DIABETES IN ANIMALS: CAUSES, DIAGNOSIS AND PHARMACOLOGICAL MANAGEMENT

DIABETES IN ANIMALS: CAUSES, DIAGNOSIS AND
PHARMACOLOGICAL MANAGEMENT
KARNATAKA VETERINARY ANIMAL AND FISHERIES SCIENCES UNIVERSITY, BIDAR
Dr N B Shridhar
Professor and Head
Department of Veterinary Pharmacology and Toxicology
Veterinary College, Shivamogga-577204, KVAFSU,Bidar
Mobile:9448059777 Mail id: shridharvet@gmail.com
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DIABETES IN ANIMALS: CAUSES, DIAGNOSIS, TREATMENT AND PREVENTION BY DR N B SHRIDHAR
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The pancreas is a glandular organ in the upper abdomen, but really it serves as two
glands in one: a digestive exocrine gland and a hormone-producing endocrine gland.
Functioning as an exocrine gland, the pancreas excretes enzymes to break down the
proteins, lipids, carbohydrates, and nucleic acids in food.
Functioning as an endocrine gland, the pancreas secretes the hormones insulin and
glucagon to control blood sugar levels throughout the day.
Both of these diverse functions are vital to the body's survival.

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Pancreas in snake and turtles

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✓ The pancreas is a narrow, 6-inch long gland that lies posterior and inferior to the
stomach on the left side of the abdominal cavity.
✓ The pancreas extends laterally and superiorly across the abdomen from the curve of
the duodenum to the spleen.
✓ The head of the pancreas, which connects to the duodenum, is the widest and most
medial region of the organ.
✓ Extending laterally toward the left, the pancreas narrows slightly to form the body of
the pancreas.
✓ The tail of the pancreas extends from the body as a narrow, tapered region on the
left side of the abdominal cavity near the spleen

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Glandular tissue that makes up the pancreas gives it a loose, lumpy
structure.
The glandular tissue surrounds many small ducts that drain into the
central pancreatic duct.
The pancreatic duct carries the digestive enzymes produced by
endocrine cells to the duodenum.

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Microscopic Anatomy
The pancreas is classified as a heterocrine gland because it contains both
endocrine and exocrine glandular tissue.
The exocrine tissue makes up about 99% of the pancreas by weight while
endocrine tissue makes up the other 1%.
The exocrine tissue is arranged into many small masses known as acini.
Acini are small raspberry like clusters of exocrine cells that surround tiny
ducts.
The exocrine cells in the acini produce digestive enzymes that are
secreted from the cells and enter the ducts.
The ducts of many acini connect to form larger and larger ducts until the
products of many acini run into the large pancreatic duct.

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The endocrine portion of the pancreas is made of small bundles of cells
called islets of Langerhans.
Many capillaries run through each islet to carry hormones to the rest of
the body.
There are 2 main types of endocrine cells that make up the islets: alpha
cells and beta cells.
Alpha cells produce the hormone glucagon, which raises blood glucose
levels.
Beta cells produce the hormone insulin, which lowers blood glucose
levels.

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Diabetes mellitus in dog and cat
Disorders of the pancreas
✓ The pancreas is composed of several types of cells that have distinct
functions involved in the production of hormones and digestive enzymes.
✓ The exocrine pancreas produces enzymes that are essential for the
digestion of complex dietary components such as proteins, triglycerides,
and complex carbohydrates.
✓ The exocrine pancreas also secretes large amounts of bicarbonate, which
buffers stomach acid.
✓ Disorders of the exocrine pancreas are discussed in the chapter on
digestive disorders, because they relate to digestion.
✓ The endocrine pancreas produces the hormones insulin and glucagon,

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✓ The islets of Langerhans in the pancreas consist of 3 different types of
cells, each of which produces a different hormone.
✓ Most of the cells, which are called beta cells, produce insulin.
✓ Insulin affects, either directly or indirectly, the function of every
organ in the body, particularly the liver, fat cells, and muscle.
✓ In general, insulin increases the transfer of glucose and other
compounds into body cells.
✓ It also decreases the rate of fat, protein, and carbohydrate
breakdown.

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(b). Fasted state Glucagon
dominates

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The other 2 cell types in the islets of Langerhans produce
the hormones glucagon and somatostatin. When blood
glucose levels drop, glucagon is released.
Glucagon helps convert stored carbohydrates into glucose
so they can be used as energy.
Insulin and glucagon work together to keep the
concentration of glucose in the blood and other body fluids
within a relatively narrow range.
Glucagon controls glucose release from the liver, and
insulin controls glucose transport into numerous body
tissues.

