15 Adherence to Practice Guidelines for People with Diabetes Mellitus Marideli Colón Scanlan and Lawrence Blonde CONTENTS Introduction Prevalence and Cost of Diabetes Demonstrated Benefits of Therapy for People with Diabetes Clinical Practice Guidelines for Diabetes Management Achievement of Guideline Recommendations Conclusions References Key Words: Adherence; diabetes; guidelines; insulin; dyslipidemia; hypertension. INTRODUCTION The incidence and prevalence of diabetes have increased to epidemic proportions. Practice guidelines largely supported by randomized controlled clinical trials provide therapeutic targets that, if met, would dramatically reduce the morbidity and mortality associated with diabetes. Yet adherence by both patients and their health care professionals to these guidelines and to specific therapeutic recommendations designed to achieve guideline targets remains much less than optimal. This chapter will discuss the level of adherence to guidelines and speculate on both causes and potential remedies for suboptimal adherence. PREVALENCE AND COST OF DIABETES The Centers for Disease Control and Prevention (CDC) estimates that in 2005 the total prevalence of diabetes in the US was 20.8 million people or 7% of the population. This was an increase from the 2002 estimate of 18.2 million or 6.3% of the population. Nearly 10% of adults and over 20% of those 60 year of age or older have diabetes, and there has been a marked increase in the incidence and prevalence of type 2 diabetes among children and adolescents (1). Both acute and chronic complications of diabetes have enormous personal and societal economic costs. Diabetes is the number one cause of adult blindness and end stage kidney disease in this country. Diabetes increases the risk for heart disease and stroke by 2- to 4-fold and is associated with many abnormalities of the nervous system collectively termed diabetic neuropathy. As a result, diabetes was estimated to account for 11% of total healthcare costs in the United States in 2002. Ninety-two billion dollars were spent on direct costs—more than double the 1997 figure of $44 billion. In 2002, indirect medical costs such as disability, work loss, or premature mortality accounted for $40 billion (2). Epidemiologic studies have clearly demonstrated the relationship between micro- and macrovascular complica- tions and hyperglycemia as well the often accompanying hypertension and dyslipidemia. More importantly, several landmark randomized prospective clinical trials have demonstrated that improving glycemia, blood pressure (BP), From: Contemporary Endocrinology: Type 2 Diabetes Mellitus: An Evidence-Based Approach to Practical Management Edited by: M. N. Feinglos and M. A. Bethel © Humana Press, Totowa, NJ 235 236 Scanlan and Blonde and dyslipidemia in addition to treating the diabetes associated hypercoagulable state will reduce the risk for diabetic complications. DEMONSTRATED BENEFITS OF THERAPY FOR PEOPLE WITH DIABETES Benefits of Improved Glycemic Control Several studies have demonstrated that lowering HbA1c reduces diabetes complications. The Diabetes Control and Complications Trial (DCCT), which randomized 1,441 type 1 diabetes patients to receive either intensive or conventional insulin therapy for an average of 6.5 year between 1983 and 1993, found that an improvement in HbA1c from 9.1% in the conventional group to 7.3% in the intensive treatment group was associated with a 63% decrease in retinopathy, a 54% decrease in nephropathy, and a 60% decrease in neuropathy (3). Another randomized study of 110 insulin-treated type 2 patients found that, compared to conventional therapy subjects, intensively treated subjects had a lower HbA1c (7.1% compared to 9.4%), a 69% decrease in retinopathy, and a 70% decrease in nephropathy (4). The United Kingdom Prospective Diabetes Study (UKPDS) reported that a reduction in HbA1c from 7.9% to 7% with intensive pharmacologic compared to conventional diet therapy was associated with a 17–21% decrease in retinopathy and a 24–33% decrease in nephropathy (5). A recent report from the DCCT-Epidemiology of Diabetes Interventions and Complications (EDIC) researchers provided follow-up information many years after the end of the DCCT. Compared to the conventional group, type 1 diabetes patients assigned to intensive treatment in the DCCT had a 42% decrease in risk for any cardiovascular outcome and a 57% reduction in the risk for nonfatal MI, stroke, or death from cardiovascular disease, even though during much of the follow-up period there was little difference in the 2 groups’ HbA1c levels (6). There are 2 important messages from this study. Improving glycemia will reduce the risk for macrovascular disease and, the earlier the treatment is begun, the greater the likely benefit because of an apparent metabolic memory of good and bad control. Furthermore, in an epidemiologic analysis of the UKPDS study, researchers found that every 1% decrement in HbA1c yielded a 21% reduction in diabetes-related death, a 14% reduction in MI, and a 37% reduction in microvascular disease (7). Because better glycemic control is associated with improved clinical outcomes, lowering HbA1c may also reduce healthcare costs. UKPDS researchers calculated that the intensive therapy program cost an additional £695 per patient but was associated with a £957 reduction in the cost of complications (8). An observational study by Wagner et al compared patients who exhibited a 1% decrease in HbA1c in the first or second year and maintained that decrease through a third year of the study to patients who did not have an improved HbA1c. In the subsequent 3 year, mean total healthcare costs per patient were reduced by $685 to $950 annually in the improved HbA1c