10th

10th IFAC
IFAC Symposium
Symposium on on Biological
Biological and
and Medical
Medical Systems
Systems
10th
10th IFAC
IFAC Symposium
São Paulo,
Paulo, on
on Biological
Brazil, September
Symposium September and
and Medical
3-5, 2018
2018
Biological Medical Systems
Systems
São
São Paulo, Brazil,
Brazil, September 3-5,
3-5, Available online at www.sciencedirect.com
2018
São
10th Paulo, Brazil, September
IFAC Symposium 3-5, 2018
on Biological and Medical Systems
São Paulo, Brazil, September 3-5, 2018
ScienceDirect
IFAC PapersOnLine 51-27 (2018) 186–191
Impact
Impact of Carbohydrate Counting Errors
Impact of of Carbohydrate
Carbohydrate CountingCounting Errors
Errors
on
on Glycemic
Impact
Glycemic Control
of Carbohydrate
Control in
in Type
Counting
Type 1
1 Diabetes
Errors
Diabetes
on Glycemic Control in Type 1 Diabetes
onFlorian
Glycemic Control in Type
Reiterer ∗∗ Guido Freckmann ∗∗
1 Diabetes ∗
∗∗ Luigi del Re ∗
Florian
Florian Reiterer ∗∗∗ Guido Freckmann ∗∗ Luigi del Re ∗∗∗
Florian ReitererReiterer Guido Guido Freckmann
Freckmann ∗∗ ∗∗ Luigi
Luigi del del Re Re
∗ ∗∗ ∗
∗ Institute for Design and Control of Mechatronical Systems, Re
Florian Reiterer Guido Freckmann Luigi del
∗
∗ Institute for Design and Control of Mechatronical Systems, Johannes
Johannes
∗ Institute
∗ Institute for Design
for Design Linz,
Kepler University and Control
and Control
Austria of Mechatronical
of(email:
Mechatronical Systems, Johannes
Systems, Johannes
florian.reiterer@jku.at).
∗ Kepler
Kepler University
University Linz,
Linz, Austria
Austria (email:
(email: florian.reiterer@jku.at).
florian.reiterer@jku.at).
Institute
Kepler∗∗ ∗∗ for Design
University
Institut für and
Linz, Control
Austria of Mechatronical
(email:
∗∗ Institut für Diabetes-Technologie, Forschungs- und
Diabetes-Technologie, Systems, Johannes
florian.reiterer@jku.at).
Forschungs-
∗∗ Institut für Diabetes-Technologie, Forschungs- und
und
Kepler ∗∗University
Institut
Entwicklungsgesellschaft für Linz, Austria (email:
Diabetes-Technologie,
mbH, University florian.reiterer@jku.at).
Forschungs-
of Ulm, und
Germany
Entwicklungsgesellschaft
Entwicklungsgesellschaft
∗∗ mbH, University
mbH, University
University of Ulm,
of Ulm, Germany
Ulm, Germany
Germany
Institut für Diabetes-Technologie,
Entwicklungsgesellschaft mbH, Forschungs-
of und
Entwicklungsgesellschaft mbH, University of Ulm, Germany
Abstract:
Abstract: Patients
Patients with
with type
type 1
11 diabetes
diabetes mellitus
mellitus (T1DM)
(T1DM) typically
typically determine
determine their
their bolus
bolus insulin
insulin
Abstract:
Abstract:
needs based Patients
Patients
on methods with
with type
type
from 1 diabetes
diabetes
Advanced mellitus
mellitus
Carbohydrate (T1DM)
(T1DM) typically
typically
Counting determine
determine
(ACC). In ACCtheir
theirthebolus
bolus insulin
insulin
amount of
needs
needs based
based on
on methods
methods from
from Advanced
Advanced Carbohydrate
Carbohydrate Counting
Counting (ACC).
(ACC). In
In ACC
ACC the
the amount
amount of
of
Abstract:
required
needs based Patients
boluson insulin
methods with is type Advanced
assumed
from 1 diabetes
to be mellitusproportional
directly
Carbohydrate (T1DM) typically
Counting to the determine
carbohydrate
(ACC). In ACCtheirthebolus
content insulin
amountof the
of
required
required bolus
bolus insulin
insulin is
is assumed
assumed to
to be
be directly
directly proportional
proportional to
to the
the carbohydrate
carbohydrate content
content of
of the
the
needs based
required
ingested bolus
meal. onIt methods
insulin
is well is from Advanced
assumed
known that to be
many Carbohydrate
directly
T1DM proportional
patients Counting
have to (ACC).
the In
carbohydrate
difficulties to ACC the amount
content
accurately of
estimate of
the
ingested
ingested meal.
meal. It is well known that many T1DM patients have difficulties to accurately estimate
required
ingested
meal bolus It
meal.
carbohydrates. is
insulin
It is well
well isknown
assumed
known
Though that
that
these tomany
many
estimatesT1DM
be directly
T1DM are patients
proportional
patients
used forhave
have todifficulties
the carbohydrate
difficulties
calculating the to
to accurately
content
accurately
meal bolus estimate
of the
estimate
amount,
meal
meal carbohydrates.
carbohydrates. Though
Though these
these estimates
estimates are
are used
used for
for calculating
calculating the
the meal bolus amount,
ingested
meal
there
there is a
is ameal.
carbohydrates.
scarcity
scarcity
It is of
well
of data
data
known
Though on how
on
thatestimation
these
how many
estimates
estimation
T1DM arepatients
errors
errors used forhave
affect
affect
difficulties
calculating
glycemic
glycemic thetomeal
control.
control. The bolus
accurately
meal
The bolus
current
current
amount,
estimate
amount,
paper
paper
there
there
analyzes is
is a
a scarcity
meal carbohydrates.
scarcity
the effect of
of
of data
Though
data
carb on
on how
how
counting estimation
theseestimation
estimates
errors on errors
are used
errors
glycemic affect
affect glycemic
for glycemic
calculating
outcomes control.
the
control.
during The
meal
The current
bolus
current
basal-bolus-therapy paper
amount,
paper in
analyzes
analyzes the
the effect
effect of
of carb
carb counting
counting errors
errors on
on glycemic
glycemic outcomes
outcomes during
during basal-bolus-therapy
basal-bolus-therapy in
in
athere
analyzes is athe
simulation scarcity
effect
study of
of data
carb
using on how estimation
counting
so-called errors
Deviation on errors
glycemic
Analyses. affect glycemic
outcomes
Furthermore, control.
during The current
basal-bolus-therapy
the effect of paper
inaccurate in
aa simulation
simulation study
study using
using so-called
so-called Deviation
Deviation Analyses.
Analyses. Furthermore,
Furthermore, the
the effect
effect of
of inaccurate
inaccurate
analyzes
a simulation
estimates the
on effect
study
the of
settingscarb
using ofcounting
so-called
the insulin errors
Deviation on
therapy glycemic
Analyses.
is studied outcomes
Furthermore,
by means during
of basal-bolus-therapy
the
the effect
previously of inaccurate