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Diabetes Mellitus
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Diabetes mellitus (often called simply diabetes) is a chronic disorder of
carbohydrate metabolism caused by either a deficiency of insulin or a
resistance to insulin.
The term "diabetes" was first coined by Araetus of Cappodocia (81-133AD).
The word mellitus (honey sweet) was added by Thomas Willis (Britain) in
1675 after rediscovering the sweetness of urine and blood of patients (first
noticed by the ancient Indians).
The ancient Indian physician, Sushruta, and the surgeon Charaka (400–500
A.D.) were able to identify the two types, later to be named Type I and Type
II diabetes

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Aretaeus the Cappadocian, who coined the word diabetes (Greek,
‘siphon’)
The term mellitus (Latin, ‘sweet like honey’) was coined by the British
Surgeon-General, John Rollo in 1798,

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In 1869, Paul Langerhans, then aged 22 and working on his medical doctorate,
identified the cells that came to be known as the ‘islets of Langerhans
The name insulin for the secretions of the islets (Latin, insula = island), which could
bring down blood glucose levels, was coined only in 1909 and 1910.
Canadian surgeon Banting and his assistant Best used bovine insulin for the treatment
of DM.
In 1980, the first human insulin was manufactured by Graham Bell.

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✓ DM is a common endocrine disorder in cats
✓ Middle-aged cats are affected most commonly.
✓ Diabetes mellitus occurs in all feline breeds equally and in both males
and females.
✓ Diabetic animals often develop chronic or recurrent infections.
✓ An enlarged liver is common.
✓ The prevalence in cats is around 7.4 per 1000.
✓ All cats are susceptible to diabetes but it is usually seen in middle
aged to older cats.
✓ A higher incidence is seen in neutered male cats.

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China is the country with the highest number of diabetics
worldwide, with around 116 million people suffering from the
disease.

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A total of 1192 veterinarians completed the survey and suggested a
median one in 10 diabetic pets are euthanased at diagnosis; a further
median one in 10 within one year because of lack of success or
compliance.

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Diabetes mellitus has been noted in Burmese cats in Australia and the
UK.
The prevalence of diabetes in Burmese cats in Australia is 22.6 per 1000
cats, significantly higher than in the general population.
This may be related to abnormalities in triglyceride metabolism in
Australian Burmese cats.

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Types of diabetes
✓ Insulin is a hormone produced by the pancreatic islet cells.
✓ When a cat eats, food is broken down into organic compounds in the
small intestine, one of which is glucose.
✓ Glucose is taken up by the cells for energy, growth, and repair.
✓ As glucose enters the bloodstream, the pancreas matches it with the
correct amount of insulin.
✓ Insulin is required to enable glucose to enter the cells, acting as a key
to unlock it.
✓ When insulin arrives at the cell, it stimulates the cell to activate
glucose transporters, pulling the glucose through the wall of the cell.

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➢ In type 1 diabetes, cells of the immune system attack and destroy
islet cells which results in a decreased number of cells producing
insulin
➢ In type 2 diabetes, cells build up a resistance to insulin (known as
insulin resistance) and despite the pancreas producing enough
insulin, it is unable to unlock the cells as efficiently.
➢ When the cells don't have enough glucose either because there isn't
enough insulin or the body resists it, they lack the energy required
to enable the cat's body to work properly

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Symptoms of diabetes in cats
Ω Diabetes mellitus, is a common disease often found in older and
overweight dogs and cats.
Ω Similar to diabetes in humans, animal diabetes occurs when there is
not enough insulin (a hormone made in the pancreas) in the animal’s
body to balance out the glucose (sugar) in the diet.
Ω In normal animals, food is broken down during digestion and the
resulting glucose enters the bloodstream. Insulin is then released to
regulate the blood's glucose levels.
Ω If animal isn't producing enough insulin, it will become diabetic.
Ω And if too much glucose builds up in his body due to the lack of insulin,
the disease can become dangerous and even life threatening.