group (9). Finally, data support the contention that diabetes control leads to a better quality of life. A study by Testa and Simonson compared placebo or sulfonylurea treatment for 16 week and found that compared to patients receiving placebo, patients who received pharmacologic treatment not only improved their HbA1c levels but also reported marked improvement in ratings of overall health, mental health, cognitive function, perceived health, and symptom distress (10). Benefits of Therapy for Dyslipidemia and Antihypertensive Therapy Trials of therapy with statins in patients with dyslipidemia have demonstrated that they are equally effective in those with and without diabetes. In a meta-analysis of both primary and secondary prevention trials, the relative risk for adverse cardiovascular outcomes was 0.76 while the absolute risk reductions were 2.8% and 8.0%, respectively. The number needed to treat to prevent one event was 35 in primary prevention and approx 12 for secondary prevention (11). There is also evidence that reducing triglycerides and/or raising HDL-C will be associated with improved cardiovascular outcomes in those with diabetes (12). In the UKPDS a reduction of 10 mmHg systolic and 5 mmHg diastolic blood pressure was associated with a 24% reduction in any diabetes endpoint, a 37% reduction in microvascular disease, and a 32% reduction in diabetes- related deaths (13). Other studies have also demonstrated the profound benefits of treatment of hypertension in those with diabetes. Chapter 15 / Practice Guidelines for People with Diabetes Mellitus 237 Benefits of Comprehensive Therapy In the Steno-2 trial, patients with type 2 diabetes and microalbuminuria were randomized into 2 groups: one group received conventional treatment in accordance with national guidelines, and the other received intensive treatment targeting hyperglycemia, hypertension, dyslipidemia, and microalbuminuria, as well as secondary prevention of cardiovascular disease with aspirin. The study reported in the intensive treatment group a 53% reduction in the occurrence of macrovascular endpoints, including cardiovascular death, nonfatal myocardial infarction (MI), coronary artery bypass graft, percutaneous transluminal coronary angiography, nonfatal stroke, amputation, and bypass, as well as a 60% reduction in microvascular diseases (14). This study demonstrated the importance of treating the often accompanying hypertension and dyslipidemia in type 2 diabetes patients as well as the benefits of aspirin and treatment of microalbuminuria. CLINICAL PRACTICE GUIDELINES FOR DIABETES MANAGEMENT As a result of the incontrovertible evidence for the benefits of improved diabetes control, many organizations, including the American Diabetes Association; the American College of Endocrinology/American Association of Clinical Endocrinologists; the American College of Physicians; The Seventh Report of the Joint National Table 1 Recommended Clinical Practice Guidelines ADA (15) AACE (16–18) ACP (19,20,21) JNC 7 (22) NCEP (23) A1C (%) <70 ∗ ≤65 <7 (as low as reasonably feasible) Fasting Glucose (mg/dL) 70–130 <110 Post-prandial Glucose (mg/dL) <180 (peak postprandial) <140 (2 hr postprandial) LDL-C (mg/dL) <100 Use statin if CVD or >40 yr old with CVD RF. (optional goal <70 if CVD present) <100; <70 if CVD No specific goal; use antidyslipidemic therapy if CVD or CVD RF present <100 (optional goal: <70) HDL (mg/dL) Men: >40 Women: >50 Men: >40 Women: >50 No specific goal; use antidyslipidemic therapy if CVD or CVD RF present Triglycerides (mg/dL) <150 <150 No specific goal; use antidyslipidemic therapy if CVD or CVD RF present Non-HDL (mg/dL) 30 higher than LDL-C (in patients with TG ≥200) Blood Pressure (mmHg) <130/80 <130/80 Target blood pressure of no more than 135/80 <130/80 Aspirin use (mg/d) 75–162 if >40 yr of age. Consider at 30–40 yrs of age with CVD RF Low dose ASA unless contraindications present ∗ The A1C goal for selected individual patients is as close to normal (<6%) as possible without significant hypoglycemia ADA, American Diabetes Association; AACE, American Association of Clinical Endocrinologists; ACP, American College of Physicians; JNC, Joint National Committee; NCEP, National Cholesterol Education Program; CV, cardiovascular; RF, risk factor 238 Scanlan and Blonde Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7); and the National Cholesterol Education Program (NCEP) have developed clinical practice guidelines to encourage physicians to improve diabetes care and outcomes by attaining and maintaining recommended treatment targets. These guidelines generally are developed by adding expert opinion to the evidence published in the medical literature (Table 1). Although there are some differences among the guidelines, a review of the recommendations in Table 1 demonstrates that they are more similar than different. Moreover, there is little debate in the diabetes community that attainment of guideline recommendations would improve outcomes for people with diabetes. ACHIEVEMENT OF GUIDELINE RECOMMENDATIONS Obtaining Information about Guideline Adherence To what degree are guideline recommendations achieved? Information about guideline adherence can be obtained from a number of sources, including the National Health and Nutrition Examination Survey (NHANES), the Behavioral Risk Factor Surveillance System (BRFSS) and the National Committee for Quality Assurance (NCQA). The National Health and Nutrition Examination Survey (NHANES) is conducted by the National Center for Health Statistics. The program began in the early 1960s and was a series of surveys until 1999 when it became a continuous program with data released every 2 year (24). It is federally funded and is designed to be representative