Hyperglycemia

Hyperglycemia means high blood sugar. It is the primary symptom of diabetes. Unlike its opposite, hypoglycemia, hyperglycemia is not immediately life-threatening. This doesn't mean it's not dangerous, though. For "how high is high", see blood glucose levels, and also the long-term symptoms discussion at the end of this page.

Increasing physical activity can mean lowering blood sugar levels for some pets and people with this disease. It can also raise them; much depends on individual reaction and knowing how you or your pet responds.

For most with diabetes, excitement or stress can cause temporary hyperglycemia. There are others who can find themselves going toward hypoglycemia because of it.

Cats in general, with or without diabetes, appear to be prone to hyperglycemia. This 1954 Lilly study was an early one with regard to the insulin/hypoglycemia countering hormone glucagon. Cats were selected because of their sensitivity to high blood sugar and their well-known responses to it. It should be remembered that back in 1954, most of the work which had been done with regard to improving insulins had dealt with various ways to extend their activity. At the time this study was done, highly purified insulin was still a long way off, so it was possible to have insulin which might contain some glucagon via the extraction process.

Some unexpected causes of hyperglycemia are discussed in detail under obstacles to regulation

Primary metabolic effects

No insulin, not enough insulin or the failure of the receptors means glucose can't get into the cells to be used as fuel. Without fuel, cells starve.

An untreated diabetic suffers primarily from lack of insulin to let nourishment into the cells, and therefore is starving to death. But hyperglycemia can kill faster than starvation; it's not unusual for one of the effects below, or diabetic ketoacidosis (DKA) brought on by the combination, to be the actual fatal blow.

Polyuria: Glucose cannot leave the body by itself--it must take water with it. Losing too much water means the body tries replacing it and this causes thirst, or polydipsia. When too much water is lost through excess urination and the excess drinking cannot make up for it, dehydration can occur.

Hyperglycemia and glycosuria are the symptoms, or signs, that the untreated or inadequately treated diabetic is unable to metabolize carbohydrates properly. This is caused by a lack of insulin, endogenous or exogenous, in the body to assist in this process.

Glycosuria: When the blood glucose level rises over a certain level, the renal threshold, glucose spills into the urine.

Depending on the severity and length of time spent in hyperglycemia, diabetics will suffer various levels of severity of symptoms, ranging from short term to long term. Almost all complications of diabetes are caused directly or indirectly by hyperglycemia.

Excess sugar in the blood is:

• An oxidizing agent, so it gradually oxidizes (burns) tissues
• Through glucose toxicity, suppresses pancreatic beta cells, meaning after 3-7 days of it, the pancreas will temporarily stop producing insulin
• Bacteria and fungus food, so it increases the incidence of infection
• Osmotically hypertonic, so it sucks water out of the tissues; this process is called diuresis
• Removed by the kidneys, once concentration reaches the renal threshold, which spill it into the urine
• A diuretic, which leads to dehydration, because of the last two problems.

Energy Production-Fasting. With adequate insulin supply-endogenous or exogenous--ketones, if produced, are slight and not problematic.

Energy Production-Untreated/Inadequately Treated Diabetes-without enough insulin to regulate fat & carbohydrate metabolism, the process intensifies. The liver, despite high blood glucose levels, produces still more in gluconeogenesis. It also speeds up the transformation of fatty acids resulting in ketones.

Vicious circles

Hyperglycemia is also at the center of several vicious circles, including:

• Insulin suppression which means that after just 3 to 7 days at 30mmol/L (540 mg/dL), insulin secretion drops to near-zero. This suppression appears to be temporary in cats.
• Amyloidosis-- Amylin produced by the pancreas is oxidized by hyperglycemia into Amyloid deposits in the islets of Langerhans. Amyloid deposits physically block insulin secretion. The resulting high blood sugar triggers the pancreas to increase insulin and amylin production, which, along with glucose toxicity from the hyperglycemia, causes more amyloid deposits. This vicious circle eventually makes the pancreas stop producing insulin, creating complete insulin-dependence. This suppression of the pancreas appears to be permanent in all animals.
• Glucose toxicity -- oxidized tissue becomes insulin-resistant, causing high blood sugar, which oxidizes tissues further.
• Dehydration -- low water levels make blood sugar levels high by comparison, which makes blood hypertonic, which sucks water out of the cells into the blood. The kidneys try to cleanse the blood by filtering out the sugar along with lots of extra water, causing more dehydration.

Dehydration can change the way subcutaneous insulin is absorbed, causing either hyperglycemia or hypoglycemia.

Those with diabetes are at risk for dehydration as it is triggered by hyperglycemia.

• Somogyi rebound -- high blood sugar causes caregiver to increase insulin dose, which causes hypoglycemia, causing Somogyi rebound, causing high blood sugar, which causes caregiver to further increase insulin dose.
• Dental infection -- infection raises blood sugar, making vets nervous about operating on the teeth. Untreated infection keeps blood sugar high.

