Study of factors influencing susceptibility and age at onset of type 1 diabetes: A review of data from Continental Italy and Sardinia.

AIM: To investigate the role of protein tyrosin phosphatase 22 (PTPN22), maternal age at conception and sex on susceptibility and age at onset of type 1 diabetes (T1D) in Continental Italy and Sardinian populations. METHODS: Three hundred seventy six subjects admitted consecutively to the hospital for T1D and 1032 healthy subjects as controls were studied in Continental Italy and 284 subjects admitted consecutively to the hospital for T1D and 5460 healthy newborns were studied in Sardinia. PTPN22 genotype was determined by DNA analysis. Maternal age at conception and age at onset of disease were obtained from clinical records. χ(2) test of independence, student t test for differences between means and odds ratio analysis were carried out by SPSS programs. Three way contingency table analysis was carried out according to Sokal and Rohlf. RESULTS: The pattern of association between PTPN22 and T1D is similar in Continental Italy and Sardinia: the proportion of *T allele carriers is 13.6% in T1D vs 6.7% in controls in Continental Italy while in Sardinia is 7.3% in T1D vs 4.4% in controls. The association between T1D and maternal age at conception is much stronger in Sardinia than in Italy: the proportion of newborn from mother aging more than 32 years is 89.3% in T1D vs 32.7% in consecutive newborn in Sardinia (P < 10(-6)) while in Continental Italy is 32.2% in T1D vs 19.1% in consecutive newborns (P = 0.005). This points to an important role of ethnicity. A slight prevalence of T1D males on T1D females is observed both in Continental Italy and Sardinia. PTPN22 genotype does not exert significant effect on the age at onset neither in Continental Italy nor and Sardinia. Maternal age does not influence significantly age at onset in Italy (8.2 years in T1D infants from mothers aging 32 years or less vs 7.89 years in T1D infants from mothers aging more than 32 years: P = 0.824) while in Sardinia a border line effect is observed (5.75 years in T1D infants from mothers aging 32 years or less vs 7.54 years in T1D infants from mothers aging more than 32 years: P = 0.062). No effect of sex on age at onset is observed in Continental Italy while in Sardinia female show a lower age at onset of T1D as compared to males (8.07 years in males vs 6.3 years in females: P = 0.002). CONCLUSION: The present data confirm the importance of ethnicity on susceptibility and on the age at onset of T1D.

Hyper-homocysteinemia is not a main feature of juvenile uncomplicated type 1 diabetes.

Total plasma homocysteine (tHcy) was measured by high pressure liquid chromatography (HPLC) method in 28 patients (12 females and 16 males) at the onset of type 1 diabetes mellitus (T1DM), 4 females during diabetes ketoacidosis (DKA) and 154 (68 females and 86 males) during follow-up. Serum folate, pyridoxal 5' phosphate (PLP) and Vitamin B12 (Vit B12) were also measured. Plasma tHcy levels were not found significantly different in T1DM patients known to have diabetes (males 9.2 +/- 7.7 and females 7.0 +/- 2.8 micromol/l) and in those who were newly diagnosed (males 9.7 +/- 4.8 and females 7.16 +/- 2.8 micromol/l) than in healthy controls (males 8.7 +/- 3.5 and females 7.8 +/- 2.55 micromol/l). Only a significant difference for sex was observed in known diabetes (p = 0.0281). Serum folate, PLP and Vit B12 were normal (12.6 +/- 3.6 ng/ml, 20.11 +/- 0.8 ng/ml and 416.7 +/- 41.9 pg/ml) in all T1DM patients. Age significantly correlated with plasma tHcy. Only in 4 patients, studied during DKA, plasma tHcy was significantly lower (2.76 +/- 1.33 micromol/l, p < 0.001) than the healthy controls.

A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes.

We report that a single-nucleotide polymorphism (SNP) in the gene (PTPN22) encoding the lymphoid protein tyrosine phosphatase (LYP), a suppressor of T-cell activation, is associated with type 1 diabetes mellitus (T1D). The variants encoded by the two alleles, 1858C and 1858T, differ in a crucial amino acid residue involved in association of LYP with the negative regulatory kinase Csk. Unlike the variant encoded by the more common allele 1858C, the variant associated with T1D does not bind Csk.