Some dogs arrive at a Cushing’s diagnosis by an unexpected route: they are being treated for diabetes, the insulin dose keeps climbing, and the blood glucose still will not come under control. Eventually someone asks why an apparently well-managed diabetic needs three times the expected insulin — and the answer turns out to be cortisol.
Cushing’s disease and diabetes mellitus occur together often enough that veterinarians actively look for one when the other behaves strangely. Understanding why they interact makes the treatment plan much easier to follow.
Cortisol Is a Counter-Regulatory Hormone
Insulin’s job is to move glucose out of the bloodstream and into cells. Cortisol’s job, among many others, is to make glucose *available* — it is one of the hormones the body uses to raise blood sugar during stress, illness, or fasting.
In a healthy dog these opposing systems balance. In a dog with hyperadrenocorticism, cortisol is elevated continuously, and it pushes glucose up through several mechanisms at once. It promotes gluconeogenesis, driving the liver to manufacture new glucose. It reduces the sensitivity of peripheral tissues to insulin, so the same amount of insulin accomplishes less. And it encourages the breakdown of muscle protein into substrate the liver can convert to yet more glucose.
The result is a state of genuine insulin resistance. The pancreas may be producing insulin perfectly well, or an owner may be injecting it faithfully, and the glucose still will not come down — because the tissue on the receiving end has stopped listening.
Two Directions of Travel
The relationship runs both ways, and which came first shapes the clinical picture.
Cushing’s first, then diabetes. Sustained cortisol elevation forces the pancreas to compensate by producing ever more insulin. In some dogs the beta cells eventually cannot sustain that output, and overt diabetes mellitus develops. This is a recognized progression, which is part of why untreated Cushing’s is not a benign condition to leave alone.
Diabetes first, then Cushing’s is uncovered. A diabetic dog whose glucose control deteriorates without explanation — rising insulin requirements, persistent hyperglycemia, poor clinical response — should raise the question. Insulin resistance in a diabetic dog has a differential list, and hyperadrenocorticism sits near the top of it.
The practical marker most owners will hear about is the insulin dose itself. A dog requiring substantially more insulin per kilogram than expected, with no dietary or dosing explanation, is a dog worth screening.
The Diagnostic Complication Nobody Warns You About
Here is where it gets genuinely tricky, and where owners deserve some advance warning: poorly controlled diabetes can itself distort Cushing’s testing.
Any significant non-adrenal illness — and uncontrolled diabetes qualifies — can produce false-positive results on the standard screening tests. The stress and metabolic disruption of illness activate the HPA axis legitimately, and the test cannot easily distinguish “this dog has Cushing’s” from “this dog is systemically unwell.”
This is why a veterinarian may decline to run Cushing’s testing until diabetic control has been stabilized as far as it can be. It can feel like delay when an owner wants answers. It is not. Testing an unstable diabetic risks a false positive, and a false positive leads to treating a dog for a disease it does not have with a drug that lowers cortisol — a genuinely bad outcome.
Treating Both at Once
When both conditions are confirmed, the management principle is straightforward to state and demanding to execute: control the cortisol, and the insulin resistance often improves substantially.
Trilostane reduces cortisol production. As cortisol falls, tissues regain sensitivity to insulin — which means the insulin dose that was appropriate last week may be too much this week. Dogs in this phase require close glucose monitoring, because the risk shifts from persistent hyperglycemia toward hypoglycemia as the resistance lifts.
Owners should expect:
Frequent recheck appointments, particularly in the first weeks after starting trilostane. Two conditions are being titrated simultaneously and each affects the other.
Downward insulin adjustments, sometimes significant ones. This is the treatment working, not the diabetes resolving — the insulin is still needed, simply in a quantity that now makes sense.
Careful attention to appetite and energy. Both diseases affect both, and a change in either is information worth reporting rather than waiting out.
Diabetes in dogs is not generally reversible in the way that feline diabetes sometimes is. The realistic goal is a stable, well-controlled diabetic dog on a rational insulin dose — which is frequently achievable once the cortisol driving the resistance is addressed.
A Note on Monitoring
Dogs managing both conditions carry more monitoring burden than dogs managing either alone. Glucose curves, ACTH stimulation or pre-pill cortisol testing, and routine bloodwork all have a role, and their timing has to be coordinated rather than run independently.
That burden is worth accepting. The alternative — a diabetic dog on escalating insulin with an unrecognized cortisol problem underneath — is a dog whose owner is working very hard for very little return.
Blood pressure and a urine protein:creatinine ratio belong on that monitoring list too. Cortisol excess drives systemic hypertension and protein loss through the kidneys in a large share of Cushing’s dogs, and neither one produces a sign an owner can see at home — they are measured, not noticed. Hypertension, proteinuria, and kidney risk in canine Cushing’s covers what to measure and how often.
For owners considering adjunct natural support alongside conventional treatment, the interaction question matters here more than usual, because glucose control is being actively titrated. Anything new should be introduced with your veterinarian’s knowledge and timed so its effect can be distinguished from the medication adjustments already underway. Background on the evidence for lignans and melatonin is available at lignans.com.
The Bottom Line
Cortisol directly opposes insulin, so Cushing’s disease produces real insulin resistance and can both cause and mask diabetes mellitus. A diabetic dog needing unexpectedly large insulin doses deserves Cushing’s screening — but ideally after diabetic control is stabilized, since illness distorts the test results. Treated together, with close monitoring, most dogs improve substantially on both fronts.
Sources
- Merck Veterinary Manual — Cushing Disease (Pituitary-Dependent Hyperadrenocorticism) in Animals. https://www.merckvetmanual.com/endocrine-system/the-pituitary-gland/cushing-disease-pituitary-dependent-hyperadrenocorticism-in-animals
- Merck Veterinary Manual — Diabetes Mellitus in Animals. https://www.merckvetmanual.com/endocrine-system/the-pancreas/diabetes-mellitus-in-dogs-and-cats
