Intensive insulin therapy

Published on 02/03/2015 by admin

Filed under Endocrinology, Diabetes and Metabolism

Last modified 02/03/2015

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Intensive insulin therapy

1. What is intensive insulin therapy?

2. List critical components of intensive therapy.

3. Summarize studies evaluating optimal glycemic control to decrease chronic diabetes complications.

The Diabetes Control and Complications Trial (DCCT), evaluating patients with recent-onset type 1 diabetes, showed that improved glycemic control (hemoglobin A1C [HbA1C] < 7%) significantly reduced rates of microvascular complications, including progression of retinopathy, nephropathy, and neuropathy, but increased rates of hypoglycemia. Intensive insulin therapy was a key part of achieving glycemic control in the DCCT. The Kumamoto Study and the United Kingdom Prospective Diabetes Study (UKPDS) confirmed that improved glycemic control (HbA1C < 7%) was associated with significantly reduced rates of microvascular complications in patients with recent-onset type 2 diabetes. The long-term extensions of the DCCT and the UKPDS showed significant reductions in cardiovascular complications with good glycemic control and demonstrated that the microvascular benefits of good glycemic control persisted for decades. Later studies in patients with more advanced type 2 diabetes (Action to Control Cardiovascular Risk in Diabetes [ACCORD] trial, Action in Diabetes and Vascular Disease [ADVANCE] trial, and VA Diabetes Trial [VADT]) failed to show that more aggressive glycemic targets (HbA1C < 6.0%-6.5%) reduced cardiovascular complications, and one study showed an increase in mortality. Rates of hypoglycemia with more aggressive glucose control were significant in all three trials.

4. Which patients are candidates for IIT?

5. What are the risks of intensive insulin therapy?

Hypoglycemia and weight gain are the most common adverse effects of insulin therapy. IIT in the DCCT resulted in a three-fold increased risk of severe hypoglycemia in comparison with conventional treatment (62 episodes per 100 patient-years of therapy). Since the completion of the DCCT, newer rapid-acting and long-acting insulin analogs have been developed that are associated with less hypoglycemia than the short-acting and intermediate-acting human insulin products used in the trial. Frequent episodes of hypoglycemia can lead to loss of clinical warning symptoms (e.g., palpitations, sweating, hunger) with hypoglycemia (known as hypoglycemia unawareness). A unique risk of pump therapy is diabetic ketoacidosis because pump malfunctions or infusion site problems can interrupt insulin delivery. Finally, IIT requires time and commitment from the patient and may have negative psychosocial and economic implications.

6. Explain the difference between basal and bolus insulin coverage.

Intensive insulin therapy attempts to mimic normal insulin secretion, which includes continuous basal coverage in addition to bursts of insulin to regulate the rise in glucose after food intake (Fig. 3-1). Basal insulin secretion suppresses hepatic glucose production to control blood glucose levels in the fasting state and premeal periods. Normal basal insulin secretion from the pancreas varies slightly throughout the day, responding to changes in activity, blood glucose levels, and regulatory hormones. Basal coverage is usually accomplished with injections of long-acting insulin preparations or with the basal infusion function on the insulin pump. Bolus insulin doses consist of two components, the nutritional dose (the amount of insulin required to manage glucose excursions following meals) and the correction dose (the amount of insulin required to reduce a high glucose level detected before a meal). Bolus coverage is accomplished by injections of rapid-acting or short-acting insulin preparations or with use of the bolus function on the insulin pump. Physiologic insulin secretion requirements are approximately 50% basal and 50% bolus.

7. How are basal and bolus insulins used with an MDI regimen?

A long-acting insulin is injected either once or twice daily to provide the basal insulin portion of an MDI regimen, which is approximately 50% of a patient’s total daily dose. Ideally, basal insulin should cover background insulin needs only, independent of food intake. A rapid-acting or short-acting insulin is injected before meals to provide the bolus insulin portion of an MDI regimen (see Fig. 3-1). Rapid-acting insulin is preferred because of the rapid onset and short duration of action. A patient can adjust each bolus dose to match the carbohydrate intake and to correct for high glucose levels before the meal, whereas the basal dose remains constant from day to day. Premixed “biphasic” insulin preparations combine either a rapid-acting insulin analog or regular human insulin with a crystalline protaminated form of the analog or NPH (neutral protamine Hagedorn) human insulin in an attempt to imitate basal and bolus therapies with fewer injections.

8. What are the currently available insulin preparations?

9. Describe the pharmacodynamics of insulin preparations.

10. When should bolus insulin be taken?

11. When should basal insulin be taken?

12. What is an insulin pump?

An insulin pump is a small, lightweight, portable, battery-operated device that is either attached directly to the body (patch pump) or worn on clothing or a belt like a pager (traditional pump). A traditional pump is composed of a pump reservoir (which holds a 2- to 3-day supply of rapid-acting or short-acting insulin) connected to an infusion set, which ends in a cannula that is inserted into the skin and changed every 2 to 3 days. A patch pump is tubing free and consists of a disposal reservoir that attaches directly to the body with self-adhesive backing and a built-in infusion set in the device for insertion into the subcutaneous tissue. The patch pump is controlled by a handheld personal digital assistant. Insulin is delivered through either system in microliter amounts continuously over 24 hours. The user is responsible for setting basal rates and determining bolus doses, depending on the meal ingested and the SMBG results. Currently, six companies offer insulin pumps in the United States; several other pumps are in development. Each pump has special features and functions that are unique and help with the flexibility of pump use. To learn more about each of these pumps, contact the companies listed in Table 3-2.

TABLE 3-2.


Roche Insulin Delivery Systems ACCU-CHEK Spirit
Sooil Development Dana Diabecare IIS
Medtronic Diabetes MiniMed Paradigm Real-Time Revel
Insulet Corporation OmniPod
Animas Corporation OneTouch Ping
Tandem Diabetes Care t:slim

13. What are the patient’s responsibilities before insulin pump therapy can be initiated?

14. Describe the benefits of insulin pump therapy.

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