Type 2 diabetes (T2D) is a chronic and progressive disease that challenges patients on a daily basis. Effective management of diabetes is crucial in preventing the long-term complications of the disease, which have a high risk of morbidity and mortality. Treatment is complex and requires frequent adjustments to take into account a patient's level of glycemic control, as well as coexisting conditions such as hypertension and dyslipidemia. Patients require frequent monitoring, particularly for early signs of both acute and long-term complications, and many different aspects of treatment must be integrated.
Recent guidance emphasizes the importance of a comprehensive approach to the treatment of T2D by a team of healthcare practitioners, and the necessity for quality diabetes self-management education (DSME; Funnell et al., 2011; Handelsman et al., 2011). Nurse practitioners (NPs) are central to care, and to the provision of DSME, with key roles in the assessment of physical health, medications, and psychosocial issues, as well as goal setting, and the implementation and coordination of treatment plans. The aim of this article is to aid NPs in monitoring and managing the early stages of T2D.
T2D: The magnitude of problem
Diabetes is a large and increasing problem. In 2010, 25.6 million Americans over 20 years old were estimated to be living with diabetes, with an additional 79 million estimated to have prediabetes (glucose levels above normal, but not high enough to be classified as diabetes; Centers for Disease Control and Prevention, 2011). Both age and obesity are associated with an increasing risk of T2D (Centers for Disease Control and Prevention, 2011). Thus the aging population, and the increasing prevalence of obesity mean that the incidence of T2D in the United States is likely to continue to increase. If recent trends persist, it is predicted that the prevalence of diagnosed and undiagnosed diabetes in the US population will rise from approximately one in 10 adults today, to between one in five, and one in three adults by the middle of this century (Boyle, Thompson, Gregg, Barker, & Williamson, 2010).
In the long term, T2D is associated with a number of macro- and microvascular complications, which make the increasing prevalence of T2D a major public-health issue. Patients with diabetes have a two- to fourfold greater risk for heart disease and stroke than those without diabetes (Ginsberg & MacCallum, 2009), and although the incidence of heart disease has declined in the general US population, the reduction is smaller in patients with diabetes (Gu, Cowie, & Harris, 1999). The microvascular complications of diabetes—including neuropathy, nephropathy, and retinopathy—also have serious consequences: recent estimates indicate that in the United States alone almost 30% of adults with diabetes have diabetic retinopathy, and approximately 3% have diabetic kidney disease (de Boer, 2011; Zhang, 2010). The burden of morbidity, mortality, and economic cost associated with diabetes is considerable: the provision of coordinated, effective care can help to mitigate these costs.
Early identification and diagnosis improve outcomes
The key feature of T2D is hyperglycemia as a result of chronic failure of the pancreatic beta cells. Patients may be identified in a number of ways, from the development of symptoms to blood tests as part of a routine physical examination, with diagnosis ultimately based on the presence of hyperglycemia. Patients with T2D are also likely to have comorbidities such as hypertension and dyslipidemia, which are themselves risk factors for cardiovascular disease. Therefore, treatment of T2D requires a comprehensive plan, including education and active involvement of the patient (Funnell et al., 2011; Handelsman et al., 2011).
Testing for T2D should be conducted if patients exhibit symptoms of hyperglycemia. It is recommended that testing for T2D should also be undertaken in asymptomatic adults if they have a body mass index (BMI) ≥25 kg/m2, and additional risk factors for diabetes, as outlined in Table 1. Additionally, in patients without risk factors, it is recommended that routine testing should begin at the age of 45 years. Repeat testing following normal results is suggested every 3 years (American Diabetes Association; ADA, 2011). Diagnosis of T2D can be made from a patient's level of glycated hemoglobin (A1c) or fasting plasma glucose (FPG), or based on their response to an oral glucose tolerance test (OGTT; in which plasma glucose is measured 2 h after the administration of a 75 g glucose load). Standards for diagnosis are agreed by both the American Association of Clinical Endocrinologists (AACE) (Handelsman et al., 2011) and the ADA (2011) (Figure 1).
