Comparative Performance of Urine Glucose with ADA and WHO Criteria for
Diagnosis of Type 2 Diabetes.
by
1. Abullahi N Adamu*. MWACP, FMCP
2. Ohwovoriole E Augustine†. FWACP, FMCP
3. Fasanmade O Adesoji†. FWACP
4. Olarinoye J Kola*. FWACP
5. Ekpebegh O Chukwuma†
*Department of Medicine, University of Ilorin, Nigeria.
†Department of Medicine, University of Lagos, Nigeria.
Name of Department and Institution to which the work should be attributed- Department of
Medicine, University of Ilorin, Nigeria.
Disclaimer- None
Contact information for corresponding authorsAbdullahi Ndaman Adamu
Department of Medicine, University of Ilorin, PMB 1515, Ilorin 240001. Nigeria
Phone- +2347058024401, +2348023435240
E-mail- abdullahiadamu2003@yahoo.com
Name and address of author to whom request for reprint should be made- same as above.
Source of support – None
Word countNumber of Tables= 3. Figures= 2
1
Conflict of Interest Notification
There is no conflict of interest of whatever form in conception to final execution of this article.
2
Abstract
Background-There are two cardinal accepted way of diagnosing diabetes mellitus; American diabetes
association criteria and WHO criteria
Objective- To compare the performance of random urine glucose with American diabetes Association
criteria and World Health Organisation criteria for diagnosis of diabetes mellitus among people with
systemic hypertension.
Methodology- Between January and March 2004, a prospective screening for Type 2 diabetes was
conducted using Clinistix® urinalysis strip. Oral glucose tolerance test was carried out in which fasting
plasma glucose and 2hour plasma glucose was estimated.
Results- We recruited 206 persons, out of which 131(63.41%) had the three tests (fasting plasma glucose,
2hour plasma glucose of oral glucose tolerance test and urinalysis) done. The mean age of the participants
was 53.11±8.69years. The prevalence rate of diabetes by urine glucose was (6.87%), fasting plasma
glucose was 19.1% (25/131) and by WHO criteria was 18.32% (24/131). Urinalysis with fasting plasma
glucose recorded a sensitivity of 28%, specificity of 98%, positive predictive value of 77.77%, negative
predictive value of 85.24%, efficiency of 84.73% and Pearson’s regression coefficient of 0.52, while
urinalysis with WHO criteria recorded a sensitivity of 25%, specificity of 97.19%, positive predictive
value of 66.66%, negative predictive value of 85.74%, efficiency of 83.96% and Pearson’s regression
coefficient of 0.55. Only the y equation and positive predictive value were statistically significant (P
≤0.05).
Conclusion- WHO criteria is preferable as ADA criteria over estimate the diagnosis of diabetes.
Key words- screening- type 2 diabetes mellitus- urinalysis- FPG-2hour plasma glucose-OGTT.
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Introduction
The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (1) has proposed
guidelines for diabetes mellitus testing in asymptomatic, undiagnosed individuals. Although screening is
not recommended in the general adult population, it is recommended for individuals with one or more
risk factors. The prevalence of diabetes is increasing rapidly all over the world, with diabetes becoming
known as an epidemic disease (2). It may remain undetected for a number of years; a significant number
of newly diagnosed type 2 diabetes has established complications (3). There is indirect evidence that early
detection and treatment of diabetes and cardiovascular risk factors reduces severe retinal, renal and
cardiovascular complications (4, 5). Thus, preventing or delaying diabetic complications may improve
patients’ quality of life and reduce health-care expense (6).
Screening for diabetes using biochemical tests (random blood sugar, fasting blood glucose) is the
common practice in most parts of the worlds. This may be better done by noninvasive and no technically
demanding method likes urine glucose measurement (urinalysis), which shall be useful in poor resource
nations. Thus, safety issues in dealing with blood specimens shall be obviated. Recommended diagnostic
criteria for diabetes differ across international associations and organizations, with the American Diabetes
Association (ADA) and World Health Oraganisation (WHO) published new criteria in 1997 and 1999,
respectively(7, 8). The ADA recommends that a fasting plasma glucose (FPG) test is preferable for
diagnosis, while WHO recommends ideally using both the FPG level and 2hrpp (2-hour plasma glucose
of OGTT).
The available studies using urinalysis as screening tests were done at community level and included those
with known diabetes and not known to have diabetes (9, 10). Some did not include those known to have
diabetes (11-13). All of them were prospective diagnostic studies, some used clinistest® and fasting blood
sugar as diagnostic test.
