This study is to evaluate copeptin values after the subcutaneous injection of glucagon in adults (healthy volunteers and patients with diabetes insipidus or primary polydipsia). It is to investigate whether glucagon stimulates the release of copeptin as a surrogate of vasopressin.

The differentiation between central diabetes insipidus (cDI) and primary polydipsia (PP) is cumbersome. To date the test with the highest diagnostic accuracy is copeptin measurement after hypertonic saline Infusion.

Instead of hypertonic saline Infusion, arginine infusion - known to stimulate growth hormone - is a potent stimulator of the neurohypophysis and provides a new diagnostic tool in the differential diagnosis of cDI. Copeptin measurements upon arginine stimulation discriminated patients with diabetes insipidus vs. patients with primary polydipsia with a high diagnostic accuracy of 94%. Glucagon has been shown to stimulate GH-secretion. In analogy to the known stimulatory effect of arginine Infusion it is hypothesized that glucagon might stimulate the posterior pituitary gland and could therefore be a novel diagnostic test in the polyuria-polydipsia syndrome.

This study is to evaluate copeptin values after the subcutaneous injection of glucagon in adults (healthy volunteers and patients with diabetes insipidus or primary polydipsia).

This study is planned as a double-blind randomized-controlled cross-over trial consisting of two parts, including healthy adults (study part 1 - proof of concept) and adults with known diagnosis of cDI or PP (study part 2 - pilot study). Study parts 1 and 2 will be conducted consecutively. If the results of study part 1 suggest that glucagon is a potent stimulator of Copeptin in healthy adults, study part 2 will be conducted. Participants will receive glucagon injection and placebo injection in random order.

Inclusion Criteria for healthy volunteers:

• no medication except hormonal contraception

Inclusion criteria for patients:

• Documented primary polydipsia or diabetes insipidus based on a water deprivation test or hypertonic saline Infusion
• Accordingly patients must have evidence of disordered drinking habits and diuresis defined as polyuria >50ml/kg body weight/24h and polydipsia >3l /24h, or must be on regular daily Desmopressin medication.

Exclusion Criteria for healthy volunteers:

• BMI > 25kg/m2 or < 18.5 kg/m2
• participation in a trial with investigational drugs within 30 days
• vigorous physical exercise within 24 hours before the study participation
• Alcohol intake within 24 hours before study participation
• pregnancy and breastfeeding
• Evidence of disordered drinking habits and diuresis defined as polyuria >50ml/kg Body weight/24h and polydipsia >3l /24h
• Intention to become pregnant during the study
• Known allergy towards glucagon
• Evidence of an acute illness
• Long QT syndrome
• Hemoglobin level below 120 g/l

Exclusion criteria for patients:

• BMI > 25kg/m2 or < 18.5 kg/m2
• participation in a trial with investigational drugs within 30 days
• vigorous physical exercise within 24 hours before the study participation
• Alcohol intake within 24 hours before study participation
• pregnancy and breastfeeding
• Evidence of an acute illness
• Long QT syndrome
• Hemoglobin level below 120 g/l