Gianfranco Meloni

Risk of type 1 diabetes in childhood and maternal age at delivery, interaction with ACPI and sex

We have investigated the possible role of ACP1 (also known as cLMWPTP: cytosolic low molecular weight phosphotyrosine phosphatase), a highly polymorphic enzyme involved in signal transduction of T‐cell receptor, insulin receptor and other growth factors in the relationship between maternal age at delivery and risk of type 1 diabetes in the offspring.

Glyburide-induced acute haemolysis in a G6PD-deficient patient with NIDDM

In a 61‐year‐old man with glucose‐6‐phosphate dehydrogenase (G6PD) deficiency and poorly controlled non‐insulin‐dependent diabetes mellitus, an episode of acute haemolysis occurred after the administration of glyburide (glibenclamide). Erythrocyte fragmentation, with haemoglobin condensation zones next to clear zones, was observed on peripheral blood smears. Since autoimmune haemolysis was excluded on the basis of laboratory data, acute haemolysis was ascribed to G6PD deficiency.

A study of three polymorphic sites of the ADA gene in children with type 1 diabetes mellitus.

BACKGROUNDnAdenosine deaminase is a polymorphic enzyme that has an important role in immune functions and in the regulation of intracellular and extracellular concentrations of adenosine and adenosine receptor activity.nnnAIMnTo search for possible association of type 1 diabetes mellitus (DM1) with three loci haplotypes (ADA1, ADA2, ADA6) of the adenosine deaminase gene.nnnPATIENTSnOne hundred and eighty-nine consecutive children with DM1 from Sassari, Sardinia, and a control sample of 239 children from the same area were studied.nnnMETHODSnADA loci genotypes were determined by DNA analysis.nnnRESULTSnCompared to controls, diabetic boys show a decrease of the 2(2)/6(1) haplotype while diabetic girls show an increase of the same haplotype. This association was replicated in an independent sample from Continental Italy.nnnCONCLUSIONSnThe 2(2)/6(1) haplotype may exert a protective action in males but may increase susceptibility to DM1 in females: OR = 0.398, 95% CI 0.16-0.96 for males, and OR = 2.31, 95% CI 1.32-4.06 for females.

High prevalence of lactose absorbers in patients with presenile cataract from northern Sardinia

EDITOR,-An elevated incidence of cataract has been observed by Simoons et al in high milk drinking populations. Other authors2 4 found that the percentage of lactose absorbers among subjects with cataract was higher than in the normal population. We studied 40 adult male subjects with cataract (they were aged less than 56 years and more than 44 years), and 50 healthy similarly aged control males from northern Sardinia. Milk drinking habits were similar for the two groups. None of the patients was affected by cataract dueto congenital, inflammatory, iatrogenic, diabetic, traumatic factors, or other causes. Thirty five of the 40 catarac-

Evidence of decreased fertility in women carrying the gene for G6PD deficiency: a study in the Sardinian population

The current trend toward reduced feritility and delayed childbearing has stimulated an interest in the genetic and environmental factors capable of modifying fertility. The evaluation of fertility in G6PD-deficient females is of great theoretical interest in view of the proposed heterozygote advantage of G6PD deficiency in malarial environments. Toncheva and Tzoneva have reported population data from Bulgaria suggesting decreased fertility of women carrying the risk allele for G6PD deficiency. We have applied a model of maternal-age related differences within the distribution of ‘fertility-types’ among women, described by Gimelfarb and Bottini (1989) to a sample of 5182 Sardinian mothers. Mothers of infants with G6PD deficiency are underrepresented in the group of women having children at younger ages, suggesting a reduction of so-called ‘natural fertility’ among women carrying the risk allele for G6PD deficiency. Female infants with G6PD deficiency from young mothers have a lower birth weight compared to infants without G6PD deficiency from older mothers, suggesting that in younger mothers there is a negative effect of G6PD deficiency on intrauterine growth.

Evaluation of the difference in caries experience in diabetic and non-diabetic children—A case control study

