Diabetes Mellitus

Question 1

What cells create insulin?

Side effects of no insulin

Answer 1

Beta cells in pancreas

• Glucose cannot enter cells
• Cell “starvation”
• Hyperglycemia

Question 2

Type I: Insulin dependent diabetes mellitus (IDDM) is due to what?

What % of dogs have this type? cats?

Answer 2

Beta cell destruction

• > Virtually ALL DOGS
• > 30-‐50% of cats

Question 3

Type II: Non‐insulin dependent diabetes mellitus (NIDDM)

Answer 3

Insulin resistance and/or beta cell dysfunction

• > 50‐70% of cats; Note: The term “non‐insulin dependent” is misleading
• We should instead be thinking of the pathophysiology
• Likely have some residual beta cell function
• Insulin resistance, impaired insulin secretion; - Keep in mind - most of these cats are treated with insulin

Question 4

Causes of DM

Answer 4

 Genetics  Immune-‐mediated;  Insulin-‐antagonizing drugs;  Progesterone, cortisol  Obesity;  Pancreatitis

Question 5

Dog DM Signalment

Answer 5

Dogs:;  4-‐14 years (7-‐9 y peak)  Female > male;  Breed predispositions;  Aust Terrier  Schnauzers  Beagles;  Samoyeds  Etc

Question 6

Cat DM Signalment

Answer 6

 Cats:;  Usually >9 y (peak 10 y)  Male neutered;  No breed predispositions (?)

Question 7

Common features of DM

Answer 7

 Common:  PU/PD;  Weight loss;  If diabetic ketoacidosis, can have history and PE reflecting systemic illness; - UTIs (50% of dogs);  May be obese or low body condition;  ± dull hair coat;  ± hepatomegaly;  ± cataracts (dogs);  ± plantigrade stance (cats)

Question 8

Other differentials for DM

Answer 8

 Cats  DM;  Hyperthyroidism  Renal insufficiency

 Dogs:  DM;  Hyperadrenocorticism  Renal insufficiency;

      Also consider:;  Urinary tract infections, hypercalcemia, liver disease, etc

Question 9

Initially document 3 things for diagnosing DM

Answer 9

1. Consistent clinical signs
2. Persistent fasting hyperglycaemia
3. Glucosuria

   When BG approx. \> 12 mmol/L in dogs

Question 10

Differentials for DM (Pathologic, Physiologic, Pharmacologic)

Answer 10

1. Pathological  Diabetes mellitus  Pancreatitis;  Hyperadrenocorticism
2. Physiological  Post-‐prandial ( < 2 hours)  Stress/excitement  Diestrus
3. Pharmacological/ toxicity

      Dextrose-‐containing IV fluids
   
      Steroids
   
      Progesterone

Question 11

Things to rule out with DM

Answer 11

 Rule out stress hyperglycemia especially in cats;  Document glucosuria and/or elevated fructosamine

Question 12

Goals of initial DM diagnosis

Answer 12

1. Identify persistent hyperglycemia & glycosuria
2. Diagnose DM
3. Identify any contributing causes of DM
4. Concurrent problems that make glucose regulation difficult
5. Complications that may be secondary to persistent hyperglycemia

Question 13

Recommended DM Diagnostics

Answer 13

• CBC
• Biochemical profile
• Urinalysis
• Urine culture & sensitivity
• ± Fructosamine level
• ± cPLI or fPLI (pancreatic lipase immunoreactivity)
• ± Abdominal ultrasound

Question 14

Common Clinicopathologic Findings for DM - CBC/Biochem

Answer 14

• CBC usually unremarkable
• Biochemistry profile
  
  • Hyperglycemia
  • incr ALP & ALT (especially in dogs)
    
    • Mild-moderate ( < 500 U/L)
    • Usually due to DM effects on liver (lipidosis, etc)
  • incr cholesterol, triglycerides

