Statistics and genetics between Italy and Britain in the 20th century: an interview with A. W. F. Edwards

The statistician and geneticist Anthony Edwards is interviewed about his career and the scientific connections between Italy and Britain in the past century. Last student of Fisher and witness and link of the relation between R. A. Fisher and L. L. Cavalli-Sforza, he started his career in Italy working on statistical methods for evolutionary trees, after studying the sex ratio at birth, a problem previously attacked by C. Gini at the beginning of the 20th century. Some emerging themes from the interview are briefly highlighted and related to subsequent developments in statistical genetics and the role of statistics

Dietary fat intake as a risk factor for the development of diabetes. Multinational, multicenter study of the Mediterranean Group for the Study of Diabetes (MGDS)

In the context of the Multinational MGSD Nutrition Study, three groups of subjects were studied: 204 subjects with recently diagnosed diabetes(RDM),42subjectswithundiagnoseddiabetes(UDM)(AmericanDiabetesAssociation criteria—fasting plasma glucose [FPG] 126 mg/dl), and 55 subjects with impaired fasting glucose(IFG)(FPG 110and126mg/dl).Eachgroupwascomparedwithacontrolgroupof nondiabetic subjects, matched one by one for center, sex, age, and BMI. Nutritional habits were evaluated by a dietary history method, validated against the 3-day diet diary. In RDM, the questionnaire referred to the nutritional habits before the diagnosis of diabetes. Demographic data were collected, and anthropometrical and biochemical measurements were taken. RESULTS— Compared with control subjects, RDM more frequently had a family history of diabetes(49.0vs.14.2%;P0.001),exercisedless(exerciseindex53.5vs.64.4;P0.01),and more frequently had sedentary professions (47.5 vs. 27.4%; P 0.001). Carbohydrates contributed less to their energy intake (53.5 vs. 55.1%; P 0.05), whereas total fat (30.2 0.5 vs. 27.8 0.5%; P 0.001) and animal fat (12.2 0.3 vs. 10.8 0.3%; P 0.01) contributed moreandtheplant-to-animalfatratiowaslower(1.50.1vs.1.80.1;P0.01).UDMmore frequentlyhadafamilyhistoryofdiabetes(38.1vs.19.0%;P0.05)andsedentaryprofessions (58.5vs.34.1%;P0.05),carbohydratescontributedlesstotheirenergyintake(47.61.7vs. 52.81.4%;P0.05),totalfat(34.71.5vs.30.41.2%;P0.05)andanimalfat(14.2 0.9 vs. 10.6 0.7%; P 0.05) contributed more, and the plant-to-animal fat ratio was lower (1.6 0.2 vs. 2.3 0.4; P 0.05). IFG differed only in the prevalence of family history of diabetes (32.7 vs. 16.4%; P 0.05). CONCLUSIONS— Our data support the view that increased animal fat intake is associated with the presence of diabetes

Mediterranean diet and the metabolic syndrome

Mediterranean diet and the metabolic syndrome Background: The metabolic syndrome refers to a clustering of risk factors including abdominal obesity, hyperglycaemia, low HDL-cholesterol, hypertriglyceridaemia, and hypertension and it is a risk factor for diabetes mellitus type 2 and cardiovascular disease. In this thesis we studied whether a Mediterranean diet favourably affects the metabolic syndrome. Methods: We assessed the association between a Mediterranean diet and the metabolic syndrome in apparently healthy elderly European subjects (SENECA study) and in a Dutch study population that was oversampled with subjects with impaired glucose tolerance or diabetes mellitus type 2 (CoDAM study). In addition, we conducted a controlled-feeding trial to compare the effects of replacing a high saturated fatty acids (SFA) diet with a high monounsaturated fatty acids (MUFA) diet or a Mediterranean diet on characteristics of the metabolic syndrome: HDL-cholesterol, triglycerides and glucose metabolism (glucose concentration and insulin sensitivity). Results: In both the SENECA study and the feeding trial we find support for the hypothesis that a Mediterranean diet has a beneficial effect on two characteristics of the metabolic syndrome, namely HDL-cholesterol and triglyceride concentrations. In addition, the findings of the SENECA study suggested that subjects with good adherence to a Mediterranean diet had a lower prevalence of the metabolic syndrome (prevalence ratio 0.81, 95%CI 0.65; 1.03) and a smaller waist circumference (-1.1 cm, 95%CI -2.4; 0.3) than subjects with poor adherence. In the CoDAM study, we did not find these associations. In none of our studies we found support for the hypothesis that a Mediterranean diet has a beneficial effect on glucose concentration, insulin sensitivity or blood pressure. Conclusion: This thesis finds support for a beneficial effect on two out of five characteristics of the metabolic syndrome and also suggests a beneficial effect on a third characteristic (abdominal obesity). We therefore conclude that a Mediterranean diet may help to prevent the metabolic syndrome and consequently diabetes mellitus type 2 and cardiovascular disease. <br/

