Abstract
The International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines represent a rich repository that serves as the only comprehensive set of clinical recommendations for children, adolescents, and young adults living with diabetes worldwide. This chapter builds on the 2022 ISPAD guidelines, and updates recommendations on the principles of intensive insulin regimens, including more intensive forms of multiple daily injections with new-generation faster-acting and ultra-long-acting insulins; a summary of adjunctive medications used alongside insulin treatment that includes details on pramlintide, metformin, glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RA) and sodium-glucose cotransporter inhibitors; and key considerations with regard to access to insulin and affordability to ensure that all persons with diabetes who need insulin can obtain it without financial hardship.
Journal Section:
Clinical Practice Committee Publication
References
1.
Effect of intensive diabetes treatment on the development and progression of long-term complications in adolescents with insulin-dependent diabetes mellitus: diabetes Control and complications trial. Diabetes Control and Complications Trial Research Group
.J Pediatr
. 1994
;125
(2
):177
–88
.2.
Cefalu
WT
, Rodgers
GP
. Diabetes control and complications trial/epidemiology of diabetes interventions and complications study: continuing to build on 40 years of diabetes research
. Diabetes Care
. 2024
;47
(9
):1518
–21
. 3.
Schuit
FC
, Huypens
P
, Heimberg
H
, Pipeleers
DG
. Glucose sensing in pancreatic beta-cells: a model for the study of other glucose-regulated cells in gut, pancreas, and hypothalamus
. Diabetes
. 2001
;50
(1
):1
–11
. 4.
de Beaufort
CE
, Houtzagers
CM
, Bruining
GJ
, Aarsen
RS
, den Boer
NC
, Grose
WF
, et al. Continuous subcutaneous insulin infusion (CSII) versus conventional injection therapy in newly diagnosed diabetic children: two-year follow-up of a randomized, prospective trial
. Diabet Med
. 1989
;6
(9
):766
–71
. 5.
Zaykov
AN
, Mayer
JP
, DiMarchi
RD
. Pursuit of a perfect insulin
. Nat Rev Drug Discov
. 2016
;15
(6
):425
–39
. 6.
Cengiz
E
, Xing
D
, Wong
JC
, Wolfsdorf
JI
, Haymond
MW
, Rewers
A
, et al. Severe hypoglycemia and diabetic ketoacidosis among youth with type 1 diabetes in the T1D exchange clinic registry
. Pediatr Diabetes
. 2013
;14
(6
):447
–54
. 7.
Haynes
A
, Hermann
JM
, Clapin
H
, Hofer
SE
, Karges
B
, Jones
TW
, et al. Decreasing trends in mean HbA1c are not associated with increasing rates of severe hypoglycemia in children: a longitudinal analysis of two contemporary population-based pediatric type 1 diabetes registries from Australia and Germany/Austria between 1995 and 2016
. Diabetes Care
. 2019
;42
(9
):1630
–6
. 8.
Arbelaez
AM
, Semenkovich
K
, Hershey
T
. Glycemic extremes in youth with T1DM: the structural and functional integrity of the developing brain
. Pediatr Diabetes
. 2013
;14
(8
):541
–53
. 9.
Haahr
H
, Heise
T
. Fast-acting insulin aspart: a review of its pharmacokinetic and pharmacodynamic properties and the clinical consequences
. Clin Pharmacokinet
. 2020
;59
(2
):155
–72
. 10.
Heise
T
, Stender-Petersen
K
, Hövelmann
U
, Jacobsen
JB
, Nosek
L
, Zijlstra
E
, et al. Pharmacokinetic and pharmacodynamic properties of faster-acting insulin aspart versus insulin aspart across a clinically relevant dose range in subjects with type 1 diabetes mellitus
. Clin Pharmacokinet
. 2017
;56
(6
):649
–60
. 11.
Gonzalvo
JD
, Patel
DK
, Olin
JL
. Concentrated insulins: a review and recommendations
. Fed Pract
. 2017
;34
(Suppl 8
):S38
–s43
.12.
Hirsch
IB
, Juneja
R
, Beals
JM
, Antalis
CJ
, Wright
EE
. The evolution of insulin and how it informs therapy and treatment choices
. Endocr Rev
. 2020
;41
(5
):733
–55
. 13.
Cengiz
E
. Closer to ideal insulin action: ultra fast acting insulins
. Panminerva Med
. 2013
;55
(3
):269
–75
.14.
Haahr
H
, Heise
T
. A review of the pharmacological properties of insulin degludec and their clinical relevance
. Clin Pharmacokinet
. 2014
;53
(9
):787
–800
. 15.
Lajara
R
, Cengiz
E
, Tanenberg
RJ
. The role of the new basal insulin analogs in addressing unmet clinical needs in people with type 1 and type 2 diabetes
. Curr Med Res Opin
. 2017
;33
(6
):1045
–55
. 16.
Heise
T
, Nørskov
M
, Nosek
L
, Kaplan
K
, Famulla
S
, Haahr
HL
. Insulin degludec: lower day-to-day and within-day variability in pharmacodynamic response compared with insulin glargine 300 U/mL in type 1 diabetes
. Diabetes Obes Metab
. 2017
;19
(7
):1032
–9
. 17.
Heise
T
, Kaplan
K
, Haahr
HL
. Day-to-Day and within-day variability in glucose-lowering effect between insulin degludec and insulin glargine (100 U/mL and 300 U/mL): a comparison across studies
. J Diabetes Sci Technol
. 2018
;12
(2
):356
–63
. 18.
Home
PD
. The pharmacokinetics and pharmacodynamics of rapid-acting insulin analogues and their clinical consequences
. Diabetes Obes Metab
. 2012
;14
(9
):780
–8
. 19.
Plank
J
, Wutte
A
, Brunner
G
, Siebenhofer
A
, Semlitsch
B
, Sommer
R
, et al. A direct comparison of insulin aspart and insulin lispro in patients with type 1 diabetes
. Diabetes Care
. 2002
;25
(11
):2053
–7
. 20.
Cemeroglu
AP
, Kleis
L
, Wood
A
, Parkes
C
, Wood
MA
, Davis
AT
. Comparison of the effect of insulin glulisine to insulin aspart on breakfast postprandial blood glucose levels in children with type 1 diabetes mellitus on multiple daily injections
. Endocr Pract
. 2013
;19
(4
):614
–9
. 21.
Philotheou
A
, Arslanian
S
, Blatniczky
L
, Peterkova
V
, Souhami
E
, Danne
T
. Comparable efficacy and safety of insulin glulisine and insulin lispro when given as part of a Basal-bolus insulin regimen in a 26-week trial in pediatric patients with type 1 diabetes
. Diabetes Technol Ther
. 2011
;13
(3
):327
–34
. 22.
Cengiz
E
, Bode
B
, Van Name
M
, Tamborlane
WV
. Moving toward the ideal insulin for insulin pumps
. Expert Rev Med Devices
. 2016
;13
(1
):57
–69
. 23.
Fath
M
, Danne
T
, Biester
T
, Erichsen
L
, Kordonouri
O
, Haahr
H
. Faster-acting insulin aspart provides faster onset and greater early exposure vs insulin aspart in children and adolescents with type 1 diabetes mellitus
. Pediatr Diabetes
. 2017
;18
(8
):903
–10
. 24.
Bode
BW
, Iotova
V
, Kovarenko
M
, Laffel
LM
, Rao
PV
, Deenadayalan
S
, et al. Efficacy and safety of fast-acting insulin aspart compared with insulin aspart, both in combination with insulin degludec, in children and adolescents with type 1 diabetes: the onset 7 trial
. Diabetes Care
. 2019
;42
(7
):1255
–62
. 25.
Lyumjev® (insulin lispro-aabc) injection approved by U.S. FDA for children with diabetes
. [cited 2024 April 9]; Available from: https://www.lilly.com/news/media/media-kits/lyumjev26.
