Managing Diabetes Complications: Focus on the Fundamentals of Care

The serious complications of diabetes are well known: cardiovascular disease, nephropathy, retinopathy, and neuropathy. These microvascular and macrovascular complications can have devastating consequences on the health of people with diabetes.^[1]

Health plans can improve the quality of care in this area by:

• Educating members about the risks and consequences of diabetic complications and steps they can take to prevent or delay diabetes complications
• Promoting regular screening for complications and early treatment

The first step in preventing or delaying the onset of diabetes complications is raising patients’ awareness of risk. Table 1 gives a brief overview of the risks of cardiovascular disease (CVD), nephropathy, retinopathy, and neuropathy in different populations. Other common complications of diabetes include periodontal disease, birth defects or spontaneous abortions of babies in mothers with uncontrolled diabetes, and biochemical imbalances that can cause life-threatening events, such as diabetic ketoacidosis and hyperosmolar (nonketotic) coma. There is also a greater risk of contracting and dying from other illnesses, such as pneumonia or influenza.^[2]

The top priorities for minimizing the risks of all microvascular and macrovascular diabetes complications are the “ABCs of Diabetes”—A1c control, lowering blood pressure, and lowering cholesterol.^[1,8] The ADA and the ACC have developed an initiative called Make the Link! Diabetes, Heart Disease and Stroke to educate diabetes patients and health care professionals about the importance of managing these important risk factors. The initiative includes a Web site with information and an interactive program for patients. For professionals, the site contains a newsletter, a tool kit with patient handouts, clinical practice recommendations, and a links library.^[9]

The foundation of diabetes treatment is improved glycemic control, which reduces the risk of microvascular complications and is associated with lower risk of macrovascular disease and atherosclerosis.^[1] In patients with type 2 diabetes, the risk of diabetic complications is strongly associated with previous hyperglycemia.^[10]

Evidence is accumulating that controlling hypertension and cholesterol levels is also important for reducing diabetic vascular complications.^[1] Blood pressure control can reduce CVD by 33% to 50% and can reduce microvascular disease by about 33%. Improved lipid control can reduce CVD complications by 20% to 50%.^[2]

As discussed previously, the HEDIS rates for control of A1c and lipid levels in diabetic patients are improving. However, in the NHANES 1999-2000 survey (which assesses the general population), only 7.3% of people with diabetes met the ADA recommended guidelines for all three risk factors: blood glucose, cholesterol, and blood pressure levels.^[11] To improve quality of care, health plans need to promote screening and proactive treatment to reach the ABC goals.

Studies have shown that, in general, every reduction in A1c level of 1% (e.g., from 8% to 7%) reduces the risk of developing microvascular complications by 40%.2 The ADA recommends a treatment goal of A1c <7%. In the NHANES 1999-2000 survey, about 37% of patients with diabetes had an A1c level higher than 8%, the level at which the ADA recommends focused treatment action. ^[1] Achieving glycemic control requires an active partnership between the patient and his or her physician.

Self-monitoring of blood glucose (SMBG) allows patients to evaluate their response to therapy and assess whether they are reaching their A1c target. Physicians can use SMBG results to adjust medications. Patients who take insulin need to monitor blood glucose at least daily to prevent asymptomatic hypoglycemia and hyperglycemia. Most patients with type 1 diabetes need to monitor three or more times per day. Patients with type 2 diabetes on oral drug therapy need to monitor often enough to reach their A1c goal.^[12]

Because accuracy of SMBG depends on the instrument used and the user’s technique, caregivers must ensure that patients learn how to use the instrument and monitor the patients’ technique at regular intervals. Patients also need to know how to use the data to adjust their food intake, physical activity, or drug therapy to achieve specific glycemic goals.^[12]

Lifestyle changes (diet and exercise) are typically the first-line treatment for type 2 diabetes and can be very effective in controlling blood glucose levels early in the disease. When this treatment fails to maintain adequate glucose control, oral antihyperglycemic agents are usually the next step.^[13]Over time, due to the progressive nature of type 2 diabetes, a combination of oral agents is frequently necessary to maintain glucose control.^[14]

In type 2 diabetes, insulin is generally initiated only after oral agents are no longer able to maintain adequate glucose control.^[14] Unfortunately, physicians may delay the appropriate use of insulin, at least in part because of resistance from the patient.^[15] Techniques to address patient and physician resistance to the initiation of insulin are discussed in the section titled “Addressing the Quality Gaps in Diabetes Prevention and Care”.

