Managing Insulin Deficiency in Patients with Type 2 Diabetes

Current statistics indicate that there is an unprecedented increase in the prevalence of type 2 diabetes in the United States, paralleling the national increase in adult obesity in the last decade. Even more striking is a recent report that 25% of obese children and 21% of very obese adolescents already have prediabetes (Sinha L et al. New Engl J Med 2002;346:802), formerly known as impaired glucose tolerance and impaired fasting glucose. This trend is worrisome, because type 2 diabetes has traditionally been regarded as an adult-onset disease. Prediabetes is a new term used to identify those individuals with elevated fasting glucose levels in the range of 110 to 125 mg/dL, but who do not meet the minimal criterion for diabetes (over 125 mg/dL). Prediabetes, which may affect as much as 16% of the American population, will be the subject of a major awareness campaign to be launched by the Centers for Disease Control and Prevention in the autumn of 2002.

In the United States, the estimated 17.5 million cases of diabetes previously predicted for the year 2010 has already been surpassed. African-Americans are twice as likely to have diabetes as Caucasians, and the prevalence in the Hispanic population is 50% higher than among Caucasians. Almost half of adult Native American males are affected. Health authorities now anticipate increases of 25% in most of the Western industrialized world and 50% in the developing and Asian/ Pacific countries in the current decade.

This program was supportedby an unrestricted educationalgrant from Pfizer Inc.

Managing Insulin Deficiency in Type 2 Diabetes

Richard J. Comi, MD (Dartmouth Hitchcock Medical Center) defined type 2 diabetes as a “metabolic disorder characterized by increased blood glucose sufficient to lead to diabetes microvascular complications despite continued pancreatic secretion of insulin.” He emphasized the point that the objective of glucose control in the patient with diabetes is prevention of complications that occur over time. The Diabetes Control and Complications Trial (DCCT) indicated that patients with high glycosylated hemoglobin (HbA1c) levels, which correspond with elevations in plasma glucose, have a very high risk of developing complications over a period of 10 to 20 years. If average blood glucose can be controlled to a level of 155 to 160 mg/dL rather than 220 mg/dL, and if the HbA1c can be controlled to 6.5% rather than 9.5%, the risk of diabetes complications can be reduced by 50% over the same period of time.

There is, however, a continuum of risk for vascular complications of diabetes. For patients with average postprandial blood glucose levels of 140 to 200 mg/dL, the risk for macrovascular disease is double that of individuals maintained at lower levels. Furthermore, at average levels above 200 mg/dL, there is also a doubling of risk for complications in the microvascular beds leading to diabetic retinopathy and nephropathy. Inadequately controlled type 2 diabetes is the principal cause of the steep rise in the number of American adults dependent on hemodialysis.

The Epidemiology of Diabetes Intervention and Complications (EDIC) trial demonstrated that once vascular complications begin, they progress even if glucose levels are subsequently controlled. This observation increases the urgency of achieving and maintaining effective control prior to the onset of vasculopathy. Similarly, the United Kingdom Prospective Diabetes Study (UKPDS) found that in patients with new-onset type 2 diabetes with an average blood glucose of approximately 150 mg/dL and an average HbA1c of 7.0%, immediate intervention was associated with a lower complication rate than patients who remained untreated until symptoms developed. Nonetheless, because chronic elevation of plasma glucose at any level is associated with increased risk of vascular complications, the goal of therapy should be tight control, with normalization the ideal objective.

Type 1 diabetes, an autoimmune disease, has a typical onset at age 14 and comprises only about 5% of all diabetes in the United States. Type 2 diabetes, a disease that combines gradual pancreatic beta cell dysfunction and increased insulin resistance, most commonly occurs in the age range of 35 to 40 years, though it is now being observed in obese children and adolescents. Following a period of approximately 20 years, during which the pancreas compensates for insulin resistance by overproduction, beta cell function begins to decline and the patient becomes hyperglycemic. Studies using intravenous glucose tolerance testing indicate, however, that even during the period of heightened islet cell activation, patients respond slowly to injected glucose. This indicates that although islet cells are able to secrete insulin during this stage of disease evolution, they do not function normally. There is a loss of approximately 50% of acute secretion prior to the onset of hyperglycemia.

This complicated and multifaceted natural history presents several points for intervention. Patients require more therapy over time as insulin deficiency progresses. Early in its course, when the pancreas is still secreting insulin, reducing the challenge to the pancreas by decreasing carbohydrate intake may suffice to control blood glucose. If this is not sufficient, disaccharidase inhibitors such acarbose and miglitol block the absorption of dietary carbohydrates, thus placing less demand on the beta cells of the islets. Another approach is to enhance the response of beta cells with sulfonylureas or a new class of agents, the meglinides. Meglinides, such as nateglinide and repaglinide, induce rapid increases in insulin secretion.