published in
estimates
estimates on
on the
the settings
settings of
of the
the insulin
insulin therapy
therapy is
is studied
studied by
by means
means of
of the
the previously
previously published
published
a simulation
estimates
Adaptive Bolus on study
the
Bolus Calculator using
settings
Calculator (ABC) so-called
of the insulinDeviation
(ABC) algorithm. therapy
algorithm. It Analyses.
is
It is studied
is found Furthermore,
found thatby means
that whereas of the
the
whereas random effect
previously
random carb of inaccurate
published
carb counting
counting
Adaptive
Adaptive
estimates Bolus
Adaptive
inaccuracies Bolusthe Calculator
on indeed settings
Calculator
do leadof (ABC)
the
(ABC)
to an algorithm.
insulin therapy
algorithm.
inferior It
Itis is
glycemic found
isstudied
found
control, that
by means
that whereas
of the
whereas
systematic random
random
biases in carb
previously
carb
the counting
published
counting
estimates
inaccuracies
inaccuracies indeed
indeed do
do lead
lead to
to an
an inferior
inferior glycemic
glycemic control,
control, systematic
systematic biases
biases in
in the
the estimates
estimates
Adaptive
inaccuracies
are expected Bolusindeed
to Calculator
hardlydo lead
affect (ABC)
tothean algorithm.
inferior
results since It is found
glycemic
these control,
are that
usually whereas
systematic
implicitly random
biases in
accountedcarb
the counting
estimates
for
are
are expected
expected to
to hardly
hardly affect
affect the results since these are usually implicitly accounted for in
in the
the
inaccuracies
are
therapyexpected indeed
to
settings. hardlydo leadaffect tothe
theanresults
inferiorsince
results since these
glycemic
these are
are usually
control,
usually implicitly
systematic
implicitly accounted
biases in the for
accounted in
estimates
for in the
the
therapy
therapy settings.
settings.
are expected
therapy to hardly affect the results since these are usually implicitly accounted for in the
settings.
© 2018, IFAC
therapy (International Federation of Automatic Control) Hosting by Elsevier Ltd. All rights reserved.
settings.
Keywords:
Keywords: Diabetes
Diabetes management, system identification, bolus calculator, type 1 diabetes,
Keywords: control.
Keywords:
metabolic Diabetes management,
Diabetes management, system
management, system identification,
system identification, bolus
identification, bolus calculator,
bolus calculator, type
calculator, type 111 diabetes,
type diabetes,
diabetes,
metabolic
metabolic control.
control.
Keywords: control.
metabolic Diabetes management, system identification, bolus calculator, type 1 diabetes,
metabolic 1. control.
1. INTRODUCTION
1. INTRODUCTION for calculating
for calculating the the bolus
bolus needsneeds are are the
the proportionality
proportionality
1. INTRODUCTION
INTRODUCTION for
for
factors
factors
calculating
calculating
CIR,
CIR, the
the
the
the bolus
bolus needsneeds are are the
carbohydrate-to-insulin-ratio,
carbohydrate-to-insulin-ratio, the proportionality
proportionality
and
and ISF,
ISF,
1. 1INTRODUCTION factors
for
factors
the CIR,
calculating
CIR, the
the thecarbohydrate-to-insulin-ratio,
bolus needs are
carbohydrate-to-insulin-ratio,
insulin-sensitivity-factor. CIR and
the proportionality
represents the and ISF,
ISF,
amount
Patients
Patients with
with type
type 1 diabetes
diabetes mellitus
mellitus (T1DM)
(T1DM) need
need to
to the insulin-sensitivity-factor. CIR represents the amount
Patients with type 1 diabetes mellitus (T1DM) need to the
factors
the
of ainsulin-sensitivity-factor.
CIR,
meal’s the CIR represents
carbohydrate-to-insulin-ratio,
insulin-sensitivity-factor.
carbohydrates CIR
(in represents
grams) whose the
the amount
and ISF,
amount
effect
Patients
supply
supply their
supply
with
their
their body type
body
body with 1
with diabetes
insulin
with insulin
insulin frommellitus
from
from external (T1DM)
external
external sources need
sources
sources in to
in
in of of aa meal’s
meal’s carbohydrates
carbohydrates (in (in grams)
grams) whosewhose effecteffect isis
is
Patients
supply
order to with
their
manage type
body 1
with
their diabetes
insulin
blood mellitus
from
glucose (T1DM)
external
(BG) need
sources
concentration to
in the
of ainsulin-sensitivity-factor.
meal’s
counteracted carbohydrates
per injected insulinCIR
(in represents
grams)
unit (IU) whose
of the
bolus amount
effect
insulin,is
order to
order to manage
manage their their blood
blood glucose
glucose (BG) concentration counteracted
(BG) concentration counteracted
of a meal’s
per
per injected
injected
carbohydrates
insulin
insulin unit
unit
(inmany
(IU)
(IU)
grams)
of
of
whose
bolus
bolus insulin,
insulin,
effect is
supply
order
and totheir
manage
mitigate body
the withblood
their
long–term insulin from of
glucose
effects external
(BG)a sources in-
concentration
chronically in counteracted
whereas ISF per injected
describes by insulin
how unit (IU)
mg/dl of bolus
the BGinsulin,
level
and mitigate
and mitigate the the long–term
long–term effects effects of of aa chronically
chronically in- in- whereas
whereas
counteracted
ISF
ISF describes
describes
per injected
by
by how
how
insulin
many
many mg/dl
mg/dl
unit (IU)
the
the
of bolus
BG
BG level
level
insulin,
ordermitigate
and
creased toBGmanage the
level. their blood
long–term
Most patients glucose
effects
apply (BG)
ofthea concentration
chronically
so-called in-
basal- whereas
will decreaseISF describes
per injected by how
IU. many mg/dl the BG level
creased BG
creased BG level. Most Most patients
patients apply apply the so-calledso-called basal- basal- will will decrease
decrease per
per injected
injected IU.
IU.
creased BG level.
and mitigate
bolus-therapy
bolus-therapy
the
level. long–term
Most
consisting
consisting patients
of
of a
a applyofthe
effects
combination
combination thea so-called
chronically
of
of basal
basal
in- will
basal-
insulin
insulin
whereasdecreaseISF describes
per injected by IU.how many mg/dl the BG level
bolus-therapy
creased BG consisting
level. Most of a
patients combination
apply the of basal
so-called insulin
basal- The
will
The quality
