Internal Medicine Service Puget Sound Veterinary Referral Center Diabetes Mellitus Brad Green Internal Medicine Service Puget Sound Veterinary Referral Center

CGMS experience CGMS = continuous glucose monitoring system Measures interstitial glucose every 5 minutes for 72+ hours There was little correlation between days. Even consecutive days at home. At the end of this talk, I will come back to these and how they can be useful.

Value of blood glucose curve So if measuring glucose every 5 minutes for 72 hours wasn’t helpful, how helpful is measuring glucose every hour for 12 hours? Still the best practical tool that we have. Most helpful to ensure that hypoglycemia is not occurring. Therefore, it is necessary to check BGs q 1 hours when doing BG curve

Value of fructosamine A reflection of mean glucose Most helpful to determine how much time is spent in the range of hyperglycemia. Remember Somogyi but also remember it is rare

Clinical signs are very important Weight gain suggests good control Weight loss suggests poor control PU/PD suggests poor control or concurrent disease Resolution of PU/PD is highly supportive of good control (or an inobservant owner)

At-home blood glucose curves Valuable when done correctly Seldom done correctly Nearly always leads to owner and veterinarian frustration Often results in worse control of diabetes Can be difficult to get owners to pay for your interpretation and recommendations Which results in self directed dosing changes

Urine glucose testing Somewhat useful Can be done at home Should not be over-interpreted; should not be used alone to adjust insulin dosing Negative urine glucose can mean ideal control but it can also mean that insulin dose is too high and patient is experiencing hypoglycemia Affected by renal tubular flow

Owner education - cats Often owners of newly diabetic cats will say, I could give an injection once daily but not twice daily. This is an opportunity to explain that good diabetic control up front – which requires BID insulin – may result in not having to use any insulin long-term. Many owners will realize twice daily injections aren’t so bad Glargine is not an SID insulin Diabetic cats should be fed a high-fat, high-protein, low-carbohydrate diet. Purina DM, Prescription Diet M/d Kitten food is an alternative if a prescription diet is cost-prohibitive.

Owner education – dogs 70% of diabetic dogs will develop cataracts within 1 year. To prevent cataracts and to slow their progression, tight glycemic control is the goal. Other complications are uncommon Once cataracts have developed and have been surgically removed, control does not need to be quite as stringent

Owner education Glucose control for owners who are nurses (or similarly intense) We are not going to have your pet’s glucose perfectly controlled. We will have it adequately controlled to prevent most complications except cataracts. I have only seen one dog with perfectly controlled diabetes. The owner was a nurse for diabetic people and managed her dog as she would her patients: She gave lente insulin BID then gave a sliding-scale dose of regular insulin based on BG levels with meals. This owner was exceptional. I do not recommend this. Continuous glucose monitoring glucose devices and insulin pumps would likely work well.

Owner education - Insulin dosing Insulin doses are determined by body weight, glucose levels, fructosamine levels, and clinical signs. Glucose levels (and hence insulin doses) are affected by many factors: steroids (endogenous or exogenous), epinephrine, glucagon, insulin Insulin dosing will change over time It may even occur that at some point, we need to start over

Poco 10 year old, male neutered, Siamese cat Presents for PU/PD of 2 to 3 weeks duration Chemistry panel: BG = 302; mild elevations of ALT and alk phos. UA: 2+ glucosuria; no ketones

Poco – uncomplicated feline diabetic Insulin options: Glargine or ProZinc Glargine starting dose: Usually 1 unit BID but may start lower on cats < 4 kg May start higher on very large or very hyperglycemic cats U-100 syringes

Poco – uncomplicated feline diabetic Insulin options: Glargine or ProZinc ProZinc starting dose: 0.25+ units/kg BID This insulin and the above dose are intended to be administered via U-40 syringes. However, I find that dosing adjustments are easier with U-100 syringes since the units are smaller. 1 unit with U-40 equals 2.5 units with U-100 . For a 4 kg cat, I will write instructions as give 3 units with a U-100 syringe (or 1 unit with a U-40) every 12 hours.

Poco – uncomplicated feline diabetic DIET IS VERY IMPORTANT IN CATS High fat High protein Low carbohydrates Purina DM, Prescription Diet M/d, etc. Kitten food is an alternative when cost prohibits use of prescription diet.

Poco – uncomplicated feline diabetic REEVALUATIONS It is important to remember and to educate owners that many diabetic cats can be returned to the non-insulin dependent state. This seems to be more likely if treatment is aggressive early. There is a theory that prolonged hyperglycemia is toxic to the beta cells.

Poco – uncomplicated feline diabetic REEVALUATIONS Start with single blood glucose 6 to 8 hours after insulin administration. BG curves would be ideal but be careful to AVOID OWNER FATIGUE Recheck weekly. Slowly increase dose until BG < 225. If BG > 225, it is almost always safe to increase insulin. Remember Somogyi but also remember it is rare Once BG < 200-225, do BG curve and fructosamine 7 days later

Poco – uncomplicated feline diabetic Day 1: Glargine insulin and diet started Day 7: BG = 242. Glargine increased to 2 units BID Day 14: BG = 176. Continue 2 units. Day 21: BG curve

Poco – uncomplicated feline diabetic

Poco – uncomplicated feline diabetic Possible interpretations: Diabetes is fairly well controlled but not ideally controlled Diabetes no longer requires insulin

Poco – uncomplicated feline diabetic Fructosamine in fair range Diabetes is fairly well controlled but not ideally controlled Increase insulin (to 2.5 units) Fructosamine is in very good range Diabetes probably no longer requires insulin There is some response to insulin but the high points may be attributable to stress Decrease insulin (to 1 unit BID) and repeat curve in a week. *usually I don’t do curves more often than every 10 to 14 days but I am more aggressive here to ensure that this newly diagnosed diabetic does not relapse.