of the US civilian, noninstitutionalized population. Samples of this population are obtained by a complex, stratified, multistage probability cluster sample design. The participants are interviewed in their homes to obtain sociodemographic, medical, and family history data, and have a physical examination and laboratory studies performed in a mobile examination center. NHANES III was the third survey conducted before it became a continuous program. It represents information gathered from 1988–1994, and is often used as the baseline for assessing progress compared to more current data sets. NHANES reports after 1999 are generally referred to using the years of data that were analyzed (i.e., NHANES 1999–2000) (24–27). Study populations for papers about patients with diabetes using NHANES data were derived using various criteria, depending on the focus of the particular study. One such population included/subjects aged 18 year and older who answered “yes” when asked whether a physician (or a health care professional in NHANES beginning in 1999) ever told them they had diabetes. Analyses of adults with diabetes generally did not include women reporting a diagnosis of diabetes only during pregnancy. Another federally funded survey that provides evidence of rates of achievement of guideline targets is the Behavioral Risk Factor Surveillance System (BRFSS). The CDC established this program in 1984. It began with 15 state health departments participating in monthly data collection, and by 1994 included the 50 state health departments as well as those in the District of Columbia, Puerto Rico, Guam, and the U.S. Virgin Islands. It is the world’s largest, on-going random-digit telephone health survey system, tracking health conditions and risk behaviors of noninstitutionalized persons in the United States each year using a standard core questionnaire. The BRFSS does not utilize physical examination or laboratory studies. Examples of information from the BRFSS used to study diabetes include data about diabetes itself, alcohol use, hypertension, obesity, physical activity, and tobacco use. Examples of study populations for papers about patients with diabetes included participants of ages 18–75 year who reported a previous diagnosis of diabetes by a healthcare professional. Women with gestational diabetes were generally excluded (25,28). Studies of Adherence to Diabetes Guidelines A few key studies from these sources demonstrate the status of adherence to guidelines for the treatment of diabetes in the United States, and particularly the progress made when comparing older data sets to more recent data. Saydah et al (25) analyzed glycemic, blood pressure and cholesterol control in NHANES III compared to NHANES 1999–2000 among patients who reported a diagnosis of type 2 diabetes. There were 1,265 participants from NHANES III and 441 from NHANES 1999–2000 who were analyzed. The study found that the proportion of adults with diagnosed type 2 diabetes and an HbA1c < 7% decreased between 1988 and 2000. The percentage of patients with an HbA1c <7% declined from 44.3% in NHANES III to 35.8% in NHANES 1999-2000. The Chapter 15 / Practice Guidelines for People with Diabetes Mellitus 239 mean A1C levels were not significantly different, with a change from 7.6 to 7.8%, and 35.8% of subjects achieved a blood pressure of <130/80 mmHg in NHANES 1999–2000 compared to 29% in NHANES III. Almost half (48.2%) of subjects had a total cholesterol <200 mg/dL, a significant increase from the 33.9% in NHANES III. Only 7.3% of those with diabetes achieved all 3 goals in NHANES 1999–2000, which represented a minimal increase compared to NHANES III. A study of the more recent data assessing progress in the overall quality of diabetes care was published in 2006 by Saaddine et al (25). Comparison of quality of diabetes care in 2 different time periods was performed using the measures of the National Diabetes Quality Improvement Alliance whenever data were available as well as some additional measures felt to be possible indicators of quality of care in the future, such as pneumococcal vaccination, diabetes education, and others. The study population included adults of ages 18–75 year who reported a previous diagnosis of diabetes by a health care professional, excluding those women who had gestational diabetes. In this study, 1,024 participants from NHANES III and 750 participants from NHANES 1999–2002 who reported a diagnosis of diabetes and completed the clinical examination were analyzed. Participants from BRFSS 1995 (3,065) and BRFSS 2002 (13,078) who identified themselves as having diabetes were studied. The authors used data from NHANES III (1988–1994) and BRFSS data from 1995 as a baseline; the more current data were from NHANES 1999–2002 and BRFSS from 2002. The mean HbA1c (%) was essentially unchanged, with a value of 7.8 at baseline and 7.7 more recently. The percentage of patients who were poorly controlled, with an HbA1c >9, was 24.5% in the baseline surveys and 20.6% in the recent surveys, a change that did not reach statistical significance. The ADA states that although the glycemic goal in general is a value of < 7%, the HbA1c goal for an individual patient is as close to normal (<6%) as possible without significant hypoglycemia. In the study from Saaddine et al, the proportion of patients with an HbA1c of <6%, actually decreased significantly from 23.4% to 16.4%. The proportion of participants achieving an HbA1c < 7 was not statistically different, changing from 41.3% to 42.3%. Hoerger et al studied only A1C levels from NHANES 1999–2000, 2001–2002, and 2003–2004 and found that glycemic control had steadily improved from 1999 to 2004, with a decline in mean A1C level from 7.82% in 1999–2000 to 7.18% in 