Effects of Insulin Treatment on Postprandial Platelet Activation in Patients With Non-insulin-dependent Diabetes Mellitus (NIDDM)
The postprandial phase in diabetic patients is characterized by a rapid increase in blood glucose levels, increase in platelet aggregation, LDL oxidation and over production of thrombin.
The aim of the study is to determine whether meal induced platelet activation is related to post-prandial hyperglycemia, and can be attenuated by good postprandial glucose control with rapidly acting insulin in patients with T2DM.
Type 2 Diabetes Mellitus
Drug: Insulin aspart (Novorapid®)
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
|Official Title:||Effects of Insulin Treatment on Postprandial Platelet Activation in Patients With NIDDM: a Placebo-controlled Dose-response Study With Insulin Aspart (Novorapid®)|
- To evaluate if platelet activation following a carbohydrate rich meal is related to the post-prandial hyperglycemia, and thus can be attenuated by premeal insulin treatment in patients with T2DM. [ Time Frame: 90 minutes after the meal ] [ Designated as safety issue: No ]
- Co- primary platelet response variables: U46619 stimulated platelet P- selectin activation, platelet-leukocyte aggregation, platelet-platelet aggregates and platelet-monocyte aggregates. [ Time Frame: After completion of the study in 20 patients ] [ Designated as safety issue: No ]
- To elucidate if short-term lowering of blood glucose by insulin infusion (pretreatment standardization of blood glucose) reduces platelet activity in patients with T2DM. [ Time Frame: After completion of the glucose normalization (before the meal) ] [ Designated as safety issue: No ]
|Study Start Date:||May 2007|
|Study Completion Date:||August 2010|
|Primary Completion Date:||August 2010 (Final data collection date for primary outcome measure)|
Drug: Insulin aspart (Novorapid®)
Each patient is admitted in the fasting state, on 3 different occasions . Blood glucose levels are normalized using intravenous infusion of insulin aspart , to a blood glucose level of 6-7 mmol/l. 15 minutes after normalization ,and right before a standardized meal, the patient is given a subcutaneous injection of insulin aspart 0.1 U/kg, 0.2 U/kg or placebo. The order of injections in the cross over study is randomized and blinded to the patient and to the investigators. The patient eats the meal and is followed up for 90 minutes after completion of the meal.
Blood tests for platelet function and other parameters are taken at 3 main points: 1. before glucose normalization.
2. 15 minutes after glucose normalization, and right before the meal. 3. 90 minutes after the meal.
Platelet function is evaluated by flow cytometry in whole blood (P- Selectin expression, Fibrinogen binding,aggregate formation: platelet- leukocyte, platelet-platelet, platelet-monocyte). Agonists that are used for platelet activation in flow cytometry are the thromboxane analogue U46619, ADP, and a collagen peptide that activates GPVI. Platelet adhesion is measured by the IMPACT cone and platelet analyser.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00771693
|Department of Medicine, Clinical pharmacology Unit, Karolinska University Hospital, Solna.|
|Stockholm, Sweden, SE 171 76|
|Principal Investigator:||Paul Hjemdahl, MD, PhD||Department of Medicine, Clinical Pharmacology Unit, Karolinska institute, Stockhom, Sweden|