Procedure
MAY
The data collection was done from May 2019 to March 2021. The study procedures are presented in Figure S2, Supplemental Digital Content, Eligible participants were invited to the laboratory of the Clinical Research Unit of the Leiden University Medical Center for two visits. They were asked to refrain from eating, drinking alcohol and caffeinated drinks, and exercising for a minimum of 12 hours before the study. Patients who received metformin as a treatment were asked not to take it the morning of the study, but they were allowed to take it immediately after the end of the session.On day 1, upon arrival to the laboratory, participants signed an informed consent form. Their weight and height were measured, and their health status and medication use were assessed. After that, an intravenous catheter was inserted into the median cubital vein by a licensed nurse followed by a baseline blood draw immediately after. Subsequently, participants were asked to smell a fragrant pen for 1 minute by holding the pen approximately 1 cm away from their nose. Immediately thereafter, participants in the conditioned group received 20 units of intranasal insulin spray into one nostril with one puff. Participants in the control group received a placebo spray. Right after administration of the spray, participants were asked to smell the fragrant pen for 1 more minute. Afterward, another sample of blood was drawn. After the blood draw, participants were asked to rate how well they could smell the odor, and their hunger was measured. This procedure of smell-spray-smell administration followed by blood draw and hunger rating was repeated six times every 15 minutes. In between, participants could read a newspaper. After the last spray, participants were given the first part of the memory task. Fifteen minutes after the last spray, the last blood sample was drawn and the catheter was removed. Subsequently, the second part of the memory task was done followed by a mobile food Approach Avoidance Task and a bogus taste test. Day 2 was identical to day 1; however, participants in both conditioned and control groups received a placebo nasal spray. At the end of day 2, participants were fully debriefed about the aims of the study and received a reward of 100 euros.