DIABETES AND METABOLISM UNIT

Director: Agostino Consoli
Phone: +39 0871 541 305
E-Mail: consoli@unich.it

Description of activities
Studies and projects of the diabetes and metabolism unit mainly focus on diabetes macrovascular complications, investigated both in vivo and in vitro, as well as on clinical studies (phase 1 to 3) aimed at the development of new treatments for diabetes and its complications. In vivo studies have been designed to look at the effect of loosing visceral and subcutaneous fat on inflammation and coagulation markers and insulin resistance as well as to look at the effect of different insulin sensitizing agents on endothelial function and NO production and availability. These studies are performed with the use of several ad hoc in vivo procedures such as Euglycemic Insulin Clamp, Hyperglycemic Clamp (Pancreatic Clamp), Indirect Calorimetry, Endothelial Function in vivo assessment, Strain-Gauge Plethismography, Bio-Impedance for Fat Mass Determination and NMR determination of visceral and subcutaneous fat, Frequent Sampling IVGTT and Muscle Biopsy. The in vitro lab is dedicated to vascular cell culture and to investigating the effect of hyperglycemia, hyperinsulinemia and insulin resistance on the molecular pathways leading to insulin signal transduction, NO production and availability, adhesion molecules and inflammatory molecule synthesis and expression.

Description of available services
Available services include: determination of insulin sensitivity by modified OGTT, frequent sampling IVGTT or insulin clamp, complete metabolic profiling of subjects, determination of endothelia function by strain-gauge plethismography and ultrasonographic determination of brachial artery dilation, determination of oxidation of carbohydrates and lipids by indirect calorimetry. The Unit also offers cell culture facilities and it is creating a bank of human endothelial cells strains obtained from umbilical cords of both healthy women or women affected by diabetes, gestational diabetes or other metabolic diseases.

Completed and on-going studies
1) Differential effect of visceral or subcutaneous fat loss on insulin resistance, inflammatory pattern and adipokines in obese subjects undergoing caloric restriction. The study has been completed and has shown that loss of visceral fat is followed by an improvement in several inflammatory parameters much greater than that following subcutaneous fat loss.
2) Effects of in vivo exposure to hyperglycemia on eNOS expression and NO production in endothelia cells. The study has been completed and has shown that endothelia cells from umbilical cords of women with gestations diabetes show increased eNOS expression as compared to cells from cords of healthy women. The same cells also show greater peroxinitrate production and greater protein nitrosylation.
3) Effect of treatment with pioglitazione or metformin on endothelial function in diabeteic subjects. The study is ongoing and aimed at evaluate a potential improvement in endothelial function on diabetic subjects undergoing therapy with insulin sensitizing agents
4) Efficacy and safety of liraglutide in the treatment of type 2 diabetes. Completed, multicentric study phase 3
5) Efficacy and safety of sitagliptin on the top of metformin and rosiglitazone in the treatment of type 2 diabetes. On-going. Multicentric study phase 2b
6) Impact of sitagliptin in the pathophysiology of type 2 diabetes. On-going, multicentric study, phase 1
7) Effect of the combination of ezetimibe+sinvastatin in the treatment of hypercholesterolemia in type 2 diabetic patients. On-going. Multicentric study, phase 3
8) Efficacy and safety of Vildagliptin on the top of metformin in the treatment of type 2 diabetes. On-going, multicentric study, phase 2b

List of International Multicenter Studies to which Prof.Consoli has collaborated over the last 3 years as Principal Investigator at his Centre.

1) Sponsor : TAKEDA
Study No Pio/LAN07/TIF – Phase III: "Double-blind, Randomized, Multicenter, Parallel-group Study to evaluate the effects of pioglitazone on Metabolic Syndrome in patients with Type 2 Diabetes treated with Metformin"

2) Sponsor: ELI LILLY
Study No H80-EW-GWBE –EUREXA (European Exenatide Study) – Phase III: "Long-Term Treatment with Exenatide Versus Glimepiride in Patients with Type 2 Diabetes Pretreated with metformin"

3) Sponsor: NOVONORDISK
Study No NN 1998-2161 – EUDRACT N. 2005-005378-58 Phase IIIa: "Inhaled pre-prandial human insulin with the AERx iDMS versus s.c. Insulin aspart in Type 2 Diabetes: A 104-week, open-label, multicentre, randomised trial followed by 12-week re-randomised extension to investigate safety and efficacy"

4) Sponsor PFIZER
Study No A 2171018 EUDRACT N 2004-001258-94 “EXUBERA”- Phase IIIb: "A One Year, Open-label Outpatient, Parallel Group Triale Assessing the Impact of the Availability of Inhaled Insulin (Exubera) on Glycemic Control in Patients with Type 2 Diabetes Mellitus Who Are Poorly Controlled on a Minimum of Two Oral Anti Diabetic Agents"

5) Sponsor NOVONORDISK
Study NN304-1632- Phase IIIb "A 20 week multi-national, open-labelled, randomised, three-group parallel trial comparing administration of insulin detemir morning, insulin detemir evening and NPH insulin evening as add-on to oral antidiabetic drug(s) in subjects with type 2 diabetes" - Trial Phase: 3b

6) Sponsor NOVO NORDISK
Study NN2211-1697 “LEAD-5” Phase IIIa: “Liraglutide Effect and Action in Diabetes (LEAD-5): Effects on glycaemic control after once daily administration of liraglutide in combination with glimepiride and metformin versus glimepiride and metformin combination therapy in subjects with type 2 diabetes. A six-month randomised, double-blind, parallel-group, multi-centre, multi-national trial with an open-label treat-to-target insulin glargine control arm”.

7) Sponsor NOVARTIS
Study CLAF237A23104 – Phase IV: A multicentric, randomized, double blind, parallel groups study to test safety and efficacy of Vildagliptin 100 mg as add on therapy to Metformin in patient with T2DM unadequately controller by Metformin 500 mg B.I.D.”

8) Sponsor MERCK SHARP & DHOME
Study 005-00-01 MK-0533 - Phase IIb.” Efficacy and safety of MK-0533 in T2DM subjetcs in sub-optimal glycemic control”

9) Sponsor MERCK SHARP & DHOME
Study 431-052-00 – Phase III. “ A randomized, placebo controlled trial to evaluate efficacy and safety of sitagliptin as add on therapy in T2DM subjects treated by metformin+ PPAR? agonist combination and not in adequate glycemic control”

10) Sponsor MERCK SHARP & DHOME
Study 431-061-00 – Phase Ib. “A Phase I Double-Blind, Randomized, Placebo-Controlled Clinical Trial to Study the Safety, Efficacy, and Mechanism of Action of Sitagliptin and Pioglitazone in Patients With Type 2 Diabetes Mellitus Who Have Inadeguate Glycaemic Control on Diet and Exercise”.

11) Sponsor MERCK SHARP & DHOME
Study 653A 107-01- Phase III:”“A Multicenter, Randomized, Double-Blind, Parallel Arm, 6-Week Study to Evaluate the Efficacy and Safety of Ezetimibe/Simvastatina Versus Atorvastatina in Patients with Metabolic Syndrome and Hypercholesterolemia at High Risk for Coronary Heart Desease”.