decrease
quality of
ofperthe
the BG
injected
BG control
IU.
control with
with ACC
ACC is
is directly
directly linked
linked
bolus-therapy
and bolus
and bolus
bolus insulin. consisting
insulin.
insulin. Since Since
Since bolusof
bolusa combination
insulin
bolus insulin
insulin (i.e. (i.e. of
(i.e. thethe basal insulin
fast-acting
fast-acting The
the fast-acting The quality
quality of
of the
the BG
BG control
control with
with ACC
ACC is
is directly
directly linked
linked
and
bolus-therapy consisting of counteract
a combination of basal insulin to
to the
the ability
ability of
of a
a patient
patient to
to correctly
correctly estimate
estimate the
the carbo-
carbo-
and bolus
insulin
insulin insulin.
injected
injected Since
mainly
mainly bolus
to
to insulin
counteract (i.e.
the
the the
effect
effect fast-acting
of
of meals
meals to
The
to the
the ability
quality
ability of of
ofthea
a patient
BG
patient to
control
to correctly
with
correctly ACCestimate
is
estimate the
directly
the carbo-
linked
carbo-
insulin
andBG) injected
bolus insulin. mainly
Since to to counteract
bolus insulin the
(i.e. effect
the of meals
fast-acting hydrate
hydrate amountamount
amount of of meals
of meals
meals to be
to be ingested.
be ingested.
ingested. It It is
It is well
is well known
well known
known
insulin
on
on BG) injected
makes
makes mainly
up
up roughly
roughly counteract
half
half of
of the
the the effect
daily
daily insulin
insulin of needs,
meals hydrate
needs, to the
hydrate ability
amount of a
ofpatient
meals to correctly
be ingested.estimate
It is the
well carbo-
known
on BG) makes up roughly to half of that many T1DM patients have difficulties to correctly
insulin
on
andBG)
and injected
since
sincemakes
the up
the mainly
severe
severeroughly
health
health half of the
counteract
risks
risks the of daily
the
of daily
insulin
effect
insulin
hypoglycemia
hypoglycemia
of needs,
meals
needs,
and
and that
that many
hydrate
that many
many
T1DM
T1DM
amount
T1DM
patients
patients
of meals
patients
have
have
to be
have
difficulties
difficulties
ingested.
to correctly
It isato
difficulties correctly
well
to known
correctly
and
on since
BG) the
makes severe
up health
roughly half risks
of the of hypoglycemia
daily insulin and
needs, estimate
estimate meal
meal carbohydrates.
carbohydrates. There
There exist
exist a variety
variety of
of
and since
hyperglycemia the
hyperglycemia would severe
would
would arise health
arise from
arise from risks
a
from aa poor poor of hypoglycemia
dosing,
poor dosing,
dosing, it it is
it is and
crucial
is crucial
crucial estimateestimate
that many meal
T1DM carbohydrates.
patients haveThere exist
difficulties atovariety
correctlyof
hyperglycemia
andT1DM
since patients
the would
severe health risks of dosing,
hypoglycemia and scientific publications
meal
scientific publications
publications on on
carbohydrates.
on thethe topic
the topicTherethat
topic that have
exist
that have ainvestigated
variety
have investigated
investigated of
hyperglycemia
for
for T1DM patients to
to arise
have
have from
a
a way
way a to
topoorreliably
reliably it
determine
determineis crucial
the
the scientific
estimate
scientific meal carbohydrates.
publications on the There
topic that exist
have a variety
investigated of
for T1DM
hyperglycemia patientswould to have a way to reliably determine the size and
size and
and (to(to a lesser
(to aa lesser extent)
lesser extent) effect
extent) effect
effect ofof carbohydrate
of carbohydrate
carbohydrate countingcounting
counting
for T1DM
correct
correct patients
amount
amount of
of to arise
have from
required
required wayato
abolus
bolus
poor
insulin.
dosing,
reliably
insulin. Among
Among
it ispatients
determine crucial
the size
patients scientific
size and publications
(to a lesser on
extent) the topic
effect of that have
carbohydrate investigated
counting
correct
for T1DM amount
patients ofbyrequired
tofar
have abolus
way toinsulin.
reliably Amongdetermine patients
the errors:
errors:
correct
with
with T1DM amount
T1DM
T1DM theofby
the byrequired most
far most
most bolus insulin.
widespread
widespread Among
way
way of patients
doing
of doing
doing so
so errors:
size and (to a lesser extent) effect of carbohydrate counting
errors:
with
correct
with
is by amount
T1DM
means the
the
of of
by
advanced far
required
far most widespread
bolus insulin.
widespread
carbohydrate way
Among
way
counting of
of patients
doing
(ACC).In so
so In Brazeau
Brazeau et et al.al. (2013)
(2013) the the systematic
systematic and and random
random
is by
by means
means of of advanced
advanced carbohydrate
carbohydrate counting counting (ACC).In (ACC).In In errors:
is
with
is
ACCby T1DM
means
the theadvanced
of
required by far most
bolus widespread
carbohydrate
insulin amount way of(ACC).In
counting
is computed doing
basedso In In Brazeau
Brazeauerrors
estimation et
et al. (2013)
al.when
(2013) the
the systematic
calculating systematic
the and
and random
carbohydrates random of
ACC
ACC the
the required
required bolus
bolus insulin
insulin amount
amount is
is computed
computed based
based estimation
estimation errors
errors when
when calculating
calculating the
the carbohydrates
carbohydrates of
of
is by
ACC
on themeans
the of advanced
required
carbohydrate bolus carbohydrate
insulin
(CHO) amount
amount of counting
is
the computed
ingested (ACC).In
based
meal, In
meals Brazeau
estimation have et al.
errors
been (2013)
when
investigated the
calculating
in systematic
an the
adult and random
carbohydrates
population of
with
on
on the
the carbohydrate
carbohydrate (CHO)
(CHO) amount
amount of
of the
the ingested
ingested meal,
meal, meals
meals have
have been
been investigated
investigated in
in an
an adult
adult population
population with
with
ACC
on thethe required
carbohydrate bolus insulin
(CHO) amount
amount of is
the computed
ingested based
meal, estimation
meals
T1DM. have
It errors
been
was found when
investigated
that calculating
in in
averagean the
adult
an carbohydrates
error population
of 15.4 ± of
with
7.8
usually using
usually using
using the the following
the following