A fundamentally different approach is to reduce insulin resistance. Studies on diabetes prevention and on controlling early diabetes indicate that body weight is a key factor in insulin resistance, and that a loss of 5% to 10% of body weight significantly improves glucose tolerance. If weight loss is not sufficient, metformin may contribute to improved glucose tolerance. The newer thiazolidinediones are very efficient at improving insulin sensitivity in striated muscle and fat. When oral hypoglycemic agents fail to control glucose, a bedtime dose of NPH insulin is employed in an effort to normalize the fasting blood glucose. This enables the patient to awaken in the morning with a blood glucose level of approximately 120 mg/dL rather than 150 mg/dL or higher.

As insulin deficiency progresses, more aggressive strategies are required to maintain blood glucose control. Moreover, single agent therapy with any of the aforementioned drugs reduces blood glucose by approximately 20 mg/dL and HbA1c by approximately 1%. In general, therefore, any patient with a blood glucose level above 150 and/or a HbA1c above 8% will require combination therapy. Some combinations (see Table 1) are synergistic rather than additive. Whenever possible, combinations that are not associated with weight gain should be selected, and patients taking sulfonylurea agents should be monitored for hypoglycemia. Evening NPH insulin and daytime metformin is an additional synergistic combination

Eventually, type 2 diabetes progresses to the point at which none of these medications or combinations suffice to control blood glucose. At this point, insulin therapy is required to manage both basal needs and mealtime needs and to moderate excursions of blood glucose.

Insulin Therapy in Type 2 Diabetes Mellitus

Ronald A. Arky, MD (Harvard Medical School) cited a study involving 432 people followed by homeostatic metabolism assessment (HOMA), a measure of insulin secretion, that demonstrated the wide variation in the interval from diagnosis to need for pharmacologic intervention with either oral hypoglycemic agents or insulin among patients with type 2 diabetes (Levy J et al. Diabetic Med 1998;15:290). Approximately 20% of participants required medication within 2 to 4 years, and approximately 25% were maintained on behavioral modification for more than 7 years. All of the remainder required the initiation of medical therapy between 4 and 7 years following diagnosis. This study underscores the heterogeneity of the type 2 diabetes population.

The three most common causes for initiating insulin therapy in type 2 diabetes are: (i) acute decompensation with severe symptoms, either old or new; (ii) progressive failure of oral hypoglycemic agents marked by increasing HbA1c, fasting and/or postprandial blood glucose levels; and (iii) need for more aggressive therapy to prevent or reverse complications and to control the HbA1c level of 7.0%.

To illustrate the role of insulin in acute circumstances, Dr. Arky reviewed the case of an overweight and hypertensive mechanic who sought emergency treatment for a grossly infected hand wound. He had a strong family history of diabetes, but had never had a diagnosis of diabetes prior to this event. Normally, newly diagnosed patients are treated with oral hypoglycemic agents; but in light of the acute circumstances, he was a candidate for immediate insulin therapy to get the infection under control. Once that was achieved, his therapy was stepped down to oral hypoglycemic agents.

Dr. Arky next presented the case of a 58-year-old patient diagnosed with diabetes 8 years earlier and subsequently maintained on alternative therapies consisting of metformin, sulfonylureas, and thiazolidinediones. Despite all this treatment, her HbA1c remained at 10.3%. In addition to elevated blood glucose and HbA1c levels, the patient had dyslipidemia, suggesting metabolic syndrome, or syndrome X. Her therapy was switched to daytime metformin and bedtime insulin in an effort to normalize the fasting blood glucose level prior to the morning meal in spite of the possibility of nocturnal hypoglycemia, a potential complication that develops gradually. The combination of thiazolidinediones and intermediate-acting insulin may also be effective, but can cause weight gain, fluid retention, and edema. Thiazo-lidinediones are contraindicated in patients with congestive heart failure.

Metformin should be avoided in patients with elevated creatinine levels, and one of its potential side effects is lactic acidosis. Metformin should be discontinued 24 hours prior to X-ray contrast studies.

Type 2 diabetes that progresses to total insulin deficiency is treated much the same as is type 1 diabetes, formerly referred to as insulin-dependent diabetes. A new and popular strategy for dealing with this is to combine a nightly long-acting basal insulin with a short-acting insulin with a rapid onset of action before meals. The normal pancreas secretes between 0.5 and 0.8 units of insulin per hour or approximately 20 units of insulin basally per day, plus an additional 7.0 to 10.0 units per meal. Contemporary insulin therapy attempts to mimic nature. The current combination that most nearly approximates normal physiology is glarine for 24-hour basal needs plus lispro insulin for controlling postprandial blood glucose levels. Dr. Arky stressed that with basal insulin, nocturnal hypoglycemia is a risk, especially in older patients.

