81 results on '"M. Songini"'
Search Results
2. Incidence of type 1 diabetes in age groups above 15 years: facts, hypothesis and prospects for future epidemiologic research
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Gabriella Gruden, Graziella Bruno, and M Songini
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Gerontology ,Adult ,Male ,Pediatrics ,medicine.medical_specialty ,Adolescent ,Epidemiology ,Endocrinology, Diabetes and Metabolism ,Population ,030209 endocrinology & metabolism ,Type 2 diabetes ,Disease ,Adulthood diabetes, Incidence, Registries, Epidemiology ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Bias ,Diabetes mellitus ,Internal Medicine ,medicine ,Humans ,030212 general & internal medicine ,Registries ,education ,Aged ,Type 1 diabetes ,education.field_of_study ,business.industry ,Incidence (epidemiology) ,Incidence ,General Medicine ,Middle Aged ,medicine.disease ,Natural history ,Diabetes Mellitus, Type 1 ,Adulthood diabetes ,Female ,business - Abstract
Although onset of type 1 diabetes can occur in adulthood, epidemiological data are scarce, limiting our potential to identify unknown determinants of the disease. Paucity of registries expanding the recruitment of incident cases up to adulthood, atypical clinical features of type 1 diabetes at onset, misclassification of type 1 as type 2 diabetes and little use of markers of β-cell autoimmunity represents major obstacles in studying the risk of type 1 diabetes in adults. New strategies in study design, data collection and analyses may overcome these problems in the future. Population-based surveys and registries including adulthood; use of etiological rather than clinical criteria to define type 1 diabetes; availability of electronic health records as prescription data sources to avoid missing data; and application of proper statistical methods will be instrumental to gain better insight on the epidemiology and natural history of the disease.
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- 2016
3. Retinopathy and Vision Loss in Insulin-dependent Diabetes in Europe
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Anne Katrin Sjølie, Judith Stephenson, Steve Aldington, Eva Kohner, Hans Janka, Lynda Stevens, John Fuller, B. Karamanos, C. Tountas, A. Kofinis, K. Petrou, N. Katsilambros, M. Cignarelli, R. Giorgino, M.L. De Geco, I. Ramunni, C. Ionescu-Tirgoviste, C.M. Iosif, C. Pitei, S. Buligescu, G. Tamas, Z. Kerenyi, A.M. Ahmed, J. Toth, P. Kempler, S. Muntoni, M. Songini, M. Stabilini, M. Fossarello, S. Pintus, B. Ferriss, C.C. Cronin, M. Toeller, A. Klischan, T. Forst, F.A. Gries, R. Rottiers, H. Priem, P. Ebeling, M. Sinisalo, V.A. Koivisto, B. Idzior-Walus, B. Solnica, L. Szopinska-Ciba, K. Solnica, H.M.J. Krans, H.H.P.J. Lemkes, J.J. Jansen, J. Nunes-Cornea, J. Boavida, G. Michel, R. Wirion, A.J.M. Boulton, H. Ashe, D.J.S. Fernando, G. Pozza, G. Slaviero, G. Comi, B. Fattor, F. Bandello, H. Mehnert, A. Nuber, H. Janka, D. Ben Soussan, M.C. Fallas, P. Fallas, E. Jepson, S. McHardy-Young, J.H. Fuller, D.J. Betteridge, M. Milne, G. Crepaldi, R. Nosadini, G. Cathelineau, B. Villatte Cathelineau, M. Jellal, N. Grodner, P. Gervais Feiss, F. Santeusanio, G. Rosi, M.R.M. Ventura, C. Cagini, C. Marino, R. Navalesi, G. Penno, R. Miccoli, M. Nannipieri, S. Manfredi, G. Ghirlanda, P. Cotroneo, A. Manto, C. Teodonio, A. Minnella, J.D. Ward, S. Tesfaye, C. Mody, C. Rudd, G.M. Molinatti, F. Vitelli, M. Porta, G.F. Pagano, P. Cavallo Perin, P. Estivi, R. Sivieri, Q. Carta, G. Petraroli, N. Papazoglou, G. Manes, G. Triantaphyllou, A. Ioannides, M. Muggeo, V. Cacciatori, F. Bellavere, P. Galante, M.L. Gemma, K. Irsigler, H. Abrahamian, C. Gurdet, B. Hornlein, C. Willinger, S. Walford, E.V. Wardle, G. Roglic, Z. Resman, Z. Metelko, and Z. Skrabalo
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medicine.medical_specialty ,Visual acuity ,business.industry ,Diabetic retinopathy ,medicine.disease ,Surgery ,Ophthalmology ,chemistry.chemical_compound ,Blood pressure ,chemistry ,Internal medicine ,Diabetes mellitus ,medicine ,Glycated hemoglobin ,medicine.symptom ,Risk factor ,business ,Glycemic ,Retinopathy - Abstract
Purpose: To assess the frequency of retinopathy and vision loss in patients with insulin-dependent diabetes mellitus and their relations to potentially modifiable risk factors. Methods: The authors conducted a multicenter cross-sectional study of diabetic complications and their risk factors using standardized methods of assessment. The sample was comprised of 3250 insulin-dependent diabetic patients (1668 men, 1582 women) aged 15 to 60 years with mean (standard deviation) duration of diabetes of 14.7 (9.3) years from 31 European diabetes centers; 2991 of the patients were eligible for retinal photography. Visual acuity was measured using the Snellen chart. Retinopathy was evaluated by retinal photographs (two fields per eye) graded at a central facility. Glycated hemoglobin (HbA,c), cholesterol, triglyceride, fibrinogen, von Willebrand factor, and urinary albumin excretion rate were assessed at a single location. Results: Corrected visual acuity was greater than or equal to 1.0 in both eyes in 69.7% of patients and less than or equal to 0.1 in the best eye in 2.3%. Factors significantly related to vision loss were age, duration of diabetes, glycated hemoglobin (HbA 1c ), and level of retinopathy. Mild nonproliferative retinopathy was found in 25.8% of the patients, moderate-severe nonproliferative retinopathy in 9.8% of the patients, and proliferative retinopathy in 10.6% of the patients. After adjustment for age, duration of diabetes, HbA 1c , and albumin excretion rate, significant risk factors for moderate-severe nonproliferative retinopathy were blood pressure and triglyceride, and risk factors for proliferative retinopathy were triglyceride and fibrinogen. Conclusion: Vision loss is a common complication of patients with insulin-dependent diabetes, with diabetic retinopathy an important cause. Apart from poor glycemic control, several other potentially modifiable risk factors for retinopathy may be important, including elevated blood pressure, plasma triglyceride, and fibrinogen. In view of the possible barriers to the full implementation of strict glycemic control in this type of diabetes, additional strategies for the prevention and slowing of progression of retinopathy should be investigated, such as blood pressure and lipid lowering therapies.
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- 1997
4. Variation by age group and seasonally at diagnosis of childhood IDDM in Europe
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C. Lévy-Marchal, C. Patterson, A. Green, E. Schober, G. Ullreich, C. Vandewalle, A. Svendsen, R. Lounamaa, J. Tuomilehto, H. K. Åkerblom, P. Czernichow, C. Levy-Marchal, C. de Beaufort, J. Doutreix, J. Voirin, C. S. Bartsocas, C. Dakou-Voutetakis, S. Pantelakis, H. Theodoridis, K. Kassiou, P. Kyriakou, A. Kyriakou, N. Papazoglou, C. H. Manes, E. Papadeli, G. Scaragas, N. Gotsis, G. Soltesz, Z. Laron, O. Gordon, T. Shohat, G. Chiumello, E. Bognetti, F. Meschi, C. Malavasi, E. Balzano, P. Pozzilli, N. Visalli, A. Suppa, A. Guglielmi, M. L. Sebastiani, M. Songini, M. Loche, M. Silvetti, E. Angius, F. Purrello, M. Arpi, S. Italia, L. Tomaselli, M. Mancuso, G. Michel, R. Wirion, M. Reeser, G. Joner, R. O. Sovik, D. Woznicka, M. Walczak, G. Woznicki, W. Stankiewicz, A. Kedzia, Z. Szybinski, A. Czyzyk, R. Wasik, S. Abreu, C. Menezes, E. Pina, C. Ionescu-Tirgoviste, C. Dragomirescu, A. Nicolau, C. Krzisnik, T. Battelino, N. Bratanic, A. Goday, C. Castell, R. Tresserras, J. L. Taberner, G. Lloveras, D. Hadden, D. Carson, and P. Bingley
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business.industry ,Endocrinology, Diabetes and Metabolism ,Incidence (epidemiology) ,Regression analysis ,Seasonality ,medicine.disease ,symbols.namesake ,El Niño ,Diabetes mellitus ,Internal Medicine ,medicine ,symbols ,Poisson regression ,Age of onset ,business ,Demography ,Sex characteristics - Abstract
Recent data provided by the EURODIAB ACE study group have confirmed wide variation in the incidence of insulin-dependent diabetes mellitus (IDDM) across Europe. The aim of this report is to compare age-specific incidence and seasonality at clinical onset of IDDM between study regions. Using a uniform methodology, the EURODIAB ACE framework ascertained 3,168 newly-diagnosed cases of IDDM in children under the age of 15 years during 1989–1990. Eighteen percent of the cases were age 0–4 years at diagnosis, 34 % were age 5–9 years and 48 % were age 10–14 years. Poisson regression analysis suggested that there were highly significant statistical differences in incidence between the three age groups and between the 24 regions. Although incidence rates in the 0–4 year and 5–9 year age groups varied from region to region in a similar fashion, the pattern of variation in the older age group was different. Seasonality of diagnosis conformed to a sinusoidal model with a peak occurring in winter, a feature which was consistently observed in both sexes and in all age groups. However, a statistically significant heterogeneity in the seasonal distribution was present among regions, those in Scandinavia showing the smallest relative amplitude. The first insulin injection was given the same day or the day after diagnosis in 93 % of the cases for whom data were available.
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- 1995
5. Increasing prevalence of juvenile onset Type 1 (insulin-dependent) diabetes mellitus in Sardinia: the military service approach
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M. Songini, M. Loche, Sa. Muntoni, M. Stabilini, A. Coppola, G. Dessi, A. Green, G. F. Bottazzo, and Se. Muntoni
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Adult ,Male ,medicine.medical_specialty ,Pediatrics ,Adolescent ,Endocrinology, Diabetes and Metabolism ,Prevalence ,Disease ,Cohort Studies ,Diabetes mellitus ,Epidemiology ,Internal Medicine ,medicine ,Humans ,Registries ,Demography ,Type 1 diabetes ,business.industry ,medicine.disease ,Confidence interval ,Diabetes Mellitus, Type 1 ,Military Personnel ,Italy ,Cohort ,business ,Cohort study - Abstract
In order to obtain new and more detailed information about temporal trends and geographic distribution of Type 1 (insulin-dependent) diabetes mellitus in Sardinia, we screened a series of birth cohorts (1936-1973) of all male army conscripts aged 18-19 years, filed in the Sardinian Conscript Register where Type 1 diabetes is a cause of rejection. A total of 678 diabetic subjects, born and permanently residing in Sardinia, was identified. The point prevalence (x 1000) at the age of 20 years in the birth cohorts ranged from values close to zero for the first ten cohorts (1936-1945) up to a maximum of 3.08 (95% confidence limits 2.28-4.08) for the 1966 cohort and continued high thereafter although an apparent decrease was observed from the early 1970s birth cohorts. Type 1 diabetes was distributed throughout the four provinces of Sardinia with no particularly significant heterogeneity; however, in accordance with the geographical distribution of diabetes cases of the Eurodiab Ace survey (1989-1990), the highest prevalence of the disease was observed in the Cagliari and Oristano provinces, followed by Nuoro and Sassari. These data suggest a gradually increasing trend of male Type 1 diabetes prevalence in Sardinia with a 29-fold increase between the late 1930s and the late 1960s birth cohorts. This seems to confirm the high incidence of Type 1 diabetes in the 0-14 and 0-29 year age groups recently reported among Sardinians during the Eurodiab Ace collaborative multicentre study.