Question 15

Common Clinicopathologic Findings - Urinalysis

Answer 15

• Glucosuria (a.k.a. “glycosuria”)
• ± Ketonuria
• ± Proteinuria
• ± Bacteriuria, RBCs, WBCs
• UTI’s common
• May have unremarkable urine sediment, no clinical signs
• Urine culture / sensitivity recommended in all patients

Question 16

Goals of DM treatment

Answer 16

1. Minimize/eliminate clinical signs
2. Delay/prevent DM-associated complications
3. Prevent hypoglycemia secondary to treatment
   
   • Want to control [glucose] within/close to normal range
   • Address hyperglycemia
   • Insulin or oral hypoglycemic agents (cats only)
   • Diet
   • Consistent exercise
   • Control concurrent diseases that can lead to insulin resistance

Question 17

Intermediate acting therapy for DM

Answer 17

NPH; Caninsulin; (Vetsulin in USA - not currently available)

Question 18

Longer acting therapy for DM

Answer 18

Glargine; Protamine zinc insulin (PZI) - currently available in USA, approval pending in Canada

Question 19

Cats vs dogs in insulin response

Answer 19

 Cats usually require a longer-‐acting insulin than dogs;  And have a more unpredictable response

Question 20

Insulin Treatment; - Concentrations; - Amount of therapy (x times a day); Typical doses; Method of dose

Answer 20

Note different concentrations;  U‐40 (Caninsulin) versus U‐100 (most other insulins);  Require different syringes;  Most patients will require twice daily therapy;  Typical starting doses for most insulins:;  0.25-‐0.5 U/kg of lean body weight twice daily ;  SQ injection over truncal region;  Alternate sides each injection

Question 21

NPH

Answer 21

 Human recombinant product ;  U‐100 product (100 U per mL) ;  Typical duration of activity:;  2‐8 h in cats (may be too short);  Usually < 12 hours in dogs

Question 22

Caninsulin; Length of duration

Answer 22

 Veterinary‐approved product (cats & dogs);  Combination of a short & intermediate acting insulin ; - 30% amorphous zinc (short-‐acting); - 70% crystalline zinc (long-‐acting);  Porcine product;  U-40 insulin (40 units per mL);  Typical duration of action: ; - 2-‐10 hours in cats; - Close to 12 hours in dogs

Question 23

Protamine Zinc Insulin

Answer 23

 Long-‐acting insulin;  Recombinant human PZI;  Approved for cats in US, approval pending in Canada;  U-‐40 product (40 U per mL);  Compounded PZI (bovine) not recommended;  Typical duration of action: ; - 4-‐14 hours in cats; - >12 hours in dogs (maybe too long acting?)

Question 24

Glargine

Answer 24

 Long-‐acting insulin, U-‐100 product;  Recombinant human insulin product;  Forms a “depot” when injected SQ;  Gives a “peakless” insulin release in humans (flat-‐; line glucose curve)  Not in cats;  Typical duration of action  8-‐18 hours in cats;  >12 hours in dogs

Question 25

3 goals for dietary therapy

Answer 25

1. Correct obesity, maintain appropriate weight; 2. Minimize impact of meal on glucose fluctuations; 3. Two main meals coinciding with injections; - Ideal to offer snacks in between to promote more continuous glucose release rather than two large; spikes per day; - Some pets are grazers (ok)

Question 26

3 principles for dietary therapy in dogs

Answer 26

1. High fiber diets (soluble fibers); - Slow GI glucose absorption; - Contraindicated in thin dogs; - No proven benefit of high fiber diets for diabetic dogs; 2. In general, avoid highly digestible diets ; - E.g., low residue, Gastro (absorbed easily, spike); 3. Moderate fat restriction (fat \<30% ME) if: ; - Chronic pancreatitis; - Persistent hypertriglyceridemia

