Type 2 diabetes: the role of insulin

Journal of Family Practice, May, 2005 by Stephen Brunton, Blaine Carmichael, Martha Funnell, Daniel Lorber, Robert Rakel, Richard Rubin

Diabetes mortality rates continue to escalate despite advances in therapy and more aggressive management guidelines promulgated by the American Diabetes Association (ADA) and the American College of Endocrinology (ACE). The Diabetes Control and Complications Trial (DCCT) and United Kingdom Prospective Diabetes Study Groups (UKPDS) trials have clearly demonstrated the benefits of intensive diabetes control, and an increasing body of evidence has been focused on the contribution of post-prandial glucose (PPG) levels to elevated levels of glycosylated hemoglobin AIC. Moreover, the results of large, randomized, controlled clinical trials such as these have clearly demonstrated that improved glycemic management is associated with reductions in the microvascular complications, specifically retinopathy, nephropathy, and neuropathy, that are associated with inadequately managed diabetes. (1-7)

Since publication of the DCCT and UKPDS findings, it has become clear that tighter control of blood glucose in type 2 diabetes can significantly reduce the development and progression of microvascular complications. Furthermore, the frequency of macrovascular complications may be decreased by near-normalization of blood glucose levels. (8)

Despite these benefits, blood glucose levels continue to be poorly controlled in many patients with type 2 diabetes. (9) Results from UKPDS showed a gradual decline of glycemic control from the time of randomization in patients receiving conventional treatment, while in the United States, the number of patients in good glycemic control (A1C <7%) has declined from 44.5% during 1988-1994 to 35.8% in 1999-2000. (10) Even with the most effective therapeutic interventions available, control of the rising levels of glycemia associated with type 2 diabetes can be a challenge for the patient and physician alike.

The progression of diabetes is associated with declining insulin secretion, increased insulin resistance, and eventual [beta]-cell failure. Deterioration of glycemic control is directly related to the progressive loss of [beta]-cell function. (11) On average, patients have lost approximately half of their [beta]-cell function by the time the diagnosis of diabetes is made. (11-14) Insulin resistance and progression of insulin secretory dysfunction are major confounders of effective long-term glycemic management, (12,13) directly contributing to the diminished efficacy of oral antidiabetic agents (OADs), even when used in combination. Although [beta]-cell function is temporarily increased with the use of sulfonylureas, there is no concomitant increase in the longevity of [beta] cells, and the rate of failure remains the same as with other therapeutic strategies. (12,13)

Diet, exercise, weight loss, and a healthy lifestyle remain essential in the initial and ongoing management of type 2 diabetes. The addition of 1 or more OADs is appropriate when glycemic control can no longer be achieved through the use of the initial nonpharmacologic measures. Similarly, insulin should be added when the combined use of OADs and nonpharmacologic measures are no longer able to achieve glycemic control. (15) The addition of insulin to sulfonylurea therapy improves glycemic control, as shown by a subset analysis of the UKPDS, without promoting weight gain or increased risk of hypoglycemia. (16) Subsequent clinical trials have further corroborated the benefits of insulin in patients with type 2 diabetes. Benefits associated with early initiation of insulin therapy include prevention of glucose toxicity, preservation of existing [beta]-cell function, and prevention or delay of microvascular and macrovascular complications. (17)

The initiation of insulin administration is often delayed in patients with type 2 diabetes for several reasons, including a perception that insulin therapy is complex, lacks resources in an office-based practice, fear of hypoglycemia, (18) and provider and patient resistance to its use (TABLE 1). Even when insulin is prescribed early in treatment, low doses are often employed due to the fear of hypoglycemia. (19,20) Appropriate patient education early in treatment can do much to alleviate fears and misconceptions (TABLE 2). (21)

The safety of insulins has been closely evaluated, particularly with respect to the incidence and severity of hypoglycemia. Although severe hypoglycemia can be life-threatening, most hypoglycemic episodes are mild in patients with type 2 diabetes, involving symptoms that can be readily recognized and effectively self-treated. The variety of options and resources available for diabetic patients who are new to insulin is another area where comprehensive education can be helpful. Many of these options, such as insulin analog premixes, less painful needles, and pen devices, can help simplify aspects of insulin therapy, thereby making it easier to teach and initiate in an office-based setting and increasing its acceptability among patients. The remainder of this review focuses on the role of insulin in patients with type 2 diabetes and provides a comparison of the advantages and disadvantages of selected types of insulin.