Diabetes Mellitus

Presented by…Rajeev MishraL-2015-V-38-MVeterinary MedicineGADVASU, Ludhiana

Diabetes Mellitus

Disease in which the body doesn’t produce or properly use insulin, leading to hyperglycemia.

Diabetes is a life-long disease marked by high levels of glucose in the blood

It can be caused by too little insulin, resistance to insulin, or both

Pancreas

The pancreas functions as both an exocrine and an endocrine gland

Exocrine function is associated with the digestive system because it produces and secretes digestive enzymes

Endocrine Function: produces two important hormones in Islets of Langerhans, insulin and glucagon

Pancreatic Hormones

Insulin (beta cells) stimulates the uptake of glucose by body cells thereby

decreasing blood levels of glucose

  Glucagon (alpha cells)

stimulates the breakdown of glycogen and the release of glucose, thereby increasing blood levels of glucose

Glucagon and insulin work together to

regulate & maintain blood sugar levels

Action of Insulin on the Cell Metabolism

Functions of insulin

Enables glucose to be transported into cells for energy for the body

Converts glucose to glycogen to be stored in muscles and the liver

Facilitates conversion of excess glucose to fat

Prevents the breakdown of body protein for energy

What goes wrong in diabetes?

Multitude of mechanisms Insulin

Regulation Secretion Uptake or breakdown

Beta cells damage

Frequency

Dogs: 1:100 reaching 12 yrs will develop DM

Cats: 1:50-1:500 Prevalence increasing over time: aging

population, obesity, physical inactivity

Signalment

Dogs: female : male 2-3:1 7-9 yrs of age Rare form of congenital lack of β cells

Cats: >95% >5 yrs of age 70-80% male Majority are overweight, few underweight

Genetic Predisposition

German Shepherd Dogs Schnauzers Beagles Poodles Golden retrievers & Keeshonds: more prone

to juvenile diabetes Cats: Burmese??

Etiology: Dogs

Risk factors: genetic, environmental, insulin antagonistic rx (GC’s and megestrol acetate), & diseases (e.g. pancreatitis)

Immune-mediated destruction of islets occurs leading to B-islet cell dysfunction relative or absolute deficiency of insulin

Etiology: Dogs

Progression is slow; likely >90% of islets are lost before DM occurs

Is the most common disorder of the endocrine pancreas

Etiology: Cats

Most Type II Multifactorial:

Obesity: 4 X more likely to develop DM Pancreatitis Genetics? Drugs: GC’s, progestins Amyloidosis of the pancreatic cells

Etiology: Cats

Factors lead to impaired insulin action in liver, muscle and adipose tissue and β–cell failure hyperglycemia

If some β–cell function exists, diabetes may be transient

Diabetes Mellitus

There are two major types of diabetes: Type 1 Diabetes Type 2 Diabetes

Aetiology of DiabetesAetiology of Diabetes

Type One Diabetes results when the body’s immune system

destroys its own beta cells in the pancreas. No insulin production is then possible.

Type Two Diabetesresults from either

Insulin resistance (overweight patients) Inadequate insulin production (lean

patients) A combination of both

Type I Diabetes Cell

Type II Diabetes

Insulin levels may be normal, elevated or depressed Characterized by insulin resistance, Diminished tissue sensitivity to insulin, Impaired beta cell function (delayed or

inadequate insulin release)Risk factors: family history, sedentary lifestyle,

obesity and aging

What is Insulin Resistance?

