As per the Centers for Disease Control and Prevention (CDC), 34.2 million people, or 1 in every 10, in the United States have diabetes. Diabetes is 7^th on the list of leading causes of death while the total estimated medical costs and costs associated with lost work and wages equates to an estimated $327 billion.

Diabetes, otherwise known as increased sugar levels (hyperglycemia) may be a result of decreased insulin secretion, decreased insulin sensitivity, or both. It can present itself in one of two forms of the following:

• Type 1
  • Autoimmune destruction of beta cells
  • Loss of insulin production
  • Must use insulin injections
• Type 2
  • Insulin resistance
  • Decreased insulin production over time
  • Associated with obesity, physical inactivity, family history

• Signs and symptoms of diabetes include:

• Risk factors:

• General Screening Criteria:
  • All patients with BMI greater than or equal to 25 kg/m² + 1 risk factor
  • Children/adolescents with obesity + 1 risk factor
  • 45 years old if no risk factors are present
  • Pregnant women at 24-48 weeks

• Diagnosis (per ADA guidelines):

Prediabetes	Diabetes
->Fasting plasma glucose (FPG) 100-125 mg/dL; or ->2-hour glucose after glucose tolerance test 140-199 mg/dL; or ->A1c 5.7-6.4%	->Symptoms + random plasma glucose > 200 mg/dL; or ->2-hour glucose after glucose tolerance test > 200 mg/dL; or ->FPG > 126 mg/dL; or ->A1c > 6.5%

• Glycemic targets (per ADA guidelines):
  • A1c < 7%
  • 80-130 mg/dL pre-prandial plasma glucose
  • < 180 mg/dL post-prandial plasma glucose
  • A1c should be measured quarterly if not at goal
    • Or twice yearly if at goal
    • (A1c – 2) x 30 = average blood glucose

• Drugs that may increase blood glucose levels:

• Non-drug treatment options:
  • Smoking cessation
  • Weight loss
    • 3500 kcal weekly reduction = 1 lb weight loss
    • Waist circumference < 35 inches for females and < 40 inches for males
  • Nutrition
    • Carbs from vegetables, fruits, grains, and dairy
    • Omega-3 fatty acids and fiber
    • Limit saturated fat, cholesterol, and sodium
    • 15 g = 1 serving of carbohydrates
  • Physical activity
    • 150 min/week, moderate intensity
    • No more than 2 consecutive days off
    • Resistance training at least 2x/week

• Additional notes on oral drug classes:
  • Biguanides
    • Take with food
    • Use of alcohol increases the risk of lactic acidosis
    • Discontinue before any imaging with iodinated contrast; resume after 48 hrs
  • Meglitinides
    • Take 1-30 minutes before meals
    • If skipping a meal, skip dose as well
  • Sulfonylureas
    • Take with breakfast
      • Exception: Glipizide IR 30 minutes before breakfast
    • Glyburide – avoid in elderly and patients with renal impairment
  • Thiazolidinediones
    • Take with meals
    • May take weeks to take effect
    • Additional warnings:
      • Bladder cancer (pioglitazone only)
      • Risk of macular edema
      • Fracture risk
      • Hepatic failure
      • Resumption of ovulation
  • SGLT-2 Inhibitors
    • Caution when taking with diuretics and NSAIDs (due to risk of hypotension and acute kidney injury)
    • Additional warnings:
      • Genital infections
      • Hypotension
      • Increased LDL
      • Renal insufficiency
      • Ketoacidosis
    • Monitor K⁺ with Canagliflozin
  • DPP-4 Inhibitors
    • Take in the morning

Additional notes on injectable drug classes:

• GLP-1 Agonists:
  • Exenatide and lixisenatide are administered 60 minutes before a meal
  • All others given without regard to food

• Amylin Analog
  • Used in treatment of both type I and II diabetes
  • Reduce mealtime insulin by 50%

• Drug treatments (Insulin)
  • For all insulins:
    • Side effects: weight gain
    • Warnings; hypoglycemia, hypokalemia
    • Never use pens for more than one individual
    • Most are 100 units/mL concentration
    • High risk medications
  • Dosing strategies
    • Basal insulin
      • Long or intermediate acting
      • Mainly affect fasting blood glucose
    • Bolus insulin
      • Rapid or short acting
      • Two purposes:
        • Prandial (mealtime) & correction (acute elevation)