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The signs of diabetes are difficult to recognize as they are similar to
those of other disorders like chronic kidney disease and hyperthyroidism.
Signs and symptoms of diabetes:
✓ Increased thirst
✓ Rapid weight loss
✓ Not eating
✓ Tired, lack of energy
✓ Vomiting
✓ Increased urination
Lack of insulin is preventing cells from absorbing and getting energy
from glucose and the resulting excess glucose in his blood is making
animal thirsty

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Monitoring food and water intake, waste output and weight will be
important in making sure his diabetes is properly treated.
Some trial and error might be necessary in finding the best treatment,
call vet right away if symptoms return.
A plantigrade stance may be noted secondary to prolonged or severe
hyperglycemia, resulting in a peripheral neuropathy.

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❑ About 50 to 75 percent of cats with diabetes need to receive insulin
injections, and some may also be prescribed pills to help regulate their
glucose levels.
❑ Crucial to the treatment of diabetes is revisiting diet.
❑ Feeding smaller portions of foods specially designed to help his body
handle sugar.
❑ Monitoring food and water intake, waste output and weight will be
important in making sure in diabetes

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Complications of diabetes in cats
➢ Diabetes has many effects on the cat's body.
➢ Glucose builds up in the bloodstream (high blood sugar), this is known as
hyperglycemia.
➢ Because the glucose is unable to enter the cells, the body is starved of
energy and the cat begins to lose weight, despite having a healthy
appetite.
➢ If the diabetes goes untreated, the body will begin to break down its own
fats and proteins to use as energy, leading to further weight loss.
➢ The cat will have a characteristic “Plantigrade stance” due to diabetic
neuropathy

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Plantigrade stance in diabetic cat

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Plantigrade stance in cat

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Ketones in the urine and blood are a by-product of the body's digestion
of its own tissues.
Check cat for ketones in the urine.
This test is performed using strips (readily available) which are dipped
in the urine.
The strip will change colour, which is compared to a guide on the back
of the pack to determine if ketones are present.
Ketones in blood or urine are a sign the disease has progressed.
Ketoacidosis is a serious complication and requires immediate
veterinary attention

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Medications
➢ Oral hypoglycemic drugs (such as glipizide) may be prescribed.
➢ The exact mechanism of glipizide isn't known, but it is believed that it
stimulates the pancreas to release insulin.
➢ This treatment is only effective if the pancreas is still producing some
insulin.
➢ Even though the diabetes may be mild, careful monitoring of the cat is
vital.
➢ If becomes unwell, develops ketones, or remain persistently
hyperglycaemic, then the next step will be insulin.
➢ Insulin: This involves the injection of insulin once or twice a day. It is
administered subcutaneously (under the skin) at the scruff of the neck.
These can be given at home, usually at regular, daily times.

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✓ Individual cats respond differently to insulin, and doses may need to be
adjusted based on blood glucose profiles, clinical response, and urine
glucose monitoring.
✓ Hypoglycemia (low blood sugar) is a potentially life threatening
complication of insulin therapy.
✓ This is caused by either too much insulin or the cat not eating enough
food.
✓ The cat's blood sugar levels dip dangerously low. Feeding small but
frequent meals will help avoid this condition, but careful monitoring of
your cat's blood sugar levels is important.
✓ Signs of hypoglycemia include weakness, listlessness, lethargy, wobbly
gait, convulsions, and coma. If left untreated, it can lead to death

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Canine Diabetes mellitus
All dogs are susceptible to diabetes but it is usually seen in middle aged
to older dogs.
A higher incidence is seen in entire bitches.
Breeds that appear to be at increased risk of developing Diabetes mellitus
include:
➢ Poodle
➢ Daschund
➢ Alaskan malamute
➢ Miniature schnauzer
➢ Chow chow Beagle
➢ Doberman pinscher
➢ Labrador retriever
➢ Puli
➢ Old English Sheepdog
➢ Golden retriever
➢ Miniature pinscher
➢ English Springer spaniel
➢ Rhodesian Ridgeback
➢ Schipperke
➢ Finnish spitz
➢ West Highland white terrier

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• Canine diabetes is a common endocrine disorder with an estimated
breed-related prevalence ranging from 0.005% to 1.5% in pet dogs
• All breeds can be affected by diabetes
• Canine diabetes has been compared with human type 1 diabetes
• Dog breeds viz., Golden Retrievers, Miniature Schnauzers,
Keeshonden, German Shepherd Dogs and Poodles have the highest
incidence.
• canine insulin-deficiency diabetes (IDD) occurs more commonly in
older dogs, aged 7–12 years.
• Females are at increased risk, regardless of neuter status. Neutered
males are at greater risk than intact males.

