Diabetes mellitus

Contributors: David Bruyette, Carmel Mooney, Nicki Reed

Species: Feline | Classification: Diseases

Introduction Pathogenesis Diagnosis Treatment Outcomes Further Reading

Introduction

Common endocrine disease of middle-aged cat (approx. 1 in 400).
Cause: syndrome characterized by relative or absolute lack of insulin.
Signs: polyuria/polydipsia.
Diagnosis: glycosuria, persistent hyperglycemia, fructosamine.
Treatment: insulin, dietary management.
Prognosis: generally good if uncomplicated by concurrent condition.
Print off the owner factsheets on Diabetes mellitus Diabetes mellitus and Monitoring diabetes in cats Monitoring diabetes in cats to give to your client.

Presenting Signs

Uncomplicated:
- Polydipsia/polyuria.

Weight loss.
Anorexia (particularly if ketotic).

Lethargy.
Gait abnormalities (plantigrade stance).

Vomiting Vomiting.
Polyphagia

Acute Presentation

Signs of diabetic ketoacidosis Diabetic ketoacidosis (anorexia, vomiting, dehydration, coma, death).
Hyperosmolar non-ketotic diabetes has been reported in the cat but appears to be rare.

Age Predisposition

Middle-aged to old - mean 11 y (range 7-14 years).
Rarely juvenile.

Breed Predisposition

Burmese Burmese reported to be over-represented in Australia, New Zealand and UK.
Maine Coon Maine Coon, Domestic longhair, Russian Blue Russian Blue, and Siamese Siamese possibly over-represented in USA.

Special Risks

Anesthesia Anesthesia: in diabetic patient requires careful planning.
Usually administer half dose of insulin prior to surgery and administer glucose in fluids during procedure.
Aim to get animal eating and back on usual regime as soon as possible after surgery.
Warn owner of risks associated with anesthesia.

Pathogenesis

Etiology

Type 1: inadequate secretion of insulin (immune-mediated, destruction of islet cells).
Type 2: resistance to insulin activity, eg obesity Obesity leading to relative lack of insulin (most common).
Type 3: antagonism to insulin (cortisol, progesterone, growth hormone, catecholamines, glucagon).
Inactivation of insulin (immune response).

Predisposing Factors

General

Increasing age (may be due to increased presence of diseases causing insulin resistance in older cats).
Obesity:
- Associated with indoor lifestyle.
Concurrent disease:
- Acromegaly Acromegaly.
- Pancreatitis/pancreatic neoplasia Pancreatitis Pancreas: neoplasia.
- Urinary tract infection Cystitis: bacterial.
- Dental disease Periodontal disease.
- Hyperthyroidism Hyperthyroidism .
- Hyperadrenocorticism Hyperadrenocorticism.
Drug therapy:
- Progestagen therapy, eg megestrol acetate.
- Glucocorticoids.
- Cyclosporin may alter glucose homeostasis in humans and dogs (not documented in cats).
Genetic susceptibility.

Pathophysiology

Type 1: (insulin dependent - rare) destruction of beta cells (immune-mediated/congenital/neoplastic → failure of insulin response to hyperglycemia.
Type 2: (non-insulin dependent - most common) peripheral insulin resistance → increased insulin production required → glucose toxicity and increased amylin secretion → fall in insulin levels and islet amyloidosis → beta cell degeneration → type 1 diabetes.
Type 3: (concurrent disease - 5-10%) endocrinopathies or insulin antagonistic drugs → increased requirement for insulin → initial hyperinsulinemia → beta cell degeneration → type 1 diabetes.

Timecourse

Weeks to months.

Diagnosis

Presenting Problems

Polydipsia/polyuria.

Client History

Developing over a few weeks:
- Polydipsia/polyuria.
- Gait abnormalities.

Anorexia.
Vomiting.
Polyphagia.
Weakness.

Clinical Signs

Depression.
Abnormal weight (obesity or thin).

Muscle wastage.
Hepatomegaly Hepatomegaly.
Unkempt hair coat.
Dehydration.
Bacterial infections (urinary tract, respiratory tract).

Icterus.

Thickened intestinal loops.
Plantigrade stance (peripheral neuropathy) .

Diagnostic Investigation

Urinalysis

Persistent glycosuria Urinalysis: glucose.
Ketonuria (if ketoacidosis) Urinalysis: ketone.
Active sediment Urinalysis: centrifuged sediment (evidence of urinary tract infection).
Proteinuria Urinalysis: protein appears common in cats with untreated diabetes mellitus.
Specific gravity Urinalysis: specific gravity except if azotemic.

