Diabetes Update: Living Life after Lente Stacey B. Hoffman, DACVIM November 4, 2010

ProZinc Insulin (Boehringer) Protamine zinc insulin (PZI), human recombinant product (4 aa difference) Replaces PZI Vet (Idexx), beef/pork source insulin no longer manufactured Pilot studies suggest that both products have similar potency, onset & duration of action (PZI onset 1-4 hrs, duration 9-10 hrs)

Treatment of diabetic cats with ProZinc, Norsworthy et al (Vet Therapeutics 10(1-2): Spring-Summer 2009 50 diabetic cats, on PZI Vet > 90 days No change in diet or insulin dose, converted to ProZinc at PZI Vet dose 47 cats completed study, 38/47 did not have any change in dose over 30 days Evaluated weight, fructosamine, clinical signs @ 15 days (dose change < 2 units)

Long-acting insulin analogues Synthetic human products: detemir (Levemir®) , glargine (Lantus®) “Peakless” in humans, continuous basal insulin concentrations Glargine: very efficacious in cats, unpredictable serum levels in dogs

Use of insulin detemir in dogs, Ford et al (ACVIM Forum 2010) Prospective study 13 dogs Most (10/13) previously txd with NPH or Vetsulin- poor response All dogs monitored with home blood glucose monitoring

Use of detemir in dogs Initial dose: 0.1-0.2 U/kg BID (thought to be about 4x more potent than prev. insulins) Improved glycemic control all dogs Biochemical hypoglycemia more common small dogs Not a first choice (particularly small dogs) but could be option for refractory cases

Use of insulin glargine in DKA cats I.V. glargine lowers blood glucose like regular insulin (humans) Adding SQ glargine to CRI regular insulin lead to faster resolution DKA in kids (1 study) Two recent studies using glargine DKA cats

Glargine administered IM effective for tx feline DKA (Marshall, et al ACVIM 2010) Retrospective 15 cats, substituted IM glargine for IM regular insulin 1-2 U glargine IM +/- 1-3 U glargine SQ Continue SQ glargine q. 12 hours, additional IM doses 2-22 hours later until glucose 180-250 mg/dl

IM glargine DKA cats All cats survived to discharge (historical survival rate ~ 80%) after 2-5 days hosp. Half of cats that received both IM and SQ glargine (6/12) able to be managed SQ insulin only after 18 hours

Intermittent insulin protocol improves acidosis faster than CRI (Buob et al, ACVIM 2010) 16 ketoacidotic cats: 8 CRI regular insulin sliding scale, 8 SQ glargine + intermittent regular insulin IM Intermittent protocol: 0.25 U/kg glargine SQ BID plus 1 U regular insulin IM up to q. 8 hours Primary endpoint: time to resolution acidosis

Intermittent insulin protocol vs. CRI DKA cats No differences between groups at baseline 11/16 cats survived to discharge (6/8 CRI cats, 5/8 intermittent cats) Time to resolution of metabolic acidosis: 16 hours (intermittent) vs. 38 hours (CRI)

Modified feline DKA protocol using insulin glargine All cats receive SQ glargine 0.25 U/kg BID (small cat= 1U, larger cat= 2U) Supplemental 1-2 unit IM glargine injections q. 8 hours (monitor BG) Less technical monitoring, can use 1 bottle insulin Resolution of ketoacidosis not resolution of illness!

Continuous glucose monitoring in ketoacidotic diabetics Glucose of interstitial fluid mimics blood glucose concentrations several species DKA patients often have rapid changes in blood glucose (compromised homeostasis, therapeutics) Continuous interstitial glucose monitoring systems (CGMS) allow semicontinuous estimates of BG concentration

Continuous blood glucose monitoring Interstitial fluid equilibrates 10-12 minutes following glucose bolus Correlates well with blood glucose (dog, cat) Record data q. 5 minutes (288 times/day)

Accuracy of CGMS in DKA patients Reineke et al (JVECC 20(3): 2010) 23 patients, prospective study (13 dogs, 11 cats) Data collected min. 3 days (8 days max) Monitor calibrated q.8-12 hours with portable BG monitor Interpatient variability, but no difference in accuracy between dogs and cats

Accuracy of CGMS in DKA Good correlation between CGMS measurements and lab BG measurements (r=0.86) Based on error grid measurements, 97-99% of readings clinically acceptable (no change in treatment recommendation) Not real-time monitoring

Real-time Continuous Glucose Monitoring in Cats (JVIM 2010: 24: 120-126) Guardian REAL-Time system, provides instantaneous interstitial glucose conc. Initial report: used in one diabetic cat, identified hypoglycemia due to insulin overdose Studied 32 diabetics, 2 insulinoma suspects, 5 healthy cats

Continuous glucose monitoring cats Clinically accurate in euglycemic and hyperglycemic cats (less in hypoglycemia) Delay after IV glucose administration to increased interstitial glucose= 11 min. Advantages: real time info, patient doesn’t have to wear monitor (just sensor/transmitter)

Uses of Guardian REAL-Time CGMS Inpatient monitoring: ketoacidosis, hypoglycemia Outpatient monitoring: continuous blood glucose curves Advantages: reduces stress, collects information up to 3 days Disadvantages: glucose range 40-400 mg/dL, needs calibration 2x/day

Any questions?