Feline diabetes mellitus is a chronic disease in cats whereby either insufficient insulin response or insulin resistance leads to persistently high blood glucose concentrations. Diabetes affects up to 1 in 230 cats, [1] and may be becoming increasingly common. Diabetes is less common in cats than in dogs. The condition is treatable, and if treated properly the cat can experience a normal life expectancy. In cats with type 2 diabetes, prompt effective treatment may lead to diabetic remission, in which the cat no longer needs injected insulin. Untreated, the condition leads to increasingly weak legs in cats and eventually to malnutrition, ketoacidosis and/or dehydration, and death.
Diabetes in cats can be classified into the following:
Cats will generally show a gradual onset of the disease over a few weeks or months, and it may escape notice for even longer. [5]
The first outward symptoms are sudden weight loss (or occasionally gain) accompanied by polydipsia and polyuria. Polyphagia or anorexia may be observed. Neuropathy in the hind legs may cause the cat to develop a plantigrade stance, walking on its hocks rather than its toes. The front legs may develop a corresponding palmigrade stance, with the cat standing on its "palms" rather than its toes. [6]
A fasting glucose blood test will normally be suggestive of diabetes at this point. The same home blood test monitors used in humans are also used on cats, usually by obtaining blood from the ear edges or paw pads. As the disease progresses, ketone bodies will be present in the urine, which can be detected with the same urine strips used for testing human urine.
In the final stages, the cat starts wasting, with the body breaking down its own fat and muscle to survive. Lethargy/limpness and acetone-smelling breath are acute symptoms of ketoacidosis and/or dehydration and constitute a medical emergency.
Untreated, diabetes leads to coma and then death.
Too little insulin over time can cause tissue starvation, as glucose cannot reach the brain or body. In combination with dehydration, fasting, infection, or other body stresses, the condition may progress to diabetic ketoacidosis, a medical emergency with a high fatality rate that cannot be treated at home. Symptoms include lethargy, a fruit-like smell of the breath or urine, shortness of breath, and an increase in thirst. Emergency care includes fluid therapy, insulin, management of presenting symptoms and 24-hour hospitalization.
The back legs may become weak and the gait may become stilted or wobbly owing to diabetic neuropathy, which is caused by damage to the myelin sheath of the peripheral nerves due to glucose toxicity and cell starvation, which are in turn caused by chronic hyperglycemia. [7] Most common in cats, the back legs become weaker until the cat displays a plantigrade stance, standing on its hocks instead of on its toes as normal. The cat may also have trouble walking and jumping and may need to sit down after a few steps. Neuropathy sometimes heals on its own within 6–10 weeks once blood sugar is regulated.
The signs of diabetes are caused by a persistently high blood glucose concentration, which may be caused by either insufficient insulin or by a lack of response to insulin. [8] Most cats have a type of diabetes similar to human type 2 diabetes, with β-cell dysfunction and insulin resistance. [9] Factors which contribute to insulin resistance include obesity and endocrine diseases such as acromegaly. [9] Acromegaly affects 20–30% of diabetic cats; it can be diagnosed by measuring the concentration of insulin-like growth factor-1 (IGF-1) in the blood. [10]
Quite frequently, a cat which is under stress because it has been transported in a car and/ or brought to a veterinarian will experience an artificial temporary spike in blood glucose levels called "stress hyperglycemia" which will subside after a few hours. This spike, however, will not affect the cat's blood fructosamine levels, which are therefore often a better measure of overall blood sugar. [11]
Diabetes is a condition which can be treated, but it is invariably lethal if ignored. Early diagnosis and treatment by a qualified veterinarian can help in preventing nerve damage, and, in rare cases, may even lead to remission. [12] Diabetic cats do best with long-lasting twice-daily injections of insulin such as glargine (which as of 2022 is available worldwide as a synthetic generic drug) combined with a low carbohydrate diet. Because diabetes is a disease of carbohydrate metabolism, a move to a primarily protein and fat diet reduces the occurrence and recurrence of hyperglycemia.
