Hypoglycaemia is a well-known complication of insulin treated diabetes. The counterregulatory response to hypoglycaemia, with glucagon as the most important mediator, is initially diminished within a few years of onset of Type 1 diabetes and subsequently lost and thus increasing the risk of hypoglycaemia. Dipeptidyl Peptidase (DPP)-4 inhibitors augment the glucagon response to insulin-induced hypoglycaemia in type 2 diabetes. The investigators hypothesize that treatment with a DPP-4 inhibitor in patients with type 1 diabetes will recover the alpha cell response to hypoglycaemia.
The 16 type 1 patients will be randomised to one of two treatment sequences: DPP-4 inhibitor followed by placebo or placebo followed by a DPP-4 inhibitor. Each treatment period lasts 6 weeks, so all patients will receive treatment for 12 weeks in total. Induction of hypoglycaemia will take place at 0 weeks, 6 weeks and 12 weeks to determine the glucagon response.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Masking
TRIPLE
Enrollment
16
100 mg once daily for six weeks
placebo, once daily for six weeks
Academic Medical Center
Amsterdam, North Holland, Netherlands
Glucagon Response to Acute Hypoglycaemia
Change in glucagon concentration from the initialisation phase to 40 minutes after occurrence of the autonomic reaction to hypoglycaemia
Time frame: Change from initialisation phase to 40 minutes after onset of hypoglycaemia
Glucagon Response to Acute Hypoglycaemia
Area under the curve (AUC) from onset of the autonomic response to hypoglycaemia to 40 minutes after onset of the autonomic response. AUC values were calculated by the trapezoid method.
Time frame: 0, 10, 20 and 40 minutes
Intact and Total Glucagon Like Peptide-1 (GLP-1), Intact and Total Gastric Inhibitory Peptide (GIP) Response to Acute Hypoglycaemia
Area under the curve (AUC) from onset of the autonomic response to hypoglycaemia to 40 minutes after onset of the autonomic response. AUC values were calculated by the trapezoid method.
Time frame: 0, 10, 20, 40 minutes
Epinephrine Response to Acute Hypoglycaemia
Area under the curve (AUC) from onset of the autonomic response to hypoglycaemia to 40 minutes after onset of the autonomic response. AUC values were calculated by the trapezoid method.
Time frame: 0, 10, 20, 40 minutes
Norepinephrine Response to Acute Hypoglycaemia
Area under the curve (AUC) from onset of the autonomic response to hypoglycaemia to 40 minutes after onset of the autonomic response. AUC values were calculated by the trapezoid method.
Time frame: 0, 10, 20, 40 minutes
Growth Hormone Response to Acute Hypoglycaemia
Area under the curve (AUC) from onset of the autonomic response to hypoglycaemia to 40 minutes after onset of the autonomic response. AUC values were calculated by the trapezoid method.
Time frame: 0, 10, 20, 40 minutes
Cortisol Response to Acute Hypoglycaemia
Area under the curve (AUC) from onset of the autonomic response to hypoglycaemia to 40 minutes after onset of the autonomic response. AUC values were calculated by the trapezoid method.
Time frame: 0, 10, 20, 40 minutes
Symptomatic Hormone Responses to Acute Hypoglycaemia.
The symptomatic responses to hypoglycaemia were assessed using a standard validated symptom questionnaire adapted for experimental hypoglycaemia (McCrimmon et al (2003) Diabet.Med. 20: 507-509). A 7-point Likert scale (1=symptom absent; 7=symptom experienced with great intensity) was used to score presence and intensity of autonomic and neuroglycopenic symptoms of hypoglycaemia. Symptom scores were obtained during the initialisation phase, at occurrence of autonomic reaction and again 30 minutes later. For analyses the scale was considered as a continuous variable.
Time frame: Change from baseline symptomatic response at hypoglycaemia and 30 minutes after hypoglycaemia
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