Alessandra Errigo

Lifestyle and nutrition related to male longevity in Sardinia: An ecological study

BACKGROUND AND AIMS A demographic analysis in the Mediterranean island of Sardinia revealed marked differences in extreme longevity across the 377 municipalities and particularly identified a mountain inner area where the proportion of oldest subjects among male population has one of the highest validated value worldwide. The cause(s) of this unequal distribution of male longevity may be attributed to a concurrence of environmental, lifestyle and genetic factors. METHODS AND RESULTS In this study we focussed on some lifestyle and nutrition variables recorded in the islands population in early decades of 20th century, when agricultural and pastoral economy was still prevalent, and try to verify through ecological spatial models if they may account for the variability in male longevity. By computing the Extreme Longevity Index (the proportion of newborns in a given municipality who reach age 100) the islands territory was divided in two areas with relatively higher and lower level of population longevity. Most nutritional variables do not show any significant difference between these two areas whereas a significant difference was found with respect to pastoralism (P = 0.0001), physical activity estimated by the average slope of the territory in each municipality (P = 0.0001), and average daily distance required by the active population to reach the usual workplace (P = 0.0001). CONCLUSION Overall, these findings suggest that factors affecting the average energy expenditure of male population such as occupational activity and geographic characteristics of the area where the population mainly resides, are important in explaining the spatial variation of Sardinian extreme longevity.

Influence of β0-Thalassemia on the Phenotypic Expression of Heterozygous Familial Hypercholesterolemia

One of the genetic features of the Sardinian population is the high prevalence of hemoglobin disorders. It has been estimated that 13% to 33% of Sardinians carry a mutant allele of the alpha-globin gene (alpha-thalassemia trait) and that 6% to 17% are beta-thalassemia carriers. In this population, a single mutation of beta-globin gene (Q39X, beta(0) 39) accounts for >95% of beta-thalassemia cases. Because previous studies have shown that Sardinian beta-thalassemia carriers have lower total and low density lipoprotein (LDL) cholesterol than noncarriers, we wondered whether this LDL-lowering effect of the beta-thalassemia trait was also present in subjects with familial hypercholesterolemia (FH). In a group of 63 Sardinian patients with the clinical diagnosis of FH, we identified 21 unrelated probands carrying 7 different mutations of the LDL receptor gene, 2 already known (313+1 g>a and C95R) and 5 not previously reported (D118N, C255W, A378T, T413R, and Fs572). The 313+1 g>a and Fs572 mutations were found in several families. In cluster Fs572, the plasma LDL cholesterol level was 5.76+/-1.08 mmol/L in subjects with beta(0)-thalassemia trait and 8.25+/-1.66 mmol/L in subjects without this trait (P<0.001). This LDL-lowering effect was confirmed in an FH heterozygote of the same cluster who had beta(0)-thalassemia major and whose LDL cholesterol level was below the 50th percentile of the distribution in the normal Sardinian population. The hypocholesterolemic effect of beta(0)-thalassemia trait emerged also when we pooled the data from all FH subjects with and without beta(0)-thalassemia trait, regardless of the type of mutation in the LDL receptor gene. The LDL-lowering effect of beta(0)-thalassemia may be related to (1) the mild erythroid hyperplasia, which would increase the LDL removal by the bone marrow, and (2) the chronic activation of the monocyte-macrophage system, causing an increased secretion of some cytokines (interleukin-1, interleukin-6, and tumor necrosis factor-alpha) known to affect the hepatic secretion and the receptor-mediated removal of apolipoprotein B-containing lipoproteins. The observation that our FH subjects with beta(0)-thalassemia trait (compared with noncarriers) have an increase of blood reticulocytes (40%) and plasma levels of interleukin-6 (+60%) supports these hypotheses. The lifelong LDL-lowering effect of beta(0)-thalassemia trait might slow the development and progression of coronary atherosclerosis in FH.

