Hypoglycemia is often referred to as “low blood sugar.” When your cat’s body is deprived of sugar, its main source of energy, his ability to function declines and, in severe situations, loss of consciousness or even death can result.
Low blood sugar is not a disease itself; rather, it is a symptom of an underlying disease or problem. There are many causes of hypoglycemia.
Kittens, especially those under 3 months of age, have not fully developed their ability to regulate their blood glucose (sugar) levels. Hypoglycemia can be brought on when kittens are introduced to other stress factors, such as poor nutrition, cold environments, and intestinal parasites. Fasting combined with rigorous exercise can also bring on hypoglycemia in cats. Cats treated for diabetes mellitus are at risk, as well as those with severe liver disease, severe bacterial infections, tumors of the pancreas (rare in cats), or portosystemic shunts.
If your pet is hypoglycemic, you may notice the following symptoms:
- Extreme lethargy
- Muscle twitches
- Loss of appetite
- Lack of coordination
- Unusual behavior
If your cat is suspected to be hypoglycemic, your veterinarian will perform a thorough physical exam, take a complete history of your cat, and may recommend diagnostic tests that could include:
- Measurement of blood glucose levels (sugar levels in the blood)
- Chemistry tests to evaluate kidney, liver, and pancreatic function
- A complete blood count (CBC) to rule out blood-related conditions
- Electrolyte tests to ensure your pet is not dehydrated or suffering from an electrolyte imbalance
- Urine tests to screen for urinary tract infection and other disease, and to evaluate the ability of the kidneys to concentrate urine
- A thyroid test to determine if the thyroid gland is producing too much thyroid hormone
- Ultrasound examination of the abdomen to rule out tumors
Your veterinarian will want to immediately treat the low blood sugar, as well as the underlying cause. Treatment may include oral or intravenous glucose supplements; other treatments will depend on the underlying cause.
Keeping a vigil eye on your pet, especially when she is a kitten, is an important factor in preventing hypoglycemia. Providing proper nutrition on a routine schedule is also very important. Screening for hypoglycemia in situations where your cat must fast, such as before surgery or anesthetic events, can also prevent her from becoming hypoglycemic.
If you have any questions or concerns, you should always visit or call your veterinarian – they are your best resource to ensure the health and well-being of your pets.
Aftermath [ edit | edit source ]
Its also important to remember that it takes a little time to fully come back from a hypo incident. In people, cognitive function is impaired at levels below 54mg/dL. Full recovery from the hypo can take 40-90 minutes after blood glucose levels have returned to normal  . Like insulin, the sugar given doesn't have a total effect instantaneously.
Swift intervention after a hypo incident with doses of Pyruvate may reduce brain damage.
Sometimes a mild hypoglycemic episode will go unnoticed, or leave evidence such as an "accident" where kitty fails to make it to the litterbox  . In these cases the blood sugar will often be paradoxically high upon the next test hours later, since the pet's body will react to the low blood sugar by stimulating the liver to release stored glycogen. This condition is known as Somogyi rebound, and requires a lowered insulin dosage for the next few days. The Somogyi rebound may also occur when the pet's blood glucose drops too rapidly, even if it never actually reaches a low reading.
A single hypoglycemia or near hypoglycemia episode  can result in hyperglycemia for up to 3 days following it. In response to the threat of low blood sugar, the body releases counter-regulatory hormones intended to raise bg's the body's way of trying to save itself.
Why can the presence of hypoglycemia be a diagnostic dilemma?
Being confronted with a dog with hypoglycemia is not an infrequent occurrence in veterinary practice and may be a disconcerting problem for the clinician. This may be due in part to the numerous physiological and pathological causes for hypoglycemia, which are listed in Table 1 . However, even this table is not exhaustive. Hypoglycemia may also be the product of artifactual causes which may lead the clinician astray. In order to better understand the potential causes of hypoglycemia it is necessary to start with background information on normal glucose homeostasis.
