Increasing evidence suggests pancreatic islet beta-cell regeneration occurs throughout the course of the disease in patients with type 1 diabetes. Therefore, decreased beta-cell mass in type 1 diabetes may be improved through inhibition of beta-cell destruction and stimulation of proliferation, even after prolonged duration of disease. Physical activity improves insulin secretion via unknown underlying mechanisms. We recently observed that Interleukin-6 induces glucagon like Peptide (GLP)-1 production and release from the islet alpha-cell and the intestinal L-cell. Furthermore, exercise induces release of Interleukin-6 from skeletal muscle resulting in elevated circulating Interleukin-6 levels. Therefore we hypothesize that exercise-induced Interleukin-6 promotes glucagon like peptide-1 secretion from the islet α-cell and the intestinal L-cell, thereby providing a mechanism how physical activity can help maintain and improve beta-cell function in patients with type 1 diabetes. This mechanism can be enhanced by concomitant dipeptidyl peptidase-IV inhibition. Physical activity is also known to enhance insulin sensitivity and to attenuate the immune system activity. Therefore by combining physical activity and dipeptidyl peptidase-IV inhibition we aim to allow for beta-cell regeneration in a interventional randomized open-label study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
24
University Hospital Basel
Basel, Switzerland
Change in beta-cell function as derived from change in C-peptide and glucose levels during the mixed meal test
Time frame: Day 90 compared to baseline (Day 1 pre-dose)
Change in insulin sensitivity as derived from change in C-peptide and glucose levels during the mixed meal test
Time frame: Day 90 compared to baseline (Day 1 pre-dose)
Change in insulin requirements: 3-day average daily insulin dose
Time frame: baseline (Day -3 through Day -1) compared to Day 90 (Day 87 through Day 89)
Change in HbA1c levels
Time frame: baseline (Day 1 pre-dose) at Day 90
Change in fasting glucose
Time frame: baseline (Day 1 pre-dose) at Day 90
Change in fasting glucagon and cortisol
Time frame: baseline (Day 1 pre-dose) at Day 90
Change in total number of hypoglycemic events compared to treatment groups
Time frame: baseline (Day 1 pre-dose) to Day 90
Change in markers of systemic inflammation
Time frame: from baseline (Day 1 pre-dose) at Day 90
Change in composition of immune cells
Time frame: from baseline at Day 90
Change in meal-stimulated GLP-1 and gastric inhibitory peptide
Time frame: Day 90 compared to baseline
Change in lipids profile
Time frame: baseline at Day 90
Change in fatigue according to the Fatigue Scale for Motor and Cognitive Functions questionnaire
Time frame: from baseline at Day 90
Change in plasma copeptin and procalcitonin levels
Time frame: from baseline (Day 1 pre-dose) at Day 90
Change in retinal vascular diameter
Time frame: Day 90 compared to baseline (Day 1 pre-dose)
Change in arterial stiffness
Time frame: Day 90 compared to baseline (Day 1 pre-dose)
Change in fractalkine
Time frame: Day 90 compared to baseline (Day 1 pre-dose)
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