Regular screening in type 2 diabetes

A mnemonic approach for improving compliance, detecting complications

Thomas J. Beckman, MD

VOL 115 / NO 4 / APRIL 2004 / POSTGRADUATE MEDICINE

CME learning objectives

• To recognize the problem of inadequate healthcare maintenance in patients with type 2 diabetes
• To review existing recommendations and supporting literature about healthcare maintenance in diabetic patients
• To develop a method of organizing and remembering issues to address during office visits with diabetic patients

The author discloses no financial interests in this article and no unlabeled uses of any product mentioned.

Preview: Physicians caring for patients with type 2 diabetes often do not adequately conduct recommended screenings for diabetes-related conditions. In this article, Dr Beckman reviews existing guidelines for healthcare maintenance in patients with type 2 diabetes and offers a mnemonic-based technique for organizing and remembering which issues to address during office visits. Beckman TJ. Regular screening in type 2 diabetes: a mnemonic approach for improving compliance, detecting complications. Postgrad Med 2004;115(4):19-27

Patients with diabetes have twice as many healthcare expenditures (1), consume more healthcare resources, and account for twice as many office and hospital visits (2) as patients without diabetes. In addition to the overall burden of diabetes on the healthcare system, individual physicians may find patients with type 2 diabetes difficult to manage because of the number of diabetes-related screenings that should be performed on a regular basis. Supporting this observation are studies showing that physicians caring for patients with diabetes do not adequately address diabetes-related healthcare screening (3). There is also evidence that the challenge of managing diabetes per se may interfere with routine cancer screening in these patients (4).

In light of the need to improve healthcare maintenance in patients with type 2 diabetes, I have devised a mnemonic, HELP, which has proved useful for remembering which issues to address during each office visit:

H	Hemoglobin A1c (HbA1c), Hypertension
E	Eye screening
L	Lipid screening
P	Urinary Protein, Podiatry (foot examinations), and Pneumococcal and influenza vaccinations

The American Diabetes Association (ADA), the National Cholesterol Education Program, the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7), and the Centers for Disease Control and Prevention have made recommendations regarding management issues in patients with diabetes (5-8). Here, I review these recommendations for the healthcare issues covered in the HELP mnemonic in terms of the basis, frequency of assessment, and goals of screening and therapy. I also present the medical literature supporting these recommendations and summarize the highlights of this discussion in table 1.

Recurring healthcare issues

Appropriate management of patients with type 2 diabetes requires that a number of healthcare screenings be performed on a regular basis. Using the HELP mnemonic is one way to organize and recall these measures.

Hemoglobin A_1c
HbA_1c measurement and patient self-monitoring of blood glucose are the mainstays for objectively assessing long-term glycemic control in patients with diabetes. Present in all humans, HbA_1c is a component of hemoglobin that increases with hyperglycemia (9). The HbA_1c level reflects the average blood glucose concentration over the preceding 3 months, which roughly corresponds to the average life span of a red blood cell.

Patients with type 2 diabetes should have their HbA_1c level evaluated every 3 months until adequate glycemic control is achieved, after which it may be assessed biannually (5). Although a discussion of treating diabetic-range hyperglycemia with oral antidiabetic agents or insulin is beyond the scope of this article, it should be emphasized that achieving weight reduction through appropriate diet and exercise is the cornerstone of therapy for all overweight patients with type 2 diabetes.

The goal of glycemic control is an HbA_1c level less than 7%, assuming a patient can achieve this goal without undue risk of significant hypoglycemia. Justification for this recommendation derives primarily from the UK Prospective Diabetes Study 33 (UKPDS 33) (10). This arm of the study was a randomized controlled trial involving 3,867 subjects with type 2 diabetes. The subjects were randomly assigned to intensive treatment with a sulfonylurea or insulin or to treatment with diet alone. After 10 years, the HbA_1c level was 7.0% in the intensive treatment group versus 7.9% in the group receiving diet therapy. The investigators demonstrated a 25% reduction in the risk of microvascular complications in subjects with intensive glycemic control. This risk reduction was attributed primarily to a reduced need for photocoagulation to treat diabetic retinopathy. There was also a reduced risk of myocardial infarction in the intensive treatment group, although this finding was just short of reaching statistical significance.

