Conditioning of insulin responses

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 volunteers. Additionally, we will examine the effects of conditioning on C-Peptide, hunger, food consumption, approach-avoidance tendencies towards food, and cognitive performance.
Thirty-two patients with diabetes type-2 and thirty-two healthy volunteers will be randomized based on a 1:1 ratio to a conditioned or control group in a double-blind manner. A validated two-phase experimental design will be used involving an acquisition and an evocation day. During the acquisition day, participants in the conditioned 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 conditioned 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 and the evocation day. Blood levels of insulin, glucose and C-Peptide will be measured each session on baseline, after each spray administration, and additionally 15 minutes after the last spray administration (in total 8 measurements per day). Moreover, hunger of participants will be measured 8 times during each session. Additionally, at the end of each session, a memory test, an approach avoidance task (with food items) and a bogus test will be administered.

We expect to find increased insulin and decreased glucose in the patient conditioned group in comparison to the patient control group after the placebo administration during the evocation day when controlling for baseline insulin and glucose levels, respectively. The same hypothesis pertains the healthy volunteers groups: we expect to find increased insulin and decreased glucose in the conditioned group in comparison to the control group after the placebo administration during evocation, when controlling for baseline insulin and glucose levels, respectively. Moreover, we expect that the conditioned patient group and the conditioned healthy volunteer group will demonstrate increased C-peptide levels, less hunger, better memory, less food approach bias and less food consumption during the Bogus test on both sessions in comparison to the patient control and healthy volunteers control groups.

The study consists of a telephone screening and 2 test days. Blood samples (for measuring insulin, glucose and c-peptide) will be drawn 8 times during each day. Hunger will be measured 8 times during each day. Memory, approach-avoidance tendencies towards food and food consumption will be measured twice, at the end of the acquisition and evocation days.

In the conditioned 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 6 placebo sprays during both days.