Causes of hypoglycemia in the dog broadly divided by the presence or absence of an underlying disease resulting in hypoglycemia (1,6).
|Physiological causes of hypoglycemia||Chief mechanism or mechanisms|
|Extreme exercise (e.g., hunting dog hypoglycemia)||Excess glucose utilization and inadequate glycogen stores|
|Neonatal/juvenile or toy breed juvenile hypoglycemia||Inadequate glycogen stores, limited fat and muscle mass|
|Malnutrition/starvation||Inadequate intake and depletion of glycogen stores|
|Drug and toxin associated causes such as iatrogenic insulin overdose, xylitol toxicity, oral hypoglycemic agents (usually sulfonylureas), beta blockers||Excess glucose utilization due to hypersecretion of insulin and increased tissue sensitivity to insulin. Beta blockers via suspected interference of counter- regulatory mechanisms|
|Pathological causes of hypoglycemia|
|Severe hepatic disease such as hepatitis, cirrhosis, neoplasia, amyloidosis, hepatotoxins||Decreased hepatic gluconeogenesis|
|Congenital portosystemic shunt||Decreased hepatic gluconeogenesis|
|Hypoadrenocorticism||Decreased glucose production from lack of a counter-regulatory hormone (i.e., cortisol)|
|Hypopituitarism||Decreased glucose production from lack of a counter-regulatory hormone (i.e., growth hormone or adrenocorticotropic hormone)|
|Insulinoma||Excess glucose utilization due to hypersecretion of insulin|
|Islet cell hyperplasia a||Excess glucose utilization due to hypersecretion of insulin|
|Extra-pancreatic tumors (e.g., hepatocellular carcinoma, hepatoma, leiomyosarcoma, leiomyoma)||Increased glucose utilization by the tumor but also due to secretion of insulin analogues|
|Chronic renal failure||Decreased hepatic gluconeogenesis|
|Infection (e.g., sepsis, severe canine babesiosis)||Decreased hepatic glycogenesis and increased glucose utilization|
|Glycogen storage disease||Deficiency of enzymes required for glycogen conversion|
|Artifactual/spurious||Laboratory error from improper sample handling or submission, use of a human glucometer, leukemia/polycythemia vera|
This pancreatic pathology has been documented in dogs but without hyperinsulinemic hypoglycemia syndrome.
Glucose in the body is derived from 3 sources: i) intestinal absorption from the digestion of carbohydrates, ii) dissolution of glycogen (the storage form of glucose) via glycogenolysis predominantly in the liver but also in the muscle, and iii) synthesis of glucose (gluconeogenesis), mostly by the liver, from non-carbohydrate sources e.g., lactate, pyruvate, amino acids, and glycerol, but also a significant amount by the kidneys (1).
In the clinically normal animal, the body maintains euglycemia primarily via equilibrium between the glucose-lowering hormone insulin and the glucose-elevating hormones glucagon, cortisol, epinephrine, norepinephrine, and growth hormone (diabetogenic hormones or counter-regulatory hormones) (2). However, hepatic autoregulation, independent of counter regulatory hormones is also vitally important in modulating blood glucose levels (3). After a meal, glucose, amino acids, and gastrointestinal hormones (gastrin, secretin, cholecystokinin, and gastric inhibitory peptide) rise in the plasma. The release of insulin from pancreatic beta cells is signaled when glucose is > 6 mmol/L (110 mg/dL) (4). Insulin serves to temporarily halt gluconeogenesis and glycogenolysis, stimulate glucose uptake and utilization by insulin-sensitive cells, promote production and storage of glycogen, and inhibit glucagon secretion (1,2) the net effect being prevention of sustained hyperglycemia. Insulin also promotes production of triglyceride in adipose tissue and of protein and glycogen in skeletal muscle (1). After the initial post-prandial insulin peak, insulin concentrations begin to decline due to inhibitory feedback from decreasing plasma glucose concentration ( 55%, which is not uncommon in some sighthounds and dehydrated dogs (19). Thus, it is prudent to ensure that hypoglycemia as determined by a human PBGM is always verified by an external reference laboratory or a point-of-care chemistry analyzer.