Plasma cholesteryl ester fatty acids do not mediate the association of ethnicity with type 2 diabetes: results from the HELIUS study

Scope: Ethnic minority groups have a higher risk of type 2 diabetes (T2D) than the host population. Our aim was to identify whether plasma cholesteryl ester fatty acids (CEFA) mediate the ethnic differences in type 2 diabetes. Methods and results: We included 202 Dutch, 206 South-Asian Surinamese, 205 African Surinamese, 215 Turkish and 213 Moroccan origin participants of the HELIUS study (Amsterdam, the Netherlands). Logistic regression was used to determine the associations between plasma CEFA and T2D. Mediation analysis was used to identify whether CEFA contributed to the association between ethnicity and T2D. We adjusted for ethnicity, age, sex, smoking, physical activity and BMI. Associations between plasma CEFA and T2D were similar across all ethnic groups. Although differences in plasma CEFA across ethnic groups were observed, CEFA did not mediate the differences in T2D prevalence between ethnic groups. Conclusion: Although ethnic differences in plasma CEFA were found and CEFA were associated with T2D, CEFA did not contribute to the difference in T2D prevalence between ethnic groups. If confirmed, this implies that maintenance of the more beneficial CEFA profiles in the non-Dutch ethnic groups may be encouraged to prevent an even higher prevalence of T2D in these groups

Characterisation of metabolites of the putative cancer chemopreventive agent quercetin and their effect on cyclo-oxygenase activity

Quercetin (3,5,7,3′,4′-pentahydroxyflavone) is a flavone with putative ability to prevent cancer and cardiovascular diseases. Its metabolism was evaluated in rats and human. Rats received quercetin via the intravenous (i.v.) route and metabolites were isolated from the plasma, urine and bile. Analysis was by high-performance liquid chromatography and confirmation of species identity was achieved by mass spectrometry. Quercetin and isorhamnetin, the 3′-O-methyl analogue, were found in both the plasma and urine. In addition, several polar peaks were characterised as sulphated and glucuronidated conjugates of quercetin and isorhamnetin. Extension of the metabolism studies to a cancer patient who had received quercetin as an i.v. bolus showed that (Quercetin removed) isorhamnetin and quercetin 3′-O-sulphate were major plasma metabolites. As a catechol, quercetin can potentially be converted to a quinone and subsequently conjugated with glutathione (GSH). Oxidation of quercetin with mushroom tyrosinase in the presence of GSH furnished GSH conjugates of quercetin, two mono- and one bis-substituted conjugates. However, these species were not found in biomatrices in rats treated with quercetin. As cyclo-oxygenase-2 (COX-2) expression is mechanistically linked to carcinogenesis, we examined whether quercetin and its metabolites can inhibit COX-2 in a human colorectal cancer cell line (HCA-7). Isorhamnetin and its 4′-isomer tamarixetin were potent inhibitors, reflected in a 90% decrease in prostaglandin E-2 (PGE-2) levels, a marker of COX-2 activity. Quercetin was less effective, with a 50% decline. Quercetin 3- and 7-O-sulphate had no effect on PGE-2. The results indicate that quercetin may exert its pharmacological effects, at least in part, via its metabolites