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- 1993
6. Rischio di diabete al di sotto del primo anno di vita: Sardegna versus resto d’Italia
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Cherubini V, P. Frongia, M. Songini, A. Ogana, F. Carle, M. Cotellessa, E. de Conciliis, A. iannilli, R. Dhamo, G. V. Coppa Gruppo di Studio SIEDP F. Chiarelli, L. Bellu, A. R. Fifi, L. Cavallo, E. Frezza, E. Piccinno, A. Vergerio, E. Cacciari, S. Salardi, E. Angius, C. Pintor, A. La Loggia, M. Cicchetti, G. Reitano, M. Mancuso, M. Pocecco, G. Cerasoli, A. Verrotti, R. Vanini, L. Spallino, A. Vaccà, P. Banin, S. Toni, R. Lorini, P. Picco, A. Monaci, F. De Luca, F. Lombardo, G. Chiumello, F. Meschi, S. Bernasconi, S. Mariani, A. Franzese, O. Stoppoloni, Bona, C. Monciotti, F. Cardella, M. Vanelli, G. Chiari, G. D’Annunzio, G. De Giorgi, L. Calisti, G. Zanette, E. Bartolotta, A. Crinò, L. Lucentini, I. P. Patera, G. Marietti, G. Multari, N. Sulli, A. M. Marinaro, A. Falorni, I. Rabbone, V. Cauvin, A. Visentin, G. Tonini, E. Buratti, P. Salvatoni, L. Pinelli, IAFUSCO, Dario, Cherubini, V, Iafusco, Dario, P., Frongia, M., Songini, A., Ogana, F., Carle, M., Cotellessa, E., de Concilii, A., Iannilli, R., Dhamo, G. V. Coppa Gruppo di Studio SIEDP F., Chiarelli, L., Bellu, A. R., Fifi, L., Cavallo, E., Frezza, E., Piccinno, A., Vergerio, E., Cacciari, S., Salardi, E., Angiu, C., Pintor, A., La Loggia, M., Cicchetti, G., Reitano, M., Mancuso, M., Pocecco, G., Cerasoli, A., Verrotti, R., Vanini, L., Spallino, A., Vaccà, P., Banin, S., Toni, R., Lorini, P., Picco, A., Monaci, F., De Luca, F., Lombardo, G., Chiumello, F., Meschi, S., Bernasconi, S., Mariani, A., Franzese, O., Stoppoloni, Bona, C., Monciotti, F., Cardella, M., Vanelli, G., Chiari, G., D’Annunzio, G., De Giorgi, L., Calisti, G., Zanette, E., Bartolotta, A., Crinò, L., Lucentini, I. P., Patera, G., Marietti, G., Multari, N., Sulli, A. M., Marinaro, A., Falorni, I., Rabbone, V., Cauvin, A., Visentin, G., Tonini, E., Buratti, P., Salvatoni, and L., Pinelli
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- 1999
7. L’incidenza del diabete tipo 1 al di sotto del primo anno di vita. Sardegna versus resto d’Italia
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Cherubini V, Frongia P, M. Songini, A. Ogada, F. Carle, M. Cotellessa, E. De Conciliis e. Gruppo di Studio di Diabetologia Pediatrica F. Chiarelli, U. Iannilli, R. Dhamo, A. Pinelli, GV Coppa, L. Bellu, A. R. Fifi, L. Cavallo, E. Frezza, E. Piccinno, A. Vergerio, E. Cacciari, S. Salardi, E. Angius, P. Frongia, C. Pintor, A. La Loggia, M. Cicchetti, G. Reitano, M. Mancuso, ML Arpi, M. Pocecco, G. Cerasoli, A. Verrotti, E. Altobelli, R. Vanini, L. Spallino, A. Vaccà, P. Banin, S. Toni, R. Lorini, P. Picco, A. Monaci, F. De Luca, F. Lombardo, G. Chiumello, F. Meschi, S. Bernasconi, S. Mariani, A. Franzese, O. Stoppoloni, F. Prisco, Bona, C. Monciotti, F. Cardella, M. Vanelli, G. Chiari, G. D’Annunzio, G. De Giorgi, L. Calisti, G. Zanette, E. Bartolotta, A. Crinò, L. Lucentini, I. P. Patera, G. Marietti, G. Multari, N. Sulli, A. M. Marinaro, A. Falorni, F. Cerutti, I. Rabbone, Bruno, V. Cauvin, A. Visentin, G. Tonini, E. Buratti, P. Salvatoni, L. Pinelli, IAFUSCO, Dario, Cherubini, V, Iafusco, Dario, Frongia, P, M., Songini, A., Ogada, F., Carle, M., Cotellessa, E. De Conciliis e. Gruppo di Studio di Diabetologia Pediatrica F., Chiarelli, U., Iannilli, R., Dhamo, A., Pinelli, Gv, Coppa, L., Bellu, A. R., Fifi, L., Cavallo, E., Frezza, E., Piccinno, A., Vergerio, E., Cacciari, S., Salardi, E., Angiu, P., Frongia, C., Pintor, A., La Loggia, M., Cicchetti, G., Reitano, M., Mancuso, Ml, Arpi, M., Pocecco, G., Cerasoli, A., Verrotti, E., Altobelli, R., Vanini, L., Spallino, A., Vaccà, P., Banin, S., Toni, R., Lorini, P., Picco, A., Monaci, F., De Luca, F., Lombardo, G., Chiumello, F., Meschi, S., Bernasconi, S., Mariani, A., Franzese, O., Stoppoloni, F., Prisco, Bona, C., Monciotti, F., Cardella, M., Vanelli, G., Chiari, G., D’Annunzio, G., De Giorgi, L., Calisti, G., Zanette, E., Bartolotta, A., Crinò, L., Lucentini, I. P., Patera, G., Marietti, G., Multari, N., Sulli, A. M., Marinaro, A., Falorni, F., Cerutti, I., Rabbone, Bruno, V., Cauvin, A., Visentin, G., Tonini, E., Buratti, P., Salvatoni, and L., Pinelli
- Published
- 1999
8. Increased prevalence of proliferative retinopathy in patients with type 1 diabetes who are deficient in glucose-6-phosphate dehydrogenase
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G. Cappai, Mara Lorenzi, M. Songini, Alessandro Doria, and Jerry D. Cavallerano
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,Endocrinology, Diabetes and Metabolism ,Pentose phosphate pathway ,Carbohydrate metabolism ,Biology ,Glucosephosphate Dehydrogenase ,medicine.disease_cause ,chemistry.chemical_compound ,Young Adult ,Polyol pathway ,Internal medicine ,Internal Medicine ,medicine ,Prevalence ,Glucose-6-phosphate dehydrogenase ,Humans ,Endothelial dysfunction ,Glycated Hemoglobin ,Type 1 diabetes ,Diabetic Retinopathy ,Diabetic retinopathy ,Middle Aged ,medicine.disease ,Endocrinology ,Diabetes Mellitus, Type 1 ,Glucosephosphate Dehydrogenase Deficiency ,chemistry ,Italy ,Oxidative stress - Abstract
Impaired activity of the pentose phosphate pathway of glucose metabolism caused by hereditary deficiency of its key regulatory enzyme glucose-6-phosphate dehydrogenase (G6PD) has consequences that may worsen or attenuate the course of diabetic complications. Decreased availability of NADPH can predispose to oxidative stress and endothelial dysfunction, but can also limit the activity of the polyol pathway and cholesterol synthesis. Reduced availability of pentose phosphates for nucleic acid synthesis could impair cell proliferation. We sought to learn in which direction G6PD deficiency affects diabetic retinopathy.We enrolled patients who were G6PD-deficient or -sufficient with type 1 diabetes of duration 15 years or longer for whom HbA(1c) records were available for at least the previous 3 years. Renal failure and smoking were exclusion criteria. For each participant seven standard field colour photographs were obtained of each eye, and retinopathy was graded in a masked fashion.The clinical characteristics of the 19 G6PD-deficient patients studied (age 42 ± 9 years, diabetes duration 24 ± 6 years, average HbA(1c) over 3 years 6.7 ± 0.8%) were similar to those of the 35 G6PD-sufficient patients. Almost 90% of patients in both groups had retinopathy; however, proliferative retinopathy was noted solely among G6PD-deficient patients (28%, p = 0.0036 vs G6PD-sufficient). The G6PD-deficient patients also showed a trend for increased frequency of microalbuminuria.The data suggest that G6PD deficiency accelerates the microvascular complications of diabetes, and that among the consequences of G6PD deficiency those that can enhance the damage caused by diabetes outweigh those that could be protective.
- Published
- 2010
9. Lower fasting blood glucose, glucose variability and nocturnal hypoglycaemia with glargine vs NPH basal insulin in subjects with Type 1 diabetes
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Gabriele Riccardi, Mariella Trovati, Renzo Cordera, R. Trevisan, M. Songini, Geremia B. Bolli, Giovanni Ghirlanda, C. Noacco, S. Del Prato, Bolli, G, Songini, M, Trovati, M, Del Prato, S, Ghirlanda, G, Cordera, R, Trevisan, R, Riccardi, G, Noacco, C, Bolli, Gb, De Prato, S, Riccardi, Gabriele, and Noacco, C.
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Blood Glucose ,Male ,type 1 diabetes ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Insulin, Isophane ,Medicine (miscellaneous) ,Insulin Glargine ,NPH insulin ,Basal insulin, Insulin analogues, Glargine, Intensive therapy ,Insulin ,Basal insulin ,Glargine ,Insulin analogue ,Nutrition and Dietetics ,Insulin Lispro ,Fasting ,Middle Aged ,Intensive therapy ,Circadian Rhythm ,Insulin, Long-Acting ,Treatment Outcome ,Italy ,fasting blood glucose ,Female ,Cardiology and Cardiovascular Medicine ,medicine.drug ,Adult ,medicine.medical_specialty ,Adolescent ,Young Adult ,Internal medicine ,Blood Glucose Self-Monitoring ,Diabetes mellitus ,medicine ,Insulin lispro ,Humans ,Hypoglycemic Agents ,Adverse effect ,glucose variability ,Glycated Hemoglobin ,Type 1 diabetes ,Insulin analogues ,Insulin glargine ,business.industry ,medicine.disease ,hypoglycemia ,Endocrinology ,Diabetes Mellitus, Type 1 ,Quality of Life ,business ,Biomarkers - Abstract
Background and aims: To compare switching from NPH insulin (NPH) to insulin glargine (glargine) with continuing NPH for changes in fasting blood glucose (FBG) in patients with Type 1 diabetes on basal-bolus therapy with insulin lispro as bolus insulin. Secondary objectives included self-monitoring blood glucose, mean daily blood glucose (MDBG) and mean amplitude glucose excursion (MAGE) values alongside changes in HbA1c and safety profiles. Methods and results: This was a 30-week, parallel, open-label, multicentre study. Seven-point profiles were used to calculate MDBG and MAGE. Hypoglycaemia and adverse events were recorded by participants. FBG improved significantly with both glargine (baseline-endpoint change: -28.0 mg/dL; 95% CI: -37.3, -18.7 mg/dL; p < 0.001) and NPH (-9.8 mg/dL; 95% CI: -19.1, -0.5 mg/dL; p = 0.0374). The improvement was significantly greater with glargine than NPH (mean difference: -18.2 mg/dL; 95% CI: -31.3, -5.2 mg/dL; p = 0.0064). MDBG (-10.1 mg/dL; 95% CI: -18.1, -2.1 mg/dL; p = 0.0126) and MAGE (-20.0 mg/dL; 95% CI: -34.5, -5.9 mg/dL; p = 0.0056) decreased significantly with glargine, but not NPH although endpoint values were no different with the two insulins. Baseline to endpoint change in HbA1c was similar (-0.56 vs -0.56%) with no differences at endpoint. Overall hypoglycaemia was no different, but glargine reduced nocturnal hypoglycaemia ("serious episodes" with BG < 42 mg/dl, p = 0.006) whereas NPH did not (p = 0.123), although endpoint values were no different. Conclusion: Switching from NPH to glargine is well tolerated and results into lower FBG, and lower glucose variability while reducing nocturnal hypoglycaemia. These data provide a rationale for more aggressive titration to target with glargine in Type 1 diabetes.