The other main contributor to artifactual hypoglycemia is the generation of pseudohypoglycemia from improper handling of samples. Blood should be submitted to an external reference laboratory in a sodium fluoride tube, which prevents continual glucose consumption via glycolysis by erythrocytes and leukocytes. Post-sampling glucose utilization can be particularly marked if the dog has polycythemia or leukocytosis (8).
If collected whole blood is not submitted in a sodium fluoride tube, prolonged storage of blood before separation into plasma or serum should be avoided, as this will cause the glucose concentration to decrease at a rate of approximately 0.4 mmol/L per hour (7 mg/dL per hour) (8).
Physiological and iatrogenic causes of hypoglycemia
While prolonged fasting or starvation can theoretically lead to hypoglycemia, this is seldom a cause for significant hypoglycemia in the adult dog without concomitant disease affecting glucose homeostasis (1,2,4). This contrasts with adult humans, in whom fasting hypoglycemia is reported to be a frequent event (20). The reason behind this interspecies difference is unclear.
Exertional hypoglycemia (hunting dog hypoglycemia)
Intense exercise or prolonged physical activity can significantly increase glucose utilization and rapidly deplete glycogen stores, especially in lean dogs, with the sequela of hypoglycemia (2). This is referred to as exertional hypoglycemia and colloquially as “hunting or working dog hypoglycemia” (1), as it is considered more common in this type of dog due to their natural behavior. The prevalence of hunting dog hypoglycemia is unknown. Other than an abstract of a case report on 3 dogs with suspected exertional hypoglycemia and an experimental study of the physiological effects of exercise-induced hypoglycemia in dogs, there is a lack of published information on this phenomenon (21,22). The paucity of reported information on this condition is likely due to the fact that the clinical signs are often self-limiting, effective counter-regulatory mechanisms come into play, and by the time the dog is presented for examination at the veterinary hospital, the dog is asymptomatic and blood glucose concentration has normalized.
In humans, continuous exercise for 2 to 3 h at 65% maximal oxygen uptake results in the development of hypoglycemia (20). Therefore, it is more than conceivable that hypoglycemia would readily occur in dogs undertaking extreme exercise coupled with the presence of poor body condition. The word extreme is emphasized as one should not anticipate that well-conditioned working dogs participating in routine field and search and rescue activities, should readily develop hypoglycemia. Two studies did not document hypoglycemia in working dogs subjected to field training (23,24).
Thus, while hunting dog hypoglycemia should be considered in dogs with an appropriate signalment and history, it is nevertheless a diagnosis of exclusion and other differentials for hypoglycemia should always be considered. This point is reinforced by a case report in which a hunting dog had recurring seizures associated with exercise but diagnostic investigation revealed that the dog’s hypoglycemia was in fact secondary to hypoadrenocorticism (25).
Neonatal/juvenile and toy breed hypoglycemia
Neonatal dogs have a propensity for developing hypoglycemia due to several factors: they have limited glycogen reserves, decreased ability for hepatic gluconeogenesis, a low body mass index leading to lack of lipolysis for an alternative fuel source, immature counter-regulatory hormonal systems, and the heart, in addition to the brain, relies heavily on glucose for energy (26). These factors cause neonates to poorly cope with stressors such as inadequate or poor-quality food intake, fasting, dehydration, infection, and hypothermia (1,26), all of which rapidly deplete their blood glucose, in a setting of diminished ability to conserve and replenish glucose. In the absence of normal compensatory mechanisms, hypoglycemia may ensue in a neonate within 2 to 3 h of decreased food intake (26). Similar to neonates, small stature juveniles, especially toy and miniature breeds, are at an increased risk of developing hypoglycemia due to their low body mass index (BMI). In addition to this, a suspected alanine deficiency, which contributes to dysregulation of gluconeogenesis during the fasted state, may also be a contributing factor (6). Diagnosis of neonatal or toy breed hypoglycemia is based on signalment however, concurrent diseases such as sepsis and portosystemic shunt should be explored, especially if episodes of hypoglycemia persist into adulthood (6).
