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A HIGHLY CORRELATED METHOD TO ASSESS INSULIN RESISTANCE IN BROAD POPULATIONS. T Lotz 1 J G Chase 1 , KA McAuley 2 , GM Shaw 3 , CE Hann 1 , JI Mann 2 1 Department of Mechanical Engineering, University of Canterbury, Christchurch, New Zealand - PowerPoint PPT Presentation
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A HIGHLY CORRELATED METHOD TO A HIGHLY CORRELATED METHOD TO ASSESS INSULIN RESISTANCEASSESS INSULIN RESISTANCE
IN BROAD POPULATIONSIN BROAD POPULATIONS
T Lotz1
J G Chase1, KA McAuley2, GM Shaw3, CE Hann1, JI Mann2
1Department of Mechanical Engineering, University of Canterbury, Christchurch, New Zealand
2Edgar National Centre for Diabetes Research, University of Otago, Dunedin, New Zealand
3Department of Intensive Medicine, Christchurch Hospital, Christchurch, New Zealand
The ProblemThe Problem
• Insulin resistance is a major risk factor in the development of type-2 Diabetes and cardiovascular disease
• Early and regular monitoring is crucial to assess effects of intervention
• Accurate assessment is difficult and stressful with current methods
Current methodsCurrent methods
ACCURACY
ST
RE
SS
+ L
EN
GT
H +
CO
ST
CLAMP3-6 hours
IVGTT2-4 hours
HOMA10 mins
GOAL FOR NEW TEST
Can we be accurate, yet simple and short??
Insu
lin
Glu
cose
• Short, simple, no steady state necessary (30-60 min)
• Physiological doses of glucose+insulin
1. Measure glucose, insulin, C-peptide
2. Fit model to data
3. Determine SI from model
Physiological model necessary!
0 5 10 15 20 3025
Glucose profile
glucose
ConceptConcept
Model of Glucose and Insulin Model of Glucose and Insulin KineticsKinetics
GGEIG V
tP
Q
QGGSGpG
)(
1)(
P
en
P
ex
P
I
I
LK V
tu
V
tuQI
V
n
I
InInI
)()()(
1
)( QIV
nQnQ
Q
IC
PLASMAINTERSTITIAL
FLUID
KIDNEYS
LIVER
diff
usio
nCELLS
PANCREAS
nC
nK nL
nI
uen
uexGLUCOSE
(Lotz et al ICBME 2005)
Model validation on ‘gold-standard’ Model validation on ‘gold-standard’ clamp testclamp test
• High correlations at steady and transient states
ISI vs. … r (95% CI)
SI (steady state) 0.98 (0.97-0.99)
SI (transient) 0.94 (0.91-0.96)
Log-HOMA -0.31 1 2 3 4 5 6 7 8 9 10
x 10-4
0
1
2
3
4
5
6x 10
-4 ISI vs. SIss
(r=0.98)
ISI G
SIss
ISIG
=0+0.56SIss
r=0.98
transient steady
Test simulationTest simulation
• Simulated population from clamp data (N=195)
• Correlation r=0.93 between model SI and clamp ISI during 40 minute transient test
• Model captures dynamics of insulin and glucose within measurement error
• Low, physiological dosing Increased safety and accuracy
-10 0 10 20 30 40 504
5
6
7
8
9
10
t [min]
Blo
od
Glu
co
se
[m
mo
l/l]
-10 0 10 20 30 40 500
50
100
150
200
250
300
t [min]
Pla
sm
a I
ns
ulin
[m
U/l
]
ConclusionsConclusions
• Simple model-based dose response test to assess insulin resistance
• Physiological dosing, short duration, cost efficient, yet highly accurate!
• Simulation results correlate r=0.93 with ‘gold standard’ clamp test
• Potential for application in a clinical setting