- Published
- 2009
10. Outcome of pregnancy in type 1 diabetic patients treated with insulin lispro or regular insulin: an Italian experience
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R. Gentilella, Aldo Galluzzo, R. Spezia, Domenico Valle, G. Di Cianni, L. Scaldaferri, Elena Parretti, M. Songini, Claudia Santini, Roberto Anichini, Matteo Bonomo, Angela Napoli, G. Noacco, Annunziata Lapolla, L. Tonutti, M. G. Dalfrà, Andrea Rossi, Guido Menato, E. Scaldaferri, Elisabetta Torlone, Giorgio Mello, I. Franzetti, Daniela Bruttomesso, LAPOLLA A, DALFRÀ MG, SPEZIA R, ANICHINI R, BONOMO M, BRUTTOMESSO D, DI CIANNI G, FRANZETTI I, GALLUZZO A, MELLO G, MENATO G, NAPOLI A, NOACCO G, PARRETTI E, SANTINI C, SCALDAFERRI E, SCALDAFERRI L, SONGINI M, TONUTTI L, TORLONE E, GENTILELLA R, ROSSI A, and VALLE D
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medicine.medical_specialty ,Pediatrics ,neonatal mortality ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,Birth weight ,Endocrinology ,Pregnancy ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,Birth Weight ,Humans ,Hypoglycemic Agents ,Insulin ,Medicine ,Insulin lispro ,Chromatography, High Pressure Liquid ,Retrospective Studies ,Glycated Hemoglobin ,Type 1 diabetes ,Insulin Lispro ,diabetes ,business.industry ,Infant, Newborn ,nutritional and metabolic diseases ,Retrospective cohort study ,General Medicine ,medicine.disease ,malformations ,pregnancy ,Pregnancy Complications ,Diabetes Mellitus, Type 1 ,Italy ,Infant, Small for Gestational Age ,Regular insulin ,Small for gestational age ,Female ,business ,medicine.drug - Abstract
Some studies have shown that fetal outcome observed in patients using insulin lispro is much the same as in pregnant women using regular insulin. This study aims to analyze the Italian data emerging from a multinational, multicenter, retrospective study on mothers with type 1 diabetes mellitus before pregnancy, comparing those treated with insulin lispro for at least 3 months before and 3 months after conception with those treated with regular insulin. The data collected on pregnant women with diabetes attending 15 Italian centers from 1998 to 2001 included: HbA1c at conception and during the first and third trimesters, frequency of severe hypoglycemic episodes, spontaneous abortions, mode and time of delivery, fetal malformations and mortality. Seventy-two diabetic pregnancies treated with lispro and 298 treated with regular insulin were analyzed, revealing a trend towards fewer hypoglycemic episodes in the former, who also had a significantly greater reduction in HbA1c during the first trimester. The rate of congenital malformations was similar in the offspring of the two groups of women treated with insulin lispro or regular insulin. These findings suggest that insulin lispro could be useful for the treatment of hyperglycemia in type 1 diabetic pregnant women.
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- 2008
11. Sardinia: A Battlefield Approach to Type I Diabetes Epidemiology
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Gian Franco Bottazzo, Fernanda Velluzzi, R Cirillo, Angelo Balestrieri, V. Sepe, Stefano Mariotti, Efisio Cossu, M. Songini, Giuseppe Delitala, and Andrea Loviselli
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education.field_of_study ,medicine.medical_specialty ,endocrine system diseases ,Cold spot ,business.industry ,Endocrinology, Diabetes and Metabolism ,Incidence (epidemiology) ,Population ,nutritional and metabolic diseases ,Disease ,medicine.disease ,Endocrinology ,Battlefield ,Diabetes mellitus ,Internal medicine ,Epidemiology ,medicine ,Type i diabetes ,education ,business ,Demography - Abstract
Sardinia and Finland have the highest incidence of insulin-dependent diabetes mellitus (IDDM) in the world. Therefore, both regions represent ideal observatories for investigating the environmental, genetic and immunological factors which have led to this dramatic increase. We have concentrated our efforts on Sardinia. Among several projects, there is the mapping of the island for hot and cold spots for overt IDDM. In order to map the island for pre-IDDM, we have collected and bled around 10,000 school children (age 6-14 years) and we are now in the process of enrolling around 30,000 new-born babies. We report here our initial results, which show that progression to IDDM is accompanied in both cohorts by the presence of a combination of islet-cell antibodies with either glutamic acid decarboxylase or IA-2 antibodies or both. This approach should lead to the design of reliable models of IDDM prediction in the general population, which will benefit an early insulin treatment and, hopefully, an effective prevention of the disease.
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- 1997
12. Seasonality of birth in children (0-14 years) and young adults (0-29 years) with type 1 diabetes mellitus in Sardinia differs from that in the general population. The Sardinian Collaborative Group for Epidemiology of IDDM
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M, Songini, A, Casu, I, Ashkenazi, and Z, Laron
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Adult ,Labor, Obstetric ,Adolescent ,Infant, Newborn ,Infant ,Cohort Studies ,Diabetes Mellitus, Type 1 ,Italy ,Pregnancy ,Child, Preschool ,Humans ,Female ,Seasons ,Child - Abstract
A cohort of 1,118 children (0-14 years) and 810 adolescents and young adults (15-29 years) with type 1 diabetes mellitus (DM) diagnosed in Sardinia between 1989 and 1998 were analyzed for seasonality of month of birth, and compared to the pattern registered in 314,084 live births. Patients with DM of both age groups had a statistically significant different seasonality pattern from the general population, revealing an increased birth rate during the summer months, a mirror image of the seasonality of onset of disease.
- Published
- 2001
13. Human herpes virus-8 infection among pregnant women and their children: results from the Sardinia-IDDM Study 2
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D, Serraino, M, Locatelli, M, Songini, R, Cirillo, G F, Bottazzo, M, Andreoni, S, Franceschi, and G, Rezza
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Family Health ,Infant ,Mothers ,Herpesviridae Infections ,Fetal Blood ,Infectious Disease Transmission, Vertical ,Pregnancy Complications ,Italy ,Microscopy, Fluorescence ,Pregnancy ,Child, Preschool ,Herpesvirus 8, Human ,Humans ,Female - Published
- 2001
14. Markers of Insulin Resistance Are Strong Risk Factors for Retinopathy Incidence in Type 1 Diabetes
- Author
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N, Chaturvedi, A K, Sjoelie, M, Porta, S J, Aldington, J H, Fuller, M, Songini, and E M, Kohner
- Subjects
Adult ,Glycated Hemoglobin ,Diabetic Retinopathy ,Adolescent ,Fibrinogen ,Fasting ,gamma-Glutamyltransferase ,Middle Aged ,Cholesterol ,Diabetes Mellitus, Type 1 ,Logistic Models ,Risk Factors ,von Willebrand Factor ,Albuminuria ,Body Constitution ,Humans ,Insulin ,Insulin Resistance ,Biomarkers ,Triglycerides ,Follow-Up Studies - Abstract
To determine the incidence of retinopathy and the relative importance of its risk factors in type 1 diabetes.This is a 7.3-year follow-up of 764 of 1,215 (63%) people with type 1 diabetes across Europe, aged 15-60 years at baseline with no retinopathy (the EURODIAB Prospective Complications Study). Retinal photographs were taken at baseline and follow-up and risk factors were assessed to a standard protocol.Retinopathy incidence was 56% (429/764, 95% CI 52-59%). Key risk factors included diabetes duration and glycemic control. We found no evidence of a threshold effect for HbA1c on retinopathy incidence. Univariate associations were observed between incidence and albumin excretion rate, cholesterol, triglyceride, fibrinogen, von Willebrand factor, gamma-glutamyltransferase, waist-to-hip ratio, and insulin dose. No associations were observed for blood pressure, cardiovascular disease, or smoking. Independent risk factors, as assessed by standardized regression effects, were HbA1C (1.93, P = 0.0001), duration (1.32, P = 0.008), waist-to-hip ratio (1.32, P = 0.01), and fasting triglyceride (1.24, P = 0.04).Retinopathy incidence in type 1 diabetes remains high. Key risk factors include diabetes duration and glycemic control, with no evidence of a threshold for the latter. Other independent risk factors, such as waist-to-hip ratio and triglyceride levels, both markers of insulin resistance, were strongly related to incidence.
- Published
- 2001
15. Sardinia: a battlefield approach to type I diabetes epidemiology. Sardinia-IDDM Study Groups
- Author
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G F, Bottazzo, E, Cossu, R, Cirillo, A, Loviselli, F, Velluzzi, S, Mariotti, A, Balestrieri, G, Delitala, V, Sepe, and M, Songini
- Subjects
Adolescent ,Glutamate Decarboxylase ,Incidence ,Age Factors ,Histocompatibility Antigens Class II ,Infant, Newborn ,Environment ,Cohort Studies ,Islets of Langerhans ,Diabetes Mellitus, Type 1 ,Italy ,Humans ,Child ,Finland ,Autoantibodies - Abstract
Sardinia and Finland have the highest incidence of insulin-dependent diabetes mellitus (IDDM) in the world. Therefore, both regions represent ideal observatories for investigating the environmental, genetic and immunological factors which have led to this dramatic increase. We have concentrated our efforts on Sardinia. Among several projects, there is the mapping of the island for hot and cold spots for overt IDDM. In order to map the island for pre-IDDM, we have collected and bled around 10,000 school children (age 6-14 years) and we are now in the process of enrolling around 30,000 new-born babies. We report here our initial results, which show that progression to IDDM is accompanied in both cohorts by the presence of a combination of islet-cell antibodies with either glutamic acid decarboxylase or IA-2 antibodies or both. This approach should lead to the design of reliable models of IDDM prediction in the general population, which will benefit an early insulin treatment and, hopefully, an effective prevention of the disease.
- Published
- 1997
16. High incidence rate of IDDM in Sardinia. Sardinian Collaborative Group for Epidemiology of IDDM
- Author
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S, Muntoni and M, Songini
- Subjects
Adult ,Male ,Sex Characteristics ,Adolescent ,Incidence ,Age Factors ,Infant ,Europe ,Diabetes Mellitus, Type 1 ,Italy ,Child, Preschool ,Humans ,Female ,Registries ,Child - Abstract
To provide reliable data on the incidence of IDDM in Sardinia and contribute to a better understanding of its geographical variability throughout Europe.All newly diagnosed cases of IDDM with onset less than 30 yr of age between 1 January 1989 and 31 December 1990 among residents in Sardinia were recorded. Primary ascertainment was based on notification by all Sardinian hospitals, outpatient clinics, family doctors, and pediatricians. The local IDDM patient association served as the secondary and independent source.The completeness of ascertainment was 92.8%. The annual incidence rate of IDDM (per 100,000) over the 2-yr period was 30.7 in the 0-14-yr-old age-group and 24.1 in the entire 0-29-yr-old range, respectively, with no significant differences between the two groups. Male/female ratios were 1.25 and 1.55, respectively. No significant seasonal variation in incidence was observed.Sardinia appears to have the second-highest IDDM incidence rate in Europe after Finland, and the island contradicts the generally accepted rule of a south-to-north incidence gradient.
