Wendy Blount, DVM Practical Clinical Pathology - PowerPoint Presentation

1. Wendy Blount, DVMPractical Clinical PathologyUps and Downsof Blood Sugars

2. Attendee 1 – City TX

3. GlucoseDanger values - <40 g/dl; >1000 g/dlHyperglycemiaBrain dehydration due to hyperosmosisCNS signs (cerebral, brain stem) and seizuresDDx Hyperglycemia other than DM and stress (especially in prediabetics):Beta adrenergics (terbutaline, albuterol, etc.)Glaucoma treatments – acetazolamide, etc.Corticosteroids, levothyroxine, progestagens, estrogens(Thiazide diuretics, Diazoxide)Near death experienceTicked off Cat

4. GlucoseDanger values - <40 g/dl; >1000 g/dlHyperglycemiaBrain dehydration due to hyperosmosisCNS signs (cerebral, brain stem) and seizuresDDx Hyperglycemia other than DM and stress (especially in prediabetics):Beta adrenergics (terbutaline, albuterol, etc.)Glaucoma treatments – acetazolamide, etc.Corticosteroids, levothyroxine, progestagens, estrogens(Thiazide diuretics, Diazoxide)Near death experienceTicked off Cat

5. DM - Clinical PresentationMost dogs & cats >5 yearsHistoryPU-PD – bigger clumps in the litter boxweight loss, polyphagiaVomiting, illness of DKARecent administration of corticosteroidsHistory of triaditis, pancreatitisRecent heatVision problems (cataracts)Skin problems – infections, alopecia

6. DM - Clinical PresentationExamEndocrine alopecia, pyoderma, poor grooming in the catPot bellied – hepatomegalyCranial abdominal mass – pancreatitis + pain10% Diabetic neuropathy in the catPregnancy, vulvar discharge, coming out of heat, abdominal distensionCats are more likely to be overweight with recent weight lossDogs more likely to be underweight

7. Stress Hyperglycemia or DM?Stressed cats can have transient hyperglycemia (200-400)Critically ill non-diabetic dogs can have marked hyperglycemia (>400)Stress hyperglycemia due to glucocorticoids, epinephrine and insulin resistanceAcute hyperglycemia has adverse effects on the immune system, coagulation, heart and brainChronic hyperglycemia is toxic to beta cellsTreat with judicious insulin PRN – time will tellHyperglycemia due to DM can be intermittent at first

8. Stress Hyperglycemia or DM?“No glycosuria” makes untreated DM unlikelyStressed cats can have glycosuriaRenal threshold 180-220 mg/dl in the dog200-300 mg/dl in the catKetones in the urine indicate catabolism – investigate DKADKA = Diabetic ketoacidosisAny sick cat who has not eaten for days can have ketonuriaIf all else fails, run a fructosamineFructosamine elevated with DM >> a few other systemic diseasesDecreased with a number of systemic diseasesNormal with stress hyperglycemia

9. Fructosamineglycosylated serum proteinAverages blood glucose levels over the past 1-3 weeksNot affected by acute stress hyperglycemiaFalsely decreased by - pancreatitisHypoproteinemia, HemolysisHyperlipidemiaAzotemiaProlonged storage at room temperatureHyperthyroidism, thin body conditionFalsely increased by HyperglobulinemiaHypothyroidism In house – HESKA, Idexx, AbaxisOr send out (freeze until shipped)

10. Pattern Recognition - Diabetes MellitusCBC low HCT with normal Hb (hemolysis) if Phos <1.6Blood pressurepredisposition to hypertension

11. Pattern Recognition - Diabetes Mellitus3. Serum panelHyperglycemia (of course)Hypophosphatemia – especially if DKAHypokalemia – especially if DKAElevated liver enzymes and hepatomegaly - Almost all unregulated diabetics have bothSymptoms of DM and Cushing’s overlapEndocrine alopeciaPU-PDElevated liver enzymes with hepatomegalyCushing’s alone causes mild hyperglycemia that is not usually insulin dependentBegin diabetic regulation before Dx HAC, fine tune after Dx & Tx