It is generally accepted that early identification and intensive treatment of hyperglycemia in T2D can help to improve outcomes. Evidence for this comes from large trials of glycemic control in patients with T2D. For instance, in the United Kingdom Prospective Diabetes Study (UKPDS), which enrolled patients with newly diagnosed T2D, each 1% reduction in A1c was found to be associated with a 21% reduction in diabetes-related deaths; a 14% reduction in myocardial infarction; and 37% reduction in microvascular complications (Stratton et al., 2000). In addition, subanalyses of three trials including patients with longer duration of diabetes and high cardiovascular risk (the ACCORD, VADT, and ADVANCE trials), suggest that positive effects of glycemic control on vascular disease may be stronger in patients with a shorter duration of diabetes, less advanced disease, or an absence of cardiovascular disease at the time that treatment is initiated (Handelsman et al., 2011).
Even when increased plasma glucose levels do not reach the threshold for T2D, patients have an increased risk of cardiovascular disease (Ford, Zhao, & Li, 2010), suggesting that the complications associated with T2D can begin early in disease progression, and again reinforcing the importance of early treatment for people on the T2D disease continuum. Patients who do not meet the criteria for T2D, but who nevertheless have impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) can be considered to have prediabetes. Specific levels for diagnosis are recommended by the ADA and AACE as shown in Figure 1 (American Diabetes Association, 2010; Handelsman et al., 2011).
Patients with prediabetes, particularly those with both IFG and IGT, have an increased risk of developing T2D (Gerstein et al., 2007). Management of prediabetes is, therefore, an important aspect of primary prevention of T2D. A variety of studies suggest that both lifestyle changes and pharmacologic therapy have the potential to improve outcomes in patients with prediabetes, although no pharmacologic therapies are currently approved in the United States (Crandall et al., 2008; Gillies et al., 2007). The two sets of recommendations for prediabetes management both recommend intensive lifestyle modification as the main treatment for prediabetes (American Diabetes Association, 2011; Garber et al., 2008), a goal that is echoed by the AACE guidelines for development of a comprehensive care plan for treatment of diabetes (Handelsman et al., 2011). The primary goals recommended are reduction of weight by 5%–10%, and increase in physical activity to at least 150 min per week of moderate activity. The AACE/ACE recommendations also suggest a calorie-restricted diet, increased fiber intake, and a lower sodium and alcohol consumption, to limit hypertension. The ADA suggests that metformin therapy be considered for those at the highest risk of developing diabetes, although this use is off-label.
Because T2D is associated with both insulin resistance and an alteration and eventual deficiency in insulin secretion, and because there are clear benefits associated with management of hyperglycemia, a variety of therapies are recommended throughout disease progression, including lifestyle changes and pharmacologic therapies (Figures 1 & 2): it is in the management of these sometimes complex treatment regimens that the implementation of a coordinated treatment program is vital.
Tips for early management of type 2 diabetes
- Early diagnosis and treatment can minimize the risk of long-term complications.
- Disease education and self-management education lay the foundation for successful treatment.
- Treatment individualization is an important factor in achieving goals.
- Ongoing support is vital to help patients implement and sustain lifestyle changes.
- Even modest improvements in weight (5%–10% reductions) can lessen cardiovascular risk.
Management of hyperglycemia in the early stages of T2D
The main aims of treatment of T2D are to produce sustained reductions in A1c, FPG, and postprandial glucose. Two major treatment algorithms for the management of diabetes are in use in the United States: from the AACE/American College of Endocrinology (ACE) (Rodbard et al., 2009), and the ADA and European Association for the Study of Diabetes (EASD) (Nathan et al., 2009). These two algorithms make recommendations for the management of the early stages of T2D, and provide an important roadmap to help the patient and healthcare practitioner ascertain treatment expectations and develop a treatment plan that is based on the achievement of near normal glucose levels. Treatment progression options given by these two algorithms to treat patients from diagnosis of T2D are summarized in Figure 2. It is often helpful to present the treatment targets to the patient (A1c, pre-, and postmeal blood glucose levels), and use them as a means to initiate discussion of options that are available to modify the identified problem areas. In this way, the treatment algorithms provide a guide that can be used to assist a patient in selecting the treatment option that is most fitting.
