Diabetes mellitus Flashcards
Differential diagnoses of PU/PD
Endocrine
○ Diabetes mellitus
○ Hyperadrenocorticism
○ Hypoadrenocorticism
○ Hyperthyroidism
○ Diabetes insipidus (central or nephrogenic)
Renal disease
○ Chronic kidney disease
○ Pyelonephritis
○ Primary renal glucosuria
Liver failure
Hypercalcaemia
Pyometra or other large infectious/toxic states
Psychogenic polydipsia
Iatrogenic e.g. medications
Definition of diabetes mellitus
A disorder of persistent hyperglycaemia, regardless of the cause, and is due to a relative or absolute lack of insulin.
Aetiology of DM in dogs
Several mechanisms are known to result in DM, and both genetic and environment factors play an important role.
All diabetic dogs are insulin dependent.
- Hormonal antagonism e.g. hyperadrenocorticism, growth hormone release from mammary glands in dioestrus/ metoestrus, exogenous progestagens, exogenous corticosteroids
- Chronic pancreatitis – probably under-diagnosed in diabetic patients. Some dogs will present with acute pancreatitis at the onset of DM, Certain breeds predisposed (especially terriers and spaniels)
- Other mechanisms e.g. autoimmunity, as in human Type 1 DM. Immune mediated islet destruction/autoimmunity. Presence of antibodies to pancreatic autoantigens in a number of cases
- Congenital islet disease (has been reported but rare). Usually the result of beta cell aplasia or degeneration.
Aetiology of DM in cats
- Most cats appear to have type 2 (previously called adult-onset or non-insulin dependent) DM.
- Glucose toxicity.
- Hormonal antagonism (hyperadrenocorticism, acromegaly, exogenous steroids or progestagens)
- Pancreatitis – less well documented and difficult to diagnose in cats but acute pancreatitis can be seen concurrently with DM
- Congenital disease (very rare)
Type 2 DM in cats
Insulin resistance is the hallmark of type 2 DM, and is associated with genetics and acquired factors.
Risk factors of acquired insulin resistance associated with feline DM include obesity, inactivity, and drug therapies.
Weight gain has a particularly profound effect in insulin resistance.
Loss of beta cell function is another hallmark of type 2 DM.
A major hallmark of beta cell loss is thought to be apoptosis triggered by beta cell damage.
Beta cell damage is associated with chronic hyperfunction that occurs secondary to chronic insulin resistance.
Other causes of loss of beta cells include pancreatitis and islet amyloid deposition.
Loss of beta cells occurs in the later stages of glucose toxicity, resulting in the irreversible loss of beta cell insulin secretion.
Glucose toxicity in cats
Regardless of the cause of DM, endogenous insulin secretion at diagnosis is usually low because of the interaction between glucose toxicity and beta cell failure.
Glucose toxicity describes the suppression of insulin secretion from beta cells secondary to prolonged hyperglycaemia.
Glucose toxicity is especially important when superimposed on hyperfunctioning beta cells that are already compromised because of loss of beta cell mass from amyloid deposition or pancreatitis.
With hyperfunctioning beta cells, even mild hyperglycaemia can cause a further rapid deterioration of beta cell function and worsening hyperglycaemia, eventually contributing to signs of overt DM.
Suppression of insulin secretion by glucose toxicity is usually reversible but later on results in structural damage to beta cells.
Over weeks to months such changes become irreversible and beta cells are lost.
Transient diabetes in cats
Approximately 20% of diabetic cats become transiently diabetic, usually within 4-6 weeks after the diagnosis has been made and treatment initiated
In these cats, hyperglycaemia, glucosuria and clinical signs of DM resolve and insulin treatment can be discontinued
These cats appear to be in a subclinical diabetic state that becomes clinical when the pancreas is stressed by drugs or disease
Persistent hyperglycaemia can, in turn, cause hypoinsulinaemia by suppressing beta cell function - glucose toxicity
Clinical signs of diabetes mellitus
Usually develop over several weeks and include polyuria, polydipsia, weight loss, muscle wasting, hepatomegaly.
Concurrent infections are common e.g. UTI, pyoderma, respiratory tract infections
Peripheral neuropathy is common in cats.
Cataracts are frequently seen in dogs, but less common in cats.
Long standing cases might present with ketosis or ketoacidosis.