following simplesimple
simple formulaformula
formula (see (see
(see e.g.e.g. Walsh
e.g. Walsh
Walsh T1DM. T1DM. It It was
was found
found thatthat in in average
average an an error
error of of 15.4
15.4 ± 7.8 g
± 7.8 g
usually
on the
usually carbohydrate
using
and Roberts
and the
Roberts (2013)):
(2013)): (CHO)
following amount
simple of
formula the ingested
(see e.g. meal,
Walsh meals
T1DM.
or 20.9
or 20.9 ±have
It
± 9.7been
was
9.7 % foundinvestigated
% was that
was made in
made for in
averagean
for each adult
an error
each meal population
of
meal (with 15.4 averageg
±
(with average with
7.8 g
and
and Roberts
usually
Roberts (2013)):
using(2013)):
the following simple formula (see e.g. Walsh or
T1DM.
or
meal 20.9
20.9 CHO ±
It
± 9.7
was
9.7 %
found
%
contents was
was made
that
made
of in
72.4 for
average
for
± each
each
34.7 an meal
error
meal
g). (with
of
(with
Usually 15.4 average
± 7.8
average
patients g
CHO
CHO + BG BG
BGpre −
− BG
BG target meal
meal CHO
CHO contents
contents of
of 72.4
72.4 ±
± 34.7
34.7 g).
g). Usually
Usually patients
patients
and Roberts BI =
BI = CIR + CHO
(2013)):
CHO + BG pre
pre −
− BG
BG target
target −
− IOBIOB
IOB (1)
(1) had or
meal
had 20.9
a CHO ± 9.7 %
contents
pronounced was made
of 72.4
negative for
± each
34.7
estimation meal
g). (with
Usually
bias, with average
patients
63 %
BI
BI =
pre ISF target target − (1) had aa pronounced
pronounced negative estimation bias, with 63 %
= CHOCIR + BGpre
CIR pre −
ISF
ISFBGtarget − IOB (1) meal had
of the aCHO contentsnegative
pronounced
448 analyzed of 72.4being
negative
meals estimation
± 34.7
estimation g). bias,
Usually
bias,
underestimated. with
with It63
patients%
63was
%
In (1) BI BI = CIR
corresponds to the ISF
bolus insulin
+to the bolus insulin−needs, needs,
IOB CHO(1) CHO is of
of the
the 448
448 analyzed
analyzed meals
meals being
being underestimated.
underestimated. It
It was
was
In
In (1)
(1) BI
BI corresponds
corresponds to the bolus insulin needs, CHO is
is had
of the a
furthermore pronounced
448 analyzed
found negative
meals
that larger estimation
being
carb bias,
underestimated.
counting with It63 %
was
inaccuracies
In
the (1) BI corresponds
carbohydrate CIR contentto the of ISF
bolus
the meal,insulinBG needs,
pre is CHO
the pre- furthermore
is furthermore found
found that
that larger
larger carb
carb counting
counting inaccuracies
inaccuracies
the carbohydrate
the(1)
carbohydrate content
content of the
of the
the meal,
meal, BG
BGneeds,
pre is the
is the
the pre-
pre- of
were the
furthermore 448 analyzed
associated found with meals
that
lower largerbeing
time carb
in underestimated.
counting
target range It was
inaccuracies
and higher
In
the BI BG,
corresponds
carbohydrate contenttodescribes
the
of bolus meal,insulinBG is CHO is were associated with lower time in target range and higher
for pre-
prandial pre
prandial
prandial BG, BG
BG, BGtarget
BG target describes
describes
the
the
the
target
target
target
pre
pre value
value
value
for
for
the
the were
the were
glycemic associated
furthermore
associated found with
withthat
variability. lower
lower time
larger in
in target
timecarb target range
counting and
and higher
rangeinaccuracieshigher
the carbohydrate
prandial BG,
post-prandial BG
BG content
target
and
target IOB of
describes the
stands meal,
the
for BG
target is
value
insulin-on-board,
pre the
for pre-
the
i.e. glycemic
glycemic variability.
variability.
post-prandial
post-prandial BG
BG and
target
and IOB
IOB stands
stands for
for insulin-on-board,
insulin-on-board, i.e.
i.e. were
glycemic associated with lower time in target range and higher
variability.
prandial BG,
post-prandial
the bolus insulin BGfrom
BG target describes
and previous
IOB stands the
injections target
for insulin-on-board,
that value
is stillfor the
i.e. In
active Deeb et al. (2017) the carb counting errors in a T1DM
the
the bolus
bolus insulin
insulin from previous injections that is still active glycemic
In Deeb etvariability.
al. (2017) the carb counting errors in a T1DM
post-prandial
the
in bolus
the insulin
body. BGfrom
The first previous
and term
from IOB stands
previous in injections
(1) forused
injections
is that
for is
insulin-on-board,
that is still
still
counteractingactive
i.e. In
active In Deeb
Deeb
population et
et al.
al.
of (2017)
(2017)
children the
the
and carb
carb counting
counting
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errors
have beenin
in a
a T1DM
T1DM
studied.
in
in the
the body.
body. The
The first
first term
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in (1)
(1) is
is used
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for counteracting
counteracting population
population of
of children
children and
and adolescents
adolescents have
have been
been studied.
studied.
the
in
the bolus
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body. of Thethe from
first
meal previous
term in
intake injections
(1) on is used
the that
for
BG, is still
counteracting
whereas active
the In Deeb
population
It was et
foundal.
of (2017)
children
that forthe
and
67 carb counting
adolescents
% of meals errors
have
the beenin a T1DM
studied.
carbohydrate
the effect
the effect ofof thethe meal
meal intake
intake on on the BG, BG, whereaswhereas the the It It was
was found
found that that for for 67 67 % % ofof meals
meals thethe carbohydrate
carbohydrate
in
thethe
second body.
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term of The
is the
usedfirst
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intake
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the been studied.
carbohydrate
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second termofis
the effect used
is the
usedmealfor
for BG
BG corrections.
intake on theCrucial
corrections. BG, whereas
Crucial parameters
parameters the It was found that for 67 % of meals the carbohydrate
second term is used for BG corrections.
2405-8963 © 2018, IFAC (International Federation of Automatic Crucial parameters Control) Hosting by Elsevier Ltd. All rights reserved.
Copyright
Copyright © 2018 IFAC 186
Peer review©under