Aim To evaluate the caries prevalence and related variables in Type 1 diabetic and non-diabetic children and among the diabetic children according to their metabolic status. Methods Sixty-eight diabetic and 136 non-diabetic children, matching by gender and age (4–14 years) were enrolled. The diabetic children were divided: a) 20 children in good metabolic control (Hb1ac≤7.5) and b) 48 children in bad metabolic control (Hb1ac>7.5). Dietary and oral hygiene habits were investigated. Caries status was registered using the International Caries Detection and Assessment System. Oral microflora was analysed using the checkerboard DNA-DNA hybridisation method. Plaque acidogenicity was recorded after a sucrose rinse. Results Sugared beverage and snack intake was higher in diabetic group compared to non-diabetic group (p = 0.03 and p = 0.04, respectively) and in subjects in bad metabolic control (p = 0.03 and p<0.01, respectively). Oral hygiene habits were similar, except for the use of fluoridated adjuvants, higher in non-diabetic children (p = 0.04). No statistically significant differences were observed regarding caries figures, but a higher number of caries free subjects was found in diabetic subjects in good metabolic control (p<0.01). Significant difference for the main cariogenic bacteria was found between diabetic and non-diabetic subjects (p<0.05). The pH values showed statistically significant differences between diabetic and non-diabetic subjects and between diabetic subjects in good and bad metabolic control (p<0.01). Conclusions Diabetic children in good metabolic control might even be considered at low caries risk, while those in bad metabolic control showed an oral environment prone to a high caries risk.

Are distinctive risk indicators associated with different stages of caries in children? A cross-sectional study

BackgroundActual caries figures emphasize the need to identify the risk indicators involved in the disease’s development. The hypothesis that certain risk indicators might affect the dynamic evolution of the caries process was assessed; to clarify this premise, a cross-sectional survey was performed in school children.MethodsA total of 390 subjects aged 6–8 years old were randomly selected. Caries was assessed, and the subjects were stratified as follows: i) highest caries score; ii) most prevalent caries score; and iii) number of affected teeth. Parents/guardians completed a questionnaire regarding vital statistics, socio-economic indicators, dietary habits, oral hygiene habits and oral health behaviours.ResultsCaries was detected in 42.31% of the subjects. Maternal nationality, parental education level, use of a sweetened pacifier at night, intake of lactose-free milk and toothbrushing frequency were statistically significant associated (pu2009<u20090.05) with subjects stratified according to the highest caries score. Parental educational level, maternal occupational status and use of a sweetened pacifier at night were associated (pu2009<u20090.05) with affected children stratified according to the most prevalent caries score. Maternal educational level and intake of lactose-free milk were associated with subjects with moderate caries stages compared to being caries-free (pu2009=u20090.01 and pu2009=u20090.02, respectively). Maternal nationality (pu2009<u20090.01) and toothbrushing frequency (pu2009=u20090.01) were associated with subjects affected by extensive lesions compared to caries-free children. In subjects affected by initial lesions as the most prevalent figure, gender (male) and paternal occupation status (unemployed) were statistically significant associated (pu2009=u20090.03 and pu2009=u20090.04, respectively) compared to those affected by highest prevalence of extensive caries lesions. In children with the highest prevalence of moderate caries lesions, maternal education level (pu2009<u20090.01), paternal occupational status (pu2009=u20090.03) and use of a sweetened pacifier at night (pu2009<u20090.01) were statistically significantly associated.ConclusionsMaternal nationality, maternal low level of education, intake of lactose-free milk and low toothbrushing frequency were involved in the change from caries-free status to different caries stages. Gender, paternal unemployment, maternal low educational level and use of a sweetened pacifier were correlated with caries progression, showing how distinctive risk indicators were associated with different caries stages.

Cyclic Seasonal Variation of G-6-PD Deficiency in Newborn Infants from Sardinia

Glucose-6-Phosphate Dehydrogenase has been studied in 5267 consecutive newborn infants from Sardinian population during a four years period. The proportion of G-6-PD deficient female infants is much higher in those conceived in the winter-spring than among those conceived in summer-autumn, resulting in a lower sex ratio among G-6-PD deficient infants conceived in winter-spring as compared to G-6-PD deficient infants conceived in the summer-autumn. The overall frequency of the gene for G-6-PD deficiency is much lower in infants conceived in the summer period than in infants conceived in the other seasons. A greater reproductive efficiency of G-6-PD deficient males in the winter-spring season and/or some effect at post zygotic level favouring the survival of heterozygous G-6-PD deficient females conceived in the winter-spring period could contribute to the pattern described. Fresh vegetables containing oxidative substances are more abundant in the spring time. These substances may interact with seasonal reproductive cycles influencing reproduction efficiency of G-6-PD deficient males and/or the relative survival rate of heterozygous female embryos.

Further observations on associations between the ADA gene and past malaria morbidity in Sardinia

Adenosine Deaminase (ADA) contributes to the regulation of adenosine concentration and in turn to T cell activation. Genetic variability of ADA activity may have, therefore, an important role in resistance to malaria. Indeed, previous studies in Sardinia have shown a lower frequency of ADA1*2 allele (associated with low ADA activity) in areas, where malaria was heavily endemic compared to areas where malaria was not endemic. We have now studied the ADA2 locus, another polymorphic site with two alleles ADA2 *1 and ADA2 *2 within the ADA gene.