L Puddu

Università degli Studi di Sassari, Sassari, Sardinia, Italy

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Publications (12)30.73 Total impact

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    ABSTRACT: Background To investigate the role of the Cytotoxic T Lymphocyte Associated-4 (CTLA-4) 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). Methods The study included 202 LADA, 1373 early-onset type 1 diabetes (T1D), 130 late-onset T1D, 188 patients with non-autoimmune diabetes and 1904 healthy controls. Thyrotropin (TSH) and antibodies against thyreoperoxidase were analysed in all patients. The CTLA-4 G6230A variant was assessed in LADA, early- and late-onset T1D patients as well as in the controls. ResultsThe frequency of CTLA-4 G alleles and genotypes in LADA patients did not significantly differ from the other groups, regardless of its association with AITD. We found increased frequency of G allele containing genotypes within LADA patients who had higher TSH, compared with those with normal TSH (p=0.002). Moreover, LADA patients carrying G allele containing genotypes were more likely to require insulin therapy within 4 years from the diagnosis (p=0.002). Conclusions The G6230A CTLA-4 do not confer susceptibility to LADA in Sardinian patients even when associated with AITD. However, it helps to identify a particular subset of LADA patients with more clinically severe disease, both for thyroid dysfunction and diabetes.
    Journal of Diabetes 02/2014; · 2.94 Impact Factor
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    ABSTRACT: Background. L'ipercolesterolemia autosomica recessiva è un disordine monogenico presente con frequenza relativamente elevata in Sardegna (1:40.000). Due mutazioni, G65A (W22→stop) situata nell’esone 1 del gene LDLRAP1 e 432insA (E170→stop) situata nell’esone 4 dello stesso gene sono responsabili di tutti i casi finora riportati. E' stato effettuato uno screening di tali mutazioni per la stima della frequenza degli eterozigoti in un campione di popolazione sarda. Sono stati sottoposti ad analisi molecolare 2448 campioni di DNA rappresentativi della popolazione del Nord e Sud Sardegna. Metodi. L’analisi è stata effettuata mediante amplificazione PCR del primo e del quarto esone del gene LDLRAP1 con primers mutagenizzati, seguita da analisi di restrizione (rispettivamente BstNI e MvaI per le mutazioni nell’esone 1 e 4). Per la mutazione G65A il primer reverse è stato modificato nella penultima base all'estremità 3' per creare un nuovo sito di restrizione BstNI, mentre per la mutazione 432insA il primer generava un nuovo sito di restrizione MvaI. Nel caso della mutazione G65A in presenza dell’allele mutato viene eliminato il sito di restrizione e si osserva la banda dell’amplificato di 157 bp. Nel caso della mutazione 432insA in presenza dell’allele mutato viene eliminato il sito di restrizione e si osserva la banda dell’amplificato di 144 bp. Risultati. Sono stati riscontrati 3 eterozigoti su 2448 (0,122%) per la mutazione G65A e 16 eterozigoti su 2448 (0,653%) per la mutazione 432insA. Inoltre è stata riscontrata la presenza di un omozigote su 2448 (0,040%) per la mutazione 432insA. Dai dati suddetti la stima della frequenza degli eterozigoti nella popolazione sarda risulterebbe essere di 1:820 per la mutazione G65A e 1:153 per la mutazione 432insA. Conclusioni. La prevalenza osservata per la mutazione 432insA non si discosta significativamente da quella attesa (1:135), stimata sulla base della frequenza degli omozigoti nella popolazione generale. Al contrario la frequenza osservata per la mutazione G65A è notevolmente più bassa di quella teorica (1:141) per cui l'elevata prevalenza con cui è stata riscontrata in aree specifiche dell’isola potrebbe essere spiegata con l’esistenza di un “hot-spot” per tale mutazione.
    Giornale italiano dell'arteriosclerosi. 01/2013; 4:90.