The goal of insulin therapy is strict glycemic control without significant hypoglycemia. Because older insulin products do not closely mimic normal insulin secretory patterns, they can be problematic. Insulin analogs, both rapid-acting (postprandial) and long-acting (basal), are now available. Three of these analogs—lispro, aspart, and glargine—have been widely studied, and others are being developed.^[16]

Researchers have been attempting to find alternative methods of delivering insulin for the past 75 years,^[17] but success has been limited. Recent clinical studies suggest that inhaled insulin, either a dry powder formulation or a liquid aerosol formulation, may become the first nonsubcutaneous route of insulin administration for widespread clinical use.^[18]

Hypertension is also a well-known cardiovascular risk factor that is highly prevalent in type 2 diabetes and in persons with overweight/obesity.^[12] It is also a component of metabolic syndrome.^[19,20] A recent study of young white men found that elevations in blood pressure preceded the development of type 2 diabetes in middle age by 20 to 25 years.^[20] The ADA recommends a blood pressure (BP) treatment goal of <130 mm Hg systolic and <80 mm Hg diastolic.^[1]

According to the United Kingdom Prospective Diabetes Study (UKPDS), each decrease of 10 mm Hg in mean systolic BP was associated with the following reductions in risk^[8]:

• 12% for any complication related to diabetes
• 15% for deaths related to diabetes
• 11% for myocardial infarction
• 13% for microvascular complications

Patients should have BP measured at every scheduled diabetes visit, both in the supine and standing positions. Those whose BP is elevated on two occasions separated by at least one week can be diagnosed with hypertension.^[8]

Research has shown that angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers, low-dose thiazide diuretics, and ß-blockers are all effective antihypertensives.^[21] Some patients require three or more drugs to achieve target levels of BP control.^[21] In the UKPDS, 29% of patients in the tight BP control group required three or more antihypertensive drugs after nine years of follow-up.^[21]

The ADA recommends the following treatment goals for lipid control^[22]:

• Low-density lipoprotein (LDL) <100 mg/dL
• High-density lipoprotein (HDL): men >45 mg/dL, women >55 mg/dL
• Triglycerides <150 mg/dL

Adults with diabetes need to be screened for high cholesterol levels at least once a year. Children over two years of age should be tested at diagnosis, after glucose control has been achieved, and every five years thereafter.^[22]

If the patient is at high risk for CVD, the ADA and the ACC recommend that physicians consider beginning drug therapy at the same time as behavioral therapy for cholesterol, even in patients with borderline values. For patients otherwise not at high risk for CVD, lifestyle behavioral changes may be tried first and evaluated at six-week intervals. If these changes do not result in achieving treatment goals within three to six months, drug therapy should be initiated.^[22]

Statins are the first-line medication for lowering LDL levels. Fibrates reduce CVD risk for patients with low HDL and slow carotid intimal medial thickness progression. When prescribing both a statin and a fibrate or niacin in combination, physicians need to be cautious of adverse effects.

Achieving the 90th Percentile in HEDIS Comprehensive Diabetes Care Measures Since 1982, this staff-model HMO has operated its own health care delivery system with 23 primary care practitioners at seven locations in the northern Midwest area and achieved the 90th percentile for HEDIS Comprehensive Diabetes Care measures three years running. The plan implemented interventions in three areas: changes in the delivery of primary care services, increased patient involvement in health care, and support systems to better track and manage diabetes care. Primary Care Delivery Changes Adopted criteria for managing diabetes successfully Designated staff resources for member education and tracking Implemented “block scheduling” for members with diabetes Scheduled patient appointments in30-minute increments: five minutes with a primary care practitioner and 15 minutes with a nurse for patient education Adopted medication guidelines indicating the order in which medications are to be prescribed Developed a team approach to diabetes care with specific staff members responsible for different aspects of diabetes care Patient Involvement Began intensive individual patient education with licensed nurses Developed individual diabetes management care plans Distributed patient satisfaction surveys Support Systems Continued to identify patients with diabetes Developed standardized forms for documentation of diabetes care Developed tracking systems for care needed and received Developed tracking systems for diabetes management; nurses mailed reminders to patients before follow-up visits Created a Diabetes Advisory Council (included PCPs, nurses, and registered dietitians) to oversee all aspects of diabetes management Identified pharmaceutical companies willing to help with the cost of diabetic supplies (e.g., blood sugar testing) for patients lacking benefit coverage

