Microalbuminuria in Diabetes Mellitus
E. Choo-Kang,* FRCPC and H.L. Reid** PhD
Departments of Pathology* and Basic Medical Sciences (Physiology Section)**
University of the West Indies
Diabetes Mellitus is a common condition worldwide. One of the complications is
Diabetic Nephropathy which is detected in its early stage by the presence of
Microalbuminuria. Microalbumin was determined on random urine specimens by an
immunoassay method on 258 patients attending the Diabetic outpatients clinic at the
University Hospital of the West Indies. Overall, there were 173 (67.05%) patients with
nephropathy. Of these, 150 (58.14%) had microalbuminuria and 23(8.91%) had
macroalbiminuria. In the 68 patients with Type 1 diabetes 52(76.47%) had nephropathy - 41(60.29%) with microalbuminuria and 11(16.18%) with macroalbuminuria. In the 190
patients with Type 2 diabetes 121(63.68%) had nephropathy – 109(57.37%) with
microalbuminuria and 12(6.32%) with macroalbuminuria. In all groups over 70% had
elevated Glycosylated Haemoglobin(HbA1c). This emphasises the need for proper control of the diabetes.
Diabetes Mellitus is one of the most common diseases worldwide. Its incidence varies
from country to country. It is estimated to be about 15% in the Caribbean (13). Many of
these patients have hypertension which accelerates the vascular complications associated
with diabetes, including those of the retinal, renal cardiac and peripheral vascular
systems(9). One of the more chronic complications is diabetic nephropathy which can
lead to end stage renal disease (ESRD). Early detection of nephropathy is important as
intense glycaemic control (11) and treatment with Angiotensin Converting Enzyme
(ACE) inhibitors(5) may delay its onset and progression.
METHODS AND AIMS
Sampling : Patients were selected randomly during attendance at the Diabetic Out-Patient Clinic at the University Hospital of the West Indies. The first patient to arrive and every third patient thereafter were selected. Informed consent was obtained from each patient. Venous blood was collected in KEDTA (2.5 mg/ml) tubes for the determination of glycosylated haemoglobin .
Measurement of Blood Pressure : Blood pressure was measured by the standard sphygmomanometer technique. Patients were allowed to rest for 30 minutes. All measurements were made in the morning between 9:00 and 10:00 a.m. The mean of two blood pressures were recorded while the patients were seated. Hypertension was defined as a systolic blood pressure reading greater than 140 mmHg and/or a diastolic reading greater than 90 mmHg.
Measurement of Glycosylated Haemoglobin (HbA1c): The HbA1c was determined by an affinity chromatographic method (GLYCO-Tek Affinity Column Kit. Helena Laboratories).
Measurement of Microalbuminuria : Microalbuminuria was determined on
fresh morning mid-stream urine by the immunoassay method of Silver et al (17).
Urinary tract infection was excluded by testing the urine for leucocytes and performing the Nitrite Test by the Dipstick method.
Statistical analysis was done by the GraphPad InStat software. A p value <0.05 was
regarded as significant. All values are Mean(Standard Deviation).
The present study aims to determine the incidence of microalbuminuria in diabetic
patients attending the Diabetic Clinic at the University Hospital of the West Indies
(UHWI). The classification of Diabetes was based on the clinical diagnosis.
Blood and urine samples were obtained from 313 patients, 83 males and 230 females with ages ranging from 16 to 85 years. However, complete sets of data were obtained in only 258 patients. Microalbuminuria was defined as an albumin concentration between 20 and 300 mg/L(8).
Values above these are defined as macroalbuminuria or proteinuria. There were 85 (32.95%)
patients without nephropathy and 173 (67.05%) with nephropathy, 150 (58.14%) with
microalbuminuria and 23(8.91%) with macroalbuminuria . In the 68 patients with Type 1
diabetes16(23.53%) had no nephropathy and 52(76.47%) had nephropathy – 41(60.29%)
with microalbuminuria and 11(16.18%) with macroalbuminuria. In the 190 patients with
Type 2 diabetes 69(36.32%) patients had no nephropathy and 121(63.68%) had nephropathy
– 109(57.37%) with microalbuminuria and 12(6.32%) with macroalbuminuria. The
duration of diabetes was longer in those patients with nephropathy - 9.39(8.25) years in
those without proteinuria and 11.85(8.63) years in those with microalbuminuria and
15.48(8.89) years in those with macroalbuminuria. However, their glycosylated
haemoglobin concentrations were not significantly different . It was 10.04(3.71)% in those
without proteinuria ,10.25(3.50)% in those with microalbuminuria and 11.16(4.41)% in
those with macroalbuminuria. There were also no significant differences in the percentages
of those patients with poor glycaemic control (HbA1c > 7%). It was 72.94% in those without proteinuria and 83.33% in those with micoalbunimuria and 74.91% in those with macroalbuminuria .
