Somogyi Effect in Cats with Diabetes
SOMOGYI EFFECT IN CATS: REBOUND HYPERGLYCEMIA OR INSULIN-INDUCED HYPERGLYCEMIA
DR. AMIT BHARDWAJ, PET CONSULTANT, PUNE
Canine and feline diabetes is a disease that results in an abnormal increase in blood glucose levels. When treated with insulin, the blood glucose levels are decreased and, hopefully, kept within the normal range.
Insulin overdose, however, is possible and can lead to a phenomenon known as the Somogyi effect. If you have a diabetic pet, you’ll want to know about Dr. Somogyi. He was a scientist who developed the first insulin treatment given to a (human) child. He also discovered the “Somogyi Effect.” Oh, and it’s pronounced so-MOH-gee. This phenomenon is what makes regulating insulin doses in dogs and cats extra challenging.
If a dog or cat is getting too much insulin, the blood sugar will drop too low. This is bad. The body knows this, and tries to fix it.
So, if the blood sugar drops very very rapidly, the brain detects the problem and says “help!!!” Always to the rescue are the liver and the adrenal glands. Hey, it takes a team effort! They release glucose that may be stored, make more glucose, and release hormones to help with making and releasing even more! The result? We now have a bunch of over-achievers who have over-shot their goal. The blood sugar was low, and now it is super high! The body has been saved, because these organs did their job.
Let’s say you give the insulin at 7am. The blood sugar crashes at 10am, and by 11am, we’re hyperglycemic, with a sky-high blood sugar over 500! If we check the blood sugar then, we have no idea that it actually got too low. So what do we think? If the pet’s blood sugar is high, increase the insulin dose!
What is the Somogyi Effect?
Glucagon and insulin are released by the pancreas.
Glucagon and insulin have opposite effects:
insulin makes the blood sugar go down and glucagon causes blood sugar to go up. They work together to balance blood glucose levels. Glucagon can increase blood glucose levels by causing the liver to release its stored glucose to the blood stream. Insulin lowers blood glucose by allowing tissues to use or store glucose.
When too much insulin is given the blood glucose drops rapidly and hypoglycemia (low blood sugar) results. This can trigger the body to release glucagon (and other hormones) and the result is that glucose is dumped into the blood. This can lead to hyperglycemia (high blood sugar). So, you have hyperglycemia induced by hypoglycemia, or the Somogyi effect. (Somogyi was a scientist who did research on glucose production by liver during times of stress.)
The method of determining if Somogyi effect is occurring is to do a blood glucose curve. Your cat will have a specific pattern of hyperglycemia if the Somogyi effect is occurring. Although at first it seems odd, the treatment for this type of hyperglycemia is to DEcrease the insulin dose. This prevents the hypoglycemia from occurring and triggering the Somogyi effect.
The Somogyi phenomenon should be suspected if clinical signs of poorly controlled diabetes are present with a serum fructosamine level less than 400 µmol/L. A high dose of insulin can cause glucose counterregulation and transient insulin resistance. The Somogyi phenomenon results from normal physiologic response to impending hypoglycemia induced by excessive insulin administration. Hypoglycemia (blood glucose <65 mg/dl) stimulates hepatic glycogenolysis and secretion of blood glucose-elevating hormones, most notably epinephrine and glucagons. This raises the blood glucose level, causing marked hyperglycemia within 12 hours of the glucose counterregulation. The dose of insulin that can induce the Somogyi phenomenon is variable and unpredictable. When tested at home, these animals would have high blood glucose levels at the time of the next injection, with 1 to 2+ glucose on the urine dipstick. If relying on only blood glucose level for insulin adjustment, the reaction to these results would be to increase the insulin dose given, which would continue the phenomenon until a hypoglycemic crisis was precipitated
Combating an Incorrect Insulin Dose
An important reason for conducting a blood glucose curve, ie, evaluating blood glucose levels every 2 hours following the morning Vetsulin® (porcine insulin zinc suspension) treatment is the possibility of Somogyi effect or rebound hyperglycemia.
