Microcirculatory flow is subject to cyclic changes under the influence of heart rate, respiration, myogenic activity, neurogenic factors and endothelial factors. Microcirculatory oscillations (vasomotion) contribute significantly to tissue perfusion. Vasomotion analysis allowed to discriminate normoglycemic subjects, prediabetic subjects and diabetic subjects. Furthermore, changes in vasomotion can precede the emergence of global signs of microangiopathy complications in type 2 diabetes. In fact, few studies reported impaired vasomotion in type 2 diabetes with peripheral neuropathy. Vasomotion analysis after vasodilator (6-min walking test and hyperthermia) and after vasoconstrictor (foot lowering) stimulus could be an effective diagnostic tool to sharpen the diagnostic.

Objectives and Methodology: to study vasomotion at baseline and after exercise, hyperthermia and foot lowering within 3 groups of patients: diabetic without peripheral neuropathy, diabetic with subclinical peripheral neuropathy and diabetic with peripheral neuropathy and one group of sex- age- and body mass index-matched healthy control subjects.

All the subjects will benefit from a clinical, anthropometric, level of physical activity and biological evaluations. Type 2 diabetes participants will benefit from neuropathy evaluation. In addition, cutaneous microcirculation (perfusion and vasomotion) by means of Laser Doppler Flowmetry and Laser Speckle Imaging will be recorded at rest and after different stimuli (exercise, hyperthermia and foot lowering).

All the subjects will benefit from a:

• clinical: diabetes duration, treatments
• anthropometric: weight, height, BMI
• level of physical activity by means of the International Physical Activity Questionary, pedometers and the 6 minutes walking test
• biological evaluations: glycemia, HbA1C, lipids, high sensitive C-reactive protein, fibrinogen, 25(OH)D, creatinine, albumine Type 2 diabetes participants will benefit from neuropathy evaluation: sensory tests by means of Semmes-Weinstein monofilament and of Nerve Check, amplitude and velocity sural nerve and neuropathic symptom score (NSS) In addition, cutaneous microcirculation (perfusion and vasomotion) by means of Laser Doppler Flowmetry and Laser Speckle Imaging will be recorded at rest and after different stimuli (exercise, hyperthermia and foot lowering).

Inclusion Criteria:

• For diabetic patients, HbA1C >6.5 and diabetes duration >5years
• For healthy control no diabetes mellitus, no cardiovascular or renal pathology

Exclusion Criteria:

• nondiabetic neuropathy
• on medication known to affect microcirculation
• presence of active foot ulcer or wound healing history <3months
• inability to walk 6 minutes
• alcohol consumption of more than 3 units per day