Diet is a critical component of treatment and is in some cases effective on its own following treatment with insulin. For example, a recent mini-study [13] showed that many diabetic cats stopped needing insulin after changing to a low carbohydrate diet. The rationale is that a low-carbohydrate diet reduces the amount of insulin needed and keeps the variation in blood sugar low and easier to predict. Also, fats and proteins are metabolized slower than carbohydrates, reducing dangerous blood sugar peaks right after meals.
Recent recommended diets are trending towards a low-carbohydrate diet for cats [14] [15] rather than the formerly recommended high-fiber diet. Carbohydrate levels are highest in dry cat foods made out of grains (even the expensive "prescription" types), so cats are better off with a canned diet that is protein and fat focused. Both prescription canned foods made for diabetic cats and regular brand foods are effective. Owners should aim to supply no more than 10% of the daily energy requirement of cats with carbohydrates.
Oral medications like Glipizide that stimulate the pancreas, promoting insulin release (or in some cases, reduce glucose production), are less and less used in cats, [16] and these drugs may be completely ineffective if the pancreas is not working. These drugs have also been shown in some studies [17] to damage the pancreas further or to cause liver damage. Some owners are reluctant to switch from pills to insulin injections, but the fear is unjustified; the difference in cost and convenience is minor (most cats are easier to inject than to pill), and injections are more effective at treating the disease.
Bexagliflozin (Bexacat) was approved for medical use in the United States in December 2022. [18] [19] It is the first sodium-glucose cotransporter 2 (SGLT2) inhibitor new animal drug approved by the US Food and Drug Administration (FDA) in any animal species. [18]
The method usually employed is a dose of slow-acting insulin twice daily to keep the blood sugar within a recommended range for the entire day. With this method, it is important for the cat to avoid large meals or high-carbohydrate food. Meals may also be timed to coincide with peak insulin activity. Once-daily doses are not recommended, [20] since insulin usually metabolizes faster in cats than in humans or dogs. [21] For example, an insulin brand that lasts 24 hours in people may only be effective for about 12 in a cat. [22]
Cats may be treated with animal insulin (bovine-based insulin is most similar to cat insulin) or with human synthetic insulin. The best choice of insulin brand and type varies from animal to animal and may require some trial and error. The human synthetic insulin, Humulin N /Novolin N/ NPH, is usually a poor choice for cats, [22] since cats metabolize insulin about twice as fast. The Lente and Ultralente versions were popular for feline use until summer 2005, when they were discontinued.
Until the early 1990s, the most recommended type for pets was bovine/porcine-derived PZI, [23] but that type was phased out over the 1990s and is now difficult to find in many countries. There are sources in the US and UK, and many vets are now starting to recommend them again for pets, but they have been discontinued by most manufacturers as of 2007 [update] -2008. A new synthetic PZI analogue called ProZinc is now available.
Caninsulin (known in the US as Vetsulin) is a brand of porcine-based insulin approved for cats which is available with a veterinarian's prescription. According to the manufacturer's website, the insulin's action profile in cats was similar to that of NPH insulin, and it lowered blood sugar quickly, but for only about 6–8 hours. Vetsulin was recalled in the US in November 2009 due to inconsistent strength; it was available again as of April 2013 [update] . [24]
Two ultra-slow time-release synthetic human insulins became available in 2004 and 2005, generically known as insulin detemir (Levemir) and insulin glargine (Lantus). Studies have had good results with insulin glargine in cats. [25] Follow-up research [26] shows that Levemir can be used with a similar protocol and that either insulin on this protocol can lead uncomplicated feline cases to remission, with the most success being in cats who start on these protocols as soon as possible after diagnosis.
Cats may have their mealtimes strictly scheduled and planned to match with injection times, especially when on insulin with a pronounced peak action like Caninsulin/Vetsulin or Humulin N. If the cat free-feeds and normally eats little bits all day or night, it may be best to use a very slow-acting insulin to keep a constant level of blood glucose. Some veterinarians still use the outdated recommendation of using Humulin "N" or NPH insulin for cats, which is very fast-acting for most cats. [20] The slower-acting Lente and Ultralente (Humulin L and Humulin U) insulins were discontinued in 2005), so most cats are treated with either the veterinary PZI insulins or the new full-day analogs glargine (Lantus) and detemir (Levemir).