- Published
- 1992
17. The HLA DQB1*0502 allele is neutrally associated with insulin-dependent diabetes mellitus in the Sardinian population
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Sandro Muntoni, Mario Pirastu, M. Songini, Mauro Congia, S. Porcu, A. Gao, Francesco Muntoni, F Frau, M. Arnone, Francesco Cucca, and P Cossu
- Subjects
musculoskeletal diseases ,Adult ,Male ,Heterozygote ,endocrine system diseases ,Adolescent ,Immunology ,Genes, MHC Class II ,Molecular Sequence Data ,chemical and pharmacologic phenomena ,Locus (genetics) ,Human leukocyte antigen ,Biology ,Compound heterozygosity ,Biochemistry ,Autoimmune Diseases ,Gene Frequency ,immune system diseases ,Diabetes mellitus ,HLA-DQ Antigens ,Genetics ,medicine ,Immunology and Allergy ,HLA-DQ beta-Chains ,Humans ,Genetic Predisposition to Disease ,Allele ,Alleles ,HLA-DQB1 ,Base Sequence ,Haplotype ,nutritional and metabolic diseases ,General Medicine ,Middle Aged ,medicine.disease ,Diabetes Mellitus, Type 1 ,Italy ,Female ,Disease Susceptibility ,Restriction fragment length polymorphism - Abstract
In the Sardinian population a very high incidence of insulin-dependent diabetes mellitus (IDDM) and the lack of HLA-DR2 protective effect due to the high frequency of the A2, Cw7, B17, 3F31, DR2, DQw1 extended haplotype has been reported. This haplotype, carrying a Serine at position 57 of the DQB1*0502 allele, has been previously reported to be underrepresented in patients when compared to controls. In order to provide an explanation for this finding, we defined by RFLP analysis the HLA haplotype of 45 Sardinian IDDM patients and 49 controls. All DR-2DQw1 subjects were molecularly characterized at the HLA DQA and DQB loci. All DR2-positive patients and the vast majority of the DR2-positive controls had the DQB1*0502 allele at the DR2-linked DQB1 locus, with no statistically significant difference between the two groups. All DQA1 genes were the ones expected, with only two exceptions. Nine out of 10 of the DR2-positive patients were compound heterozygotes for DQB1*0201/DQB1*0502 alleles; only this allele combination was significantly increased (p less than 0.0003). Our data suggests that a) the DQB1*0502 allele is neutral for IDDM development and b) the susceptibility to IDDM in our DR2-positive patients is related to the compound heterozygous state between the neutral DQA1*0102/DQB1*0502 and the susceptibility DQA1*0501/DQB1*0201 alleles.
- Published
- 1992
18. Incidence of IDDM in southern Europe
- Author
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M. Songini
- Subjects
medicine.medical_specialty ,business.industry ,Endocrinology, Diabetes and Metabolism ,Public health ,Incidence (epidemiology) ,Environmental health ,Internal Medicine ,Medicine ,Human physiology ,Metabolic disease ,business - Published
- 1995
19. Eurodiab Tiger Supplement. Diabetologia (2001) 44 (Suppl 3):A 9
- Author
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M. Songini
- Subjects
business.industry ,Anthropology ,Tiger ,Endocrinology, Diabetes and Metabolism ,Internal Medicine ,Medicine ,Human physiology ,business - Published
- 2002
20. Diabetes and cows' milk
- Author
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H. Wasmuth, J. Hill, M. Songini, R. B. Elliot, and G. F. Bottazzo
- Subjects
medicine.medical_specialty ,Endocrinology ,biology ,business.industry ,Internal medicine ,Diabetes mellitus ,medicine ,biology.protein ,General Medicine ,medicine.disease ,business ,Immunoglobulin G - Published
- 1996
21. High incidence of type I diabetes in Sardinia
- Author
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M. Songini and S. Muntoni
- Subjects
Pediatrics ,medicine.medical_specialty ,business.industry ,Incidence (epidemiology) ,medicine ,Type i diabetes ,General Medicine ,High incidence ,business ,Infant newborn - Published
- 1991
22. The epidemiology of type 1 diabetes mellitus is not the same in young adults as in children
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Neil T. Raymond, Frans Gorus, Anders Green, Lennarth Nyström, D Michalkova, Constantin Ionescu-Tirgoviste, C. Castell, J Oestman, E Guyrus, Patricia A. McKinney, M. Songini, Rytas Ostrauskas, Kirsten Ohm Kyvik, Medical Biochemistry, and Pathologic Biochemistry and Physiology
- Subjects
Adult ,Pediatrics ,medicine.medical_specialty ,Cumulative incidence ,Adolescent ,type 1 diabetes ,Epidemiology ,Endocrinology, Diabetes and Metabolism ,Diabetes mellitus ,Internal Medicine ,medicine ,Humans ,Registries ,Young adult ,Prospective cohort study ,Type 1 diabetes ,business.industry ,Incidence (epidemiology) ,Incidence ,Age Factors ,medicine.disease ,Europe ,Diabetes Mellitus, Type 1 ,El Niño ,business - Abstract
Aims/Hypothesis: This prospective study examined the epidemiology of type 1 diabetes in young adults in Europe. Methods: We ascertained incident cases of type 1 diabetes in the 15 to 28 years (both inclusive) age group throughout Europe over a period of 2 years. Diabetes registries in nine countries, in which incidence rates for type 1 diabetes in the 0 to 14 age group were available, took part. Incidence rates were estimated per 100 0000 person years and standardised for secx and age. Cumulative incidences per 1000 from birth to age 30 were estimated. Heterogeneity between centres was tested with a Poisson regression model. Results: A total of 2112 diabetes cases were ascertained in 1996 and 1997, of which 61.4% were considered to be type 1 diabetes. Completeness of ascertainment varied from 70 to 90%. Standardised incidence varied from 4.8 per 100 000 person years to 13.4 per 100 000 person years. The male-female ratio was estimated to be one or more, and in the 25 to 29 age group 1.5 or more in all countries. Cumulative incidences for males and females indicate that the former exceeds the latter from age 24. In the two centres with highest childhood incidence, this applied already from 14 years of age. Conclusions/interpretation: The incidence of type 1 diabetes in adults is lower than in children and the range of incidence is also reduced, with a less than threefold variation in adults, against an eightfold variation in children. There is a male excess in incidence, especially in the age group 25 to 29 years.
23. Geographical variation and rising trend of type 1 diabetes in Italy
- Author
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Cherubini V, Carle F, Gesuita R, Bruno G, Cotellessa M, Devoti G, Falorni A, Martinucci ME, Pinelli A, Prisco F, Sondini M, Visalli N, RIDI Study Group (P Barbieri, L Carpinelli, A Casu, F Cerutti, GV Coppa, G D'Annunzio, G De Giorgi, M Di Meio, P Frongia, A Gentili, Iafusco D, A Iannilli, R Lorini, G Marietti, AM Marinaro, M Mazzella, A Medici, F Merletti, G Pagano, ML Picchio, P Pozzilli, F Santeusanio, MT Tenconi, S Toni. ), F. Carle, R. Gesuita, G. Bruno, M. Cotellessa, G. Devoti, A. Falorni, M. E. Martinucci, A. Pinelli, F. Prisco, M. Songini, N. Visalli, RIDI Study Group, Barbieri, L Carpinelli, A Casu, F Cerutti, GV Coppa, G D' Annunzio, G De Giorgi, M Di Meio, P Frongia, A Gentili, D Iafusco, A Iannilli, R Lorini, G Marietti, AM Marinaro, M Mazzella, A Medici, F Merletti, G Pagano, ML Picchio, P Pozzilli, F Santeusanio, MT Tenconi, S Toni., Cherubini, V, Carle, F, Gesuita, R, Bruno, G, Cotellessa, M, Devoti, G, Falorni, A, Martinucci, Me, Pinelli, A, Prisco, F, Sondini, M, Visalli, N, RIDI Study Group (P, Barbieri, L, Carpinelli, A, Casu, F, Cerutti, Gv, Coppa, G, D'Annunzio, G De, Giorgi, M Di, Meio, P, Frongia, A, Gentili, Iafusco, D, A, Iannilli, R, Lorini, G, Marietti, Am, Marinaro, M, Mazzella, A, Medici, F, Merletti, G, Pagano, Ml, Picchio, P, Pozzilli, F, Santeusanio, Mt, Tenconi, and S, Toni. ).
- Published
- 2002
24. Autoimmune Polyendocrine Syndromes.
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Sepe V, Velluzzi F, and Songini M
- Subjects
- Humans, Syndrome, Autoimmune Diseases, Genetic Predisposition to Disease
- Published
- 2018
- Full Text
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25. Metformin associated lactic acidosis: a case series of 28 patients treated with sustained low-efficiency dialysis (SLED) and long-term follow-up.
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Angioi A, Cabiddu G, Conti M, Pili G, Atzeni A, Matta V, Cao R, Floris M, Songini M, Mulas MF, Rosner M, and Pani A
- Subjects
- Acidosis, Lactic diagnosis, Aged, Aged, 80 and over, Female, Follow-Up Studies, Humans, Male, Middle Aged, Renal Dialysis adverse effects, Retrospective Studies, Time Factors, Treatment Outcome, Acidosis, Lactic chemically induced, Acidosis, Lactic epidemiology, Hypoglycemic Agents adverse effects, Metformin adverse effects, Renal Dialysis trends
- Abstract
Background: Metformin associated lactic acidosis (MALA) is a well-known serious side effect of biguanides. However, the best treatment strategy remains a matter of debate. In the last 14 years, we observed a significant increase in hospitalizations for MALA to our Center. We report the outcomes of our clinical and therapeutic approach., Methods: This is a single-center case series. Twenty-eight patients affected with MALA and acute kidney failure admitted between January 2000 and September 2014 were included. We analyzed comorbidities, laboratory tests and clinical parameters at admission, at 36 h and at discharge. All patients were treated with sustained low-efficiency dialysis (SLED) until normalization of serum lactate (≤ 3 mmol/L), bicarbonate (between 20 and 25 mmol/L) and potassium (between 4.0 and 5.1 mmol/L)., Results: The mortality rate was 21.4%, with all of the events occurring within 24 h from admission, and before or during the first hemodialysis treatment. Precipitating causes included; acute dehydration (86.4%), systemic inflammatory response syndrome (SIRS) (57.1%), sepsis (10.7%), nephrolithiasis (14.6%) and exposure to iodinated contrast (7.1%). No further episodes of lactic acidosis were described after discontinuing the drug over a mean follow-up of 27.2 months. Furthermore, while in 2010, we had a peak incidence of MALA of 76.8 cases per 100,000 patients on metformin, this rate fell after an education campaign conducted by specialists on the proper usage of metformin in patients at risk of MALA. Although the fall in incidence after the educational program was not necessarily causal, in 2014 the incidence was 32.9/100,000., Conclusions: We report an improved mortality rate in patients affected with MALA and acute kidney injury treated with SLED compared with other series published in literature. Rapid introduction of effective hemodialysis is critical in improving outcomes.
- Published
- 2018
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26. Effect of Hydrolyzed Infant Formula vs Conventional Formula on Risk of Type 1 Diabetes: The TRIGR Randomized Clinical Trial.