2003–2004 (29). The percentage of people with A1C <7% increased from 36.9% to 56.8% in the same time period, and the percentage of people who were poorly controlled with an A1C >9 decreased from 21% in 1999–2000 to 12.4% in 2003–2004. This study certainly shows a small improvement over older trends, but also demonstrates that, while most people should be able to get to goal, many (about 45%) are not. Moreover, in the most recent survey period, only 33.8% of diabetic subjects achieved an LDL-C <100 mg/dL. Although almost 74% of individuals with diabetes achieved a diastolic blood pressure of <80 mmHg, only 48.4% had a systolic blood pressure <130 mmHg. The “State of Diabetes in America” report released by the American Association of Clinical Endocrinologists (AACE) in 2005 demonstrated that 2 out of 3 individuals with type 2 diabetes did not achieve the HbA1c goals recommended by the ACE. The report, which analyzed a laboratory database of >157,000 people in 39 states during 2003–2004, found that 67% of patients had HbA1c levels higher than the ACE goal of < 6.5%. In no state did more than half of the type 2 diabetic patients achieve the HbA1c goal (30). Other studies also demonstrate failure to achieve therapeutic goals among people with diabetes. Andros et al assessed blood pressure goal attainment according to JNC 7 guidelines and use of antihypertensive drug therapy in a random sample of commercial members with type 1 or type 2 diabetes in a managed care organization comprising 30 health plans across the United States (31). A retrospective medical record review in October 2003 collected data from 4,814 patient charts. BP goal attainment according to JNC 7 guidelines was determined for each patient from the most recent BP reading documented in the medical chart. 751 (20.6%) of the 3,647 patients who required antihypertensive drug therapy were at JNC 7 BP goal, and 788 (21.6%) received no antihypertensive drug therapy. For the patients with DM who received antihypertensive drug therapy and had a BP value recorded in the medical chart, only 26.3% were at JNC 7 BP goal. The proportion of diabetic patients with hypertension was 59.6% (n = 2,870), and 28.4% (n = 814) of these patients were not taking either an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB). There were 704 patients with albuminuria or nephropathy (14.6%), and 35.4% (n = 249) of them were taking neither an ACEI nor an ARB. 240 Scanlan and Blonde Winkelmayer et al (32) reported underuse of ACE inhibitors and angiotensin II receptor blockers in elderly patients with diabetes. Using linked medical claims from Medicare and the Pennsylvania Pharmaceutical Assistance Contract for the Elderly program, they studied a cohort of patients older than 65 yr with diabetes. Of 30,750 patients with diabetes studied, 21,138 patients (68.7%) also had hypertension and/or proteinuria. Of these, only 50.7% (95% confidence interval, 50.0 to 51.4) were administered an ACE inhibitor or ARB in the quarter studied. In multivariate analyses, failure to be administered either agent was associated significantly with one or more of the following: older age, male sex, chronic lung disease, depression, dementia, and other mental illness. Greater rates of ACE-inhibitor or ARB use were found in patients with coronary artery disease or congestive heart failure. Why Aren’t Guideline Targets Achieved? The failure to achieve recommended guidelines is perhaps surprising in view of the strong evidence supporting benefit from adherence and the availability of effective pharmacologic therapies for hyperglycemia, hypertension and dyslipidemia in diabetic patients. Since 1994, five new classes of oral antidiabetic agents (the biguanide metformin, thiazolidinediones, alpha glucosidase inhibitors, meglitinides, and DPP-IV inhibitors) have been introduced in this country. In addition, availability of single pill combination agents, exenatide (the 1st incretin mimetic), human insulin, premixed insulins, and rapid-acting and long-acting insulin analogs, and pramlintide acetate comprise an extensive pharmacologic armamentarium. Similarly there are many antihypertensive and antidyslipidemic agents available. Finally, the diabetes epidemic and the importance of achieving good diabetes control have been extensively reported. The reasons for failure to achieve guideline targets include a frequent lack of optimal systems of diabetes care delivery, a failure of some clinicians to adopt a treat-to-target approach, and suboptimal adherence of some patients to both lifestyle and pharmacologic therapy. Suboptimal Systems of Diabetes Care Delivery The Institute of Medicine in its publication entitled Crossing the Quality Chasm stated, “The healthcare system is poorly designed. Even for the most common conditions like diabetes and cancer, there are few programs that use multidisciplinary teams to provide comprehensive services for patients” (33). In many if not most clinical settings, clinicians cannot easily look across their patient populations and identify individuals not attaining treatment goals. Instead, they usually wait for patients to visit and then evaluate and make therapy adjustments. If patients present with acute problems, their chronic illnesses may not be addressed. Lack of an organized system of care contributes to suboptimal diabetes control and outcomes as well as increased costs. Bodenheimer et al (34) and others have proposed a chronic illness care model with 6 interrelated components—self-management support, clinical information systems, delivery systems redesign, decision support, health care organization, and community resources. When this model is optimally functioning, informed patients interact with proactive practice teams to address clinical