Nocturnal hypertension in type 1 diabetes

From the Division of Nephrology and Hypertension, Feinberg School of Medicine, Northwestern University, Chicago; the Pediatric Nephrology Unit, Department of Pediatrics, Hospital General and University of Valencia, Spain; and the Hypertension Clinic, Department of Medicine, Hospital Clinico and University of Valencia, Spain

The prevalence of hypertension in patients with type 1 diabetes and normal albumin excretion is similar to that of the general population when determined by blood pressure readings at regular office visits.1,2 These patients usually remain normotensive even when microalbuminuria develops, unlike those with type 2 diabetes, who are usually hypertensive by the time kidney disease is detected.2,3 Using ambulatory blood pressure monitoring, however, nocturnal hypertension is often detected in patients with type 1 diabetes who are in the microalbuminuric phase of the disease.4

Our study showed that nocturnal hypertension develops before the onset of microalbuminuria in type 1 diabetic patients.5 If an elevation in blood pressure, manifested by nocturnal hypertension, occurs before the onset of microalbuminuria, it could be a causative factor or a predictor of microalbuminuria, or both. More studies are needed to show that nocturnal hypertension should be used to target patients for early therapeutic intervention.

Results

We performed a prospective study to assess whether nocturnal hypertension antedates incipient nephropathy, or microalbuminuria, in type 1 diabetics, or if the two occur concurrently.5 We recruited 75 diabetic patients who had normal albumin excretion and normal blood pressure. Patients underwent ambulatory blood pressure monitoring at intervals of approximately 2 years, provided that their urinary albumin excretion remained normal. Urinary albumin excretion was measured using two separate 24-hour urine specimens. Microalbuminuria was classified as a urinary albumin excretion between 30 and 299 mg over a period of 24 hours. This was confirmed by two consecutive measurements taken less than 6 months apart.

Microalbuminuria developed in 14 of the 75 patients after a mean follow-up of 63 months. The remaining 61 subjects did not develop microalbu-

minuria during a mean follow-up of 66 months.5 The two groups did not

differ significantly with regard to office systolic or diastolic blood pressure. At the initial evaluation, there was no significant difference in the

mean daytime and nighttime systolic blood pressures between those who developed microalbuminuria and those who remained normoalbuminuric. There was also no significant difference in daytime or nighttime heart rate between the two groups.5

At the final evaluation, the office systolic and diastolic blood pressures still did not differ significantly between the two groups. In those who developed microalbuminuria, however, the nighttime systolic blood pressure increased from 109.9 ± 11.3 mm Hg at the initial evaluation to 114.9 ± 11.7 mm Hg at the last evaluation (P < .01). In contrast, nighttime systolic blood pressure was essentially unchanged in the group that remained normoalbuminuric.

The increase in nighttime systolic blood pressure was significantly related to the development of microalbuminuria, according to a logistic-regression analysis. The relative risk of microalbuminuria was 1.44 (95% confidence interval [CI], 1.03—2.02) for each 5-mm Hg increase in nocturnal systolic pressure.5

The ratio of nighttime to daytime blood pressure was used to describe an abnormal pattern of nighttime pressure. A ratio above 0.9 was considered abnormal. As a marker of progression to microalbuminuria, a normal pattern of nocturnal blood pressure had a negative predictive value of 91% at the final evaluation, indicating a low risk. Microalbuminuria developed in 10 of the 32 patients who had an abnormal pattern at the last evaluation.5

The Kaplan-Meier curve shows the risk of progression to microalbuminuria was significantly different between the subjects with a normal pattern of nocturnal blood pressure and those with an abnormal pattern (figure). Based on the final evaluation, the risk of microalbuminuria

in the group with a normal nocturnal blood pressure pattern was

70% lower than that for the group with an abnormal pattern (95% CI, 44%—110%).5

A separate analysis of data was performed to determine whether high nocturnal systolic blood pressure or poor metabolic control accounts for the progression to microalbuminuria. We compared 16 of

the patients who remained normoalbuminuric with 14 who de-veloped microalbuminuria. Both groups had similar poorly controlled glycosylated hemoglobin levels. We analyzed data from ambulatory blood pressure readings and found that daytime blood pressure did not differ significantly between the two groups. Nighttime systolic blood pressure, however, was significantly lower in the subgroup with normoalbuminuria and high glycosylated hemoglobin levels compared with the microalbuminuria group.5

Discussion

Our study showed a temporal relationship between an increase in nighttime systolic blood pressure and the development of microalbuminuria in normotensive patients with type 1 diabetes.5 We found that an increase in blood pressure during the sleep period precedes the development of microalbuminuria in type 1 diabetic patients.

Our data also suggest that the level of glycosylated hemoglobin influences the risk of progression to microalbuminuria.6 In a subgroup of patients with poor glycemic control but normal nocturnal blood pressure, however, microalbuminuria did not develop, which is in keeping with the notion that nephropathy develops only in susceptible persons with type 1 diabetes.7,8 Because early elevations in nighttime blood pressure precede the microalbuminuric stage, we think that an elevation in nocturnal blood pressure plays an important role in its development, regardless of the level of metabolic control. Early elevations in nocturnal blood pressure could play a role in the development of diabetic nephropathy by causing intrarenal hemodynamic changes, structural renal damage, or both.5 Regardless of the mechanism, an increase in nocturnal systolic blood pressure precedes the development of microalbuminuria in type 1 diabetics and may be an early marker of kidney involvement. This is particularly important because only some patients with type 1 diabetes progress to nephropathy.9

Conclusion

Assessing the risk early and in-stituting timely therapy should be

a goal to prevent the progression

to microalbuminuria in type 1 diabetics. Early documentation of an

increase in nocturnal blood pressure might merit the use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers in these patients; however, this re-mains to be demonstrated by prospective studies. A normal pattern of nocturnal blood pressure

has a strong negative predictive value for the progression to microalbuminuria.4 Documentation of normal nocturnal blood pressure might indicate that early therapeutic interventions, other than those needed

to improve glycemic control, are

not necessary.10