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Miriam Longo,1,2 Lorenzo Scappaticcio,1 Giuseppe Bellastella,1,2 Vlenia Pernice,1 Paolo Cirillo,1 Antonietta Maio,1 Filomena Castaldo,1,2 Dario Giugliano,1,2 Katherine Esposito,1,3 Maria Ida Maiorino1,2 On Behalf of the METRO Study Group1Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy; 2Unit of Endocrinology and Metabolic Diseases, University of Campania “Luigi Vanvitelli”, Naples 80138, Italy; 3Unit of Diabetes, University of Campania “Luigi Vanvitelli”, Naples 80138, ItalyCorrespondence: Maria Ida MaiorinoUnit of Endocrinology and Metabolic Diseases, Department of Advanced Medical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, Piazza Miraglia 2, Naples 80138, ItalyTel +39 0815665289Fax +39 0815665032Email mariaida.maiorino@unicampania.itPurpose: Type 1 diabetes is associated with high risk of cardiovascular disease (CVD). Reduced levels of circulating progenitor cells (CPCs) and endothelial progenitor cells (EPCs) have been indicated as a risk factor for adverse cardiovascular outcomes and death in people at high cardiovascular risk. The aim of the present study was to evaluate the change in CPCs and EPCs levels in a population of young type 1 diabetic patients treated with intensive insulin regimen over a period of 2 years.Patients and Methods: A total of 204 type 1 diabetic patients, of whom 84 treated with insulin pump (CSII) and 120 with multiple daily insulin injections (MDI), completed a 2-year follow-up. Clinical measurements, including the indices of glycemic control and glucose variability, were collected at baseline and after 2 years. Both CPC and EPC cell count were assessed by flow cytometry.Results: Mean age of participants was 24.5 years and mean diabetes duration was 13.6 years. After 2 years, we found a significant reduction of HbA1c (− 0.3% versus baseline, P < 0.001), associated with decrease in mean amplitude of glucose excursion (MAGE) (− 0.5 mmol/L versus baseline, P< 0.001), continuous overall net glycemic action (CONGA) (− 0.2 mmol/L versus baseline, P=0.006), and blood glucose standard deviation (BGSD) (− 0.2 mmol/L versus baseline, P< 0.001). The number of all EPCs phenotypes, but not CPC cell count, significantly raised up in the entire population, with higher increase in CSII group. MAGE resulted as an independent predictor for increased levels of both CD34+ (P = 0.020) and CD34+KDR+ (P = 0.004) cell count in the whole population.Conclusion: Over a 2-year follow-up, young type 1 diabetic patients showed an increase in circulating EPCs levels, which was higher in patients with CSII. Glucose variability resulted as an independent predictor of the raised levels of EPCs in this selected population.Keywords: endothelial progenitor cells, circulating progenitor cells, glucose variability, type 1 diabetes, CSII, MDI

Antonio Ceriello,1,2 Marco Gallo,3 Riccardo Candido,4 Alberto De Micheli,5 Katherine Esposito,6 Sandro Gentile,6 Gerardo Medea71Department of Endocrinology, Hospital Clinic de Barcelona, Institut d’Investigacions Biomèdiques August Pi iSunyer, 2Centro de Investigacion Biomèdica en Red de Diabetes y Enfermedades Metabolicas Asociadas, Barcelona, Spain; 3Oncological Endocrinology, AOU Città della Salute e della Scienza-Molinette, Turin, 4Diabetes Center, ASS 1 Triestina, Trieste, 5Ligurian Health Agency, Genoa, 6Department of Clinical and Experimental Medicine, Second University of Naples, Naples, 7Italian College of General Practitioners, Florence, ItalyAbstract: Type 2 diabetes is a progressive disease with a complex and multifactorial pathophysiology. Patients with type 2 diabetes show a variety of clinical features, including different "phenotypes" of hyperglycemia (eg, fasting/preprandial or postprandial). Thus, the best treatment choice is sometimes difficult to make, and treatment initiation or optimization is postponed. This situation may explain why, despite the existing complex therapeutic armamentarium and guidelines for the treatment of type 2 diabetes, a significant proportion of patients do not have good metabolic control and at risk of developing the late complications of diabetes. The Italian Association of Medical Diabetologists has developed an innovative personalized algorithm for the treatment of type 2 diabetes, which is available online. According to the main features shown by the patient, six algorithms are proposed, according to glycated hemoglobin (HbA1c, ≥9% or ≤9%), body mass index (≤30 kg/m2 or ≥30 kg/m2), occupational risk potentially related to hypoglycemia, chronic renal failure, and frail elderly status. Through self-monitoring of blood glucose, patients are phenotyped according to the occurrence of fasting/preprandial or postprandial hyperglycemia. In each of these six algorithms, the gradual choice of treatment is related to the identified phenotype. With one exception, these algorithms contain a stepwise approach for patients with type 2 diabetes who are metformin-intolerant. The glycemic targets (HbA1c, fasting/preprandial and postprandial glycemia) are also personalized. This accessible and easy to use algorithm may help physicians to choose a personalized treatment plan for each patient and to optimize it in a timely manner, thereby lessening clinical inertia.Keywords: type 2 diabetes, treatment guidelines, personalized treatment, Italian Association of Medical Diabetologists, Italian algorithm