problems. The model can be applied in most practice settings – large or small, primary or specialty – and can be implemented incrementally. Using the chronic care model, clinicians can prospectively identify patients not achieving goals so that early interventions to improve control can be implemented. Patient and clinician reminders can prompt appropriate actions. For example, Sequist et al reported that an integrated electronic reminder system resulted in definite though somewhat variable improvement in care for patients with diabetes and coronary artery disease (35). The majority of physicians (76%) thought that reminders improved quality of care. The National Diabetes Education Program (NDEP) has created the BetterDiabetesCare website, a resource designed to help practitioners better organize and deliver care to their patients with diabetes (36). The Better- DiabetesCare website is focused on how to improve the way diabetes care is delivered rather than the clinical care itself. The content of the website is based on current, peer-reviewed literature and evidence-based practice recommendations. It provides models, links, resources, and tools to help assess practice needs, develop and plan strategies, implement actions, and evaluate results. Health care professionals who use this resource can also receive continuing education credit for doing so. One can pose questions focused on improving practice: 1) How to make patient-centered team care a reality; 2) How to better manage patient notes, laboratory results, and other information; 3) How to assess the organizational status of a practice, make informed practice improvement decisions, and evaluate outcomes. Health care professionals Chapter 15 / Practice Guidelines for People with Diabetes Mellitus 241 can then choose the tools and resources needed to find the answers, and if they document the process, for a nominal administrative fee of $10, they can receive a certificate documenting up to 10 continuing education or continuing medical education credits per year from the Indiana University School of Medicine. There is evidence that such practice improvement interventions can have an impact on diabetes care delivery. Meigs et al (37) assessed a web-based decision support tool in a randomized controlled trial comparing 12 intervention and 14 control staff providers and 307 intervention and 291 control patients with type 2 diabetes in a hospital-based internal medicine clinic. The decision support tool provided patient-specific clinical data, treatment advice, and links to other web-based care resources. The number of HbA1c tests obtained per year, the number of LDL cholesterol tests, and the percentage of patients who received at least one foot examination per year all increased significantly in the intervention group. HbA1c levels decreased by 0.2% in the intervention group and increased by 0.1% in the control group (p = 0.09); proportions of patients with LDL cholesterol levels <130 mg/dL increased by 20.3% in the intervention group and 10.5% in the control group (p = 0.5). The authors concluded that web-based patient-specific decision support has the potential to improve parameters of diabetes care. However, an accompanying editorial by Dr. Patrick O’Connor (38) expressed disappointment that key care outcomes such as HbA1c and LDL levels did not improve more. Another study (39) also showed increased rates of test ordering but no improvement in metabolic parameters such as HbA1c, lipids, or blood pressure levels. Dr. O’Connor suggested that reminders to physicians would have a greater impact if they also included suggestions for specific clinical interventions for a particular patient at a particular point in time. Suboptimal Adherence of Patients to Lifestyle and Pharmacologic Therapy When primary care general internists were asked in a survey conducted by the Council for the Advancement of Diabetes Research and Education (CADRE) to identify barriers to achieving optimal diabetes care, patient lack of adherence to nonpharmacologic (medical nutrition therapy and appropriately prescribed physical activity) and pharmacologic therapy were among the most frequently cited responses. The fact that almost two-thirds of American adults are overweight or obese and 30% are frankly obese (40) attests to the difficulty patients experience in adhering to lifestyle recommendations. Mokdad et al have demonstrated that for every kilogram increase in self-reported weight, diabetes increased by approx 9% (41). A systematic review by Cramer noted that retrospective analyses have shown that adherence to oral antidiabetic agents during clinical trials ranged from 36–93% in patients remaining on treatment for 6–24 month. Further, studies documented that patients took 67–85% of oral agent doses as prescribed and that insulin adherence among patients with type 2 diabetes was only 62–64% (42). Ho et al recently studied nonadherence in diabetes patients who were members of a private managed care organization (43). The effects of medication nonadherence on hospitalization and mortality were specifically evaluated in this population, with attainment of treatment targets for HbA1c, blood pressure, and LDL-C levels as secondary outcomes. Adherence was assessed using outpatient pharmacy records to determine the proportion of days covered based on prescriptions filled. The study identified medication nonadherence in 21% of patients and found that this was associated with significantly higher HbA1c, blood pressure, and LDL- C levels. Also, nonadherent patients had significantly higher risk for all-cause hospitalization and all-cause mortality (43). The same journal issue contained several articles on adherence that identified potential harms and potential