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Literature Compendium |
Current Concepts in Type 2 Diabetes
Volume 2
The Appropriate Application of Oral Pharmacological Therapy, Non-Insulin Injectable Agents, and Insulin in the Management of Type 2 Diabetes
Chapter 4
Insulin in the Management of Type 2 Diabetes: Goals and Strategies
Insulin preparations are prescribed for a substantial proportion of individuals with Type 2 diabetes, yet few appear to achieve the American Diabetes Association-recommended HbA1c target of ≤7.0 %. Hence, sub-optimal insulin therapy may be a common phenomenon. A growing understanding of insulin physiology has led to the development of novel insulin preparations, thereby providing new options for clinicians seeking to integrate insulin therapy into the management paradigm for individuals with Type 2 diabetes. This chapter contains key papers that provide a comprehensive overview of insulin therapy in Type 2 diabetes, with emphasis on goals and strategies involving newer agents. In addition, it highlights the need for increased awareness of the benefits of insulin therapy in individuals with Type 2 diabetes.
Blood glucose concentration is based on carbohydrates absorbed from the gut and those produced in the liver. Insulin release from β-cells in the pancreas is stimulated by increased blood glucose levels. The postprandial glucose influx can be up to 30 times greater than hepatic production between meals. Phase 1 insulin release, which lasts approximately 10 minutes, suppresses hepatic glucose production and facilitates phase 2 release, which lasts up to 2 hours and covers postprandial glucose elevations. Between meals, a low continuous insulin level, called basal insulin, serves ongoing metabolic needs. In Type 2 diabetes, phase 1 insulin release is absent, and phase 2 release is delayed and inadequate. The sharp spike of mealtime insulin release occurring in normal persons is delayed, prolonged, and inadequate in persons with Type 2 diabetes.
Injectable insulin is categorized as basal or bolus insulin based on the duration of action. Basal insulins include neutral protamine Hagedorn (NPH), or isophane insulin; ultralente; and the insulin analogue glargine. Bolus or mealtime insulins include regular insulin and the analogue forms aspart and lispro. Premixed formulations incorporate NPH and regular or rapid-acting analogues in various relative concentrations. Several inhaled insulin formulations are in development, as are transdermal, oral, and intranasal insulin formulations.
Wright and colleagues1 evaluated glycaemic control, hypoglycaemia, and body weight over a 6-year period in 826 individuals with newly diagnosed Type 2 diabetes who participated in the United Kingdom Prospective Diabetes Study (UKPDS). Individuals were randomized to receive conventional therapy with either diet alone (n=242) or intensive therapy with insulin alone (n=245), as in the main UKPDS study. For individuals randomized to intensive treatment with a sulfonylurea (n=339), insulin was added if the fasting plasma glucose remained >6.0 mmol/l (108.1 mg/dl) despite maximal sulfonylurea doses. Over the 6-year study period, roughly 53% of individuals allocated to treatment with a sulfonylurea required additional insulin therapy, and mean HbA1c reduction in the sulfonylurea/insulin group was significantly lower than that in the insulin monotherapy group. The incidence of weight gain was similar in both intensive-therapy groups, and hypoglycaemia occurred less often in the sulfonylurea/insulin group than in the insulin-monotherapy group. This study was important because it demonstrated that the addition of insulin to a maximized sulfonylurea regimen can significantly improve glycaemic control without increasing the rate of adverse sequelae.
Gallagher and colleagues2 performed a single-center, open-label, crossover study to evaluate whether restoration of a more physiological insulin profile by using rapid-acting insulin can improve insulin secretion rate (ISR) and markers of vascular risk. Eighteen individuals with Type 2 diabetes were enrolled. ISR did not differ between insulin aspart and human insulin, and there was no appreciable change in markers of vascular risk.
Initiating insulin earlier in the course of Type 2 diabetes may lead to better glycaemic control and prevent or delay diabetes-related complications. The paper by Meneghini3 is an informative review written from the perspective of the practicing clinician. The author notes that insulin therapy is the most effective method of managing hyperglycaemia, yet it is often delayed because of concerns about the complexity and inconvenience of treatment regimens; fear of injections, hypoglycaemia, or weight gain; and the time required to learn how to effectively manage it. He believes that the development of insulin analogues, biphasic insulin analogues, and more convenient insulin delivery systems, such as inhaled insulin, may make insulin therapy more manageable and help more patients achieve their treatment goals, and he compares the various insulin preparations with regard to rapidity of action, efficacy in Type 1 and Type 2 diabetes, and clinical outcomes.
The use of insulin therapy in individuals with Type 2 diabetes is currently sub-optimal and has been a focal point at recent professional meetings. A consensus report launched at the 42nd Annual Meeting of the European Association for the Study of Diabetes, held in September 2006, in Copenhagen, Denmark, urges the increased acceptance of insulin. The report was produced by a panel of 25 diabetes experts from 16 different countries who convened to address the growing diabetes epidemic. The panel was formed to examine ways to address the growing burden of diabetes using the results of the Optimizing Control in Diabetes (OPTIMIZE) survey, in which a multinational sample of 1444 persons with Type 2 diabetes were questioned about their attitudes towards diabetes management. Significant patient-related barriers to achieving optimal blood sugar control were identified, one of the most significant being patient resistance to injections. For example, in one sub-analysis of the OPTIMIZE study sample, Davidson4 evaluated patient attitudes in a sample of 406 interviewees from Mexico and Brazil, many of whom used subcutaneous (SC) insulin. Eighty-four percent of respondents were not aware of their most recent HbA1c. When respondents who were not using SC insulin were asked how they felt about using SC insulin in the future, more than half said they would avoid it if possible. In this survey, the majority of respondents reported that they would prefer to take SC insulin another way, whether they were currently using SC insulin or not. The investigator concluded that improving patients’ perceptions of insulin could encourage earlier use and facilitate the achievement of long-term glycaemic control.
Despite the barriers to insulin administration, it is increasingly recognized as a major component of the treatment paradigm for individuals with Type 2 diabetes and is, of course, an absolute necessity for those with Type 1 diabetes. The guidelines reviewed in Chapter 1 call for earlier and more aggressive use of insulin in individuals with Type 2 diabetes in order to reduce blood glucose concentration and control the disease. Ongoing investigations focus on new formulations of insulin and alternate routes of administration in an effort to increase convenience, acceptance, and tolerability.
References
2. Gallagher A, Butler TJ, Home PD. The effect of the optimal use of rapid-acting insulin analogues on insulin secretion in type 2 diabetes. Diabetes Res Clin Pract. 2007;76:327-334.
Click to proceed to Programme Evaluation and Post-test.
Click to return to Opening Page.
Click to return to Table of Contents.
Click to return to Introduction.
Click to return to Chapter 1.
Click to return to Chapter 2.
Click to return to Chapter 3.
The Literature Compendium is funded by an educational grant from Pfizer Inc.
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