Short-term symptoms

Very high blood sugar over just a few days can therefore cause:

• Blindness in dogs
• High risk of ketones, and DKA
• Neuropathy (nerve damage to legs) especially in cats
• Dehydration
• Malaise or lethargy
• Urinary tract or kidney infection (which both can raise blood sugar)
• Permanent pancreatic damage due to amyloidosis, reducing chance of remission
• Tissue damage everywhere due to glucose toxicity
• Insulin resistance causing apparent unresponsiveness to insulin
• Hyperactivity in some dogs; they become like some small children who've had far too many sweets. Our non-medical term for it is "sugar buzz".
• Inflamation of the eye blood vessels in dogs. The whites become an angry, "fire" red. They also become inflamed as a hypoglycemia symptom, but the redness is not as intense. The difference in inflamation can best be likened to the difference in the color of arterial blood to venous blood. Arterial blood is a brighter red than venous blood. Hyperglycemic inflamation is of an "arterial blood" color.

Both revert to no inflammation when blood glucose levels are normal; lessening of inflammation visible as the bg's go down or up. This symptom was discovered and verified--first with the individual dog and then with all diabetic dogs in the veterinary practice. All presented with the same symptoms for hyperglycemia, hypoglycemia, and euglycemia. The eyes were examined prior to blood glucose testing with results matching the degree or lack of inflammation each time.

• Similar inflammation of the eye's blood vessels noted in cats. Feline Diabetes For Dummies: Watch closely and learn the signs of early HYPERglycemia. This could be PU/PD or more nebulous signs. For Darlene's cat, Pooter, one fairly reliable early sign of insufficient insulin is bloodshot eyes. Pull back the skin in front of the ear until you can see the whites of the eyes ... if there are more veins than usual, or the white part is actually pink, check the BG levels. There appear to be no recorded instances where a similar hypoglycemia effect was also noted in cats.

Medium-term symptoms

Medium-high blood sugar over weeks can be nearly as bad:

• Vision problems in dogs
• Medium risk of ketones, and DKA
• Neuropathy (nerve damage to legs)
• Urinary tract or kidney infection, risk of nephropathy
• Permanent damage to the pancreas, reducing chance of remission
• Tissue damage everywhere due to glucose toxicity
• Insulin resistance causing apparent unresponsiveness to insulin

Long-term symptoms and safe levels

What about the usual levels we see while regulating our dogs and cats? Normal non-diabetic range is from 50 - 125mg/dL (2.2 - 7mmol/L). Typical regulation ranges recommended for dogs and cats are from 100 - 250mg/dL (5.5 - 14mmol/L). Are these levels damaging?

Actual long-term effects of high blood sugar in cats and dogs have not been well-studied, so we turn to human studies for clues. Any blood sugar level over 200mg/dL (11 mmol/L), and in more recent studies, even over 126mg/dL (7mmol/L), is considered to cause some damage in humans. A famous 10-year clinical NIH study in the US called the Diabetes Control & Complications Trial (DCCT) (in humans) compared tightly-regulated diabetics to traditionally-regulated diabetics and their incidence of complications from diabetes. They found that the tightly-regulated patients showed:

• 76% reduced risk of eye disease
• 50% reduced risk of kidney disease
• 60% reduced risk of nerve disease

For this reason, humans are now strongly encouraged to keep their A1C levels (similar to a fructosamine test in animals, showing an average glucose level over time) under 7%. This equates to an average plasma BG reading of 170 (9.5 mmol/L). So if human studies are any guideline, a cat or dog should be kept at or below an average BG of about 170 / 9.5.

Other recent studies show that even temporary numbers over 140 can cause damage to pancreatic beta cells.

Stress hyperglycemia

Stress hyperglycemia (the "white coat" syndrome some pets display with visits to the veterinarian) can approach diabetic levels, and can in some instances be high enough to cause glycosuria--glucose in the urine. (Personal experience of one canine caregiver indicates a reading can be 50+ points higher, depending on whether or not the pet liked the doctor or tech doing the blood draw.) Both fructosamine and glycosylated hemoglobin tests can help distinguish stress hyperglycemia from diabetic hyperglycemia when viewed in conjunction with other test results and clinical signs.

Medications

Some medications can produce hyperglycemia; they are listed on the Medication warnings page.

Further Reading

• Stress Hyperglycemia in Non-diabetic Cats

• Good intro to hyperglycemia
• Wikipedia:Hyperglycemia
• Research connecting Organ Damage with Blood Sugar Level
• Wikipedia:Diabetic ketoacidosis
• Kidney damage from hyperglycemia
• Standards of Care-2001-Persistent Hyperglycemia in Diabetic Dogs & Cats-Pages 6-14
• Troubleshooting Persistent Hyperglycemia in Treated Diabetics--WSAVA 2008
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• Pancreatitis in dogs
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