Pharmacy Times

ABCs of Avoiding Microvascular Comorbidities of Diabetes

Author: Marile L. Santamarina, MS, PharmD

Diabetes is a chronic disease demanding comprehensive medical care to prevent serious long-term comorbidities or complications. Comorbidities are defined as multiple coexisting chronic conditions in addition to a primary disease. Epidemiologic data indicate that ~20% of patients with diabetes will develop 2 or more comorbidities.1 Diabetic complications decrease quality of life, increase health care utilization, and place a significant economic burden on the health care system.2

A US Department of Health and Human Services 2005 report stated that 7% of the population, or 20.8 million people, have diabetes.3 An additional 5.2 million Americans have undiagnosed diabetes, according to the National Diabetes Education Program.4 During 2002, $132 billion was spent on diabetes.3 Long-term poorly managed diabetes likely will result in patients developing macrovascular complications (heart disease, stroke, and arthrosclerosis) and/or microvascular complications (nephropathy, retinopathy, and neuropathy).5,6 This article will discuss the microvascular complications of diabetes.

Landmark clinical trials, such as the Diabetes Control and Complications Trial (DCCT)7 and the United Kingdom Prospective Diabetes Study (UKPDS),8 have demonstrated that achieving tight glycemic control is the cornerstone of preventing or delaying diabetes complications.

Nephropathy

Diabetic nephropathy is one of the most serious complications of diabetes and the leading cause of end-stage renal disease. It occurs in 20% to 40% of patients with diabetes.9 According to the American Diabetes Association (ADA), optimizing glucose and blood pressure control are both grade A recommendations (considered the strongest recommendations for clinical practice based on well-conducted randomized, multicenter, and adequately powered clinical trials) for reducing the risk and/or slowing the progression of nephropathy. 9

Nephropathy first manifests as increased urinary albumin excretion, or microalbuminuria (30-299 mg albumin/ 24 hours), which may progress to macroalbuminuria (>300 mg albumin/24 hours) and eventually to renal failure requiring dialysis. Current recommendations are to screen annually for microalbuminuria those patients with type 1 diabetes who have been diagnosed for >5 years, and to screen all patients with type 2 diabetes at the time of diagnosis and during pregnancy.9

According to the DCCT findings, patients who achieved intense glycemic control, defined as blood glucose as close to normal levels as possible, had a 39% reduction in microalbuminuria and a 54% reduction in macroalbuminuria, compared with patients having less intense glucose control.7

Hypertension also is a contributing factor for developing microalbuminuria. The Hypertension in Diabetes Study10 demonstrated that hypertensive patients had a 24% incidence of microalbuminuria, compared with a 14% incidence in normotensive individuals.

Smoking is a modifiable risk factor associated with the development of nephropathy in patients with diabetes. Smokers with type 1 diabetes had a 2.8% greater incidence of microalbuminuria, compared with nonsmoking patients.11

The ADA recommends using an angiotensin-converting enzyme (ACE) inhibitor as first-line therapy or an angiotensin-receptor blocker (ARB) except during pregnancy. For patients intolerant of ACE inhibitors or ARBs who have microalbuminuria, health care providers should consider nondihydropyridine, ?-blockers, or diuretics as alternatives for blood pressure control. 9

Retinopathy

The Centers for Disease Control and Prevention reports that diabetic retinopathy is the leading cause of new cases of blindness in adults, accounting for 12,000 to 24,000 new cases per year.12 Retinopathy is caused by changes in the blood vessels of the retina. It ranges in seriousness from mild nonproliferative, with swelling of blood vessels, to severe proliferative, with blockage and newly grown fragile, leaky blood vessels supplying the retina.13

In the DCCT, patients with diabetes following intense glycemic control and without retinopathy at baseline had a 76% reduced risk for developing retinopathy, compared with patients with diabetes on conventional glycemic therapy. Furthermore, patients following intensive glycemic control who had progression of retinopathy were twice as likely to recover from retinopathy as patients on a conventional glycemic regimen.7

Individuals with high blood pressure had a greater risk for developing retinopathy. Findings from the UKPDS demonstrated that individuals having tight blood pressure control had a 47% reduced risk of deterioration of visual acuity, compared with patients on less tight blood pressure control, after 8.4 years of follow-up. 8 Patients with diabetes and elevated lipids had an increased risk for the development and progression of retinopathy.14

The ADA recommends optimal glycemic and blood pressure control as grade A recommendations to reduce the risk and progression of retinopathy. Patients with type 1 diabetes should have an initial comprehensive eye examination within 3 to 5 years of diagnosis. Patients with type 2 diabetes should have the same comprehensive eye examination after diagnosis.The examination should be repeated yearly for both groups.9 Laser photocoagulation surgery is an efficacious therapy to control vision loss in all patients with diabetes. 15

Neuropathy

Diabetic neuropathy affects nerve blood flow and neuronal signaling. It results in numbness, pain, and weakness in the feet, legs, hands, and arms; resting tachycardia; gastroparesis; erectile dysfunction; and other problems. Diabetic peripheral neuropathies are commonly associated with limb amputations and ulcerations. Neuropathies affect up to 50% of patients with diabetes. Epidemiologic data are unclear, however, due to varying criteria for diagnosis.16

Results from the DCCT demonstrated that individuals following tight glycemic control had a 64% reduction in neuropathy, compared with individuals on conventional glycemic therapy. The ADA recommends screening patients with diabetes at least annually for peripheral neuropathies as a grade A recommendation.9

Pharmacists' Role

After reviewing the seriousness of diabetes complications, how can pharmacists help patients with diabetes? First, pharmacists must be educated in the comprehensive management of diabetes to prevent or delay diabetic complications. Second, pharmacists' access to patients' medication records gives them a unique opportunity to evaluate and provide therapeutic recommendations to patients with diabetes. Third, it is imperative for pharmacists, the most accessible health care professionals, to increase awareness and encourage patients to achieve diabetic goals.