Copyright 2018 responsibility
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of International Federation of Automatic
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2018 IFAC
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IFAC BMS 2018
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estimates were within ±20 % of the real amount. It
was furthermore found that patients were more likely to
underestimate the carbohydrate content of meals than to
overestimate it. For 36 % of meals a carbohydrate amount
was estimated that was more than 20 % lower than the
true amount, whereas for only 8 % of meals the estimated
carbohydrate amount was more than 20 % higher than the
true amount. Additionally, it was found in the study that
underestimated meals tend to lead to above-target glucose
values (in 87 % of those cases), whereas overestimated
meals tend to give too low postprandial glucose values (in
63 % of those cases). Having a good carbohydrate estimate
(error smaller 20 %) led to postprandial glucose values in
the target range in 55 % of the cases.
In Smart et al. (2010) the carb counting errors have been
investigated for children with T1DM, as well as for their
caregivers. In average the children were able to estimate
the carbohydrate content of meals relatively accurately,
73 % of the estimates were within 10 to 15 g of the real
carbohydrate quantity. Additionally, it was found that
patients tend to overestimate carbs in small meals and
underestimate them in big meals.
Regarding the effect of carbohydrate counting errors on
the quality of glycemic control it was found in Smart
et al. (2009) that errors of within ±10 g of the real
carbohydrate quantity do not have a significant effect
on the postprandial glucose levels or the glucose area
under the curve (AUC), whereas in Smart et al. (2012)
it is stated that carbohydrate counting errors of ±20 g
lead to a significant deterioration in glycemic control. In
Smart et al. (2012) an insulin bolus calculated for 60 g
of carbohydrates was applied for meals containing 40,
50, 60, 70 and 80 g of carbohydrates. These tests led to
postprandial hypoglycemia for the 40 g meals, as well as
to postprandial hyperglycemia for 80 g meals, but resulted
in no statistically significant differences among the other
meal responses.
Additionally, there are several in silico studies in which the
performance of a specific (often closed-loop) insulin dosing
algorithm is studied, considering carbohydrate counting
errors as one of the disturbing factors. However, there are
only few publications that explicitly analyze the impact of
carbohydrate counting errors during standard basal-bolus-
therapy.
2. METHODS
In the current work the effect of carb counting errors on
glycemic control during basal-bolus-therapy is studied by
means of so-called Deviation Analysis calculations (Reit-
erer et al. (2016)). These combine real recorded clinical
data with a simulation model of the glucose metabolism
and allow to estimate retrospectively how a difference
in insulin dosing (resulting from a specific carb counting
error) would have affected glycemic control. Furthermore,
it is analyzed how inaccuracies in the carbohydrate es-
timates affect the insulin therapy settings. This is done
using the previously published Adaptive Bolus Calculator
(ABC) algorithm (Reiterer et al. (2015a,b)) which can
retrospectively identify estimates for CIR and ISF from
recorded data.
187
187
Fig. 1. Workflow for assessing a control strategy in Devia-
tion Analyses
2.1 Deviation Analysis
To estimate the effect of a newly proposed insulin dos-
ing algorithm so called Deviation Analyses can be used.
The basic workflow for performing Deviation Analyses is
displayed in Fig. 1. The rough idea is to assume a model
of insulin action, a transfer function model G2 (s) in the
case of Fig. 1, and then subtract the effect of the measured
insulin (Ins) and add the effect of the proposed insulin dos-
ing (Insmod ) to measured continuous glucose monitoring
(CGM) traces. The estimated effect of a new insulin dosing
strategy is thus extrapolated using the real clinical data
as a baseline. Several methods for performing Deviation
Analyses have been proposed over the last couple of years
which are all very similar, but differ in the model that is
used for describing insulin action (see Reiterer et al. (2016)
for an overview). For the current paper the slightly more
complex, nonlinear Deviation Analysis approach presented
in Reiterer et al. (2017) is used for the performance assess-
ment.
2.2 Adaptive Bolus Calculator (ABC)
In Reiterer et al. (2015a,b) the so-called ABC method
is proposed to identify diurnal profiles of insulin action
from standard diabetes data, i.e. CGM data together with
recordings about meal carbohydrates and bolus insulin
injections. In order to do so, the control oriented model
from Kirchsteiger et al. (2014) is used to describe the
effect of carbohydrates and bolus insulin on the glucose
concentration:
K1 K2
IG(s)= ·Carbs(s) + ·Ins(s) (2)
(1+s·T1 )2 ·s (1+s·T2 )2 ·s
In (2) IG(s) is the glucose level (measured by the CGM),
Carbs(s) are the meal carbohydrates and Ins(s) the bolus
injections, all in the Laplace domain. The model param-
eters K1 and K2 are not assumed constant, but for each
meal intake and insulin injection a specific value is cal-
culated assuming a second order polynomial function of
daytime:
K1,i = K11 + K12 ·ti + K13 ·t2i (3a)
K2,j = K21 + K22 ·tj + K23 ·t2j (3b)
The specific K1 and K2 is calculated using the time
of the meal (ti ) and insulin injection (tj ). A separate
model is fitted to the data of each day considered in the
system identification, so for each day 8 parameter values
are determined (K11 , K12 , K13 , K21 , K22 , K23 , T1 , T2 ).
Additional constraints restrict the parameter space to a
physiologically meaningful range and limit the level of
intrapatient variability.
The settings for a bolus calculator (BC) can be obtained
directly using the parameters of the model fitted to data:
IFAC BMS 2018
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188

