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Elena Matteucci,1 Ottavio Giampietro,1 Vera Covolan,2 Daniela Giustarini,3 Paolo Fanti,4 Ranieri Rossi3 1Department of Clinical and Experimental Medicine, 2Department of Chemistry and Industrial Chemistry, University of Pisa, 3Department of Life Sciences, Laboratory of Pharmacology and Toxicology, University of Siena, Siena, Italy; 4Division of Nephrology, University of Texas Health Science Center San Antonio, South Texas Veteran Health Care System, San Antonio, Texas, USA Abstract: Insulin is a life-saving medication for people with type 1 diabetes, but traditional insulin replacement therapy is based on multiple daily subcutaneous injections or continuous subcutaneous pump-regulated infusion. Nonphysiologic delivery of subcutaneous insulin implies a rapid and sustained increase in systemic insulin levels due to the loss of concentration gradient between portal and systemic circulations. In fact, the liver degrades about half of the endogenous insulin secreted by the pancreas into the venous portal system. The reverse insulin distribution has short- and long-term effects on glucose metabolism. Thus, researchers have explored less-invasive administration routes based on innovative pharmaceutical formulations, which preserve hormone stability and ensure the therapeutic effectiveness. This review examines some of the recent proposals from clinical and material chemistry point of view, giving particular attention to patients’ (and diabetologists’) ideal requirements that organic chemistry could meet. Keywords: type 1 diabetes mellitus, drug formulations, drug administration routes, insulin, portal system, nanoparticles, biodegradable polymers

Ottavio Giampietro, Chiara Giampietro, Luca Della Bartola, Maria Chiara Masoni, Elena MatteucciDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, ItalyBackground: Sitagliptin has been proven to be effective and safe as add-on to insulin in adult patients with type 2 diabetes and absolute insulin deficiency. Recently, it has been suggested to extend the use of dipeptidyl-peptidase-4 inhibitors to type 1 diabetes. The aim of this study was to evaluate and compare the effects of a long-term, fixed-dose combination of sitagliptin and metformin as add-on to insulin on body mass index, fasting plasma glucose, fructosamine, HbA1c, lipids, and daily dose of insulin in both type 1 diabetes and insulin-treated type 2 diabetes.Methods: We recruited 25 patients with type 1 diabetes (mean age 51 ± 10 years, mean disease duration 26 ± 13 years) and 31 insulin-treated type 2 diabetic patients (mean age 66 ± 8 years, mean disease duration 19 ± 9 years), who received sitagliptin with metformin as a fixed-dose combination (50/1000 mg once or twice daily) or sitagliptin (100 mg once daily, if intolerant to metformin) in addition to ongoing insulin therapy for 46 ± 19 weeks and 56 ± 14 weeks, respectively.Results: After 21 ± 9 weeks, patients with type 1 diabetes had a significantly lower body mass index, fasting plasma glucose, fructosamine, HbA1c, and daily insulin requirement. After 49 ± 17 weeks, they maintained their weight loss and total daily insulin dose and showed a significant reduction in low-density lipoprotein cholesterol levels, whereas their HbA1c had returned to baseline values. In patients with type 2 diabetes, long-term treatment remained weight-neutral but had persistent beneficial effects on short-term, intermediate-term, and long-term biomarkers of metabolic control, as well as on low-density lipoprotein cholesterol levels and insulin requirement.Conclusion: Clinical outcomes differed according to type of diabetes in terms of quality and over time. In type 2 diabetes, the combination therapy significantly improved metabolic control and the lipid profile, and decreased insulin requirements, even in the absence of clinically significant weight loss. In type 1 diabetes, the combined therapy only temporarily improved metabolic control, but significantly decreased body weight, low-density lipoprotein cholesterol levels, and insulin requirements.Keywords: dipeptidyl-peptidase-4 inhibitors, drug therapy combination, metformin, synthetic analogs of insulin, diabetes mellitus, type 1, type 2

Individuals who have type 1 diabetes need individualised medical nutrition therapies whose goals are to improve overall health and metabolic outcomes. However, interventions in the field of nutrition are challenging, as diet-related correlations with disease remain difficult to detect and the certainty of outcome in this area is elusive. Currently, patients are not meeting recommended dietary guidelines. Several alternative approaches for teaching meal planning to people with diabetes have been proposed: basic nutrition guidelines, basic diabetes guidelines, menu approaches to meal planning, exchange lists for meal planning and carbohydrate counting. The review provides an overview of suggested strategies for achieving the proposed goals and summarises evidence of outcomes. European Journal of Clinical Nutrition (2015) 69, 285-290; doi:10.1038/ejcn.2014.214; published online 8 October 2014, INTRODUCTION Individuals who have diabetes need individualised medical nutrition therapy, which can result in cost-savings and improved outcomes. (1) According to the American Diabetes Association (ADA) for youth with type [...]