Peripheral neuropathy in diabetic cats
The most common complication in cats that are chronically hyperglycaemic is diabetic neuropathy- about 10% of cats are affected
Aetiology multifactorial
The progression to this condition may take several months, and, if properly treated, it can resolve within six to 12 months
The femoral nerve is most commonly affected leading to a plantigrade stance
Signalment of diabetes mellitus
Generally a disease of middle aged and older animals
Dogs - 5-12 yrs
Cats - 10-13 yrs
Several dog and cat breeds are predisposed and some appear protected
- cross breed
- labrador
Clinical pathology of diabetes mellitus
Persistent fasting hyperglycaemia above 12-14mmol/l in dogs (renal threshold), or 14-16mmol/l in cats
Cats can show sterss hyperglycaemia
Fructosamine (describes plasma proteins), reflects average glucose conc. over the preceeding 1-2 weeks so elevated if diabetic
Elevation in liver enzymes and hypercholesteraemia
Glucosuria (shouldnt happen with stress in a cat)
Combination of hyperglycaemia and glucosuria is diagnostic
Pathology of diabetes mellitus
Relative or absolute deficiency of insulin
Decreased glucose uptake by adipose tissue and muscle
Increased catabolism, especially of fats
Hyperglycaemia which exceeds the renal threshold resulting in an osmotic diuresis
Biochemical changes in diabetes mellitus
Hyperglycaemia (above renal threshold)
Hypercholesterolaemia
Hypertriglyceridaemia (lipaemia)
Increased ALP
Increased ALT
Therapy options for diabetes mellitus
Management requires understanding by owner, regular daily routine, and is insulin dependent in the dog and nearly all cats.
Insulin – the only effective therapy for dogs and also required in the majority of cats
Oral hypoglycaemic drugs (cats only)
Dietary management (usually in combination with insulin)
Neutering entire females as soon as practical (dogs)
In-patient management (e.g. intravenous fluid therapy, hourly blood glucose measurement) is required for ‘sick’ diabetic patients – especially those with ketoacidosis
Aims of diabetes mellitus therapy
To reduce clinical signs
Improve quality of life
Maintain good appetite and body weight
Minimise complications:
○ Cataracts
○ Neuropathy
○ Ketoacidosis
○ Hypoglycaemia
Types of insulin available
Short (neutral)
Lente
PZI
Glargine
Soluble (neutral) insulin
IV, IM, and SQ
Immediate onset
Peak activity 3-5hrs
Duration 6-8hrs (very short acting)
Lente insulin
SQ
Onset within 2hrs
Peak activity 6-10hrs
Duration 8-20hrs (intermediate)
PZI insulin
SQ
Onset in 4-8hrs
Peak activity 4-14hrs
Duration 6-30hrs (longer acting)
Glargine insulin
SQ
Onset in 2-4hrs (slow release)
Peak activity ?
Duration 10-16hrs (long acting)
Insulin choices in cats
Caninsulin and Prozinc licensed
Prozinc: 0.2-0.4 IU/kg BW every 12 hrs
Initial dose of caninsulin 1IU or 2IU per injection based on baseline blood glucose conc. - requires twice daily administration
Cats are more likely to have varied insulin requirements
Glargine, a synthetic insulin analogue, which is slowly released from the subcutaneous space, is designed for once daily administration in humans. It is marketed as a ‘peakless’ insulin with respect to its glucose-lowering effect. In cats clinical experience demonstrates that glargine has a long duration of action.
Varied doses on caninsulin in cats
Blood glucose <20mmol/l or <3.6g/l: 1IU twice daily
Blood glucose >20mmol/l or >3.6g/l: 2 IU twice daily
Insulin choices in dogs
Caninsulin (same amino acid sequence as canine insulin): 0.5-1.0 IU/kgBW once daily, but may require twice daily (more stable)
Prozinc 0.5-1.0 IU/kg once daily
Oral hypoglycaemic drugs
In cats:
○ Increased insulin secretion
○ Reduced peripheral insulin resistance
○ Decreased glucose absorption from the GI tract
○ Inhibiting hepatic glucose production
Depending on the population studied and how early Dx is made, (much) less than 20% of cats achieve adequate glycaemic control on oral hypoglycaemic drugs
Likely only effective as sole Tx in cats with some beta cell function
Caution is advised when using these drugs alone
If adequate glycaemic control is not achieved in 4-6 weeks, or if ketonuria develops, insulin administration should be instituted
Glipizide is most widely used oral hypoglycaemic
Major side effects are vomiting and anorexia
Glipizide also stimulates the insulin and amylin from beta cells. Chronic stimulation of insulin secretion of insulin secretion may further exacerbate the situation by promoting beta cell exhaustion
DO NOT USE INSTEAD OF INSULIN
Dietary management of diabetes mellitus
Consistency of diet
Composition of diet
Fibre content
Calorie content and caloric density
Feeding schedule
Needs to be low carbohydrate (<15% ME) in cats
Methods of monitoring diabetes
Clinical signs
Blood glucose curves (not repeatable or perfect)
‘Random’ blood glucose measurements (not reliable)
Fructosamine
Glycosylated haemoglobin (not commercially available)
Urinalysis (look for ketones and other side effects)
The ideal stable diabetic
Free of clinical signs such as PU/PD, have a stable weight, and a ‘normal’ appetite