Pharmacists should recommend that diabetic patients closely adhere to the ABCs of diabetes care:

? A is for A1C and aspirin. A1C stands the abbreviation for hemoglobin A1C, a blood test that determines the average blood glucose level over the previous 8 to 12 weeks. Patients with diabetes should strive to attain an A1C level of <7%, or as close as possible to 6% without significant hypoglycemia. Reducing A1C by 1% decreases the risk of developing microvascular nephropathy and neuropathy complications by 37%. 8 Patients with diabetes must perform self-monitoring blood glucose testing to achieve A1C goals. Patients with diabetes and without contraindications to aspirin use may benefit from low-dose aspirin therapy for cardiovascular protection.17

? B is for blood pressure. The blood pressure goal for patients with diabetes is <130/80 mm Hg. Patients with diabetes may benefit from ACE inhibitor or ARB therapy, whether or not they have achieved the recommended blood pressure goal, because of the renal-protection properties of these agents.18

? C is for cholesterol. The primary goal of lipid therapy is a low-density lipoprotein (LDL) level of <100 mg/ dL.19 Additionally, statin therapy is recommended in diabetics =40 years of age to attain a 30% to 40% LDL reduction regardless of baseline LDL. Both of these are grade A recommendations, according to the ADA.9

In summary, comprehensive diabetic care will delay or prevent microvascular complications. Pharmacists must intervene and encourage patients with diabetes to achieve the ABCs of diabetes care to lead active, long, and productive lives.

References

1. Morgan CL, Currie CJ, Stott NC, Smithers M, Butler CC, Peters JR. The prevalence of multiple diabetes-related complications. Diabet Med. 2000;17:146-151.

2. Testa MA, Simonson DC. Health economic benefits and quality of life during improved glycemic control in patients with type 2 diabetes mellitus. JAMA. 1998;280:1490-1496.

3. National Institute of Diabetes and Digestive and Kidney Diseases. National Diabetes Statistics fact sheet: general information and national estimates on diabetes in the United States, 2005. Bethesda, MD: US Department of Health and Human Services, National Institutes of Health; 2005. Available at: www.diabetes.niddk.nih.gov/dm/pubs/statistics. Accessed July 20, 2007.

4. National Diabetes Education Program. Guiding principles for diabetes care providers. Available at: http://ndep.nih.gov. Accessed July 20, 2007.

5. 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.

6. Stratton IM, Adler AI, Neil HA, et al. Association of glycemia with macrovascular and microvascular complications of diabetes (UKPDS 35): prospective observational study. BMJ. 2000;321:405-412.

7. The Diabetes Control and Complications Trial Research group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 93;329:977-986.

8. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ. 1998;317:703-713.

9. American Diabetes Association. Standards of medical care in diabetes. Diabetes Care. 2007;30 (suppl 1):S4-S41.

10. The Hypertension in Diabetes Study Group. Hypertension in Diabetes Study (HDS). Prevalence of hypertension in newly presenting type 2 diabetic patients and the association with risk factors for cardiovascular and diabetic complications. J Hypertens. 1993;11:309-317.

11. Chase H, Garg SK, Marshall G, et al. Cigarette smoking increases the risk of albuminuria among subjects with type 1 diabetes. JAMA. 1991;265:614-617.

12. Centers for Disease Control and Prevention. National Diabetes Fact Sheet 2005. Available at: www.cdc.gov/od/oc/media/pressrel/fs051026.htm. Accessed July 20, 2007.

13. Diabetic Retinopathy. National Eye Institute. US National Institutes of Health. Available at: www.nei.nih.gov/health/diabetic/retinopathy.asp#1b. Accessed July 24, 2007.

14. Fong DS, Ferris FL, Davis MD, Chew EY. Causes of severe visual loss in the Early Treatment Diabetic Retinopathy Study: Early Treatment Diabetic Retinopathy Study Research Group report no. 24. Am J Ophthalmol. 1999;127:137-141.

15. Fong DS, Aiello L, Gardner TW, et al for the American Diabetes Association: Retinopathy in Diabetes (position statement). Diabetes Care. 2004;27(suppl 1):S84-S87.

16. Dickinson PJ, Carrington AL, Frost GS, Boulton AJ. Neurovascular disease, antioxidants and glycation in diabetes. Diabetes Metab Res Rev. 2002;18:260-272.

17. Campbell CL, Smyth, Montalescot G, Smyth SR. Aspirin dose for the prevention of cardiovascular disease. JAMA. 2007; 297:2018-2024.

18. Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin-converting enzyme inhibition on diabetic nephropathy. N Engl J Med. 1993;329:1456-1462.

19. Grundy SM, Cleeman JI, Merz CN et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004;110:227-239.