Recommendations for lifestyle management of early diabetes
Both the AACE/ACE and ADA/EASD treatment recommendations for T2D, as well as the AACE guidelines for developing a comprehensive treatment plan, emphasize the importance of lifestyle modification in early disease stages, and across the disease continuum (Handelsman et al., 2011; Nathan et al., 2009; Rodbard et al., 2009). However, both sets of treatment recommendations also recognize the difficulty that patients face in achieving long-standing lifestyle changes, and it is noted that ongoing support is an important factor in the success of these interventions. Provision of this support is one of the essential roles of the NP.
As lifestyle modification is recognized as an integral aspect of treatment across the T2D disease spectrum, it is particularly important that patients are educated thoroughly on the importance of lifestyle changes, and given strategies to implement them early in disease progression. In educating and supporting patients it is critical to learn what they know about T2D and its progression, as well as to gauge attitudes toward health and illness, and assess any facilitators and barriers to treatment that may be present: patient education is unlikely to be effective without a clear understanding of the patient's knowledge, as well as the steps the patient is prepared to undertake.
Recommended lifestyle modifications center around healthy eating and increased activity levels, and it is critical that patients understand the impact of both these factors on their health and well-being. There is a great deal of evidence supporting the role of both weight loss and increased activity in the management of T2D. For example, in the Look Ahead study, which included 5000 overweight or obese patients with T2D, an intensive lifestyle intervention program was found to result in a significant reduction in A1c, along with improvements in blood pressure, lipid profiles, and kidney function (Look AHEAD Research Group et al., 2007; Wing, 2010). Furthermore, a meta-analysis of 47 clinical trials determined that there is an association between structured exercise training and reduction in A1c (Umpierre et al., 2011). It has also been found that physical exercise alone can be effective in reducing A1c even without concomitant weight loss, although even modest weight loss of 5%–10% is associated with reductions in cardiovascular risk in T2D (Boule, Haddad, Kenny, Wells, & Sigal, 2001; Wing, Lang, & Wadden, 2011).
One particularly useful strategy that can aid patients in understanding the effects of lifestyle changes is the use of patterned glucose monitoring. For instance, a patient could be advised to check glucose levels before a meal, and then again 1–2 h afterwards, or before and after exercise. Such monitoring can provide direct feedback on the impact of changing both the type and quantity of food and activity levels. In line with this, it is important to note that intensive intervention (involving group and individual meetings) has been found to be more effective than a simple diabetes support and education program (Look AHEAD Research Group et al., 2007; Wing, 2010). When recommending any strategy though, it is important to discover which steps the patient is willing to take, and to help them develop a realistic plan. It is extremely helpful to impress upon patients that lifestyle changes take time to provide effects, and that relapses are a normal part of implementing changes.
There is clear evidence that, with the right support from healthcare professionals, lifestyle modification can result in prolonged changes (Li et al., 2008; Lindstrom et al., 2006). Despite this, both treatment algorithms recognize that these interventions alone are likely to be inadequate, and so recommend that pharmacotherapy is initiated along with diabetes education at diagnosis.