Early detection of complications has the potential to alter the course of the complication and reduce mortality through recommendations for modifying lifestyle and pharmacological and other therapy.^[23] Adding screening and treatment for complications to control the ABCs can have a large impact on the quality of life for patients with diabetes.

More than 65% of people with diabetes die from heart disease or stroke.^[24] Unfortunately, according to a 2001 survey by the ADA and the ACC, 68% of diabetic patients did not think CVD was a serious complication of diabetes, and only 18% believed that they were at increased risk for CVD.^[25-27] The proportion of Hispanics and older adults who lacked knowledge of CVD risk was even higher at 75%.^[26] The ADA recommends that physicians assess cardiovascular risk factors in their patients with diabetes at least once a year and consider use of aspirin therapy, which is effective and inexpensive.^[12,28]

For more information on CVD, please refer to Quality Profiles™: The Leadership Series—Focus on Cardiovascular Disease.

Nephropathy occurs in 10% to 21% of all people with diabetes and is the leading cause of end-stage renal disease (ESRD).^[5] ESRD occurs in 50% of patients with type 1 diabetes with overt nephropathy within 10 years and in more than 75% by 20 years.^[29] The risk of nephropathy in type 1 diabetes is 12 times as high as in type 2 diabetes.^[5] Risk factors for nephropathy include race, genetic susceptibility, hypertension, hyperglycemia, hyperfiltration, smoking, and possibly advanced age, male sex, and dyslipidemia.^[29]

Control of blood glucose and blood pressure are important strategies for slowing the progression of nephropathy. Large prospective randomized studies have shown that intensive diabetes management with the goal of achieving near normoglycemia delays the onset of microalbuminuria and delays the progression of microalbuminuria to macroalbuminuria in patients with both type 1 and type 2 diabetes.^[12]

Controlling blood pressure can also reduce the risk of developing nephropathy.^[12] One study demonstrated that the use of ACE inhibitors to treat hypertension was more effective than other classes of antihypertensives in delaying the progression from microalbuminuria to macroalbuminuria.^[12]

The ADA recommends yearly screening for microalbuminuria in patients who have had type 1 diabetes for five years or more and in all patients with type 2 diabetes. Protein restriction may benefit patients whose nephropathy is progressing despite optimal glucose and blood pressure control.^[12]

Depression May Accompany Diabetes Studies suggest that patients with diabetes are two to four times more likely to develop depression than people without the disease, and their chances of becoming depressed increase as diabetes complications worsen.[30,31] Fifteen percent to 20% of patients with diabetes will become depressed,[31] often leaving a patient feeling unmotivated and unable to care for their diabetes. A person with diabetes may not even realize they are depressed, but instead assume the diabetes is causing them to feel low. Regular screening and accurate diagnosis of depression is vital to helping patients successfully manage their diabetes.[32] Consider adding depression screening and treatment to your diabetes program; the associated investment in prevention could end up being a fraction of the cost of treating the complications of uncontrolled diabetes. For more information on QI strategies for depression, please refer to Quality Profiles™: The Leadership Series—Focus on Depression

The prevalence of retinopathy is strongly related to the duration of diabetes. Nearly all patients with type 1 diabetes develop retinopathy, and most type patients with type 2 diabetes eventually develop some degree of it.^[6]

As in nephropathy, control of blood glucose and blood pressure are important strategies for reducing the risk and slowing the progression of retinopathy; in fact, nephropathy and retinopathy are frequently seen together in patients with diabetes.