Based on the available studies on urinalysis as screening test, none to our understanding has carried out a
direct comparison between ADA criteria and WHO criteria as a gold standard. Thus, the aim of this study
is to compare the performance of the two gold standards using urinalysis as a screening test among people
with systemic hypertension. This comparison shall be useful in giving credence to the one that gives a
better performance and help in choice selection of diagnostic yardstick in subsequent studies.
Methodology
Study Design: Cross sectional study
Study Location: This study was carried out at the Department of Medicine of the Lagos University
Teaching Hospital (LUTH) and the Endocrine Unit Laboratory of the Department of Medicine of the
College of Medicine, University of Lagos over a period of three months, spanning from January to March
2004.
Subjects: The subjects recruited for screening for type 2 diabetes were those with known history of
systemic hypertension on life-style modification and/ or drug (s) for the control of the hypertension. They
were those attending the Cardiology and Renal units’ Medical out Patients’ department of the hospital.
Those patients with established secondary form of hypertensions, chronic renal failure and chronic liver
disease were excluded from the study.
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Sample Size:
We recruited 206 persons to give room for attrition. One hundred and thirty one giving participation rate
of 63.41% turn up for all the tests; urinalysis (urine glucose estimation using clinistic®) and OGTT (FPG
and 2hrpp sampling). This was made up of 87 (65.64%) females, while males were 44 (34.35%).
Approval was obtained from the Ethical Committee of the Lagos University Teaching Hospital. An
informed consent was obtained from the patients/ subjects before commencing the studies.
The patients on usual medical follow up were approached and given a brief health talk on the importance
of screening for diabetes among people with systemic hypertension. A questionnaire containing biodata
and anthropometry of the subjects were taken. The information taken included: name, age, gender,
hospital number, height (m) with measurement taken to the closest centimeter, weight (kg) to the closest
mg, and BMI calculated as the ratio of weight in kg to the square of height in metres. Waist
circumference was taken at umbilical level, to the closest centimeter, Hip circumference was measured at
the widest dimension of the buttocks, to closest centimeters. Waist to hip ratio was calculated by finding
the ratio of the waist to that of hip (14).
Performance of Urine Glucose Estimation
The Urinalysis was carried out in the clinic after the administration of the questionnaire. The patients
usually take break fast before coming for the clinic. Since they don’t know for how long they may stay in
the clinic. Plain bottles were given to the patients to pass 3-5ml of non-fasting urine. The urine was mixed
thoroughly and tested by dipping the reagent area of the Clinistix® strip directly into the urine and
removed immediately. The edge of the strip was run against the rim of the container to remove excess
urine during removal. The colour change was read within 5- 10seconds by matching and comparing it
with the colours on the strip container for glucose grade. The result of one positive (+) and upward was
considered to be positive test.
Performance of OGTT
Every subjects recruited from the clinic were given two weeks to come for oral glucose tolerance test.
They were advised to come in a fasting state after the previous day dinner, but could take non-caloric
drinks like water. At 7.30am of the appointed day, tourniquet was applied to the upper arm of the
subjects; the area over cubital artery was cleansed with spirit impregnated cotton wool. Five millimeters
syringe and needles was used to withdraw 3-5mls of fasting venous blood sample and were given 75gm
of dissolved anhydrous glucose in chilled water to drink at once and another blood sample was taken at
9.30am using the same method.
Preservation of Blood Specimen
Immediately, after the venous blood was drawn, all were centrifuged, and aliquots were prepared within
30min of collection. Plasma aliquots were frozen at -80oC until conduction of the analyses in the same
laboratory. Plasma glucose was analyzed according to the method of Trinder (15) using glucose oxidase
enzyme buffered in phenoxylate and dissolved in colour reagent. The coefficient of variation for intraassay was 3.5% and inter-assay was 9%. Diabetes was diagnosed based on the ADA of FPG ≥7.0mmol/l
and WHO criteria of 2 hrpp of ≥11.1mmol-1.
5
Statistics
The data were entered into a Microsoft Excel database. Analysis of data was with SPSS version 11. The
Means±SDs were assessed for continuous variables, and frequencies and proportions were assessed for
categorical variables. Differences among groups of ADA (FPG) and WHO (2hr pp) parameters were
assessed using t- test and p ≤ 0.05 is considered significant. Sensitivity, specificity, predictive values and
efficiency were assessed from 2x2 table made between urinalysis and the two diagnostic tests, ADA and
WHO. Sensitivity is the proportion of those with FPG ≥7.0mmol/l(126mg/dl) and 2hr pp ≥11.1mmol/l
(≥200mg/dl) that were detected as positive by urinalysis, specificity is the proportion of those with normal
FPG (<7mmol/l or <126mg/dl) and 2r pp (<11.1mmol/l or <200mg/dl) and were found to have no glucose
in the urine. Positive predictive result is the proportion of urine positive results in a mixed population of
sick and healthy people using ADA and WHO criteria, negative predictive value is the proportion of urine
negative results in a mixed population of sick and healthy people using ADA and WHO criteria, while
efficiency is the percentage of the sum of the true positives and the true negatives is of the grand total
population.