Recommendations for the pharmacological management of early diabetes
The AACE/ACE (Rodbard et al., 2009) algorithm is based on the treatment goal of an A1c of 6.5% or less: recommended treatments are stratified by A1c level at diagnosis, with the earliest stage being patients in the A1c band 6.5%–7.5%. The ADA/EASD (Nathan et al., 2009) consensus algorithm has the slightly higher treatment goal of an A1c of 7.0% or less, and recommends two tiers of treatment across disease stages, with Tier 1 using well-validated core therapies, and Tier 2 using less well-validated therapies. The aim of this article is to discuss the early stages of the treatment of T2D, when pharmacologic monotherapy is likely to be more effective. Other articles in this supplement focus on later disease stages, as well as more decompensated diabetes, when the use of dual and triple therapy and insulin therapy is required to affect sufficient glucose control (Kruger, 2012; Spollett, 2012; Tierney, 2012).
Metformin is the treatment of choice at diagnosis in both recommendations, unless contraindicated (e.g., in renal impairment; Nathan et al., 2009; Rodbard et al., 2009; Figure 2). This oral biguanide inhibits hepatic glucose production and increases the sensitivity of peripheral tissue to insulin, and has been shown to reduce A1c by approximately 1.5% (DeFronzo & Goodman, 1995). The ADA/EASD algorithm specifically recommends titrating metformin to a final effective dose of 850–1000 mg twice daily (Nathan et al., 2009). Metformin treatment has been shown to limit diabetic complications (Turner, 1998), and is generally well tolerated, with the most frequent adverse events related to treatment being gastrointestinal. Taking metformin with meals is recommended, and in many cases is an effective means of blunting gastrointestinal side effects (Glucophage SPC, 2007).
Although metformin is the first-choice monotherapy, the AACE/ACE treatment recommendations suggest alternatives in patients with an A1c of 6.5%–7.5% (Rodbard et al., 2009; Figure 2). In particular, thiazolidinediones (TZDs) and dipeptidyl-peptidase-4 (DPP-4) inhibitors are possibilities at this early disease stage, as all carry a low risk of hypoglycemia. It should be noted, however, that TZDs can result in fluid retention and reduce bone mineralization, and are contraindicated in patients with moderate to severe heart failure (use of rosiglitazone has been restricted in the United States because of concerns over the risk of cardiovascular disease; Actos label, 2011; Handelsman et al., 2011). In addition, the Food and Drug Administration (FDA) has issued a warning that use of pioglitazone for more than 1 year may be associated with an increased risk of bladder cancer (FDA, 2011). Insulin secretagogues are not recommended for patients with this range of A1c values, as they are associated with a substantial risk of hypoglycemia and weight gain, particularly in drug-naïve patients. It should be noted that although the glucagon-like peptide-1 (GLP-1) receptor agonists liraglutide and exenatide have been approved for use as monotherapy in the United States on the basis of clinical trial data (Garber et al., 2009; Moretto et al., 2008), neither the ADA/EASD or AACE/ACE recommendations suggest them for use as first-line therapy.
If glycemic goals are not reached by lifestyle modification and monotherapy, then both treatment algorithms recommend the addition of second-line, and potentially third-line, therapies, with eventual progression to insulin therapy (Figure 2). Although discussion of these later steps in T2D treatment falls outside the scope of this review, it is important to remember that the goal of diabetes therapy is to lower the A1c. The higher the A1c level the more likely it is that the glucose abnormality is as a result of both higher fasting glucose levels and higher postprandial glucose levels. The specific issues and approaches surrounding the application of combination therapies that target the multiple deficiencies of T2D are discussed in the later articles within this supplement (Kruger, 2012; Spollett, 2012; Tierney, 2012).
Insulin is only recommended as an initial therapy for those patients with an A1c higher than 9.0% (Rodbard et al., 2009). Evidence that early use of insulin provides additional benefits beyond glycemic control is currently limited, and there are some suggestions that it may have negative consequences (Chiasson, 2009; Lebovitz, 2011). Limitations to the early use of insulin include the fact that it reduces the number of agents that can be given in combination with therapy, and that it can be associated with hypoglycemia and weight gain. Interestingly, however, there is a subset of patients who present with severe hyperglycemia at diagnosis, and who may benefit from an initial period of several weeks of intensive insulin therapy (e.g., Chen et al., 2008; McFarlane et al., 2001; Weng et al., 2008). When making a decision about the appropriate treatment for T2D, the fact that insulin has the capacity to bring any patient to blood glucose target (limited only by compliance and potential hypoglycemia) should not be forgotten. Again, it is important to remember that the maintenance of near-normal glycemic control is the key goal of therapy for T2D, and that insulin therapy should be introduced as soon as it is needed to maintain A1c target levels (please see later articles of this supplement for information and advice on the initiation and intensification of insulin treatment [Kruger, 2012; Spollet, 2012]).
