Feline diabetes is one of the most common. diseases we manage Diabetes inhibits normal immune response. therefore, there may not be WBCs in urine …
Update on Management of Feline Diabetes Mellitus
Karin Wagner, DVM, DACVIM Capital Area Veterinary Emergency Service Continuing Education Seminar June 20, 2007
Update on Management of Feline Diabetes
Review of pathophys of type II diabetes Initial clinical evaluation Therapy
Insulin options PZI, glargine Diet Oral hypoglycemics
Update on Management of Feline Diabetes
Monitoring therapy
Glargine vs other insulins
Trouble shooting problem diabetics
Feline Diabetes in 2007
The Bad News:
Feline diabetes is one of the most common diseases we manage And, it is likely becoming more common
The Good News:
New tools available to treat and prevent diabetes Diabetic remission is a realistic goal
? Pathophysiology ?
Type II Diabetes characterized by:
Primary insulin resistance Decreased insulin production by ß -cells Gradual loss of ß -cells amyloid
Feline Diabetes Mellitus
Compared to Type I Diabetes dogs:
Primary loss of ß -cells immune-mediated? Permanent lack of insulin production
? Pathophysiology ?
Where does insulin resistance come from?
Obesity Decreased activity indoor cats Diet fats and carbohydrates Disease via counter-regulatory hormones Drugs steroids Genetic
predisposition?
Feline Diabetes Mellitus
Pathogenesis of Type 2 Diabetes
insulin resistance ? blood glucose ? insulin amylin production glucose toxicity
amyloid deposition
ß -cell destruction
? insulin production
Diabetes Mellitus
Type I dogs vs Type II cats:
When most dogs initially become diabetic, no functional ß -cells remain and they are insulin dependent forever When most cats initially become diabetic, they have dysfunctional ß -cells that can produce insulin again with appropriate and early intervention
Feline Diabetes Mellitus
Clinical Signs
Weight loss Polyuria, polydipsia Polyphagia Poor coat condition Plantigrade stance Constipation 2 to dehydration Sick, dehydrated, ketotic
Feline Diabetes Mellitus
Diagnosis
Hyperglycemia Glucosuria when BG 290mg/dL Ketonuria Consistent clinical signs
differentiate stress from true hyperglycemia
Elevated fructosamine can help
Feline Diabetes Mellitus
Diagnosis
Hyperglycemic, glucosuric cat is diabetic until proven otherwise If diagnosis is not clear, it is arguably safer to start insulin therapy and monitor closely Stress hyperglycemia can be 290 mg/dL
and cause glucosuria but usually isnt
Feline Diabetes
Mellitus
Initial Evaluation
CBC, chemistry, UA, T4 Urine culture even with inactive sediment
Dilute urine less likely to see bacteria Diabetes inhibits normal immune response therefore, there may not be WBCs in urine
Concurrent diseases common
Look for cause of insulin resistance
Feline Diabetes Mellitus
Owner Education
Knowledge is power
Several very helpful websites for owners My favorite is wwwpetdiabetesorg Another good one is Cornell Feline Health Center video of giving insulin injections
For owners of new diabetic cats, possibility of achieving diabetic remission improves willingness to treat
Treatment Guidelines
Secrets of success:
Early control of hyperglycemia reduces glucose toxicity and allows ß -cells to recover The sooner you start therapy, the more likely they are to achieve diabetic remission Identify and treat concurrent diseases if possible
Feline Diabetes Mellitus
Treatment Considerations
Insulin therapy most effective way to control hyperglycemia, avoid ketoacidosis Diet combined with other therapies, improves glycemic control, weight loss Oral hypoglycemic drugs
Feline Diabetes Mellitus
Feline Diabetes Mellitus
Insulin Therapy
Insulin
products currently available:
NPH intermediate-acting, twice daily administration Vetsulin pork lente insulin intermediateacting, twice daily admin PZI protamine zinc longer acting, once or twice daily administration Glargine Lantus insulin analogue, longer acting, once or twice daily
Feline Diabetes Mellitus
Insulin Profiles
Rand, Marshall 2004 ACVIM Proceedings
Feline Diabetes Mellitus
Insulin Therapy
Cats have long post-prandial hyperglycemia Intermediate-acting insulins lente, NPH have short duration of action Longer-acting insulins more appropriate for cats PZI, glargine Research on glargine started in Australia shortly after approved for people 2001
Feline Diabetes Mellitus
PZI
Longer acting insulin 10-14 hr duration
SID vs BID administration
Produced as feline product now Available through Blue Ridge Pharmaceuticals More reliable product now U-40 syringes
Feline Diabetes Mellitus
Glargine Insulin
