Diabetes Update: Living Life after Lente

Stacey B. Hoffman, DACVIMStacey B. Hoffman, DACVIM

November 4, 2010November 4, 2010

ProZinc Insulin (Boehringer)ProZinc Insulin (Boehringer)

Protamine zinc insulin (PZI), human Protamine zinc insulin (PZI), human recombinant product (4 aa difference)recombinant product (4 aa difference)

Replaces PZI Vet (Idexx), beef/pork Replaces PZI Vet (Idexx), beef/pork source insulin no longer manufacturedsource insulin no longer manufactured

Pilot studies suggest that both products Pilot studies suggest that both products have similar potency, onset & duration of have similar potency, onset & duration of action (PZI onset 1-4 hrs, duration 9-10 action (PZI onset 1-4 hrs, duration 9-10 hrs)hrs)

Treatment of diabetic cats with Treatment of diabetic cats with ProZinc, Norsworthy et al ProZinc, Norsworthy et al (Vet Therapeutics (Vet Therapeutics

10(1-2): Spring-Summer 200910(1-2): Spring-Summer 2009

50 diabetic cats, on PZI Vet > 90 days50 diabetic cats, on PZI Vet > 90 days No change in diet or insulin dose, No change in diet or insulin dose,

converted to ProZinc at PZI Vet doseconverted to ProZinc at PZI Vet dose 47 cats completed study, 38/47 did not 47 cats completed study, 38/47 did not

have any change in dose over 30 dayshave any change in dose over 30 days Evaluated weight, fructosamine, clinical Evaluated weight, fructosamine, clinical

signs @ 15 days (dose change < 2 units)signs @ 15 days (dose change < 2 units)

Long-acting insulin analoguesLong-acting insulin analogues

Synthetic human products: detemir Synthetic human products: detemir (Levemir(Levemir®) , glargine (Lantus®)®) , glargine (Lantus®)

““Peakless” in humans, continuous basal Peakless” in humans, continuous basal insulin concentrationsinsulin concentrations

Glargine: very efficacious in cats, Glargine: very efficacious in cats, unpredictable serum levels in dogsunpredictable serum levels in dogs

Use of insulin detemir in dogs, Use of insulin detemir in dogs, Ford et al Ford et al (ACVIM Forum 2010)(ACVIM Forum 2010)

Prospective study 13 dogsProspective study 13 dogs Most (10/13) previously txd with NPH or Most (10/13) previously txd with NPH or

Vetsulin- poor responseVetsulin- poor response All dogs monitored with home blood All dogs monitored with home blood

glucose monitoringglucose monitoring

Use of detemir in dogsUse of detemir in dogs

Initial dose: 0.1-0.2 U/kg BID (thought to Initial dose: 0.1-0.2 U/kg BID (thought to be about 4x more potent than prev. be about 4x more potent than prev. insulins)insulins)

Improved glycemic control all dogsImproved glycemic control all dogs Biochemical hypoglycemia more Biochemical hypoglycemia more

common small dogscommon small dogs Not a first choice (particularly small dogs) Not a first choice (particularly small dogs)

but could be option for refractory casesbut could be option for refractory cases

Use of insulin glargine in DKA catsUse of insulin glargine in DKA cats

I.V. glargine lowers blood glucose like I.V. glargine lowers blood glucose like regular insulin (humans)regular insulin (humans)

Adding SQ glargine to CRI regular insulin Adding SQ glargine to CRI regular insulin lead to faster resolution DKA in kids (1 lead to faster resolution DKA in kids (1 study)study)

Two recent studies using glargine DKA Two recent studies using glargine DKA catscats

Glargine administered IM effective Glargine administered IM effective for tx feline DKA for tx feline DKA (Marshall, et al ACVIM 2010)(Marshall, et al ACVIM 2010)

Retrospective 15 cats, substituted IM Retrospective 15 cats, substituted IM glargine for IM regular insulinglargine for IM regular insulin

1-2 U glargine IM +/- 1-3 U glargine SQ1-2 U glargine IM +/- 1-3 U glargine SQ Continue SQ glargine q. 12 hours, Continue SQ glargine q. 12 hours,

additional IM doses 2-22 hours later until additional IM doses 2-22 hours later until glucose 180-250 mg/dlglucose 180-250 mg/dl

IM glargine DKA catsIM glargine DKA cats

All cats survived to discharge (historical All cats survived to discharge (historical survival rate ~ 80%) after 2-5 days hosp.survival rate ~ 80%) after 2-5 days hosp.

Half of cats that received both IM and SQ Half of cats that received both IM and SQ glargine (6/12) able to be managed SQ glargine (6/12) able to be managed SQ insulin only after 18 hoursinsulin only after 18 hours

Intermittent insulin protocol Intermittent insulin protocol improves acidosis faster than CRI improves acidosis faster than CRI

(Buob et al, ACVIM 2010)(Buob et al, ACVIM 2010)

16 ketoacidotic cats: 8 CRI regular insulin 16 ketoacidotic cats: 8 CRI regular insulin sliding scale, 8 SQ glargine + intermittent sliding scale, 8 SQ glargine + intermittent regular insulin IMregular insulin IM

Intermittent protocol: 0.25 U/kg glargine Intermittent protocol: 0.25 U/kg glargine SQ BID plus 1 U regular insulin IM up to SQ BID plus 1 U regular insulin IM up to q. 8 hoursq. 8 hours