Overall hypertension was present in 119 (46.12%) patients with a significantly higher proportion in patients with nephropathy. Twenty eight (32.94%) of the patients without microalbuminuria were hypertensive compared to 76 (50.67%) in the patients with microalbuminuria and
15(65.21%) in the patients with macroalbuminuria.
In the 150 patients with microalbuminuria there were no significant differences in the
duration of diabetes : 13.18(8.59) years in Type 1 and 11.24(8.75) years in Type 2. In
Type 1 the HbA1c concentration was10.47(3.40) % and microalbumin 80.58(59.14) mg/L . In Type 2 the HBA1c concentration was 10.15(3.55)% and microalbumin 62.67(48.20) mg/L . Microalbuminuria concentrations were higher in both groups with hypertension. In Type 1 it was 65.31(55.56) mg/L in the normotensive and 95.10(65.55) mg/L in the hypertensive patients . In Type 2 it was 53.84(41.02) mg/L in the normotensive and 73.24(52.71) mg/L in the hypertensive patients.
The determination of microalbuminuria in diabetes mellitus is important as it is the earliest indication of diabetic nephropathy which, left untreated, will eventually lead to end stage renal disease. The pathological changes are identical in Type 1 and 2. The main changes occur in the glomeruli. Rarely, changes may occur in the renal tubules (16). Aggressive and sustained treatment of the nephropathy would slow the progression of the condition (5,11,19). Microalbuminuria is best determined on a 24 hour urine sample. For convenience a random
sample can also be used and the test done with the Micral Test Strip (10,14). The definition of microalbumin used here in a random urine sample is expressed as mg/100mL(8). This is not the present recommended method. We subsequently compared the present method with the recommended method ,mg albumin/gm creatinine, in 400 samples from the routine laboratory. There was agreement in 345(86.25%) samples , both normal in 203(50.75%) and both abnormal in 142(35.50%). There were 37(9.25%) samples where the concentration was abnormal but the ratio was normal and there were 18(4.50%) samples where the ratio was abnormal and the concentration normal. This would mean a misclassification of about 14%.
The incidence of nephropathy in diabetes mellitus varies between Type 1 and Type 2. In the United States it is between 20 and 40 % in Type 1 and 5 and 60 % in Type 2 (6,7,8). The highest incidence has been shown to occur in the Pima Indians (60%) and the lowest in Caucasians (5 to 10%). In Afro-Americans it is between 10 and 20% (6,20). Other reported incidences are 23% in Type 1 in Denmark (7) and 54.8% in all diabetics in Saudi Arabia (2).
Our present findings showed higher incidences both in Type 1 and Type 2. This is a reflection of the poor degree of glycaemic control seen in our patients treated at a tertiary institution. The poor control is due mainly to the low compliance rate (12). It is worth noting that in the three groups – no proteinuria, microalbuminuria or macroalbuminuria - over seventy percent showed poor long term control (HbA 1c > 7.0%) suggesting that perhaps good control may not necessarily prevent the development of nephropathy. However, macroalbuminuria is more likely to develop the longer the duration of the nephropathy where the mean duration of diabetes in those with microalbuminuria was about 12 years and those with macroalbumin was about 15 years.
Hypertension could occur as a coexisting condition or develop as a complication of diabetes. The incidence of hypertension was found to be 26.7% among diabetic patients, as a group, attending the outpatient clinic at the UHWI(12) . The same study also showed that diabetics with or without peripheral vascular disease had incidences of hypertension of 72.2% and 46.8% respectively (12). Overall, our data showed a greater incidence of hypertension, which was even greater when nephropathy was present. Early and aggressive treatment of the diabetes and hypertension could delay the onset and progression of nephropathy(1,4,5,11,19). The excretion of microalbumin in both Type 1and Type 2 was greater in those patients with hypertension compared to the normotensives. This would suggest that hypertension has a significant influence on the severity of microalbuminuria.