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Knip M, Åkerblom HK, Al Taji E, Becker D, Bruining J, Castano L, Danne T, de Beaufort C, Dosch HM, Dupre J, Fraser WD, Howard N, Ilonen J, Konrad D, Kordonouri O, Krischer JP, Lawson ML, Ludvigsson J, Madacsy L, Mahon JL, Ormisson A, Palmer JP, Pozzilli P, Savilahti E, Serrano-Rios M, Songini M, Taback S, Vaarala O, White NH, Virtanen SM, and Wasikowa R
- Subjects
- Child, Diabetes Mellitus, Type 1 epidemiology, Disease-Free Survival, Double-Blind Method, Female, Follow-Up Studies, Humans, Infant Nutritional Physiological Phenomena, Infant, Newborn, Male, Nutrition Policy, Risk, Caseins, Diabetes Mellitus, Type 1 prevention & control, Infant Formula
- Abstract
Importance: Early exposure to complex dietary proteins may increase the risk of type 1 diabetes in children with genetic disease susceptibility. There are no intact proteins in extensively hydrolyzed formulas., Objective: To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of type 1 diabetes in young children., Design, Setting, and Participants: An international double-blind randomized clinical trial of 2159 infants with human leukocyte antigen-conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries; 1081 were randomized to be weaned to the extensively hydrolyzed casein formula and 1078 to a conventional formula. The follow-up of the participants ended on February 28, 2017., Interventions: The participants received either a casein hydrolysate or a conventional adapted cow's milk formula supplemented with 20% of the casein hydrolysate. The minimum duration of study formula exposure was 60 days by 6 to 8 months of age., Main Outcomes and Measures: Primary outcome was type 1 diabetes diagnosed according to World Health Organization criteria. Secondary outcomes included age at diabetes diagnosis and safety (adverse events)., Results: Among 2159 newborn infants (1021 female [47.3%]) who were randomized, 1744 (80.8%) completed the trial. The participants were observed for a median of 11.5 years (quartile [Q] 1-Q3, 10.2-12.8). The absolute risk of type 1 diabetes was 8.4% among those randomized to the casein hydrolysate (n = 91) vs 7.6% among those randomized to the conventional formula (n = 82) (difference, 0.8% [95% CI, -1.6% to 3.2%]). The hazard ratio for type 1 diabetes adjusted for human leukocyte antigen risk group, duration of breastfeeding, duration of study formula consumption, sex, and region while treating study center as a random effect was 1.1 (95% CI, 0.8 to 1.5; P = .46). The median age at diagnosis of type 1 diabetes was similar in the 2 groups (6.0 years [Q1-Q3, 3.1-8.9] vs 5.8 years [Q1-Q3, 2.6-9.1]; difference, 0.2 years [95% CI, -0.9 to 1.2]). Upper respiratory infections were the most common adverse event reported (frequency, 0.48 events/year in the hydrolysate group and 0.50 events/year in the control group)., Conclusions and Relevance: Among infants at risk for type 1 diabetes, weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 1 diabetes after median follow-up for 11.5 years. These findings do not support a need to revise the dietary recommendations for infants at risk for type 1 diabetes., Trial Registration: clinicaltrials.gov Identifier: NCT00179777.
- Published
- 2018
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27. Identification of Unique Antigenic Determinants in the Amino Terminus of IA-2 (ICA512) in Childhood and Adult Autoimmune Diabetes: New Biomarker Development.
- Author
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Acevedo-Calado M, James EA, Morran MP, Pietropaolo SL, Ouyang Q, Arribas-Layton D, Songini M, Liguori M, Casu A, Auchus RJ, Huang S, Yu L, Michels A, Gianani R, and Pietropaolo M
- Subjects
- Adolescent, Adult, Autoantibodies immunology, Autoantigens immunology, Biomarkers analysis, Child, Child, Preschool, Diabetes Mellitus, Type 2 immunology, Female, Glutamate Decarboxylase immunology, Humans, Leukocytes, Mononuclear immunology, Male, Middle Aged, T-Lymphocytes immunology, Young Adult, Diabetes Mellitus, Type 1 immunology, Epitopes immunology, Receptor-Like Protein Tyrosine Phosphatases, Class 8 immunology
- Abstract
Objective: The characterization of diverse subtypes of diabetes is a dynamic field of clinical research and an active area of discussion. The objective of this study was to identify new antigenic determinants in the neuroendocrine autoantigen IA-2 (ICA512) and assess whether circulating autoantibodies directed to new IA-2 epitopes identify autoimmune diabetes in young and adult populations with diabetes., Research Design and Methods: Clinically diagnosed patients with type 2 diabetes ( n = 258; diabetes duration: 0.01-31 years) were evaluated using a new biomarker detecting autoantibodies directed to the extracellular domain of the neuroendocrine autoantigen IA-2 (IA-2ec). The proportion of IA-2ec autoantibodies was also evaluated in newly diagnosed patients with type 1 diabetes ( n = 150; diabetes duration: 0.04-0.49 years). In addition, IA-2 (intracellular domain), GAD65, and zinc transporter 8 autoantibodies were assayed., Results: IA-2ec autoantibodies were detected in patients with type 1 diabetes and, surprisingly, in 5% of patients with type 2 diabetes without serologic responses to other IA-2 antigenic epitopes or other islet autoantigens. We also assessed the ability of IA-2ec-derived peptides to elicit CD4
+ T-cell responses by stimulating peripheral blood mononuclear cells from patients with type 1 diabetes ( n = 18) and HLA-matched healthy subjects ( n = 13) with peptides and staining with the peptide/DQ8-specific tetramers, observing disease-associated responses to previously unreported epitopes within IA-2ec., Conclusions: We developed a new antibody biomarker identifying novel antigenic determinants within the N terminus of IA-2. IA-2ec autoantibodies can be detected in patients with type 1 diabetes and in a subgroup of adult autoimmune patients with type 2 diabetes phenotype negative for conventional islet autoantibody testing. These observations suggest that islet autoimmunity may be more common in clinically diagnosed type 2 diabetes than previously observed., (© 2017 by the American Diabetes Association.)- Published
- 2017
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28. Type 1 diabetes in Sardinia: facts and hypotheses in the context of worldwide epidemiological data.
- Author
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Songini M, Mannu C, Targhetta C, and Bruno G
- Subjects
- Diabetes Mellitus, Type 1 genetics, Environment, Environmental Pollution, Humans, Italy epidemiology, Metals, Heavy analysis, Registries, Risk Factors, Diabetes Mellitus, Type 1 epidemiology
- Abstract
Type 1 diabetes (T1D) results from an autoimmune destruction of insulin-producing beta cells that requires lifelong insulin treatment. While significant advances have been achieved in treatment, prevention of complications and quality of life in diabetic people, the identification of environmental triggers of the disease is far more complex. The island of Sardinia has the second highest incidence of T1D in the world (45/100,000), right after Finland (64.2/100,000). The genetic background as well as the environment of the island's inhabitants makes it an ideal region for investigating environmental, immunological and genetic factors related to the etiopathogenesis of T1D. Several epidemiological studies, conducted over the years, have shown that exposures to important known environmental risk factors have changed over time, including nutritional factors, pollution, chemicals, toxins and infectious diseases in early life. These environmental risk factors might be involved in T1D pathogenesis, as they might initiate autoimmunity or accelerate and precipitate an already ongoing beta cell destruction. In terms of environmental factors, Sardinia is also particular in terms of the incidence of infection with Mycobacterium avium paratuberculosis (MAP) that recent studies have linked to T1D in the Sardinian population. Furthermore, the unique geochemical profile of Sardinia, with its particular density of heavy metals, leads to the assumption that exposure of the Sardinian population to heavy metals could also affect T1D incidence. These factors lead us to hypothesize that T1D incidence in Sardinia may be affected by the exposure to multifactorial agents, such as MAP, common viruses and heavy metals.
- Published
- 2017
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29. Incidence of type 1 diabetes in age groups above 15 years: facts, hypothesis and prospects for future epidemiologic research.
- Author
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Bruno G, Gruden G, and Songini M
- Subjects
- Adolescent, Adult, Aged, Bias, Female, Humans, Incidence, Male, Middle Aged, Registries statistics & numerical data, Diabetes Mellitus, Type 1 epidemiology
- Abstract
Although onset of type 1 diabetes can occur in adulthood, epidemiological data are scarce, limiting our potential to identify unknown determinants of the disease. Paucity of registries expanding the recruitment of incident cases up to adulthood, atypical clinical features of type 1 diabetes at onset, misclassification of type 1 as type 2 diabetes and little use of markers of β-cell autoimmunity represents major obstacles in studying the risk of type 1 diabetes in adults. New strategies in study design, data collection and analyses may overcome these problems in the future. Population-based surveys and registries including adulthood; use of etiological rather than clinical criteria to define type 1 diabetes; availability of electronic health records as prescription data sources to avoid missing data; and application of proper statistical methods will be instrumental to gain better insight on the epidemiology and natural history of the disease.
- Published
- 2016
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30. Prediction of type 1 diabetes in Sardinian schoolchildren using islet cell autoantibodies: 10-year follow-up of the Sardinian schoolchildren type 1 diabetes prediction study.
- Author
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Velluzzi F, Secci G, Sepe V, Klersy C, Shattock M, Foxon R, Songini M, Mariotti S, Locatelli M, Bottazzo GF, and Loviselli A
- Subjects
- Adolescent, Child, Child, Preschool, Diabetes Mellitus, Type 1 blood, Diabetes Mellitus, Type 1 epidemiology, Diabetes Mellitus, Type 1 immunology, Disease Progression, Female, Follow-Up Studies, Glutamate Decarboxylase immunology, Humans, Italy epidemiology, Male, Prognosis, Protein Tyrosine Phosphatases immunology, Schools statistics & numerical data, Sensitivity and Specificity, Autoantibodies blood, Diabetes Mellitus, Type 1 diagnosis, Islets of Langerhans immunology
- Abstract
Aims: Stable genetic background makes individuals from the Mediterranean island of Sardinia ideal to define the predictive power of islet-related autoantibodies (IRAs): glutamic acid decarboxylase antibodies (GADA), tyrosine phosphatase-like antibodies (IA-2A), islet cell antibodies (ICA) to identify T1DM progressors. The aims of the present study were: (1) determination of IRAs reference limits in healthy non-diabetic Sardinian schoolchildren (SSc). (2) Predictive power evaluation of IRAs as single or combined determination to identify islet to identify T1DM progressors., Methods: Between 1986 and 1994, 8448 SSc were tested for IRAs. All were followed up for 10 years. The predictive power of single or combination of IRAs was determined as hazard ratio (HR), sensitivity, specificity, area under the ROC curve, negative and positive predictive value (NPV, PPV)., Results: All 43 progressors to T1DM, but three showed at least one autoantibody positivity. HR for any single-autoantibody positivity was 55.3 times greater when compared to SSc negative for all IRAs. Any single autoantibody performed at least 64.9 % sensitivity with PPV always lower than 16 %. The best performing combination was ICA, plus IA-2A (showing 52.6 % sensitivity, 99.8 % specificity, 0.76 area under the ROC curve, 51.3 % PPV and 99.8 % NPV., Conclusions: Determination of IRAs reference limits in healthy SSc by standard statistical methods is crucial to establish the power of IRAs as progression markers to T1DM. Our data offer a solid rationale for future testing of ICA and IA-2A as routine laboratory markers to identify individuals at high risk of T1DM in the general population.
- Published
- 2016
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31. Recognition of ZnT8, Proinsulin, and Homologous MAP Peptides in Sardinian Children at Risk of T1D Precedes Detection of Classical Islet Antibodies.