Question 27

Principles for dietary therapy in cats

Answer 27

(Cats are carnivores); 1. Carbohydrate-restricted diet preferred; 2. Canned diets have higher protein than kibble; 3. High protein / low carbohydrate diets;  Improve control of DM, improve rate of diabetic remission ;  Some canned over-‐the-‐counter diets that are low carb /high protein;  Preferred to have \<7% carbohydrate per dry matter basis

Question 28

Treatment considerations in dogs & cats

Answer 28

1. Control concurrent disease ;  Insulin resistance; 2. Avoid insulin-‐antagonizing drugs or states  Glucocorticoids;  OHE for intact females once stable; (progesterone);  Consistent exercise -\> Increases glucose delivery to cells, insulin mobilization; 3. If there are some functional pancreatic beta cells remaining:;  Alternatives to insulin therapy;  Potential for cats to have diabetic remission; 4. No reliable indicators of which diabetic cats have residual beta cell activity

Question 29

When can you use non-insulin treatment

Answer 29

 Diabetic cats with remaining beta cell; function may respond to medical therapy:;  Oral "hypoglycemic agent" plus high protein diet;  Very mild cases may respond to high protein diet change alone; -\> Selecting candidates: ;  Stable / no DKA;  Mild clinical signs;  Owner's desires;  Must have a concurrent diet change

Question 30

Glipizide, glyburide

Answer 30

 Stimulate insulin secretion from pancreas  Need some functional pancreas remaining

Question 31

Chances of remission in cats, depends on?

Answer 31

1. Cats with remaining beta cell function:;  Resolution of hyperglycemia may allow beta cells to recover function...; 2. Most common within first few weeks-months of treatment;  Depends on early, well regulated glucose control;  Few predictive factors for remission;  Higher remission rates in cats treated with insulin + high protein diet

Question 32

What do you do if remission is suspected?

Answer 32

 Gradual withdrawal of insulin;  Avoid rebound hyperglycemia that may induce; glucose toxicity of the recovering beta cells ;  Recommend high protein diet for life;  Some may never require treatment for DM again;  Others become insulin‐dependent within weeks to months

Question 33

Purpose of a Glucose Curve (w.r.t. DM)

Answer 33

Curves allow assessment of:;  Insulin efficacy;  Glucose nadir;  Peak insulin effect;  Duration of action;  Degree of fluctuation in BG; Used to evaluate a newly treated patient, recent dose change or if clinical signs are present

Question 34

Drawbacks to glucose curves (w.r.t. DM)

Answer 34

 Time‐consuming;  10-‐12 hour curve recommended;  Can be expensive;  Stress hyperglycemia (especially cats);  Natural day‐to‐day variation;  Poor repeatability, highly variable

Question 35

Tecnique to giving a Glucose Curve

Answer 35

1. Breakfast & insulin as usual; 2. To clinic ASAP (if monitoring at home, can start just before breakfast/insulin); 3. Blood samples taken every 1‐2 hours through day; 4. Until next insulin injection; 5. Usually 10‐12 hours in duration; 6. Occasionally a 24‐hour curve recommended

Question 36

Glucometer readings that are acceptable

Answer 36

- Usually underestimate BG by 10-‐15%; - Compared to reference laboratory; - Exception is AlphaTrak (veterinary glucometer - can slightly under or overestimate BG)

Question 37

Bottom part of the glucose curve where it is the lowest is called the

Answer 37

Nadir; (Ideal is 5-9 mmol/L)

Question 38

Desired Recheck Results (3 elements)

Answer 38

1. Resolution of clinical signs;  PU/PD, weight loss, etc; 2. Blood glucose curves;  Obtain glucose nadir 5-‐9 mmol/L;  Maintain BG \< 16 mmol/L throughout day;  \< 13 mmol/L feasible in many cases ; 3. Avoid hypoglycemia;  Hypoglycemia activates counter‐regulatory hormones that may cause a subsequent rapid spike in glucose levels;  "Somoygi" effects