Effect of Autonomic Neuropathy on the Efficacy of a DPP-IV Inhibitor (Galvus) Therapy

Recently published work has demonstrated in animals that the control of pancreatic hormone secretion is due, at least in part, to the action of GLP-1 on the via the autonomic nervous system. Therefore, rhe investigators hypothesized that altered autonomic nervous system could explain, at least in part, the altered therapeutic efficacy of DPP-IV inhibitors observed in some patients. Our aim is to validate this concept in humans.

The objective of this physiopathological, monocentric, comparative, open, parallel study is to compare the effect of a single administration of a DPP-IV (vildagliptin: Galvus ®) over two populations of type 1 diabetic patients: a control group of 12 patients without diabetic autonomic neuropathy (NA) and a group of 12 patients with NA.

This proof of concept study will enrol type 1 diabetic patients to avoid confounding factors related to endogen insulin secretion and frequent polymedication of type 2 diabetic patients. The response will be evaluated for each patient by the relative difference between pre-and post-glucagon concentrations following a test meal, measured in the absence and presence of treatment with DPP4 inhibitor. Expected results: the DPP-4 inhibitor should lead to a reduction of about 20 to 30% of the glucagon level in patients without NA and a smaller or no decrease in patients with NA.

Inclusion criteria

• type 1 diabetes mellitus
• multiple daily insulin injections therapy or continuous insulin infusion (insulin pomp) therapy
• recent (<1 year) written diagnosis of autonomic neuropathy available
• ewing score > 2 for patients to be included in the "neuropathy" group
• ewing score <= 0.5 for patients to be included in the '"control" group
• HbA1C <= 10% at the screening visit and stable (+/- 1%)between the autonomous neuropathy diagnosis and the inclusion visit

Exclusion criteria

• severe chronic renal insufficiency defined by an estimated GFR<30 ml/min calculated by MDRD formula)
• proliferative retinopathy needing panphotocoagulation
• hepatic enzymes (ALAT, ASAT) greater than 3 times the upper limit
• congestive heart failure of NYHA functional class III-IV
• clinical signs of gastroparesis
• ongoing gastric emptying therapy
• history of bariatric surgery
• galvus therapy contra indications: known allergy or hypersensitivity of princeps or excipients, galactose intolerance, lapp lactase deficiency, glucose - galactose malabsorption
• ongoing systemic corticoids therapy
• metformin therapy during the day before each study visit
• haemoglobin alteration
• pregnancy or pregnancy willing
• lactation
• ongoing clinical study participation