DIABETES MELLITUS
Meg J McBrien, DVMDipl ACVIM, Internal
MedicineNortheast Veterinary
Referral Hospital
Management Management in Dogs & in Dogs &
CatsCats
What does it Mean???
• ‘To pass through’ + ‘honey-sweet’
Frequency• Dogs: 1:100 reaching 12 yrs will
develop DM
• Cats: 1:50-1:500
• Prevalence increasing over time: aging population, obesity, physical inactivity
Etiology: Dogs
• Risk factors: genetic, environmental, insulin antagonistic rx (GC’s and megestrol acetate), & diseases (e.g. pancreatitis)
• Immune-mediated destruction of islets occurs leading to B-islet cell dysfunction relative or absolute deficiency of insulin
Etiology: Dogs
• Progression is slow; likely >90% of islets are lost before DM occurs
• Is the most common disorder of the endocrine pancreas
Etiology: Cats
• Most Type II• Multifactorial:
– Obesity: 4 X more likely to develop DM – Pancreatitis– Genetics?– Drugs: GC’s, progestins– Amyloidosis of the pancreatic cells
Etiology: Cats
• Factors lead to impaired insulin action in liver, muscle and adipose tissue and –cell failure hyperglycemia
• If some –cell function exists, diabetes may be transient
Signalment
• Dogs: female : male 2-3:1– 7-9 yrs of age– Rare form of congenital lack of cells
• Cats: >95% >5 yrs of age– 70-80% male– Majority are overweight, few
underweight
Genetic Predisposition
• German Shepherd Dogs• Schnauzers• Beagles• Poodles• Golden retrievers & Keeshonds:
more prone to juvenile diabetes• Cats: Burmese??
PATHOPHYSIOLOGY
• Insulin deficiency– Decreased tissue utilization of glucose,
AA’s, fatty acids– Increased hepatic glycogenolysis and
gluconeogenesis– Renal tubular cells: ability to resorb
glucose is exceeded, leading to glucosuria
Clinical Signs
• pU/pD due to hyperglycemia and 2° osmotic diuresis
• Polyphagia and weight loss• Dehydration• Cataracts in dogs; rare (?) in cats
Clinical Signs: Cats
• Icterus common with DKA• Plantigrade stance ~10%
DIFFERENTIALS
• Hyperthyroidism• GI lymphoma• Hepatic disease• Renal disease• Pancreatitis• Hyperadrenocorticism
DIFFERENTIALS for Hyperglycemia
• Dextrose-containing fluids• Parenteral nutrition• Diestrus, pheochromocytoma (dogs)• Acromegaly (Cats)• Head trauma• Exocrine Pancreatic Neoplasia
DIAGNOSIS
• Fasting BG >200 mg/dl & glucosuria– Transient hyperglycemia?– Stress hyperglycemia?
• Fructosamine: supports sustained hyperglycemia
• Urine dipsticks for home use if stress hyperglycemia suspected
Hyperglycemia
• Cats: stress alone: up to 592 mg/dl• Fructosamine: usually >400 umol/L
– Caution: hypoproteinemia or hyperthyroidismlower fructosamine than healthy cats
Fructosamine
Normal (nondiabetic) reference ranges:• Canine: 260-378 μmol/L• Feline: 191-349 μmol/L
Interpretive guidelines for diabetic patients:• Fructosamine: Glycemic Control:• 300-350 Excellent• 350-400 Good• 400-450 Fair• >450 Poor• <250 Prolonged hypoglycemia
CLINICAL PATHOLOGY
• CBC: +/- normal, anemia, stress leukogram
• Profile: hyperglycemia, ALT/SAP, chol, bilirubin (cats)
• UA: proteinuria, pyuria
CLINICAL PATHOLOGY
• UA: renal threshold for glucose:– Dogs:180-220 mg/dl– Cats: 240-300 mg/ld– Culture!!: Up to 40% will have a UTI w/o
an active sediment
• Blood Pressure
TREATMENT(for the non-ketotic diabetic)
• Work to establish Euglycemia over time
• Insulin types:– Short acting (Regular)– Intermediate acting (NPH, Glargine, PZI,
ProZinc, Vetsulin, Detemir)– Long acting (Ultralente-no longer available)
NPH
• Dogs and cats• BID dosing needed
• DOGS: 0.25-0.5 units/kg BID• CATS: 1-3 units BID
Protamine Zinc InsulinProZinc
• Hu recombinant• U-40 concentration, app’d for cats• BID dosing most common• Start @ 1U/cat BID• Dogs: not rec’d d/t unpredictable
onset & duration of action
GLARGINE/LANTUS™
• Recombinant human insulin• “peakless” in humans
– Not in cats
Glargine
• Dose: – If BG >360 mg/dl: 0.5U/kg BID– If BG<360 0.25 U/kg BID
• Perform 12 hr BG curves for the 1st 3 days (q 4 hrs) ???