The first goal is to regulate the cat's blood glucose by keeping the blood glucose values in a comfortable range for the cat during most of the day. This may take a few weeks to achieve.
The most successful documented method is tight regulation with Lantus or Levemir. [27]
Typical obstacles to regulation include:
Absolute numbers vary between pets, and with meter calibrations. Glucometers made for humans are generally accurate using feline blood except when reading lower ranges of blood glucose (<80 mg/dl–4.44 mmol/L). At this point the size difference in human and animal red blood cells can create inaccurate readings. [29]
Too much insulin may result in a contradictory increase of blood glucose. This "Somogyi effect" is often noted by cat owners who monitor their cat's blood glucose at home. Any time the blood glucose level drops too far to hypoglycemia, the body may defensively dump glucose (converted from glycogen in the liver), as well as hormones epinephrine and cortisol, into the bloodstream. The glycogen raises the blood glucose, while the other hormones may make the cat insulin-resistant for a time. If the body has no glycogen reserves, there will be no rebound effect and the cat will just be hypoglycemic. [30]
Rebound hyperglycemia occurs rarely in cats treated with glargine in a protocol aiming for tight control of blood glucose concentrations. [31]
An acute hypoglycemic episode (very low blood sugar) can happen to even careful pet owners, since cats' insulin requirements sometimes change without warning. The symptoms include depression/lethargy, confusion/dizziness, loss of excretory/bladder control, vomiting, and then loss of consciousness and/or seizures. Immediate treatment includes administering honey or corn syrup by rubbing on the gums of the cat (even if unconscious, but not if in seizures). Symptomatic hypoglycemia in cats is a medical emergency and the cat will require professional medical attention. The honey/corn syrup should continue to be administered on the way to the vet, as every minute without blood sugar causes brain damage.
A cat with hypoglycemia according to a human-calibrated blood glucose meter (<2.2 mmol/L or 40 mg/dL), but with no symptoms, should be fed as soon as possible. Hypoglycemic cats that refuse to eat can be force-fed honey or corn syrup until they stabilize, though this may not be done if the animal is unconscious or having a seizure, as the liquid is likely to enter the animal's lungs and cause choking and asphyxiation.
Mild hypoglycemic episodes can go unnoticed or leave evidence such as urine pools outside the litter box. In these cases the blood sugar will probably appear paradoxically high upon the next test hours later, since the cat's body will react to the low blood sugar by stimulating the liver to release stored glycogen.
Remission occurs when a cat no longer requires treatment for diabetes and has normal blood glucose concentrations for at least a month. [32]
Approximately one in four cats with type 2-like diabetes achieves remission. Some studies have reported a higher remission rate than this, which may in part be due to intensive monitoring that is impractical outside of a research environment. Research studies have implicated a variety of factors in successful remission; in general, the following factors increase the likelihood of remission: [32]
Cats may present with type 2 (insulin-resistant) diabetes, at least at first, but hyperglycemia and amyloidosis, left untreated, will damage the pancreas over time and progress to insulin-dependent diabetes.[ citation needed ]
Glipizide and similar oral diabetic medicines designed for type 2 diabetic humans have been shown to increase amyloid production and amyloidosis and therefore may reduce likelihood of remission. [17]
Approximately one-third of cats who achieve remission will later relapse. [32]
Diabetes is rare in cats younger than five years old. [33] Typically, affected cats are obese. [34] Burmese cats in Europe and Australia have increased risk of developing diabetes; American Burmese cats do not have this increased risk due to genetic differences between American Burmese and Burmese in other parts of the world. [35]
Hyperglycemia or Hyperglycaemia is a condition in which an excessive amount of glucose (glucotoxicity) circulates in the blood plasma. This is generally a blood sugar level higher than 11.1 mmol/L (200 mg/dL), but symptoms may not start to become noticeable until even higher values such as 13.9–16.7 mmol/L (~250–300 mg/dL). A subject with a consistent fasting blood glucose range between ~5.6 and ~7 mmol/L is considered slightly hyperglycemic, and above 7 mmol/L is generally held to have diabetes. For diabetics, glucose levels that are considered to be too hyperglycemic can vary from person to person, mainly due to the person's renal threshold of glucose and overall glucose tolerance. On average, however, chronic levels above 10–12 mmol/L (180–216 mg/dL) can produce noticeable organ damage over time.
