Influencing the Insulin System by Placebo Effects in Patients With Diabetes Type 2 and Healthy Controls: A Randomized Controlled Trial.

OBJECTIVE: The objective of this study was to investigate whether placebo effect induced by pharmacological conditioning with intranasal insulin can affect glucose, insulin, C-peptide, hunger, and memory in patients with diabetes type 2 and healthy controls. METHODS: Placebo effect was induced by pharmacological conditioning. Thirty-two older patients (mean age = 68.3 years) with diabetes type 2 and age- and sex-matched thirty-two healthy older adults (mean age = 67.8 years) were randomly assigned to a conditioned or a control group. On day 1, conditioned group received six administrations of intranasal insulin with a conditioned stimulus (CS; smell of rosewood oil), whereas the control group received a placebo with the CS. On day 2, both groups received a placebo spray with the CS. Glucose, insulin, and C-peptide were repeatedly measured in blood. Hunger and memory were assessed with validated measures. RESULTS: Intranasal insulin stabilized dropping glucose levels in patients ( B = 0.03, SE = 0.02, p = .027) and healthy men ( B = 0.046, SE = 0.02, p = .021), and decreased C-peptide levels in healthy controls ( B = 0.01, SE = 0.001, p = .008). Conditioning also prevented the drop of glucose levels but only in men (both healthy and patients; B = 0.001, SE = 0.0003, p = .024). Conditioning significantly decreased hunger in healthy participants ( B = 0.31, SE = 0.09, p < .001). No effects were found on other measures. CONCLUSIONS: Placebo effect induced by conditioning with intranasal insulin modifies blood glucose levels and decreases hunger in older adults, but its effects depend on health status and sex. Insulin conditioning might be beneficial for groups suffering from intensive hunger but seems not be particularly suitable for blood glucose reduction. TRIAL REGISTRATION: Netherlands Trial Register, NL7783 ( https://www.trialregister.nl/trial/7783 ).

How should uncertainty about upcoming painful procedures be communicated? An experimental study into highly uncertain pain predictions.

OBJECTIVE: Uncertainty is unavoidable in the context of painful medical procedures. It is important to investigate the impact of different ways of communicating uncertainty on upcoming pain. METHODS: In our exploratory study, healthy participants (n = 30) were repeatedly presented with three highly uncertain pain predictions communicated by a hypothetical doctor. A direct statement of high uncertainty ("I don't know") was compared to more indirect predictions (social prediction: "It varies widely among people"; range prediction: "… not painful at all to very highly painful"), followed by individually calibrated electrical stimuli of non-, moderately, or very highly painful intensity. RESULTS: The direct expression of uncertainty led to the most intense pain sensation (for moderately painful stimuli only), lowest and most certain pain expectations, lowest trust in the hypothetical doctor, and lowest feeling of being well-informed, especially as compared to the social prediction. No differential effects on anxiety were observed. CONCLUSIONS: Expressing high uncertainty indirectly, with reference to the common experiences of others, may be beneficial for optimizing pain experiences and enhancing patients' trust in a medical professional. PRACTICE IMPLICATIONS: Our findings inform on how high uncertainty about upcoming pain may impact patient and health outcomes, pointing to some advantages of indirect communication.