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Associated metabolic complications
➢ Initially, dogs having incompetency to metabolize enough sugar have
an increase in appetite and a desire to consume more food.
➢ The amount to feed is determined by dividing the daily caloric
requirement by the amount of calories per cup or can of food.
➢ The insulin requirements are computed on that basis by keeping
constancy in daily calorie requirement in relation to body weight gain.
➢ The meal should be divided into two or three equal portions or as
directed by your veterinarian.
➢ It is equally important to maintain a strict schedule for insulin
injections.
➢ Ideally, the affected dog should have the same levels of exercise and
activity

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➢ Some breeds (e.g. Samoyed) being over-represented, whereas others
(e.g. Boxer) seem to be relatively resistant to developing the disease.
➢ Pathogenesis of diabetes is influenced by genetic factors and
similarities between canine and human diabetes
➢ This indicate that the same genes and/or genetic pathways might be
involved in both species.
➢ There could be differences in the individual susceptibility genes that
contribute to the overall genetic risk for different dog breeds

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Type I Diabetes Mellitus
Sometimes also caused Insulin Dependent Diabetes Mellitus,results from
total or near-complete destruction of the beta-cells.
This is the most common type of diabetes in dogs. As the name implies,
dogs with this type of diabetes require insulin injections to stabilize
blood sugar.
"Type I Diabetes Mellitus is the most common type of diabetes in dogs."

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Type II Diabetes Mellitus
Sometimes called Non-insulin Dependent Diabetes Mellitus, is different
because some insulin-producing cells remain.
✓ However, the amount of insulin produced is insufficient, there is a
delayed response in secreting it, or the tissues of the dog's body are
relatively resistant to it (also referred to as insulin resistance).
✓ Type II diabetes may occur in older obese dogs.
✓ This form may be treated with an oral drug that stimulates the
remaining functional cells to produce or release insulin in an
adequate amount to normalize blood sugar.
✓ Unfortunately, dogs tend not to respond well to these oral
medications and usually need some insulin to control the disease

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Complication occurred due to diabetes mellitus in animals

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α Canine diabetes mellitus (DM), classified as either Type I or Type II, is
a generally treatable condition caused by insulin deficiency.
α At diagnosis, most diabetic dogs are suspected of having type I.
α Type I patients, characterized by permanent inability to produce
insulin, often require exogenous insulin administration.
α DM has a potential immune-mediated cause (though this is not firmly
established).
α Diabetogenic drugs, pregnancy, and chronic pancreatitis are also
possible causes of canine DM.

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(Kamal Niaz et al., 2018)

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(Kamal Niaz et al., 2018)

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Mechanism initiating
insulin resistance

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Golden Retriever
German Shepherd

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Poodle Daschund

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Alaskan Malamute Miniature Schnauzer

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Samoyed
(Highly susceptible)

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Pathophysiology
Insulin deficiency results in hyperglycemia by causing:
➢ Uninhibited hepatic glucose production,
➢ Impaired entry of glucose into tissues,
➢ Accelerated protein and lipid catabolism.
Persistent hyperglycemia results in glucosuria when the renal
tubularthreshold for glucose excretion >180–220 mg/dL.
Increased proteolysis leads to muscle wasting and poor wound healing.
As the accelerated lipid catabolism persists, hepatic lipidosis develops
and ketoacidosis can result secondary to enhanced ketone body
production, endothelial damage and immune suppression ultimately occur.
Approximately 50% of recent identified dog cases suggested that β-cell
damage may be due to autoantibodies

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Simultaneous occurrence of insulin-dependent diabetes mellitus
(IDDM) and non-IDDM in animals

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❖ Diabetes mellitus is diagnosed by the presence of the typical clinical
signs (excess thirst, excess urination, excess appetite, and weight loss)
❖ The presence of a persistently high level of glucose in the blood stream,
and the presence of glucose in the urine.
❖ The normal level of glucose in the blood is 80-120 mg/dl (4.4-6.6
mmol/l).
❖ It may rise to 250-300 mg/dl (13.6-16.5 mmol/l) following a large or
high-calorie meal.
❖ However, diabetes is the only common disease that will cause the blood
glucose level to rise above 400 mg/dl (22 mmol/l).
❖ Some diabetic dogs will have a glucose level as high as 700-800 mg/dl (44
mmol/l), although most will be in the range of 400-600 mg/dl (22-33 mmol/l).