Intensive diabetes management with the goal of achieving near normoglycemia prevents or delays the onset of retinopathy, and lowering blood pressure reduces its progression.^[12] The ADA recommends an initial eye exam for those who have type 1 diabetes within five years of diagnosis and shortly after diagnosis for those who have type 2 diabetes. Thereafter, nearly all patients with diabetes should have annual exams, and more often if retinopathy is progressing.^[12] One of the main reasons for screening is to allow for early detection of the condition when interventions such as laser photocoagulation surgery can prevent vision loss.^[12]

Approximately 45% of patients with diabetes have neuropathy during the course of the disease. Neuropathy is associated with pain in about 4% to 5% of all patients with diabetes.^[33]

Foot ulceration and amputation are the most common consequences of diabetic neuropathy and are major causes of morbidity and disability in people with diabetes.^[12]

The risk of ulcers or amputations is higher in people who^[12]:

• Have had diabetes more than 10 years
• Are male
• Have poor glucose control
• Have cardiovascular, retinal, or renal complications

Approximately 60% of nontraumatic lower-limb amputations in the United States occur among people with diabetes, and 85% of those are preceded by a foot ulcer.^[34] Comprehensive foot care programs can reduce amputation rates by 44% to 85%.^[34]

Preventive strategies should focus on^[34]:

• Glycemic control to reduce neuropathy
• Smoking cessation or prevention
• Early detection and appropriate management of persons with high-risk foot conditions
• Provider education on the importance of annual or more frequent foot examinations
• Patient education on daily foot care and use of proper footwear
• Health care interventions to improve care (e.g., chart reminders and patient tracking)

The ADA recommends that all patients with diabetes receive a comprehensive foot exam annually and those with neuropathy at every health care visit.^[12] High-risk patients should be referred to a foot care specialist.^[12]

Because peripheral arterial disease (PAD) is a major risk factor for lower-extremity amputation^[35] and because many patients are asymptomatic, screening for PAD is another important way to prevent amputations.^[35]

Strategies to Improve Rates of Retinal Eye Examinations A mixed model health plan in the South was determined to improve the rate of retinal eye examinations in members with diabetes. Forty-five percent of the plan’s members were seen by practitioners in a clinic setting, while the remaining members were treated by independent practitioners, many of whom were in rural locations. The organization examined the barriers to providing eye exams and identified the following: Physician Barriers Lack of feedback on performance against guidelines Loss of opportunities to refer patients for examinations when members were in office for other services Lack of appropriate resources, including staffing and documentation tools, to track services provided to members Member Barriers Lack of access to eye care specialists in rural areas Lack of knowledge of the importance of eye care and potential complications Addressing the Barriers to Eye Exams Physician Quality indicator profile sent to all PCPs twice a year, showing individual performance in comparison to HEDIS® diabetes rates as reported in Quality Compass® Standardized preventive services flow sheet implemented in the staff model clinic(s) to make eye examinations a prominent component of the medical record Financial incentives offered for all high-volume PCPs who meet targets for eye examinations annually A full-time optometrist added at the staff model eye care center Member Optometrists from the staff model traveled to rural PCP practices and provided eye examinations Saturday appointments were implemented for eye care exams at the staff model eye care center so that working members could access services at a convenient time Multiple educational mailings reminded members to seek yearly eye care examinations The health plan realized it had an opportunity in its staff model to standardize systems with centralized services, so documentation tools and additional staffing were effective in this situation. The health plan also realized that the staff model experience could be brought to the remote areas of its network by sharing resources: practitioners from the clinic traveled to physician offices in remote areas. When the health plan started this initiative, its HEDIS® retinal eye examination rate was 59.4%; three years later the rate had improved significantly to 69.6%. This example demonstrates how a health plan can adapt its interventions to meet the diverse needs of members and the variety of challenges associated with diabetes eye care.