Hypertension
Cardiovascular disease is the primary cause of death in patients with diabetes, and the coronary death rate for patients with diabetes is over twice that for patients without diabetes (11). Consequently, cardiovascular risk reduction is essential in the effective management of patients with diabetes. Physicians are encouraged to assess blood pressure in these patients during each office visit.

The ADA and the JNC7 recommend that the goal blood pressure for a patient with diabetes be less than 130/80 mm Hg (5,7). Support for this recommendation comes from the UKPDS 38 (12). In this randomized controlled trial involving 1,148 subjects with type 2 diabetes and hypertension, 758 subjects were assigned to tight blood pressure control (blood pressure, <150/85 mm Hg) and 390 subjects were assigned to less tight control (blood pressure, <180/105 mm Hg). The investigators demonstrated that after 8.4 years of follow-up, subjects with tightly controlled blood pressure experienced significant risk reduction for diabetes-related deaths (32%) and stroke (44%). Subjects with type 2 diabetes and tightly controlled blood pressure also had a significant reduction in the progression of retinopathy.

Attempts to lower blood pressure in all patients, including those with diabetes, should emphasize lifestyle modifications such as weight loss through exercise and a high-fiber, calorie-restricted, low-sodium diet; moderation of alcohol intake; and smoking cessation (7). A preferred therapeutic approach for lowering blood pressure in patients with diabetes is to use an angiotensin-converting enzyme (ACE) inhibitor. Studies in patients with diabetes have demonstrated that ACE inhibitors can prevent microvascular and macrovascular complications (12) as well as the progression of albuminuria (13).

Both the UKPDS 39 (14) and a study by Nielsen and colleagues (15) demonstrated that ACE inhibitors and beta-blockers were equally efficacious in reducing macrovascular end points and slowing renal function decline in patients with diabetes. These findings are especially valuable in light of the incidence of coronary artery disease (CAD) in patients with diabetes and the utility of beta-blockers in secondary risk reduction of fatal outcomes in patients with CAD (16). Accordingly, beta-blockers are an important antihypertensive therapy in patients with diabetes who lack contraindications to this class of medications. In addition, since two or more medications are often required to achieve the recommended blood pressure goals, the JNC7 notes that beta-blockers, ACE inhibitors, angiotensin II receptor blockers, and thiazide diuretics are all beneficial for treating hypertension in patients with diabetes (7).

Eye screening
Diabetes is the leading cause of blindness in the United States (17), and diabetic retinopathy is one of the most dreaded complications in patients with diabetes (18). The microvascular retinal changes associated with diabetes follow a recognizable pattern of pathologic sequelae. Initially, patients suffer from vascular leakage, which may progress to retinal ischemia and eventually neovascularization, or proliferation of new retinal blood vessels (18,19). This last stage of pathologic characteristics, termed proliferative diabetic retinopathy, is commonly treated with laser photocoagulation.

For diabetic retinopathy screening, it is recommended that patients have a dilated retinal examination at the diagnosis of type 2 diabetes and yearly thereafter (5,19). Patients need to be examined more often if pathologic changes are discovered (19).

The recommendation to screen for diabetic retinopathy is based largely on two randomized trials: the Early Treatment Diabetic Retinopathy Study (20) and the Diabetic Retinopathy Study (21). These studies found that laser photocoagulation reduced progression to visual loss in patients with diabetes and proliferative diabetic retinopathy. The UKPDS 33 (10) demonstrated the importance of glycemic control in the prevention of retinal eye disease in patients with type 2 diabetes. Specifically, the investigators demonstrated a 25% reduction in risk of microvascular end points in subjects with intensive glycemic control. This risk reduction was attributed primarily to a reduced need for photocoagulation to treat diabetic retinopathy.

Lipid screening
Several studies emphasize that patients with diabetes have an exaggerated risk of cardiovascular disease (11). Consequently, serum lipid management is central to mortality risk reduction in patients with diabetes. Physicians should monitor fasting serum lipid levels yearly in patients with type 2 diabetes, more frequently as required for the adjustment of lipid-lowering therapy, and every 2 years once serum lipid levels are within goal range (5).

The goals of therapy for all diabetic patients are a low-density lipoprotein cholesterol (LDL-C) concentration of less than 100 mg/dL (2.59 mmol/L), a high-density lipoprotein cholesterol (HDL-C) level higher than 40 mg/dL (1.03 mmol/L), and a triglyceride level less than 150 mg/dL (1.69 mmol/L) (5).