12. Pattern Recognition - Diabetes Mellitus3. Serum panelCholesterol hightriglycerides highAzotemia if dehydratedAlbumin increased if dehydrated without pancreatitis

13. Pattern Recognition - Diabetes Mellitus4. UrinalysisLook for UTI – predisposed by glucosuria, dilute urine and immunosuppression25% of new diabetics have UTI >50% UTI if also CushingoidImmunosuppression may result in benign sediment & lack if symptomsDilute urine may make bacteriuria hard to detect on urine sedimentMany rec. either culture or empirical treatment for UTI for new diabeticsProteinuria – pancreatitis, HAC, UTI

14. Pattern Recognition - Diabetes Mellitus5. Thyroid testingTT4 and fT4 for all diabetic cats >5 yrs oldRetest cats if regulation difficultIf regulation difficult and other signs of hypothyroidism in the dog – TSH, TT4, fT4TT4 in euthyroid unregulated diabetics will often be lowGlucose >350-450 mg/dl means condition is potentially life threateningLook for CRF if glucose >800 mg/dl

15. Pattern Recognition - Diabetes MellitusIndications of DKAneed hospitalization and careful monitoring, higher level of K+ and phos supplementationMetabolic acidosis - Low HCO3, low TCO2, low blood pH, high anion gapKetosis - ketonuria, vomiting, lethargyPhos <1.5 can cause severe hemolysisK+ <2.5 can cause weakness and paralysis

16. Pattern Recognition - Diabetes MellitusPancreatitis patternneed fluid support, pain meds, antiemetics, maybe plasma if really badCBCThrombocytopenia – vasculitis, DICneutrophilia + left shift – pancreatic necrosis, fat necrosisAnemia – Anemia of Chronic Inflammatory Disease (ACID), hemolysis

17. Pattern Recognition - Diabetes MellitusPancreatitis patternPanel - lipemia while fasting (esp. the cat)Hypocalcemia – saponification of fatHypoalbuminemia – systemic inflammation, vasculitiselevated liver enzymes, icteruswhacked out glucoseHypophosphatemia – lack of insulin, renal loss, lack of intakeHypochloridemia – vomitingHypokalemia – lack of insulin, acidosis, vomiting, diarrhea, lack of intake

18. Pattern Recognition - Diabetes MellitusPancreatitis patterncPL, fPLcPL best test for pancreatitis in the dogUS best test for pancreatitis in the catAmylase is seldom helpful, and a weak indicatorLipase has very low sensitivity, but specificpancreatitis is the most common cause of hyperlipidemia in the catPancreatitis is on the short list of things that will cause icterus without anemia or elevated liver enzymes in the cat

19. Pattern Recognition - Diabetes MellitusFatty liver pattern – need nutritional support for cats (feeding tube?)Hx – heavy cat has not eaten in several daysExam - liver enlarged, + icterus, sickFatty liver with HE indicates poor prognosisPanel - ALKP significantly exceeds GGT only in feline hepatic lipidosis+ elevated biliElevated ALT is commonChanges associated with co-morbidities that may be initial causeAbd US diffusely hyperechoic liverCo-morbidities that may be initial causeFatty liver Often diagnosed on cytology

20. Pattern Recognition - Diabetes MellitusFatty liver pattern – need nutritional support for cats (feeding tube?)Hx – heavy cat has not eaten in several daysExam - liver enlarged, + icterus, sickFatty liver with HE indicates poor prognosisPanel - ALKP significantly exceeds GGT only in feline hepatic lipidosis+ elevated biliElevated ALT is commonChanges associated with co-morbidities that may be initial causeAbd US diffusely hyperechoic liverCo-morbidities that may be initial causeFatty liver Often diagnosed on cytology

21. K+ & Phos in DKA PatientInsulin carries K+ & Phos into the cellInsulin administration can make hypokalemia and hypophosphatemia worse – supplement firstWithout insulin, both get washed out the kidneys due to PU-PD90-95% of the body K+ is intracellularTotal body K+ can be depleted even if serum K+ is normalH+ is exchanged for K+  Correcting acidosis worsens K+

