Cardiometabolism and clinical trials
Cardiovascular disease is substantially increased in insulin-resistant individuals with sub-diabetic hyperglycaemia, notably impaired glucose tolerance (IGT), which carries a cardiovascular risk that is little short of recently diagnosed type 2 diabetes. Increased cardiovascular risk can often be traced back 10–15 years before the diagnosis of diabetes, usually with evidence of insulin resistance and sub-diabetic hyperglycaemia. Moreover, amongst individuals presenting with a myocardial infarction, about one third are found to have undiagnosed type 2 diabetes and another third have IGT. Cardiovascular complications are now the leading cause of diabetes-related morbidity and mortality, particularly among women and the elderly. In adults with diabetes, the risk of cardiovascular disease (CVD) is two to four-fold greater than in non-diabetics. Comorbid conditions (hypertension, dyslipidemia and smoking) combine with hyperglycemia to contribute to accelerated atherosclerosis. One third of people with type 2 diabetes are undiagnosed. In addition a significant proportion of patients are diagnosed with diabetes only when they present with cardiopathy.
The CARDIO-DIABETES project will help to recognize new pathogenetic mechanisms and innovative therapies with the final goal to prevent type 2 diabetes and cardiovascular disease with a reduction of costs for the national health ministry.
Galluccio E, Cassina L, Russo I, Gelmini F, Setola E, Rampoldi L, Citterio L, Rossodivita A, Kamami M, Colombo A, Alfieri O, Carini M, Bosi E, Trovati M, Piatti P, Monti LD, Casari G. A novel truncated form of eNOS associates with altered vascular function. Cardiovasc Res. 2014 Mar 1;101(3):492-502.
Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson J, Hirshberg B, Ohman P, Frederich R, Wiviott SD, Hoffman EB, Cavender MA, Udell JA, Desai NR, Mosenzon O, McGuire DK, Ray KK, Leiter LA, Raz I; SAVOR-TIMI 53 Steering Committee and Investigators (Piatti PM). Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013. 369:1317-26;
White WB, Cannon CP, Heller SR, Nissen SE, Bergenstal RM, Bakris GL, Perez AT, Fleck PR, Mehta CR, Kupfer S, Wilson C, Cushman WC, Zannad F; EXAMINE Investigators. (Piatti PM). Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med. 2013. 369:1327-35.
Kozakova M, Natali A, Dekker J, Beck-Nielsen H, Laakso M, Nilsson P, Balkau B, Ferrannini E; RISC Investigators (Piatti PM). Insulin sensitivity and carotid intima-media thickness: relationship between insulin sensitivity and cardiovascular risk study. Arterioscler Thromb Vasc Biol. 2013 Jun;33(6):1409-17.
Baldi S, Bonnet F, Laville M, Morgantini C, Monti L, Hojlund K, Ferrannini E, Natali A; RISC Investigator (Piatti PM). Influence of apolipoproteins on the association between lipids and insulin sensitivity: a cross-sectional analysis of the RISC Study. Diabetes Care 2013. 36:4125-31.
Piatti PM, Marone E, Mantero M, Setola E, Galluccio E, Lucotti P, Shehaj E, Villa V, Perticone F, Venturini M, Palini A, Airoldi F, Faglia E, Del Maschio A, Colombo A, Chiesa R, Bosi E, Monti LD. Effect of normalization of fasting glucose by intensified insulin therapy and influence of eNOS polymorphisms on the incidence of restenosis after peripheral angioplasty in patients with type 2 diabetes: a randomized, open-label clinical trial. Acta Diabetol. 2013 Jun;50(3):373-82.
Monti LD, Casiraghi MC, Setola E, Galluccio E, Pagani Ma, Quaglia L, Bosi E, Piatti P. L-Arginine enriched biscuits improve endothelial function and glucose metabolism: A pilot study in healthy subjects and a cross-over study in subjects with impaired glucose tolerance and metabolic syndrome. Metabolism 2013 Feb;62(2):255-64.
Parving HH, Brenner BM, Mcmurray JJ, De Zeeuw D, Haffner SM, Solomon SD, Chaturvedi N, Persson F, Desai AS, Nicolaides M, Richard A, Xiang Z, Brunel P, Pfeffer MA; ALTITUDE INVESTIGATORS (Piatti PM). Cardiorenal end points in a trial of aliskiren for type 2 diabetes. N Engl J Med. 2012 Dec; 367:2204-13
Bonnet F, Disse E, Laville M, Mari A, Hojlund K, Anderwald CH, Piatti P, Balkau B; RISC Study Group. Moderate alcohol consumption is associated with improved insulin sensitivity, reduced basal insulin secretion rate and lower fasting glucagon concentration in healthy women. Diabetologia 2012 Dec;55(12):3228-37.
Hermans MP, Delibasi T, Farmer I, Lohm L, Maheux P, Piatti P, Malvolti E, Jörgens S, Charbonnel B. Effects of saxagliptin added to sub-maximal doses of metformin compared with uptitration of metformin in type 2 diabetes: the PROMPT study. Curr Med Res Opin. 2012 Oct;28(10):1635-45.
Valentina Giulia Crippa