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    XVIII Congresso Nazionale AMD; 05/2011
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    ABSTRACT: In latent autoimmune diabetes of adults (LADA), the progression into insulin-dependent diabetes is usually faster than in type 2 diabetes (T2D) but the factors influencing this progression are not completely known. In this study, we searched for sensitive markers associated with early development of insulin dependence. The screening of 5568 T2D patients for glutamic acid decarboxylase autoantibodies (GAD65Ab) identified 276 LADA patients (M=131; F=145) and in 251 of them, tyrosine phosphatase-2 (IA-2Ab) and thyroperoxidase autoantibodies (TPOAbs), some clinical features and genotype variation of the main type 1 diabetes (T1D) disease susceptibility loci (HLA-DRB1 and HLA-DQB1) were analyzed. Four years after the diagnosis of diabetes, high GAD65Ab titer was not significantly associated with faster progression toward insulin deficiency (P=0.104). Patients with GAD65Ab and TPOAb or IA-2Ab or triple positivity for both islet and TPOAbs (GAD65Ab/IA-2Ab/TPOAb) showed a significantly faster disease progression (P=0.002). Among 104 TPOAb-positive LADA patients, 10 received replacement therapy (l-thyroxine), 43 showed high TSH levels (62.7% developed insulin dependence), and 3 had hyperthyroidism treated with methimazole. Multivariate analysis revealed a significant effect on disease progression only for TPOAb (P=0.022), female gender (P=0.036), low body mass index (BMI; P=0.001), and T1D high/intermediate risk HLA-DRB1/DQB1 genotypes grouped (P=0.020). High GAD65Ab titers per se are not a major risk factor for disease progression in LADA, while the number of positive autoantibodies and HLA DRB1-DQB1 genotypes at high risk for T1D are significant predictors. Moreover, clinical characteristics such as low BMI and female gender are more likely to identify patients who will require insulin therapy within 4 years of diagnosis.
    European Journal of Endocrinology 10/2010; 163(4):541-9. · 3.14 Impact Factor
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    ABSTRACT: A case report of a non-diabetic alcoholic patient (ethanol intake >220 g/d) who experienced severe hypertriglyceridemia (12.679 mg/dL) without pancreatitis or detectable genetic factors responsible for severe dyslipidemia is described. Following the normalization of triglyceride and cholesterol levels, through lipid-free parenteral nutrition therapy, a regimen of alcohol withdrawal and a well-balanced diet with less than 10% saturated fat maintained a normal lipid profile without requiring any lipid-lowering drug. The absence of organ damage in the patient is likely to be attributed to the short duration of the elevated triglyceride peak. The treatment of this disorder does not necessarily require LDL-apheresis but can be simply managed by parenteral therapy provided that no other risk factors are present.
    La Clinica terapeutica 01/2009; 160(3):217-21. · 0.33 Impact Factor
  • Il Patologo Clinico. 01/2005; P2/31:80.
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    ABSTRACT: The 65-kDa glutamic acid decarboxylase (GAD65) autoantibodies (GAD65Abs), commonly found in type 1 diabetes mellitus (T1DM) patients, are also found at lower frequencies in type 2 diabetes mellitus (T2DM) patients. GAD65Abs in T1DM patients are epitope specific, in contrast to those found in other GAD65Ab-positive individuals, including T2DM patients. Our aim was to assess whether epitope-specific GAD65Abs, or the additional presence of islet antigen 2 (IA-2) autoantibodies, better define T1DM phenotypes among T2DM patients. GAD65 and IA-2 autoantibodies were analyzed in 1436 Sardinian subjects classified with T2DM and in 384 nondiabetic patient controls. Autoantibody binding specificity to the N-terminal, middle (M), and C-terminal (C) portions of the GAD65 molecule was evaluated. Among the T2DM patients, 5.1% had GAD65 (P < 0.001) and 2.4% had IA-2 autoantibodies, compared with 1.3 and 1.6%, respectively, among the controls. GAD65Ab-positive T2DM patients with M+C (epitope-specific) reactivity were found to have the lowest body mass index (P < 0.001), followed by GAD65Ab/IA-2Ab-positive patients (P < 0.01), and non-M+C-reactive (non-epitope-specific) patients (P < 0.02). In GAD65Ab-positive T2DM patients, c-peptide levels were lower in M+C-reactive compared with non-M+C-reactive patients. Sardinian T2DM patients with M+C-predominant GAD65Ab reactivity have clinical features more similar to those of T1DM patients. Thus, GAD65Ab epitope analysis may help to define T1DM phenotypes among newly diagnosed GAD65Ab-positive patients classified with T2DM.
    Journal of Clinical Endocrinology &amp Metabolism 11/2004; 89(11):5675-82. · 6.43 Impact Factor
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    ABSTRACT: Twenty consecutive infertile women (mean age +/- SD, 36.9 +/- 5.4 years) undergoing ovarian stimulation with recombinant follicle stimulating hormone (rFSH) were recruited. Serial measurements of plasma total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), apolipoprotein A1 (ApoA1), apolipoprotein B (Apo-B), lipoprotein(a) (Lp(a)), oestradiol and progesterone were performed on day 3 before starting ovarian stimulation, on the day of human chorionic gonadotrophin (HCG) administration and on day 15 after HCG administration, respectively. The relationship between lipid and apolipoprotein concentrations and serum oestradiol and progesterone concentrations was sought. All women completed the ovarian stimulation protocol successfully. Plasma concentrations of HDL-C and Apo-A1 were significantly raised on the day of HCG administration and then returned to baseline values within 2 weeks. LDL-C, TG, Apo-B and Lp(a) were significantly increased on day 15 after HCG administration. Lp(a) variation between the first sample and the third sample correlated positively with serum progesterone concentrations (r = 0.472, P < 0.04). No other significant correlations were found between lipid and apolipoprotein variations and either oestradiol or progesterone concentrations. It was concluded that an increase of plasma lipid and apolipoprotein concentrations deserves particular consideration and all women undergoing ovarian stimulation should be monitored for long-term atherogenic and thrombogenic risks.