Biochemistry

Persistent fasting hyperglycemia Blood biochemistry: glucose (>9 mmol/l, although typically >20 mmol/l).
Hyperglycemia up to 20 mmol/l in a single blood sample is a common finding in cats with concurrent disease or stressed by sampling techniques.
Elevated serum fructosamine Blood biochemistry: fructosamine:
- Concurrent hyperthyroidism Hyperthyroidism may reduce fructosamine values into the reference range due to increased protein turnover.
Elevated gylcosylated hemoglobin.
If serum fructosamine and glycosylated hemoglobins are raised then diagnosis of diabetes mellitus is likely.Cannot rule out acute onset of diabetes mellitus if fructosamine is normal.
Moderate increases in ALP Blood biochemistry: alkaline phosphatase, AST Blood biochemistry: aspartate aminotransferase, and ALT Blood biochemistry: alanine aminotransferase (SGPT, ALT) .
Hyperosmolar serum.

Elevated bilirubin Blood biochemistry: total bilirubin.
Hypokalemia Blood biochemistry: potassium (osmotic diuresis and vomiting/diarrhea) and other electrolyte changes hypernatremia Blood biochemistry: sodium, hypophosphatemia Blood biochemistry: phosphate are also common.

Increased cholesterol Blood biochemistry: cholesterol.
Prerenal azotemia Pre-renal azotemia Blood biochemistry: urea due to dehydration.

Radiography

Thyroxine Blood biochemistry: free thyroxine assay may be suppressed and hyperthyroidism may be masked by suppression of [T4] into normal range.

Hematology

Stress leukogram may or may not be present, as hyperglycemia may reduce mobilization of neutrophils.
PCV Hematology: packed cell volume may be increased due to hemoconcentration in dehydrated patients.
PCV may be reduced due to Heinz body anemia (particularly if ketotic).

2D Ultrasonography

Hepatomegaly and increased echogenicity of liver Ultrasonography: liver.

Gross Autopsy Findings

Hepatomegaly.

Histopathology Findings

Pancreatic amyloidosis.

Differential Diagnosis

Many cats with diabetes mellitus have concurrent disease.

Hyperthyroidism Hyperthyroidism .
Chronic renal disease Kidney: chronic kidney disease.
Inflammatory bowel disease Inflammatory bowel disease: overview.

Acromegaly Acromegaly.

Hepatic disease Liver: chronic disease.
Neoplasia, eg small intestine lymphoma Lymphoma.
Hyperadrenocorticism Hyperadrenocorticism.

Treatment

Initial Symptomatic Treatment

If cat is depressed or anorexic fluid therapy and nutritional support may be required.
The aim of treatment is to address the underlying cause:
- Primary disease treat with insulin.
- Secondary disease treat underlying condition (although may need insulin support in interim).

Standard Treatment

Aims of treatment

Resolve clinical signs.
Avoid hypoglycemia Hypoglycemia.
Achieve diabetic remission.

Dietary control

High protein/low carbohydrate diets, with <15% of energy requirements from carbohydrates, should be fed unless concurrent chronic kidney disease, as increased rates of remission have been demonstrated.
High fiber, moderate protein diets may be used as an alternative.
Wet foods appear to be better than dry foods at controlling weight.
Meal feeding in association with insulin injections is not necessary:
- There is not such a marked post-prandial hyperglycemic peak in cats.
- Ad lib 'grazing' is more consistent with their natural feeding pattern.
If the patient is obese reduce caloric level to 75% of cat's ideal weight.
In non-obese patients normal maintenance rations should be fed.

Oral hypoglycemic agents

Best reserved for normal or obese, non-ketotic cats with no underlying disease and only mild increases in blood glucose.
See component oral hypoglycemics for further details Oral hypoglycemic agents but most commonly used is glipazide:
- Stimulates beta cells to produce more insulin.
- May be less likely to induce recovery from glucose toxicity.

Insulin therapy

Different insulins available - few have veterinary licences:
- Bovine insulin is very similar to feline insulin (differing by a single amino acid):
  - Bovine Protamine zinc insulin Insulin is considered to be long-acting.
  - Once or twice daily by subcutaneous injection (Blue Ridge Pharmaceuticals).
- Porcine lente insulin:
  - Must be given twice daily, sometimes 3-4 times daily.
  - 40 iu/ml formulation is useful for small doses required in cats.
- Glargine Insulin glargine and detemir Insulin detemir:
  - Human recombinant insulins.
  - Considered to be 'peakless' therefore risk of hypoglycemia reduced.
  - Best given twice daily.
See standard stabilization routine Diabetes: management regimens.
If animal is ketoacidotic always use insulin therapy, not oral hypoglycemics alone.

Agents for use in combination with insulin

Thiazolidinediones, eg troglitazone (Resulin) 20-40 mg/kg SID increase insulin-dependent glucose disposal, but there are no studies on efficacy in diabetic cats.
Transition metal compounds, eg vanadium Vanadium and chromium Chromium have recently been used clinically to lower blood glucose levels in non-insulin dependent diabetic cats, although latest data has shown little benefit.
Some agents, eg alpha-glucosidase inhibitors (acarbose) impair glucose absorption from the intestine, but are more effective in 'meal-fed' cats.

