GLYCOSYLATED HEMOGLOBIN AND THE RISK OF MICROALBUMINURIA IN PATIENTS WITH INSULIN-DEPENDENT DIABETES-MELLITUS

Background. The risk of microalbuminuria in patients with insulin-depe ndent diabetes mellitus (IDDM) is thought to depend on the degree of h yperglycemia, but the relation between the degree of hyperglycemia and urinary albumin excretion has not been defined. Methods. We measured urinary albumin excretion in three random urine samples obtained at le ast one month apart from 1613 patients with IDDM. Microalbuminuria or overt albuminuria was considered to be present if the ratio of albumin (in micrograms) to creatinine (in milligrams) was 17 to 299 or greate r than or equal to 300, respectively, for men and 25 to 299 or greater than or equal to 300, respectively, for women. Measurements of glycos ylated hemoglobin (hemoglobin A(1)) obtained up to four years before t he urine testing were used as an index of hyperglycemia. Twelve percen t of the patients had overt albuminuria and were excluded from subsequ ent analyses. Results. The prevalence of microalbuminuria was 18 perce nt in patients with IDDM. It increased with increasing postpubertal du ration of diabetes and, within each six-year interval of disease durat ion, it increased nonlinearly with the hemoglobin A(1) value. For hemo globin A(1) values below 10.1 percent, the slope of the relation was a lmost flat, whereas for values above 10.1 percent, the prevalence of m icroalbuminuria rose steeply (P<0.001). For example, as the hemoglobin A(1) value increased from 8.1 to 10.1 percent, the odds of microalbum inuria increased by a factor of 1.3, but as the value increased from 1 0.1 to 12.1 percent, the odds were increased by a factor of 2.4. Concl usions. The risk of microalbuminuria in patients with IDDM increases a bruptly above a hemoglobin A(1) value of 10.1 percent (equivalent to a hemoglobin A(1c) value of 8.1 percent), suggesting that efforts to re duce the frequency of diabetic nephropathy should be focused on reduci ng hemoglobin A(1) values that are above this threshold.