Wadwa
RP
, Laffel
LM
, Franco
DR
, Dellva
MA
, Knights
AW
, Pollom
RK
. Efficacy and safety of ultra-rapid lispro versus lispro in children and adolescents with type 1 diabetes: the PRONTO-Peds trial
. Diabetes Obes Metab
. 2023
;25
(1
):89
–97
. 27.
Search of: biochaperone|diabetes: list results – ClinicalTrials.gov
(accessed 26 March 2022).28.
Haller
MJ
, Jones
MC
, Bhavsar
S
, Kaiserman
KB
. Time-action profile of technosphere insulin in children with type 1 diabetes
. Diabetes Ther
. 2023
;14
(3
):611
–7
. 29.
INHALE-3
, Jaeb
R
. A 17-week randomized trial and a 13-week extension, evaluating the efficacy and safety of inhaled insulin (afrezza) combined with insulin degludec versus usual care in adults with type 1 diabetes
. Cent Health
. 2023
.30.
Lucidi
P
, Porcellati
F
, Marinelli Andreoli
A
, Carriero
I
, Candeloro
P
, Cioli
P
, et al. Pharmacokinetics and pharmacodynamics of NPH insulin in type 1 diabetes: the importance of appropriate resuspension before subcutaneous injection
. Diabetes Care
. 2015
;38
(12
):2204
–10
. 31.
Lepore
M
, Pampanelli
S
, Fanelli
C
, Porcellati
F
, Bartocci
L
, Di Vincenzo
A
, et al. Pharmacokinetics and pharmacodynamics of subcutaneous injection of long-acting human insulin analog glargine, NPH insulin, and ultralente human insulin and continuous subcutaneous infusion of insulin lispro
. Diabetes
. 2000
;49
(12
):2142
–8
. 32.
Starke
AA
, Heinemann
L
, Hohmann
A
, Berger
M
. The action profiles of human NPH insulin preparations
. Diabet Med
. 1989
;6
(3
):239
–44
. 33.
Woodworth
JR
, Howey
DC
, Bowsher
RR
. Establishment of time-action profiles for regular and NPH insulin using pharmacodynamic modeling
. Diabetes Care
. 1994
;17
(1
):64
–9
. 34.
Bolli
GB
, Perriello
G
, Fanelli
CG
, De Feo
P
. Nocturnal blood glucose control in type I diabetes mellitus
. Diabetes Care
. 1993
;16
(Suppl 3
):71
–89
. 35.
Jehle
PM
, Micheler
C
, Jehle
DR
, Breitig
D
, Boehm
BO
. Inadequate suspension of neutral protamine Hagendorn (NPH) insulin in pens
. Lancet
. 1999
;354
(9190
):1604
–7
. 36.
Thalange
N
, Bereket
A
, Larsen
J
, Hiort
LC
, Peterkova
V
. Insulin analogues in children with Type 1 diabetes: a 52-week randomized clinical trial
. Diabet Med
. 2013
;30
(2
):216
–25
. 37.
Heise
T
, Nosek
L
, Rønn
BB
, Endahl
L
, Heinemann
L
, Kapitza
C
, et al. Lower within-subject variability of insulin detemir in comparison to NPH insulin and insulin glargine in people with type 1 diabetes
. Diabetes
. 2004
;53
(6
):1614
–20
. 38.
Chase
HP
, Dixon
B
, Pearson
J
, Fiallo-Scharer
R
, Walravens
P
, Klingensmith
G
, et al. Reduced hypoglycemic episodes and improved glycemic control in children with type 1 diabetes using insulin glargine and neutral protamine Hagedorn insulin
. J Pediatr
. 2003
;143
(6
):737
–40
. 39.
Cengiz
E
, Sherr
JL
, Erkin-Cakmak
A
, Weinzimer
SA
, Burke
EN
, Sikes
KA
, et al. A bridge to insulin pump therapy: twice-daily regimen with NPH and detemir insulins during initial treatment of youth with type 1 diabetes mellitus
. Endocr Pract
. 2011
;17
(6
):862
–6
. 40.
Korytkowski
MT
, Salata
RJ
, Koerbel
GL
, Selzer
F
, Karslioglu
E
, Idriss
AM
, et al. Insulin therapy and glycemic control in hospitalized patients with diabetes during enteral nutrition therapy: a randomized controlled clinical trial
. Diabetes Care
. 2009
;32
(4
):594
–6
. 41.
Mabrey
, ME
, Barton
, AB
, Corsino
, L
, Freeman
, SB
, Davis
, ED
, Bell
, EL
, et al, Managing hyperglycemia and diabetes in patients receiving enteral feedings: a health system approach
.Hosp Pract
. 2015
;43
(2
):74
–8
. 42.
Clement
S
, Braithwaite
SS
, Magee
MF
, Ahmann
A
, Smith
EP
, Schafer
RG
, et al. Management of diabetes and hyperglycemia in hospitals
. Diabetes Care
. 2004
;27
(2
):553
–91
. 43.
Ratner
RE
, Hirsch
IB
, Neifing
JL
, Garg
SK
, Mecca
TE
, Wilson
CA
. Less hypoglycemia with insulin glargine in intensive insulin therapy for type 1 diabetes. U.S. Study Group of Insulin Glargine in type 1 diabetes
. Diabetes Care
. 2000
;23
(5
):639
–43
. 44.
Witthaus
E
, Stewart
J
, Bradley
C
. Treatment satisfaction and psychological well-being with insulin glargine compared with NPH in patients with Type 1 diabetes
. Diabet Med
. 2001
;18
(8
):619
–25
. 45.
Ashwell
SG
, Bradley
C
, Stephens
JW
, Witthaus
E
, Home
PD
. Treatment satisfaction and quality of life with insulin glargine plus insulin lispro compared with NPH insulin plus unmodified human insulin in individuals with type 1 diabetes
. Diabetes Care
. 2008
;31
(6
):1112
–7
. 46.
Robertson
KJ
, Schoenle
E
, Gucev
Z
, Mordhorst
L
, Gall
MA
, Ludvigsson
J
. Insulin detemir compared with NPH insulin in children and adolescents with type 1 diabetes
. Diabet Med
. 2007
;24
(1
):27
–34
. 47.
Nimri
R
, Lebenthal
Y
, Shalitin
S
, Benzaquen
H
, Demol
S
, Phillip
M
. Metabolic control by insulin detemir in basal-bolus therapy: treat-to-target study in children and adolescents with type 1 diabetes
. Pediatr Diabetes
. 2013
;14
(3
):196
–202
. 48.
Abali
S
, Turan
S
, Atay
Z
, Güran
T
, Haliloğlu
B
, Bereket
A
. Higher insulin detemir doses are required for the similar glycemic control: comparison of insulin detemir and glargine in children with type 1 diabetes mellitus
. Pediatr Diabetes
. 2015
;16
(5
):361
–6
. 49.
Levemir
. [cited 2024 April 9]; Available from: https://www.novocare.com/diabetes/products/levemir.html50.
Becker
RH
, Dahmen
R
, Bergmann
K
, Lehmann
A
, Jax
T
, Heise
T
. New insulin glargine 300 Units · mL-1 provides a more even activity profile and prolonged glycemic control at steady state compared with insulin glargine 100 Units · mL-1
. Diabetes Care
. 2015
;38
(4
):637
–43
. 51.
Danne
T
, Tamborlane
WV
, Malievsky
OA
, Franco
DR
, Kawamura
T
, Demissie
M
, et al. Efficacy and safety of insulin glargine 300 Units/mL (Gla-300) versus insulin glargine 100 Units/mL (Gla-100) in children and adolescents (6-17 years) with type 1 diabetes: results of the EDITION JUNIOR randomized controlled trial
. Diabetes Care
. 2020
;43
(7
):1512
–9
. 52.