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▪ To conserve glucose within the body, the kidneys do not filter glucose
out of the blood stream into the urine until an excessive level is
reached.
▪ This means that dogs with a normal blood glucose level will not have
glucose in the urine.
▪ Diabetic dogs, however, have excessive amounts of glucose in the
blood, so it will be present in the urine.
▪ After the blood sugar reaches 180 mg/dl,the excess blood sugar is
removed by the kidneys and enters the urine.

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Prognosis for a dog with diabetes mellitus
✓ Once the diabetes mellitus is properly regulated, the dog's prognosis is
good as long as treatment and monitoring are consistent.
✓ Most dogs with controlled diabetes live a good quality of life with few
symptoms of disease.
✓ Uncontrolled diabetes can lead to cataract formation, bacterial
infections (usually urinary tract), ketoacidosis, hepatic lipidosis,
persistent weight loss.
✓ DM can also be complicated by morbid conditions (e.g.,
pancreatitis,infections,hyperadrenocorticism).
✓ Attempting to control diabetes with insulin therapy can lead to
iatrogenic hypoglycemia.

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➢ Short-acting insulin (eg, regular insulin, insulin lispro) is predominately
used in the hospital for clinically ill diabetics or DKAs, as increased
potency increases risk for hypoglycemia.
➢ Intermediate-acting insulin is the common choice, as it results in the best
glycemic control.
➢ Human recombinant Neutral Protamine Hagedorn (NPH) insulin. Comparable with
NPH insulin,lente insulin is currently unavailable.
➢ Long-acting insulin effectively reduces the blood glucose level but varies in
absorption, time to nadir, and duration of action, increasing risk for
hypoglycemia and Somogyi effect.
➢ Insulin detemir, insulin glargine, and protamine zinc insulin (PZI).
➢ Treatment should be initiated q12h, although starting doses differ for
insulin types.

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Insulin therapy in dogs
o The two most effective insulin formulations in dogs are NPH and Lente
insulins.
o Use of human recombinant insulin or pure pork insulin, appear to avoid
the complications that can occur due to development of anti-insulin
antibodies in dogs treated with beef/pork insulin.
o Lente insulin (Caninsulin®/Vetsulin®) and NPH insulin (Humulin N®) are
used at a starting dose of 0.25 to 0.5 IU/kg twice a day.
o Most dogs treated with NPH and Lente insulin require twice daily
treatment, and twice daily therapy should be recommended in all
dogs.

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✓ Because Lente insulin is a mixture of ultralente and semilente insulin, the
duration tends to be longer than the duration of NPH.
✓ Long acting insulins such as PZI, glargine, and detemir are unpredictable in dogs
and are not appropriate for the initial management of most diabetic dogs.
✓ The analogue insulin, detemir has only been evaluated in a small number of
diabetic dogs.
✓ It is important to be aware that this insulin is much more potent in the dog than
other insulin products with the dose needed for good glycemic control ranging
from 0.07-0.23 U/Kg.

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Control and preventive measures
➢ Dietary control and daily injections of insulin can regulate most
diabetic dogs, allowing them to lead active, healthy lives.
➢ Oral hypoglycemic agents used for treating diabetes in people have
not been effective in dogs, but research is continuing in this area.
➢ Insulin requirements cannot be predicted solely on the basis of the
dog’s weight, because the degree of pancreatic failure is different in
every dog.
➢ The daily caloric requirements are determined by the weight and
activity level of the dog.

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Dietary management
✓ Dietary management should be instituted at the same time as insulin
therapy in the diabetic dogs.
✓ The goal of dietary therapy is to minimize postprandial fluctuations in
blood glucose and to potentiate the action of insulin.
✓ Studies support the feeding of a high complex carbohydrate (> 50% dry
matter), high fiber diet (> 10% dry matter) to dogs with DM.
✓ Diets containing increased amounts of soluble fiber (fruits,legumes,
oats) delay gastric emptying alter intestinal transit time and potentiate
the actions of insulin in tissues.

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❖ Increased amount of insoluble fiber (cellulose, vegetables, and grains) alter
intestinal transit time and slow starch hydrolysis.
❖ The net effect of a high fiber diet is to slow glucose absorption from the
intestinal tract, reduce post prandial fluctuations in blood glucose and
enhance glycemic control of the diabetic dog.
❖ Reduced fat diets are probably appropriate in diabetic dogs due to their
❖ susceptibility to hepatic lipidosis, pancreatitis and hypercholesterolemia.
❖ Canned diets tend to be lower in carbohydrates than dry diets.
❖ Complex carbohydrates require digestion before absorption, they minimize
postprandial fluctuations in blood glucose concentration.
❖ Soft moist foods contain simple carbohydrates which are rapidly absorbed.
❖ These diets may result in rapid fluctuations in blood glucose 30-45 min
after eating.

