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Etiology

Review: Microalbuminuria predicts overall mortality and cardiovascular mortality and morbidity in non-insulin-dependent diabetes mellitus

ACP J Club. 1998 Jan-Feb;128:16. doi:10.7326/ACPJC-1998-128-1-016


Source Citation

Dinneen SF, Gerstein HC. The association of microalbuminuria and mortality in non-insulin-dependent diabetes mellitus. Arch Intern Med. 1997 Jul 14;1413-8.


Abstract

Objective

To determine the association, using meta-analysis, between microalbuminuria and overall and cardiovascular mortality, and cardiovascular morbidity in patients with non-insulin-dependent diabetes mellitus (NIDDM).

Data sources

A search was done in MEDLINE (1966 to 1994) using terms relating to NIDDM, albuminuria, and cardiovascular mortality and morbidity. Further, SCISEARCH was searched for studies citing previous reports, bibliographies of relevant studies were reviewed, and experts in the field were contacted.

Study selection

Studies were selected if they were original studies that included patients with NIDDM; outcomes were reported according to the degree of albuminuria; and the future risk for all-cause mortality, cardiovascular mortality, ischemic heart disease, or stroke were reported.

Data extraction

2 independent investigators reviewed the retrieved studies according to preset criteria: patients included in the studies had a clear definition of NIDDM, microalbuminuria was assessed in the absence of bacteriuria, main outcomes were clearly defined (death, myocardial infarction, and stroke), and information on other risk factors for atherosclerotic disease was included.

Main results

11 cohort studies (all from Europe) met inclusion criteria and involved 2138 patients who had a mean duration of NIDDM ranging from newly diagnosed to 13 years. The mean follow-up was 6.4 years. Degree of microalbuminuria varied in timed urine collections from > 10.5 to 200 µg/min and in spot morning collections from 15 to 300 µg/mL or > 2.5 µg/mmol creatinine. The prevalence of microalbuminuria was calculable in 8 studies and varied from 12% to 36%. 10 studies reported overall mortality and showed a positive association between microalbuminuria and death. The crude common odds ratio (OR) was 2.4 (95% CI 1.8 to 3.1). The unadjusted mean annual mortality rates were 5.9% (SD 2) and 2.7% (SD 1.8) for microalbuminuria and normoalbuminuria, respectively. In the 5 studies that reported risk estimates adjusted for other risk factors (age, hypertension, hypercholesterolemia, smoking, and presence of coronary artery disease at baseline), microalbuminuria remained a statistically significant predictor of overall mortality. 6 studies reported cardiovascular mortality or morbidity and showed a positive relation with microalbuminuria (OR 2.0, CI 1.4 to 2.7). When the studies that included patients with clinical proteinuria were excluded, the associations were not altered.

Conclusion

Microalbuminuria is a risk factor for overall mortality and cardiovascular mortality and morbidity in patients with non-insulin-dependent diabetes mellitus.

Source of funding: No external funding.

For article reprint: Dr. S.F. Dinneen, Division of Endocrinology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. FAX 507-284-5745.


Commentary

Studies have shown that microalbuminuria may develop within 5 years of onset of insulin-dependent diabetes mellitus. In NIDDM, microalbuminuria may be present at the diagnosis of diabetes because the diagnosis is often delayed for several years after the onset of asymptomatic hyperglycemia. The most important reason for screening for microalbuminuria in patients with NIDDM has been its predictive power for progressive increases in albumin excretion and decline in renal function.

This important meta-analysis by Dineen and Gerstein also confirms microalbuminuria in patients with NIDDM as a significant risk factor for cardiovascular morbidity and mortality. Many mechanisms for this increased cardiovascular risk have been postulated. For example, it may be caused by a generalized state of vascular hyperpermeability leading to increased penetration of lipoproteins into the subendothelial space or may simply be another manifestation of an atherogenic insulin-resistant state (1, 2).

Currently, the American Diabetes Association recommends screening for microalbuminuria at the diagnosis of NIDDM (3). If the first test yields negative results, testing should be repeated every year. Simple spot urine collections may be easily done or ordered in the office setting. If the results are positive, the test should be repeated 2 more times—2 out of 3 positive values indicates confirmed microalbuminuria. Studies show that this diagnosis in a person with NIDDM, even if normotensive, can justify the use of angiotensin-converting enzyme inhibitors to prevent a progressive increase in microalbuminuria and a steady decline in renal function (4). However, most persons with NIDDM die of cardiovascular disease, not renal disease. As this study suggests, persons with microalbuminuria should be aggressively counseled to reduce other cardiovascular risk factors, such as dyslipidemias, smoking, obesity, and inactivity.

Donald A. Smith, MD, MPH
Mount Sinai School of MedicineNew York, New York, USA


References

1. Alzaid AA. Microalbuminuria in patients with NIDDM: an overview. Diabetes Care. 1996;19:79-89.

2. Gilbert RE, Cooper ME, McNally PH, et al. Microalbuminuria: prognostic and therapeutic implications in diabetes mellitus. Diabet Med. 1994;11:636-45.

3. American Diabetes Association. Diabetes Care. 1997;20(Suppl 1):S24-S27.

4. Ahmad J, Siddiqui MA, Ahmad H. Effective postponement of diabetic nephropathy with enalapril in normotensive type 2 diabetic patients with microalbuminuria. Diabetes Care. 1997;20:1576-81.