Monitoring

Laboratory monitoring

Blood glucose curves performed:
- 7-10 days into treatment to allow for decrease in glucose toxicity.
- 7-10 days after adjustment in management.
- If there is a question over stability.
Monitor serum fructosamine Blood biochemistry: fructosamine or glycosylated hemoglobin Glycosylated hemoglobin to determine long-term stability - particularly for stressed or fractious cats.
Renal function by urea, creatinine and urine SG measurements.
If oral hypoglycemics are used periodic hemograms and biochemistry to monitor for side-effects (increased hepatic enzymes, possible blood dyscrasias, hypoglycemia).

Home monitoring by owner

Monitor for hypoglycemia:
- Owners should be made aware of potential signs of hypoglycemia, namely weakness/wobbliness, tremors, twitching or seizures, dilated pupils, unusual fear or hiding behaviors.
Resolution of clinical signs (best guide to stabilization).
Water intake at home (usually <60 ml/kg/day on dry food or <20 ml/kg/day on wet food) indicates glycemic control is good.
Weight - diet should be adjusted accordingly (if losing weight increase caloric intake; if gaining reduce caloric intake.
Urine glucose 2-3 times weekly:
- If on PZI or Lente insulin:
  - Repeated negative urine glucose may indicate remission. Check blood glucose.
  - Do not use positive values to increase insulin dose.
- If on glargine/detemir:
  - Negative gluosuria may be less likely to indicate remission, as blood lgucose exceeds renal threshold less frequently.
  - Persistent glucosuria may indicate need to increase dose.
Development of complications associated with disease:
- Diabetic neuropathy (plantigrade stance) may arise with poor glycemia control.
- Cataracts rarely cause clinical complications in cats.
Purina Glucotest" is a litter additive that supposedly can be used to accurately assess glucosuria. Results suggest that the Glucotest" tends to overestimate urine glucose concentrations in the midranges (50-300 mg/dL), even when exposed to urine glucose conentrations that directly correlate with the published color chart. The 8 hr measurements were more accurate than the initial readings but the change over time is not consistent with the labeled 8-hr color stability claim.
Home blood glucose curves may be performed by committed owners. Reduce stress and inappetence that may be associated with hospital generated curves and therefore more likely to reflect true control.
If there is a discrepancy between owner reporting stability and laboratory tests indicating poor control then owner is more likely to be correct and laboratory effects may be due to stress hyperglycemia.

Subsequent Management

Treatment

Development of hypoglycemia should be treated with:
- Glucose solutions applied to gums by owner (honey can be used in an emergency).
- Glucose may be instilled into rectum if concern re getting bitten.
- Intravenous administration of 10% glucose (0.2-0.4 ml/kg) over 10 mins, followed by constant rate infusion of 2.5-5% glucose as required.
- Glucagon injection can be considered for insulin overdose given as a constant rate infusion.

Outcomes

Prognosis

Mean survival times 1-2 years.
Prognosis may be better in cats that achieve remission, which usually occurs within 4 months of initiating therapy.
Remission rates reported to be:
- 80-90% for glargine with intensive monitoring.
- 40% for protamine zinc insulin.
- 30% for porcine lente insulin.
Approximately 25-40% may relapse again after achieving remission.
Mortality rate in first year after diagnosis is high but if a case survives this period long term prognosis is better.
Presence of concurrent disease may worsen prognosis.

Expected Response to Treatment

Resolution of clinical signs.
In some cases disease may resolve completely.

Reasons for Treatment Failure

Concurrent disease Diabetes mellitus: pathophysiology. Investigate for and treat where feasible:
- Urinary tract infection.
- Pancreatitis/pancreatic neoplasia.
- Acromegaly.
- Hyperthyroidism.
- Dental disease.
- (Hyperadrenocorticism - rare.)
Owner non-compliance with treatment:
- Check insulin storage and administration.
- Inappropriate diet.
Inappropriate treatment regime:
- Adjusting insulin dose based on urine glucose.
- Only giving insulin once daily.
- Not rotating injection site.
Side effects or complications associated with treatment:
- Hypoglycemic episodes.
- Somogyi overswing.

Diabetes mellitus

Introduction

Presenting Signs

Acute Presentation

Age Predisposition

Breed Predisposition

Special Risks

Pathogenesis

Etiology

Predisposing Factors

General

Pathophysiology

Timecourse

Diagnosis

Presenting Problems

Client History

Clinical Signs

Diagnostic Investigation

Urinalysis

Biochemistry

Radiography

Hematology

2D Ultrasonography

Gross Autopsy Findings

Histopathology Findings

Differential Diagnosis

Treatment

Initial Symptomatic Treatment

Standard Treatment

Aims of treatment

Dietary control

Oral hypoglycemic agents

Insulin therapy

Agents for use in combination with insulin

Monitoring

Laboratory monitoring

Home monitoring by owner

Subsequent Management

Treatment

Outcomes

Prognosis

Expected Response to Treatment

Reasons for Treatment Failure

Further Reading

Publications

Refereed papers

Other Sources of Information