8(+4.9-+27.5)% in the highest tertile), independently from age, sex, triglycerides and insulin-resistance (standardized β = 0.24; p = 0.036). Conclusions: Elevated pro-NT levels in children are significantly associated with weight gain later in life and may represent a marker of susceptibility to metabolic impairment in presence of obesity

Measuring consumers attitudes towards health and taste and their association with food-related life-styles and preferences

The purpose of the current study, was to apply and validate the factor structure of the Health and Taste Attitude Scales in an Italian adult sample of 1224 subjects, recruited on a national basis in order to characterise consumers\u2019 food-related attitudes with weak and strong connotations of health and taste. Both exploratory and confirmatory factor analysis were used to evaluate the factor structure of the three sub-scales of Health (General health interest, Light product interest, Natural product interest) and three sub-scales of Taste (Craving for sweet foods, Using foods as a reward, Pleasure). Results showed that the internal structure was similar to the theoretical proposal, with two exceptions for the Taste scale. The Pleasure sub-scale presented strong problematic loadings and consequently was removed from the model. The Craving for sweet foods sub-scale was split into two new underlying constructs describing attitudes towards craving for sweet food based on their own experience and attitudes towards other-people\u2019s craving. The three Health sub-scales were used as a basis for the derivation of consumers clusters. Three groups of subjects with different interest in food-related health (Low, Medium, and High Interest) were identified. This segmentation confirmed an association between positive attitudes towards health and liking and familiarity with selected food groups. People more convenience-oriented and less interested in product information and food quality had higher probability to have a lower interest in food-related health. Subjects with higher positive attitudes towards using foods as a reward had a higher probability to belong to the cluster with lower interest in food-related health

Exploring influences on food choice in a large population sample: The Italian Taste project

Food choice is influenced by many interacting factors in humans. Its multidimensional and complex nature is well recognized, particularly within the sensory and consumer food science field. However, the vast majority of the studies aimed at understanding determinants of food choices, preferences, and eating behaviours are affected by important limitations: the limited number of factors that are considered at once and the sample size. Furthermore, sensory and hedonic responses to actual food stimuli are often not included in such studies. The Italian Taste project is a large-scale study (three thousand respondents in three years) launched by the Italian Sensory Science Society aimed at addressing these limitations by exploring the associations among a variety of measures – biological, genetic, physiological, psychological and personality-related, socio-cultural – describing the dimensions of food liking, preference, behaviour and choice, and their relevance in determining individual differences within a given food culture framework. In addition, the study includes also the collection of sensory and hedonic responses to actual food stimuli commonly consumed in Italy and prepared to elicit a variation in the strength (from weak to strong) of bitterness, sweetness, saltiness, sourness, pungency, umami and astringency. The aims of the present paper are twofold. Firstly, the paper is aimed to illustrate the variables selected to explore the different dimensions of food choice and to report the experimental procedure adopted for data collection. Secondly, the paper is aimed at showing the potential of the Italian Taste dataset on the basis of the data collected in the first year of the project. For the purpose, we selected a small number of variables known to influence food choices from data collected in the first year of the project on 1225 individuals

A theoretical framework for the evaluation of university-industry relationships,

Interorganizational theory applied to the issue of university-industry cooperatio