Maria Ida Maiorino,1 Giuseppe Bellastella,1 Katherine Esposito2 1Department of Medical, Surgical, Neurological, Metabolic and Geriatric Sciences, Second University of Naples, Naples, Italy; 2Department of Clinical and Experimental Medicine, Second University of Naples, Naples, Italy Abstract: Diabetes mellitus is one of the most common chronic diseases in nearly all countries. It has been associated with sexual dysfunction, both in males and in females. Diabetes is an established risk factor for sexual dysfunction in men, as a threefold increased risk of erectile dysfunction was documented in diabetic men, as compared with nondiabetic men. Among women, evidence regarding the association between diabetes and sexual dysfunction are less conclusive, although most studies have reported a higher prevalence of female sexual dysfunction in diabetic women as compared with nondiabetic women. Female sexual function appears to be more related to social and psychological components than to the physiological consequence of diabetes. Hyperglycemia, which is a main determinant of vascular and microvascular diabetic complications, may participate in the pathogenetic mechanisms of sexual dysfunction in diabetes. Moreover, diabetic people may present several clinical conditions, including hypertension, overweight and obesity, metabolic syndrome, cigarette smoking, and atherogenic dyslipidemia, which are themselves risk factors for sexual dysfunction, both in men and in women. The adoption of healthy lifestyles may reduce insulin resistance, endothelial dysfunction, and oxidative stress – all of which are desirable achievements in diabetic patients. Improved well-being may further contribute to reduce and prevent sexual dysfunction in both sexes. Keywords: diabetes mellitus, diabetes complications, erectile dysfunction, female sexual dysfunction, lifestyle changes

Annalisa Capuano,1 Liberata Sportiello,1 Maria Ida Maiorino,2 Francesco Rossi,1 Dario Giugliano,2 Katherine Esposito3 1Department of Experimental Medicine, 2Department of Medical, Surgical, Neurological, Metabolic Sciences, and Geriatrics, 3Department of Clinical and Experimental Medicine and Surgery, Second University of Naples, Naples, Italy Abstract: Type 2 diabetes mellitus is a complex and progressive disease that is showing an apparently unstoppable increase worldwide. Although there is general agreement on the first-line use of metformin in most patients with type 2 diabetes, the ideal drug sequence after metformin failure is an area of increasing uncertainty. New treatment strategies target pancreatic islet dysfunction, in particular gut-derived incretin hormones. Inhibition of the enzyme dipeptidyl peptidase-4 (DPP-4) slows degradation of endogenous glucagon-like peptide-1 (GLP-1) and thereby enhances and prolongs the action of the endogenous incretin hormones. The five available DPP-4 inhibitors, also known as 'gliptins' (sitagliptin, vildagliptin, saxagliptin, linagliptin, alogliptin), are small molecules used orally with similar overall clinical efficacy and safety profiles in patients with type 2 diabetes. The main differences between the five gliptins on the market include: potency, target selectivity, oral bioavailability, long or short half-life, high or low binding to plasma proteins, metabolism, presence of active or inactive metabolites, excretion routes, dosage adjustment for renal and liver insufficiency, and potential drug–drug interactions. On average, treatment with gliptins is expected to produce a mean glycated hemoglobin (HbA1c) decrease of 0.5%–0.8%, with about 40% of diabetic subjects at target for the HbA1c goal