DEFINITION

Primarily a disorder of carbohydrate metabolism. Diabetes mellitus is derived from the Greek word for fountain and the Latin word for honey; the term describes one of the prominent symptoms of untreated diabetes : production of large volumes of glucose-rich urine

•Diabetes is a major public health concern, most common endocrine disorder & 6th leading cause of death in the USA. 23.6 million diagnosed & about 57 million prediabetic with estimated cost of $174 billion

TYPE I DIABETES

• Insulin-dependent, juvenile-onset, & ketosis- prone
• childhood & adolescence onset;
• abrupt onset
• usually negative family history
• autoimmune process
• 5-10% of diabetics have type I
• loss of pancreatic beta cells
• insulin levels reduced early in disease & completely absent later
• treated with Insulin replacement
• Glucose levels fluctuate in response to infection, exercise, changes in calorie intake & insulin dose
• S/S’s: poluria, polydipsia, polyphagia, weight loss
• Thin & undernourished
• Ketosis is common if insulin is insufficient

TYPE II DIABETES

• Non-insulin dependent
• Onset usually over 40 & gradual
• Frequent family history
• 90- 95 % of diabetics have type II diabetes
• Unknown etiology, strong family association
• Insulin resistance & inappropriate insulin secretion
• Insulin levels are low, normal or high
• Treatment: exercise, reduced calorie diet, oral hypoglycemia and/or insulin
• Blood glucose levels are more stable than type I
• May be asymptomatic
• Frequently obese
• Uncommon ketosis

BODY SYSTEMS AFFECTED & LONG-TERM COMPLICATIONS

• Macrovascular damage: Cardiovascular disease, heart disease, hypertension, & stroke
• Microvascular damage: History of long and sustained hyperglycemia causes thickening of small blood vessels
• Retinopathy: major cause of blindness among American adults
• Neuropathy: damage to kidneys, proteinuria, reduced glomerular, & increased arterial blood pressure: Sensory & motor neuropathy: tingling in the fingers & toes(parethesia), pain, suppression of reflexes, & loss of sensation. Autonomic neuropathy: Gastroparesis (delayed stomach emptying)- 20-30 % of long standing diabetes manifested with nausea, vomiting, delayed gastric emptying, & gastric distention
• Amputations secondary to infection: Diabetes can suppress immune function, glucose-rich environment for bacteria to grow, & the neuropathy from this disorder prevents the patient from feeling discomfort from a serious infection

DIAGNOSIS (DX)

Excessive plasma glucose:
•Fasting blood glucose(FBS) of 126 or higher
•Causal plasma glucose of 200 or higher
•Oral glucose tolerance test (OGTT) 2 hours after glucose load blood glucose is 200 or higher
•Glycosylated Hemoglobin(Hemoglobin A1c) test---average blood glucose over 3-6 months of 8.6 or higher

DIABETES TREATMENT (TX)

Type I : 1. Dietary measures, exercise, insulin replacement, ACE inhibitors for managing hypertension
Type II : glycemic control: diet & exercise, drug therapy of oral or injectable antidiabetic agents
Monitoring treatment:
1. to determine whether glucose levels are safely maintained &
2. Guide changes when glucose is not safe by: Self measurement of blood glucose levels is the standard method of day to day monitoring

INSULIN PHYSIOLOGY

•Structure: Insulin consists method for day to day monitoring
•of two amino acids. Insulin is synthesized in the pancreas by beta cells with the isles of Langerhans.
•Converted from proinsulin to insulin.
•Secretion: principle stimulus for insulin release is a rise in blood glucose. Beta-adrenergic receptors in the pancreas promote secretion of insulin.
•Metabolic actions: Metabolic actions of insulin are primarily anabolic(conservative or constructive); it promotes conservation of energy buildup & buildup of energy stores, & promotes cell growth and division
•Metabolic Consequences of Insulin Deficiency:
•Increased glycogenolysis
•Increased gluconeogenesis
•Reduced glucose utilization
•Insulin: Manufactured in USA fm recombinant DNA technology