causes of nonadherence. An accompanying editorial identifies a number of challenges to adherence, suggesting changes that could improve adherence (44). In particular, the judicious use of medications is advocated: prescribing the smallest possible number of medications (including taking advantage of combination pills) and the fewest doses. Improvements in systems of care to provide information on new medications at the time of prescription and to reduce medication errors at transitions of care are suggested. Decreasing the financial burden associated with some especially beneficial medications may also improve adherence (44). The DAWN (Diabetes Attitudes, Wishes, and Needs) study examined the role that psychosocial factors play in diabetes outcomes and evaluated patient-reported levels of adherence. Respondents to the survey, administered by 30 to 50 minute long structured telephone or face-to-face interviews, included physicians, nurses, and people with diabetes, totaling 5,104 adults in 11 regions in 13 countries. A study of patient reported outcomes in the DAWN project (45) showed an overall adherence with the recommended lifestyle regimen of 3.06 on a 4 point 242 Scanlan and Blonde scale. When compared to the U.S., the level of adherence with lifestyle recommendations was higher in 7 other countries and worse in 2. In this study, adherence to the medical regimen included the respondent’s assessment of her/his success in following a combination of pharmacologic and nonpharmacologic aspects of care, such as the self-monitoring of blood glucose, medication administration, and appointment keeping recommendations given by doctors or nurses for managing diabetes. Self-reports of adherence with the recommended medical regimen were higher than lifestyle adherence, at 3.48 on the same 4 point scale overall. No country reported adherence with the medical regimen that was significantly higher than that in the US. Polonsky et al developed the Diabetes Distress Scale as an instrument to measure diabetes related emotional distress (46). It has been validated for use in both sexes and several major ethnic groups. It is a brief questionnaire for patients and identifies 4 areas of distress: emotional burden, physician-related distress, regimen-related distress, and diabetes-related interpersonal distress. Once identified, the specific concerns of a patient can be addressed by his/her clinician. Resistance to initiation of insulin therapy is a unique adherence obstacle. Even highly motivated patients with type 2 diabetes may worry about the possibility of starting insulin therapy, as demonstrated by a survey of attendees at conferences for people with diabetes (Taking Control of Your Diabetes) (47). Of respondents with type 2 diabetes who were not on insulin, 28.2% reported being unwilling to take insulin if prescribed. In a less hypothetical situation, the UKPDS, of the patients with type 2 diabetes who were randomized to insulin therapy, 28% initially refused (48). This phenomenon of nonadherence with recommended treatment has been termed “Psychological Insulin Resistance.” It has many factors, the major ones being, according to Polonsky and Jackson (49): • Perceived loss of control over one’s life—a feeling that once insulin is started, it can never be stopped, and that it will restrict the life of the patient • Poor self-efficacy—doubts about the patient’s own ability to handle the demands and complexities of insulin therapy • Personal failure—thought that the need for insulin therapy is the result of failure in diabetes self-care • Perceived disease severity—perception that insulin therapy means that the disease is now more serious and more dangerous, or that insulin therapy itself will cause more health problems. • Injection-related anxiety—fear of pain involved with injection and needle phobia (rare) • Perceived lack of positive gain—no anticipation of improved glycemic control, energy level, or improved health Optimal adherence cannot be achieved until these issues are addressed in each patient. Information Resources for Diabetes Patients. Although a substantial amount of diabetes information can be obtained from physicians’ offices, there are innumerable information resources available to patients, especially on the Internet (50,51). However, much Internet information is not peer-reviewed. Patients can find valuable and creditable information from the government (e.g., National Institutes for Health, CDC, National Diabetes Education Program, MedlinePlus, etc.), not for profit disease specific sites (e.g., American Diabetes Association, Juvenile Diabetes Research Foundation), medical specialty sites (American Association of Clinical Endocrinologists, American Association of Diabetes Educators, American Heart Association) and many other web sites. A number of such web sites are listed in Table 2. Some organizations focus on assisting patients and physicians in understanding and implementing recommended diabetes care. One such organization is the National Diabetes Education Program (NDEP) (36). The NDEP is a joint venture of the National Institutes of Health and the Centers for Disease Control and Prevention, together with more than 200 public and private organizations working to “change the way diabetes is treated.” The NDEP has 3 major campaign efforts for which both health care professional and patient information is available on-line: • Control Your Diabetes for Life – ndep.nih.gov/campaigns/ControlForLife/ControlFor/Life_index.htm  Includes information about Control the ABC’s (A1C, Blood Pressure, and Cholesterol) of diabetes – ndep.nih.gov/campaigns/BeSmart/Be/Smart_index.htm • Small Steps, Big Rewards: Prevent Type 2 Diabetes – ndep.nih.gov/campaigns/SmallSteps/SmallSteps_index.htm