T2D is a chronic disease, and from diagnosis patients are required to make changes that must last a lifetime without any possibility of respite. Long-term maintenance of treatment is made especially difficult by the fact that treatment regimens are generally complex. Patients will need to implement both lifestyle changes and pharmacologic treatments for hyperglycemia, and may also need therapy for comorbidities such as hypertension and dyslipidemia. Treatment of both hypertension and dyslipidemia is likely to require combination therapy, and this must be managed in addition to antihyperglycemic therapy (Handelsman et al., 2011). Coordination and long-term maintenance of these various treatments is challenging and it is well recognized that patient education and understanding of both the disease and therapies is an important aspect of disease management (Funnell et al., 2011). A particularly important education issue is the clarification for patients of why polypharmacy may be required for treatment of T2D: giving the reasons why so many medications are needed may help to increase adherence rates. The NP can also decrease barriers to adherence by determining if a patient's financial or insurance status is adequate to ensure that medications are affordable and that the costs do not become overwhelming.
The ADA treatment recommendations state that “any plan should recognize diabetes self-management education (DSME) and ongoing diabetes support as an integral component of care,” and they publish recommendations on DSME (American Diabetes Association, 2011; Funnell et al., 2011). The recommendations for DSME emphasize the need for development of an individualized plan, as well as for measurement of whether goals have been attained (Funnell et al., 2011). Recognition of the importance of DSME comes from the fact that coverage for diabetes education services is now provided by Medicare, and many states require insurance companies to cover diabetes education (NDIC, 2009). Educational guidance and information are also published by the American Association of Diabetes Educators (e.g., AADE, 2009, 2011). Education is important at first diagnosis, to help patients to understand their condition and the need for treatment, to develop effective self-management strategies, and to cope with the burden of diabetes and its management. Ongoing DSME and support is also needed to help patients maintain effective self-management throughout disease progression, as they face new challenges, and as new treatments become available. The overall objectives of DSME are to support informed decision-making, self-care behaviors, problem-solving, and active collaboration with the healthcare team, in order to improve clinical outcomes, health status, and quality of life in a cost-effective manner (Funnell et al., 2011). As part of the multidisciplinary team, the NP can play a vital part in educating and supporting patients in self-management throughout the progression of their disease.
The positive effects of patient education and self-management are supported by clinical studies. Patients who have participated in DSME have been shown to have improved knowledge about their diabetes, and better self-care behaviors than those who do not (Norris, Engelgau, & Narayan, 2001). This, in turn, leads to better clinical outcomes, such as lower A1c levels and body weight, improved quality of life and lower costs (Boren, Fitzner, Panhalkar, & Specker, 2009; Cochran & Conn, 2008; Minet, Møller, Vach, Wagner, & Henriksen, 2010; Norris, Engelgau, & Narayan, 2001).
Based on such findings, the standard of care is now patient-centered education, responsive to the individual patient's needs and preferences. The need for individualization of lifestyle changes is well recognized (Funnell et al., 2011; Handelsman et al., 2011), and supported by study results. In order to achieve this type of care it is important that healthcare practitioners work to engage patients in a conversation about their disease, involving sharing, active listening, and relevant feedback. Effective individualized care requires that at each visit the practitioner learns what brings the patient to the office and what they are aiming to achieve. A goal-centered approach, in which the NP aims to help patients to identify a goal and then to assist them in development of a realistic plan to achieve this goal, is a vital part of providing individualized care. At all stages of treatment, it is important to remember that effective education cannot be delivered without an understanding of what the patient already knows, and what they are aiming to learn. It is also vital to take into consideration the level of support available to patients from family members and friends, and the types of changes they are able and willing to undertake.