K2 / K1 [g CHO / IU]

150
15

Estimated Carbohydrate Amount [g]

125
10

100
5
07:00 09:00 11:00 13:00 15:00 17:00 19:00
Daytime
50 75
K2 [mg/dl/IU]

40
50
30

20 25
07:00 09:00 11:00 13:00 15:00 17:00 19:00
1 1
Fig. 2. ABC method for system identification - Illustrative 0
FCIR(x) [−]

FISF(x) [−]

0 25 50 75 100 125 150

results for CIR and ISF 0.5
profiles as a function of Calculated Carbohydrate Amount [g]
0.5
daytime (P0037)
0 0
Fig. 3. Estimated vs calculated carbohydrate amount for
the identified
5 −K 102 /K1 values
15 correspond
20 30to CIR, 40 whereas
50 the data from Zschornack et al. (2013).
K2 / K1 [g CHO / IU] K [mg/dl/IU]
−K2 has the same meaning as ISF. As 2a results of the
2.5
system identification a patient-specific diurnal profile for Data
CIR (i.e. −K2 /K1 ) and ISF (i.e. −K2 ) is obtained for each Bias (Lin.Reg,)
Bias +/− Bound (σest.)
day of the system identification. An illustrative result for 2 Norm. Dist. (fitted)
the ABC method for one patient and five days of data
is shown in Fig. 2: The top panel shows the identified
profiles for CIR vs. daytime, whereas the bottom panel 1.5

displays the corresponding profiles for ISF. Each blue PDF [−]

line corresponds to one day of the system identification, 1

whereas the bold black lines indicate the average profile
(average over all blue lines).
0.5

3. CLINICAL DATA
For the current work data from a recent clinical trial per-
formed at the Institute for Diabetes Technology, Germany
is used (Zschornack et al. (2013)). In this clinical trial 37
subjects suffering from T1DM spent seven days hospital-
ized. During this time period each of them wore either
two (28 individuals) or four (9 individuals) CGM systems
in parallel. During the study the patients calculated their
bolus needs based on the estimated carbohydrate content
of the meals (estimated by the patients themselves) using
ACC and pre-adjusted patient- and mealtime-specific CIR
and ISF values. Seen that the general BG management of
the individuals in the study is acceptable (Patient HbA1C:
7.8 +/- 1.2 %), it can be assumed that these patients were
in general using suitable basal rates and well adjusted CIR
and ISF settings. However, it should also be mentioned
that no systematic verification of the patients’ therapy
settings has been performed during the trial.
The estimated carbohydrate contents of all meals during
the trial have been recorded together with the CGM traces
and the injected/infused insulin quantities. Additionally,
most meals have been analyzed by a trained dietitian who
retrospectively calculated the composition of those meals
(carbohydrate, fat and protein content). The correspond-
ing values for the calculated carbohydrate contents of the
meals, which are deemed much more accurate than the
estimates by the patients, are used for the retrospective
analyses presented in this paper. In total detailed data for
897 meals are available. The average carbohydrate content
of those meals was 54.9 ± 27.6 g.
In order to gain an insight into the extent of carb counting
errors in this trial a detailed data analysis is performed
0
0 0.5 1 1.5 2
Estimated Divided by Calculated Carbohydrate Amount [−]
Fig. 4. Estimated divided by calculated carbohydrate
amount: distribution and fit.
similar to the ones from the literature presented in Sec. 1.
In Fig. 3 the calculated carbohydrate content (as from the
dietitian) is plotted against the estimated carbohydrate
content (as estimated by the patients during the trial)
for all meals combined. It can be seen that the difference
between those two quantities is bigger for bigger meals.
Furthermore, based on a linear regression of the data it
can be seen that there is a tendency to underestimating
the carbohydrate content of meals as is clearly visible from
the red line. In green, additionally the boundaries of a
symmetrical tolerance interval are shown that contains
roughly 68.3 % of all points. These boundaries are at:
carbsest. = (0.92 ± 0.19) · carbscalc. (4)
In Fig. 4 the comparison between estimated and calcu-
lated carbohydrate content is plotted as probability den-
sity function (PDF) where the quantity on the x-axis
corresponds to the estimated divided by the calculated
carbohydrate amount. Again, the negative estimation bias
becomes obvious (peak of the distribution at <1.0). Ad-
ditionally, it can be seen that this distribution can be
approximated reasonably well by a normal distribution
which is plotted in magenta. Additionally the results of
the linear regression as from Fig. 3 are shown (red: mean,
green: mean ± 1σ).
In Fig. 5 the error in the estimated carbohydrate amount
in g CHO is plotted as a function of the calculated

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40 300

250

Error in Estimated Carb Amount [%]

Error in Estimated Carb Amount [g]

20
200

150
0
100

−20 50

0
−40
−50

−60 −100
0 25 50 75 100 125 150 0 25 50 75 100 125 150
Calculated Carbohydrate Amount [g] Calculated Carbohydrate Amount [g]

