The Prevalence of Microalbuminuria and Associated Risk Factors in a Population with Insulin-Dependent Diabetes Mellitus*

T. M. Fiad t, Rosemarie Freaney 2, Barbara Murray =, M. J. M e K e n n # ~

1Department of Endocrinology and Diabetes and ZMetabolic Laboratory, St. Vincent's Hospital, Elm Park, Dublin 4.

Abstract The prevalence of microalbuminuria was studied in a clinic population of patients with insulin-dependent diabetes mellitus [IDDM] with disease duration longer than $ years. 75 patients were included in the study, 23 patients (30.7%) had microalbuminuria and 2 patients (2.7%) had macroalbuminuria. Comparison of the clinical and laboratory characteristics of patients with microalbuminuria (n=23) to patients with normoalbuminuria (n=50) showed no differences with respect to age, duration of diabetes, blood pressure, presence of retinopathy and glycosylated haemoglobin. The mean glomerular filtration rate (GFR) was higher in the microalbuminuric group than in the normoalbuminuric group (125_+45ml/min compared to 99+_32ml/min; P<0.05). In a multiple regression model excluding patients with macroalbuminuria the following predictors of albumin excretion rate (AER) were identified: systolic blood pressure, glyeosylated haemoglobin and GFR. Since microalbuminuria is common in Irish patients with IDDM, we suggest that AER should be determined as part of the annual routine screen. Stricter control of blood pressure and glycaemia should be considered.

Introduction Diabetic nephropathy is characterised by proteinuria, a

relentless decline in GFR, and hypertension. These pa- tients have a high risk of death from renal failure and cardiovascular disease t2. An earlier, and potentially re- versible, stage of diabetic nephropathy is a subclinical increase in AER, termed microalbuminuria. The percent- age of patients who will progress from microalbuminuria to macroalbuminuria and the time scale of this progression areasyet unknown (Figure i). Detection ofmicroalbuminuria allows early treatment aiming at altering or even halting the progression to ESRD 3s. This study was undertaken to examine the prevalence of microalbuminuria in a clinic population with IDDM and to define the relationship be- tween risk factors and microalbuminuria.

Patients and Methods Patients

75 consecutive attenders with IDDM for at least 5 years were studied. Patients in whom semiquantitative testing of urine by Albustix yielded a value of +1 or greater [total protein concentration >300mg/L] were excluded from the study. The following information was collated: age, gen- der, weight, height, duration of IDDM, insulin therapy, presence of diabetic retinopathy, history of treated hyper- tension, the average of two blood pressure readings ob- tained in the sitting position and the average of two glycosylated haemoglobin levels. A single 24-hour urine

Address for correspondence: Dr. Malschi I. McKenna, Department of Endocrinology & Diabetes, SL Vincent's Hospital, Elm Park, Dublin 4.

*Presenled, in part, at the 1st National Scientific Meeting, Dublin, March 1992.

collection was obtained for the measurement of albumin and creatinine. A simultaneous blood sample was drawn for measurement of creatinine.

Assay Methods The urine a lbumin level was measured by an

immunoturbidimetric method 6 employing a commercially available antibody to human serum albumin (DAKO). The assay has a sensitivity of 1.Smg/L and interassay impreci- sion of 4.8, 5.0 and 1.8% at concentrations of 17, 30 and 79 lag/L respectively. Results were expressed in I.tg/min based on single 24hour urine collections. Patients were classified according to their AER: normoalbuminuria [< 201xg/min], mic roa lbuminur i a [20 -200g /min i , and macroalbuminuria [> 2001.tg/minl 7,8. Serum and urine creatinine were measured by a kinetic alkaline picrate method. Glycosylated haemoglobin AI (HbAt) was as- sayed by ion exchange column chromatography. The interassay coefficient of variation was 4% and the refer- ence range was 4.5 - 7.5%.

Natural History of Diabetic NeDhroDathy

I Normoalbumlnuria 1 ' | ? risk factors

I Microalbuminuria l ~, q ? time scale

[ Macmalbuminuria I ~r S ? 5 year Interval

[Renal failure ]

Figure ] -Diagrammatic representation of the natural history of diabetic nephropathy highlighting current issues in prevention.

318

VoL 162 No. 8

Statistical Analys i s Descriptive statistics were obtained. Comparisons be-

tween two groups (normoalbuminmic and microalbuminuric) were made by two-sample Students t test for continuous variables and by chi-squarod test for categorical variables. Multiple linear regression analysis by a stepwise method was used to examine the relationship between AER and the following variables: age, duration, gender, history of hy- per~nsion, insulin therapy, systolic blood pressure, diastolic blood pressure, retinopathy, HbA~, GFR, urine creatinine and urine volume. Log transformation of AER was com- puted prior to s~tistical analysis. P values below 0.05 for 2-tailed tests were considered significant.

