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Insulin Titration

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Insulin regimen titration for T2DM

Outline

• General Principles
  • Physiologic insulin secretion is 50/50 basal/prandial
  • Insulin preparations
    • Basal supplements: NPH, Detemir (LEVEMIR®), Glargine (LANTUS®), Glargine (BASAGLAR®) *not interchangeable with LANTUS.
    • Pre-meal: short-acting (regular) or rapids: aspart (NOVOLOG®), lispro (HUMALOG®), glulisine (APIDRA®)
    • Premixed combo
  • Indications - all expert opinion really, pathophysiologic common sense?
    • Second-line med for A1c > 8.5
    • A1c > 9.5%, Fasting Glucose > 250, Random > 300, Ketonuria, Unintentional weight loss
    • Possible Type 1s (25% of type 1 cases occur after age 35), Latent Autoimmune Diabetes in Adult (GAD-65 Ab Positive)
    • Pregnant women who fail diet/exercise/nutrition and maxed out on glyburide.
  • Major drawbacks to insulin:
    • Weight gain
    • Hypoglycemia
• Different regimens are pretty much similarly effective
• Where to start?
  • Consider the 50 year-old man p/w fingerstick glucose 299, polyuria, polydipsia, fatigue, A1c 14.9%.
  • Initiate with Basal - less hypoglycemia/better patient satisfaction; [1]
    • Bedtime NPH or Detemir
      • Bedtime = After dinner, and 9-10 hours before AM Fasting Glucose measurement/breakfast the next day
    • Anytime Glargine
  • Titrate AM fasting glucoses are within target ranges 70-130 mg/dL.
    • A1cs still not at goal? Measure pre-lunch, pre-dinner, and bedtime fingersticks.
    • Pre-dinner elevations: + NPH pre-breakfast, + short/rapid pre-lunch
    • Pre-lunch or Bedtime elevations: + short/rapid pre-breakfast or pre-dinner
• Dosing
  • Initial - similar whether we are combining with oral agents, switching, or starting
    • Basal - Start at 0.2 units/kg of TBW
    • Prandial - 4-6 units vs carb count
  • Titrate - every 3 days (check out the Treat-to-Target Trial from 2003) [6]
    • 120-140 → +2 units
    • 141-160 → +4 units
    • 161-180 → +6 units
    • 180+ → +8 units
• Regimens
  • Twice daily - Bedtime and Pre-breakfast NPH - cheap and effective
  • Basal bolus - Pre-breakfast/lunch/dinner regular (30-45 min pre-meal) or lispro/aspart/glulisine (immediately pre-meal)
  • Intensive - + more frequent measurements/doses corresponding to activities, insulin pumps (even MORE physiologic)

Sources

1. McCulloch, DK. Insulin therapy in type 2 diabetes mellitus. In: UpToDate, Nathan, DM (Ed), UpToDate, Waltham, MA. (Accessed on June 24th, 2016.)

2. Petznick, A. Am. Fam. Physician 2011, 84 (2), 183–190.

3. DeFronzo, R. A.; Eldor, R.; Abdul-Ghani, M. Diabetes Care 2013, 36 (Supplement 2), S127–S138.

4. McCulloch, DK. Overview of medical care in adults with diabetes mellitus. In: UpToDate, Nathan, DM (Ed), UpToDate, Waltham, MA. (Accessed on June 24th, 2016.)

5. Bakris, GL. Treatment of hypertension in patients with diabetes mellitus. In: UpToDate, Kaplan, NM, Nathan, DM (Ed), UpToDate, Waltham, MA. (Accessed on June 24th, 2016.)

6. Riddle, M. C.; Rosenstock, J.; Gerich, J. Diabetes Care 2003, 26 (11), 3080–3086.

Supplemental

Background

Comprehensive cardiovascular risk factor reduction program for diabetics to reduce cardiovascular risk:

• Smoking Cessation
• Diet
• Exercise
• BP Control - measure every visit, goal systolic 125-130 mmHg
• Lipid Management - statins based on ASCVD Risk.
• Anti-platelet Therapy - If secondary prevention, or primary prevention + ASCVD Risk > 10% ≈ Age > 50 + 1 other CV RF (though the ADA recognizes that evidence to support this recommendation is weak)
• Metformin - may independently reduce CV risk… may (UKPDS)

Fun Fact

• NPH stands for Neutral Protamine Hagedorn - invented in 1936. Neutral protamine is a suspension of crystalline zinc and positively-charged polypeptide protamine (https://www.wikiwand.com/en/NPH_insulin). When combined with regular insulin, it yields a combination that has a longer duration of action than regular insulin.

Facts

Does diabetes have an impact on life expectancy?

• Compared with nondiabetics, men and women with diabetes have decreased life expectancy (six to eight years less). [Overview of medical care in adults with diabetes mellitus]

Does glycemic control reduce cardiovascular risk in type 1 diabetics? Type 2?

• Among patients with type 1 diabetes, the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study demonstrated long-term benefit of intensive glycemic management on cardiovascular outcomes, reducing fatal and nonfatal heart disease and stroke by 57 percent compared with conventional diabetes management. [Overview of medical care in adults with diabetes mellitus]

• With regard to CVD risk reduction among patients with type 2 diabetes, the benefit of good blood pressure control has been confirmed, whereas benefit from strict glycemic control has not been conclusively demonstrated. [Overview of medical care in adults with diabetes mellitus]