Insulin may have a role in the management of type 2 diabetes during major surgery. Dr. Arky offered unpublished evidence that when glucose is tightly controlled in patients with diabetes during the pre-, intra-, and postoperative periods, rates of infection and hospital stays are reduced and wound healing is accelerated.

Dr. Arky concluded his presentation by emphasizing the interplay among diabetes, hypertension, and dyslipidemia and the need to control all of them to prevent premature complications of the cardiac, coronary, and peripheral circulation.

Practical Tips for Effective Patient Education in Type 2 Diabetes

Erin Fitzpatrick Lepp, PA-C, CDE, MMSc from Emory University chaired the symposium and addressed the audience on diabetes education designed to enable the patient to accept responsibility for managing her/his disease. Most newly diagnosed patients are poorly informed on the subject and may, in fact, be misinformed. The national standards for diabetes self-management education comprise a set of evidence-based guidelines endorsed by the American Diabetes Association. These guidelines emphasize the role of a multidisciplinary team of specialists working interdependently with a physician supervisor. Because of the multimodal nature of treatment, the team may include a certified diabetes educator, a registered dietician, a pharmacist, a registered nurse, a pharmacist, and an exercise physiologist. Because of the nature of the disease and its complications, the team may also include a
podiatrist, an ophthalmologist, a nephrologist, a neurologist, and a psychologist or psychiatrist. Patients treated in this manner have improved clinical outcomes compared with other individuals with type 2 diabetes with respect to acute and long-term complications.

Patient education begins with assessment. This is a process of determining what the patient already knows about diabetes, how motivated she/he may be to take responsibility for behavioral modification and medication, and how confident the patient is about dietary planning, compliance, dosing schedules, and self-injection. It is also important to assess the patient’s concerns and fears about the long-term consequences of diabetes including possible amputation, loss of vision, and dependence on hemodialysis. Attitudes about health care and chronic medication, trepidations associated with the expenses of diabetes care, and domestic support mechanisms should also be assessed. The evaluator should also assess the patient’s readiness to take responsibility for self-management. (The stages of readiness are precontemplation, contemplation, preparation, action, maintenance, and termination or relapse.) The patient’s literacy, cultural or religious beliefs about health care, and any other potential obstacles to self-management also require assessment. All of these steps are designed to evaluate the patient’s “self-efficacy” for life-long management of a disease with potentially fatal complications.

Following assessment, education moves to planning. An action plan consists of written objectives and timetables to address the disease at its current point of evolution based on symptoms, physical condition, and laboratory findings. In addition to medications, this may include a weight-loss plan; individualized medical nutrition therapy to address glucose, lipid and/or HbA1c levels; a light exercise regimen; and psychological adaptation. Lifestyle-adjustment goals should be incremental rather than heroic lest the patient abandon her/his responsibility and rely on medications alone to control the disease. The plan should be matched to the patient’s readiness to take charge. Planning is a problem-solving exercise.

Implementation of the plan is largely the patient’s responsibility, making diabetes management “a constant negotiation between clinician and patient” that involves a range of clinician response from admonition to praise. Many patients require repeated positive reinforcement. The patient should keep records of diet, exercise, weight loss, and so forth for review at periodic return visits, at which time he plan is amended to improve efficacy.

Like any plan, a diabetes education plan can be validated only through evaluation of progress and outcomes with respect to specific goals. The patient is inclined to evaluate on the basis of the goals that she/he manages such as weight, frequency of exercise, and compliance with drug schedules and dietary restrictions. But the clinician’s concern is deeper, namely, the effects of these measures on glucose, HbA1c, and lipid levels and evidence of onset or progression of complications such as elevated creatinine levels, retinal changes, or signs of peripheral neuropathy and/or arterial impairment in the feet. Careful behavioral management and psychological support may be needed if discrepancies arise between the patient’s positive sense of compliance and the clinician’s finding of disease progression. Because many patients have the misguided notion that the switch from oral hypoglycemic agents to insulin dependence is a sign of approaching mortality, medication changes at the point of islet cell exhaustion may also require psychological support.

This presentation may leave the incorrect impression that these four stages of diabetes education—assessment, planning, implementation, and evaluation—are linear events. In fact, however, because type 2 diabetes is a chronic and progressive disease with a rather well-understood natural history, new learning situations may arise frequently. On such occasions, the patient’s self-efficacy for new adjustments requires reassessment, the plan of action may need revision, and implementation may seem more onerous to the patient. Thus diabetes education is a dynamic process in which the individual components, once initiated, proceed simultaneously.

In concluding her talk, Ms. Lepp urged that more physician assistants consider earning additional credentials and expertise as certified diabetes educators (CDEs) in an effort to improve the quality of care and education that patients with diabetes receive. Of the many resources available for preparation, the most comprehensive is the four-volume core curriculum offered by the American Association of Diabetes Educators. The National Certification Board for Diabetes Educators offers the certification examination twice each year.