Fig. 5. Carb counting error in g CHO vs calculated Fig. 6. Carb counting error in % vs calculated carbohy-
carbohydrate amount. drate amount.
carbohydrate amount. It can be seen that the tendency carbohydrate amounts are missing for many of the meals
to underestimating the carbohydrate content is especially on that day. In total 4 scenarios are analyzed:
pronounced for large meals, whereas for small meals there • Using the calculated carbohydrate content for iden-
seems to be even a slight trend to overestimating the carb tifying the CIR and ISF settings with the ABC ap-
content. This is quite in line with the findings from Smart proach, as well as for calculating the bolus needs on
et al. (2010). As in Smart et al. (2010) the data can day 6 according to (1).
be fitted with a quadratic model. However, contrary to • Using the calculated carbohydrate content for iden-
that publication no statistically significant axis intercept tifying the CIR and ISF settings with the ABC ap-
different from zero is found. Analyzing the data displayed proach, but the estimated carbohydrates for calculat-
in Fig. 5 it is found that the average absolute estimation ing the bolus needs on day 6. This scenario would
error in the data corresponds to 8.78 ± 8.39 g which is correspond to having the BC settings adjusted under
significantly lower than the errors listed e.g. in Brazeau controlled conditions (e.g. in a hospital).
et al. (2013), indicating that the study population in the • Using the estimated carbohydrate content for iden-
clinical trial considered here is rather well educated in tifying the CIR and ISF settings with the ABC ap-
carbohydrate counting. 66.4 % of the estimates are within proach, but the calculated carbohydrate amount for
± 10 g of the calculated carb amounts, whereas 90.6 % are calculating the bolus needs on day 6. This scenario
within ± 20 g, which is comparable to the findings in Smart would correspond to having the BC settings tested
et al. (2010). 61.7 % of the meals were underestimated by under controlled conditions.
the patients, i.e. the estimated carbohydrate content was • Using the estimated carbohydrate content for both,
lower than the calculated one. identifying the CIR and ISF settings with the ABC
In Fig. 6 the same analysis is performed for the error in the approach and calculating the bolus needs on day 6.
estimated carbohydrate amount in %. This plot looks also This scenario would correspond to patients using the
rather comparable to an analogous one in Smart et al. ABC method in an at-home setting for both, auto-
(2010). It is found that the average absolute estimation matically adjusting their BC settings and calculating
error corresponds to 21.2 ± 71.5 %. The mean value is their bolus insulin needs.
comparable to the results of Brazeau et al. (2013), but Additionally, the results are compared the scenario of
the standard deviation is much higher. This, however, can the patients using the same CIR and ISF settings that
easily be explained by the very high estimation errors for they actually used using during the trial for calculating
small meals. If only meals with a carbohydrate content their bolus insulin needs (in the following referred to as
larger than 40 g are considered the average absolute standard bolus calculator settings, StdBC). These Devia-
estimation error decreases to 11.3 ± 14.7 %. 39.8 % of the tion Analysis calculations are again performed for both,
meals have an estimation error within ± 10 %, whereas calculated and estimated carbohydrate contents. As per-
66.4 % have one within ± 20 %. These numbers are in line formance measures the percentage of time in hypoglycemia
with the findings from Deeb et al. (2017). (BG < 70 mg/dl), the percentage of time in hyperglycemia
(BG > 180 mg/dl) and the following cost function V are
4. RESULTS AND DISCUSSION used:
V = thyper /ttot + W · thypo /ttot (5)
As a first analysis the effect of the carb counting errors
V is used to condense the information about glycemic con-
actually occurring during the trial on the glycemic control
trol into one single number and is defined as the weighted
are studied in Deviation Analyses. The days 2 through 5
sum (with weighting factor W) of time in hypoglycemia
of the trial are used to identify adequate CIR and ISF
(thypo ) and hyperglycemia (thyper ), both normalized by the
settings with the ABC approach, whereas day 6 was used
total time frame of the performance assessment (ttot ).
for the testing. The data from day 1 is omitted since the
recording of data just started in the middle of the day. The The results of the analysis are summarized in Tab. 1. The
same is done for the data of day 7 because the calculated table shows mean value and standard deviation for the

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190

Table 1. Effect of carbohydrate counting errors CIR/ISF from calc. carbs: thypo [%] CIR/ISF from est. carbs: thypo [%]
observed in clinical data on glycemic control

Carb Uncertainty [%]

Carb Uncertainty [%]

3 3
50 50
2 2
Dev.Anal., Dev.Anal.,
25 25
1 1
calc. carbs est. carbs
0 0 0 0
StdBC 3.3±5.5 % 3.5±5.1 % −20 −10 0 10 −20 −10 0 10
Bias in Carb Estimate [%] Bias in Carb Estimate [%]
100 · thypo /ttot ABC, case 1 1.9±3.9 % 1.9±3.8 % CIR/ISF from calc. carbs: thyper [%] CIR/ISF from est. carbs: thyper [%]

Carb Uncertainty [%]

Carb Uncertainty [%]

ABC, case 2 2.3±4.5 % 2.1±4.6 % 30 30
50 50
StdBC 23.0±17.2 % 24.3±18.0 % 28 28
25 26 25 26
100 · thyper /ttot ABC, case 1 25.7±18.0 % 26.9±18.0 %
24 24
ABC, case 2. 23.3±17.1 % 25.2±17.3 % 0 22 0 22
−20 −10 0 10 −20 −10 0 10
StdBC 0.395±0.270 0.417±0.264 Bias in Carb Estimate [%] Bias in Carb Estimate [%]

V (W=5) ABC case 1 0.352±0.220 0.363±0.236 CIR/ISF from calc. carbs: V (W=5) [%] CIR/ISF from est. carbs: V (W=5) [%]

Carb Uncertainty [%]

Carb Uncertainty [−]