22. Continuous Glucose Monitoring (CGM) Systems (Flash)Probe measures glucose in interstitial fluid continuously to plot a curveWireless transmission to a pager size displayHuman device validated in dogs 2016Previous devices worn in a vestFreestyle Libre is disposableAvailable in the US as of Dec 2017Requires a prescriptionApproved for people – off label for pets

23. Continuous Glucose Monitoring (CGM) Systems (Flash)Shave fur over the dorsal neckClean with alcohol and let dryApply sticky disc this size of a quarter Secure with a light bandageStay on dogs pretty well – cats can be a problemApplying sport spray can help adhereDisk stores data for 8 hoursWave reader over the disk to read & save up to every 8 hrs, for 10 daysDisk $75-100, Reader $50

24. Continuous Glucose Monitoring (CGM) Systems (Flash)Dr. Greg Matt, Houston TX

25. Continuous Glucose Monitoring (CGM) Systems (Flash)Dr. Greg Matt, Houston TX

26. Continuous Glucose Monitoring (CGM) Systems (Flash)Dr. Greg Matt, Houston TX

27. Continuous Glucose Monitoring (CGM) Systems (Flash)Dr. Teleah Grand, McKinney TX

28. Attendee 2 – City TX

29. Monitoring DM – Fructosamine (FRA)Low (<200)Mild to moderate hypoglycemiaNot enough to cause Somogyi (glucose 65-80)Decrease insulin by 10-20%Normal range (200-350)Good diabetic control (350-450)High (>450 mcmol/L)>600 – danger zoneSignificant periods of hyperglycemiaNot enough insulin, or too much insulinHypoglycemia, rebound hyperglycemia (too much)Or sustained hyperglycemia (not enough insulin)

30. Monitoring DM - Fructosamine (FRA)Low FRA with poor glycemic control – check T4Remission is defined as normal FRA w/o insulinRegulation using FRA can work well when curves are not practicalBut keep in mind that FRA is ideal in only 60% of diabetic pets with good clinical regulation

31. Monitoring DM - Fructosamine (FRA)Low FRA with poor glycemic control – check T4Remission is defined as normal FRA w/o insulinRegulation using FRA can work well when curves are not practicalBut keep in mind that FRA is ideal in only 60% of diabetic pets with good clinical regulation Smut – 12 year old SF DLH Recently diagnosed as diabetic (8 wks) Diet – Innova EVO, Lantus 6 units SC BID She comes in for glucose curve weekly Each week, she loses weight All glucose checks >400 Owner says she does not feel good Considering euthanasia

32. Monitoring DM - Fructosamine (FRA)Low FRA with poor glycemic control – check T4Remission is defined as normal FRA w/o insulinRegulation using FRA can work well when curves are not practicalBut keep in mind that FRA is ideal in only 60% of diabetic pets with good clinical regulation Smut – 12 year old SF DLH Smut allows only 2-3 glucose readings each day We try seeing her on three days in a row, to complete a full glucose curve (6-9) We fool with this for 3 weeks - 9U SC BID All values >400, throughout the day Smut loses more weight and feels worse

33. Monitoring DM - Fructosamine (FRA)Low FRA with poor glycemic control – check T4Remission is defined as normal FRA w/o insulinRegulation using FRA can work well when curves are not practicalBut keep in mind that FRA is ideal in only 60% of diabetic pets with good clinical regulation Smut – 12 year old SF DLH Thoracic rads + Abd US - NSAF CBC, panel, UA WNL except glucose TT4, fT4 - WNL Urine culture negative FeLV/FIV negative No signs other than lethargy, poor appetite and weight loss

34. Monitoring DM - Fructosamine (FRA)Low FRA with poor glycemic control – check T4Remission is defined as normal FRA w/o insulinRegulation using FRA can work well when curves are not practicalBut keep in mind that FRA is ideal in only 60% of diabetic pets with good clinical regulation Smut – 12 year old SF DLH Plan – regulate with fructosamine fructosamine 140 Reduce insulin to 7 U BID, recheck 1 week CC: not much better, FRA 180 Reduce insulin to 5 U BID, recheck 1 weekHx: no weight loss, Smut feels a lot better (7/10)FRA 190 – reduce insulin to 4U BID, recheck 1 wk