Hyperinsulinemia: Iatrogenic insulin overdose and xylitol toxicity
Iatrogenic insulin overdose should be easily identified based on the history of a diabetic patient receiving insulin. Possible causes include an absolute overdose, e.g., an owner accidentally administering an increased dose of insulin versus a relative overdose, i.e., normal insulin dose administered with increased glucose utilization due to aberrant physical activity or concurrent illness or inadequate food intake.
Xylitol is a sugar alcohol which is used commercially as an artificial sweetener and has anti-microbial properties. It is commonly found in an array of products such as candy, sugar-free chewing gums, toothpaste, and baked goods (27,28). Xylitol can cause hypoglycemia in dogs through a dose-dependent release of insulin. This insulin surge can lead to hypoglycemia because the amount of insulin released is 2.5 to 7 times greater than if an equal amount of glucose was administered. Hypoglycemia ensues within 30 to 60 min of ingestion (29,30). A xylitol dose as low as 0.03 g/kg body weight (BW) may cause clinical hypoglycemia (31). In addition to hypoglycemia, xylitol may lead to liver disease, characterized by elevation of hepatocellular enzymes, chiefly alanine aminotransferase (ALT) and/or hyperbilirubinemia (27,28,31,32). Less commonly, fulminant hepatic failure may occur in which the most consistent finding is elevation of clotting times (27,28,33). Consequently, the clinical picture of xylitol ingestion may be misdiagnosed as hepatic failure. The clinician presented with a patient with hypoglycemia and concurrent liver disease must therefore ensure that an adequate toxicology history is obtained. Interestingly, erythritol, another common sugar substitute related to xylitol, does not cause toxicity in dogs (34).
The most common pathological causes of hypoglycemia in the dog
Although the list of causes of hypoglycemia is vast, there are 5 common causes of pathological hypoglycemia reported in the literature: sepsis, extrapancreatic neoplasia, insulinoma, hypoadrenocorticism, and liver dysfunction (6,8). There have been no published studies assessing the proportional prevalence of these diseases in causing hypoglycemia in the dog. However, at the authors’ veterinary institution, between 2002 and 2016, the most common pathological causes of hypoglycemia in 55 dogs were: insulinoma (69%, based on the results of an insulin assay and documentation of a pancreatic mass on imaging or exploratory celiotomy), extrapancreatic tumor (14%), sepsis (7%), hypoadrenocorticism (6%) and hepatic failure (4%). It is acknowledged that a selection bias applies since these cases were derived from a referral institution.
Other less common causes of hypoglycemia include: pituitary dwarfism renal disease (tubular acidosis, Fanconi-like syndrome) acetylcholinesterase inhibitors such as edrophonium, neostigmine, organophosphates, physostigmine ethanol disopyramide, propranolol salicylate sulfonylurea compounds and toxins from herb fenugreek (Trigonella foenum-graecum), bitter melon gourd (Momordica charantia), climbing ivy gourd (Coccinia indica), mamijava (Enicostemma littorale), Asian ginseng (Panax ginseng), American ginseng (Panax quinquefolius), Siberian ginseng (Eleutherococcus senticosus), ackee tree (Blighia sapida), prickly pear (Opuntia robusta), oleander plant (Nerium oleander), and yellow bells [Tecoma stans (family Bignoniaceae)] (6,35).
Insulinomas are functional beta cell tumors of the pancreas, which cause hypoglycemia via secretion of insulin independent of the normal suppressive effects of normoglycemia or hypoglycemia (36). The diagnosis of an insulinoma can be a challenge for a few reasons.