    Reproductive biomedicine online 11/2003; 7(3):309-12. · 2.68 Impact Factor
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    ABSTRACT: We sought to investigate the changes in circulating serum lipids and lipoproteins, including lipoprotein (a), and low-density lipoprotein size in women during normal pregnancy. Twenty-two women (mean age, 31 +/- 5 years; 13 primiparous subjects) were studied during uncomplicated pregnancy with normal outcome. Twenty-four nulliparous women of similar age (31 +/- 4 years) were studied as control subjects. Serum triglycerides and total and low-density lipoprotein cholesterol increased significantly during pregnancy in all women. Women with changes in low-density lipoprotein during the second and third trimesters showed a more marked increase in serum triglycerides, and this effect was slightly more evident in the multiparous subjects. No other differences were evident between primiparous and multiparous women apart from high-density lipoprotein cholesterol levels, which were slightly decreased in the latter subjects. Our results show that during normal pregnancy, the increase in plasma triglycerides may lead to the appearance of the atherogenic dense low-density lipoproteins in a subgroup of women. We suggest that the observed changes in low-density lipoprotein patterns during pregnancy might be used to identify those women who later in life will have these atherogenic small and dense low-density lipoproteins.
    American Journal of Obstetrics and Gynecology 09/1999; 181(2):430-4. · 3.88 Impact Factor
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    ABSTRACT: To study the long-term effects of simvastatin on urinary albumin excretion rate (AER) in normotensive microalbuminuric type 2 diabetic patients with hypercholesterolemia. A total of 19 normotensive microalbuminuric hypercholesterolemic type 2 diabetic patients entered a double-blind crossover study for 2 years, receiving either simvastatin (20 mg/day) or placebo (each treatment for 1 year). Simvastatin significantly decreased plasma cholesterol (total and LDL) after 52 weeks of treatment. A concomitant significant decrease of AER (25% from basal) with no significant changes in creatinine clearance was observed during the same period. Our data are in keeping with the hypothesis that simvastatin might be used as an additional means to preserve renal function in microalbuminuric hypercholesterolemic type 2 diabetic patients.
    Diabetes Care 01/1998; 20(12):1891-5. · 7.74 Impact Factor
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    ABSTRACT: We report herein the effects of cyclical variations of endogenous sex steroids during the menstrual cycle on plasma lipids and apolipoproteins (apo) in normal women. We examined 16 normal women (age range 25-36 yr) with normal menstrual cycles of 28-31 days. The study covered the period from the 1st day of a menstrual phase (basal) until the 1st day of the following menstrual phase. During the study all women maintained a normolipidic diet (30% fat). Plasma total cholesterol and low-density-lipoprotein cholesterol were significantly higher than basal in the preovulatory phase until progesterone started to increase in the postovulatory phase [day +8 from luteinizing hormone (LH) surge]. High-density-lipoprotein cholesterol was significantly higher than basal from day -1 to the day after LH surge, whereas plasma apoAI levels were significantly higher from day -8 to day +8 (from LH surge). Plasma apo(a) increased significantly during the luteal phase in four women characterized by a single S4 band and lower basal plasma levels of apo(a). Our results indicate that endogenous female sex steroids have significant effects on the circulating levels of plasma lipids and apolipoproteins, including apo(a). More work needs to be done to elucidate the significance of the observed apo(a) changes, and the different phases of the menstrual cycle must be taken into account when evaluating the lipidic risk profile in premenopausal women.
    The American journal of physiology 01/1996; 269(6 Pt 1):E1101-5. · 3.28 Impact Factor
  • M Maioli, L Puddu, G M Pes
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    ABSTRACT: Latent autoimmune diabetes in adults (LADA) is a disorder with onset after age 30, insulin independence for at least 6 months after diagnosis, and the presence of circulating pancreatic islet autoantibodies. The prevalence of LADA varies substantially across ethnic groups and ranges approximately from 1% to 10% among patients with type 2 diabetes. In this review we discuss the nomenclature, diagnostic criteria, immunologic and genetic markers, metabolic alterations and therapy of this form of diabetes.
    La Clinica terapeutica 157(1):69-78. · 0.33 Impact Factor