35. Monitoring DM - Fructosamine (FRA)Low FRA with poor glycemic control – check T4Remission is defined as normal FRA w/o insulinRegulation using FRA can work well when curves are not practicalBut keep in mind that FRA is ideal in only 60% of diabetic pets with good clinical regulation Smut – 12 year old SF DLH Hx: Smut gains 0.5 lb, back to old self fructosamine 250 Recheck 30 days Smut is gradually weaned off insulin, using only FRA, symptoms and weight 18 months later goes back on insulin Euthanized at 16 yrs for renal failure

36. Monitoring DM - Fructosamine (FRA)Low FRA with poor glycemic control – check T4Remission is defined as normal FRA w/o insulinRegulation using FRA can work well when curves are not practicalBut keep in mind that FRA is ideal in only 60% of diabetic pets with good clinical regulationWhy Do Glucose Curves?Early detection of occult hypoglycemiaEnsure that dose changes are effectiveTo document dysregulation as the first step to correcting it

37. Glucose Curve ProtocolOwner feeds and gives insulinBring pet to clinic within 2 hoursGlucose (+ fructosamine) on arrivalGlucose every 2 hours when >100Once you know the insulin duration, you may be able to take the first glucose 3-4 hrs after insulinGlucose every hour when <100-150Can miss nadir (low point) if you don’t do thisContinue until you get 2 values 2 hours apart that are upwardly trendingIf nadir not <120, it’s difficult to determine durationUsually can be completed in a business day, but not alwaysSome require 12-24 hours - finish at home or ECDogs on Lantus® can often do q3-4 hrs

38. Home Glucose CurvesReally are better than “in clinic”Stress increases glucose Especially in catsMany owners can learn to do itIt’s very helpful for owners to be able to check blood sugar in an emergencyEntire curve does not have to be finished the same dayHave owners come in for appointment to discuss the glucose curve – bring pet at least quarterlyIf the pet tolerates the CGM, this can be much easier on the owner

39. Home Glucose CurvesWarm the earLateral to the ear vein in cats, or inner surfaceNo need to warm lip, foot pad, elbow callusApply vaseline if area is haired If you use alcohol, allow it to dryPrick with human lancetCan use 27 gauge needleUse roll of gauze inside the ear for catsCat - Ear PrickDog – Lip, Elbow, Footpad, Ear

40. Home Glucose CurvesChoosing a glucometerLow sample volumeInadequate sample volume prevents sample from runningEDTA (purple top) and LiHep (green top) blood are fine in clinic

41. Home Glucose CurvesChoosing a glucometerLow sample volumeInadequate sample volume prevents sample from runningEDTA (purple top) and LiHep (green top) blood are finePlasma calibrated rather than whole blood𝑮𝒍𝒖𝒄𝒐𝒔𝒆𝒑𝒍𝒂𝒔𝒎𝒂 = ____𝑮𝒍𝒖𝒄𝒐𝒔𝒆𝒘𝒉𝒐𝒍𝒆 𝒃𝒍𝒐𝒐𝒅___ 𝟏. 𝟎 − (𝟎. 𝟎𝟎𝟐𝟒 ×𝑯𝒄𝒕%)

42. Home Glucose CurvesChoosing a glucometerAuto-calibration of test stripsCalibrate to in house machineEnter species code for veterinary meters if neededGlucometers are most accurate <100mg/dlAlphaTrak 2 Starter Kit $55Meter, lancets, strips, lancing device

43. Interpreting Glucose CurvesDuration of the curveIf your curve is 12 hours or less, you need to give insulin BID, not SIDI have never been able to use ProZinc SID in the dogGlucose rangeIf all values are 100-250, leave it alone if symptoms are controlledAvoid values above 300 and below 80Average of 6 values taken in a 12-hour curve should be less than 250

44. Interpreting Glucose CurvesGlucose nadirIf < 80 reduce the insulin doseIf >130, consider increasing insulin dose, unless all values less than 250Ideal nadir is 80-130Glucose PeakIf nadir 80-130 and peak too high, change to longer duration insulinregular < NPH < Lente< PZI < glargine < detemir