Bergenstal
RM
, Bailey
TS
, Rodbard
D
, Ziemen
M
, Guo
H
, Muehlen-Bartmer
I
, et al. Comparison of insulin glargine 300 Units/mL and 100 Units/mL in adults with type 1 diabetes: continuous glucose monitoring profiles and variability using morning or evening injections
. Diabetes Care
. 2017
;40
(4
):554
–60
. 53.
Matsuhisa
M
, Koyama
M
, Cheng
X
, Sumi
M
, Riddle
MC
, Bolli
GB
, et al. Sustained glycaemic control and less nocturnal hypoglycaemia with insulin glargine 300U/mL compared with glargine 100U/mL in Japanese adults with type 1 diabetes (EDITION JP 1 randomised 12-month trial including 6-month extension)
. Diabetes Res Clin Pract
. 2016
;122
:133
–40
. 54.
https://www.ema.europa.eu/en/medicines/human/EPAR/toujeo-previously-optisulin (accessed March 26, 2022).
55.
Jonassen
I
, Havelund
S
, Hoeg-Jensen
T
, Steensgaard
DB
, Wahlund
PO
, Ribel
U
. Design of the novel protraction mechanism of insulin degludec, an ultra-long-acting basal insulin
. Pharm Res
. 2012
;29
(8
):2104
–14
. 56.
Mathieu
C
, Hollander
P
, Miranda-Palma
B
, Cooper
J
, Franek
E
, Russell-Jones
D
, et al. Efficacy and safety of insulin degludec in a flexible dosing regimen vs insulin glargine in patients with type 1 diabetes (BEGIN: flex T1): a 26-week randomized, treat-to-target trial with a 26-week extension
. J Clin Endocrinol Metab
. 2013
;98
(3
):1154
–62
. 57.
Bevier
WC
, Castorino
KN
, Axelrod
C
, Haroush
G
, Farfan
CC
, Shelton
N
, et al. Traveling across time zones with type 1 diabetes: a pilot study comparing insulin degludec with insulin glargine U100
. Diabetes Care
. 2022
;45
(1
):67
–73
. 58.
Battelino
T
, Danne
T
, Edelman
SV
, Choudhary
P
, Renard
E
, Westerbacka
J
, et al. Continuous glucose monitoring-based time-in-range using insulin glargine 300 units/ml versus insulin degludec 100 units/ml in type 1 diabetes: the head-to-head randomized controlled InRange trial
. Diabetes Obes Metab
. 2023
;25
(2
):545
–55
. 59.
Moser
O
, Müller
A
, Aberer
F
, Aziz
F
, Kojzar
H
, Sourij
C
, et al. Comparison of insulin glargine 300 U/mL and insulin degludec 100 U/mL around spontaneous exercise sessions in adults with type 1 diabetes: a randomized cross-over trial (ULTRAFLEXI-1 study)
. Diabetes Technol Ther
. 2023
;25
(3
):161
–8
. 60.
Biester
T
, Blaesig
S
, Remus
K
, Aschemeier
B
, Kordonouri
O
, Granhall
C
, et al. Insulin degludec’s ultra-long pharmacokinetic properties observed in adults are retained in children and adolescents with type 1 diabetes
. Pediatr Diabetes
. 2014
;15
(1
):27
–33
. 61.
Thalange
N
, Deeb
L
, Iotova
V
, Kawamura
T
, Klingensmith
G
, Philotheou
A
, et al. Insulin degludec in combination with bolus insulin aspart is safe and effective in children and adolescents with type 1 diabetes
. Pediatr Diabetes
. 2015
;16
(3
):164
–76
. 62.
Blum
WF
, Cao
D
, Hesse
V
, Fricke-Otto
S
, Ross
JL
, Jones
C
, et al. Height gains in response to growth hormone treatment to final height are similar in patients with SHOX deficiency and Turner syndrome
. Horm Res
. 2009
;71
(3
):167
–72
. 63.
Russell-Jones
D
, Babazono
T
, Cailleteau
R
, Engberg
S
, Irace
C
, Kjaersgaard
MIS
, et al. Once-weekly insulin icodec versus once-daily insulin degludec as part of a basal-bolus regimen in individuals with type 1 diabetes (ONWARDS 6): a phase 3a, randomised, open-label, treat-to-target trial
. Lancet
. 2023
;402
(10413
):1636
–47
. 64.
[cited 2024 June 13]; Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/awiqli
65.
Kazda
CM
, Bue-Valleskey
JM
, Chien
J
, Zhang
Q
, Chigutsa
E
, Landschulz
W
, et al. Novel once-weekly basal insulin Fc achieved similar glycemic control with a safety profile comparable to insulin degludec in patients with type 1 diabetes
. Diabetes Care
. 2023
;46
(5
):1052
–9
. 66.
Kjeldsen
TB
, Hubálek
F
, Hjørringgaard
CU
, Tagmose
TM
, Nishimura
E
, Stidsen
CE
, et al. Molecular engineering of insulin icodec, the first acylated insulin analog for once-weekly administration in humans
. J Med Chem
. 2021
;64
(13
):8942
–50
. 67.
Nishimura
E
, Pridal
L
, Glendorf
T
, Hansen
BF
, Hubálek
F
, Kjeldsen
T
, et al. Molecular and pharmacological characterization of insulin icodec: a new basal insulin analog designed for once-weekly dosing
. BMJ Open Diabetes Res Care
. 2021
;9
(1
):e002301
. 68.
Mortensen
HB
, Robertson
KJ
, Aanstoot
HJ
, Danne
T
, Holl
RW
, Hougaard
P
, et al. Insulin management and metabolic control of type 1 diabetes mellitus in childhood and adolescence in 18 countries. Hvidore Study Group on Childhood Diabetes
. Diabet Med
. 1998
;15
(9
):752
–9
. 69.
Chou
WY
, Li
YR
, Chan
WK
, Chen
ST
. Association of diabetic ketoacidosis, severe hypoglycemia and glycemic control among children and young adults with type 1 diabetes mellitus treated with premixed versus basal-bolus insulin therapy
. Biomed J
. 2018
;41
(6
):348
–55
. 70.
Battelino
T
, Deeb
LC
, Ekelund
M
, Kinduryte
O
, Klingensmith
GJ
, Kocova
M
, et al. Efficacy and safety of a fixed combination of insulin degludec/insulin aspart in children and adolescents with type 1 diabetes: a randomized trial
. Pediatr Diabetes
. 2018
;19
(7
):1263
–70
. 71.
Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/ryzodeg (accessed March 23, 2022).
72.
Kurtzhals
P
, Schäffer
L
, Sørensen
A
, Kristensen
C
, Jonassen
I
, Schmid
C
, et al. Correlations of receptor binding and metabolic and mitogenic potencies of insulin analogs designed for clinical use
. Diabetes
. 2000
;49
(6
):999
–1005
. 73.
Tang
X
, Yang
L
, He
Z
, Liu
J
. Insulin glargine and cancer risk in patients with diabetes: a meta-analysis
. PLoS One
. 2012
;7
(12
):e51814
. 76.
Stickelmeyer
MP
, Graf
CJ
, Frank
BH
, Ballard
RL
, Storms
SM
. Stability of U-10 and U-50 dilutions of insulin lispro
. Diabetes Technol Ther
. 2000
;2
(1
):61
–6
. 77.
Ruan
Y
, Elleri
D
, Allen
JM
, Tauschmann
M
, Wilinska
ME
, Dunger
DB
, et al. Pharmacokinetics of diluted (U20) insulin aspart compared with standard (U100) in children aged 3-6 years with type 1 diabetes during closed-loop insulin delivery: a randomised clinical trial
. Diabetologia
. 2015
;58
(4
):687
–90
. 78.
Elleri
D
, Allen
JM
, Tauschmann
M
, El-Khairi
R
, Benitez-Aguirre
P
, Acerini
CL
, et al. Feasibility of overnight closed-loop therapy in young children with type 1 diabetes aged 3-6 years: comparison between diluted and standard insulin strength
. BMJ Open Diabetes Res Care
. 2014
;2
(1
):e000040
. 79.