Diabetes mellitus affects many people worldwide and can be fairly well controlled. If nephropathy and end stage renal disease occurs, it would have a severe effect on the health care delivery system. Adequate and sustained treatment are necessary to prevent these serious complications in the diabetic patient.
1. Agrawal B, Wolf K, Berger A, Luft PC. (1996) Effect of antihypertensive treatment on qualitative estimates of microalbuminuria. J Hum Hypertens (1996) Vol.10(8), 551 – 5.
2. Al Ghandi KS. (2001) Microalbuminuria among patients with diabetes type 1 and
type 2 at the armed forces hospital in Jubail. Ann Saudi Med . Vol. 21, Nos 3-4, 236-8.
3. Almidal T, Norgaard K, Feldf-Rasmussen B, Deckert T. (1994) Predictive value of
microalbuminuria. A five year followup study. Diabetes Care . Vol. 17, 120-5.
4. American Diabetic Association. (2004) Nephropathy in Diabetes. Diabetes Care.
Vol. 27(1Suppl), 79S – 83S.
5. Cooper ME. (1996) Renal protection and angiotensin converting enzyme inhibition in
microalbuminuric type I and type II diabetic patients. J. Hypertens. Vol. 14,11S-14S.
6. Gillis R. (1998) Diabetic Nephropathy. 11th Annual Update in Primary Care.
Landmark Resort ,Egg Harbor, Wisconsin. Oct 8 - 10. 1998.
7. Gross JL, DeAzevedo MJ, Silveiro SP, Canani LH, Caramori ML and Zelmanovitz.
(2005) Diabetic Nephropathy. Diagnosis, prevention and Treatment. Diabetes Care.
8. John AM, Rohlfs EM, Silverman LM. Proteins. (1999) In : Burtis CA, Ashwood ER.
eds. Tietz Textbook of Clinical Chemistry. Philadelphia . W.B. Saunders Company.
9. Karmal WB, McGie DC. (1979) Diabetes and Cardiovascular risk factors. The
Framingham Study. Circulation . Vol. 59, 8-13.
10. Leong SO, Lui KF, Ng WY, Thai AC. (1998) The use of semi-quantitative urine test-
strip (Micral) for microalbuminuria screening in patients with diabetes mellitus.
Singapore Med J .Vol. 39(3), 101-3.
11. Levin SR, Coburn JW, Abraira C, Hendersen WG, Colwell JA et al. (2000) Effect of intensive glycaemic control on Microalbuminuria in Type2 diabetes. Diabetes Care. Vol. 23(10),1478-85.
12. Morrison EY St.A, Bennett F. (1988)Assessment of Patient Compliance in a Diabetic
clinic using Glycated Proteins compared with Blood Sugar measurements. West Indian Med J. Vol 37, 158-61.
13. Morrison EY St.A ,Williams W. (1993) UNDOP. Diabetic Nephropathy (Foreword).
West Indian Med J. Vol. 42(2Suppl) :v.
14. Ng WY, Lui KF, Thai AC. (2000) Evaluation of a rapid screening test for
microalbuminuria with a spot measurement of urine albumin-creatinine ratio. Ann Acad Med Singapore . Vol 29,62-5.
15. Parving HH. (1996) Initiation and progression of Diabetic Nephropathy. N Eng J
16. Shah DJ. (1993) Renal pathology in diabetes mellitus. West Indian Med J. Vol
17. Silver A, Dawnay A, Landon J, Catelli WR. (1986) Immunoassays for low concentrations of albumin in urine. Clin Chem. Vol 32,1303-6.
18. Vigilance JE, Reid HL, Richards-George P. (1999) Peripheral occlusive arterial disease in diabetic clinic attendees. West Indian Med J. Vol 48(3), 143-6.
19. Warram JH, Scott LJ, Hanna LS, Wantman M, Cohen SE, Laffel LMB et al. (2000)
Progression of microalbuminuria to Proteinuria in Type 1 Diabetes. Non linear
relationship with hyperglycaemia. Diabetes. Vol 49, 94-100.
20. Young BA, Maynard C and Boyko EJ. (2003) Racial Differences in Diabetic
Nephropathy, Cardiovascular Disease and mortality in a National population of
Veterans. Diabetes Care. Vol. 26,2392-2399.
Firts Published April 2008
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