Microalbuminuria, High Blood Pressure Burden, and Nondipper Phenomenon: An interaction in normotensive type 1 diabetic patients

Type 1 diabetes is associated with hypertension and increased risk of morbidity and mortality attributable to cardiovascular disease and renal failure. Almost 40% of patients with type 1 diabetes will develop clinical diabetic nephropathy, defined as urinary albumin excretion rate (AER) >300 mg/24 h (1). We studied 37 normotensive type 1 diabetic patients without macroalbuminuria, aged 26.5 ± 6.75 years and with 9.4 years (range 1–34) of disease, and 28 normotensive nondiabetic subjects with fasting glucose blood levels ≤100 mg/dl, aged 24.9 ± 6.81 years, who were matched to the diabetic group for age, sex, skin color, weight, height, and BMI. Albumin concentration was measured by double-antibody radioimmunoassay (DPC, Los Angeles, CA). Ambulatory blood pressure monitoring (ABPM) was performed during a working day using a portable automatic oscillometric recorder (SpaceLabs 90207). The recordings provided the mean 24-h, daytime, and nighttime values of systolic (sBP) and diastolic BP (dBP) and heart rate. Subjects with a nocturnal fall in either sBP or dBP of <10% of daytime values were classified as nondippers (2). We found higher means of ABPM in microalbuminuric diabetic patients than in normoalbuminuric and nondiabetic subjects. Nighttime BP values were higher in normoalbuminuric diabetic patients than in nondiabetic subjects. The BP burden was higher in microalbuminuric than in normoalbuminuric patients and nondiabetic subjects. No difference of BP burden was found between normoalbuminuric diabetic subjects and nondiabetic subjects. During the nighttime period, a higher frequency of systolic BP burden >50% and of diastolic BP burden >30% was found in microalbuminuric patients than in normoalbuminuric diabetic patients (4 of 9 vs. 1 of 28; P = 0.008). Nondiabetic subjects had a higher decline of sBP and dBP than microalbuminuric and normoalbuminuric patients. A high frequency of nondippers for sBP was observed among diabetic patients (30 of 37 vs. 12 of 30; P = 0.001), and a high frequency of microalbuminuria (5 of 9 vs. 5 of 28; P = 0.04) and a longer duration of disease (11.7 years [5–18] vs. 8.6 years [1–34]; P < 0.05) was observed in diabetic patients who were nondippers for dBP. In agreement with other studies (3,4), we found higher mean values and burden BP in microalbuminuric diabetic patients than in normoalbuminuric and nondiabetic subjects. Despite the demonstration in our study of an association between microalbuminuria and systolic BP burden >50% and diastolic >30% during the nighttime, the value of BP burden associated with microalbuminuria in diabetic patients has not been defined. We observed a lower decline of nighttime BP in micro- and normoalbuminuric diabetic patients than in nondiabetic subjects, as noted in other studies (2,4). Although we did not evaluate autonomic function, the presence of a lower BP decline during the nighttime period in the diabetic group may suggest autonomic neuropathy (5). An interaction among poor glycemic control, higher BP during ABPM, and attenuated vagal activity in normoalbuminuric type 1 diabetic patients had been observed in patients with high-normal AER and impaired reduction in nocturnal dBP (6). The association between microalbuminuria and longer duration of diabetes with the nondipper status for dBP observed in our study has been related (4,7). Other studies have shown that type 1 diabetic patients who developed microalbuminuria had an impaired reduction in nocturnal dBP and higher AER compared with persistently normoalbuminuric patients (7), and that the nondipper status for dBP is a late alteration and is suggestive of microalbuminuria (4).

In conclusion, our study suggests that the impaired decline of BP was probably associated with diabetes itself and that higher BP burden and nondipper status for dBP were associated with microalbuminuria. Further prospective studies may determine whether an impaired nocturnal fall in BP and the nondipper phenomenon in normotensive type 1 diabetic patients could increase the risk of cardiovascular disease and nephropathy.