Incretins have become a successful drug target in the repertoire of medications used for the treatment of type 2 diabetes. However little is known about a potential benefit of GLP-1 on the vascular system in humans, independent of their glucose lowering actions and data are only derived from ex vivo studies in animals. Particularly little is known about clinically relevant benefits of GLP-1 and its analogues on the microvascular system of individuals with type 2 diabetes.

The vascular effect could be medicated by endogenous GLP-1 (9,36) amide, the breakdown product of GLP-1 (7,36) amide which has a low affinity for the GLP-1 receptor. The investigators hypothesis is that the co-administration of DPP-IV inhibitors will lack the beneficial effects of GLP-1 on the vascular system as GLP-1 (9,36) amide will not be produced by the body.

The study aims to examine the response of GLP-1 and its analogues on small blood vessels and examine the effect of the addition of DPP-IV inhibition in healthy lean individuals, obese individuals and subjects with Type 2 diabetes.

Inclusion Criteria:

• Lean BMI ≤ 25.0 kg/m2
• Obese BMI ≥30.0kg/m2
• Non diabetic subjects and subjects with Type 2 diabetes on stable medication for at least 3 months

Exclusion Criteria:

• cardiovascular disease
• Raynaud's disease
• current treatment with any anti-hypertensive
• lipid lowering therapies
• severe hepatic impairment
• pregnancy and lactation
• subjects with Type 2 diabetes on insulin therapy
• subjects with Type 2 diabetes on sulphonylureas
• subjects with Type 2 diabetes on incretin based therapies
• subjects with Type 2 diabetes and peripheral vascular disease
• subjects with Type 2 diabetes and history of advanced retinopathy
• subjects with Type 2 diabetes and advanced nephropathy
• subjects with Type 2 diabetes with uncontrolled diabetes (HbA1c > 8.5%)