• Dose likely will need to be reduced• Do NOT increase dose in 1st week• Repeat curve @ 1, 2 and 4 weeks
Glargine adjustments
• Based on pre-insulin BG • If baseline >290- mg/dl, dose by 1U/cat
– Perform BG curve in the next WEEK to check for hypoglycemia
• If baseline 220-290: keep the same dose
Glargine adjustments
• If baseline BG<180, decrease dose by 0.5U
• If signs of hypoglycemia occur, dose by 1U/cat
• Repeat curve in 7 days
Glargine
• If BG curves not possible: – Start at 2 u/cat BID– Monitor urine glucose & water intake– If signs of hyperglycemia (> trace in
urine): increase by 1U/cat/week until urine glucose is neg or water intake is <20ml/kg/24 hrs (canned food)
– Or <70 ml/kg/24 hrs (dry food)
CANINSULIN
• Porcine Lente; app’d for dogs• U-40 concentration• Produces two peaks of activity• Cats: may produce anti-insulin ab’s
CANINSULIN
• 0.5 U/KG bid• Increase by 10-15% if hyperglycemia• Decrease by 25% if BG <70mg/dl
occurs
Detemir/Levemir®
• Used in Europe, now app’d in US• Each U contains 4x as much insulin
than others (maybe SID in dogs???)• Duration of action ~13.5 hrs
Lispro
• Combination of regular+int. acting• For postprandial tx in Hu• However, SQ regular insulin onset is
slow and duration of action in dogs/cats=~5 hrs
• Has been used to treat DKA (IV) in dogs
INSULIN RESISTANCE
• If receiving >2U/kg BID of insulin• Likely due to concurrent disease or
improper handling/administration– Watch owner give injection– Query regarding any other meds
Insulin Resistance
• CBC/CHEM/UA/Urine culture• Common Concurrent dz’s: Dogs
– Hypothyroidism– Hyperadrenocorticism– Chronic pancreatitis
• Cats: – Hyperthyroidism– Acromegaly – Cushing’s dz
ORAL HYPOGLYCEMIC AGENTS
• Sulfonylureas• Meglitinides• Biguanides• Thiazolidinediones• Alpha-Glucosidase inhibitors
Oral Hypoglycemic agents
• Only work if functional B cells are present
• Acarbose: delays absorption of glucose from SI, delays digestion of complex carbs thus decreasing PP hyperglycemia
• BUT: side effects=diarrhea and weight loss
DIET
• CATS: low carbohydrate, high protein, mod-hi fiber– DM (Purina)– M/D (Science Diet)– Diabetic ds 44 (Royal Canin/Waltham)– Kitten formulas: incr’d fatHL, pancreatitis
Diet
• DOGS: low fat, high fiber– Optimal Weight Control (Iams)– W/D (Science Diet )– Diabetic HF 18, Calorie Control (Royal
Canin)
Diet: Dogs
• Increase fiber– >12% slowly fermentable , insoluble
fiber or – >8% moderately fermentable fiber
EXERCISE
• To encourage weight loss• To decrease insulin resistance
induced by obesity
Supplements/Nutraceuticals
• Vanadium• Chromium
– Trace minerals thought to increase insulin sensitivity
MONITORING Urine glucose
Appropriate to check if suspecting:• Ketonuria• Persistent negative glucose• If cats may becoming diabetic again• Cats on oral rx: worse/better
glucosuria• Stress induced or transient vs.
persistent hyperglycemia
Monitoring
• Fructosamine
• Glycosylated Hemoglobin
When to check a fructosamine
No unexplained weight lossNo XS thirstNo waking owners to go outside at
nightNo polyphagiaNo weakness/disorientation
BG curves
• Blood glucose– Alphatrak – Human BG monitors– Constant BG monitors– www.sugarcats.net/sites/harry
• Curves: q 2 hours over 12 hrs minimum
GLUCOSE CURVES
• 1-2 wks after initiating insulin • Over 12 hrs• Keep on owner’s schedule• Ck 1st BG, watch owners give insulin
then ck BG q 2 hrs, or q 3-4 hrs for glargine
Poor control
Somogyi Effect
• Rebound hyperglycemia• Toy breeds• Effect can last for 1-3 days
Somogyi
Cycle of 1-2 days of good control then several days of poor control
dose by 1-5 u, watch clinical response
Diabetic Ketoacidosis
• Occurs d/t absolute or relative deficiency of insulin &
• Counter-regulatory hormone overproduction (cortisol, growth hormone)ketogenesis
• Signs: vomiting, weakness, dehydration
• Aggressive in-hospital care needed
Informational Websites
• www.cat-dog-diabetes.com• www.petdiabetes.com• Your friends@northeastvet!
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