Male longevity in Sardinia, a review of historical sources supporting a causal link with dietary factors

The identification of a hot spot of exceptional longevity, the Longevity Blue Zone (LBZ), in the mountain population of Sardinia has aroused considerable interest toward its traditional food as one of the potential causal factors. This preliminary study on the traditional Sardinian diet has been supported by the literature available, which has been carefully reviewed and compared. Up to a short time ago, the LBZ population depended mostly upon livestock rearing, and consumption of animal-derived foods was relatively higher than in the rest of the island. The nutrition transition (NT) in urbanized and lowland areas began in the mid-1950s, fueled by economic development, whereas in the LBZ it started later owing to prolonged resistance to change by a society organized around a rather efficient pastoral economy. Even nowadays a large proportion of the population in this area still follows the traditional diet based on cereal-derived foods and dairy products. The LBZ cohorts comprising individuals who were of a mature age when NT began may have benefited both from the high-quality, albeit rather monotonous, traditional diet to which they had been exposed most of their life and from the transitional diet, which introduced positive changes such as more variety, increased consumption of fruits and vegetables and moderate meat intake. It could be speculated that these changes may have brought substantial health benefits to this particular aging group, which was in need of nutrient-rich food at this specific time in life, thereby resulting in a decreased mortality risk and, in turn, life-span extension.

Allelic variant in CTLA4 is associated with thyroid failure and faster β-cell exhaustion in latent autoimmune diabetes in adults.

The aim of the study was to investigate the role of the cytotoxic T‐lymphocyte‐associated protein 4 (CTLA4) G6230A variant on the susceptibility of latent autoimmune diabetes in adults (LADA) as a whole and in the subset of patients who share autoimmune thyroid disease (AITD).

Phenotypic heterogeneity of latent autoimmune diabetes in adults identified by body composition analysis

BackgroundIn patients with Latent Autoimmune Diabetes in Adults (LADA) a lower body mass index was reported compared with classical type 2 diabetes (T2D), and was found to be associated with a faster progression to insulin-dependence. In this study we determined the body composition in a cohort of LADA patients from Sardinia, Italy, and compared it with age– and gender–matched patients diagnosed as having adult-onset type 1 diabetes (T1D) and non-autoimmune T2D.MethodsIn 210 LADA patients, 210 T2D patients and 30 adult-onset T1D patients of Sardinian origin we assessed total and segmental body composition (weight-adjusted percent fat mass and lean mass) by using Dual Energy X-rays Absorptiometry (DXA).ResultsIn the whole cohort of LADA patients total fat mass was significantly smaller compared with T2D patients (p < 0.0001), while no difference was found between LADA and T1D patients. In LADA men fat depletion involved all body segments, while in LADA women it was observed only in the truncal segment (p < 0.0001), as in the upper and lower regions fat deposits were larger compared to T2D (p < 0.0001). However, LADA women showed a significantly elevated truncal fat compared to T1D women (p < 0.004), whereas no difference was detected in the extremities.ConclusionsBody composition in LADA patients shows substantial difference, in a gender-dependent way, compared to classic T2D. In women fat deposits tend to accumulate in peripheral regions rather than centrally, whereas in men the distribution is more homogeneous. In addition, central fat depletion in LADA women appears to be a significant predictor of faster progression to insulin dependence. Thus, routine assessment of body composition may help the physician identify LADA patients who require early insulin treatment in order to delay beta-cell exhaustion, as well those with increased CV risk due to excess truncal adiposity.

The Eating Habits of School Children from the Longevity Blue Zone of Sardinia: a Positive Model