Using Pharmacists to Coach and Monitor Patients With Diabetes The Asheville Project began in 1997 with one employer (City of Asheville) and 38 employees, retirees, or dependents with diabetes. The program expanded to a second employer, Mission-St Joseph’s Health System in March 1999, adding 47 new patients with diabetes.[36] Both employers were seeking an alternative approach to maintaining quality care while controlling health care costs.[36] Twelve community pharmacists who completed a diabetic certification program were the foundation of The Asheville Project. They acted as diabetes care managers for program participants, providing diabetes education; training in the use of blood glucose meters; clinical assessment of feet, skin, blood pressure, and weight; referrals to other health care providers; and follow-up.[36] After each patient visit, the pharmacist provided a written summary to the participant’s physician.[38] Employers compensated the pharmacists for each participant visit.[36] The program was offered on a voluntary basis to employees, dependents, and retirees with diabetes in the two employer groups. The employers offered financial incentives to promote participation: waiving diabetes prescription drug and supply co-payments and providing full coverage of diabetes education for program participants.[36] A total of 85 individuals responded to the invitation to participate in the initial pilot.[36] They visited their selected pharmacist over a seven- to nine-month period, averaging 3.7 visits per participant. The program results for the first seven to nine months were impressive.[36]: 15% of patients brought their A1c under control (<7%), with 37% decreasing their A1c by at least 1 percentage point. 10% brought their LDL-C/HDL-C ratio under control (<1.5). Although diabetes-specific costs increased by 87%, the costs for all diagnoses decreased by 16%, achieving one of the sponsoring employer’s goals of lowering costs. Participants reported a significant improvement in their satisfaction with pharmacy services. Follow-up measurement demonstrated that the program’s results were sustained over a five-year period[38]: More than half of program participants improved their A1c compared with employees before program enrollment, and the number of participants whose A1c and HDL-C values were in control also increased over time. Insurance claims costs (all diagnoses) decreased over the five years after program implementation, primarily due to the shift of expenditures from inpatient and emergency room settings to physician office settings and prescription drugs. Prescription drug costs increased each of the five succeeding years after program implementation. Sick days also decreased each subsequent year. The Asheville Project has the support of program participants, pharmacists, and the sponsoring employers who have integrated the program into their health benefit plans. The keys to its success were the participants’ view of their health as a priority, the willingness of the health care professional to take time with participants, the use of pharmacists as diabetes educators with support from the employer and medical community, and the financial incentives for participation. As a result, many organizations around the country are beginning to examine or implement the pharmacist consultation model for diabetes disease management.[38] Obtain Physician Support for Pharmacist-Driven Interventions and Education The Asheville Project team knew that physician support was critical to the success of their program. It recommended that employers who plan to use this approach send letters to area physicians inviting them to support and participate in the program. The letter should stress that the program is designed to complement the physician’s current patient care plan, and should reassure the physician that he or she will receive timely communication from the health care professionals administering supplemental care.[37]

Disease management programs help health care organizations address many of the issues patients and physicians face when dealing with a chronic disease like diabetes.^[39] Those health care organizations that use disease management programs appear to have lower medical costs over the long term while improving results (A1c testing, A1c levels, eye exams, LDL levels, nephropathy screening, and hypertension).^[40,41] Patients with diabetes in disease management programs also appear to have lower hospitalization rates, make fewer emergency room visits, and comply more often with recommended office visits.^[41,42]

While there are no definite randomized controlled trials that “prove” the value of disease management, there is a fairly large body of evidence accumulated that suggests the efficacy of disease management in improving quality of care in diabetes.

One diabetes disease management program administered by a vendor service included general education, nurse-initiated enrollment calls, clinical assessments, and ongoing telephone monitoring by a nurse. Physicians received a patient evaluation and a written action plan.^[41]

The results found^[41]:

• 33% increase in A1c monitoring
• 33% fewer hospitalizations
• 20% fewer emergency room visits
• 13% of participants reported improved functional status
• 22% of participants reported lower blood glucose levels
• 28% fewer days of diabetes-related absences from work

In another organization, a rural not-for-profit HMO, a chart review to determine the impact of a diabetes disease management program with 3,118 enrolled patients showed good results. The program involved one to four annual visits with a nurse in the primary care setting and patient education by nurse educators about self-management techniques and preventive care. The program’s treatment guidelines were based on the HEDIS diabetes care measures.^[39]

The results of the chart review found^[39]:

• Participants had higher rates of screening on HEDIS^® measures (A1c, lipids, kidney function, eye exams), fewer emergency room visits, and fewer inpatient days than nonparticipants.
• Participants had better glycemic control than nonparticipants after only three months.
• The HMO saved $4 million gross (nearly $1,300 per participant) per year (program cost was $1.8 million); a savings of $2.75 million after program costs.