TYPES OF INSULIN

•Short duration/rapid acting: Clear, given sub-q in upper arm, thigh, & abdomen &may be given IV(regular, Humulog, & Novalog)
•Insulins: Lispro/ Humalog, Aspart/Novalog, Glulisine/Apidra
•Actions: Rapid-acting analog of regular insulin
•Therapeutic uses: Can be administered immediately before eating or after eating. Provides glycemic control between meals
•Absorption: Acts within 15-30 minutes of injection
•Excretion: persists for 3-6 hours
•Side effects: hypoglycemia, tachycardia, palpitations, sweating, nervousness, headache, confusion, drowsiness & fatigue & hypokalemia

•Short Duration Slower Acting: Regular insulin/ Humulin R, Novolin R
•Therapeutic uses: Used to control postprandial hyperglycemia & basal glycemic control
•Absorption: Effects in 30-60 minutes
•Excretion: Lasts up to 6-10 hours
•Side Effects: Hypoglycemia & coma

•Intermediate Duration: NPH insulin/Humilin N/ Novolin N.,( cloudy suspension), Insulin detemir/Levemir(clear)
•Therapeutic uses: Provides glycemic control between meals & during the night
•Absorption: Effects in 60-120 minutes
•Excretion: Duration is 16-24 hours
•Side Effects: Hypoglycemia & coma

•Long duration: Insulin glargine/Lantus a clear suspension, given at bedtime
•Therapeutic uses: Provides blood equivalent glycemic control
•Absorption: Effects onset at 70 minutes
•Excretion: Duration is 24 hours
•Side effects: Hypoglycemia & coma

ORAL HYPOGLYCEMICS

1. Metformin
Mechanism of action: Lowers blood glucose & improve glucose tolerance with type II diabetic, by inhibiting glucose production in the liver, reduces glucose absorption in the gut & sensitizes insulin receptors
Pharmacokentics/ Absorption: slowly absorbed from small intestine
Excretion: unchanged by the kidneys
Therapeutic uses: It is used to lower blood sugar for type II diabetes who have not responded adequately with diet modification & exercise
Side Effects: decreased appetite, nausea, & diarrhea

2. Sulfonylureas
Mechanism of action: Stimulates the release of insulin from pancreatic islets
Therapeutic uses: Used only for type II, may be used alone or together with other hypoglycemic drugs
Excretion: metabolized by liver, renal excretion
Side Effects: Excessive hypoglycemia, cardiovascular toxicity

3. Glinides: same mechanisms of sulfonylureas
4. Thiazolidinediones(Glitazones)
Actions: reduces insulin resistance
Therapeutic uses: Only used with Type II diabetics
Side Effects: headache, mylagia, sore throat, upper respiratory infection, renal retention of fluid, raises level of plasma lipids

5. Alpha – Glucosidase Inhibitors:
Mechanism of action: Delays absorption of carbohydrates
Used with Type II diabetes
Side effects: flatulence, cramps, abdominal distension, diarrhea. Long term, high dose causes liver dysfunction
6. Sitagliptin
Mechanism of action: Enhances the actions of incretin hormones to stimulate glucose dependent of insulin, suppress postprandial release of insulin
Therapeutic uses: used as a monotherapy or combined with metformin or glitazone, Type II diabetics
Side effects: headache, upper respiratory infections, inflammation of nasal passage & throat

DKA

DKA: Severe manifestation of insulin deficiency characterized by hypoglycemia, production of ketoacids, hemoconcentration, acidosis, and coma. Common in pediatric patients with type I diabetes
Pathogenesis: derangement of glucose and fat metabolism, hyperglycemia, water loss, & hemoconcentration. Altered fat metabolism causes production of ketoacids.
• Ketones imparts smells to the urine & breath- rotten or decaying apples in the urine & breath smells sweet or like acetone/alcohol, reduced alertness, impaired gait & balance
• Treatment: Life threatening, correcting hyperglycemia & acidosis, replacing water loss, and normalize electrolytes(Na & KCL)