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❖ The feeding schedule is also very important in diabetic dogs.
❖ Feeding should occur when insulin is present in the bloodstream
in
❖ order to utilize glucose as it is absorbed.
❖ Ideally 3 - 4 small meals/day should be fed.
❖ For dogs receiving once a day insulin one meal should be given
at the time of insulin administration, and a second meal given in
the
❖ late afternoon at the time of peak insulin effect.
❖ For those dogs receiving insulin twice a day, at least 4 meals
would be ideal.

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Poor response to insulin
➢ An insulin dose higher than 2 U/Kg/dose in the dog or recurrent ketoacidosis.
➢ Adequate assessment of the cause of the problem requires performing a blood
glucose curve.
➢ Measurement of fructosamine may also be helpful.
➢ In dogs receiving twice daily insulin, most glucose curves can be performed during
working hours (8 am to 6 pm).
➢ Common problems that may lead to a poor response to insulin include problems with
owner administration, inappropriate insulin dose or formulation, insulin induced
hypoglycemia, rapid metabolism of insulin, and insulin resistance.
➢ It is important to take into consideration the level of stress of the dog while in the
hospital when interpreting the results of blood glucose curves.
➢ Other factors such as clinical signs, results of urine blood glucose measurements,
serum fructosamine concentrations, body weight, should be taken into account.

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• The monitoring of blood glucose curve (a series of blood sugar tests
drawn over 12-24 h period) is recommended for assessment of
requirement of insulin.
• An overweight dog is more prone to diabetes and should be put on a
high-fiber, high- carbohydrate diet until he reaches an ideal weight

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Nutritional Aspects
✓ Minimizing postprandial blood glucose fluctuations is the principal goal of
dietary therapy.
✓ Most studies suggest that fiber-rich diets, particularly insoluble fiber,
result in improved glycemic control.
✓ The ideal dietary composition is debatable, as improved glycemic control
may be attributed to the high-fiber, lowcarbohydrate,low fat, or
combination content.
✓ Diet change is not recommended during stabilization.
✓ If diabetes is difficult to regulate, increase fiber.
✓ Diets should be palatable to ensure predictable consumption.
✓ Equal-sized meals should be offered q12h (with insulin administration).
✓ Overweight dogs require weight reduction programs, as obesity contributes
to insulin resistance.

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DM in Wild Animals
➢ Clinical and morphological characteristics in restricted animals
explored as NIDDM Type-2.
➢ Various studies suggest that insulin resistance causes alteration of β-
cell activity and prolong pre-diabetic conditions and thus also has
shown resemblances of NIDDM in both humans and non-human
primates.
➢ As yet, synchronized amyloid disease has been identified in different
animals
➢ Pan troglodytes (chimpanzee), Pongo pygmaeus (orangutan),
Cercopithecus species, Macaca species, Mandrillus species, Papio
hamadryas, Saimiri sciureus, and Macaca mulatta

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➢ Fibrosis of islets of Langerhans and chronic pancreatitis was identified in
Procavia capensis (Rock hyrax) and California sea lion, describing
another type such as secondary DM.
➢ Panthera onca, African spotted leopard, and even their progeny
developed DM in confined conditions.
➢ Consequently, the extensive use of humanized hormone-megestrol
acetate to prevent pregnancy and following subtype of breast cancer
leads to elucidate secondary DM in Panthera onca.
➢ DM in older primates causes disorders such as venous thrombosis,
nephropathy, myocardial fibrosis, and cardiomyopathy.