Condition in which the body does not utilise insulin efficiently

Insulin resistance is the decreased response of the liver and peripheral tissues (muscle, fat) to insulin

Insulin resistance is a primary defect in the majority of patients with Type 2 diabetes

Type II Diabetes

Characteristics of DiabetesType 1 Type 2

Rapid onset Normal or underweight Little or no insulin Ketosis common Autoimmune plus

environmental factors Low familial factor Treated with insulin, diet

and exercise

Gradual onset 80% are overweight Most have insulin resistance Ketosis rare Part of metabolic insulin resistance

syndrome Strongly hereditary Diet & exercise, progressing to

tablets, then insulin

Clinical manifestations

Clinical Signs : Dogs

pU/pD due to hyperglycemia and 2° osmotic diuresis

Polyphagia and weight loss Dehydration Cataracts in dogs; rare (?) in cats Fatigue, nausea, vomiting

Clinical Signs: Cats

Icterus common with DKA Plantigrade stance ~10%

Ketoacidosis

In addition to high glucose levels, acutely ill type 1 diabetics have high levels of ketones. As cells cannot get glucose, they burn fats as an alternate

energy source Ketones are produced by the breakdown of fat and muscle, and

are toxic at high levels Ketones in the blood cause a condition called "acidosis” or

“ketoacidosis" (low blood pH) Urine testing detects ketones in the urine Blood glucose levels are also high.

Cataract

Develop frequently in dogs Related to unique sorbitol pathway

by which glucose is metabolized in the lens

Edema of lens

Disruption of normal light transmission

DIAGNOSIS

Fasting BG >200 mg/dl & glucosuria

Fructosamine: supports sustained hyperglycemia

Urine dipsticks for home use if stress hyperglycemia suspected

DIFFERENTIALS

Hyperthyroidism GI lymphoma Hepatic disease Renal disease Pancreatitis Hyperadrenocorticism

DIFFERENTIALS for Hyperglycemia

Dextrose-containing fluids Parenteral nutrition Diestrus, pheochromocytoma (dogs) Acromegaly (Cats) Head trauma Exocrine Pancreatic Neoplasia

CLINICAL PATHOLOGY

CBC: +/- normal, anemia, stress leukogram

Profile: hyperglycemia, ↑ ALT/SAP, ↑ cholesterol, ↑ bilirubin (cats)

UA: proteinuria, pyuria

CLINICAL PATHOLOGY

UA: renal threshold for glucose: Dogs:180-220 mg/dl Cats: 240-300 mg/ld Culture!!: Up to 40% will have a UTI w/o an

active sediment

Blood Pressure

TREATMENT(for the non-ketotic diabetic)

Work to establish Euglycemia over time

Insulin types: Short acting (Regular) Intermediate acting (NPH, Glargine, PZI,

ProZinc) Long acting (Ultralente-no longer available)

NPH/Lente

Dogs and cats BID dosing needed with 2 meals of equal

calories

DOGS: 0.25-0.5 units/kg BID CATS: 1-3 units BID

Protamine Zinc InsulinProZinc

U-40 concentration, app’d for cats BID dosing most common Start @ 1U/cat BID Dogs: not rec’d d/t unpredictable onset &

duration of action Glargine insulin: in newly diagnosed cats

ORAL HYPOGLYCEMIC AGENTS

Sulfonylureas Glipizide @ 2.5mg,bid Cats Glimepiride @2mg sid Meglitinides Biguanides Thiazolidinediones Alpha-Glucosidase inhibitors acarbose

in cats @12.5-25mg,bid-tid in congunction with diet

Oral Hypoglycemic agents

Only work if functional B cells are present

Acarbose: delays absorption of glucose from SI, delays digestion of complex carbs thus decreasing PP hyperglycemia

BUT: side effects=diarrhea and weight loss

Cornerstones of Diabetes Management

Healthy eating/ nutrition Exercise Monitoring Medication/Insulin

Medical Nutrition Therapy

Primary Goal – improve metabolic control

Blood glucose Lipid (cholesterol) levels CATS: low carbohydrate, high protein,

mod-high fiber DOGS: low fat, high fiber

Medical Nutrition Therapy

Increase fiber >12% slowly fermentable , insoluble fiber or >8% moderately fermentable fiber

Maintain short and long term body weight

Prevent or treat complications Improve and maintain nutritional

status

EXERCISE

To encourage weight loss To decrease insulin resistance induced

by obesity

Thank You