45. Somogyi EffectRebound hyperglycemia follows blood glucose < 60usually within 12 hoursLasts 24-72 hoursOften >400 mg/dlDue to epinephrine and glucagon release (counter-regulation)cyclic response of 1-2 days of “good control” followed by several days of poor control increases suspicionFructosamine usually >500 mcmol/dlReduce insulin and recheck FRA + curve in 1 week

46. Home Urine TestingI don’t use urine strips for glucosuriaRenal threshold 180-300 mg/dlMost diabetics exceed this dailyMany well regulated diabetic dogs and cats will have daily glucosuriaIt is reasonable to have owners keep KetoDiastixKetonuria indicates seeing the vet ASAPIncreasing insulin based on glucosuria can result in Somogyi effect

47. Willie

48. Willie17 year old DLH, has been a diabetic for about 3 yearsHad an “insulin vacation” for about six months during the first yearWas taking 2 units NPH BID for about a year prior to boarding for 10 daysEats Innova EVO dry free choice (crunchy junkie)He doesn’t eat well when he boardsSince coming home from boarding a month ago, Willie has felt terriblePU/PDDoesn’t eat chicken jerky snacks as voraciouslyVery lethargic

49. WillieIn the past monthWeekly visits to regular vet for spot checks at insulin timeFasted overnight and no insulin prior to coming in for glucose checksInsulin given at clinic, Willie doesn’t eat all dayAll glucose values > 400Insulin gradually increased to 6 units BIDWillie just keeps getting worse, now he won’t eat at home, still PU-PDNo new findings on exam, except weight loss of 1.5 lbs over past yearOther than glucose, last bloodwork done 2 yrs. ago

50. WillieBloodwork at 2pm (insulin 7am)CBC – NSAFProfile & electrolytes – BUN 68, creat 4, phos 9, glu 31UA – SG 1.015, no bacteriuriaUrine culture negativeTT4 – 6.5, fT4 – 63No chest x-rays or abdominal USThis may have sent Willie over the edgeSedation might compromise the kidneysNew Diagnoses – hyperthyroidism, CRF, insulin overdose

51. WilliePlan100 ml LRS SC (owners not ready for home fluids)No insulin tonight, reduce insulin to 4 units BIDRecheck in 1 week, or sooner if problems continueProvide owner with list of canned moderate protein, low carb foods – wishful thinking1 week later, Willie “is a new cat” ;-)Eating well and happy, but still PU-PDWith CRF & hyperT4, we likely won’t be able to use PU-PD as a marker for good regulation2 pm glucose 67, BUN 49, creat 2, phos normalReduce insulin to 3 units BID, recheck 1 week

52. Willie1 week later, Willie still feeling goodstill PU-PDFructosamine 492 (poor control)BUN 59 (was 49), creat 5 (was 2), phos normalGlucose curve Time 0 – 3652 hours – 714 hours – 1436 hours - 310Change to Lantus 3 units BID, recheck 1 week

53. Willie1 week later, Willie still feeling goodstill PU-PDFructosamine within normal rangeBegin methimazole 2.5 mg PO SIDDecrease Lantus to 2 units BID, recheck 1 weekWhy?Hyperthyroidism causes relative insulin resistance

54. Attendee 2 – City TX

55. WillieWe eventually weaned Willie down to 0.5 unit every other dayIf we stopped, he got hyperglycemic and did not feel goodIf we increased, he got hypoglycemic and did not feel goodWe continued this for 2 years, until he suffered an episode of acute renal failure at 19 years of ageHis temperament was not suitable for hospitalization, and he was humanely euthanized

56. WillieLesson from WilliePU-PD in an unregulated diabetic does not always mean more insulin is neededInsulin overdose can cause PU-PD, due to rebound hyperglycemiaOther problems can cause PU-PD – CRF & hyperT4 in this caseRegular rechecks can nip problems in the bud and prevent illness from dysregulationGlucose curves are not always necessary – one mid-day glu + FRA can tell a great deal

57. WillieLesson from WillieI prefer owners to give insulin and feed prior to bringing in for glucose curveIn-house fructosamine can preclude need for glucose curveSPOT CHECKING GLUCOSE ONLY AT INSULIN TIME SUCKS BIG TIME!!!!!