Kurnaz
E
, Aycan
Z
, Yıldırım
N
, Çetinkaya
S
. Conventional insulin pump therapy in two neonatal diabetes patients harboring the homozygous PTF1A enhancer mutation: need for a novel approach for the management of neonatal diabetes
. Turk J Pediatr
. 2017
;59
(4
):458
–62
. 80.
Rabbone
I
, Barbetti
F
, Gentilella
R
, Mossetto
G
, Bonfanti
R
, Maffeis
C
, et al. Insulin therapy in neonatal diabetes mellitus: a review of the literature
. Diabetes Res Clin Pract
. 2017
;129
:126
–35
. 81.
Welters
A
, Meissner
T
, Konrad
K
, Freiberg
C
, Warncke
K
, Judmaier
S
, et al. Diabetes management in Wolcott-Rallison syndrome: analysis from the German/Austrian DPV database
. Orphanet J Rare Dis
. 2020
;15
(1
):100
. 82.
Annan
SF
, Higgins
LA
, Jelleryd
E
, Hannon
T
, Rose
S
, Salis
S
, et al. ISPAD clinical practice consensus guidelines 2022: nutritional management in children and adolescents with diabetes
. Pediatr Diabetes
. 2022
;23
(8
):1297
–321
. 83.
Neu
A
, Lange
K
, Barrett
T
, Cameron
F
, Dorchy
H
, Hoey
H
, et al. Classifying insulin regimens: difficulties and proposal for comprehensive new definitions
. Pediatr Diabetes
. 2015
;16
(6
):402
–6
. 84.
Deeb
LC
, Holcombe
JH
, Brunelle
R
, Zalani
S
, Brink
S
, Jenner
M
, et al. Insulin lispro lowers postprandial glucose in prepubertal children with diabetes
. Pediatrics
. 2001
;108
(5
):1175
–9
. 85.
Danne
T
, Aman
J
, Schober
E
, Deiss
D
, Jacobsen
JL
, Friberg
HH
, et al. A comparison of postprandial and preprandial administration of insulin aspart in children and adolescents with type 1 diabetes
. Diabetes Care
. 2003
;26
(8
):2359
–64
. 86.
Cobry
E
, McFann
K
, Messer
L
, Gage
V
, VanderWel
B
, Horton
L
, et al. Timing of meal insulin boluses to achieve optimal postprandial glycemic control in patients with type 1 diabetes
. Diabetes Technol Ther
. 2010
;12
(3
):173
–7
. 87.
Luijf
YM
, van Bon
AC
, Hoekstra
JB
, Devries
JH
. Premeal injection of rapid-acting insulin reduces postprandial glycemic excursions in type 1 diabetes
. Diabetes Care
. 2010
;33
(10
):2152
–5
. 88.
Heise
T
, Pieber
TR
, Danne
T
, Erichsen
L
, Haahr
H
. A pooled analysis of clinical pharmacology trials investigating the pharmacokinetic and pharmacodynamic characteristics of fast-acting insulin aspart in adults with type 1 diabetes
. Clin Pharmacokinet
. 2017
;56
(5
):551
–9
. 89.
Linnebjerg
H
, Zhang
Q
, LaBell
E
, Dellva
MA
, Coutant
DE
, Hövelmann
U
, et al. Pharmacokinetics and glucodynamics of Ultra Rapid lispro (URLi) versus Humalog® (lispro) in younger adults and elderly patients with type 1 diabetes mellitus: a randomised controlled trial
. Clin Pharmacokinet
. 2020
;59
(12
):1589
–99
. 90.
Miura
J
, Imori
M
, Nishiyama
H
, Imaoka
T
. Ultra-rapid lispro efficacy and safety compared to Humalog® in Japanese patients with type 1 diabetes: PRONTO-T1D subpopulation analysis
. Diabetes Ther
. 2020
;11
(9
):2089
–104
. 91.
Shiramoto
M
, Nasu
R
, Oura
T
, Imori
M
, Ohwaki
K
. Ultra-Rapid Lispro results in accelerated insulin lispro absorption and faster early insulin action in comparison with Humalog® in Japanese patients with type 1 diabetes
. J Diabetes Investig
. 2020
;11
(3
):672
–80
. 92.
Sackey
AH
, Jefferson
IG
. Interval between insulin injection and breakfast in diabetes
. Arch Dis Child
. 1994
;71
(3
):248
–50
. 93.
Biester
T
, Berget
C
, Boughton
C
, Cudizio
L
, Ekhlaspour
L
, Hilliard
ME
, et al. ISPAD clinical practice consensus guidelines 2024: diabetes technologies: insulin delivery
. Horm Res Paediatr
. 2024
:1
–34
. 94.
Limbert
C
, Tinti
D
, Malik
F
, Kosteria
I
, Messer
L
, Jalaludin
MY
, et al. ISPAD Clinical Practice Consensus Guidelines 2022: the delivery of ambulatory diabetes care to children and adolescents with diabetes
. Pediatr Diabetes
. 2022
;23
(8
):1243
–69
. 95.
Zeng
B
, Gao
L
, Yang
Q
, Jia
H
, Sun
F
. Automated insulin delivery systems in children and adolescents with type 1 diabetes: a systematic review and meta-analysis of outpatient randomized controlled trials
. Diabetes Care
. 2023
;46
(12
):2300
–7
. 96.
Boughton
CK
, Allen
JM
, Ware
J
, Wilinska
ME
, Hartnell
S
, Thankamony
A
, et al. Closed-loop therapy and preservation of C-Peptide secretion in type 1 diabetes
. N Engl J Med
. 2022
;387
(10
):882
–93
. 97.
Holt
RIG
, DeVries
JH
, Hess-Fischl
A
, Hirsch
IB
, Kirkman
MS
, Klupa
T
, et al. The management of type 1 diabetes in adults. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)
. Diabetes Care
. 2021
;44
(11
):2589
–625
. 98.
Chowdhury
S
. Puberty and type 1 diabetes
. Indian J Endocrinol Metab
. 2015
;19
(Suppl 1
):S51
–4
. 99.
Amiel
SA
, Sherwin
RS
, Simonson
DC
, Lauritano
AA
, Tamborlane
WV
. Impaired insulin action in puberty. A contributing factor to poor glycemic control in adolescents with diabetes
. N Engl J Med
. 1986
;315
(4
):215
–9
. 100.
Dunger
DB
, Cheetham
TD
. Growth hormone insulin-like growth factor I axis in insulin-dependent diabetes mellitus
. Horm Res
. 1996
;46
(1
):2
–6
. 101.
Munoz
MT
, Barrios
V
, Pozo
J
, Argente
J
. Insulin-like growth factor I, its binding proteins 1 and 3, and growth hormone-binding protein in children and adolescents with insulin-dependent diabetes mellitus: clinical implications
. Pediatr Res
. 1996
;39
(6
):992
–8
. 102.
Nambam
B
, Schatz
D
. Growth hormone and insulin-like growth factor-I axis in type 1 diabetes
. Growth Horm IGF Res
. 2018
;38
:49
–52
. 103.
Trout
KK
, Rickels
MR
, Schutta
MH
, Petrova
M
, Freeman
EW
, Tkacs
NC
, et al. Menstrual cycle effects on insulin sensitivity in women with type 1 diabetes: a pilot study
. Diabetes Technol Ther
. 2007
;9
(2
):176
–82
. 104.
Codner
E
, Merino
PM
, Tena-Sempere
M
. Female reproduction and type 1 diabetes: from mechanisms to clinical findings
. Hum Reprod Update
. 2012
;18
(5
):568
–85
. 105.
Diaz
CJ
. Insulin replacement across the menstrual cycle in women with type 1 diabetes: an in silico assessment of the need for ad hoc technology
. Diabetes Technol Ther
. 2022
;24
(11
):832
–41
.106.