Type 2 diabetes (T2D), formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urination, fatigue and unexplained weight loss. Symptoms may also include increased hunger, having a sensation of pins and needles, and sores (wounds) that do not heal. Often, symptoms develop slowly. Long-term complications from high blood sugar include heart disease, stroke, diabetic retinopathy, which can result in blindness, kidney failure, and poor blood flow in the lower-limbs, which may lead to amputations. The sudden onset of hyperosmolar hyperglycemic state may occur; however, ketoacidosis is uncommon.
Drugs used in diabetes treat diabetes mellitus by decreasing glucose levels in the blood. With the exception of insulin, most GLP-1 receptor agonists, and pramlintide, all diabetes medications are administered orally and are thus called oral hypoglycemic agents or oral antihyperglycemic agents. There are different classes of hypoglycemic drugs, and selection of the appropriate agent depends on the nature of diabetes, age, and situation of the person, as well as other patient factors.
The blood sugar level, blood sugar concentration, blood glucose level, or glycemia is the measure of glucose concentrated in the blood. The body tightly regulates blood glucose levels as a part of metabolic homeostasis.
Carbohydrate metabolism is the whole of the biochemical processes responsible for the metabolic formation, breakdown, and interconversion of carbohydrates in living organisms.
Gestational diabetes is a condition in which a person without diabetes develops high blood sugar levels during pregnancy. Gestational diabetes generally results in few symptoms; however, it increases the risk of pre-eclampsia, depression, and of needing a Caesarean section. Babies born to individuals with poorly treated gestational diabetes are at increased risk of macrosomia, of having hypoglycemia after birth, and of jaundice. If untreated, diabetes can also result in stillbirth. Long term, children are at higher risk of being overweight and of developing type 2 diabetes.
Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that originates when cells that make insulin are destroyed by the immune system. Insulin is a hormone required for the cells to use blood sugar for energy and it helps regulate glucose levels in the bloodstream. It results in high blood sugar levels in the body prior to treatment. The common symptoms of this elevated blood sugar are frequent urination, increased thirst, increased hunger, weight loss, and other serious complications. Additional symptoms may include blurry vision, tiredness, and slow wound healing. Symptoms typically develop over a short period of time, often a matter of weeks if not months.
The term diabetes includes several different metabolic disorders that all, if left untreated, result in abnormally high concentrations of a sugar called glucose in the blood. Diabetes mellitus type 1 results when the pancreas no longer produces significant amounts of the hormone insulin, usually owing to the autoimmune destruction of the insulin-producing beta cells of the pancreas. Diabetes mellitus type 2, in contrast, is now thought to result from autoimmune attacks on the pancreas and/or insulin resistance. The pancreas of a person with type 2 diabetes may be producing normal or even abnormally large amounts of insulin. Other forms of diabetes mellitus, such as the various forms of maturity-onset diabetes of the young, may represent some combination of insufficient insulin production and insulin resistance. Some degree of insulin resistance may also be present in a person with type 1 diabetes.
For pregnant women with diabetes, some particular challenges exist for both mother and fetus. If the pregnant woman has diabetes as a pre-existing disorder, it can cause early labor, birth defects, and larger than average infants. Therefore, experts advise diabetics to maintain blood sugar level close to normal range about 3 months before planning for pregnancy.
Alpha-glucosidase inhibitors (AGIs) are oral anti-diabetic drugs used for diabetes mellitus type 2 that work by preventing the digestion of carbohydrates. Carbohydrates are normally converted into simple sugars (monosaccharides) by alpha-glucosidase enzymes present on cells lining the intestine, enabling monosaccharides to be absorbed through the intestine. Hence, alpha-glucosidase inhibitors reduce the impact of dietary carbohydrates on blood sugar.
A diabetic diet is a diet that is used by people with diabetes mellitus or high blood sugar to minimize symptoms and dangerous complications of long-term elevations in blood sugar.