58. Spot Checking DiabeticsIf you were only allowed two glucose checks in every 24 hour period, when would you want to take them?At Insulin Time? Glucose peakGlucose nadir? 2-12 hrs afterOne of each?

59. Spot Checking DiabeticsWhich values in a glucose curve are used to determine dose?Nadir (lowest glucose values - insulin peak)Which values are used to determine interval and insulin type?Peak glucose values (insulin nadir)If glucose nadir is ideal, and glucose peaks are too high, then you need to give insulin more often, or you need a longer acting insulin

60. Spot Checking DiabeticsQuiz – Glucose at insulin time250, 260

61. Spot Checking DiabeticsQuiz – Glucose at insulin time250, 260

62. Spot Checking DiabeticsQuiz – Glucose at insulin time250, 260Need to decrease insulin 350, 335

63. Spot Checking DiabeticsQuiz – Glucose at insulin time250, 260Need to decrease insulin 350, 335

64. Spot Checking DiabeticsQuiz – Glucose at insulin time250, 260Need to decrease insulin 350, 335Increasing insulin would probably make this dog or cat hypoglycemicNeed to change to longer acting insulin245, 265

65. Spot Checking DiabeticsQuiz – Glucose at insulin time250, 260Need to decrease insulin 350, 335Need to change to longer acting insulin245, 265

66. Spot Checking DiabeticsQuiz – Glucose at insulin time250, 260Need to decrease insulin 350, 335Need to change to longer acting insulin245, 265Need to increase insulin 200, 200

67. Spot Checking DiabeticsQuiz – Glucose at insulin time250, 260Need to decrease insulin 350, 335Need to change to longer acting insulin245, 265Need to increase insulin 200, 200

68. Spot Checking DiabeticsQuiz – Glucose at insulin time250, 260Need to decrease insulin 350, 335Need to change to longer acting insulin245, 265Need to increase insulin 200, 200PERFECT!! no changes needed

69. SummaryPowerPoint – Ups and Downs of Blood Sugar.pptx.pdfs – 1 and 6 slides per pageVet Articles and HandoutsJVIM – Validation of Flash Glucose Monitoring Device (FreeStyle Libre) in Dogs ASVCP - Guidelines for Glucometers in Vet MedAAHA – Guidelines for Managing Diabetes Mellitus in Dogs and CatsAAHA – Algorithm – Managing Hypoglycemia

70. SummaryVet Articles and Handouts AAHA – Monitoring Blood Glucose in DiabeticsFeldman &Nelson – Algorithm – Interpreting Glucose CurvesClient HandoutsDiabetes Mellitus in DogsDiabetes Mellitus in CatsDiabetic KetoacidosisFreeStyle LibreHome Glucose Testing, Ear Prick, Lip PrickHypoglycemia

71. AcknowledgementsRichard Nelson. Small Animal Clinical Diagnosis by Laboratory Methods, 5th Edition. Ch 8 – Endocrine, Metabolic and Lipid Disorders. Eds. Michael Willard, Harold Tvedten.Teleah Grand, DVM. Animal Care Center at Stonebridge, McKinney TX. Photo of dog with reaction to FreeStyle Libre adhesive.Greg Matt, DVM. Beechnut Animal Hospital, Houston TX. FreeStyle Libre CGMD videos.

72. AcknowledgementsWard Animal Hospital. Case – Smut – using FRA.Southwood Drive Animal Clinic. Dr, Shawn Penn, Dr. Doug Ashburn – Case - Willie – Diabetic Dysregulation.

73. AcknowledgementsEastex Vet Clinic. Dr. Jimmy Weatherly - Case – Dot with Addison’s Disease.J Catharine Scott-Moncrief. Canine & Feline Endocrinology, 4th Edition. Ch 12 – Canine Hypoadrenocorticism.Lathan & Thompson. Management of hypoadrenocorticism (Addison’s Disease) in dogs. Vet Med Res & Rpts. 2018:9 1–10.