Am Fam Physician. 2002 Oct 1;66(7):1151-1153.
In the United States, diabetes is the most common cause of both blindness and end-stage renal disease requiring dialysis. Diabetes is responsible for almost one half of the approximately 326,000 persons currently receiving dialysis, with an annual Medicare cost of more than $50,000 per patient. Hypertension is present in virtually all persons with diabetes who progress to dialysis.1 Although diabetic nephropathy can occur in persons with either type 1 or type 2 diabetes, because of the much greater prevalence of type 2 diabetes, more than one half of patients starting dialysis have this condition.2
Persons with both diabetes and hypertension have a high risk of cardiovascular events, which constitute the most prominent cause of death in persons with kidney disease.1,3,4 Data from a large, seven-year study show that patients with diabetes and no evidence of cardiac injury have the same risk of dying as non-diabetic persons who have had a myocardial infarction.5 It is clear that appropriate screening for cardiovascular and renal risk factors should be performed at least once annually in such patients.
These guidelines can be found in the Clinical Practice Guidelines set forth by the American Diabetes Association.2 Four key risk factors should be monitored and, if found to be above goal levels, an intervention should be specified. These risk factors and specified goals include the following: (1) glycosylated hemoglobin level of less than 6.5 percent; (2) low-density lipoprotein cholesterol level of less than 100 mg per dL (2.6 mmol per L); (3) systolic blood pressure of less than 130 mm Hg; and (4) a reduction in microalbuminuria (spot urine albumin:creatinine value of more than 30 mg of albumin per gram of creatinine) of at least 30 percent from baseline. Achieving these goals and adding daily low-dose aspirin therapy can reduce the risk of cardiovascular or renal events by more than 70 percent.6
To help patients adhere to a complex medication regimen, physicians must first help them understand these goals and their importance. To achieve lipid and glucose control, one or two agents are generally needed for each purpose. To achieve the systolic blood pressure goal, however, an average of two to three different medications, at moderate to high dosages, is needed.6 This necessity is well documented by Konzem and colleagues.7 Moreover, persons with an elevated serum creatinine level (i.e., more than 1.4 mg per dL [124 μmol per L]) have a much higher cardiovascular risk and usually have to take four or more agents to attain their systolic blood pressure goal.4,6
Data from a myriad of clinical trials involving more than 100,000 participants clearly demonstrate that treatment with antihypertensive agents lowers cardiovascular complications to a greater extent in patients with diabetes than in patients who do not have diabetes.8,9 Moreover, the importance of angiotensin-converting enzyme (ACE) inhibitors as initial therapy to reduce cardiovascular risk is well established and, as was more recently established, angiotensin receptor blockers help to reduce progression of nephropathy.6,10
Physicians, however, appear to be doing a poor job of helping patients with diabetes achieve blood pressure goals, because only 11 percent of diabetic patients treated for hypertension have achieved the guideline goal of 130 mm Hg or less.11 Moreover, in many cases physicians fail to prescribe ACE inhibitors or angiotensin receptor blockers as first-line therapy because they fear causing an increase in serum creatinine levels. However, a recent review12 of studies over the past decade demonstrates that a small, persistent rise in the serum creatinine level of not more than 30 percent, as long as the baseline is 3 mg per dL (265 μ mol per L) or less and there is no hyperkalemia (i.e., serum potassium level is less than 5.6 mEq per L [5.6 mmol per L]), results in better long-term preservation of kidney function than if no ACE inhibitor is used.
Actually, the most common cause of a rise in creatinine level is volume depletion. Rehydrating the patient with a fluid that contains salt, such as bouillon, will markedly reduce the creatinine level while the patient is taking an ACE inhibitor or an angiotensin receptor blocker.
After initial therapy with an ACE inhibitor or angiotensin receptor blocker, a diuretic will frequently be required to achieve the blood pressure goal, followed generally by either a calcium channel blocker or a beta blocker, depending on the condition of the patient.6 A proposed model for an approach to achieving the blood pressure goal and reducing cardiovascular risk has been put forth by the National Kidney Foundation.6
The incidence of diabetes is rising to epidemic proportions in the United States, and family physicians are on the front lines of the battle to reduce morbidity and mortality. Achieving the goals recommended by expert groups and summarized above will markedly reduce the morbidity and mortality resulting from the cardiovascular, renal, and metabolic consequences of diabetes.
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1. Cooper L. USRDS. 2001 Annual Data Report. Nephrol News Issues. 2001;15:31,34–5,38....
2. American Diabetes Association: clinical practice recommendations 2002. Diabetes Care. 2002;25(Suppl 1):S1–147.
3. Casiglia E, Zanette G, Mazza A, Donadon V, Donada C, Pizziol A, et al. Cardiovascular mortality in non-insulin-dependent diabetes mellitus. A controlled study among 683 diabetics and 683 age- and sex-matched normal subjects. Eur J Epidemiol. 2000;16:677–84.
4. Mann JF, Gerstein HC, Pogue J, Bosch J, Yusuf S. Renal insufficiency as a predictor of cardiovascular outcomes and the impact of ramipril: the HOPE randomized trial. Ann Intern Med. 2001;134:629–36.
5. Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998;339:229–34.
6. Bakris GL, Williams M, Dworkin L, Elliot WJ, Epstein M, Toto R, et al. Preserving renal function in adults with hypertension and diabetes: a consensus approach. National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group. Am J Kidney Dis. 2000;36:646–61.
7. Konzem SL, Devore VS, Bauer DW. Controlling hypertension in patients with diabetes. Am Fam Physician. 2002;66:1209–14.
8. Neal B, MacMahon S, Chapman N. Effects of ACE inhibitors, calcium antagonists, and other blood-pressure-lowering drugs: results of prospectively designed overviews of randomised trials. Blood Pressure Lowering Treatment Trialists' Collaboration. Lancet. 2000;356:1955–64.
9. Staessen JA, Wang JG, Thijs L. Cardiovascular protection and blood pressure reduction: a meta-analysis. Lancet. 2001;358:1305–15.
10. Sica DA, Bakris GL. Type 2 diabetes: RENAAL and IDNT–the emergence of new treatment options. J Clin Hypertens (Greenwich). 2002;4:52–7.
Copyright © 2002 by the American Academy of Family Physicians.
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