- Author
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Niegowska M, Paccagnini D, Mannu C, Targhetta C, Songini M, and Sechi LA
- Subjects
- Age Factors, Antibody Specificity, Biomarkers blood, Case-Control Studies, Child, Child, Preschool, Cross Reactions, Diabetes Mellitus, Type 1 diagnosis, Diabetes Mellitus, Type 1 immunology, Diabetes Mellitus, Type 1 microbiology, Early Diagnosis, Epitopes, Humans, Infant, Infant, Newborn, Italy, Predictive Value of Tests, Zinc Transporter 8, Antibodies, Bacterial blood, Antigens, Bacterial immunology, Autoantibodies blood, Cation Transport Proteins immunology, Diabetes Mellitus, Type 1 blood, Islets of Langerhans immunology, Mycobacterium avium subsp. paratuberculosis immunology, Proinsulin immunology
- Abstract
As numerous studies put in evidence the increasing incidence of type 1 diabetes (T1D) in children, an early diagnosis is of great importance to define correct treatment and diet. Currently, the identification of classical islet autoantibodies is the primary biomarker for diagnosis in subjects at risk, especially in pediatric patients. Recent studies suggest that detection of antibodies against ZnT8 protein in preclinical phase can predict the development of T1D. We previously demonstrated a significant association of Mycobacterium avium subspecies paratuberculosis (MAP) with T1D in adult Sardinian patients. To enforce this finding, we investigated the presence of antibodies against ZnT8 and proinsulin (PI) with respective homologous epitopes: MAP3865c133-141/ZnT8186-194, MAP3865c125-133/ZnT8178-186, MAP2404c70-85/PI46-61, and MAP1,4αgbp157-173/PI64-80, in 23 children at risk for T1D, formerly involved in the TRIGR study, and 22 healthy controls (HCs). Positivity to anti-MAP and homologous human peptides was detected in 48% of at-risk subjects compared to 5,85% HCs, preceding appearance of islet autoantibodies. Being MAP easily transmitted to humans with infected cow's milk and detected in retail infant formulas, MAP epitopes could be present in extensively hydrolyzed formula and act as antigens stimulating β-cell autoimmunity.
- Published
- 2016
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32. Zinc and Other Metals Deficiencies and Risk of Type 1 Diabetes: An Ecological Study in the High Risk Sardinia Island.
- Author
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Valera P, Zavattari P, Sanna A, Pretti S, Marcello A, Mannu C, Targhetta C, Bruno G, and Songini M
- Subjects
- Adolescent, Child, Child, Preschool, Diabetes Mellitus, Type 1 epidemiology, Female, Geography, Geologic Sediments chemistry, Humans, Incidence, Infant, Infant, Newborn, Islands, Italy epidemiology, Male, Mass Spectrometry methods, Metals, Heavy metabolism, Registries statistics & numerical data, Risk Assessment methods, Risk Factors, Rivers chemistry, Spectrophotometry, Atomic, Zinc deficiency, Diabetes Mellitus, Type 1 metabolism, Metals, Heavy analysis, Risk Assessment statistics & numerical data, Zinc analysis
- Abstract
Background: Type 1 diabetes incidence presents a decreasing gradient in Europe from the Nordic countries to the Mediterranean ones. Exception to this gradient is represented by Sardinia, the second largest Mediterranean island whose population shows the highest incidence in Europe, after Finland. The genetic features of this population have created a fertile ground for the epidemic of the disease, however, as well as being strikingly high, the incidence rate has suddenly presented a continuous increase from the '50s, not explainable by accumulation of new genetic variants. Several environmental factors have been taken into account, possibly interacting with the genetic/epigenetic scenario, but there are no strong evidences to date., Methods: The present study investigated the hypothesis that geochemical elements could create permissive environmental conditions for autoimmune diabetes. An ecological analysis was performed to test possible correlations between the values of eight elements in stream sediments and type 1 diabetes incidence rate in Sardinia., Results: Analyses revealed negative associations between elements, such as Co, Cr, Cu, Mn, Ni, Zn, and type 1 diabetes incidence., Conclusions: The results suggest a possible protective role of some elements against the onset of the disease.
- Published
- 2015
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33. High GADA titer increases the risk of insulin requirement in LADA patients: a 7-year follow-up (NIRAD study 7).
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Zampetti S, Campagna G, Tiberti C, Songini M, Arpi ML, De Simone G, Cossu E, Cocco L, Osborn J, Bosi E, Giorgino F, Spoletini M, and Buzzetti R
- Subjects
- Adult, Aged, Case-Control Studies, Diabetes Mellitus, Type 2 drug therapy, Female, Follow-Up Studies, Humans, Male, Middle Aged, Risk, Titrimetry, Autoantibodies blood, Diabetes Mellitus, Type 1 blood, Diabetes Mellitus, Type 1 drug therapy, Glutamate Decarboxylase immunology, Hypoglycemic Agents therapeutic use, Insulin therapeutic use
- Abstract
Objective: The aim of this study was to determine whether glutamic acid decarboxylase antibody (GADA) titer and other clinical parameters could define the risk of progression to insulin therapy in latent autoimmune diabetes in adults (LADA) patients during a 7-year follow-up., Methods: This study involved 220 LADA and 430 type 2 diabetes subjects followed up for 7 years from the time of GADA screening to evaluate their progression toward insulin therapy. Kaplan-Meier curves and multivariate logistic regression analysis were performed to identify the markers capable of influencing this progression., Results: During the follow-up, the drop out was 4% in both groups. A total of 119 (56.1%) out of 212 LADA patients required insulin during the 7 years of follow-up. The Kaplan-Meier plots showed that 74/104 (71.1%) of high GADA titer required insulin compared with 45/108 (41.6%) of low GADA titer and with 86/412 (20.9%) of type 2 diabetes (P<0.0001 for both). A BMI of ≤25 kg/m2 and IA-2IC and zinc transporter 8 (ZnT8) positivity were also shown as the markers of faster progression (P<0.0001 for both). The proportion of LADA patients requiring insulin was significantly higher in the group of subjects treated also with sulfonylurea in the first year from diagnosis compared with those treated with diet and/or insulin sensitizers (P<0.001). The multivariate analysis confirmed that the presence of high GADA titer was a significant predictor of insulin requirement (P<0.0001, OR=6.95)., Conclusions: High GADA titer, BMI ≤ 25, ZnT8 and IA-2IC positivity and sulfonylurea treatment, in the first year from diagnosis, significantly increase the progression toward insulin requirement in LADA patients., (© 2014 European Society of Endocrinology.)
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- 2014
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34. More than 20 years of registration of type 1 diabetes in Sardinian children: temporal variations of incidence with age, period of diagnosis, and year of birth.
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Bruno G, Maule M, Biggeri A, Ledda A, Mannu C, Merletti F, and Songini M
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- Adolescent, Age Distribution, Age of Onset, Analysis of Variance, Child, Child, Preschool, Female, Gene-Environment Interaction, Humans, Incidence, Infant, Infant, Newborn, Italy epidemiology, Male, Risk Factors, Sex Distribution, Diabetes Mellitus, Type 1 epidemiology, Registries statistics & numerical data
- Abstract
We analyzed Sardinian registry data to assess time trends in incidence rates (IRs) of type 1 diabetes during the period 1989-2009 (2,371 case subjects 0-14 years of age). Poisson regression models were used to estimate the effects of sex, age, period of diagnosis, and birth cohorts. IR was 44.8 cases/100,000 person-years (95% CI 43.1-46.7). The annual increase was 2.12% (1.45-2.80; test for linear trend, P < 0.001). For boys, the increasing trend was evident up to 5 years of age and for girls up to 8 years of age. Compared with the 1989-1994 birth cohort, the relative risk increased from 0.78 (0.61-1.10) in 1974-1979 to 1.62 (1.18-2.23) in 2004-2009. The increase over period was less striking, with a tendency to regress in more recent years. The best-fitting model for boys included age and a linear time trend, and for girls age and nonlinear effects of calendar period and birth cohort. In conclusion, incidence increased over time, and the increase tended to level off in more recent years by calendar period but not by birth cohort, with some evidence of a stronger increase among girls than boys. Should the increase be attributable to the effects of some perinatal environmental factor, this would mean that such a factor has started affecting females before males.
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- 2013
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35. Type 1 diabetes and measles, mumps and rubella childhood infections within the Italian Insulin-dependent Diabetes Registry.
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Ramondetti F, Sacco S, Comelli M, Bruno G, Falorni A, Iannilli A, d'Annunzio G, Iafusco D, Songini M, Toni S, Cherubini V, and Carle F
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- Adolescent, Body Mass Index, Child, Child, Preschool, Diabetes Mellitus, Type 1 blood, Diabetes Mellitus, Type 1 immunology, Female, Humans, Incidence, Infant, Infant, Newborn, Italy epidemiology, Male, Measles blood, Measles immunology, Mumps blood, Mumps immunology, Registries, Rubella blood, Rubella immunology, Antibodies, Viral blood, Diabetes Mellitus, Type 1 epidemiology, Measles epidemiology, Measles-Mumps-Rubella Vaccine administration & dosage, Measles-Mumps-Rubella Vaccine immunology, Mumps epidemiology, Rubella epidemiology
- Abstract
Aims: Several studies confirmed the growing rate of Type 1 diabetes mellitus in childhood coinciding with increasing diagnosis of viral infections. A study investigating the incidence of Type 1 diabetes during 1996-1997 showed a higher notification of viral infections in the Pavia District. The aim was to confirm these results., Methods: This study evaluated the relationship between new cases of Type 1 diabetes and those of measles, mumps and rubella in 1996-2001, analysing data of newly-diagnosed Type 1 diabetes children, aged 0-14 years and enrolled into the RIDI (Italian Insulin-dependent Diabetes Registry) during the same years. Measles, rubella and mumps rates were calculated using as denominator the estimated 'population at risk', represented by the number of 0- to 14 year-old subjects who did not undergo the MMR (measles, mumps and rubella) vaccination. In order to investigate the association between Type 1 diabetes incidence and measles, rubella and mumps respectively, Spearman's rank correlation was used., Results: The analysis of the whole Registries data did not at first show any statistical significance between age-standardized Type 1 diabetes incidence density and estimated rates of measles, mumps and rubella notifications. Excluding data from Sardinia Registry, a significant association was observed between Type 1 diabetes incidence and mumps (P = 0.034) and rubella (P = 0.014), respectively, while there was no statistical significance between the incidence of measles cases and diabetes rates (P = 0.269)., Conclusions: According to our findings, mumps and rubella viral infections are associated with the onset of Type 1 diabetes. The statistical significance observed after exclusion of the Sardinian data suggests that other environmental factors may operate over populations with different genetic susceptibility., (© 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.)
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- 2012
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36. Blue eyes as a risk factor for type 1 diabetes.
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Di Stasio E, Maggi D, Berardesca E, Marulli GC, Bizzarri C, Lauria A, Portuesi R, Cavallo MG, Costantino F, Buzzetti R, Astorri E, Pitocco D, Songini M, and Pozzilli P
- Subjects
- Adult, Diabetes Mellitus, Type 1 epidemiology, Female, Humans, Italy epidemiology, Male, Mediterranean Region, Risk Factors, White People genetics, Diabetes Mellitus, Type 1 genetics, Eye Color genetics, Skin Pigmentation
- Abstract
Background: A high frequency of blue eyes and fair skin are reported in northern European Caucasians with type 1 diabetes (T1D). Also there is an inverse relationship between latitude and T1D incidence. We determined whether iris colour and skin pigmentation are risk factors in a Caucasian population living in two Mediterranean regions located at the same latitude with higher ultraviolet B irradiance, but with different T1D incidence., Methods: We studied iris colour in 281 consecutive subjects with T1D and 298 controls. Skin type was evaluated by melanin quantification., Results: In Lazio, blue eyes and fair skin type are significantly more common in T1D subjects than in controls (21 versus 9%, p = 0.002; 50 versus 35%, p < 0.001, respectively). In Sardinia, the frequency of blue eyes in T1D subjects is twice that in controls (5.8 versus 2.6% and significantly higher when compared to the expected calculated frequency in the entire population). By logistic regression analysis, only blue eyes are independent and significant predictors of T1D [odds ratio for blue eyes = 2.2; 95% confidence interval (1.1-4.4), p = 0.019]., Conclusions: As previously shown in a Caucasian population from northern Europe, blue eyes and a trend for fair skin increase the risk for T1D also in a Caucasian population born and residing in a Mediterranean region (Continental Italy). This finding may be relevant for explaining different T1D incidence as prevalence of blue eyes differ substantially between northern and southern European Caucasians., (Copyright © 2011 John Wiley & Sons, Ltd.)