Diaz
, CJ
. Modeling the variability of insulin sensitivity during the menstrual cycle in women with type 1 diabetes to adjust open-loop insulin therapy
.Annu Int Conf IEEE Eng Med Biol Soc
. 2021
:1543
–6
.107.
Garg
SK
, Gottlieb
PA
, Hisatomi
ME
, D’Souza
A
, Walker
AJ
, Izuora
KE
, et al. Improved glycemic control without an increase in severe hypoglycemic episodes in intensively treated patients with type 1 diabetes receiving morning, evening, or split dose insulin glargine
. Diabetes Res Clin Pract
. 2004
;66
(1
):49
–56
. 108.
Tan
CY
, Wilson
DM
, Buckingham
B
. Initiation of insulin glargine in children and adolescents with type 1 diabetes
. Pediatr Diabetes
. 2004
;5
(2
):80
–6
. 109.
Danne
T
, Lüpke
K
, Walte
K
, Von Schuetz
W
, Gall
MA
. Insulin detemir is characterized by a consistent pharmacokinetic profile across age-groups in children, adolescents, and adults with type 1 diabetes
. Diabetes Care
. 2003
;26
(11
):3087
–92
. 110.
Enander
R
, Gundevall
C
, Strömgren
A
, Chaplin
J
, Hanas
R
. Carbohydrate counting with a bolus calculator improves post-prandial blood glucose levels in children and adolescents with type 1 diabetes using insulin pumps
. Pediatr Diabetes
. 2012
;13
(7
):545
–51
. 111.
Hanas
R
, Adolfsson
P
. Bolus calculator settings in well-controlled prepubertal children using insulin pumps are characterized by low insulin to carbohydrate ratios and short duration of insulin action time
. J Diabetes Sci Technol
. 2017
;11
(2
):247
–52
. 112.
Sundberg
F
, deBeaufort
C
, Krogvold
L
, Patton
S
, Piloya
T
, Smart
C
, et al. ISPAD clinical practice consensus guidelines 2022: managing diabetes in preschoolers
. Pediatr Diabetes
. 2022
;23
(8
):1496
–511
. 113.
Paterson
MA
, Smart
CEM
, Lopez
PE
, McElduff
P
, Attia
J
, Morbey
C
, et al. Influence of dietary protein on postprandial blood glucose levels in individuals with type 1 diabetes mellitus using intensive insulin therapy
. Diabet Med
. 2016
;33
(5
):592
–8
. 114.
Davidson
PC
, Hebblewhite
HR
, Steed
RD
, Bode
BW
. Analysis of guidelines for basal-bolus insulin dosing: basal insulin, correction factor, and carbohydrate-to-insulin ratio
. Endocr Pract
. 2008
;14
(9
):1095
–101
. 115.
Holl
RW
, Swift
PGF
, Mortensen
HB
, Lynggaard
H
, Hougaard
P
, Aanstoot
HJ
, et al. Insulin injection regimens and metabolic control in an International survey of adolescents with type 1 diabetes over 3 years: results from the Hvidore study group
. Eur J Pediatr
. 2003
;162
(1
):22
–9
. 116.
Cengiz
E
, Connor
CG
, Ruedy
KJ
, Beck
RW
, Kollman
C
, Klingensmith
GJ
, et al. Pediatric diabetes consortium T1D New Onset (NeOn) study: clinical outcomes during the first year following diagnosis
. Pediatr Diabetes
. 2014
;15
(4
):287
–93
. 117.
Cengiz
E
, Cheng
P
, Ruedy
KJ
, Kollman
C
, Tamborlane
WV
, Klingensmith
GJ
, et al. Clinical outcomes in youth beyond the first year of type 1 diabetes: results of the Pediatric Diabetes Consortium (PDC) type 1 diabetes new onset (NeOn) study
. Pediatr Diabetes
. 2017
;18
(7
):566
–73
. 118.
Kinmonth
AL
, Baum
JD
. Timing of pre-breakfast insulin injection and postprandial metabolic control in diabetic children
. Br Med J
. 1980
;280
(6214
):604
–6
. 119.
Randlov
J
, Poulsen
JU
. How much do forgotten insulin injections matter to hemoglobin a1c in people with diabetes? A simulation study
. J Diabetes Sci Technol
. 2008
;2
(2
):229
–35
. 120.
Burdick
J
, Chase
HP
, Slover
RH
, Knievel
K
, Scrimgeour
L
, Maniatis
AK
, et al. Missed insulin meal boluses and elevated hemoglobin A1c levels in children receiving insulin pump therapy
. Pediatrics
. 2004
;113
(3 Pt 1
):e221
–4
. 121.
Clements
MA
, DeLurgio
SA
, Williams
DD
, Habib
S
, Halpin
K
, Patton
SR
. Association of HbA1c to BOLUS scores among youths with type 1 diabetes
. Diabetes Technol Ther
. 2016
;18
(6
):351
–9
. 122.
Tascini
G
, Berioli
MG
, Cerquiglini
L
, Santi
E
, Mancini
G
, Rogari
F
, et al. Carbohydrate counting in children and adolescents with type 1 diabetes
. Nutrients
. 2018
;10
(1
):109
. 123.
Hofman
PL
, Lawton
SA
, Peart
JM
, Holt
JA
, Jefferies
CA
, Robinson
E
, et al. An angled insertion technique using 6-mm needles markedly reduces the risk of intramuscular injections in children and adolescents
. Diabet Med
. 2007
;24
(12
):1400
–5
. 124.
Hofman
PL
, Derraik
JGB
, Pinto
TE
, Tregurtha
S
, Faherty
A
, Peart
JM
, et al. Defining the ideal injection techniques when using 5-mm needles in children and adults
. Diabetes Care
. 2010
;33
(9
):1940
–4
. 125.
Birkebaek
NH
, Johansen
A
, Solvig
J
. Cutis/subcutis thickness at insulin injection sites and localization of simulated insulin boluses in children with type 1 diabetes mellitus: need for individualization of injection technique
. Diabet Med
. 1998
;15
(11
):965
–71
. 126.
Smith
CP
, Sargent
MA
, Wilson
BP
, Price
DA
. Subcutaneous or intramuscular insulin injections
. Arch Dis Child
. 1991
;66
(7
):879
–82
. 127.
Ginsberg
BH
, Parkes
JL
, Sparacino
C
. The kinetics of insulin administration by insulin pens
. Horm Metab Res
. 1994
;26
(12
):584
–7
. 128.
Wysocki
T
, Harris
MA
, Buckloh
LM
, Wilkinson
K
, Sadler
M
, Mauras
N
, et al. Self-care autonomy and outcomes of intensive therapy or usual care in youth with type 1 diabetes
. J Pediatr Psychol
. 2006
;31
(10
):1036
–45
. 129.
Halberg
IJL
, Dahl
U
. A study on selfmixing insulin aspart with NPH insulin in the syringe before injection
. Diabetes
. 1999
;48
(Suppl 1
).130.
Cengiz
E
, Tamborlane
WV
, Martin-Fredericksen
M
, Dziura
J
, Weinzimer
SA
. Early pharmacokinetic and pharmacodynamic effects of mixing lispro with glargine insulin: results of glucose clamp studies in youth with type 1 diabetes
. Diabetes Care
. 2010
;33
(5
):1009
–12
. 131.
Cengiz
E
, Swan
KL
, Tamborlane
WV
, Sherr
JL
, Martin
M
, Weinzimer
SA
. The alteration of aspart insulin pharmacodynamics when mixed with detemir insulin
. Diabetes Care
. 2012
;35
(4
):690
–2
. 132.
Frid
AH
, Hirsch
LJ
, Menchior
AR
, Morel
DR
, Strauss
KW
. Worldwide injection technique questionnaire study: injecting complications and the role of the professional
. Mayo Clin Proc
. 2016
;91
(9
):1224
–30
. 133.
