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Mordchai Ravid, MD; David Brosh, MD; Dorit Ravid-Safran, MD; Zohar Levy, MD; Rita Rachmani, MD

Arch Intern Med. 1998;158:998-1004.

Background  The control of hyperglycemia is of major importance in the treatment of patients with type 1 diabetes mellitus. However, there is no consensus about the required degree of metabolic control in patients with type 2 diabetes mellitus and about the role of hyperglycemia in diabetic nephropathy and in the development of atherosclerosis in relation to other risk factors.

Patients and Methods  A prospective, long-term follow-up study was conducted on 574 patients, aged 40 to 60 years, with recent onset of type 2 diabetes mellitus. Patients were initially normotensive and had normal renal function and a normal urinary albumin excretion rate (<30 mg/24 h). The patients were followed up for 2 to 9 years (mean ± SD, 7.8 ± 0.9 years). Levels of hemoglobin A_1c and plasma lipids, mean blood pressure, and body mass index (calculated as the weight in kilograms divided by the square of the height in meters) were determined periodically. Cigarette smoking and socioeconomic status were recorded. Renal status was evaluated by the logarithm of the final urinary albumin excretion rate and by the decline in reciprocal creatinine values. Definite clinical events including death, nonfatal myocardial infarction, angina pectoris, congestive heart failure, and peripheral vascular disease were recorded.

Results  At the end of the study the urinary albumin excretion rate remained normal (<30 mg/24 h) in 373 patients (65%), 111 (19%) had microalbuminuria (30-300 mg/24 h), and 90 (16%) had overt albuminuria (>300 mg/24 h). Logistic regression models demonstrated that the correlation between hemoglobin A_1c levels and the risk of albuminuria is exponential. Multiple logistic regression analysis indicated that levels of total cholesterol, mean blood pressure, and hemoglobin A_1c were the main factors associated with the decrease in renal function and with the increase in albuminuria. The combination of values higher than the 50th percentile of all 3 factors defined a high-risk patient population. These high-risk patients had an odds ratio of 43 (95% confidence interval, 25-106) for microalbuminuria and 15 (95% confidence interval, 9-25) for clinical events related to arteriosclerosis compared with the rest of the group. Low levels of high-density lipoprotein, body mass index, cigarette smoking, low socioeconomic status, and male sex were all significantly associated with diabetic nephropathy, as well as with the manifestations of arteriosclerosis.

Conclusions  The combination of blood pressure values in the high-normal range with moderately elevated levels of total cholesterol and hemoglobin A_1c defines a high-risk group for the progression to diabetic nephropathy and for clinical events related to arteriosclerotic cardiovascular disease.

From the Departments of Medicine (Drs Ravid, Levy, and Rachmani) and Obstetrics and Gynecology (Dr Ravid-Safran), Tel-Aviv University and Meir Hospital, Kfar-Sava, and the Department of Cardiology, Municipal Medical Center, Tel-Aviv (Dr Brosh), Israel.

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