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- 2011
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37. Increased prevalence of proliferative retinopathy in patients with type 1 diabetes who are deficient in glucose-6-phosphate dehydrogenase.
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Cappai G, Songini M, Doria A, Cavallerano JD, and Lorenzi M
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- Adolescent, Adult, Diabetes Mellitus, Type 1 epidemiology, Diabetes Mellitus, Type 1 metabolism, Diabetic Retinopathy metabolism, Glucosephosphate Dehydrogenase metabolism, Glucosephosphate Dehydrogenase Deficiency metabolism, Glycated Hemoglobin metabolism, Humans, Italy epidemiology, Male, Middle Aged, Prevalence, Young Adult, Diabetes Mellitus, Type 1 complications, Diabetic Retinopathy epidemiology, Diabetic Retinopathy etiology, Glucosephosphate Dehydrogenase Deficiency complications
- Abstract
Aims/hypothesis: Impaired activity of the pentose phosphate pathway of glucose metabolism caused by hereditary deficiency of its key regulatory enzyme glucose-6-phosphate dehydrogenase (G6PD) has consequences that may worsen or attenuate the course of diabetic complications. Decreased availability of NADPH can predispose to oxidative stress and endothelial dysfunction, but can also limit the activity of the polyol pathway and cholesterol synthesis. Reduced availability of pentose phosphates for nucleic acid synthesis could impair cell proliferation. We sought to learn in which direction G6PD deficiency affects diabetic retinopathy., Methods: We enrolled patients who were G6PD-deficient or -sufficient with type 1 diabetes of duration 15 years or longer for whom HbA(1c) records were available for at least the previous 3 years. Renal failure and smoking were exclusion criteria. For each participant seven standard field colour photographs were obtained of each eye, and retinopathy was graded in a masked fashion., Results: The clinical characteristics of the 19 G6PD-deficient patients studied (age 42 ± 9 years, diabetes duration 24 ± 6 years, average HbA(1c) over 3 years 6.7 ± 0.8%) were similar to those of the 35 G6PD-sufficient patients. Almost 90% of patients in both groups had retinopathy; however, proliferative retinopathy was noted solely among G6PD-deficient patients (28%, p = 0.0036 vs G6PD-sufficient). The G6PD-deficient patients also showed a trend for increased frequency of microalbuminuria., Conclusions/interpretation: The data suggest that G6PD deficiency accelerates the microvascular complications of diabetes, and that among the consequences of G6PD deficiency those that can enhance the damage caused by diabetes outweigh those that could be protective.
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- 2011
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38. Serum transforming growth factor β1 during diabetes development in non-obese diabetic mice and humans.
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Olivieri A, De Angelis S, Dionisi S, D'Annunzio G, Locatelli M, Marinaro M, Bonato V, Amendola A, Songini M, Velluzzi F, Schirru C, Cotichini R, Stazi MA, Dotta F, Lorini R, Bottazzo GF, and Boirivant M
- Subjects
- Adolescent, Animals, Autoantibodies blood, Child, Child, Preschool, Diabetes Mellitus, Type 1 blood, Diabetes Mellitus, Type 1 physiopathology, Disease Progression, Female, Follow-Up Studies, Humans, Inflammation, Male, Mice, Mice, Inbred C57BL, Mice, Inbred NOD, Pancreas immunology, Diabetes Mellitus, Type 1 diagnosis, Pancreas pathology, Transforming Growth Factor beta1 blood
- Abstract
Recent data show that regulatory cells with transforming growth factor (TGF)-β1-dependent activity are able to restore self-tolerance in overtly diabetic non-obese diabetic (NOD) mice. Thus, TGF-β1 seems to have a relevant role in protection from autoimmune diabetes. Our aim was to investigate the possible significance of serum TGF-β1 measurement in the natural history of diabetes in NOD mice, as well as in children positive for at least one islet-related antibody. Serum TGF-β1 (both total and active) was measured by enzyme-linked immunosorbent assay at monthly intervals in 26 NOD mice during the spontaneous development of diabetes and, on a yearly basis, in nine siblings of patients with type 1 diabetes (T1D) with a follow-up of 4 years. Diabetes appeared between the 12th week of age and the end of the study period (36 weeks) in 17 mice. TGF-β1 serum level variations occurred in the prediabetic period in both NOD mice and humans and diabetes diagnosis followed a continuing reduction of active TGF-β1 (aTGF-β1) serum levels. In mice, aTGF-β1 serum levels measured at 4 weeks of age correlated positively with severity of insulitis, and negatively with percentage of insulin-positive cells. Our findings suggest that in NOD mice serum TGF-β1 levels during the natural history of the diabetes reflect the course of islet inflammation. The measurement of aTGF-β1 in islet-related antibody-positive subjects may provide insights into the natural history of prediabetic phase of T1D., (© 2010 The Authors. Clinical and Experimental Immunology © 2010 British Society for Immunology.)
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- 2010
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39. The Sardinian way to type 1 diabetes.
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Songini M and Lombardo C
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- Adolescent, Child, Child, Preschool, Diabetes Mellitus, Type 1 immunology, Female, Genetic Predisposition to Disease, Humans, Incidence, Infant, Infant, Newborn, Italy epidemiology, Male, Diabetes Mellitus, Type 1 epidemiology, Diabetes Mellitus, Type 1 genetics
- Abstract
Sardinia and Finland are the "hottest" areas for type 1 diabetes mellitus (T1DM) worldwide. Its genetic and epidemiological background make Sardinia an ideal region for investigating environmental, immunological, and genetic factors related to the etiopathogenesis of T1DM. Consequently, in 1990, the Insulin-Dependent Diabetes Mellitus Sardinia Project was launched in order to map the geographical distribution of T1DM in the island and to investigate preclinical phases of T1DM in a large cohort of people genetically at risk. The final goal would be to design models of prediction and to formulate safe preventive measures, especially addressed to the general population living in areas at high risk., (© 2010 Diabetes Technology Society.)
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- 2010
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40. Age-period-cohort analysis of 1990-2003 incidence time trends of childhood diabetes in Italy: the RIDI study.
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Bruno G, Maule M, Merletti F, Novelli G, Falorni A, Iannilli A, Iughetti L, Altobelli E, d'Annunzio G, Piffer S, Pozzilli P, Iafusco D, Songini M, Roncarolo F, Toni S, Carle F, and Cherubini V
- Subjects
- Adolescent, Child, Child, Preschool, Cohort Studies, Female, Geography, Humans, Incidence, Infant, Italy epidemiology, Likelihood Functions, Male, Poisson Distribution, Registries, Diabetes Mellitus, Type 1 epidemiology
- Abstract
Objective: To investigate age-period-cohort effects on the temporal trend of type 1 diabetes in children age 0-14 years in Italian registries., Research Design and Methods: This report is based on 5,180 incident cases in the period 1990-2003 from the Registry for Type 1 Diabetes Mellitus in Italy (RIDI). Multilevel (random intercept) Poisson regression models were used to model the effects of sex, age, calendar time, and birth cohorts on temporal trends, taking into account the registry-level variance component., Results: The incidence rate was 12.26 per 100,000 person-years and significantly higher in boys (13.13 [95% CI 12.66-13.62]) than in girls (11.35 [10.90-11.82]). Large geographical variations in incidence within Italy were evident; incidence was highest in Sardinia, intermediate in Central-Southern Italy, and high in Northern Italy, particularly in the Trento Province, where the incidence rate was 18.67 per 100,000 person-years. An increasing temporal trend was evident (2.94% per year [95% CI 2.22-3.67]). With respect to the calendar period 1990-1992, the incidence rates increased linearly by 15, 27, 35, and 40% in the following time periods (P for trend < 0.001). With respect to the 1987-1993 birth cohort, the incidence rate ratio increased approximately linearly from 0.63 (95% CI 0.54-0.73) in the 1975-1981 cohort to 1.38 (1.06-1.80) in the 1999-2003 cohort. The best model, however, included sex, age, and a linear time trend (drift)., Conclusions: Large geographical variations and an increasing temporal trend in diabetes incidence are evident among type 1 diabetic children in Italy. Age-period-cohort analysis shows that the variation over time has a linear component that cannot be ascribed to either the calendar period or the birth cohort.
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- 2010
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41. Zinc transporter 8 antibodies complement GAD and IA-2 antibodies in the identification and characterization of adult-onset autoimmune diabetes: Non Insulin Requiring Autoimmune Diabetes (NIRAD) 4.
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Lampasona V, Petrone A, Tiberti C, Capizzi M, Spoletini M, di Pietro S, Songini M, Bonicchio S, Giorgino F, Bonifacio E, Bosi E, and Buzzetti R
- Subjects
- Adult, Case-Control Studies, Cation Transport Proteins genetics, Cation Transport Proteins immunology, Diabetes Mellitus, Type 1 genetics, Diabetes Mellitus, Type 2 genetics, Female, Humans, Male, Middle Aged, Radioimmunoprecipitation Assay, Zinc Transporter 8, Autoantibodies immunology, Cation Transport Proteins analysis, Diabetes Mellitus, Type 1 immunology, Diabetes Mellitus, Type 1 metabolism, Diabetes Mellitus, Type 2 immunology, Diabetes Mellitus, Type 2 metabolism
- Abstract
Objective: Zinc transporter 8 (ZnT8) is an islet beta-cell secretory granule membrane protein recently identified as an autoantibody antigen in type 1 diabetes. The aim of this study was to determine the prevalence and role of antibodies to ZnT8 (ZnT8As) in adult-onset diabetes., Research Design and Methods: ZnT8As were measured by a radioimmunoprecipitation assay using recombinant ZnT8 COOH-terminal or NH(2)-terminal proteins in 193 patients with adult-onset autoimmune diabetes having antibodies to either GAD (GADAs) or IA-2 (IA-2As) and in 1,056 antibody-negative patients with type 2 diabetes from the Non Insulin Requiring Autoimmune Diabetes (NIRAD) study., Results: ZnT8As-COOH were detected in 18.6% patients with autoimmune diabetes and 1.4% with type 2 diabetes. ZnT8As-NH(2) were rare. ZnT8As were associated with younger age and a high GADA titer. The use of GADAs, IA-2As, and ZnT8As in combination allowed a stratification of clinical phenotype, with younger age of onset of diabetes and characteristics of more severe insulin deficiency (higher fasting glucose and A1C, lower BMI, total cholesterol, and triglycerides) in patients with all three markers, with progressive attenuation in patients with two, one, and no antibodies (all P(trend) < 0.001). Autoantibody titers, association with high-risk HLA genotypes, and prevalence of thyroid peroxidase antibodies followed the same trend (all P < 0.001)., Conclusions: ZnT8As are detectable in a proportion of patients with adult-onset autoimmune diabetes and seem to be a valuable marker to differentiate clinical phenotypes.
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- 2010
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42. Lower fasting blood glucose, glucose variability and nocturnal hypoglycaemia with glargine vs NPH basal insulin in subjects with Type 1 diabetes.