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Procavia capensis (Rock hyrax)

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California sea lion

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Panthera onca (African spotted leopard)

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❖ The study of Spermophilus lateralis was one of the comprehensive
and widely investigations that exhibited the presence of DM in
confined rodents.
❖ Obviously, these animals are mostly characterized by blurred vision,
retinal atrophy, and opacity, plus the vacuole formation has been
observed in their islets of Langerhans in both α-and β-cells.
❖ Rodents such as Ctenomys talarum and Lagostomus
maximus provoked DM in progeny as well as in adults with noteworthy
high levels of fructosamine, glucose, fatty liver, opacity, and blurred
vision

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❖ Three various types of islets of Langerhans are responsible for
the synthesis, production, and secretion of the avian pancreatic
polypeptide, somatostatin, insulin, and glucagon.
❖ The glucagon concentration in birds is greater than mammals,
due to its activities toward glucose metabolism as well.
❖ Birds urine free of glucose, also need glucose transport protein
and sodium-glucose co-transporters to absorb glucose from
gastrointestinal track.
❖ Perhaps, it may be suggested that lower insulin and higher
glucagon are significant for provoking DM.
❖ In ducks surgical removal of pancreas express hypoglycemia.

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Diabetes in cattle
❖ In cattle, insulin-dependent diabetes mellitus (IDDM) associated
with bovine viral diarrhoea virus (BVDV) infection.
❖ It appears that BVDV does not induce IDDM directly, but rather
may be an autoimmune disease induced by autoantibodies
against islet cells.
❖ Bulls which have chronic laminitis, polyarthritis, and traumatic
injuries of the penis with edema treated by chlorothiazide,
dexamethasone, phenylbutazone, and prednisolone expressed
islets of Langerhans atrophy and fibrosis.
❖ Elephantid herpesvirus-1 could be the possible source of this
condition and treatment procedure should also contain the
essential factor such as the use of insulin antagonist.
(Tajima et al., 1999)

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Diabetes mellitus has been reported in cattle, pigs, sheep, horses,
and bison; it is relatively uncommon in cattle.
There are several possible concurrent predisposing diseases or risk
factors that are discussed in the literature,such as fatty liver, fat
cow syndrome, parturition and chronic insulitis, as well as viral
diseases, especially bovine virus diarrhea.
Cases of diabetes mellitus have been reported in various breeds of
cattle including Aberdeen Angus, Jersey, Hereford , Holstein-
Friesian, Brangus , Japanese black, and Japanese brown.

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➢ Several studies have performed glucose tolerance tests and
measured fructosamine levels to show that the hyperglycemia,
glycosuria, and ketonuria have been due to a decrease in
insulin production by the pancreas.
➢ The glucose disappearance rate and half time were markedly
longer in cattle with diabetes than in normal control cattle.
➢ Fructosamine levels were also elevated in the diseased animals.
➢ Other causes of hyperglycemia that have been reported are
enterotoxemia, parturient paresis, foot and mouth disease,
botulism, septicemia, polioencephalomalacia, and rabies.

126
Diabetes mellitus in cattle is often immune mediated and is similar to juvenile onset
diabetes mellitus in humans.
Viral infection may cause diabetes mellitus by 2 different mechanisms:
1) The virus directly destroys b cells in the pancreas
2) An immune response against the virus infection may induce an autoimmune
response in the host
Clinical signs:
Weight loss, poor hair coat, glucosuria, ketonuria and hyperglycemia.
Treatment :
May be attempted, but it is probably not economically or practically viable.

127
Diabetes mellitus in horses
➢ Many people don't think their horse has diabetes until after their horse is
battling the agony of laminitis.
➢ Horse an herbivorous species, the equine pituitary gland has a well-developed
“intermediate lobe” that secretes several proopiomelanocortin peptides or
“melanocortins” .
➢ A few cases of DM have been reported to develop in adult horses.
➢ The associated complications included chronic pancreatitis, ovarian
neoplasia, pregnancy, and immune-mediated polyendocrinopathy.
➢ Transient DM was also identified in a 3-day-old foal that presented with
diarrhea.
➢ Type 1 DM was considered likely (hyperglycemia in the absence of
hyperinsulinemia and a positive response to administered insulin), similar to
neonatal DM in human babies

128
Clinical signs of DM in horses
❖ Gains or holds weight on much less feed than other horses
❖ Fatty crest on the neck which is never normal.
❖ It may very well be extremely common in some breeds, but it's not
normal.
❖ Fat deposits at the base of the tail or elsewhere on the body, may
have a dimpled appearance (like cellulite)
❖ Bulges above the eyes in the area that is normally hollow
(supraorbital fossa)
❖ History of grass-related laminitis
❖ History of laminitis when pregnant

129
Fat deposits at the base of the tail

130
➢ Overfeeding a horse to the point it becomes obese can also result in
insulin resistance, although not all fat horses are insulin resistant.
➢ Cushing's disease, a condition common in older horses, occurs when a
tumor has grown in the pituitary gland in the brain and puts out large
amounts of adrenocorticotropic hormone (ACTH).
➢ ACTH in turn makes the adrenal gland secrete the hormone cortisol.
Cortisol blocks the action of insulin on cells, creating insulin
resistance.
➢ Not all horses with Cushing’s Disease are insulin resistant, at least
initially, but that condition does put them at high risk.

