Endocrinopathies of Dogs and Cats mellitus (DM)

dr. Ákos Máthé Department of Internal Medicine Classification of DM ~ Action of   Blood glucose  (>7.5 mmol/l) • Pathophysiologic ~ IDDM: insulin secretion  ~ NIDDM: insulin secretion  or , but insulin is less effective • Pathogenetic ~ Primary DM (pancreatic disease) – Autoimmune destruction of islets (dogs) – Islets amyloidosis (cats) – Pancreatitis, (neoplasia) ~ Secondary DM – Excess of counterregulatory hormones (GH , glucocorticoids ) – Obesity (reduced receptor binding of insulin) Consequences of extracellular

BG  glucose excess

Glycosuria Hypokalemia (Polyuria) Hyponatremia Dog: BG >10 mmol/l Hypophosphatemia Cat: BG >14 mmol/l

Intracellular dehydration Hyperglycemic coma Lens cataract Retinopathy Glycation of proteins Peripheral neuropathy Glomerulosclerosis Consequences of intracellular lack of glucose Ketonuria

Lipolysis  Ketonemia Acidosis

Weight loss Ketoacidotic coma

Hyperlipemia Fatty liver

Gluconeogenesis  Weakness

Protein synthesis  Poor wound healing

Susceptibility to infections  Diabetes Mellitus in the Dog I.

• Signalment ~ Common disease ~ Middle-aged and old dogs ~ Intact females are predisposed ~ Poodle, Dachshund, Terriers, Beagle, Puli, Labrador, Retrievers, (English cocker spaniel, Rottweiler) Diabetes Mellitus in the Dog II.

• Clinical manifestations in uncomplicated DM ~ Signs may appear 1-2 months after estrus ~ History with (possible) pancreatitis +/- ~ PD/PU, weight loss, (PP) ~ Dehydration, hepatomegaly, dull hair coat, flaking skin, cystitis, glycos- / ketonuria and ~ Chronic cases: cataracts / retinopathy, proteinuria +++, (paresis) Cataracts, dehydration, weight loss Urine strip and BG measurement Diabetes Mellitus in the Dog III.

• Clinical manifestations in complicated DM See above, and: ~ – Lethargy, weakness, anorexia, vomiting, coma, Kussmaul’s respiration, odor of acetone in the breath ~ Hyperglycemic hyperosmolar syndrome (HHS; BG >33 mmol/l) – Restlessness, ataxia, nystagmus, convulsions ~ Pancreatitis – Lethargy, vomiting / diarrhea, abdominal pain ~ Exocrine pancreatic insufficiency – Poorly digested feces, sour smell, flatulence ~ Signs of Cushing’s syndrome, acromegaly Diabetes Mellitus in the Dog IV.

• Laboratory and instrumental findings ~ WBC , PCV  ~ ALT , ALKP (SIAP?) , BUN / creatinine , K+  or , amylase / lipase , cholesterol , lipemia ~ Metabolic acidosis ~ Progesterone , cortisol , GH  ~ (, glycosylated hemoglobin, IV ) ~ Bacteriuria: sediment and culture ~ Abdominal US: diffuse hepatomegaly, pancreatitis +/-, enlarged adrenal(s) +/-, nephropathy +/-, cystitis +/-, ovarian / uterine cysts +/- Diabetes Mellitus in the Dog V. • Treatment in uncomplicated DM ~ The owner should be informed about prognosis, (lifelong) insulin therapy, dietary management, controls, costs ~ Oral antidiabetic drugs are ineffective ! ~ Insulin therapy: – Caninsulin A.U.V.: 30% amorphous, 70% crystalline zinc insulin suspension – 0.5 (BW >25 kg) – 1 (BW <15 kg) IU/kg/12h SC ~ Ovariectomy – Reduces (risk of)  insulin demand  (if DM manifested within three weeks, complete recovery is possible) Diabetes Mellitus in the Dog VI. • Diet ~ Amount and composition should be constant ~ Rich in protein, high fibre content, complex carbohydrates –Hill’s r/d, w/d, i/d, R.C. Weight Control Diabetic, Eukanuba Glucose Control etc. –Home prepared: 70% meat, 25 % rice, potatoes or pasta, 5% vegetables, cereals ~ 10-50 g/kg/24h divided into 4 equal portions ~ One portion few minutes before each insulin dose, one portion 3-4 hours later Diabetes Mellitus in the Dog VII. • Client instructions ~ Method of insulin administration must be taught in detail and tried by the owner ~ Reduction of insulin dose by half in case of anorexia or vomiting ~ Information about – Signs: excitement, tremor, weakness, falling, convulsions, coma – Treatment: honey with spoon, extra meal, following insulin dose is skipped, consultation – If there is no improvement in 15 minutes, emergency treatment is required ~ Diet ~ Daily water intake (maximum 60-70 ml/kg) Instructions for owners Diabetes Mellitus in the Dog VIII.

