New Test for Diabetes Insipidus: Could It Be Easier?

observational-study PMID: 35521789

Quick Summary: Researchers are exploring a new way to diagnose diabetes insipidus (DI), a condition that causes excessive thirst and urination. They found that a simple test using glucagon, a common medication, could accurately tell the difference between DI and other conditions with similar symptoms.

What The Research Found

This study looked at using a test with glucagon to help diagnose diabetes insipidus. Glucagon is a medicine that can stimulate the body to release a hormone called copeptin. The study found that:

Healthy people and those with a condition called primary polydipsia (excessive thirst) had a significant increase in copeptin after receiving glucagon.

People with diabetes insipidus did not have a significant increase in copeptin after receiving glucagon.

This test was very accurate in distinguishing between diabetes insipidus and primary polydipsia.

Study Details

Who was studied: 22 healthy people, 10 people with diabetes insipidus, and 10 people with primary polydipsia.

How long: The study involved a single visit where participants received either glucagon or a placebo. Researchers measured copeptin levels over 3 hours.

What they took: Participants received a single injection of either glucagon (1 mg) or a placebo (an inactive substance).

What This Means For You

If you're experiencing excessive thirst and urination, your doctor might suspect diabetes insipidus. This research suggests that a glucagon test could be a new, easier way to diagnose it. This test could potentially:

Be safer than some existing tests.

Provide a more accurate diagnosis.

Help you get the right treatment faster.

Study Limitations

It's important to remember:

The study involved a relatively small number of people.

More research is needed to confirm these findings.

The study only looked at the immediate effects of glucagon.

The results may not apply to everyone.

Key Findings

The study demonstrated that glucagon stimulates copeptin release in healthy individuals and patients with primary polydipsia but not in those with central diabetes insipidus (DI). A copeptin cut-off level of 4.6 pmol/L after glucagon injection showed 100% sensitivity (95% CI: 100–100) and 90% specificity (95% CI: 70–100) for distinguishing DI from primary polydipsia. These results suggest glucagon-stimulated copeptin testing could serve as a safe and accurate diagnostic tool for DI.

Study Design

This was a double-blind, randomized, placebo-controlled trial conducted at a single center (University Hospital Basel, Switzerland). It included 42 participants: 22 healthy controls, 10 patients with central DI, and 10 with primary polydipsia. Each participant underwent two tests: one with glucagon (1 mg subcutaneous injection) and one with placebo, administered in random order. Copeptin levels were measured at baseline and at 30, 60, 90, 120, 150, and 180 minutes post-injection.

Dosage & Administration

Participants received a single subcutaneous (s.c.) dose of 1 mg glucagon during the glucagon test, while the placebo group received a saline injection. The tests were conducted in a controlled clinical setting, with copeptin measurements taken at predefined intervals to assess neurohypophyseal response.

Results & Efficacy

Healthy participants: Glucagon induced a median copeptin increase of 7.56 pmol/L (IQR: 2.38–28.03), significantly higher than placebo (0.10 pmol/L, IQR: -0.70–0.68; P < 0.001).
Central DI patients: Minimal copeptin response to glucagon (0.55 pmol/L, IQR: 0.21–1.65).
Primary polydipsia patients: Substantial copeptin increase (15.70 pmol/L, IQR: 5.99–24.39) after glucagon.
Diagnostic accuracy: A copeptin threshold of 4.6 pmol/L post-glucagon achieved 100% sensitivity and 90% specificity for identifying DI.

Limitations

Small sample size: Only 10 DI and 10 primary polydipsia patients were included, limiting generalizability.
Single-dose design: The study used only 1 mg of glucagon; dose-response relationships were not evaluated.
Short-term follow-up: Copeptin was measured for 180 minutes, but longer-term effects of glucagon on neurohypophyseal function remain unclear.
Population specificity: Results may not apply to patients with other forms of polyuria or comorbidities affecting hormone metabolism.
Placebo comparison: The placebo group showed negligible copeptin changes, but the lack of an active comparator (e.g., hypertonic saline) limits direct validation against existing diagnostic standards.

Clinical Relevance

This study highlights glucagon’s potential to replace arginine or hypertonic saline in DI diagnostics, offering a non-osmotic stimulus for copeptin release. The high sensitivity/specificity of the glucagon-copeptin test suggests it could improve diagnostic precision while avoiding risks associated with hyperosmolar stimuli. For clinicians, this provides a novel, safe alternative to differentiate DI from primary polydipsia, though further validation in larger cohorts is needed. Patients may benefit from reduced procedural discomfort and shorter testing durations.

Note: While arginine is referenced in the background as a known neurohypophyseal stimulant, the study itself focused on glucagon’s effects, not arginine supplementation or its clinical applications.