Firstly, the blood glucose may fluctuate in and out of the normal range, because of counter-regulatory mechanisms and the effects of feeding (4,6). Therefore, patients with a suspected insulinoma may require that multiple blood glucose assessments are performed during a 12-hour fasting period to avoid missing a hypoglycemic episode (10). However, if provocative testing is employed, then diligent monitoring of blood glucose every hour should be undertaken to minimize the risk of an unobserved hypoglycemic crisis (37). In some cases of insulinoma, despite serial monitoring of fasting blood glucose, the blood glucose can be consistently within the reference range. Measurement of fructosamine may prove helpful in these difficult cases (38).
Secondly, in cases of insulinomas, seizures may be a more common clinical sign than with other pathological causes for hypoglycemia (6). It may be difficult to determine whether the hypoglycemia is the cause of the seizure, or whether the hypoglycemia is due to increased skeletal muscle utilization of glucose secondary to seizure activity. To help clarify this conundrum, the fulfilment of Whipple’s triad can be helpful. Whipple’s triad consists of clinical symptoms supportive of hypoglycemia, documentation of a low blood glucose, and resolution or improvement of clinical signs with correction of the hypoglycemia (39). Historically in human medicine, fulfilment of Whipple’s triad was tantamount to the diagnosis of an insulinoma (37). However, the criteria are not definitive and patients with other causes of hypoglycemia will readily fulfil these requirements.
A third diagnostic problem with insulinomas is that specific clinicopathologic testing for an insulinoma, namely the serum insulin concentration, is not 100% sensitive or specific for an insulinoma. To maximize the diagnostic yield of this test, blood for the insulin concentration should be measured at the same time as documented severe hypoglycemia. An insulin concentration above the upper limit of normal, or a normal insulin level, in the upper half of the reference range, in the face of significant hypoglycemia is suggestive of an insulinoma (6). However, in some cases, it is ambiguous as to whether the insulin value is inappropriate for the degree of hypoglycemia e.g., hypoglycemia, with a low normal insulin value: this may be consistent with an insulinoma but also other causes of hypoglycemia (6). In this circumstance, a repeat insulin assay may be performed. Some laboratories will perform an insulin:glucose ratio or an amended insulin:glucose ratio in equivocal insulinoma cases. However, use of any insulin:glucose ratio is not advocated but particularly the amended glucose ratio because the formula used to generate this value is extrapolated from blood glucose concentrations in clinically normal humans and the test lacks specificity (4,6).
When the history, clinical signs, and results of an insulin concentration in context of hypoglycemia are suggestive of an insulinoma, imaging such as ultrasound or computed tomography (CT) should be undertaken. The sensitivity of abdominal ultrasound in detecting an insulinoma varies from 28% to 75% (37) thus ultrasound has only a modest diagnostic yield for insulinomas. Computed tomography may fare better in the detection of insulinomas, with 1 study reporting a sensitivity of 71% compared to 35% with abdominal ultrasound (40). Preoperative diagnosis can be arduous and therefore intra-operative lesion localization with histopathology confirmation, is considered the gold standard (6). Before embarking on an exploratory celiotomy for a suspected insulinoma, staging with diagnostic imaging should be performed. In 1 study, metastatic disease was detected grossly in 30% to 50% of cases at the time of surgery (4).
Virtually any non-pancreatic neoplasm has the potential to cause hypoglycemia. The mechanism is often multifactorial and includes: a paraneoplastic effect through the liberation of insulin or insulin analogs, and direct tumor effects such as excessive glucose utilization by the tumor and impaired hepatic glucose homeostasis due to a primary liver tumor or metastasis to the liver (1,4).
The most common tumors associated with hypoglycemia are hepatocellular carcinoma, hepatoma, leiomyoma, and leiomyosarcoma (1,2,4,5). In 1 study of canine leiomyosarcomas, 6/11 dogs had documented hypoglycemia however, sepsis from peritonitis was suspected to be responsible for the hypoglycemia in 4/6 dogs (41). Diagnosis of extra-pancreatic neoplasms can usually be made based on physical examination findings, clinicopathologic data, and imaging tests, but some tumors may be occult and therefore difficult to identify prior to surgery.
