Insulin Therapy & Diabetes Management

Insulin Therapy

• Type 1 diabetes results from pancreatic beta cell destruction, requiring insulin replacement
• Type 2 diabetes involves inability to manage blood glucose with diet, exercise, and oral antidiabetics
• Must know peak action time of insulins
• U-100 insulin concentration is defined as 1 ml = 100 units

Insulin Storage

• Unopened insulin should be stored in the refrigerator and not be frozen
• Opened insulin can be kept up to 1 month at room temperature if kept out of direct sunlight and extreme heat
• Opened insulin can be kept until the expiration date if kept in the refrigerator
• Insulin mixtures can be stored for 1 month at room temperature, 3 months in the refrigerator
• Mixtures in prefilled syringes can be stored for 1-2 weeks in the refrigerator and should be stored vertically with the needle pointing up

Complications of Insulin Treatment

• Hypoglycemia occurs when glucose is less than 70 mg/dL, and necessitates rapid treatment
• Possible abrupt onset symptoms of hypoglycemia include tachycardia, palpitations, diaphoresis, shakiness
• Possible gradual onset symptoms of hypoglycemia include headache, tremors, weakness, lethargy, disorientation
• Conscious patients experiencing hypoglycemia should be given fast-acting oral carbohydrates, like glucose tabs, 4 oz of orange juice, 2 oz of grape juice, 8 oz of milk, non-diet soda, or honey (15g carbohydrate)
• For patients not fully conscious, administer IV glucose or parenteral glucagon (SQ/IM)
• Lipohypertrophy involves subcutaneous fat deposits from too many insulin injections at the same site
• Hypokalemia results from promoting potassium uptake by cells, lowering blood levels
• Sulfonylureas, meglitinides, beta-blockers, and EtOH can interact with insulin leading to additive hypoglycemia
• Thiazide diuretics and glucocorticoids can interact with insulin to raise blood glucose levels and counteract insulin

Insulin Administration Considerations

• Insulin requirements increase during pregnancy and lactation
• Insulin doses are adjusted as needed
• Increased calorie intake, infection, stress & growth spurts in the 2nd or 3rd trimester may change insulin needs
• Ensure adequate glucose control at onset and peak insulin times
• Short-acting insulins should be drawn first when mixing and gently rotated to mix
• Never mix long-acting or ultra-long acting insulins, or use IV
• Encourage diet and physical activity with insulin administration
• Ensure proper storage
• Regular insulin is most often used for IV administration
• Aspart, glulisine and lispro can be used for IV administration
• U-100 is the most common concentration for IV administration
• 100 units in 100 mL of 0.9% normal saline equals 1 unit/mL for IV administration
• Waste 50 mL through IV tubing

Oral Antidiabetic Medications

• Oral antidiabetic medications are started after new diabetics fail diet modifications
• Insulins are started after failure of two oral antidiabetic medications

Sulfonylureas

• Glipizide, glyburide, glimepiride promote insulin secretion by the pancreas
• Sulfonylureas can increase tissue response to insulin
• Advers effects may include hypoglycemia and weight gain
• Take 30 minutes before breakfast to prevent hypoglycemia
• Avoid alcohol while taking Sulfonylureas
• NSAIDs, sulfonamide antibiotics, and cimetidine can add to the risk of hypoglycemia

Meglitinides

• Repaglinide and Nateglinide are similar to Sulfonylureas
• Take with a meal, TDD (0-30 minutes before)

Biguanide

• Metformin is a first line drug that decreases glucose production in the liver, increases glucose uptake and use in fat and skeletal muscle, and decreases glucose absorption in the GI tract
• Adverse effects include GI upset (usually goes away with time), Vitamin B12 and Folic Acid deficiency (peripheral neuropathy), and Lactic acidosis (drowniess, hyperventilation)
• Metformin is not recommended for pregnancy/lactation
• Metformin is contraindicated in severe infection, shock, kidney impairment, and hypoxia
• Alcohol and Cimetidine increase risk of lactic acidosis
• Iodine increases risk of acute kidney failure
• Administer once or twice daily with a meal

Glitazones (TZDs)

• Pioglitazone, Rosiglitazone increase cellular response to insulin by decreasing its resistance and increasing cellular uptake and decreasing glucose production
• Adverse effects include fluid retention, elevated LDL, hepatotoxicity (jaundice, dark urine, RUQ pain), and ovulation in anovulatory perimenopausal
• Glitazones are contraindicated in severe heart failure, history of bladder cancer, and active hepatic disease
• Insulin and CYP450 interactions will result in fluid retention or increased levels
• Glitazones are contraindicated in pregnancy and lactation

Alpha-Glucosidase Inhibitors

• Acarbose and Miglitol decrease carbohydrate digestion and absorption
• Adverse effects include GI effects and long-term use will result in anemia, hepatotoxicity, and impaired breakdown of sucrose
• Contraindicated in GI disorders (IBD, ulcers, obstruction)
• Sulfonylureas and insulin cause additive hypoglycemia
• Take with the first bite of a meal, TID

DPP-4 Inhibitors

• Sitagliptin, saxagliptin, linagliptin, alogliptin enhance incretin activity leading to increased insulin release and decreased glucagon secretion
• Generally well-tolerated with rare headache, nausea, joint pain, hypersensitivity reaction, and pancreatitis

SGLT-2 Inhibitors

• Canagliflozin, Dapagliflozin, Empagliflozin increase glucose excretion by blocking reabsorption in urine, which decreases glucose levels and induces weight loss via urine calorie loss
• Adverse effects include cystitis, candidiasis, polyuria, dizziness, and hypotension

GLP-1

• Semaglutide
• Incretin miniepics
• Well-tolerated
• Contraindicated in T1DM

Non-Insulin Injectables

• Incretin mimetics include Exenatide, Liraglutide, Albiglutide, Dulaglutide, and Semaglutide
• Used for T2DM

Poor Glycemic Control

• Hyperglycemia Acute Complications
• DKA is the most common complication in pediatric patients
• Leading cause of death
  • Treatment includes:
    • Insulin replacement
    • I V bolus, infusion
    • Bicarbonate for acidosis - For pH