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

Acknowledgements – Questions?Acknowledgements – Questions?

Geoff Chase Geoff Shaw

Dominic LeeSteen Andreassen

Jim MannKirsten McAuley

Jessica Lin Chris HannJason Wong