• Control examinations ~ On the first two weeks: weekly ~ After control is stable: every 3-6 months ~ Blood glucose 6 hours after morning insulin dose should be 4-9 mmol/l ~ Adjust insulin dose +/- 5-10% Diabetes Mellitus in the Dog IX. • Problems with insulin therapy and controls – Insulin activity and administration problems should be ruled out ~ Hypoglycemia – Anorexia, vomiting, unusual physical activity, (relative) insulin overdose – Client instructions, reduction of insulin, IV glucose administration ~ Somogyi effect (posthypoglycemic hyperglycemia) – BG <3 mmol/l  adrenaline, glucagon, (cortisol, GH)   BG   – PD/PU, hyperglycemia – Serial BG measurements, reduction of insulin dose Continuous interstitial glucose monitoring Diabetes Mellitus in the Dog X. • Problems with insulin therapy and controls ~ Stress induced hyperglycemia at controls – No complaints at home, but hyperglycemia in the examination room – Measurement of BG at home ~ Short action of insulin – PD/PU and hyperglycemia a few hours before insulin – Longer acting insulin / dietary modification ~ Insulin resistance – Insulin dose >1.5 IU/kg is ineffective – Cortisol or progesterone / GH excess should be investegated and treated Diabetes Mellitus in the Dog XI.

• Treatment of ketoacidosis ~ Volume repletion: – Ringer’s solution + 1 mmol KCl / 100 ml – 20 ml/kg in the first hour, thereafter rate may be reduced by half every hour, until 2.5 ml/kg/h ~ Regular insulin: Actrapid HMge – 0.25 IU/kg IM, thereafter 0.1 IU/kg repeated every hour, until BG stabilizes between 8-13 mmol/l  0.3-0.5 IU/kg Caninsulin SC ~ K+ replacement: mmol KCl = (4.5 - K+) x 0.6 x BWkg ~ Bicarbonate therapy if pH <7.1 Complicated DM Diabetes Mellitus in the Dog XII.

• Prognosis ~ Uncomplicated cases have good prognosis, but –Regular control examinations are needed –Much depends on owner compliance ~ Complicated cases have poor prognosis Diabetes Mellitus in the Cat I.

• Signalment ~ Relatively rare ~ More common in male cats • Clinical manifestations ~ Sudden onset of PD/PU ~ (Weight loss, PP) ~ Cataracts are rare ~ Neuropathy: plantigrade posture of hind legs Diabetes Mellitus in the Cat II.

• Laboratory and instrumental findings ~ Hepatic lipidosis is more severe: TBr  ~ Hypokalemia is common • Diagnosis ~ Hyperthyroidism: PP and weight loss dominates, goiter ~ Stress hyperglycemia is frequently found in healthy cats  urine glucose at home (or: fructosamine) Diabetes Mellitus in the Cat III.

• Treatment ~ Glipizide (Minidiab 5 mg tabl.) –5 mg/cat 2-3 times a day PO –Stimulates insulin secretion and effectiveness –Reduction in BG levels may need 1-2 months –Many cats will require insulin therapy because of unsatisfactory control ~ Less problems with insulin treatment than in dogs (Caninsulin, glargin insulin – Lantus) ~ Diet is difficult Diabetes Mellitus in the Cat IV.

• Prognosis ~ Usually good ~ Some cats will recover after a few weeks / months of insulin therapy ~ Treatment of Cushing’s syndrome or acromegaly can cure insulin resistant DM Thank you for your attention !