Hypoglycemia secondary to sepsis is postulated to be from a culmination of processes, including decreased caloric intake, hepatic dysfunction, and increased insulin-independent glucose consumption by bacteria, neutrophils, and peripheral tissues, which is attributable to inflammatory mediators and insulin analogs (1,6). Septic patients are usually moribund and diagnosis in dogs is via documenting at least 2 of the 4 criteria for Systemic Inflammatory Response Syndrome (SIRS) and identifying a nidus of infection (42).
Any severe bacterial infection can cause hypoglycemia from sepsis and some viral infections are commonly associated with hypoglycemia. In 1 study evaluating biochemical changes, all 14 puppies with parvovirus infection and 6 of 8 puppies with coronavirus infection were hypoglycemic (43). However, as the dogs in the aforementioned study were puppies, juvenile hypoglycemia may have been a factor. Furthermore, because septic patients may have leucocytosis, hypoglycemia may have been exacerbated due to artifactual reasons.
Canine babesiosis is considered an emerging disease in Canada. Increased incidence of acquired Babesia infections may be the result of increased global movement of pets, establishment or identification of appropriate vectors in Canada and administration of canine blood products from various locations in North America (44). Hypoglycemia is thought to ensue via mechanisms similar to those for bacterial sepsis (1) and there is a relatively high prevalence of hypoglycemia in dogs infected with Babesia spp. (45).
Because glucose homeostasis largely relies on hepatic glycogen storage, hepatic gluconeogenesis and glycogenolysis, severe perturbation of hepatic function can foreseeably lead to hypoglycemia. The hypoglycemia is usually relatively mild and an incidental finding (1). Seventy percent of hepatic mass needs to be lost before hypoglycemia ensues and most dogs will have abnormalities in other functional hepatic indices such as prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT) (1,2,46). Causes of hepatic dysfunction include vascular anomalies such as a portosystemic shunt, chronic hepatitis, primary or metastatic hepatic neoplasia, hepatic lipidosis, and hepatic fibrosis/cirrhosis. Diagnosis is based on clinicopathologic data, dynamic liver functional tests, imaging studies and hepatic biopsies.
Is your cat in a diabetic coma?
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Cats with diabetes need continuous care. Unlike diabetic humans who can check their own blood sugar levels, cats rely on their owners to properly monitor what's happening in their pancreas. That twice-daily dosage of insulin given under his skin may require adjustment, depending on a variety of factors. You can keep your diabetic cat on track by knowing what's going on, and what to expect, particularly in the case of a diabetic coma.
How common is feline diabetes?
Some estimates suggest that one out of 1,200 cats will develop diabetes in their lifetimes, although this disease most often afflicts older or overweight cats. A diabetic cat suffers a deficiency of insulin, the pancreatic hormone that converts glucose, the fuel we get from food, into energy. A diabetic cat's body either cannot produce enough insulin, or cannot process it correctly. Without insulin controlling the flow of glucose from the cat's bloodstream into its body cells, the cat's body uses its own fat and protein to survive. High blood glucose levels force glucose to be processed into the urine, leading to excessive urination. Most cats contract an insulin-dependent type of diabetes, requiring insulin injections to control their illness. Felines suffering non-insulin-dependent diabetes will eventually need insulin injections as the disease progresses.
An early warning of feline diabetes is frequent urination. A diabetic cat may also urinate, or attempt to do so, outside of his litter box. You may see him straining to urinate, a symptom of a urinary tract infection common to diabetic felines. He'll consume larger amounts of water, and return to his water bowl more often, because his glucose-heavy urine passes more water from his system. His appetite may change, too, as he either loses interest in food or becomes a ravenous eater. Either way, a diabetic cat will lose weight as his metabolism cannot convert food into energy, so his fat and protein stores are broken down for fuel.