Sam – uncomplicated feline diabetic 7.5 kg MN 8 y.o. tabby cat Day 1: Glargine insulin and diet started Day 7: BG = 242. Glargine increased to 2 units BID Day 14: BG = 230. Glargine increased to 3 units BID. Day 21: BG = 116. Glargine increased to 4 units BID. Day 28: BG curve

Sam – uncomplicated feline diabetic Fructosamine at border of fair and good ranges.

Sam – uncomplicated feline diabetic Interpretation: Diabetes is fairly well controlled but not ideally controlled Control of diabetes can not be improved with this insulin Changing dose does little to change shape of curve Options: Leave well enough alone Use a different insulin

Sam – uncomplicated feline diabetic Different insulin options: Switch from glargine to PZI (or vice-versa) Combine a shorter acting insulin with the longer acting insulin Decrease glargine dose, add regular insulin This is similar to how diabetes is managed in people

Sam – uncomplicated feline diabetic 3 units glargine + 1 unit regular insulin (separate syringes)

Sam – uncomplicated feline diabetic 3 units glargine + 2 units regular insulin (separate syringes)

Sam – uncomplicated feline diabetic All of these curves look fine. The mean BG is best with 3 units glargine + 2 units regular insulin. This curve is also “safer” since the nadir is not as low. IS IT WORTH GIVING 2 INJECTIONS? Depends on the owner

Mandy – 6 year old golden retriever Similar curves can be seen in dogs and a similar approach can be taken. However, in dogs it is a little easier in that it does not necessarily require two injections. There is a proprietary formulation that is 70% NPH and 30% regular insulin (Novolin 70/30). There used to be a Lente 70/30 that went off the market with Lente. I do not know if Vetsulin (a Lente insulin) and regular insulin can be mixed.

Fritz – 7 year old min schnauzer Presents for SEVERE PU/PD of several weeks duration. Good appetite. No vomiting. PE: seemingly hydrated, no significant findings CBC: stress leukogram UA: 4+ glucose, 3+ ketones Chem: alk phos=342; Na=132; K=5.2; P=4.4; bicarb=11 To hospitalize or not to hospitalize???

Fritz – 7 year old min schnauzer I do not hospitalize healthy ketotics but this is admittedly debatable. I would guess that it is 50:50 amongst internists to hospitalize or not. Subcutaneus fluids: 0.9% NaCl with 20 mEq Kphos per liter; 50-60 ml/kg Start long-acting insulin: 0.5 units/kg NPH or Vetsulin BID Call the next day to hear the owners tell you how great Fritz is doing. Recheck in 1 week as described for Poco.

Vetsulin – my perspective This is a good product BUT it is poorly labeled. The manufacturer chose to have it labeled for once daily usage with a starting dose of 1 unit/kg. This is not appropriate. Even in the study that was used for FDA approval, there were unexplained deaths. Vetsulin is a BID insulin. When I have started it at 0.4 units/kg BID, I have had no problems and have found it to work well.

Glargine in dogs, PZI in dogs Several years ago, I tried glargine in a dog It didn’t work PZI label says that it is not for use in dogs but it doesn’t state that it doesn’t work.

Sage – 11 year old FS cocker spaniel Hospitalized for last 3 days for diabetic ketoacidosis. Not previously known to be a diabetic No concurrent disease. Urine culture negative Always do urine culture on new diabetics Now eating and drinking What is our immediate goal for this patient? What treatments are appropriate to accomplish that goal?

Sage – 11 year old FS cocker spaniel What is our immediate goal for this patient now that she is eating and drinking? Get her home Medicate her in such a way that she will be stable at home It is not a reasonable or appropriate goal to send the patient home with the expectation that the diabetes will be controlled.

Sage – 11 year old FS cocker spaniel What treatments are appropriate to accomplish that goal? Sage is no longer a sick ketoacidotic patient. At worst, she is a healthy ketotic like Fritz. She can be treated like a new diabetic that has not been hospitalized for treatment of ketosis Long-acting insulin: NPH or Vetsulin 0.4 to 0.5 units/kg BID +/- subcutaneous fluids

Sage – 11 year old FS cocker spaniel What monitoring is appropriate to accomplish that goal? It is ok to continue to check BGs but it must be remembered: The purpose should be to ensure that hypoglycemia is occurring so check at the expected nadir Hypoglycemia is unlikely at this dose particularly when there is up-regulation of epinephrine and cortisol The diabetes will not be controlled at discharge That’s ok. Most importantly, 0.5 units/kg will prevent ketosis is 99% of patients.

Future directions Continuous glucose monitors Insulin pumps Islet cell transplant

Any questions???