The threshold at which medical therapy is initiated may depend on the LDL-C level and whether other comorbidities are present. For example, the ADA recommends that in patients with diabetes who have CAD or another type of vascular disease, medical therapy should be initiated if the LDL-C level exceeds 100 mg/dL (5). Otherwise, patients with diabetes who have an LDL-C level between 100 and 130 mg/dL (2.59 and 3.36 mmol/L) should attempt lifestyle modifications, including dietary changes, exercise, and improved glycemic control, before they start taking a medication (5,6). Medical therapy should be initiated for all diabetic patients with an LDL-C level higher than 130 mg/dL (5,6).

Preferred medical therapy for hyperlipidemia in patients with diabetes is the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors ("statins") (22). Support for this recommendation comes mainly from two secondary prevention trials. The first trial is the Scandinavian Simvastatin Survival Study (4S) (23), which involved 202 patients with diabetes and prior myocardial infarction or angina and 4,242 patients with prior myocardial infarction or angina and no diabetes. Patients were randomly assigned to receive simvastatin or placebo. After 5 years of follow-up, the investigators demonstrated significant risk reductions in major CAD events (relative risk, 0.45) and any atherosclerotic event (relative risk, 0.63) in patients with diabetes who received simvastatin.

Current lipid-lowering guidelines in patients with diabetes are also justified by the Cholesterol and Recurrent Events (CARE) trial (24). This trial involved 586 subjects with a history of myocardial infarction and diabetes and 3,573 subjects with a history of myocardial infarction and no diabetes. Subjects were randomly assigned to receive pravastatin sodium or placebo. In diabetic patients, pravastatin significantly reduced the relative risk of coronary events by 25% and of revascularization by 32%. The investigators in the 4S and CARE trials concluded that the use of the HMG-CoA reductase inhibitors studied might improve the prognosis and reduce the risk of recurrent coronary events in patients with diabetes.

Urinary protein
Type 2 diabetes is one of the leading causes of end-stage renal disease (25). Urine microalbumin is the best early indicator of renal decline (26), and the most sensitive means to detect proteinuria is by measuring urine microalbumin. Moreover, detecting microalbuminuria and initiating treatment with an ACE inhibitor (13), optimizing glycemic control (10), managing hypertension (13,14), and avoiding intravenous contrast agents and nephrotoxic drugs, such as nonsteroidal anti-inflammatory drugs, are all interventions that may decrease progression to renal failure in diabetic patients. Therefore, it is recommended that patients with type 2 diabetes have their urinary microalbumin level assessed at diagnosis and yearly thereafter (5).

Microalbuminuria is defined as urinary albumin losses between 20 and 200 micrograms/min (26). Although the standard method for assessing microalbumin level is by obtaining a timed urine collection, single-sample determinations have been shown to correlate well with 24-hour samples (27). One method for detecting urinary microalbumin is to measure the urinary albumin-creatinine ratio in a random sample.

In patients with diabetes, it has been shown that single voided urine samples corrected for creatinine have high sensitivity and specificity compared with 24-hour urinary albumin as the "gold standard" (28). Because vigorous exercise can increase microalbuminuria, patients should refrain from exercise for 24 hours before providing a urine sample for assessing microalbumin.

Podiatry (foot examinations)
Diabetes predisposes patients to peripheral vascular disease as well as peripheral neuropathies, which largely account for the complications of foot ulcers, gangrene, and amputations of the extremities in patients with diabetes (18,29). Hence, physicians are urged to perform a careful foot examination at least yearly in all asymptomatic patients with diabetes, and more frequent examinations should be performed if the patient is known to have neuropathy or peripheral vascular disease (5,29). Additionally, risk factors such as improper footwear, smoking, and the presence of tinea foot infections should be addressed (29).

At least one study has shown that periodic foot examinations reduce the incidence of diabetic foot ulcers. In a trial by Litzelman and colleagues (30), 352 subjects with type 2 diabetes were randomly assigned to an intervention group receiving patient- and physician-based interventions aimed at enhancing foot care over 12 months or to a control group not receiving these interventions. Subjects in the intervention group were significantly less likely to have serious foot lesions than the control subjects (odds ratio, 0.41).