Primary endpoint: time to resolution Primary endpoint: time to resolution acidosisacidosis

Intermittent insulin protocol vs. Intermittent insulin protocol vs. CRICRI

DKA catsDKA cats

No differences between groups at No differences between groups at baselinebaseline

11/16 cats survived to discharge (6/8 CRI 11/16 cats survived to discharge (6/8 CRI cats, 5/8 intermittent cats)cats, 5/8 intermittent cats)

Time to resolution of metabolic acidosis:Time to resolution of metabolic acidosis:

16 hours (intermittent) vs. 38 hours 16 hours (intermittent) vs. 38 hours (CRI)(CRI)

Modified feline DKA protocol using Modified feline DKA protocol using insulin glargineinsulin glargine

All cats receive SQ glargine 0.25 U/kg All cats receive SQ glargine 0.25 U/kg BID (small cat= 1U, larger cat= 2U)BID (small cat= 1U, larger cat= 2U)

Supplemental 1-2 unit IM glargine Supplemental 1-2 unit IM glargine injections q. 8 hours (monitor BG)injections q. 8 hours (monitor BG)

Less technical monitoring, can use 1 Less technical monitoring, can use 1 bottle insulin bottle insulin

Resolution of ketoacidosis Resolution of ketoacidosis notnot resolution resolution of illness!of illness!

Continuous glucose monitoring in ketoacidotic diabetics

Glucose of interstitial fluid mimics blood Glucose of interstitial fluid mimics blood glucose concentrations several speciesglucose concentrations several species

DKA patients often have rapid changes in DKA patients often have rapid changes in blood glucose (compromised blood glucose (compromised homeostasis, therapeutics)homeostasis, therapeutics)

Continuous interstitial glucose monitoring Continuous interstitial glucose monitoring systems (CGMS) allow semicontinuous systems (CGMS) allow semicontinuous estimates of BG concentrationestimates of BG concentration

Continuous blood glucose Continuous blood glucose monitoringmonitoring

Interstitial fluid equilibrates 10-12 minutes Interstitial fluid equilibrates 10-12 minutes following glucose bolusfollowing glucose bolus

Correlates well with blood glucose (dog, Correlates well with blood glucose (dog, cat)cat)

Record data q. 5 minutes (288 times/day)Record data q. 5 minutes (288 times/day)

Accuracy of CGMS in DKA patientsAccuracy of CGMS in DKA patientsReineke et alReineke et al (JVECC 20(3): 2010)(JVECC 20(3): 2010)

23 patients, prospective study (13 dogs, 23 patients, prospective study (13 dogs, 11 cats)11 cats)

Data collected min. 3 days (8 days max)Data collected min. 3 days (8 days max) Monitor calibrated q.8-12 hours with Monitor calibrated q.8-12 hours with

portable BG monitor portable BG monitor Interpatient variability, but no difference Interpatient variability, but no difference

in accuracy between dogs and catsin accuracy between dogs and cats

Accuracy of CGMS in DKAAccuracy of CGMS in DKA

Good correlation between CGMS Good correlation between CGMS measurements and lab BG measurements and lab BG measurements (r=0.86)measurements (r=0.86)

Based on error grid measurements, 97-Based on error grid measurements, 97-99% of readings clinically acceptable (no 99% of readings clinically acceptable (no change in treatment recommendation)change in treatment recommendation)

Not real-time monitoringNot real-time monitoring

Real-time Continuous Glucose Real-time Continuous Glucose Monitoring in CatsMonitoring in Cats (JVIM 2010: 24: 120-126)(JVIM 2010: 24: 120-126)

Guardian REAL-Time system, provides Guardian REAL-Time system, provides instantaneous interstitial glucose conc.instantaneous interstitial glucose conc.

Initial report: used in one diabetic cat, Initial report: used in one diabetic cat, identified hypoglycemia due to insulin identified hypoglycemia due to insulin overdoseoverdose

Studied 32 diabetics, 2 insulinoma Studied 32 diabetics, 2 insulinoma suspects, 5 healthy catssuspects, 5 healthy cats

Continuous glucose monitoring Continuous glucose monitoring catscats

Clinically accurate in euglycemic and Clinically accurate in euglycemic and hyperglycemic cats (less in hyperglycemic cats (less in hypoglycemia)hypoglycemia)

Delay after IV glucose administration to Delay after IV glucose administration to increased interstitial glucose= 11 min.increased interstitial glucose= 11 min.

Advantages: real time info, patient Advantages: real time info, patient doesn’t have to wear monitor (just doesn’t have to wear monitor (just sensor/transmitter)sensor/transmitter)

Uses of Guardian REAL-Time CGMSUses of Guardian REAL-Time CGMS

Inpatient monitoring: ketoacidosis, Inpatient monitoring: ketoacidosis, hypoglycemiahypoglycemia

Outpatient monitoring: continuous blood Outpatient monitoring: continuous blood glucose curvesglucose curves

Advantages: reduces stress, collects Advantages: reduces stress, collects information up to 3 daysinformation up to 3 days

Disadvantages: glucose range 40-400 Disadvantages: glucose range 40-400 mg/dL, needs calibration 2x/daymg/dL, needs calibration 2x/day

Any questions?