Intensive Insulin Therapy in Diabetes Management

Intensive Insulin Therapy in Diabetes Management Lillian F. Lien, MD Medical Director, Duke Inpatient Diabetes Management Assistant Professor of Medicine Division of Endocrinology, Metabolism, & Nutrition Sarah W. Stedman Center for Nutrition and Metabolism Duke University Medical Center

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Disclosures for Dr. Lillian F. Lien The Department of Medicine requests the following disclosures to the lecture audience: Disclose relevant financial relationships with any commercial interest: Sanofi-Aventis: consultant Merck: consultant Eli Lilly: consultant Novo Nordisk: consultant

Diabetes Mellitus: The need for optimal control Glycemic control has been shown to promote white blood cell function and facilitate wound healing Improvements in hyperglycemia have also reduced morbidity and mortality Lien et al. In-hospital Management of Type 2 Diabetes Mellitus Medical Clinics of North America. Vol. 88, No. 4: p.1085-1105, July 2004

Summary of glycemic recommendations ADA Position Statement 2012 DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 A1C <7.0% Lowering A1C to below or around 7% has been shown to reduce microvascular complications of diabetes, and if implemented soon after the diagnosis is associated with longterm reduction in macrovascular disease. Providers might reasonably suggest more stringent A1C goals (such as <6.5%) for selected individual patients, if this can be achieved without significant hypoglycemia or other adverse effects Less stringent A1C goals (such as <8%) may be appropriate for patients with a history of severe hypoglycemia, limited life expectancy, advanced microvascular or macrovascular complications, and extensive comorbid conditions

Summary of glycemic recommendations ADA Position Statement 2012 DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012 A glucose range of 140 180 mg/dl (7.8 to 10 mmol/l) is recommended for the majority of critically ill pts More stringent goals, such as 110 140 mg/dl (6.1 7.8 mmol/l) may be appropriate for selected patients, as long as this can be achieved without significant hypoglycemia. Non critically ill patients: If treated with insulin, premeal blood glucose targets generally <140 mg/dl (7.8 mmol/l) with random blood glucose <180 mg/dl (10.0 mmol/l) are reasonable, provided these targets can be safely achieved. Less stringent targets may be appropriate in those with severe comorbidities.

Insulin Source: Lien and Rodgers Insulin Pharmacology Talk 2009

Types of Insulin Type Product Brand Rapid-Acting Lispro Aspart Glulisine Humalog Novolog Apidra Short-Acting Regular R Humulin, Novolin, ReliOn Intermediate-Acting NPH N Humulin, Novolin, ReliOn Basal Premixed Glargine Detemir 70/30 regular 75/25 lispro 70/30 aspart 50/50 Lantus Levemir Humulin, Novolin, ReliOn Humalog 75/25 Novolog Mix 70/30 Humulin, Humalog Source: Lien and Rodgers Insulin Pharmacology Talk 2009 JAMA 2003;289:2254-64 Clin Pharmacology Online, 2009

Comparison of Human Insulins and Analogues Insulin Preparations Onset of Action Peak Duration of Action Lispro, Aspart, Glulisine* 5-15 min 30-90 min 4-6 h (*6-8 h) Regular 30-60 min 2-4 h 6-10 h NPH 1-2 h 4-8 h 10-20 h Glargine 1-2 h None 24 h Detemir 1-2 h 6-8 h 12-24 h Source: Lien and Rodgers Insulin Pharmacology Talk 2009 JAMA 2003;289:2254-64 Clin Pharmacology Online, 2009

Insulin Dynamics Lispro Aspart Glulisine Plasma Insulin Level Regular NPH Glargine (Lantus) Or Detemir (Levemir) 2 4 6 8 10 12 Time (h) Source: Lien and Rodgers Insulin Pharmacology Talk 2009

Diabetes Management Dosing Info for SQ Insulin: KEY is WEIGHT-BASED Total Daily Dose Type 1 start 0.3-0.5 units/kg/day Often quite sensitive; start on low end Type 2 start 0.3-0.7 units/kg/day New to insulin: start on low end Some patients may require > 1 unit/kg/day EXAMPLE: 100 kilogram patient X 0.3 units/kg/day = 30 units /day = Total Daily Dose Lien LF, Cox ME, Feinglos MN, Corsino L. (eds.) Glycemic Control in the Hospitalized Patient, 1 st Edition. Springer, 2010

Diabetes Management Distribution of the Total Daily Dose Basic Starting Regimens: (Oral plus) Basal Insulin Therapy (1-injection) Premixed Insulin Therapy (2-injections) Intensification: Most Intensive: Basal-Bolus Insulin Therapy (4-shots) In between: Stepwise Addition of Bolus Insulin to Basal Insulin Leahy JL. Insulin Therapy in Type 2 Diabetes Mellitus Endocrinol Metab Clin North Am 01-MAR-2012; 41(1): 119-44

Diabetes Management Key Points: Basal Insulin Therapy Lien et al. In-hospital Management of Type 2 Diabetes Mellitus Medical Clinics of North America. Vol. 88, No. 4: p.1085-1105, July 2004 Lien LF, Cox ME, Feinglos MN, Corsino L. (eds.) Glycemic Control in the Hospitalized Patient, 1 st Edition. Springer, 2010 Once daily insulin injection seldom provides adequate glucose control alone But may be used in combination with oral hypoglycemic agents in patients with Type 2 DM The basal component should be estimated at approximately 50% of the Total Daily Dose Should not equal 100% Total Daily Dose to avoid inappropriate coverage of prandial needs with basal insulin risk of hypoglycemia EXAMPLE: 100 kilogram patient X 0.3 units/kg/day = 30 units /day = Total Daily Dose BASAL (Lantus or Levemir)* Insulin = Give only 15 units once* daily! * Discussion: BID analogues for type 1. BID NPH for cost.