Pneumococcal and influenza vaccinations
Patients with diabetes have impaired cell-mediated immunity (31), and it has been shown that hyperglycemia increases the risk of infection in such patients (32). Data also suggest an increased incidence of streptococcal infection and an increased morbidity from influenzal illness in patients with diabetes (33,34). Furthermore, the pneumococcal vaccine (Pneumovax 23, Pnu-Imune 23) is considered effective in patients with diabetes, because their antibody response to this vaccine is similar to that of patients without diabetes (35).

It is important that all patients with diabetes receive pneumococcal and influenza vaccinations. Influenza virus vaccine (FluShield, Fluvirin, Fluzone) should be provided to diabetic patients annually, and special attention should be given to providing influenza and pneumococcal vaccinations to patients who are older than 64 years or who have coexisting chronic diseases (8,36). Healthcare providers should also consider repeating the pneumococcal vaccination for patients 65 years or older if the initial dose was given before age 65 and it has been 5 years since the initial dose or if the diabetic patient is immunocompromised with conditions such as chronic renal disease or nephrotic syndrome (8,36).

Summary

Healthcare providers can be overwhelmed by the complexity of issues to address during follow-up visits with patients who have type 2 diabetes. On this basis alone, it is not surprising that physicians often fail to adequately address both diabetes-related and non-diabetes-related healthcare screening in these patients. Special recommendations exist for HbA_1c level, hypertension, eye screening, hyperlipidemia, urinary protein, foot examinations, and vaccinations in patients with diabetes. I have found the HELP mnemonic useful for systematically and efficiently addressing recurring issues in patients with diabetes during routine office visits. It has also been accepted by medical students and residents as a valuable aid in the management of diabetes. My hope is that this system of organization will help the reader provide more effective care to these patients as well.

