Abstract
The responsibility of diabetes management and insulin therapy has definitively moved to primary care physicians. Within the primary care setting, there is a growing need for clear, evidence-based guidelines related to the management of insulin therapy. Straightforward algorithms regarding insulin initiation, titration, and follow-up management can help physicians effectively treat patients with type 2 diabetes mellitus. Once 2 oral diabetic drugs have failed in a patient whose disease duration is 7 to 10 years, use of insulin therapy with a basal insulin analog should be considered. For patients who receive maximal basal insulin doses without reaching fasting blood glucose and target glycated hemoglobin levels with basal insulin analogs, a mealtime-insulin intensification approach should be considered. The authors discuss how simplified insulin initiation and titration regimens allow primary care physicians and other health care professionals to care for patients with type 2 diabetes mellitus.
Diabetes affects 25.8 million people in the United States; most (90-95%) adults with a diagnosis of diabetes have type 2 diabetes mellitus (T2DM).
1 Primary care physicians (PCPs) deliver approximately 90% of diabetes care in the United States.
2 Type 2 diabetes mellitus is characterized by progressive β-cell failure and increasing difficulty in maintaining glycemic control.
3,4 Even with multiple oral antidiabetic drugs, many patients need insulin therapy to achieve and maintain glycated hemoglobin (HbA
1c) target levels.
4
The intensification of diabetes treatment—that is, the transition from oral antidiabetic drugs to injectable treatments such as insulin—is often delayed in many patients, which substantially increases the risk of diabetes-related complications.
5-10 In a population-based analysis,
5 25% of patients with T2DM initiated insulin therapy within 1.8 years and 50% of patients initiated insulin therapy within 5 years of failure to achieve or maintain glycemic control despite multiple oral antidiabetic drugs, even in the presence of diabetes-related complications.
There are several barriers to initiation of insulin therapy. For patients, barriers include fears about injections and the risk of hypoglycemia, difficulties in managing insulin therapy, perceptions that insulin may impose life-style restrictions, and beliefs that insulin use indicates greater severity of disease and failure of self-management.
11-13 Physicians' barriers to initiation of insulin therapy include concerns about potential adverse effects (eg, increased hypoglycemia and weight gain) and practical concerns (eg, patient anxiety about insulin, perceived adherence issues, difficulties in training patients to administer insulin).
14,15 In an international survey
16 and a clinical practice review,
17 PCPs and diabetes specialists reported that insulin initiation was prevented by lack of:
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time required to train patients
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clear guidelines and definitions
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support, as represented by Certified Diabetes Educators
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experience in taking a proactive role in insulin initiation
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coordination of care between PCPs and endocrinologists
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motivation
Conversely, improved adherence to insulin therapy can be achieved through better patient-provider communication regarding risks and benefits, shared decision making, and training patients in how to self-manage their disease and their insulin regimen.
18 At the provider level, solutions to overcome barriers to insulin intensification should be appropriately tailored to the setting (ie, specialist or primary care) and could include education, training, and improving collaborative or supportive working practices and communication.
17 Improvements in diabetes care have been reported in pilot studies
19,20 of patient-centered medical homes and health care settings designed to provide comprehensive primary care and to facilitate partnerships between patients, their families, and their physicians.
We offer that insulin therapy should be simplified for PCPs, nurse practitioners, physician assistants, and other health care professionals, as they will have a pivotal role in helping patients manage T2DM. The current guidelines are nonprescriptive and lack practical guiding principles. The present article, however, does not present a set plan that will be applicable to all patients with T2DM, but rather it will address the relative scarcity of simple, scientifically based guiding principles related to the management of insulin therapy in the primary care setting.
“Overbasalization”
52 describes an issue that arises from increased use of basal insulin in primary care, as well as the complexities of β-cell dysfunction. Early in the management process, adding basal insulin seems to assist β cells and be an efficient step in controlling FBG levels. This premise assumes that the β cell still functions well enough to cover meals with intrinsic insulin synthesis and secretion. However, when basal insulin levels are titrated appropriately on the basis of units per kilogram (while also considering any insulin resistance) and glycemic control remains elusive, adding basal insulin may become detrimental. Overbasalization occurs in clinical practice because upper dose limits for insulin have not been well established. Whereas basal insulin titration has become part of clinical practice, there is no standard ceiling for titration. As currently defined, overbasalization occurs when FBG is not controlled with uptitration of basal insulin and HbA
1c targets remain elusive. Providers must understand the concept of overbasalization because it should trigger progression to mealtime insulin intensification in patients.
To understand overbasalization, providers should consider the following simple formula and 1 simple rule. In the clinical experience of our lead author (J.R.L.), the total daily insulin requirement for an insulin-resistant patient with T2DM is approximately 1.0 to 1.5 U/kg per day. According to this formula, if a patient weighed 100 kg, the total daily insulin requirement would be between 100 and 150 U. Further, total daily insulin is divided so that 50% is basal insulin and 50% is postprandial insulin. If this same patient demonstrated a low level of insulin resistance (1 U/kg per day), the total daily insulin requirement would be 100 U (1 U × 100 kg/d=100 U), and the basal insulin requirement would be half the daily requirement (50 U) of NPH, insulin glargine, or insulin detemir. If this patient's basal insulin level had to be titrated beyond 50 U of a basal insulin analog because the FBG level was not less than 100 mg/dL or the HbA1c level was not less than 7%, it is usually time to reassess the overall clinical case rather than add more insulin.
Maximal amounts of basal insulin can be achieved but should not comprise more than 50% of the total daily insulin calculation.
53 Violating the 50/50 rule may lead to overbasalization. At this point, administering additional basal insulin may change the pharmacokinetics of the basal insulin from having a profile without pronounced peaks of activity to a profile with an insulin peak. This addition in turn increases the risk of adverse reactions such as hypoglycemia. If a physician believes the reason for lack of glycemic control is insulin resistance and that more basal insulin is necessary to overcome this resistance, the physician should proceed with the titration schedule for an additional 20 U of insulin. If this degree of basal insulin supplementation has not reduced the FBG level to less than 100 mg/dL or the HbA
1c level to less than 7%, then adding further basal insulin may be fruitless. If 2 common oral antidiabetic drugs have failed to improve a patient's condition and if the patient has received basal insulin amounts that account for up to 50% of the calculated total daily dose of insulin, there may be a high degree of insulin resistance and the amount of both basal and mealtime insulin that is needed cannot be synthesized and secreted appropriately. Management strategies at this stage include moving to the next level of insulin intensification or referring the patient to an endocrinologist.