Synthetic insulin designed to control basal glucose levels in human diabetics
No peak effect in humans Shorter-acting insulins used with meals
Unique feature: acidic pH causes it to precipitate in SQ tissue for very gradual absorption
Cannot be diluted or
mixed
Feline Diabetes Mellitus
Glargine Insulin
Available at human pharmacies Approximately 80 for 10 mL vial
Similar to PZI and Vetsulin
Lasts 4-6 months if refrigerated Use U-100 syringes Duration of action: 16-23hrs
Glargine in Diabetic Cats
Initial study results: Glargine given twice daily, 100 diabetic remission in newly diagnosed diabetic cats Combined with low carb diet All able to discontinue insulin within 4 months
Feline Diabetes Mellitus
Glargine in Diabetic Cats
Glargine compared with lente Vetsulin and PZI in newly diagnosed diabetic cats:
Only 3/8 and 2/8 of PZI and lente cats went into remission during study SID glargine similar to BID lente
Feline Diabetes Mellitus
Glargine in Diabetic Cats
Remission likely results from:
Relative lack of peaks and troughs in glucose curves Overall better glycemic control Reversal of glucose toxicity in ß -cells
Feline Diabetes Mellitus
Indications for Using Glargine
All newly diagnosed diabetic cats Poorly controlled diabetic cats Treatment of diabetic ketoacidosis only in combination with regular insulin If SID dosing required
Feline Diabetes Mellitus
Starting Glargine Insulin
Glargine use guidelines on VIN FAQs
included in
your handout
Feline Diabetes Mellitus
Initial dose based on pre-insulin BG and ideal body weight 025-05 U/kg BID dosing recommended Glucose curves recommended earlier after starting insulin
Spot check BG in 1st 3 days Risk of hypoglycemia
Monitoring Glargine Therapy
Initial BG check within 1st 3 days only change dose if hypoglycemic Full 8-12 hr curve in 7-10 days Measure BGs q 2-4 hrs flatter curve Dose adjustments based on pre-insulin BG, nadir BG and clinical signs
Body weight, water consumption, urine glucose
Feline Diabetes Mellitus
Monitoring Glargine Therapy
Typical maintenance glargine dose is 2 units/cat BID Some cats will require much higher doses they are just as likely to go into remission, so monitor closely for hypoglycemia
Feline Diabetes Mellitus
Monitoring Glargine Therapy
BG curves q 1-2 weeks initially due to likelihood of diabetic remission and lower required doses Tapering insulin dose, rather than just discontinuing, more effective Monitoring for remission at home urine glucose
Feline Diabetes Mellitus
Monitoring Glargine Therapy
Once cat is in remission no clinical signs, no
glucosuria, pre-insulin BG 200 Withhold insulin Monitor for
recurrence of clinical signs, hyperglycemia Continue diabetic diet if appropriate Careful with steroids, weight gain, illness
Feline Diabetes Mellitus
Monitoring Insulin Therapy
Glucose curves critical to evaluation of all insulin therapy
Establish nadir and duration of action BG at nadir w 
ill determine dosage changes Spot checks: time of nadir can vary by a few hours so best to check BG over 2-4 hour period around nadir
Feline Diabetes Mellitus
Monitoring Insulin Therapy
That being said
In-hospital BG measurements can be falsely elevated due to stress, daily variation Clinical signs, physical exam findings also extremely important in evaluating therapy Educate owners to monitor PU/PD, appetite, energy level /- urine glucose and keep diary
Feline Diabetes Mellitus
Monitoring Therapy
At each visit: record owners observations, keep track of body weight, gait, hydration Develop checklist of questions to ask every time Clinical signs trump BG curve results they reflect trends
Feline Diabetes Mellitus
Monitoring Therapy
Goals of therapy:
Resolution of symptoms PU/PD, wt loss, etc Avoid hypoglycemia Owner satisfaction Blood glucose levels ideally 100-300mg/dL Ultimately
diabetic remission
Feline Diabetes Mellitus
Monitoring Therapy
Long term monitoring:
Recommend office visits q 4-6 months BG curve or spot checks, but focus on clinical signs, physical exam Monitor for other diseases UTIs, renal disease, hyperthyroidism, etc
Feline Diabetes Mellitus
Monitoring Insulin Therapy
What about at-home glucose curves?
Relatively easy with newer glucometers Have not been shown to be more accurate Can lead to confusion and micromanagement by owners and many extra phone calls May be best saved for fractious cats
Feline Diabetes Mellitus
Monitoring Insulin Therapy
What about the new Abbott Veterinary glucometer?
So far only manufacturers info available Calibrated for cats and dogs
Feline Diabetes Mellitus
Monitoring Insulin Therapy
What about fructosamine levels?
