Visit-to-visit variability in systolic blood pressure predicts development and progression of diabetic nephropathy, but not retinopathy, in patients with type 2 diabetes

https://doi.org/10.1016/j.jdiacomp.2013.11.003Get rights and content

Abstract

Objective

To investigate whether visit-to-visit variability in systolic blood pressure (SBP) can predict development and progression of diabetic nephropathy and retinopathy in patients with type 2 diabetes mellitus (T2DM).

Methods

From 1995 through 1996, 664 T2DM patients visited our hospital for the first time and were subsequently examined 4 times or more and at least once annually.

At first visit, 326 had normoalbuminuria, 644 had an estimated glomerular filtration rate (eGFR) of ≥ 45 ml/min/1.73 m2, 526 had no diabetic retinopathy and 609 had no severe non-proliferative diabetic retinopathy (NPDR). They were followed through June 2012, at the latest.

Results

Ninety patients developed microalbuminuria, 76 showed decrease of eGFR to < 45 ml/min/1.73 m2, 113 developed mild–moderate NPDR and 50 progression to severe NPDR. The unadjusted, age- and sex-adjusted and multivariate-adjusted hazard ratios for development and progression of nephropathy, but not retinopathy, increased across tertiles of the standard deviation (SD) of SBP. Both the SD and coefficient of variation (CV) of SBP were significant predictors of development and progression of nephropathy, but not retinopathy, independently of mean SBP.

Conclusion

Visit-to-visit SBP variability is an independent predictor of development and progression of diabetic nephropathy, but not retinopathy, in T2DM patients.

Introduction

Hypertension is associated with the risk of macrovascular and microvascular complications in patients with type 2 diabetes mellitus (T2DM) (Adlar et al., 2000). Recent studies, mostly of treated hypertensive patients, found an increased visit-to-visit variability in blood pressure (BP) to be predictive of cerebrovascular events (Hata et al., 2000, Rothwell et al., 2010a, Rothwell et al., 2010b), acute myocardial infarction (Hata et al., 2002) and all-cause mortality (Muntner, Shimbo et al., 2011), independently of the mean BP. In patients with chronic kidney disease without diabetes, visit-to-visit BP variability was an independent determinant of deterioration of renal function (Yokota et al., 2013). In T2DM patients, visit-to-visit BP variability was a significant predictor of all-cause mortality, independent of the mean BP (Hsieh et al., 2012). It has been suggested that increased BP variability may reflect arterial stiffness and baroreceptor dysfunction, which have been associated with arteriosclerosis and result in vascular events (Floras et al., 1988, Hata et al., 2000, Hata et al., 2002, Rothwell, 2010, Shan et al., 2001).

Regarding diabetic microangiopathy, visit-to-visit BP variability was found to be an independent predictor of nephropathy, but not retinopathy, in patients with type 1 diabetes in the Diabetes Control and Complications Trial (DCCT) (Kilpatrick, Rigby, & Atkin, 2010). Visit-to-visit systolic BP (SBP) variability was also found to be a predictor of development of microalbuminuria (Okada et al., 2013) in T2DM patients, most of whom were taking antihypertensive agents. However, reports regarding the relationship between visit-to-visit BP variability and diabetic microangiopathy in T2DM patients remain limited. In particular, there has been no demonstration of a role of visit-to-visit SBP variability in advanced-stage diabetic microangiopathy. In addition, it is unknown whether visit-to-visit SBP variability has different effects on diabetic nephropathy and retinopathy in T2DM patients.

This study aimed to determine whether visit-to-visit SBP variability can predict development and progression of diabetic nephropathy and retinopathy, independently of the mean SBP, in T2DM patients.

Section snippets

Study subjects

A total of 1912 patients first visited our hospital between January 1995 and December 1996, and 664 T2DM patients who visited the hospital at least 4 times and at least once a year were enrolled in the study. Patients with impaired glucose tolerance had been excluded. At first visit, of the 664 patients, 326 had normoalbuminuria defined as urinary albumin excretion (UAE) of < 30 mg/g Cr and 644 had an estimated glomerular filtration rate (eGFR) of ≥ 45 ml/min/1.73 m2. These two cohorts were followed

Results

Table 1 shows the baseline clinical characteristics of the patients in the 4 groups. The clinical features and laboratory data were similar in each group. The patients comprised around 5 times more men than women. At baseline, the mean SBP was only slightly elevated compared with the target recommended by the diabetes guidelines in Japan, while the mean eGFR values were normal. The most commonly used antihypertensive agents were calcium channel blockers, followed by ACE inhibitors. Statins

Discussion

This retrospective cohort study reveals that visit-to-visit SBP variability is a significant predictor of development and progression of diabetic nephropathy, but not development or progression of diabetic retinopathy, in T2DM patients, independently of the mean SBP.

In patients with type 1 diabetes in the DCCT, visit-to-visit BP variability was an independent predictor of nephropathy, but not retinopathy (Kilpatrick et al., 2010). We have now generated similar results in T2DM patients. Our

Acknowledgments

We would like to thank Kumiko Kimura of our institute for her excellent secretarial and technical assistance with collecting the research data, and Machi Suka (the Jikei University School of Medicine) for her advice on revision of this paper.

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