131
Diagnosis
✓ Early insulin resistance can only be diagnosed for sure with
specialized blood tests, such as tubing the horse with glucose to see
the insulin response or intravenous infusions of glucose and insulin.
✓ Later cases can be detected simply by checking the horse's insulin.
✓ Horse not to be given any grain on the day of testing, but grass hay is
OK.
✓ A chemistry screen with glucose and triglycerides should be checked
at the same time.
✓ If a horse is showing the signs of insulin resistance but insulin is still
testing within the lab's normal ranges, it's wise to assume the horse
does have IR and manage accordingly.

132
Treatment
✓ A variety of drugs are available for people with insulin resistance,
but none come even close to having the effectiveness of exercise
and diet control.
✓ Those drugs haven't been tested in horses, but the good news is that
exercise and diet also work extremely well.
✓ Controlling the diet is the key to getting the horse to a normal
weight and avoiding or treating laminitis.
✓ Regular exercise is very much required.

133

134

135
HERBAL THERAPIES IN THE TREATMENT OF DIABETES
➢ Herbal therapies in diabetes cover a wide range of studies and
investigations.
➢ A total of 27 medicinal plants used in animal models for the treatment
of DM.
➢ Silymarin a well-known phytochemical (A standardized extract of the
seeds of Silybum marianum) is believed to lessen inflammatory
cytokines and oxidative stress biomarkers to prevent the IDDM type-1
in patients
➢ Herbal therapeutic agents the potential to reverse diabetes in
streptozotocin-induced diabetic models

136
❑ Today, the utilization of herbal agents is passing a growing route in Asia,
Europe, and North Africa as a tonic, anti-diabetic, anti-pyretic, and anti-
allergic.
❑ Phlomis species such as Phlomis persica boiss or its extract significantly
downregulate blood glucose level and are also effective against the
complication that occurs due to the lipid peroxidation by antioxidant
activity in streptozotocin-induced rats.
❑ Bixa orellana (Annatto) extract decreased blood glucose levels in fasting
normoglycaemic and streptozotocin-induced diabetic dogs by stimulating
peripheral utilization of glucose .
❑ The uses of conventional antidiabetic drugs along with herbal remedies
have shown possible antihyperglycemic and therapeutic adjuncts of the
oral route for controlling diabetes.

137
➢ Plant combination with polyphenols or flavonoids such as curcumin and
quercetin have much stronger antioxidant effects in reversion of
diabetes, yet preclinical and clinical trials should be elucidated for
exact mechanism.
➢ Besides herbal agents, other trace elements such as selenium act as
antioxidants; however, patients with diabetes express an increased
level of oxidative stress along with deficient selenium.

138
❖ The spontaneous DM in small and wild animals comprises all types of
diabetes defined in humans.
❖ In dogs, pregnancy, obesity, diestrus phase, and obstinate corpus
luteum may generate diabetes.
❖ The appearance of DM in wild animals can be correlated with different
stimuli such as confinement, food changes, low physical exercises,
pancreatitis, and hormonal imbalance in the body.
❖ In cats, spontaneous NIDDM related to the islets of Langerhans amyloid
disease is considered as the proper animal model but infrequently
identified.

139
✓ To date, several herbal therapeutic agents with remedial potential are
known to treat diabetes in humans and should be introduced in small
and laboratory animals as well.
✓ DM in animal models is not only a substantial area of research due to
the various similarities with humans but also will play a key role in
veterinary medicine and its progression.
✓ The investigation and the establishment of therapeutic protocols for
diabetic animals comprise different issues.
✓ This should start with the recognition of etiological and risk factors in
association with diabetes diagnosis of the DM initiators and suitable
treatment protocols to terminate DM, in combination with other herbal
therapies.

140

DIABETES IN ANIMALS: CAUSES, DIAGNOSIS AND PHARMACOLOGICAL MANAGEMENT

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DIABETES IN ANIMALS: CAUSES, DIAGNOSIS AND PHARMACOLOGICAL MANAGEMENT