Effects of Insulin Treatment on Postprandial Platelet Activation in Patients With Non-insulin-dependent Diabetes Mellitus (NIDDM)

Effects of Insulin Treatment on Postprandial Platelet Activation in Patients With Non-insulin-dependent Diabetes Mellitus (NIDDM)

Effects of Insulin Treatment on Postprandial Platelet Activation in Patients With NIDDM: a Placebo-controlled Dose-response Study With Insulin Aspart (Novorapid®)

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.

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.

a cross-over study with subcutaneous injection of insulin aspart 0.1U/kg, 0.2u/kg or placebo, before the meal, on 3 different occasions.

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.

Co- primary platelet response variables: U46619 stimulated platelet P- selectin activation, platelet-leukocyte aggregation, platelet-platelet aggregates and platelet-monocyte aggregates.

To elucidate if short-term lowering of blood glucose by insulin infusion (pretreatment standardization of blood glucose) reduces platelet activity in patients with T2DM.

Inclusion Criteria: Type II Diabetes Mellitus. Antecubital forearm veins allowing technically good sampling for platelet studies. HbA1c 6-9 % (Mono-S method). Below 70 years Exclusion Criteria: History of a cardiovascular disease; Ischemic heart disease, Stroke, Peripheral vascular disease. Acute or chronic renal or liver disease Contraindication to insulin treatment Treatment with Glitazones, Sulphonylurea, antiplatelet drugs, Thrombocytopenia <150 X109/l.

Spectre G, Ostenson CG, Li N, Hjemdahl P. Postprandial platelet activation is related to postprandial plasma insulin rather than glucose in patients with type 2 diabetes. Diabetes. 2012 Sep;61(9):2380-4. doi: 10.2337/db11-1806. Epub 2012 Jun 11.