40 40
ABC case 2 0.350±0.243 0.358±0.263 50
38
50
38

36 36
25 25
selected performance criteria for all 6 analyzed scenarios 34 34

as calculated from the results of all 37 patients of the 0

−20 −10 0 10
32 0
−20 −10 0 10
32

trial combined. The scenarios with CIR and ISF settings Bias in Carb Estimate [%] Bias in Carb Estimate [%]

identified with the ABC approach based on the calcu-

lated carbohydrate amount are marked as “ABC, case 1”,
whereas those with BC settings identified based on the
estimated carbohydrate amount are marked as “ABC, case
2”. The first column of results (“Dev.Anal., calc. carbs”)
corresponds to using the calculated carbohydrate amount
for computing the bolus insulin in the Deviation Analyses,
whereas the results in the second column (“Dev.Anal.,
calc. carbs”) are for the case of using the estimated carbo-
hydrate amount in the Deviation Analyses.
It is interesting to see in Tab. 1 that all of the four analyzed
scenarios with CIR and ISF values identified from data
lead to a significantly lower value of cost function V (as
from (5) with W=5, same weighting factor as in Reiterer
et al. (2016)) than the two scenarios with the StdBC
settings. This is due to the higher level of hypoglycemic for
the StdBC settings which is an indication for a suboptimal
adjustment of the clinically used CIR and ISF values. In
general it can be seen that the differences between the four
scenarios with CIR and ISF identified from data are rather
small. However, both scenarios that use the calculated
carbohydrate content for computing the bolus needs lead
to a lower value of V than the two corresponding scenarios
with estimated carbohydrate content. This is due to a
reduced time in hyperglycemia. Surprisingly, the scenario
of using the estimated carbohydrate content for identifying
the BC settings and the calculated carbs for bolus dosing
on day 6 leads to a lower value of V than the scenario
with calculated carbs for both, identifying the BC settings
and later bolus dosing. This is due to the lower time
in hyperglycemia for this scenario. As discussed earlier,
the patients tend to have a negative estimation bias,
which leads to lower values of CIR and ISF in the system
identification and afterwards to higher insulin doses when
calculating the bolus needs with the identified BC settings
and the real carbohydrate amount. This can also be seen
by the fact that this settings leads to higher values for the
time in hypoglycemia than the other three scenarios with
identified BC settings.
In order to better understand the effect of carb counting
errors on the glycemic control in ACC an additional
analysis is performed in which bias and random errors
in the carb estimates are analyzed separately. For this
Fig. 7. ABC – Effect of carb counting errors on the
glycemic control.
analysis the calculated carbohydrates are used as a basis
and are manipulated according to the following formula:
carbsest.,i = carbscalc.,i · (1 + bias + ei ) (6)
with
2
ei ∼ N (0, (uncertainty/1.96) ) (7)
So, the estimated carb content of each meal i is computed
by taking the calculated carbohydrate content, subtracting
or adding a bias (between -20 % and +10 %) and then
adding a random estimation error which is assumed to
be normally distributed with zero mean and a standard
deviation between 0 % and 30 %. In order to better un-
derstand the extent of the random errors the values of the
standard deviation are transformed to an “uncertainty”,
which corresponds to the boundaries that enclose 95 % of
the errors and can easily be calculated as 1.96 · σ. The
corresponding uncertainties are thus between 0 % and
roughly 60 %.
The basic setup of the performance assessment is chosen
as for the first set of analyses described earlier in this
section. Two scenarios are analyzed: In the first one
(from now on referred to as “case A”) the calculated
carbohydrates are used for identifying the BC settings with
the ABC approach, and the estimated carbs are used only
afterwards for calculating the bolus needs, whereas in the
second scenario (from now on referred to as “case B”)
the estimated carbohydrate amounts are used for both,
identifying the BC settings and calculating the bolus needs
afterwards.
The combined results with all combinations of bias and
uncertainty in the carbohydrate estimates are shown in
Fig. 7. The left plots show the results for case A, whereas
the right ones show the results for case B. The first row
of plots displays the percentage of time in hypoglycemia,
the center ones the percentage of time in hyperglycemia
and the bottom ones the value for cost function V with
W=5. Each point in the plot visualizes the corresponding
value of the average over all 37 patients. It is interesting
to see that for case A the time in hypoglycemia and
hyperglycemia is determined almost entirely by the bias in

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the carb estimate, whereas for case B the bias has basically
no effect on the time in hypoglycemia and hyperglycemia.
This is due to the fact that in case B the same bias is
used also in the identification step, which means that the
identified CIR and ISF values implicitly contain the same
bias which allows to compensate for it when using the
factors afterwards for glucose control. It can be assumed
that patients with well adjusted BC settings have their
estimation bias counterbalanced by their CIR and ISF.
When analyzing the effect of the random estimation errors
on the glycemic control it is evident that a higher un-
certainty in the estimated carbohydrates leads to a worse
glycemic control, both in terms of time in hypoglycemia,
as well as for time in hyperglycemia, which holds for case
A, as well as for case B.
When analyzing the values of V the results for case A
and case B look somewhat similar. For the value of V
the bias in the estimation has a smaller impact than the
uncertainty in the estimates. For case B this is expected
since the bias has basically no impact on the time in
hypoglycmia and the time in hyperglycemia. For case A
on the other hand this can be explained by the fact that
a bias will have opposing effects on time in hypoglycemia
and time in hyperglycemia. When adding up those effects
for calculating V according to (5) they counterbalance each
other to a certain degree. For the case of W=5 the cost V
is slightly more favorable for negative estimation biases
since these lead to a reduced time in hypoglycemia. For
other values of W this will of course look differently.
5. CONCLUSIONS
In the current paper the effect of carb counting errors on
glycemic outcomes during basal-bolus-therapy is analyzed
in Deviation Analysis calculations. It is found in the anal-
yses that systematic estimation biases in the carbohydrate
counting hardly affect the results since the same biases are
usually implicitly accounted for in the therapy settings
if CIR and ISF are well adjusted. Random carb count-
ing inaccuracies on the other hand do lead to a certain
deterioration of glycemic control, but ACC is relatively
robust towards this type of inaccuracies. Still, an improved
performance should be possible by decreasing the level
of random estimation errors. This could potentially be
achieved by assisting the patients in their efforts of carb
counting, e.g. using specialized software like GoCarb, a
computer vision based software that tries to estimate the
carb content in meals based on pictures taken with a
smartphone (Anthimopoulos et al. (2015)).
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