Kordonouri
O
, Biester
T
, Weidemann
J
, Ott
H
, Remus
K
, Grothaus
J
, et al. Lipoatrophy in children, adolescents and adults with insulin pump treatment: is there a beneficial effect of insulin glulisine
. Pediatr Diabetes
. 2020
;21
(7
):1285
–91
. 134.
Fröhlich-Reiterer
E
, Elbarbary
NS
, Simmons
K
, Buckingham
B
, Humayun
KN
, Johannsen
J
, et al. ISPAD Clinical Practice Consensus Guidelines 2022: other complications and associated conditions in children and adolescents with type 1 diabetes
. Pediatr Diabetes
. 2022
;23
(8
):1451
–67
. 135.
Chantelau
E
, Lee
DM
, Hemmann
DM
, Zipfel
U
, Echterhoff
S
. What makes insulin injections painful
. BMJ
. 1991
;303
(6793
):26
–7
. 136.
Hanas
R
, Adolfsson
P
, Elfvin-Akesson
K
, Hammarén
L
, Ilvered
R
, Jansson
I
, et al. Indwelling catheters used from the onset of diabetes decrease injection pain and pre-injection anxiety
. J Pediatr
. 2002
;140
(3
):315
–20
. 137.
Burdick
P
, Cooper
S
, Horner
B
, Cobry
E
, McFann
K
, Chase
HP
. Use of a subcutaneous injection port to improve glycemic control in children with type 1 diabetes
. Pediatr Diabetes
. 2009
;10
(2
):116
–9
. 138.
Hanas
SR
, Ludvigsson
J
. Metabolic control is not altered when using indwelling catheters for insulin injections
. Diabetes Care
. 1994
;17
(7
):716
–8
. 139.
Mudaliar
SR
, Lindberg
FA
, Joyce
M
, Beerdsen
P
, Strange
P
, Lin
A
, et al. Insulin aspart (B28 asp-insulin): a fast-acting analog of human insulin: absorption kinetics and action profile compared with regular human insulin in healthy nondiabetic subjects
. Diabetes Care
. 1999
;22
(9
):1501
–6
. 140.
ter Braak
EW
, Woodworth
JR
, Bianchi
R
, Cerimele
B
, Erkelens
DW
, Thijssen
JH
, et al. Injection site effects on the pharmacokinetics and glucodynamics of insulin lispro and regular insulin
. Diabetes Care
. 1996
;19
(12
):1437
–40
. 141.
Vaag
A
, Pedersen
KD
, Lauritzen
M
, Hildebrandt
P
, Beck-Nielsen
H
. Intramuscular versus subcutaneous injection of unmodified insulin: consequences for blood glucose control in patients with type 1 diabetes mellitus
. Diabet Med
. 1990
;7
(4
):335
–42
. 142.
A F. Injection and absorption of insulin
. PhD Thesis. Stockholm, Sweden
: Faculty of Medicine, Karolinska Institute
; 1992
.143.
Bantle
JP
, Neal
L
, Frankamp
LM
. Effects of the anatomical region used for insulin injections on glycemia in type I diabetes subjects
. Diabetes Care
. 1993
;16
(12
):1592
–7
. 144.
Gradel
AKJ
, Porsgaard
T
, Lykkesfeldt
J
, Seested
T
, Gram-Nielsen
S
, Kristensen
NR
, et al. Factors affecting the absorption of subcutaneously administered insulin: effect on variability
. J Diabetes Res
. 2018
;2018
:1205121
. 145.
Guerci
B
, Sauvanet
JP
. Subcutaneous insulin: pharmacokinetic variability and glycemic variability
. Diabetes Metab
. 2005
;31
(4 Pt 2
):4S7
–4S24
. 146.
Owens
DR
, Coates
PA
, Luzio
SD
, Tinbergen
JP
, Kurzhals
R
. Pharmacokinetics of 125I-labeled insulin glargine (HOE 901) in healthy men: comparison with NPH insulin and the influence of different subcutaneous injection sites
. Diabetes Care
. 2000
;23
(6
):813
–9
. 147.
Nosek
L
, Coester
HV
, Roepstorff
C
, Thomsen
HF
, Kristensen
NR
, Haahr
H
, et al. Glucose-lowering effect of insulin degludec is independent of subcutaneous injection region
. Clin Drug Investig
. 2014
;34
(9
):673
–9
. 148.
Frid
A
, Gunnarsson
R
, Güntner
P
, Linde
B
. Effects of accidental intramuscular injection on insulin absorption in IDDM
. Diabetes Care
. 1988
;11
(1
):41
–5
. 149.
Hirsch
L
, Byron
K
, Gibney
M
. Intramuscular risk at insulin injection sites--measurement of the distance from skin to muscle and rationale for shorter-length needles for subcutaneous insulin therapy
. Diabetes Technol Ther
. 2014
;16
(12
):867
–73
. 150.
Cengiz
E
, Weinzimer
SA
, Sherr
JL
, Tichy
EM
, Carria
L
, Cappiello
D
, et al. Faster in and faster out: accelerating insulin absorption and action by insulin infusion site warming
. Diabetes Technol Ther
. 2014
;16
(1
):20
–5
. 151.
Raz
I
, Bitton
G
, Feldman
D
, Alon
T
, Pfutzner
A
, Tamborlane
WV
. Improved postprandial glucose control using the InsuPad device in insulin-treated type 2 diabetes: injection site warming to improve glycemic control
. J Diabetes Sci Technol
. 2015
;9
(3
):639
–43
. 152.
Pitt
JP
, McCarthy
OM
, Hoeg-Jensen
T
, Wellman
BM
, Bracken
RM
. Factors influencing insulin absorption around exercise in type 1 diabetes
. Front Endocrinol
. 2020
;11
:573275
. 153.
Frid
A
, Ostman
J
, Linde
B
. Hypoglycemia risk during exercise after intramuscular injection of insulin in thigh in IDDM
. Diabetes Care
. 1990
;13
(5
):473
–7
. 154.
Peter
R
, Luzio
SD
, Dunseath
G
, Miles
A
, Hare
B
, Backx
K
, et al. Effects of exercise on the absorption of insulin glargine in patients with type 1 diabetes
. Diabetes Care
. 2005
;28
(3
):560
–5
. 155.
Karges
B
, Boehm
BO
, Karges
W
. Early hypoglycaemia after accidental intramuscular injection of insulin glargine
. Diabet Med
. 2005
;22
(10
):1444
–5
. 156.
Young
RJ
, Hannan
WJ
, Frier
BM
, Steel
JM
, Duncan
LJ
. Diabetic lipohypertrophy delays insulin absorption
. Diabetes Care
. 1984
;7
(5
):479
–80
. 157.
Sindelka
G
, Heinemann
L
, Berger
M
, Frenck
W
, Chantelau
E
. Effect of insulin concentration, subcutaneous fat thickness and skin temperature on subcutaneous insulin absorption in healthy subjects
. Diabetologia
. 1994
;37
(4
):377
–80
. 158.
Bitton
G
, Rom
V
, Hadelsberg
U
, Raz
I
, Cengiz
E
, Weinzimer
S
, et al. Effect of injection site cooling and warming on insulin glargine pharmacokinetics and pharmacodynamics
. J Diabetes Sci Technol
. 2019
;13
(6
):1123
–8
. 159.
Schuler
G
, Pelz
K
, Kerp
L
. Is the reuse of needles for insulin injection systems associated with a higher risk of cutaneous complications
. Diabetes Res Clin Pract
. 1992
;16
(3
):209
–12
. 160.
Arendt-Nielsen
L
, Egekvist
H
, Bjerring
P
. Pain following controlled cutaneous insertion of needles with different diameters
. Somatosens Mot Res
. 2006
;23
(1–2
):37
–43
. 161.
