INSUlin Regimens and VASCular Functions

Vago-sympathetic activity, arterial stiffness and endothelial function are integrators of cardiovascular risk. The effect of controlling fasting or post-prandial blood glucose or both on these parameters has not been studied in type 2 diabetic patients.

The aim of this pilot study is to compare the effects of improving fasting or post-prandial blood glucose glycemic control or both with 3 different insulin regimens for 4 to 5 weeks, on vago-sympathetic activity, arterial stiffness and endothelial function.

Patients will be recruited in the department of Endocrinology-Diabetology-Nutrition of Jean VERDIER hospital, AP-HP, and the department of Endocrinology and Metabolism of AVICENNE hospital, BOBIGNY, AP-HP, France. After an half day of cardiovascular explorations, 42 patients will be randomized in 3 groups determining their treatment for the following 4-5 weeks : insulin therapy with detemir at dinner or bed time, or with aspart at each meal, or with both of them.

Investigations will be performed in the morning 1) at the time of randomisation and 2) 4-5 weeks after the beginning of insulin therapy. We will evaluate at fasting and each hour after a standardized breakfast biological and metabolic parameters, arterial stiffness, endothelial function and nervous autonomic system with non-invasive devices: Sphygmocor®, Finapres®, laser-doppler et Endopat2000®. Body composition will be evaluated with impedance maestri and BodPod®.

Inclusion criteria

• Consent patient
• Adults from 30 to 72 years old
• type 2 diabetic patients for at least 1 year
• able to self measure capillary blood glucose
• body mass index 20-37 kg/m²,
• HbA1c 7.1-12% under Metformin and SULFUNYREAS therapy for at least 2 months
• anti-hypertensive treatment or dyslipidemic treatment unchanged for 3 months

Exclusion criteria

• pregnancy
• other antidiabetic medication in the previous 2 months,
• anti-hypertensive or lipid-lowering therapies having been changed in the previous 2 months,
• insulin allergy,
• uncontrolled preproliferative or proliferative diabetic retinopathy
• uncontrolled hypertension
• renal failure(creatinin clearance <40 ml/min)
• hepatocellular deficiency (prothrombin time <70%)
• anemia
• peripheral occlusive arterial disease
• cardiac arrhythmia