The positive benefits of patient-centered care and education are borne out by the finding that better outcomes have been reported for DSME interventions that were longer and included follow-up support, and that were culturally and age appropriate (Hawthorne, Robles, Cannings-John, & Edwards, 2008; Norris, Engelgau, & Narayan, 2001; Sarkisian, Brown, Norris, Wintz, & Mangione, 2003). It is through such education that patients gain tools to allow them to make lifestyle changes that take into account their personal context, including any family members involved in their care and support, and any associated difficulties.
Implications for NPs and their role in diabetes care
Because patients often find it difficult to implement the lifestyle modifications that are recommended in the early stages of T2D, ongoing support is recommended. A variety of treatment strategies are suggested (Figure 1). A patient-centered approach is vitally important in helping patients to manage body weight and maintain their therapies. Treatment should place emphasis on patient well-being, and aim to provide the clarity and support necessary for a patient to make informed choices and reach relevant goals. NPs have a key role for patients with T2D, in delivering patient education, explaining treatment strategies, and supporting patients in making lifestyle changes and maintaining self-management. This role is especially important as patients move through the disease continuum, and as new therapies continue to come to market—each transition to a new therapy or regimen requires renewed support and education.
As with any chronic disease, treatment adherence is an important aspect of the management of T2D. Contact with diabetes educators and/or ongoing support in setting goals and making the required changes is a necessity in helping patients adhere to their treatment regimens and achieve their treatment goals. In providing this support it is important to avoid framing the question of adherence in terms of success or failure: instead, it can be useful to initiate discussion of change as a “journey,” and of the need to undertake a series of experiments to find the most useful approach. In addition, patients should always be provided with ample reassurance that relapse is a normal occurrence and should not be a reason to abandon a particular approach. A survey of patients with diabetes underlined the role of healthcare practitioners in maintaining treatment: patients who had been recommended to exercise were much more likely to do so if their physician helped to develop an exercise plan and followed up on how well the patient was adhering to the recommendations (Weidinger et al., 2008). A particularly important role for the NPs is in providing this type of follow-up.
As well as helping patients adhere to treatment plans, NPs play an important role in the formulation of these plans, and in ensuring that they are individualized to involve the patient, family, and healthcare team. Treatment plans need to take into account the effectiveness of a therapy, as well as lifestyle factors, such as age, schedule, physical activity, eating patterns, social/cultural factors, and any medical complications. It is also essential that NPs recognize the challenges facing patients in making and adhering to lifestyle changes and treatment, and can provide information to help patients implement useful techniques. This education and support should not take place in the context of the patient alone, but should involve family members and social contacts who can help the patient reach and maintain their goals.
Despite the best efforts of the patient and their treatment team, continuing loss of beta-cell function means that most patients with T2D will eventually progress to a level of hyperglycemia that cannot be managed by lifestyle changes and pharmacologic monotherapy. At this point, patients usually progress to use of dual and then triple therapy, and eventually to use of insulin. These later stages in the management of T2D are outside the scope of this article, but are discussed in detail in later articles in this supplement Kruger, 2012; Spollett, 2012; Tierney, 2012). It should be remembered that the diabetes education and advice that patients receive in the early stages of treatment will aid in management of the disease and its treatment through all stages of progression. It is important that as well as understanding the necessity for early treatment to limit disease progression, patients also continue to receive the help and support they require to manage increasingly complex treatment regimens in more advanced disease stages.
The assistance of Watermeadow Medical, Witney, UK, funded by Novo Nordisk Inc, Princeton, NJ, USA, in preparing this article is gratefully acknowledged.
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