Resu l t s Descriptive statistics for the entire group are given in

Table I. The prevalence of microalbuminuria was 30.7%, and 2 patients (2.7%) had macroalbuminuria. The fre- quency distribution of AER values following log transfor- mation is shown in Figure 2. Comparisons between IDDM patients with normoalhuminuriaand microalbuminuria are shown in Table II. Significant differences between the 2 groups were found only for GFR.

For the total group, multiple regression analysis identi- fied the following variables as predictors of AER: systolic and diastolic blood pressure, urine volume (r=0.54; p<0.05). Excluding those with macroalbuminuria (n=2), the follow - ing variables were identified: systolic blood pressure, HbA 1 and GFR (r=0.50; p<0.05). When patients with hypertension (n=8) and macroalbuminuria (n=2) were excluded, systolic blood pressure, HbA~ and GFR were still identified as predictor variables (r=0.50; p<0.05).

Table I CLINICAL AND LABORATORY CHARACTERISTICS OF

PATIENTS WITH IDDM (1'4=75)

Age (years) 37(17)

Duration of IDDM (years) 16(11 )

Sex (M:F) 52:48

Hypertension 89:11 (absent:present) %

BP systolic (mmHg) 132(17)

BP diastolic (nunHg) 77(9)

Retinopathy % absent 74 background 11 laser therapy 9 proliferative 6

nbA t (%) 9.3(1.5)

GFR (ml/m~) 107(37)

AER (gg/min)

Normoalbuminuric % 66.7 Mieroalbuminuric % 30.7 M acroalbuminuric % 2.7

Values are mean (SD) unless otherwise indicated

Prevalence of microalbuminuria 319

40-

30- e ~ 2o-

lO: Refer

o ~ . . . . . " ~ . . . . . . . . ~ / lO lOO AER (uglmln) Figure 2 - Frequency distribution of Iog-uansformed AER results.

Discuss ion This study showed a high prevalence of microalbuminuria

(30.7%). Systolic blood pressure, glycosylated haemo- globin and GFR were positively associated with AER. Prospective studies have indicated that microalbuminaria predicts the later development of clinical proteinuria and diabetic nephropathy ~'~2.

In this study the GFR was significantly higher in the microalbuminuric group in keeping with an early stage of hyperfiltration and glomerular hypertension J2. The preva- lence of microalbuminuria was considerably higher than in a study in American patients reported by McKenna et al ~3. The Irish and American groups were similar with respect to age, duration of IDDM, gender, prevalence of hyperten- sion, glycaemic control and diastolic blood pressure. However, the mean systolic blood pressure was higher in the Irish subjects (132~.17mmHg versus 120~_12mmHg). Systolic blood pressure which is a predictor of AER in the study could partly explain the higher prevalence of

Table 11

COMPARISON OF CLINICAL & LABORATORY CHARACTERISTICS IN IDDM PATIENTS WITH

NORMOALBUMINURIA ( n = 5 0 ) AND MICROALBUMINURIA (n = 23)

Normo- Micro-

Age (years) 36(16) 40(19) Duration (years) 15(10) 17(12) Sex M:F (%) 42:58 60:40 Hypertension

(absent:present) 90:I0 87:13 BP (mmHg) '

systolic 129(13) 137(20) diastolic 76(9) 79(10)

Retinopathy (%) (absent:present) 78:22 82:18 ItbA~ (%) 9.0(1.5) 9,5(1.5) GFR (ml/min) 101(32) 122(45)*

Values are mean (SD) unless otherwise stated * Significant difference between two groups: P<0.05

320 Fiad et al.

microalbuminuria reported although familial and genetic factors could not be outruled. These findings may indicate the need to treat systolic blood pressure at a lower thresh- old.

Therapeutic intervention using antihypertensive agents may reduce or halt further increase in AER in both normotensive and hypertensive diabetic patients 1~-16. Pres- ently, ACE inhibitors appear to be the agents of choice but calcium channel blockers and centrally acting alpha- adrenergic agonists are reasonable alternative tT. With most of these agents one could achieve lowering of AER or prevent an increase. Whether such a reduction in AER has a beneficial effect on renal function in the long-term remains unclear.

Other risk factors for microalbuminuria include poor metabolic control duration o f diabetes, family history of diabetic nephropathy, hypertension and atherosclerotic diseaselS-lL Clustering of diabetic renal disease to families has been attributed to positive family history of hyperten- sion and undefined genetic factors. Recently, Watts et al 2~ have demons t ra t ed that mic roa lbuminur ia and over t nephropathy were positively associated with the expres- sion of the H L A - A 2 antigen.

We conclude that microalbuminuria is common in Irish patients with IDDM, and that AER should be determined as part o f the annual routine screen. Both the natural history and effect of intervention need further elucidation. A more stringent control of blood pressure and blood glucose concentration in IDDM is recommended.

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