Hanas
R
, Ludvigsson
J
. Side effects and indwelling times of subcutaneous catheters for insulin injections: a new device for injecting insulin with a minimum of pain in the treatment of insulin-dependent diabetes mellitus
. Diabetes Res Clin Pract
. 1990
;10
(1
):73
–83
. 162.
Hanas
SR
, Carlsson
S
, Frid
A
, Ludvigsson
J
. Unchanged insulin absorption after 4 days' use of subcutaneous indwelling catheters for insulin injections
. Diabetes Care
. 1997
;20
(4
):487
–90
. 163.
Engwerda
EEC
, Tack
CJ
, de Galan
BE
. Pharmacokinetic and pharmacodynamic variability of insulin when administered by jet injection
. J Diabetes Sci Technol
. 2017
;11
(5
):947
–52
. 164.
Chiasson
JL
, Ducros
F
, Poliquin-Hamet
M
, Lopez
D
, Lecavalier
L
, Hamet
P
. Continuous subcutaneous insulin infusion (Mill-Hill Infuser) versus multiple injections (Medi-Jector) in the treatment of insulin-dependent diabetes mellitus and the effect of metabolic control on microangiopathy
. Diabetes Care
. 1984
;7
(4
):331
–7
. 165.
Houtzagers
CM
, Visser
AP
, Berntzen
PA
, Heine
RJ
, van der Veen
EA
. The Medi-Jector II: efficacy and acceptability in insulin-dependent diabetic patients with and without needle phobia
. Diabet Med
. 1988
;5
(2
):135
–8
. 166.
Engwerda
EE
, Abbink
EJ
, Tack
CJ
, de Galan
BE
. Improved pharmacokinetic and pharmacodynamic profile of rapid-acting insulin using needle-free jet injection technology
. Diabetes Care
. 2011
;34
(8
):1804
–8
. 167.
Litton
J
, Rice
A
, Friedman
N
, Oden
J
, Lee
MM
, Freemark
M
. Insulin pump therapy in toddlers and preschool children with type 1 diabetes mellitus
. J Pediatr
. 2002
;141
(4
):490
–5
. 168.
Berghaeuser
MA
, Kapellen
T
, Heidtmann
B
, Haberland
H
, Klinkert
C
, Holl
RW
, et al. Continuous subcutaneous insulin infusion in toddlers starting at diagnosis of type 1 diabetes mellitus. A multicenter analysis of 104 patients from 63 centres in Germany and Austria
. Pediatr Diabetes
. 2008
;9
(6
):590
–5
. 169.
Skogsberg
L
, Fors
H
, Hanas
R
, Chaplin
JE
, Lindman
E
, Skogsberg
J
. Improved treatment satisfaction but no difference in metabolic control when using continuous subcutaneous insulin infusion vs. multiple daily injections in children at onset of type 1 diabetes mellitus
. Pediatr Diabetes
. 2008
;9
(5
):472
–9
. 170.
Bolli
GB
, Kerr
D
, Thomas
R
, Torlone
E
, Sola-Gazagnes
A
, Vitacolonna
E
, et al. Comparison of a multiple daily insulin injection regimen (basal once-daily glargine plus mealtime lispro) and continuous subcutaneous insulin infusion (lispro) in type 1 diabetes: a randomized open parallel multicenter study
. Diabetes Care
. 2009
;32
(7
):1170
–6
. 171.
Colquitt
J
, Royle
P
, Waugh
N
. Are analogue insulins better than soluble in continuous subcutaneous insulin infusion? Results of a meta-analysis
. Diabet Med
. 2003
;20
(10
):863
–6
. 172.
Sulmont
V
, Souchon
PF
, Gouillard-Darnaud
C
, Fartura
A
, Salmon-Musial
AS
, Lambrecht
E
, et al. Metabolic control in children with diabetes mellitus who are younger than 6 years at diagnosis: continuous subcutaneous insulin infusion as a first line treatment
. J Pediatr
. 2010
;157
(1
):103
–7
. 173.
Danne
T
, Battelino
T
, Jarosz-Chobot
P
, Kordonouri
O
, Pánkowska
E
, Ludvigsson
J
, et al. Establishing glycaemic control with continuous subcutaneous insulin infusion in children and adolescents with type 1 diabetes: experience of the PedPump Study in 17 countries
. Diabetologia
. 2008
;51
(9
):1594
–601
. 174.
Heinemann
L
, Braune
K
, Carter
A
, Zayani
A
, Krämer
LA
. Insulin storage: a critical reappraisal
. J Diabetes Sci Technol
. 2021
;15
(1
):147
–59
. 175.
Braune
K
, Kraemer
LA
, Weinstein
J
, Zayani
A
, Heinemann
L
. Storage conditions of insulin in domestic refrigerators and when carried by patients: often outside recommended temperature range
. Diabetes Technol Ther
. 2019
;21
(5
):238
–44
. 176.
Virmani
A
, Avni
TCA
. A case for expanding thermochromic vial monitor technology to insulin and other biologics
. Indian Pediatr
. 2020
;57
(1
):17
–9
. 177.
Virmani
A
, Brink
SJ
, Middlehurst
A
, Mohsin
F
, Giraudo
F
, Sarda
A
, et al. ISPAD Clinical Practice Consensus Guidelines 2022: management of the child, adolescent, and young adult with diabetes in limited resource settings
. Pediatr Diabetes
. 2022
;23
(8
):1529
–51
. 178.
Herr
JK
, Keith
S
, Klug
R
, Pettis
RJ
. Characterizing normal-use temperature conditions of pumped insulin
. J Diabetes Sci Technol
. 2014
;8
(4
):850
–4
. 179.
Richter
B
, Bongaerts
B
, Metzendorf
MI
. Thermal stability and storage of human insulin
. Cochrane Database Syst Rev
. 2023
;2023
(11
). 180.
Kaufmann
B
, Boulle
P
, Berthou
F
, Fournier
M
, Beran
D
, Ciglenecki
I
, et al. Heat-stability study of various insulin types in tropical temperature conditions: new insights towards improving diabetes care
. PLoS One
. 2021
;16
(2
):e0245372
. 181.
Pendsey
S
, James
S
, Garrett
TJ
, Nord
AB
, Pendsey
S
, Malmodin
D
, et al. Insulin thermostability in a real-world setting
. Lancet Diabetes Endocrinol
. 2023
;11
(5
):310
–2
. 182.
Ogle
GD
, Abdullah
M
, Mason
D
, Januszewski
AS
, Besançon
S
. Insulin storage in hot climates without refrigeration: temperature reduction efficacy of clay pots and other techniques
. Diabet Med
. 2016
;33
(11
):1544
–53
. 183.
Srinivasan
S
, Ekhlaspour
L
, Cengiz
E
. Adjunctive therapies to optimize closed-loop glucose control
. J Diabetes Sci Technol
. 2021
;15
(6
):1243
–51
. 184.
Andersen
G
, Eloy
R
, Famulla
S
, Heise
T
, Meiffren
G
, Seroussi
C
, et al. A co-formulation of pramlintide and insulin A21G (ADO09) improves postprandial glucose and short-term control of mean glucose, time in range, and body weight versus insulin aspart in adults with type 1 diabetes
. Diabetes Obes Metab
. 2023
;25
(5
):1241
–8
. 185.
Andersen
G
, Meiffren
G
, Famulla
S
, Heise
T
, Ranson
A
, Seroussi
C
, et al. ADO09, a co-formulation of the amylin analogue pramlintide and the insulin analogue A21G, lowers postprandial blood glucose versus insulin lispro in type 1 diabetes
. Diabetes Obes Metab
. 2021
;23
(4
):961
–70
. 186.
Frias
JP
, Deenadayalan
S
, Erichsen
L
, Knop
FK
, Lingvay
I
, Macura
S
, et al. Efficacy and safety of co-administered once-weekly cagrilintide 2·4 mg with once-weekly semaglutide 2·4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial
. Lancet
. 2023
;402
(10403
):720
–30
. 187.
