Blood pressure and renal function in type 2 diabetes mellitus
ACP J Club. 1993 Jan-Feb;118:18. doi:10.7326/ACPJC-1993-118-1-018
Ravid M, Savin H, Lang R, et al. Proteinuria, renal impairment, metabolic control, and blood pressure in type 2 diabetes mellitus. A 14-year follow-up report on 195 patients. Arch Intern Med. 1992 Jun;152:1225-9.
To study the association of renal function with blood pressure (BP) and glycemic control in patients with type 2 diabetes mellitus.
Inception cohort followed for 14 years.
University medical center in Israel.
174 patients (83 women) < 45 years with type 2 diabetes mellitus diagnosed within the previous 2 years were recruited through referral clinics. The diagnosis was based on World Health Organization criteria. Exclusion criteria were obesity (body mass index [BMI] > 35); hypertension (systolic BP ≥ 150 mm Hg or diastolic BP ≥ 95 mm Hg); overt proteinuria (urinary protein level ≥ 0.3 g/L by Labstix); and other diseases that could affect renal function. Patients had a mean duration of diabetes of 15 years at study end. Patients were followed by their family physicians. 4 patients died, and 17 (9%) were lost to follow-up.
Assessment of prognostic factors
BP (average of 2 readings) and blood and urine tests were done every 3 to 4 months; funduscopic measurement of retinopathy was done twice a year by an ophthalmologist.
Main outcome measures
Hypertension (BP ≥ 150/95 mm Hg), decline in renal function (reciprocal creatinine value expressed as a percent of initial value), and onset of overt diabetic nephropathy (urinary protein level ≥ 0.3 g/L on 2 consecutive visits).
Hypertension developed in 30 patients (mean, 6.4 y from diagnosis of diabetes). Patients with hypertension did not differ from the other patients for mean fasting blood glucose, mean glycosylated hemoglobin levels, or BMI. Patients with hypertension had higher creatinine levels (153 vs. 126 mol/L) and a decline in reciprocal creatinine (39% vs. 26% decline). Renal function gradually declined in all patients. This decline was positively correlated with mean BP (r = 0.63; P <0.005). Macroproteinuria developed in 30 of 144 patients (21%) with normal BP and 18 of 30 patients (60%) with hypertension. For patients with normal BP, the onset of macroproteinuria and rate of decline of renal function were not correlated with fasting blood glucose levels or mean value of glycosylated hemoglobin. Diabetic retinopathy developed in 38 patients (26%) with normal BP and in 10 patients (30%) with hypertension.
Renal function declined gradually in all patients with type 2 diabetes mellitus. This decline was associated with increased blood pressure but not with metabolic control.
Source of funding: Not stated.
For article reprint: Dr. M. Ravid, Meir Hospital, Kfar-Saba 44281, Israel. FAX 972-52-912-135.
The 14-year study of patients with type 2 diabetes by Ravid and colleagues, who used simple measurements of BP, proteinuria, and glucose control, provides evidence to support the temporal association between mild elevations in BP and diabetic nephropathy. It also provides an estimate of the risk for nephropathy, retinopathy, and important hypertension in patients with type 2 diabetes.
Currently used outcome measures can provide more relevant information but were unavailable for this study. These measures include glycosylated hemoglobin (which was only used for the latter part of this 14-year study), urinary albumin excretion, ambulatory BP monitoring (1), and retinal photography. Because proteinuria is an independent risk factor for vascular disease in people without diabetes (2), a comparison of renal function changes over many years in patients without diabetes would have been welcome. Moreover, exclusion of other causes of proteinuria may have been incomplete because the authors do not mention nonsteroidal anti-inflammatory drugs, H2 blockers, or angiotensin-converting enzyme inhibitors used for nonhypertensive purposes. Finally, significance levels for final outcomes and additional data on retinopathy would have been helpful.
Further studies are needed to clarify the natural history of type 2 diabetes and the elusive relation between retinopathy and nephropathy in diabetes. The 90% concordance between the retinopathy and nephropathy among patients with hypertension is intriguing. The lack of statistical significance of the authors' measures of metabolic control in association with retinopathy and nephropathy deserves further study (3).
Robert Bloomfield, MD
Caroline Pedley, MD Bowman Gray School of Medicine Winston-Salem, North Carolina, USA