NDEP educational materials and public service announcements are especially designed to reach the ethnic/racial groups and older adults hard hit by the diabetes epidemic. Focus group findings help NDEP develop many Chapter 15 / Practice Guidelines for People with Diabetes Mellitus 243 Table 2* Internet information resources for diabetes patients AACE Power of Prevention http://www.powerofprevention.com American Association of Clinical Endocrinologists/American College of Endocrinology www.aace.com American Association of Diabetes Educators www.diabeteseducator.org American Diabetes Association www.diabetes.org American Dietetic Association www.eatright.org Centers for Disease Control and Prevention www.cdc.gov/diabetes Lawson Wilkins Pediatric Endocrine Society www.lwpes.org MedlinePlus www.medlineplus.gov National Diabetes Education Program www.ndep.nih.gov National Institute of Diabetes and Digestive and Kidney Diseases www.diabetes.niddk.nih.gov National Agricultural Library Food and Nutrition Information Center, US Department of Agriculture www.nutrition.gov Diabetes at work from NDEP, NBGH, NBCH, AHIP www.diabetesatwork.org ∗ Modified (used with permission) from Endocr Pract. 2006/2 (suppl 1):131–137(51). NDEP, National Diabetes Education Program; NBGH, National Business Group on Health; NBCH, National Business Coalition on Health; AHIP, American Health Insurance Plans. appropriate culturally sensitive materials including community partnership guides for these audiences and for health care professionals (all may be accessed via www.ndep.nih.gov, are copyright free, and can be reproduced or reprinted at no charge). The American Diabetes Association (ADA) also has extensive information resources that can help patients to understand treatment goals and assist in achieving them (http://www.diabetes.org). ADA’s initiative, Doing Better: Tools for Diabetes Care, addresses weight loss and exercise in 2 separate programs: Weight Loss Matters, and Club Ped. The ADA also has a Visit Planning Tool booklet designed to help diabetes patients better prepare for, and get more benefit from, office visits with health care professionals; it provides spaces for patients to write down questions before the visit and to keep track of their treatment goals, medications, and lab values. The Visit Planning Tool is available to health professionals for only the cost of shipping, and is appropriate for all patients with diabetes, especially the newly diagnosed. Diabetes PHD (Personal Health Decisions https://www.diabetes.org/phd/profile/default.jsp) is an interactive internet-based risk assessment tool designed to identify the risks for developing diabetes or its complications and the effects of various health care interventions. Patients answer questions about their health and risk factors and are given their current risk for developing diabetes or diabetes microvascular, neurologic, and/or macrovascular complications. They subsequently can see the impact on their risk that could be achieved by interventions that modify their risk factors, e.g., how the risk for stroke would be changed if a patient were, to stop smoking (52). The software underpinning for Diabetes PHD is Archimedes, which was developed by Kaiser Permanente with support from a grant to the ADA from Bristol-Myers Squibb Co. Archimedes is an extremely comprehensive model that simulates the biologic processes underlying the development of diabetes. The developers, Drs. David Eddy and Leonard Schlessinger, believe that no other simulation model is as comprehensive, and it is generally agreed that no other model used in medicine has been validated as extensively as Archimedes. ACE and AACE have launched the Power of Prevention Web site (http://www.powerofprevention. com), which focuses on helping patients to understand and address key risks for diabetes and its complications, dyslipidemia, thyroid and pituitary disorders, and osteoporosis. In addition, a specific section focuses on healthier lifestyles for children; it provides extensive information for patients in a very easy-to-use format. Patients can input personal goals for health improvement and bring printouts of those goals to discuss with their physicians during appointments. AACE has used this information to develop a formal outreach program, which AACE members 244 Scanlan and Blonde are presenting in schools around the United States to promote healthy lifestyles for children and adolescents. The Power of Prevention web site has extensive nutrition information, and the Power of Prevention Guide to Physical Activity is now available. One crucial resource that can help patients to better adhere to both non pharmacologic and pharmacologic therapy is diabetes self-management training education. Such education is ideally offered by certified diabetes educators working within an ADA recognized diabetes education program that is part of a multidisciplinary diabetes management team. Self-monitoring of blood glucose (SMBG) is a critical skill for all diabetic patients and may help patients and their health care professionals to achieve treatment goals (53). SMBG supplements the HbA1c measurement by providing timely feedback on daily glucose patterns. SMBG results show patients and their health care professionals how diet, physical activity, and medication impact blood glucose patterns. As a result, appropriate management changes can be made to better control blood glucose and thereby further reduce risk of diabetic complications. Failure of Clinicians to Adopt a Treat-to-Target Approach to Diabetes Management Some clinicians may fail to take a treat-to-target approach to diabetes management. A study by Brown et al (54) noted that patients in their large staff model managed care