• Insulins that do not require a prescription:
  • Regular insulin, NPH, and the premixed 70/30 combination

• Insulin dosing for Type I diabetes:
  • Rapid-acting and basal insulin preferred
  • If using NPH and regular insulin
    • 2/3 NPH, 1/3 regular
  • Initiating basal/bolus insulin:
    • Calculate total daily dose (TDD)
      • 0.6 units/kg/day using TBW
    • Step 2: Divide TDD
      • 50% basal
      • 50% bolus
    • Step 3: Divide the bolus among 3 meals
  • Based on the amount of carbohydrates in a meal, meal-time insulin can be adjusted using rule of 500 (rapid-acting insulin) or rule of 450 (regular insulin)
    • (500 or 450)/TDD = g of carbs covered by 1 unit of insulin

• Correction factor/dose
  • Factor:
    • Determines how much blood sugar will drop for every 1 unit of insulin. Uses the rule of 1800 (rapid-acting insulin) or rule of 1500 (regular insulin)
      • (1800 or 1500)/TDD = correction factor for 1 unit of insulin

• Dose:
  • Amount of insulin required to bring blood glucose back to normal: [(blood glucose now) – (target blood glucose)]/   correction factor = correction dose

• General treatment algorithm for Type II Diabetes:

• For A1c greater than or equal to 8.5%: Jump straight to dual treatment
• A1C > 10%: Think insulin
• Cardiovascular benefit:
  • GLP1 agonists: liraglutide, semaglutide, exenatide
  • SGLT2 inhibitors: empagliflozin, canagliflozin
• Patient-specific factors
  • Drugs that minimize hypoglycemia:
    • DPP4 inhibitor, GLP1 agonist, SGLT2 or TZD
  • Drugs that promote weight loss:
    • GLP1 agonist or SGLT2 inhibitors
  • Drugs with cost concerns:
    • Sulfonylurea or TZD
• Combinations to avoid:
  • DPP4 inhibitors + GLP1
  • Sulfonylureas + insulin

• Insulin dosing for Type II diabetes:
  • Initiate basal insulin after patient fails to reach or maintain goal on multiple oral therapies
  • Starting dose: 0.1-0.2 units/kg/day or 10 units/day
  • Titrate by 10-15% or 2-4 units once or twice weekly until fasting blood glucose at goal
  • If patient reaches fasting blood glucose goal but their A1c is still above goal:
    • Consider the addition of rapid acting mealtime insulin or GLP-1 agonist
• Insulin administration:
  • Abdomen is the injection site (avoid belly button)
  • May also inject in thighs, buttocks, arms
    • Be consistent with administrations
  • Prime before each dose
  • Rotate sites

• Hypoglycemia is common with insulin products, thus important to be aware of what to look out for and how to treat it
  • Defined as a blood glucose < 70 mg/dl
  • Symptoms: sweating, pallor, irritable, hunger, lack of coordination, sleepy
    • Beta blockers mask most except hunger and sweating
  • Treatment
    • Consume 15-20 g of glucose/simple carbohydrates
    • Recheck glucose levels after 15 minutes
    • Repeat if needed
    • Eat a small meal/snack to prevent recurrence
  • Glucagon is used only if patient is unconscious

• Diabetes in pregnancy
  • Gestational diabetes: during pregnancy
    • Risks
      • Macrosomia
      • Hypoglycemia at birth
      • Obesity and type 2 diabetes
    • Management
      • Lifestyle modifications
      • Insulin added if needed (preferred)
      • Metformin and glyburide used
    • Goals:
      • Fasting < 95 mg/dL
      • 1-hour post-meal less than or equal to 140
      • 1-hour post-meal less than or equal to 120

We hope this review helped refresh your clinical knowledge on diabetes. Next up, we will take a look at dyslipidemia.

Best of luck,

Sam Tamjidi

RxPharmacist Team

References:

1. National Diabetes Statistics Report, 2020. Centers for Disease Control and Prevention. https://www.cdc.gov/diabetes/data/statistics-report/index.html. Accessed October 26, 2020.
2. Micromedex Solutions. Greenwood Village, CO: Truven Health Analytics. http://micromedex.com/. Accessed October 26, 2020.