Type Product Brand Premixed 70/30 regular 75/25 lispro 70/30 aspart Humulin, Novolin, ReliOn Humalog 75/25 Novolog Mix 70/30 Pre-Mixed Insulin: Two Injections Daily In patients who are eating, the estimated daily insulin dose should be divided into 2 injections. 2/3 of the total daily dose is administered in the morning, before breakfast. 1/3 of the total daily dose is administered prior to the evening meal. EXAMPLE: 100 kilogram patient X 0.3 units/kg/day = 30 units /day = Total Daily Dose Lien et al. In-hospital Management of Type 2 Diabetes Mellitus Medical Clinics of North America. 2004; 88(4): 1085-1105 Breakfast Dose: 20 units Evening Meal Dose: 10 units

Diabetes Management Key Points: Basal-Bolus Insulin Insulin strategy: Basal + bolus + correctional insulin scale (optimal insulin regimen) Correctional insulin scale: Avoid using as the only insulin regimen. Not necessarily appropriate for all patients. Best to be used for wellmotivated patients who are at risk for hyperglycemia. Patients with type 1 diabetes always require basal insulin, even if they are not eating. Lien LF, Cox ME, Feinglos MN, Corsino L. (eds.) Glycemic Control in the Hospitalized Patient, 1 st Edition. Springer, 2010

Insulin Regimens Four Injections Daily *Basal Insulin can be given Before Bedtime, or at any other time of day, As long as it is the SAME TIME EACH DAY Using rapid-acting insulin (bolus) and long-acting, peakless insulin (basal) One-sixth of the total daily dose is administered before breakfast, lunch, and dinner as rapid-acting insulin (Humalog or Novolog or Apidra) One-half of the total daily dose is administered once daily* as a long-acting, peakless insulin (Lantus or Levemir) EXAMPLE: 100 kilogram patient X 0.3 units/kg/day = 30 units /day = Total Daily Dose Basal Dose: 15 units daily Bolus Dose: 5 units with each meal Lien et al. In-hospital Management of Type 2 Diabetes Mellitus Medical Clinics of North America. Vol. 88, No. 4: p.1085-1105, July 2004

Insulin Regimens Four Injections Daily Using regular insulin and NPH insulin One-fourth of the total daily dose is administered as regular insulin before breakfast, lunch, and dinner One-fourth of the total daily dose is administered as NPH insulin prior to bedtime Lien et al. In-hospital Management of Type 2 Diabetes Mellitus Medical Clinics of North America. Vol. 88, No. 4: p.1085-1105, July 2004

Diabetes Management Stepwise Addition of Bolus Insulin to Basal Insulin Adding prandial insulin in a stepwise fashion to patients with optimized basal insulin is still being validated One-by-one addition of mealtime insulin to optimized basal insulin is less intimidating for most patients and providers Leahy JL. Insulin Therapy in Type 2 Diabetes Mellitus Endocrinol Metab Clin North Am 01-MAR-2012; 41(1): 119-44

Regardless of which style of insulin regimen is chosen, the most important governing principle is individualization of the regimen

Insulin Stacking Repeating SQ insulin dose before prior dose wears off. How to avoid this? Next dose no sooner than 3 hours after last dose of SQ rapidacting (log) insulin Wait at least 4 hours between SQ regular insulin doses N Engl J Med 2005;352:174-83 Source: Lien and Rodgers Insulin Pharmacology Talk 2005

Factors that affect insulin absorption: Exercise Massage of area Temperature Site of Injection Lipohypertrophy Large doses (>80 units) Factors in the hospitalized patient Severity of illness Strenuous use of injected limb within one hour Do not rub site vigorously Medications: glucocorticoids, pressors Diet: different, unpredictable Heat increases, cold decreases Abdomen>arms>thigh (R & N only) Delays absorption Delay onset and duration Adapted from www.endotext.org, 2004 Caution: coordination of timing of insulin administration and meals or NPO status Inzucchi SE. N Engl J Med 2006;355:1903-11

Outstanding Issues? Intravenous Insulin Any critically ill patient with persistent hyperglycemia for 24 h is a candidate for an IV insulin infusion, particularly if the hyperglycemia lingers despite increasing doses of subcutaneous insulin Mabrey M and Lien LF. IV Insulin Infusions: How to Use an Insulin Drip Chapter 3 in Glycemic Control in the Hospitalized Patient, First Edition,eds. Lien LF, Cox ME, Feinglos MN, Corsino L. New York: Springer, 2010 Lien L, Spratt S, Woods Z, Osborne K, Feinglos M. Optimizing Hospital Use of Intravenous Insulin: Improved hyperglycemic management and error reduction with a new nomogram Endocrine Practice. Vol. 11, No. 4: p.240-253, July/Aug 2005 CSII continuous subcutaneous insulin infusion (pumps) Role of Incretin (GLP-1, DPP-IV) Therapies

Lillian F. Lien, MD Medical Director, Duke Inpatient Diabetes Management Assistant Professor of Medicine Duke Division of Endocrinology, Metabolism, and Nutrition & the Sarah W. Stedman Nutrition and Metabolism Center Particular Clinical and Research Interests: Intravenous Insulin (Lien-Spratt Insulin Nomogram) Safety and Efficacy in inpatient diabetes management Obesity lillian.lien@duke.edu Lien LF, Cox ME, Feinglos MN, Corsino L. (eds.) Glycemic Control in the Hospitalized Patient, First Edition. Springer, 2010