Florida: A Healthy State is a patient-centered disease management program for Medicaid beneficiaries with any of four chronic diseases, including diabetes.^[43] It comprises a clinical support network that uses community-based care teams operating out of hospitals and an off-site call center. The care teams use one-on-one contact and technology tools provided by the program to educate patients about their disease, improve their ability to change behaviors, and reinforce changes with home health devices and individualized care plans.

Educational materials are culturally sensitive and written at appropriate literacy levels in both English and Spanish. Results for the targeted patients with diabetes, based on disease-specific measures and utilization analysis, included^[43]:

• 40% decrease in number of patients whose diabetes inhibited their usual activities all or most of the time
• 50% of patients improved their A1c levels within three months of care management
• 17% drop in inpatient visits
• 4% drop in emergency room visits

Setting Intervention Priorities Through Risk Stratification Members enrolled in a diabetes disease management program are certainly at various points along the continuum of disease control. Some are well controlled, others have A1c and other levels above the recommended limits, and still others have multiple comorbidities and need more intensive management. Stratifying members by the severity of their condition helps to focus intervention resources on those who need it most. One group model health plan in an urban area has worked since 1997 to refine its process for stratifying members with diabetes in its disease management program, and delivering focused interventions based on the stratification level. The organization categorizes patients with diabetes based on the presence of comorbidities and whether their disease is in control. The health care team is responsible for providing direct patient care, and the care management program team provides administrative support and overall program coordination (Table 2). Table 2: Diabetes Disease Management Program Interventions by Stratification Level Risk Assignment Criteria Interventions By Health Care Team By Care Management Program Entry Level Entry into program in the past six months Educate patient about disease, including self-management skills Enroll into disease management program and begin monitoring member’s health Low risk Diabetes under good control Provide routine recommended care Mail annual newsletter Coordinate self-care Moderate risk Metabolic parameters not controlled Use member-specific reports to identify and intervene with members not in ideal control. Reach out to a set number of patients each week to improve adherence to therapy. Provide physicians with patient lists stratified with patients at highest risk for complications at the top Provide practice sites with tools including letter templates, bulk phone messaging templates for outreach; system to identify members coming to the office for other reasons to facilitate adherence during scheduled visit High risk Evidence of disease complications present Provide case management and physician-led care coordination as appropriate Track outcomes The health plan provides specific resources at each risk level to help patients and practitioners to improve self-management and control diabetes and other related conditions. For example, a variety of patient education materials are available on the Web, in the physician’s office, at health education workshops, and via newsletters. Information technology helps the health care team focus its efforts on patients who need the most assistance. To help identify patients whose diabetes is not in control, the physician receives risk-stratified reports on a quarterly basis that list the patients in his/her panel, complete with lab results and other risk factor information that placed them in the moderate- to high-risk level. In addition, the health care team uses a database to run a daily search for members with appointments for that particular day. The database highlights tests that are due for each patient, which helps the health care team maximize each office encounter. Finally, physicians receive quarterly feedback reports that compare their performance to their office peers, and to other offices within the group. These feedback reports help physicians assess their own performance and the impact of actions they have taken to improve the management of their patients’ diabetes. This systematic approach has steadily increased adherence to the diabetes clinical guidelines over the last two years, as illustrated in Table 3. The physician group expects that over time, their patients with diabetes will have a lower risk of microvascular and macrovascular complications. Table 3: Disease Management Program Results Measure 2002 2003 A1c <8% 55.1% 67.3% LDL <130 mg/dL 53.2% 55.3% Retinal Eye Exams 89.4% 88.3% Nephropathy Screening 72.6% 73.6% For examples of the risk-stratified patient and physician-specific clinical quality of care reports, please see Appendix 5.

