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Diagnosis and Management of Type 2 Diabetes, Tenth Edition, Ch 9, Pt 2

Oct 12, 2010

Selecting an Insulin Preparation, Chapter 9 – Part 2

Steve V. Edelman, MD, Professor of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego
Robert R. Henry, MD, Professor of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego

Diagnosis_and_Management_of_Type_2_DiabetesThere are three types of insulin: animal, human, and insulin analogues. Although purified insulin from animal sources, (e.g., beef and pork) were the original type, they are no longer manufactured in the United States. Currently, human insulin is the predominant form used. More recently, a number of insulin analogues have been developed. These include the fast-acting analogues, lispro (Humalog), aspart (Novolog), and glulisine (Apidra) (Figure 9.1), as well the long-acting analogues, insulin detemir (Levemir), and insulin glargine (Lantus). An ultra-fast-acting formulation of regular human insulin (Afrezza ) that is administered by inhalation using the patented Technosphere delivery system is currently under review by the FDA. In addition, there are several premixed formulations containing a rapid-acting or short-acting insulin or analogue and a short- or intermediate-acting insulin (Humalog Mix 75/25, Humalog 50/50, Novolog Mix 70/30, Novolin 70/30) (see below for further discussion of these preparations). Therefore, the insulin preparations available to control blood glucose in patients with type 2 diabetes mellitus include:

• Fast-acting insulin analogues (lispro, aspart, glulisine)
• Short-acting preparations (regular insulin)
• Intermediate-acting insulins (NPH)
• Long-acting insulins (glargine and detemir)
• Premixed preparations (lispro+lispro prolamine suspension, aspart+aspart protamine suspension).

The fast-acting insulin analogues are preferential to regular insulin due to their favorable clinical features. Administration is convenient as they can be given imme-diately prior to or with meals. Their faster onset of action limits postprandial hyperglycemic peaks by matching serum insulin availability to appearance of meal-derived glucose into the circulation. Their shorter duration of action also reduces development of late postprandial hypoglycemia. The analogues are used to control PPG and need to be given in concert with basal insulin replacement regimens.

Figure_9-1Short/fast-acting insulins, as well as long-acting insulin preparations, are needed to mimic the pattern of insulin delivery that normally controls blood glucose in nondiabetic individuals. Basal insulin therapy with long-acting insulin is required to suppress hepatic glucose production overnight and between meals, while short’ rapid insulin preparations are needed as bolus insulin to prevent hyperglycemia after meals.

Human insulin is particularly useful for patients with:

• Insulin allergy
• Severe insulin resistance caused by insulin anti¬bodies
• Lipotrophy
• A requirement for intermittent insulin therapy ( ie, during pregnancy and acute problems such as infection, MI, and emergency surgery).

Many of the complications of insulin therapy are now uncommon because of the advent of more purified human preparations and insulin analogues.

Selecting an appropriate insulin preparation also depends on the desired time course of action or pharmacokinetics. The values shown in Table 9.1 are general guidelines that can vary considerably among individuals, especially those with type 2 diabetes.

Other factors that influence the action of insulin in an individual include: Dose, Site and depth of injection, Local tissue blood flow, Skin temperature, and Exercise.


The time courses of action of the various insulins are shown graphically in Figure 9.2. The recommended interval between an injection of regular or fast-acting insu¬lin and mealtime is 30 to 45 and 5 minutes, respectively, when the preprandial blood glucose is adequate (



© Copyright 2010. Steven V. Edelman, MD, Robert R. Henry, MD, Professional Communications, Inc. All rights reserved.


Next Week: Application of Intensive Insulin Therapy (Chapter 9)

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