Conditioning of insulin responses: a high rist- high gain intervention for diabetes type-2

Recent studies in healthy volunteers demonstrated that insulin and glucose
levels can be altered though the mechanism of classical conditioning. This is
particularly relevant for patients who suffer from a dysfunction of the insulin
system such as diabetes type-2. It however remains unknown whether this
mechanism of classical conditioning of endocrine parameters can be applied to
patients with diabetes type-2.

The primary objective of this study is to investigate the effects of classical
conditioning with intranasal insulin on endogenous insulin and glucose levels
in diabetes type-2 patients and healthy controls. Additionally, we will examine
the effects of conditioning on hunger, food consumption, approach-avoidance
behaviour and cognitive performance.

Thirty-two patients with diabetes type-2 and thirty-two healthy controls will
be randomized based on a 1:1 ratio to an experimental or control group in a
double-blind manner. A validated two-phase experimental design will be used
involving an acquisition day and an evocation day. During the acquisition day,
participants in the experimental groups will receive 6 intranasal applications
of 20 International Units (IU) of soluble insulin intranasal spray within a
period of 75 minutes. The odour of aroma oil will serve as a conditioned
stimulus (CS). During the subsequent evocation day, the participants in the
experimental groups will receive 6 administrations of a placebo spray combined
with the odour of aroma oil. Participants in the control groups will receive
placebo spray with an odour of aroma oil during both the acquisition day and
the evocation day. Insulin, glucose and C-peptide levels will be measured 8
times during each experimental day in the blood. After each spray
administration, hunger will be measured. After the last blood measurement,
participants will be asked to do a simple computer test (approach-avoidance
task with food items), a memory task and a food intake task (Bogus test).

In the experimental groups, participants will receive 6 intranasal
applications of 20 IU insulin during the acquisition day and 6 applications of
a placebo nasal spray during the evocation day. In the control groups,
participants will receive a placebo spray during both days.

Risks associated with the study procedures are minimal. Participants will be
invited to two sessions that will take place on two consecutive days and will
last 5 hours (2,5 hour per session) in total. The blood samples will be taken
during the sessions with an intravenous infusion that will be placed by a
professional nurse. The administration of intranasal insulin is safe and easy.
Adverse events are uncommon for intranasal application of insulin except for
transient local side effects such as irritation of the nose, sneezing or nasal
discharge. Since intranasal insulin has direct effects on the brain, it avoids
common serious side effects as observed with intravenous insulin injections
such as hypoglycaemia and hypertension. Several studies have been conducted in
healthy volunteers and patients with diabetes type-2 with dosages up to 160
units of intranasal insulin without reporting adverse events.