- Author
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Bolli GB, Songini M, Trovati M, Del Prato S, Ghirlanda G, Cordera R, Trevisan R, Riccardi G, and Noacco C
- Subjects
- Adolescent, Adult, Biomarkers blood, Blood Glucose Self-Monitoring, Diabetes Mellitus, Type 1 blood, Diabetes Mellitus, Type 1 physiopathology, Female, Glycated Hemoglobin metabolism, Humans, Hypoglycemia blood, Hypoglycemia physiopathology, Hypoglycemic Agents administration & dosage, Insulin administration & dosage, Insulin adverse effects, Insulin Glargine, Insulin Lispro, Insulin, Isophane administration & dosage, Insulin, Long-Acting, Italy, Male, Middle Aged, Quality of Life, Treatment Outcome, Young Adult, Blood Glucose drug effects, Circadian Rhythm, Diabetes Mellitus, Type 1 drug therapy, Fasting blood, Hypoglycemia chemically induced, Hypoglycemic Agents adverse effects, Insulin analogs & derivatives, Insulin, Isophane adverse effects
- Abstract
Background and Aims: To compare switching from NPH insulin (NPH) to insulin glargine (glargine) with continuing NPH for changes in fasting blood glucose (FBG) in patients with Type 1 diabetes on basal-bolus therapy with insulin lispro as bolus insulin. Secondary objectives included self-monitoring blood glucose, mean daily blood glucose (MDBG) and mean amplitude glucose excursion (MAGE) values alongside changes in HbA(1c) and safety profiles., Methods and Results: This was a 30-week, parallel, open-label, multicentre study. Seven-point profiles were used to calculate MDBG and MAGE. Hypoglycaemia and adverse events were recorded by participants. FBG improved significantly with both glargine (baseline-endpoint change: -28.0 mg/dL; 95% CI: -37.3, -18.7 mg/dL; p<0.001) and NPH (-9.8 mg/dL; 95% CI: -19.1, -0.5 mg/dL; p=0.0374). The improvement was significantly greater with glargine than NPH (mean difference: -18.2 mg/dL; 95% CI: -31.3, -5.2 mg/dL; p=0.0064). MDBG (-10.1 mg/dL; 95% CI: -18.1, -2.1 mg/dL; p=0.0126) and MAGE (-20.0 mg/dL; 95% CI: -34.5, -5.9 mg/dL; p=0.0056) decreased significantly with glargine, but not NPH although endpoint values were no different with the two insulins. Baseline to endpoint change in HbA(1c) was similar (-0.56 vs -0.56%) with no differences at endpoint. Overall hypoglycaemia was no different, but glargine reduced nocturnal hypoglycaemia ("serious episodes" with BG < 42 mg/dl, p=0.006) whereas NPH did not (p=0.123), although endpoint values were no different., Conclusion: Switching from NPH to glargine is well tolerated and results into lower FBG, and lower glucose variability while reducing nocturnal hypoglycaemia. These data provide a rationale for more aggressive titration to target with glargine in Type 1 diabetes.
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- 2009
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43. Type 1 diabetes risk and autoantibody positivity in Sardinian migrants in the province of Pavia.
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Tenconi MT, Devoti G, Rizzo M, Roncarolo F, Bernasconi A, Lanati N, Calcaterra V, Songini M, Locatelli M, and Bottazzo GF
- Abstract
Background: Type 1 diabetes is an autoimmune disease. Genetics as well as environmental factors seem to play a role in the pathogenesis of type 1 diabetes., Aims: We sought to investigate the possible relationship between migration from Sardinia to a low incidence area of type 1 diabetes (Lombardy) and the prevalence of autoantibody positivity., Methods: We enrolled 554 Sardinian immigrants and 226 of their offspring. All subjects underwent a complete anamnestic evaluation. Fasting blood glucose, HbA1c, GADA and IA-2 were measured in all study participants. Additionally, the presence of risk haplotypes (HLA-DR3 -DR4 and DQB1/0302) was determined. After a seven-year follow-up, high genetic risk and/or autoantibody positivity subjects were re-evaluated., Results: Among Sardinian immigrants, the prevalence of type 1 diabetes was 0.9%, while in the offspring group, the prevalence was 0.4%. After removing type 1 diabetic patients, the GADA prevalence was 2.4% in the immigrant group and 3.8% among their offspring. Among Sardinian immigrants, the IA-2 prevalence was 0.7%, while all offspring were IA-2 negative. After a seven-year follow-up, 85.7% of GADA-positive migrants had persistent GADA positivity. Two GADA-negative offspring subjects turned positive. None of the study participants developed diabetes during the follow-up., Conclusions: The present study showed a higher prevalence of GADA positivity within Sardinian immigrants at high genetic risk; GADA positivity may represent the first detectable phase of type 1 diabetes. After a seven-year follow-up, none of the high genetic/antibody risk group subjects developed type 1 diabetes. However, it seems reasonable to strictly control high-risk individuals in order to diagnose subclinical diabetes.
- Published
- 2009
44. Technology. Hospitals urged to plan now for shift to ICD-100.
- Author
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Songini M
- Subjects
- Centers for Medicare and Medicaid Services, U.S., Forms and Records Control legislation & jurisprudence, Humans, International Classification of Diseases legislation & jurisprudence, Organizational Innovation, Planning Techniques, United States, Forms and Records Control classification, Hospital Information Systems organization & administration, International Classification of Diseases classification, Medical Records Department, Hospital organization & administration
- Published
- 2008
45. Outcome of pregnancy in type 1 diabetic patients treated with insulin lispro or regular insulin: an Italian experience.
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Lapolla A, Dalfrà MG, Spezia R, Anichini R, Bonomo M, Bruttomesso D, Di Cianni G, Franzetti I, Galluzzo A, Mello G, Menato G, Napoli A, Noacco G, Parretti E, Santini C, Scaldaferri E, Scaldaferri L, Songini M, Tonutti L, Torlone E, Gentilella R, Rossi A, and Valle D
- Subjects
- Birth Weight, Chromatography, High Pressure Liquid, Diabetes Mellitus, Type 1 complications, Female, Glycated Hemoglobin metabolism, Humans, Infant, Newborn, Infant, Small for Gestational Age, Insulin Lispro, Italy, Pregnancy, Retrospective Studies, Diabetes Mellitus, Type 1 drug therapy, Hypoglycemic Agents therapeutic use, Insulin analogs & derivatives, Insulin therapeutic use, Pregnancy Complications drug therapy
- Abstract
Some studies have shown that fetal outcome observed in patients using insulin lispro is much the same as in pregnant women using regular insulin. This study aims to analyze the Italian data emerging from a multinational, multicenter, retrospective study on mothers with type 1 diabetes mellitus before pregnancy, comparing those treated with insulin lispro for at least 3 months before and 3 months after conception with those treated with regular insulin. The data collected on pregnant women with diabetes attending 15 Italian centers from 1998 to 2001 included: HbA1c at conception and during the first and third trimesters, frequency of severe hypoglycemic episodes, spontaneous abortions, mode and time of delivery, fetal malformations and mortality. Seventy-two diabetic pregnancies treated with lispro and 298 treated with regular insulin were analyzed, revealing a trend towards fewer hypoglycemic episodes in the former, who also had a significantly greater reduction in HbA1c during the first trimester. The rate of congenital malformations was similar in the offspring of the two groups of women treated with insulin lispro or regular insulin. These findings suggest that insulin lispro could be useful for the treatment of hyperglycemia in type 1 diabetic pregnant women.
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- 2008
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46. Detrimental action of thiazolidinediones on bone.
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Mascitelli L, Pezzetta F, and Songini M
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- 2007
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47. Can plasma glucose and HbA1c predict fetal growth in mothers with different glucose tolerance levels?
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Lapolla A, Dalfrà MG, Bonomo M, Castiglioni MT, Di Cianni G, Masin M, Mion E, Paleari R, Schievano C, Songini M, Tocco G, Volpe L, and Mosca A
- Subjects
- Adult, Cross-Sectional Studies, Diabetes Mellitus, Female, Gestational Age, Glucose Tolerance Test, Humans, Infant, Newborn, Mothers, Pregnancy, Birth Weight, Blood Glucose analysis, Fetal Development, Glucose Intolerance, Glycated Hemoglobin analysis, Predictive Value of Tests
- Abstract
To assess whether HbA1c and plasma glucose predicts abnormal fetal growth, 758 pregnant women attending 5 Diabetic Centers were screened for gestational diabetes mellitus (GDM). On glucose challenge (GCT) at 24-27 weeks of gestation (g.w.), negative cases formed the normal control group (N1). Positive cases took an oral glucose tolerance test (OGTT): those found negative were classed as false positives screening test (N2); if they had an OGTT result at least as high as their normal glucose levels, they were classed as having one abnormal glucose value (OAV) at OGTT; two values as GDM. HbA1c was assayed on the day of GCT. We considered fetal macrosomia, large for gestational age (LGA), ponderal index and mean growth percentile. Mean age, pre-pregnancy BMI, fasting plasma glucose (FPG) and HbA1c were progressively higher from N1 to GDM patients. The newborn of N2 mothers were heavier than those with N1 or GDM. The mean growth percentile was significantly higher in N2 than in N1. More LGA babies were born to OAV than to N1 or N2 women. Macrosomia and ponderal index did not differ significantly in the four groups. At logistic regression only plasma glucose at GCT could predict LGA babies and a ponderal index above 2.85. At risk analysis, GDM and OAV significantly predicted LGA babies, and GDM a ponderal index >2.85. In conclusion, FPG at GCT could predict fetal overgrowth and plasma glucose >85mg/dl doubles the risk of LGA infants. HbA1c at 24-27g.w. does not predict fetal overgrowth. Mild alterations in glucose tolerance correlate with fetal overgrowth and needs monitoring and treatment.
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- 2007
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48. Type 1 diabetes and autism association seems to be linked to the incidence of diabetes.
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Iafusco D, Vanelli M, Songini M, Chiari G, Cardella F, Fifi A, Lombardo F, Marinaro A, Melia A, Marsciani A, Vaccà A, and Prisco F
- Subjects
- Humans, Autistic Disorder complications, Autistic Disorder epidemiology, Diabetes Mellitus, Type 1 complications, Diabetes Mellitus, Type 1 epidemiology
- Published
- 2006
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49. Reference intervals for hemoglobin A1c in pregnant women: data from an Italian multicenter study.
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Mosca A, Paleari R, Dalfrà MG, Di Cianni G, Cuccuru I, Pellegrini G, Malloggi L, Bonomo M, Granata S, Ceriotti F, Castiglioni MT, Songini M, Tocco G, Masin M, Plebani M, and Lapolla A
- Subjects
- Adolescent, Adult, Chromatography, High Pressure Liquid, Female, Humans, Reference Values, Glycated Hemoglobin analysis, Pregnancy blood
- Abstract
Background: The reference intervals for hemoglobin A1c (Hb A1c) in pregnant women without diabetes are not well defined, and few examples of reference intervals established by networks of different laboratories are available., Methods: Five Italian Diabetic Care Units were involved in the study. Data were collected from 445 pregnant women without diabetes, selected on the basis of glucose challenge test results, and from 384 nonpregnant control women. The Hb A1c measurements were performed with HPLC systems aligned to the Diabetes Control and Complications Trial. Plasma glucose measurements were also performed locally. Both Hb A1c and glucose measurements were harmonized by running appropriate external quality assessment schemes. The reference intervals were calculated in terms of nonparametric 2.5th to 97.5th percentiles with 0.90 confidence intervals., Results: The Hb A1c measurements were reproducible (CV = 2.0%) and accurate [mean (SE) difference from the target values, -0.10 (0.06)%]. Glucose measurements were also reproducible (mean CV = 3.2%) and accurate [difference from the target values, -0.01 (0.04) mmol/L]. To calculate common reference intervals, we merged the data collected in the different centers. The Hb A1c reference intervals were 4.0%-5.5% for pregnant nondiabetic women and 4.8%-6.2% for nonpregnant controls., Conclusions: Healthy pregnant women have lower Hb A1c concentrations than nonpregnant women. The reference intervals for Hb A1c in pregnant women should therefore be lower than those currently in use.
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- 2006
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50. Epidemiology of childhood diabetes.
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Songini M and Casu A
- Subjects
- Adolescent, Adult, Age of Onset, Celiac Disease epidemiology, Child, Child, Preschool, Europe epidemiology, Female, Humans, Hypothyroidism epidemiology, Infant, Iodide Peroxidase immunology, Italy epidemiology, Male, Multiple Sclerosis epidemiology, Pregnancy, Puerperal Disorders epidemiology, Registries, Sarcoma, Kaposi epidemiology, Thyroiditis, Autoimmune epidemiology, Diabetes Mellitus, Type 1 epidemiology
- Published
- 2005
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