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

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.

• 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.

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.