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Mortalitate la 1 an:
65% nainte de 1915
45% ntre 1915-1922
naintea insulinoterapiei
George HA Clowes
George B Walden
1923 Insulina in Europa - Denemarca
August Krogh
Nordisk Insulin
Laboratorium Hans Christian Hagedorn
Novo insulin
Pedersen Brothers
1923 Insulina in Europa - Germania
Farbwerke Hoechst,
1920s Frankfurt, Germany.
Primele seringi de insulina
Insulinoterapia in anii 1920-1950
R
Primele preparate de insulina cu durata
prelungita de actiune Insulina NPH
Frederick Sanger
1983
Insulinoterapia Conventionala
NPH R Premix
Insulinoterapia Conventionala
R + R + Premix
Tratamentul DZ tip 1: 1950-1980
Diet rigid
Timp (ore)
Analogi de insulina cu actiune rapida
Analogi prandiali
2004 - Glulisine
Analogi de insulina cu actiune prelungita
Analogi bazali
2001 2005
Profil actiune insuline utilizate
curent in practica
Insulin Productor Debut Vrf aciune Durat
(ore) (ore) (ore)
Analogi rapizi insulin
Lispro (Humalog) Eli Lilly 10-15 min 1-2 3-5
Aspart (Novorapid) Novo Nordisk 10-15 min 1-2 3-5
Glulisin (Apidra) Sanofi 10-15 min 1-2 3-5
Analogi leni insulin
Glargine U100 (Lantus) Sanofi 2-4 - pn la 24 h
Glargine U300 (Toujeo) Sanofi 2-4 - > 24 h
Detemir (Levemir) Novo Nordisk 1-2 12h ? 20-24
Degludec (Tresiba) Novo Nordisk 0.5-1.5 - > 24
Insulin uman rapid (regular)
Actrapid HM (uman) Novo Nordisk 0.5 2-3 5-8
Humulin R (uman) Eli Lilly 0.5 2-3 5-8
Insuman Rapid (uman) Sanofi 0.5 2-3 5-8
Insulin NPH
Insuman Bazal (uman) Sanofi 1.5-4 4-10 12-20
Humulin N (uman) Eli Lilly 1.5-4 4-10 12-20
Insulin premixat
Humulin M 1-5 Eli Lilly 0.5 4-10 12-20
Mixtard 10-50 Novo Nordisk 0.5 4-10 12-20
Insuman Comb 25, 50 Sanofi 0.5 4-10 12-20
Insulin premixat analog
Humalog Mix 25, 50 Eli Lilly 10-15 min 4-10 12-20
NovoMix 30 Novo Nordisk 1-8 12-18
Insulinoterapia in DZ1
Insulinoterapie bazal-bolus
(functionala / fiziologica)
Principii
intolerance or If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):
contraindication Metformin Metformin Metformin Metformin Metformin Metformin
+ + + + + +
Dual Sulfonylurea Thiazolidine- DPP-4 SGLT2 GLP-1 receptor Insulin (basal)
therapy dione inhibitor inhibitor agonist
Efficacy* high high intermediate intermediate high highest
Hypo risk moderate risk low risk low risk low risk low risk high risk
HbA1c Weight gain gain neutral loss loss gain
9% Side effects hypoglycemia edema, HF, fxs rare GU, dehydration GI hypoglycemia
Costs low low high high high variable
If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):
Metformin Metformin Metformin Metformin Metformin Metformin
+ + + + + +
Triple Sulfonylurea Thiazolidine-
dione
DPP-4
Inhibitor
SGLT-2
Inhibitor
GLP-1 receptor
agonist
Insulin (basal)
therapy + + + + + +
TZD SU SU SU SU TZD
Basal Insulin
(usually with metformin +/-
other non-insulin agent)
If not
controlled after
FBG target is reached
(or if dose > 0.5 U/kg/day),
treat PPG excursions with
meal-time insulin.
(Consider initial
Add 1 rapid insulin* injections GLP-1-RA Change to
before largest meal trial.) premixed insulin* twice daily
Start: 4U, 0.1 U/kg, or 10% basal dose. If Start: Divide current basal dose into 2/3 AM,
A1c<8%, consider basal by same amount. 1/3 PM or 1/2 AM, 1/2 PM.
Adjust: dose by 1-2 U or 10-15% once- Adjust: dose by 1-2 U or 10-15% once-
twice weekly until SMBG target reached. twice weekly until SMBG target reached.
For hypo: Determine and address cause; For hypo: Determine and address cause;
corresponding dose by 2-4 U or 10-20%. corresponding dose by 2-4 U or 10-20%.
If not If not
controlled, Add 2 rapid insulin* injections controlled,
consider basal-
bolus.
before meals ('basal-bolus) consider basal-
bolus.
Start: 4U, 0.1 U/kg, or 10% basal dose/meal. If
A1c<8%, consider basal by same amount.
Adjust: dose by 1-2 U or 10-15% once-twice
weekly to achieve SMBG target.
For hypo: Determine and address cause;
Diabetes Care 2015;38:140-149; corresponding dose by 2-4 U or 10-20%.
Diabetologia 2015;58:429-442
Bariere psihologice la iniierea insulinoterapiei
Tratamentul obezitii
EP Joslin 1917
The Treatment of Diabetes Mellitus
Jean Pirart
Diab Metab 1977
Diabetes Care 1978
Studiul DCCT - Scop
Sa determine daca:
Ameliorarea controlului metabolic in DZ1 prin
insulinoterapie intensificat (Bazal Bolus) cu
scderea HbA1c sub 7% duce la scderea
frecvenei complicaiilor cronice comparativ cu
insulinoterapia conventional
DCCT Impact pe HbA1c si glicemie
300 - 11 -
Conventional
10 -
Conventional
250 -
9-
200 -
8-
7-
150 -
6-
Intensive
Intensive
100 - 5-
Breakfast Lunch Dinner Bedtime 0 1 2 3 4 5 6 7 8 9 1
Time Year of study 0
NewEngl J Med 1993, 329, 977
DCCT: Impact pe retinopatie
60 -
50 -
% pacieni
40 -
76%
30 -
Conventional
20 -
p<0.001
10 -
Intensiv
0-
0 1 2 3 4 5 6 7 8 9
Year of study
Intensiv
30 Conventional
Patients (%)
20
34%
10
0
0 2 4 6 8 10
Year
Intensiv
Conventional Pacientii tratai
11
convenional au trecut
10 la tratament intensificat
HbA1c (%)
0
1 2 3 4 5 6 7 8 9 DCCT1 2 3 4 5 6 7
end
DCCT EDIC
Ani
1. White et al 2008 Dec;126(12):1707-15. 2. Genuth Endocrine Practice 2006 Jan-Feb;12 Suppl 1:34-41.
DCCT / EDIC Memorie Metabolic
1. White et al 2008 Dec;126(12):1707-15. 2. Genuth Endocrine Practice 2006 Jan-Feb;12 Suppl 1:34-41.
De reinut ! (1)
Insulinoterapia n DZ1:
Insulinoterapia n DZ2: