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Oral Glucose Tolerance Test Modeling For Diabetes Characterization

Conference Paper · July 2004

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 Oral Glucose Tolerance Test Modeling For Diabetes Characterization
Loh Kah Meng1, Prof Dhanjoo Ghista2
1
School of Engineering (Electronics), Nanyang Polytechnic, Singapore
2
Department of Mechanical Engineering, Nanyang Technological University, Singapore

impaired fasting glucose. This is considered a risk factor

Abstract— This paper provides a systems-engineering
analysis of the glucose-insulin responses to an ingested
bolus of glucose for OGTT (Oral Glucose Tolerance
Test). The clinical data of patients is fitted by either
under-damped or over-damped or critically-damped
solutions of the model’s governing equations for glucose
and insulin responses to glucose bolus ingestion. Based
on the best fit of the three types of solutions, we
designate the patients (and their response) to be normal
(and under-damped), diabetic (and over-damped) and
either border-line or at-risk of becoming diabetic (and
critically-damped). In this way, the model simulation of
the clinical data enables more reliable diagnosis relative
to the clinical assessment.
Keywords—diabetic, systems-engineering model, under-
damp, over-damp, critically-damped, R-square, fitting, clinical
diagnosis
for future diabetes and will likely trigger another test in the
future, but, by itself, does not make the diagnosis of
diabetes.
A person is said to have impaired glucose tolerance
when the 2-hour glucose results from the oral glucose
tolerance test are greater than or equal to 140 but less than
200 mg/dl. This is also considered a risk factor for future
diabetes. A person has diabetes when oral glucose tolerance
tests show that the blood glucose level at 2 hours is equal to
or more than 200 mg/dl. This must be confirmed by a
second test (any of the three) on another day.
II. SYSTEM SOLUTIONS FOR DIABETIC, NON-
DIABETIC AND AT-RISK PATIENTS
The governing differential equation for glucose response to
glucose bolus intake is:

I. INTRODUCTION y′ = q (t ) − γ x − δ y (1)
The governing differential equation for insulin response to
Oral Glucose Tolerance Testing Protocol glucose bolus intake is:
The test subjects need to fast for 12 hours before the test
x′ = p ( t ) - α x + β y (2)
and during the 2-hour test. A blood sample of the subject is
taken before the beginning of the test. Then after the subject
drinks a 75 g of glucose solution dissolved in 250–300 mL y(t) : Glucose response of the patient to the oral bolus of
of water, the subject’s blood glucose and insulin glucose.
concentrations are measured at specified intervals 30 x(t) : Insulin response of the patient due to y(t).
minutes, 60 minutes, 90 minutes and 120 minutes [1, 2, 4].
Solution For Underdamped Case (non-diabetic):
Qualitative interpretation of the results, for preliminary
categorization of the patients [1, 2, 4]: y(t) = (G/ ω) e-At sinωt (3)

(a) Blood glucose normal values: ⎡ −(sin( wt ) Ae(− At ) ⎤

⎢ ⎥
fasting: 70 to 115 mg/dl ⎢ − sin( wt )α e(− At ) ⎥
⎢ ⎥
30 min.: less than 200 mg/dl ⎢ −e(−α t ) w + cos( wt )e(− At ) w) ⎥
⎢ ⎥
⎢ G ⎥
1 hour : less than 200 mg/dl ⎢⎣×β w ⎥⎦ (4)
x(t ) =
2 hour : less than 140 mg/dl ( A2 − 2 Aα + α 2 + w2 )
(b) Normal insulin level (reference range): 1-30 mU/L

When a person has a fasting glucose equal to or greater

than 110 mg/dl and less than 126 mg/dl, it is considered as

1
Solution For Overdamped Case (diabetic): The below table displays the values of the model parameters
and the R-Square coefficients of fitness and the model slution
G -At to the clinical data.
y(t) = e sinhwt (5)
ω

⎛1 ⎞
⎜ 2 (cosh( wt + At − α t ) A + sinh(− wt + At − α t ) A ⎟
⎜ ⎟
⎜ − cosh(− wt + At − α t ) A − sinh( wt + At − α t ) A ⎟
⎜ + sinh( wt − At − α t ) w − cosh(− wt + At − α t ) w ⎟
⎜ ⎟
⎜ − sinh(− wt − At − α t )α + sinh( wt + At − α t )α ⎟
⎜ − cosh( wt + At − α t )α − cosh( wt − At − α t ) w ⎟
⎜ ⎟
⎜ + cosh(− wt + At − α t )α + 2w ⎟
⎜ ⎟
⎜⎜ + sinh(− wt + At − α t ) w)e − (α t ) β G ⎟⎟
x(t ) = ⎝ w ⎠ (6)
( − w2 + A2 − 2 Aα + α 2 ) Figure 1: Patient S14 is designated to be under-damped and
normal. However, this patient is quite hyper-insulinemic; in
Solution For Critically Damped Case (at the dangerous other words, this patient has elicited considerable insulin
boundary): response in order to maintain an under-damped glucose
response.
y(t) = Gte-At (7) Over-damped Category of Patients Designated as Diabetic
( − At ) ( − At ) ( − At ) ( −α t )
− β G (tAe − tα e +e −e ) For patients D05, our over-damped model solution fits the
x (t ) = (8) clinical data best of the 3 solution categories. Hence, this
2
(A −α) patient is designated to be diabetic. His Glucose and Insulin
responses are shown in Figure 2, and the model parameters are
III. CLINICAL APPLICATION AND DISCUSSION given in the Table.

Under-damped Category and Normal Designated Patient

These y(t) and x(t) response solutions are fitted to the

monitored glucose and insulin data, and the fitness
coefficients are determined. Based on the high degree of fit,
patient S14 fits best the under-damped category, and hence
is designated to be normal. His Glucose and Insulin
responses, shown in Figure 1, illustrates the fast recovery of
blood glucose and insulin concentrations.

2
Figure 2: This patient D05 has the higher R-Square value when
fitted by the over-damped solution, and is hence classified as
diabetic.

Critically-damped Category of Patients

There are some patients clinically diagnosed to be

normal for which the critically-damped solution gives a
better fit of the data (and a higher value of R-Square) than
the under-damped solution. One such patient is S04, whose
under-damped and critically-damped model response-curves
are shown in Figures 3 and 4. Similarly, patients S06 and
S19 are not normal as clinically diagnosed, but at the risk of
becoming diabetic. Their response curves are illustrated in
Figures 5 and 6.

Figure 4: This S04 patient’s data is better fitted (i.e. at higher

R-Square value) by the critically-damped solution than by the
under-damped solution. Because of the critically-damped
model solution giving us a better fit (terations of a higher
value of R-Square), we differ from the clinical diagnosis and
alert this patient that he is at risk at becoming diabetic.

Figure 3: This S04 patient’s data is fitted by the under-damped

solution. Next, we will compare the results fitted by the
critically-damped solution as shown in the following figure.

3

Figure 5: This S06 patient’s data is better fitted (i.e. at higher
R-Square value) by the critically-damped solution than by the
under-damped solution. Hence, we will differ from the clinical
diagnosis and designate this patient to be at risk of becoming
diabetic.
Figure 6: This S19 patient’s response curves are best fitted
(with a higher value of R-Square) by the critically-damped
solution than by the under-damped solution.
V. CONCLUSION
We have shown that we can obtain more accurate
assessment of diabetic patients by means of our under-
damped, over-damped and critically-damped simulation
model solutions. Some patients (diagnosed to be normal)
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were designated by us to be in the borderline category.
However, some patients who were clinically declared to be
diabetic turned out to be only border-line. As we continue
this work, we will develop a clinically-implementable
software for model parameter identification and designation
of the subjects as normal or at-risk of becoming diabetic or
border-line diabetic or distinctly diabetic.
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Characterization Based on Glucose-Insulin Regulatory
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Academy of Medicine.
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Modelling and patients-simulation for diagnosis,
Journal of Mechanics in Medicare and Biology, Vol.1,
No.2 2001.
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[4] Allen A. Frethem, Clinic on Endocrine and Metabolic
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