In cats, the “Somogyi overswing” occurs when the insulin dose is too high and the patient’s blood glucose drops too quickly or plummets below 60 mg/dL.
The Somogyi effect occurs when the body attempts to counteract the life-threatening decline in the blood glucose concentration through a chain of reactions:
- The blood glucose concentration falls rapidly or approaches hypoglycemia (blood glucose concentrations of less than 60 mg/dL [3.3 mmol/L]) following the injection of insulin. The cat becomes hungry and restless or lethargic.
- In response to a declining blood glucose concentration in the central nervous system, adrenaline and subsequently cortisol, glucagons, and growth hormone are released.
- These hormones increase blood glucose concentration (through gluconeogenesis, release of glucose from hepatic glycogen, and increased peripheral resistance to insulin).
- The resulting hyperglycemia produces polyuria and polydipsia. This can be mistakenly attributed to an inadequate insulin dose.
If the morning polyuria is thought to result from an insufficient insulin dose and a higher dose is given, the problem will be aggravated. An even more pronounced Somogyi effect will follow. Eventually the counter-regulatory mechanisms may become exhausted, resulting in severe hypoglycemia.
The Somogyi effect can occur in both cats and dogs, but cats are particularly prone to develop this rebound hyperglycemia. The appropriate corrective action is to decrease the patient’s insulin dose to prevent insulin-induced hypoglycemia.
When to Suspect a Somogyi Overswing
- Minimal glycemia: <65 mg/dL or 3.6 mmol/L
- Maximum glycemia: 400–800 mg/dL or 22–44 mmol/L
- Persistent morning glucosuria: >1% or 1–2 g/dL (strips)
- Morning glycemia: >400–450 mg/dL or 22 mmol/L
- Clinical signs:
- Polyuria, polydipsia
- Absence of weight loss
- Hypoglycemia (weakness, convulsions, ataxia, behavior changes)
- High insulin dose: close to 2.2 IU/kg and greater
Diagnosing Somogyi Effect
A blood glucose curve can help detect a Somogyi effect and confirm that a cat’s insulin dose needs to be reduced.
Any of the following blood glucose curves can be suggestive of the Somogyi effect:
- Hypoglycemia (low nadir) followed by rebound hyperglycemia.
- A rapid decrease in glycemia with an adequate nadir followed by rebound hyperglycemia.
- Persistently high blood glucose values with no discernible nadir (rebound hyperglycemia can persist for a few days following the hypoglycemic event).
Blood Glucose Curve Indicating Somogyi Effect
See the following graph for an example of a blood glucose curve in a case of rebound hyperglycemia. Insulin was injected at time=0 hours.
The solution is to decrease dose by 50%, or return to starting dose of 1 IU twice daily, whichever is lower.
Blood glucose measured in mg/dL
What Is the Somogyi Effect and How Does It Affect a Diabetic Dog or Cat?
The Somogyi effect occurs when an overdose of insulin occurs. The insulin acts to lower the blood glucose (blood sugar) level. However, because too much insulin was given, the blood glucose level may fall lower than the normal range.
When the blood glucose becomes too low (a condition known as hypoglycemia), the body has defense mechanisms that go into effect to force the glucose to increase again. However, the dog or cat may not be able to control how high the blood glucose goes and it may rebound to an abnormally high level. This is known as the Somogyi effect.
This effect may become circular in its effect if the insulin overdosage is ongoing. When the insulin dose is given, the blood glucose level first falls to below normal then rebounds to an abnormally high level. The insulin dose is repeated, which again leads to first an abnormally low glucose level and then a rebound to an abnormally high level. And the circle goes on and on.
How Is the Somogyi Effect Diagnosed in Dogs and Cats with Diabetes?