Cree-Green
M
, Bergman
BC
, Cengiz
E
, Fox
LA
, Hannon
TS
, Miller
K
, et al. Metformin improves peripheral insulin sensitivity in youth with type 1 diabetes
. J Clin Endocrinol Metab
. 2019
;104
(8
):3265
–78
. 188.
Mathieu
C
, Zinman
B
, Hemmingsson
JU
, Woo
V
, Colman
P
, Christiansen
E
, et al. Efficacy and safety of liraglutide added to insulin treatment in type 1 diabetes: the ADJUNCT ONE treat-to-target randomized trial
. Diabetes Care
. 2016
;39
(10
):1702
–10
. 189.
Ahrén
B
, Hirsch
IB
, Pieber
TR
, Mathieu
C
, Gómez-Peralta
F
, Hansen
TK
, et al. Efficacy and safety of liraglutide added to capped insulin treatment in subjects with type 1 diabetes: the ADJUNCT TWO randomized trial
. Diabetes Care
. 2016
;39
(10
):1693
–701
. 190.
Guo
H
, Fang
C
, Huang
Y
, Pei
Y
, Chen
L
, Hu
J
. The efficacy and safety of DPP4 inhibitors in patients with type 1 diabetes: a systematic review and meta-analysis
. Diabetes Res Clin Pract
. 2016
;121
:184
–91
. 191.
Bode
BW
, Cengiz
E
, Wadwa
RP
, Banks
P
, Danne
T
, Kushner
JA
, et al. Effects of sotagliflozin combined with intensive insulin therapy in young adults with poorly controlled type 1 diabetes: the JDRF sotagliflozin study
. Diabetes Technol Ther
. 2021
;23
(1
):59
–69
. 192.
Kaku
K
, Isaka
H
, Sakatani
T
, Toyoshima
J
. Efficacy and safety of ipragliflozin add-on therapy to insulin in Japanese patients with type 1 diabetes mellitus: a randomized, double-blind, phase 3 trial
. Diabetes Obes Metab
. 2019
;21
(10
):2284
–93
. 193.
JDRF calls for AstraZeneca to explain type 1 diabetes drug withdrawal
. [cited 2024 April 9]; Available from: https://jdrf.org.uk/news/jdrf-calls-for-astrazeneca-to-explain-type-1-diabetes-drug-withdrawal/194.
(Sotagliflozin), Z
. [cited 2024 April 5]; Available from: https://www.ema.europa.eu/en/documents/overview/zynquista-epar-medicine-overview_en.pdf195.
Umpierrez
GE
, Jones
S
, Smiley
D
, Mulligan
P
, Keyler
T
, Temponi
A
, et al. Insulin analogs versus human insulin in the treatment of patients with diabetic ketoacidosis: a randomized controlled trial
. Diabetes Care
. 2009
;32
(7
):1164
–9
. 196.
Pérez
A
, Ramos
A
, Carreras
G
. Insulin therapy in hospitalized patients
. Am J Ther
. 2020
;27
(1
):e71
–e78
. 197.
Tosur
M
, Viau-Colindres
J
, Astudillo
M
, Redondo
MJ
, Lyons
SK
. Medication-induced hyperglycemia: pediatric perspective
. BMJ Open Diabetes Res Care
. 2020
;8
(1
):e000801
. 198.
Fram
RY
, Cree
MG
, Wolfe
RR
, Mlcak
RP
, Qian
T
, Chinkes
DL
, et al. Intensive insulin therapy improves insulin sensitivity and mitochondrial function in severely burned children
. Crit Care Med
. 2010
;38
(6
):1475
–83
. 199.
Wolfsdorf
JI
, Glaser
N
, Agus
M
, Fritsch
M
, Hanas
R
, Rewers
A
, et al. ISPAD clinical practice consensus guidelines 2018: diabetic ketoacidosis and the hyperglycemic hyperosmolar state
. Pediatr Diabetes
. 2018
;19
(Suppl 27
):155
–77
. 200.
Glaser
N
, Fritsch
M
, Priyambada
L
, Rewers
A
, Cherubini
V
, Estrada
S
, et al. ISPAD clinical practice consensus guidelines 2022: diabetic ketoacidosis and hyperglycemic hyperosmolar state
. Pediatr Diabetes
. 2022
;23
(7
):835
–56
. 201.
Cohen
M
, Leibovitz
N
, Shilo
S
, Zuckerman-Levin
N
, Shavit
I
, Shehadeh
N
. Subcutaneous regular insulin for the treatment of diabetic ketoacidosis in children
. Pediatr Diabetes
. 2017
;18
(4
):290
–6
. 202.
Della Manna
T
, Steinmetz
L
, Campos
PR
, Farhat
SCL
, Schvartsman
C
, Kuperman
H
, et al. Subcutaneous use of a fast-acting insulin analog: an alternative treatment for pediatric patients with diabetic ketoacidosis
. Diabetes Care
. 2005
;28
(8
):1856
–61
. 203.
Ersöz
H
, Ukinc
K
, Köse
M
, Erem
C
, Gunduz
A
, Hacihasanoglu
AB
, et al. Subcutaneous lispro and intravenous regular insulin treatments are equally effective and safe for the treatment of mild and moderate diabetic ketoacidosis in adult patients
. Int J Clin Pract
. 2006
;60
(4
):429
–33
. 204.
Umpierrez
GE
, Cuervo
R
, Karabell
A
, Latif
K
, Freire
AX
, Kitabchi
AE
. Treatment of diabetic ketoacidosis with subcutaneous insulin aspart
. Diabetes Care
. 2004
;27
(8
):1873
–8
. 205.
Savoldelli
RD
, Farhat
SC
, Manna
TD
. Alternative management of diabetic ketoacidosis in a Brazilian pediatric emergency department
. Diabetol Metab Syndr
. 2010
;2
(1
):41
. 206.
Cohen
MLN
, Leibovitz
N
, Shilo
S
, Zuckerman-Levin
N
, Shavit
I
, Shehadeh
N
. Subcutaneous regular insulin for the treatment of diabetic ketoacidosis in children
. Pediatr Diabetes
. 2017
;18
(4
):290
–6
. 207.
Ayyavoo
A
, Ravikulan
A
, Palany
R
. Treatment of diabetic ketoacidosis with subcutaneous regular insulin in a non-ICU setting is effective and economical: a single-center experience
. J Pediatr Endocrinol Diabetes
. 2022
;2
(2
):50
–5
. 208.
Bali
IA
, Al-Jelaify
MR
, AlRuthia
Y
, Mulla
JZ
, Amlih
DF
, Bin Omair
AI
, et al. Estimated cost-effectiveness of subcutaneous insulin aspart in the management of mild diabetic ketoacidosis among children
. JAMA Netw Open
. 2022
;5
(9
):e2230043
. 209.
Organization W.H
. First-ever global coverage targets for diabetes adopted at the 75th World Health Assembly
. [cited 2022 august 30]; Available from: https://www.who.int/news-room/feature-stories/detail/first-ever-global-coverage-targets-for-diabetes-adopted-at-the-75-th-world-health-assembly210.
Cernea
S
, Raz
I
. Insulin therapy: future perspectives
. Am J Ther
. 2020
;27
(1
):e121
–e132
. 211.
Limbert
C
, Kowalski
AJ
, Danne
TPA
. Automated insulin delivery: a milestone on the road to insulin independence in type 1 diabetes
. Diabetes Care
. 2024
;47
(6
):918
–20
. 212.
Michael
J
, Haller
KJB
, Rachel
EJB
, Casteels
K
, Couper
JJ
, Craig
ME
, et al. ISPAD clinical practice consensus guidelines 2024: screening, staging, and Strategies to Preserve beta cell function in children and adolescents with type 1 diabetes
. Horm Res Pediat
. 2024
; In preparation.© 2025 S. Karger AG, Basel
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
2025
You do not currently have access to this content.