organization often experienced extended periods of time with poorly controlled glycemia. Whenever patients had an HbA1c of 8.0%, their next HbA1c result was as likely to be more than 8.0 as less than 8.0%. For patients on monotherapy with either metformin or a sulfonylurea, their first HbA1c on treatment was 7.6–8.2 %, their best HbA1c on treatment was 7.1–7.7% and their last HbA1c before a change in therapy was 8.1–8.8 %. Moreover, the time interval from the best HbA1c to a change in therapy was 27–35 month. One major contributor to this clinical inertia seems to be a reluctance to initiate insulin therapy. In the study by Brown et al, the average patient had spent nearly 5 year with an HbA1c >8.0% from diagnosis until starting insulin and about 10 year with an HbA1c >7.0%. Another barrier to optimal diabetes management is that diabetes patients usually have multiple comorbidities, each having its own set of guidelines. A paper by Boyd and Leff (55) examined care for older patients with multiple comorbid diseases, pointing out that half of the population older than 65 has 3 or more chronic diseases. In such cases, a balance must be struck between adhering to guidelines and individualizing treatment to patients’ circumstances. Treatment of each comorbidity comes with risk and the burden of treatment on the patient and caregiver. The analysis suggested that, in some patients, following recommended guidelines of each individual disease state could result in an unsustainable treatment burden, making independent self-management and adherence difficult. Additional possible reasons for apparent nonadherence in this setting include limitations of function and of social support. A focus on those comorbidities with a shorter time to benefit and a consensus between the patient and the physician that incorporates the patient’s preferences are required in this patient population (55). Data from the DAWN study reveal that, globally, the level of resistance on the part of physicians is variable, but that only in India and Japan were physicians more predisposed to delay insulin therapy than U.S. physicians (56). Concern about efficacy was the factor most strongly correlated with delay of insulin therapy. Just over half of surveyed physicians and nurses agreed that insulin can have a positive impact on care. In other studies, self-blame has been identified as the attitude most predictive of patients’ unwillingness to begin insulin therapy (45), and physicians contribute to this perception. Over half of the health care professionals from the DAWN study reported using the threat of eventual insulin therapy as a strategy, referring to insulin as a consequence of inaction to encourage more active self-care among nonadherent patients (56). Several specific factors contributing to psychological insulin resistance on the part of the physician have been identified (57): • Sense of inadequacy or perceived inability to manage a patient’s diabetes with treatments other than insulin • A lack of adequate time or personnel to instruct a patient on how to use insulin and titrate the dose • Concerns about weight gain and hypoglycemia • Fear of losing or alienating the patient [...]... Intern Med 2005; 165 :9 36 9 46 66 Dahlof B, Sever PS, Poulter NR, et al Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes TrialBlood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial Lancet 2005; 366 :895–9 06 67 Marre M,... effect of angiotensin-converting enzyme inhibition in noninsulin-dependent diabetes mellitus A 7-year follow-up study Arch Intern Med 19 96; 1 56: 2 86 289 72 Schnack C, Hoffmann W, Hopmeier P, Schernthaner G Renal and metabolic effects of 1-year treatment with ramipril or atenolol in NIDDM patients with microalbuminuria Diabetologia 19 96; 39: 161 1– 161 6 73 Ahmad J, Siddiqui MA, Ahmad H Effective postponement of. .. either apoA-I or apoB or, in the case of chylomicrons, both ApoA-I and apoA-II are the major apolipoproteins of HDL All lipoproteins of density less than 1. 063 g/mL (chylomicrons, VLDL, IDL, and LDL) contain apoB ApoB-48 is synthesized only in the intestine and is found Table 2 Major apolipoproteins Apolipoprotein Molecular weight A-I 28,000 HDL, chylomicrons A-II B-48 B-100 17,000 264 ,000 550,000 C-II 9,100... noncovalently to each VLDL particle in the liver and remains with the particle through its metabolism to IDL and LDL Because of its huge size (550 kDa) and hydrophobicity, the binding of apoB to lipoprotein particles is irreversible, lasting until cellular uptake and lysosomal hydrolysis of the particles (11) The regulatory functions of apoA-I, apoB-100, apoC-II, apoC-III, and apoE are now well established,... despite the use of 2 medications on average (64 ) In ASCOT, 53% of participants reached both their systolic and diastolic blood-pressure targets, but only 32% of patients with diabetes reached their intensive targets of SBP < 130 and DBP < 80 mm Hg ASCOT also limited the use of therapies to amlodipine plus perindopril versus atenolol plus bendroflumethiazide (66 ) In UKPDS, just over 60 % of participants... SBP < 120 mm Hg SBP > 120 mm Hg Relative Risk (≥ 120/ . clinical practice for the diagnosis and treatment of dyslipidemia and prevention of atherogenesis. Endocr Pract 2000 Mar-Apr ;6( 2): 162 –213. 19. Snow V, Aronson MD, Hornbake ER, Mottur-Pilson C, Weiss KB;. relationship between micro- and macrovascular complica- tions and hyperglycemia as well the often accompanying hypertension and dyslipidemia. More importantly, several landmark randomized prospective. collection, and by 1994 included the 50 state health departments as well as those in the District of Columbia, Puerto Rico, Guam, and the U.S. Virgin Islands. It is the world’s largest, on-going random-digit