A plot of correlation was made using a linear regression model where r, r-square and y were estimated.
Results
The mean age of the subjects was 53.11±8.69years and ranged from 31 to 78yrs and median of 52. The
mean parameters of the subjects studied were height of 1.63±0.68m, weight of 81.31±17.78kg, BMI of
30.43±6.66kg/m2, waist measurement of 98.21±11.65cm, hip measurement of 107.92±11.50cm, waist to
hip ratio of 0.91±0.08 and duration of hypertension was 8.56±8.80years. Nine (6.87%) of the subjects
tested positive for urinalysis, constituting 6(4.58) females and 3(2.26%) males, while 122(93.13%) tested
negative; 81(61.83%) females and 41(31.30%) males. The comparative profiles of those that were
urinalysis positive and urine negative are as shown in table 1. The anthropometric parameters were not
significantly different except the biochemical profiles, FPG and 2hr plasma glucose values (P v <0.05).
The two diagnostic criteria had similar age pattern of distribution, except that more proportion of subjects
were diagnosed to have diabetes in the age ≤ 40years using WHO criteria compare to the ADA criteria.
Most of the diagnosed diabetes was within the age group 60-69years for ADA criteria while it fell in the
age group 50-59years for WHO criteria as shown in figures 1 and 2. The prevalence score of diabetes
using the two diagnostic criteria shows that 19.1% of newly diagnosed type 2 diabetes was established by
ADA criteria while 18.32% was found by WHO criteria which are not statistically significant (Pv=0.87)
as shown in table 2. The 2x2 tables used to calculate the performance of the tests and assessment of the
correlations of urine glucose in relation to ADA criteria and WHO criteria had been presented in other
studies (Adamu AN, Ohwovoriole AE, Olarinoye JK, Fasanmade OA, Ekpebegh CO. Comparison of
Urinalysis with Fasting Plasma Glucose. In press with Nig. End. Pract. and Adamu AN, Ohwovoriole AE,
Fasanmade OA, Olarinoye JK, Ekpebegh CO. Comparison of Urinalysis with 2-hour Plasma Glucose. In
Press with Afr. J End and Met.).
Moreover, the summary of the result of ADA criteria versus urinalysis test are- true positive was 7, true
negative was 104, false positive was 2 and false negative was 18, while for WHO criteria versus urine
glucose test are- true positive was 6, true negative was 104, false positive was 3 and false negative was
18.The comparative summary is presented in table 3 showing only the y of regression equation and
positive predictive factor are significant.
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Discussion
A 2-hr pp ≥11.1 mmol/liter is considered to be the gold standard diagnostic criterion for diabetes mellitus
(8). By contrast, fasting plasma glucose (FPG) has not been adequately justified as a diagnostic criterion.
The FPG cutoff point for diagnosing diabetes was revised by the Expert Committee of the American
Diabetes Association (ADA) (7) in 1997; namely, the cutoff point for defining diabetes was put to more
than or equal to 7.0 mmol/liter (7). The World Health Organization adopted an FPG of ≥7.0 mmol/liter as
a diagnostic criterion of diabetes in 1998 (16).
There is no comparable result available from our search that uses urinalysis as a screening tool, and
comparing the results of the performance using the two different diagnostic standards; ADA and WHO
criteria. However, our results showed that there is no much difference in terms of figure in the
performance of the two cardinal diagnostic tests and were not also statistically significant. An assessment
of the features of those that had urinalysis test stratifying them into screen positive and screen negative
showed that the two groups had no statistically significant anthropometry but significant biochemical
values as shown in table 1. Also the prevalence yields of the two cardinal diagnostic tests were
comparable with no significant difference between them in table 2. The statistical performances of the
two tests were equally comparable in table 3.