Can be misleading because high fructosamine may result from too much insulin or too little insulin Somogyi effect insulin overdose produces periods of hyperglycemia ? fructosamine Results must be combined with owners observations, physical exam findings, etc
Feline Diabetes Mellitus
Feline Diabetes Mellitus
Diet
Historically, high fiber, low fat diets were recommended to slow glucose
uptake, reduce body weight High protein, low carbohydrate diets recently shown to be more effective in diabetic cats
Prescriptions diets Growth diets
Feline Diabetes Mellitus
Diet
Combined with insulin therapy, high protein, low carb diets increased rate of remission Likely to maintain remission, and possibly prevent clinical diabetes in predisposed cats Diet change alone will not treat diabetes
Feline Diabetes Mellitus
Diet
Common sense alert: make sure cat will eat new food Ad lib feeding schedule is A-OK Weight reduction should be encouraged in obese cats
Oral Hypoglycemic Therapy
Various medications developed for human type II DM:
Glipizide sulfonylurea Troglitazone Rezulin Metformin biquanide Vanadium/chromium
Feline Diabetes Mellitus
Limited efficacy in diabetic cats
Oral Hypoglycemic Therapy
Methods of action:
Stimulate insulin release glipizide Increase tissue insulin sensitivity metformin, Rezulin, /chromium/vanadium Decrease hepatic glucose output metformin
Feline Diabetes Mellitus
More likely to work early in disease or in pre-diabetic stage
Oral Hypoglycemic Therapy
Pros:
Gives owners alternative to injections, euthanasia
Feline Diabetes
Mellitus
Cons:
Pilling a cat just isnt that much fun Can delay glycemic control and decrease chance of diabetic remission May increase ß -cell damage Side effects hepatic toxicity, GI signs
Glipizide Treatment Protocol
per Feldman and Nelson
Start at 25 mg/cat PO q 12h with food Recheck weekly for at least first month After 2 weeks, can increase to 5 mg/cat q 12h if still hyperglycemic, no side effects If icteric or ? LEs, d/c drug until resolved, and can then restart at lower dose If cat becomes ketotic or sick, d/c and start insulin therapy
Problem Diabetics
Definition: cats who dont do what the textbooks say they should all diabetic cats
Erratic control Increasing insulin requirements
Feline Diabetes Mellitus
Diabetic cats are puzzles to treat because:
Insulin production/sensitivity are unpredictable Counter-regulatory hormones galore stress Multifactorial nature of type II diabetes
Problem Diabetics
Try to avoid or minimize problems in diabetic control:
Thorough initial clinical evaluation Good diabetes education for owner Choose longer acting insulin to start Choose high protein, low carb diet Close monitoring and careful reevaluation with each dose change
Feline
Diabetes Mellitus
Problem Diabetics
If you run into problems anyway:
Go back to basics Review treatment and clinical history, owners treatment techniques, diet, etc Perform complete glucose curve, consider 24 hr curve nocturnal hypoglycemia Somogyi effect reactive hyperglycemia can look like insulin resistance dont be fooled
Feline Diabetes Mellitus
Problem Diabetics
Feline Diabetes Mellitus
Reactive hyperglycemia can last 24 hours
Problem Diabetics
If cat requires excessive insulin doses: 15-2 u/kg BID
Consider reactive hyperglycemia, reduce dose and monitor curve Try new bottle of insulin lower dose, consider administration errors Switch to a longer acting insulin PZI, glargine Look again for concurrent diseases
Feline Diabetes Mellitus
Problem Diabetics
Common concurrent diseases:
Hyperthyroidism - increases insulin metabolism and requirements, symptoms similar to DM Urinary tract and oral infections predisposition to infection Pancreatitis - 50 of diabetic cats subclinical dz fPLI, ultrasound
Feline Diabetes Mellitus
Problem Diabetics
More common concurrent diseases:
Inflammatory bowel disease Neoplasia Renal disease Obesity
Feline Diabetes Mellitus
Any source
of inflammation or stress can lead to insulin resistance
Problem Diabetics
Less common concurrent diseases
Hyperadrenocorticism ? cortisol Acromegaly ? growth hormone Excessive hormones counteract effects of insulin
Feline Diabetes Mellitus
Diagnostic evaluation: CBC, chemistry, UA, urine culture, T4, ultrasound, rads
Problem Diabetics
Iatrogenic insulin resistance
Steroid therapy Asthma IBD Skin allergies If steroids cannot be avoided, minimize dose, consider local steroids inhalant, GI, topical
Feline Diabetes Mellitus
Problem Diabetics
Ellie 4 year old FS DSH
Thin body condition, never obese Initial presentation: congestive heart failure HCM Lasix therapy Hyperglycemia was secondary finding Inconsistent insulin therapy, continued weight loss, PU/PD, dehydration heart meds?
Feline Diabetes Mellitus
Problem Diabetics
Ellie 4 year old FS DSH
Persistent fever resistant to antibiotics eventually identified UTI Elevated fPLI chronic pancreatitis Required 6 units glargine BID 2 units/kg Tapered to lower dose when UTI, CHF controlled, but no remission
Feline Diabetes Mellitus
Feline Diabetes Mellitus Prevention?
An ounce of prevention is worth a pound of cure Prevent
causes of insulin resistance:
Campaign against feline obesity, inactivity Identify pre-diabetic cats Diet change in pre-diabetic cats Cautious, conscientious use of steroids Monitor for hyperglycemia
Feline Diabetes Mellitus Summary
Transient diabetes can be the rule rather than the exception in new diabetic cats
Preserve ß -cell function Treat early with most effective insulin Screen for concurrent diseases, causes of insulin resistance Consider diet, lifestyle changes Monitor thoroughly, watch for remission
Source:eyeupdate.com