1. Saydah SH, Fradkin J, Cowie CC. Poor control of risk factors for vascular disease among adults with previously diagnosed diabetes. JAMA. 2004;291:335-342.

2. American Diabetes Association. National diabetes fact sheet. Available at: http://www.diabetes.org/utils/printthispage.jsp?PageID=STATISTICS_233193. Accessed March 14, 2005.

3. American Diabetes Association, American College of Cardiology. Diabetes & Cardiovascular Disease Review. Coronary Heart Disease in Women with Diabetes. Issue 5. Available at: http://www.diabetes.org/uedocuments/Issue5.women.diabetes.cvd.pdf. Accessed March 14, 2005.

4. Hillier TA, Pedula KL. Complications in young adults with early-onset type 2 diabetes: losing the relative protection of youth. Diabetes Care. 2003;26:2999-3005.

5. American Diabetes Association. Diabetes and nephropathy (kidney complications). Available at: http://www.diabetes.org/utils/printthispage.jsp?PageID=STATISTICS_233191. Accessed March 14, 2005.

6. American Diabetes Association. Diabetes and retinopathy (eye complications). Available at: http://www.diabetes.org/diabetes-statistics/eye-complications.jsp. Accessed March 14, 2005.

7. Bloomgarden ZT. American Diabetes Association 60th Scientific Sessions, 2000: the diabetic foot. Diabetes Care. 2001;24:946-951.

8. American Diabetes Association, American College of Cardiology. Diabetes & Cardiovascular Disease Review. Hypertension in diabetes. Issue 2. Available at: http://www.diabetes.org/uedocuments/ADACardioReview_2.pdf. Accessed December 18, 2004.

9. American Diabetes Association. Make the Link! Diabetes, Heart Disease and Stroke. Available at: http://www.diabetes.org/utils/printthispage.jsp?PageID=TYPE1DIABETES3_232972. Accessed March 11, 2005.

10. Stratton IM, Adler AI, Neil HAW, et al, on behalf of the UK Prospective Diabetes Study Group. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000;321:405-412.

11. American Diabetes Association. Fight against diabetes and heart disease link intensifies: more efforts needed to help people with diabetes manage the “abcs of diabetes” [press release]. Available at: http://www.diabetes.org/utils/printthispage.jsp?PageID=MISCELLANEOUS3_273474. Accessed March 16, 2005.

12. American Diabetes Association. Standards of medical care in diabetes. Diabetes Care. 2005;28(suppl):S4-S36.

13. Cooppan R. The changing model of insulin use in type 2 diabetes. Techniques, tactics for getting to goal. Postgrad Med. 2003;113:59-64.

14. White JR Jr, Davis SN, Cooppan R, et al. Clarifying the role of insulin in type 2 diabetes management. Clin Diabetes. 2003;21:14-21.

15. Haran C. A passage to insulin: natural progression or failure? Available at: http://www.healthology.com/focus_article.asp?f=diabetes&b=healthology&c=diabetes_insulin. Accessed March 18, 2005.

16. White JR Jr, Campbell RK, Hirsch IB. Novel insulins and strict glycemic control: analogues approximate normal insulin secretory response. Postgrad Med. 2003;113:1-11.

17. Heinemann L, Pf¨utzner A, Heise T. Alternative routes of administration as an approach to improve insulin therapy: update on dermal, oral, nasal and pulmonary insulin delivery. Curr Pharm Des. 2001;7:1327-1351.

18. Owens DR, Zinman B, Bolli G. Alternative routes of insulin delivery. Diabet Med. 2003;20:886-898.

19. Adams K, Corrigan J. Priority Areas for Quality Improvements: Obesity. Washington, DC: National Academy of Sciences; 2005.

21. Arauz-Pacheco C, Parrott MA, Raskin P. The treatment of hypertension in adult patients with diabetes. Diabetes Care. 2002;25:134-147.

22. American Diabetes Association, American College of Cardiology. Diabetes & Cardiovascular Disease Review. Diabetic dyslipidemia. Issue 3. Available at: http://www.diabetes.org/uedocuments/ADIACardioReview3.pdf. Accessed March 9, 2005.