A healthy diet should balance caloric intake (quality calories) with a variety of foods poor in simple sugars, such as cereals and legumes, fruits and vegetables, nuts, low-fat dairy products, fish, meat, and eggs prepared with culinary skills and minimally processed. This paper investigates the eating habits of school children of Villagrande, Italy, a rural village characterized by the remarkable longevity of its inhabitants, and makes a comparison with a sample of school children of the same age from an urban setting in the island. A specific questionnaire was used to collect demographic data, meals structure and composition, frequency of food consumption, and characteristic of the usual diet. The frequency of healthy eating habits, according to the current standards, was superior in the rural compared to the urban setting. The consumption of vegetables was higher in rural than in urban students (≥ once a week, 94% vs 54%, p<0.01) whereas for fruit and legumes the percentages were comparable (≥ once a week, 97% vs 94% and 79% vs 71%, respectively). Cheese, which is a typical product of Sardinia and mostly homemade, was consumed more than once a week in 86% of rural compared to 73% of urban school children. Fish consumption was consistently higher in the rural compared to the urban area (more than once a week 81% vs 65% (p<0.001). Alcoholic beverages were consumed in small quantities in both cohorts surveyed, while soft drinks to a greater extent among urban school children. The overall nutrition pattern observed in the rural village could be considered the result of persistent traditional household influence and may prove useful to prevent early onset of obesity if extended to a broader school children population, although the implementation of such observations may be the biggest challenge.

The association of adult height with the risk of cardiovascular disease and cancer in the population of Sardinia

The relationship between body height and the risk of non‒communicable diseases such as cardiovascular disease and cancer has been the subject of much debate in the epidemiological literature. Concerns have recently arisen over spurious associations due to confounding factors like birth cohort, especially in the context of epidemiological transition. The population of Sardinia represents an interesting case study, as the average physical stature of inhabitants was the lowest recorded in Europe until a few decades ago. In this population we tested whether height is an independent risk factor for cardiovascular disease and cancer. We analysed the stature of 10,427 patients undergoing endoscopy for any reason, for whom a detailed clinical history of cardiovascular disease and/or malignancies had been documented. Poisson regression modelling was used to test the association between stature and disease risk. When patients were subdivided according to sex and height tertiles, the risk of cardiovascular disease proved significantly greater for subjects in the lowest tertile irrespective of sex (men: 1.87; 95%CI 1.41‒2.47; women: 1.23; 95%CI 0.92‒1.66) and smaller for those in the highest tertile (men: 0.51; 95%CI 0.35‒0.75; women: 0.41; 95%CI 0.27‒0.61). However, after adjusting the risk for birth cohort and established risk factors, it mostly resulted in non-significant values, although the overall trend persisted. Similar results were obtained for all-cancer risk (relative risk for men and women in the lowest tertile: 1.44; 95%CI 1.09–1.90 and 1.17; 95%CI 0.93–1.48, in the highest tertile: 0.51; 95%CI 0.36–0.72 and 0.62; 95%CI 0.47–0.81, respectively) as well as for some of the most common types of cancer. We concluded that the risk of developing cardiovascular disease and malignancies does not vary significantly with stature in the Sardinian population, after adjusting for birth cohort and more obvious risk factors.

Effect of age, period and birth-cohort on the frequency of glucose-6-phosphate dehydrogenase deficiency in Sardinian adults.

Abstract Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an inherited disorder common in Sardinia. In this study, the frequency variation of G6PD-deficiency across age groups and birth cohorts was investigated using Age–Period–Cohort analysis. Methods: Data were collected from the clinical records of 11,252 patients (6975 women, age range 17–94 years) who underwent endoscopy between 2000 and 2016 at a teaching hospital (University of Sassari), Italy. G6PD status was assessed by enzymatic assay based on G6PD/6GPD ratio. A Poisson log-linear regression model was used to identify age and time trend in G6PD deficiency. Results: Enzyme deficiency was detected in 11.4% of the entire cohort (men: 7.9%; women: 13.6%). Age–Period–Cohort analysis showed no inflection points across age groups, especially after age 80. The effects of time period and birth cohorts on G6PD deficiency were negligible (frequencies before and after 1950 were 11.0% and 11.8%, respectively). Conclusions: These findings indicate that the frequency of G6PD deficiency does not vary significantly in oldest subjects. The lack of evidence for selection across the malaria eradication time may be explained by other factors, including somatic cell selection or misclassification of heterozygotes women as G6PD normal in the older birth cohorts. Additional molecular studies may help clarify these issues. Key message The frequency of glucose-6-phosphate dehydrogenase deficiency is stable across age groups and does not vary in generations born before or after malaria eradication.