Similarly, comparison of our finding with similar studies using clinistix® for urinalysis as screening tool
among people with systemic hypertension was lacking, however analysis from previous urinalysis studies
showed a sensitivity of 35% and specificity of 99.7% using FPG as a diagnostic tool, while sensitivity of
38.9% and specificity of 94.4% was derived using 2-4hour plasma glucose estimation as a diagnostic tool,
in a prospective diagnostic study comprising of 50 known diabetics in a sample size of 4262 subjects in
ten countries (9). The general remark from these studies showed that urinalysis performance has low
sensitivity as screening test for diabetes but high specificity. There is also incongruent result of sensitivity
of this study compare to ours, while ADA (FPG) sensitivity in our study is higher compare to WHO
criteria, it is lower in this other study, although, both studies had similar specificities in the two categories
of ADA and WHO. This much disparity between this result compare to our study may be due to the fact
that this study included those known to have diabetes in their study sample. Also the diagnostic blood
glucose is lower than current WHO criteria, false negative rate was not extrapolated to whole population
in sensitivity calculation and sample size was not drawn among high risk subjects.
Moreover, another study that used glucotest®, also a urinalysis strip specific for glucose reported a
sensitivity of 20.80% and specificity of 99.1% in a prospective diagnostic study using FPG as a
diagnostic test (13). The sensitivity result reported in this study is lower compare to our study but had
similar specificity result. However, the results are comparable in the two studies. Some degree of
similarity and difference noticed in the two studies may be as a result of similar age pattern of distribution
of recruited subject ≥40yrs and did not include diabetes subjects in the sampling process.
This study has made a significant contribution to medical library particularly in the field of diabetes
screening because we were able to correlate and compare random urinalysis test with two cardinal
diagnostic biochemical parameters for type 2 diabetes mellitus. We also evaluated efficiency, r square
which others did not include in their study. This is the first time urinalysis is done in clinical screening
and comparison of the performance of the results using ADA and WHO diagnostic criteria in people with
systemic hypertension to our knowledge.
Conclusion derived from this study suggest that FPG is as good as 2hour plasma glucose value in
screening for type 2 diabetes among people with hypertension using random urine sample as a screening
test. A general statement can not be made about this result as it affects other screening tests.
7
Way forward should be directed towards using other screening tests and compare the results obtained
using different diagnostic criteria for diabetes. The outcome of such studies will determine whether FPG
will replace 2 hour plasma glucose estimation as a diagnostic test.
Limitation of the study is that the sample size of 131 subjects is small to make a general statement about
our findings. The study was confined to people with hypertension alone; there need to be a wider
coverage of the strata of the society in subsequent studies.
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8
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9
Table 1. Characteristic features of Urine Glucose Results.
Features
Urinalysis
P value
Positive
Negative
Numb.=9
Numb.=122
Age(years)
54.44±9
53.02±8.66
0.63
Height(m)
1.66±0.07
1.63±0.08
0.025
Weight(Kg)
85.39±11.70
81±18.15
0.48
Body Mass Index(Kg/m2)
31.06±6.60
30.39±6.69
0.77
Waist (cm)
101.89±7.80
97.94±11.86
0.33
Hip (cm)
110.56±8.56 107.73±11.69
0.48
Waist to Hip ratio
0.92±0.05
0.91±0.08
0.69
Duration of Hypertension
8.56±8.80
9.31±8.07
0.79
Means Fasting Plasma Glucose (mg/dl)
267.91±184
105.25±52.07
0.00
Mean 2 hour plasma glucose (mg/dl)
359.36±187.86 155.47±65.38 0.00
10
50
40
30
20
MeanFbsCat
Count
10
Negave
0
Positive
Less than 40yrs
40 - 49yrs
50 - 59yrs
70yrs and above
60 - 69yrs
Age in category
Fig. 1. Prevalence of Diabetes by age and ADA criteria
11
50
40
30
20
Mean 2hrs in categor
Count
10
Less than 200mg/dl
0
200mg/dl and above
Less than 40yrs
50 - 59yrs
40 - 49yrs
70yrs and above
60 - 69yrs
Age in category
Fig 2. Prevalence of diabetes by age and WHO criteria
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Table 2. Prevalence estimate of undiagnosed diabetes among 131 hypertensive subjects
Diagnostic Criteria People Diagnosed with Diabetes Prevalence of Diabetes
ADA
25
19.1%
WHO
24
18.32%
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Table 3. Shows the statistical performance of the diagnostic tests
Features
y equation
ADA
WHO
105.25 +162.65
P-value
155.47+203.90
0.00
0.55
0.49
30
0.45
Regression coefficient
0.52
R square
27
Sensitivity
28%
25%
0.42
Specificity
98%
97.19%
0.53
Positive predictive value
77.77%
66.66%
0.00
Negative predictive value
85.24
85.24
0.54
Efficiency
84.73
83.96
0.79
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