References

1. Selby JV, Ray GT, Zhang D, et al. Excess costs of medical care for patients with diabetes in a managed care population. Diabetes Care 1997;20(9):1396-402
2. Rendell M, Kimmel DB, Bamisedun O, et al. The health care status of the diabetic population as reflected by physician claims to a major insurer. Arch Intern Med 1993;153(11):1360-6
3. Peters AL, Legoretta AP, Ossorio RC, et al. Quality of outpatient care provided to diabetic patients: a health maintenance organization experience. Diabetes Care 1996;19(6):601-6
4. Beckman TJ, Cuddihy RM, Scheitel SM, et al. Screening mammogram utilization in women with diabetes. Diabetes Care 2001;24(12):2049-53
5. American Diabetes Association. Clinical practice recommendations. Available at: http://care.diabetesjournals.org. Accessed Jan 26, 2004
6. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285(19):2486-97
7. Chobanian AV, Bakris GL, Black HR, et al. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC7 report. JAMA 2003;289(19):2560-72
8. Advisory Committee on Immunization Practices (ACIP). Recommendations of the ACIP. Available at: http://www.cdc.gov/nip/publications/ACIP-list.shtml. Accessed Jan 26, 2004
9. Foster DW. Diabetes mellitus. In: Isselbacher KJ, Braunwald E, Wilson JD, et al, eds. Harrison's principles of internal medicine. 13th ed. New York: McGraw-Hill, 1994:1979-2000
10. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352(9131):837-53
11. Kleinman JC, Donahue RP, Harris MI, et al. Mortality among diabetics in a national sample. Am J Epidemiol 1988;128(2):389-401
12. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ 1998;317(7160):703-13
13. Ravid M, Savin H, Jutrin I, et al. Long-term stabilizing effect of angiotensin-converting enzyme inhibition on plasma creatinine and on proteinuria in normotensive type II diabetic patients. Ann Intern Med 1993;118(8):577-81
14. Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. UK Prospective Diabetes Study Group. BMJ 1998;317(7160):713-20
15. Nielsen FS, Rossing P, Gall MA, et al. Long-term effect of lisinopril and atenolol on kidney function in hypertensive NIDDM subjects with diabetic nephropathy. Diabetes 1997;46(7):1182-8
16. Yusuf S, Peto R, Lewis J, et al. Beta blockade during and after myocardial infarction: an overview of the randomized trials. Prog Cardiovasc Dis 1985;27(5):335-71
17. Klein R, Klein B. Vision disorders in diabetes. In: Harris MI, Cowie CC, Stern MP, et al, eds. Diabetes in America. 2nd ed. Bethesda, Md: US Dept of Health and Human Services, 1995. NIH publication 95-1468: pp 293-338
18. Nathan DM. Long-term complications of diabetes mellitus. N Engl J Med 1993;328(23):1676-85
19. Aiello LP, Gardner TW, King GL, et al. Diabetic retinopathy. Diabetes Care 1998;21(1):143-56
20. Early photocoagulation for diabetic retinopathy. ETDRS report No. 9. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology 1991;98(5 Suppl):766-85
21. Indications for photocoagulation treatment of diabetic retinopathy: diabetic retinopathy study report No. 14. The Diabetic Retinopathy Study Research Group. Int Ophthalmol Clin 1987;27(4):239-53
22. Haffner SM. Management of dyslipidemia in adults with diabetes. Diabetes Care 1998;21(1):160-78
23. Pyorala K, Pedersen TR, Kjekshus J, et al. Cholesterol lowering with simvastatin improves prognosis of diabetic patients with coronary heart disease: a subgroup analysis of the Scandinavian Simvastatin Survival Study (4S). Diabetes Care 1997;20(4):614-20
24. Goldberg RB, Mellies MJ, Sacks FM, et al. Cardiovascular events and their reduction with pravastatin in diabetic and glucose-intolerant myocardial infarction survivors with average cholesterol levels: subgroup analyses in the Cholesterol and Recurrent Events (CARE) trial. The CARE Investigators. Circulation 1998;98(23):2513-9
25. Nelson RG, Knowler WC, Pettitt DJ, et al. Kidney diseases in diabetes. In: Harris MI, Cowie CC, Stern MP, eds (17), pp 349-400
26. Mauer M, Mogensen CE, Friedman EA. Diabetic nephropathy. In: Schrier RW, Gottschalk CW, eds. Diseases of the kidney. Vol 3. 6th ed. Boston: Little, Brown, 1997:2019-61
27. Schwab SJ, Dunn FL, Feinglos MN. Screening for microalbuminuria: a comparison of single sample methods of collection and techniques of albumin analysis. Diabetes Care 1992;15(11):1581-4
28. Nathan DM, Rosenbaum C, Protasowicki VD. Single-void urine samples can be used to estimate quantitative microalbuminuria. Diabetes Care 1987;10(4):414-8
29. Mayfield JA, Reiber GE, Sanders LJ, et al. Preventive foot care in people with diabetes. Diabetes Care 1998;21(12):2161-77
30. Litzelman DK, Slemenda CW, Langefeld CD, et al. Reduction of lower extremity clinical abnormalities in patients with non-insulin-dependent diabetes mellitus: a randomized, controlled trial. Ann Intern Med 1993;119(11):36-41
31. Katz S, Klein B, Elian I, et al. Phagocytotic activity of monocytes from diabetic patients. Diabetes Care 1983;6(5):479-82
32. Rayfield EJ, Ault MJ, Keusch GT, et al. Infection and diabetes: the case for glucose control. Am J Med 1982;72(3):439-50
33. Bayer AS, Chow AW, Anthony BF, et al. Serious infections in adults due to group B streptococci: clinical and serotypic characterization. Am J Med 1976;61(4):498-503
34. Bouter KP, Diepersloot RJ, van Romunde LK, et al. Effect of epidemic influenza on ketoacidosis, pneumonia and death in diabetes mellitus: a hospital register survey of 1976-1979 in the Netherlands. Diabetes Res Clin Pract 1991;12(1):61-8
35. Beam TR Jr, Crigler ED, Goldman JK, et al. Antibody response to polyvalent pneumococcal polysaccharide vaccine in diabetics. JAMA 1980;244(23):2621-4
36. Smith SA, Poland GA, for the American Diabetes Association. Immunization and the prevention of influenza and pneumococcal disease in people with diabetes. Diabetes Care 2001;24(Suppl 1):S99-101

The author acknowledges Amit K. Ghosh, MD, and Haitham S. Abu-Lebdeh, MD, division of general internal medicine, Mayo Clinic, for their thoughtful and valuable input in the preparation of this article.

Dr Beckman is assistant professor of medicine, division of general internal medicine, department of medicine, Mayo Clinic, Rochester, Minnesota. Correspondence: Thomas J. Beckman, MD, Division of General Internal Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905. E-mail: beckman.thomas@mayo.edu.

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