Chronic Somogyi rebound is a contested explanation of phenomena of elevated blood sugars experienced by diabetics in the morning. Also called the Somogyi effect and posthypoglycemic hyperglycemia, it is a rebounding high blood sugar that is a response to low blood sugar. When managing the blood glucose level with insulin injections, this effect is counter-intuitive to people who experience high blood sugar in the morning as a result of an overabundance of insulin at night.
Equine metabolic syndrome (EMS) is an endocrinopathy affecting horses and ponies. It is of primary concern due to its link to obesity, insulin dysregulation, and subsequent laminitis. There are some similarities in clinical signs between EMS and pituitary pars intermedia dysfunction, also known as PPID or Cushing's disease, and some equines may develop both, but they are not the same condition, having different causes and different treatment.
The dawn phenomenon, sometimes called the dawn effect, is an observed increase in blood sugar (glucose) levels that takes place in the early-morning, often between 2 a.m. and 8 a.m. First described by Schmidt in 1981 as an increase of blood glucose or insulin demand occurring at dawn, this naturally occurring phenomenon is frequently seen among the general population and is clinically relevant for patients with diabetes as it can affect their medical management. In contrast to Chronic Somogyi rebound, the dawn phenomenon is not associated with nocturnal hypoglycemia.
As a medication, insulin is any pharmaceutical preparation of the protein hormone insulin that is used to treat high blood glucose. Such conditions include type 1 diabetes, type 2 diabetes, gestational diabetes, and complications of diabetes such as diabetic ketoacidosis and hyperosmolar hyperglycemic states. Insulin is also used along with glucose to treat hyperkalemia. Typically it is given by injection under the skin, but some forms may also be used by injection into a vein or muscle. There are various types of insulin, suitable for various time spans. The types are often all called insulin in the broad sense, although in a more precise sense, insulin is identical to the naturally occurring molecule whereas insulin analogues have slightly different molecules that allow for modified time of action. It is on the World Health Organization's List of Essential Medicines. In 2021, it was the 179th most commonly prescribed medication in the United States, with more than 2 million prescriptions.
MODY 2 or GCK-MODY is a form of maturity-onset diabetes of the young. It is due to any of several mutations in the GCK gene on human chromosome 7 for glucokinase. Glucokinase serves as the glucose sensor for the pancreatic beta cell. Normal glucokinase triggers insulin secretion as the glucose exceeds about 90 mg/dl. These loss-of-function mutations result in a glucokinase molecule that is less sensitive or less responsive to rising levels of glucose. The beta cells in MODY 2 have a normal ability to make and secrete insulin, but do so only above an abnormally high threshold. This produces a chronic, mild increase in blood sugar, which is usually asymptomatic. It is usually detected by accidental discovery of mildly elevated blood sugar. An oral glucose tolerance test is much less abnormal than would be expected from the impaired (elevated) fasting blood sugar, since insulin secretion is usually normal once the glucose has exceeded the threshold for that specific variant of the glucokinase enzyme.
Diabetes mellitus is a disease in which the beta cells of the endocrine pancreas either stop producing insulin or can no longer produce it in enough quantity for the body's needs. The disease can affect humans as well as animals such as dogs.
Dysglycemia is a general definition for any abnormalities in blood glucose levels. They include hyperglycemia, hypoglycemia, impaired glucose tolerance test, impaired fasting glucose, among others.
Diabetes mellitus, often known simply as diabetes, is a group of common endocrine diseases characterized by sustained high blood sugar levels. Diabetes is due to either the pancreas not producing enough insulin, or the cells of the body becoming unresponsive to the hormone's effects. Classic symptoms include thirst, polyuria, weight loss, and blurred vision. If left untreated, the disease can lead to various health complications, including disorders of the cardiovascular system, eye, kidney, and nerves. Diabetes accounts for approximately 4.2 million deaths every year, with an estimated 1.5 million caused by either untreated or poorly treated diabetes.
Hypersomatotropism, also known as acromegaly, is an endocrine disorder caused by excessive growth hormone production in cats and dogs.
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