C. Pretty, A. Le Compte, J. G. Chase, G. Shaw, S. Penning, J-C Preiser, T. Desaive

Introduction Insulin sensitivity defines the metabolic balance between insulin concentration and

insulin-mediated glucose disposal.

→ When using exogenous insulin, variable insulin sensitivity can cause highly variable outcome glycaemia.

Insulin sensitivity is affected by the acute stress response to critical injury.

This study quantifies and compares the evolution of insulin sensitivity level and variability for critical care patients receiving glycaemic control during their first 4 days of ICU stay.

Subjects & MethodsA retrospective analysis of patient data from the SPRINT tight glycaemic control (TGC)

study in the Christchurch Hospital ICU.

All patients commenced TGC within 12 hours of ICU admission and spent at least 24 hours on the SPRINT protocol.

Model-based insulin sensitivity (SI) was identified each hour for every patient.

Absolute level and hour-to-hour percent changes in SI were assessed on cohort and per-patient bases.

Levels and variability of SI were compared over time on 24-hour and 6-hour timescales for the first 4 days of ICU stay.

ResultsCohort and per-patient median SI levels increased by

34% and 33% (p<0.001) between days 1 and 2 of ICU stay.

Cohort and per-patient SI variability reduced by 32% and 36% (p<0.001).

Analysis of the first 24 hours using 6-hour blocks of SI data showed that most of the improvement in insulin sensitivity level and variability seen between days 1 and 2 occurred during the first 12-18 hours of day 1.

This rapid improvement was likely due to the decline of counter-regulatory hormones as the acute phase of critical illness progressed.

ICU patients have significantly lower and more variable insulin sensitivity on day 1 than later in their ICU stay and particularly during the first 12 hours.

Clinically, these results suggest that while using TGC protocols with patients during their first few days of ICU stay, extra care should be afforded.

Variability of insulin sensitivity during the first 4 days of critical illness

Brain

Glucose

Othercells

Liver

BloodGlucose

Insulin losses (liver, kidneys)

Insulin

Effective insulin

PlasmaInsulin

Pancreas

PatientsN 164Age (yrs) 65 [56-74]Gender (M/F) 102/62APACHE II score 19 [16-25]APACHE II ROD (%) 32 [17-52]Operative/Non-Operative 66/98Hospital mortality 25%ICU mortality 18%ICU length of stay (hrs) 142 [70-308]Diabetic history: Type I/Type II 10/22

I

enL

I

exI

ILK

GCI

GGG

VGux

VtutQtIn

tItIntInI

tQtQntQtInQ

VCNSEGPtP

tQtQtGSItGpG

)()1()())()(()(1

)()(

)(1)())()((

)()(1

)()(.)(.

-100 -50 0 50 1000

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1Cohort variability analysis

Percentage change (%)

F(x)

0-24hrs (3772 hours)24-48hrs (3221 hours)48-72hrs (2456 hours)72-96hrs (2092 hours)

0 50 100 150 200 250 300 350 400

Per-patient variability analysis

50% range of hour-to-hour variability

0-24hrs (162 patients)24-48hrs (155 patients)48-72hrs (112 patients)72-96hrs (94 patients)

0 0.5 1 1.5x 10

-3

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1Cohort level analysis

SI [L/mU.min]

F(x)

0-24hrs (3936 hours)24-48hrs (3376 hours)48-72hrs (2568 hours)72-96hrs (2187 hours)

0 0.5 1 1.5x 10

-3

Per-patient level analysis

SI [L/mU.min]

0-24hrs (164 patients)24-48hrs (155 patients)48-72hrs (112 patients)72-96hrs (95 patients)

24-hour analysis

0 0.5 1 1.5x 10

-3

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1Cohort level analysis

SI [L/mU.min]

F(x)

0-6hrs (984 hours)6-12hrs (984 hours)12-18hrs (984 hours)18-24hrs (984 hours)24-48hrs (3376 hours)

0 0.5 1 1.5x 10

-3

Per-patient level analysis

SI [L/mU.min]

0-6hrs (164 patients)6-12hrs (164 patients)12-18hrs (164 patients)18-24hrs (164 patients)24-48hrs (155 patients)

-100 -50 0 50 1000

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1Cohort variability analysis

Percentage change (%)

F(x)

0-6hrs (820 hours)6-12hrs (820 hours)12-18hrs (820 hours)18-24hrs (820 hours)24-48hrs (3221 hours)

0 50 100 150 200 250 300 350 400

Per-patient variability analysis

50% range of hour-to-hour variability

0-6hrs (149 patients)6-12hrs (161 patients)12-18hrs (163 patients)18-24hrs (163 patients)24-48hrs (155 patients)

6-hour analysis

SI Level

Cohort analysis Per-patient analysis

% Increase at median p-value % Increase

at median p-value

Days 1-2 34 <0.0001 33 0.0004

Days 2-3 16 <0.0001 21 0.2559

Days 3-4 6 0.0013 4 0.6306

SI Variability

Cohort analysis Per-patient analysis

% Reduction

of IQRp-value

% Reduction at median

p-value

Days 1-2 32 <0.0001 36 <0.0001Days 2-3 20 0.0028 18 0.0091Days 3-4 14 0.0269 17 0.0369

SI Level

Cohort analysis Per-patient analysis

% Increase

at medianp-value

% Increase

at medianp-value

0-6 vs. 6-12hrs 42 <0.0001 40 0.00076-12 vs. 12-18hrs 28 <0.0001 26 0.012312-18 vs. 18-24hrs 1 0.0335 3 0.482918-24 vs. 24-48 hrs 9 0.0452 7 0.3776

SI Variability

Cohort analysis Per-patient analysis%

Reduction of IQR

p-value%

Reduction at median

p-value

0-6 vs. 6-12hrs 40 0.0017 36 < 0.00016-12 vs. 12-18hrs 24 0.0628 28 0.067312-18 vs. 18-24hrs 0 0.0931 9 0.103218-24 vs. 24-48hrs 18 0.1682 14 0.1075

-100 -50 0 50 100

0.25

0.75

IQR2

IQR1

1

21100IQRIQRIQR

% Reduction of IQR =