A blood glucose curve will be necessary to diagnose this phenomenon. The blood glucose curve is a series of blood glucose measurements taken at regular intervals after the administration of insulin.
When evaluating a blood glucose curve for a dog or cat that is experiencing the Somogyi effect, it will be possible to see the blood glucose value drop first to an abnormally low level and then, if the curve is continued long enough, you will see the blood glucose level going up to an excessively high level.
The existence of the Somogyi effect is one of the reasons that a solitary blood glucose reading cannot be used to evaluate whether a diabetic dog or cat is receiving an adequate dose of insulin or not. A solitary blood glucose reading can fall anywhere between abnormally low to normal to excessively high even if the animal is being overdosed with insulin.
The Somogyi effect is also the reason that fructosamine values must be used with caution in evaluating the progress of a diabetic dog or cat. Fructosamine values represent an average blood glucose value for the dog or cat over roughly two weeks. Because it does represent an average and gives no indication of high low or how high the actual glucose values have gone, the fructosamine level may be normal for a dog or cat that is being overdosed with insulin and undergoing the Somogyi effect.
The Somogyi Response
The Somogyi response, also called rebound hyperglycemia and insulin-induced hyperglycemia, is the physiologic response to impending hypoglycemia. This response is characterized by stimulation of hepatic gluconeogenesis and secretion of diabetogenic hormones, including catecholamines and glucagon.
Incidence & Risk Factors
Limited literature supports the documentation of the Somogyi response in dogs and cats. A recent study suggests that, in cats receiving long-acting insulin analogs (eg, insulin glargine, insulin detemir), the Somogyi response is less common than initially suspected.
Factors that may increase risk for the Somogyi response in dogs and cats include:
- Insulin adjustments made very frequently, which does not give the patient time to equilibrate between doses
- Insulin adjustments made in large increments
- Lente insulin therapy q12h.
Clinical Signs
Clinical signs of hypoglycemia are often subtle and overshadowed by signs of hyperglycemia that go unnoticed by the client. Table 4 provides a list of common clinical signs of hyperglycemia and hypoglycemia.
Diagnosis
Diagnosis of the Somogyi response requires documentation of hypoglycemia (glucose <65 mg/dL) followed by hyperglycemia (glucose >300 mg/dL) after insulin administration.
Rebound hyperglycemia is often between 400 and 800mg/dL. It is suspected that patients exhibit sustained hyperglycemia and insulin resistance (up to 24–72 H) after a hypoglycemic event.1,2,4
The Somogyi response should be suspected when:
- Blood glucose rapidly drops regardless of nadir.
- Duration of insulin is greater than 12 hours.
- The patient is receiving a high dose of insulin (>1.5 U/kg).
- There is a cyclic history of good glycemic control for 1 to 2 days, followed by poor glycemic control for several days.
- The patient has gained weight despite suboptimal diabetic control.
- The patient has failed to improve despite increasing the insulin dose.
Challenges With Recognition
Several challenges surround diagnosis of a Somogyi response. The Somogyi response:
- Is rare in dogs and cats. Previously believed to be more common in cats on lente insulins. Perceived to be less common in feline patients receiving new analog insulin preparations, although there is limited literature describing prevalence in diabetic animals.1,2,4
- Does not happen in every episode of hypoglycemia. Reasons for this are unclear, but may include lack of a counterregulatory hormone response and duration of hypoglycemia.
- Can be challenging to detect with blood glucose curves because the period of hypoglycemia can be very short and easily missed.
- Is associated with unpredictable serum fructosamine measurements. Usually, a concentration greater than 500 mcmol/L confirms poor diabetic control.1,2,4
Because of these challenges, when insulin overdose is suspected, but not documented on a blood glucose curve, consider reducing the insulin dose. Once the dose has been reduced, instruct the owner to carefully monitor clinical signs for any subtle change and repeat monitoring at least 4 to 7 days after reducing the insulin dose.
REFERENCE-ON REQUEST
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