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!