23. Eyre H, Kahn R, Robertson RM, on behalf of the ACS/ADA/AHA Collaborative Writing Committee. Preventing cancer, cardiovascular disease, and diabetes: a common agenda for the American Cancer Society, the American Diabetes Association, and the American Heart Association. Diabetes Care. 2004;27:1812-1824.

24. American Diabetes Association. Diabetes and cardiovascular (heart) disease. Available at: http://www.diabetes.org/utils/printthispage.jsp?PageID=STATISTICS_233190. Accessed March 15, 2005.

25. Inzucchi SE. Poll shows people with diabetes unaware of risk for heart disease [press release: March 15, 2002]. Available at: http://www.ynhh.org/healthlink/cardiac/cardiac_3_02.html. Accessed February 10, 2005.

26. American Diabetes Association, American College of Cardiology. The diabetes-heart disease link: surveying attitudes, knowledge and risk. Survey results at a glance. Available at: http://www.diabetes.org/uedocuments/ataglance_1.pdf. Accessed January 27, 2005.

27. American Diabetes Association, American College of Cardiology. Diabetes & Cardiovascular Disease Review. Redefining diabetes control. Issue 1.Available at: http://www.diabetes.org/uedocuments/DCVDissue1.pdf. Accessed October 20, 2004.

28. Persell SD, Baker DW. Aspirin use among adults with diabetes: recent trends and emerging sex disparities. Arch Intern Med. 2004;164:2492-2499.

29. Ayodele OE, Alebiosu CO, Salako BL. Diabetic nephropathy—a review of the natural history, burden, risk factors and treatment. J Natl Med Assoc. 2004;96:1445-1454.

30. National Institute of Mental Health. Depression and diabetes. Available at: http://www.nimh.nih.gov/publicat/NIMHdepdiabetes.pdf. Accessed March 17, 2005.

31. McMan’s Depression and Bipolar Web site. Depression and diabetes. Available at: http://www.mcmanweb.com/article-42.htm. Accessed March 18, 2005.

32. Watkins CE. Diabetes, depression, and stress. Available at: http://www.baltimorepsych.com/dmdepression.htm. Accessed March 18, 2005.

33. Hospital Practice. Managing painful diabetic neuropathy. Available at: http://www.hosppract.com/issues/1999/10/ceback.htm. Accessed April 18, 2005.

34. Centers for Disease Control and Prevention. History of foot ulcer among persons with diabetes—United States, 2000-2002. MMWR Weekly. 2003;52:1098-1102. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5245a3.htm. Accessed March 15, 2005.

35. American Diabetes Association. Peripheral arterial disease in people with diabetes. Clin Diabetes. 2004;22:181-189.

36. Cranor CW, Christensen DB. The Asheville Project: Short-term outcomes of a community pharmacy diabetes care program. J Am Pharm Assoc. 2003;43:149-159.

37. Garrett DG, Martin LA. The Asheville Project: Participants’ perceptions of factors contributing to the success of a patient self-management diabetes program. J Am Pharm Assoc. 2003;43:185-190.

38. Cranor CW, Bunting BA, Christensen DB. The Asheville Project: Long-term clinical and economic outcomes of a community pharmacy diabetes care program. J Am Pharm Assoc. 2003;43:173-184.

39. The National Pharmaceutical Council. Disease Management for Diabetes. Reston, Va: The National Pharmaceutical Council; 2004.

40. Snyder JW, Malaskovitz J, Griego J, Persson J, Flatt K. Quality improvement and cost reduction realized by a purchaser through diabetes disease management. Dis Manag. 2003;6:233-241.

41. Lynne D. Diabetes disease management in managed care organizations. Dis Manag. 2004;7:47-60.

42. Villagra VG, Ahmed T. Effectiveness of a disease management program for patients with diabetes. Health Aff. 2004;23:255-266.

43. Florida: A Healthy State. A Florida First Health Care Initiative. November 2004 update. Available at: http://www.pfizerhealthsolutions.com/pdf/ProgramOverview2.pdf. Accessed February 23, 2005.