Terapia insulinica
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Il trattamento insulinico: approccio prandiale e basale
Dott. G. GRUTTADAURIA
Unità operativa di Medicina Interna
Presidio ospedaliero S’Elia- Caltanissetta
Caltanissetta 18 Dicembre 2010 Hotel San Michele
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Diabete MellitoDiabete MellitoPrevalenza stimata nel Prevalenza stimata nel
mondo*mondo*
Diabete MellitoDiabete MellitoPrevalenza stimata nel Prevalenza stimata nel
mondo*mondo*Diabete 1994 2000 2010
Tipo 1 12 18 24
Tipo 2 99 157 216
TOTALE 110 175 239
Diabete 1994 2000 2010
Tipo 1 12 18 24
Tipo 2 99 157 216
TOTALE 110 175 239
*x milione*x milione
OMSOMSOMSOMS
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Diabete MellitoDiabete MellitoPrevalenza stimata in Prevalenza stimata in
ItaliaItalia
Diabete MellitoDiabete MellitoPrevalenza stimata in Prevalenza stimata in
ItaliaItalia
Diabete 1994 2000 2010
Tipo 1 293 307 320
Tipo 2 2.602 2.721 2.840
TOTALE 2.895 3.028 3.160
Diabete 1994 2000 2010
Tipo 1 293 307 320
Tipo 2 2.602 2.721 2.840
TOTALE 2.895 3.028 3.160
OMSOMSOMSOMS
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Il DMT2 è caratterizzato da carenza di insulina e da insulino resistenza
FFA=acidi grassi liberi. Adattata da Yki-Järvinen H. In: Textbook of Diabetes 1. 3rd ed. Oxford, UK: Blackwell; 2003:22.122.19.
Gluco-lipotossicit
à
Produzione di glucosio
nel fegato
Sovrappeso, inattività(ereditata/acquisita)
FFA
Diabete di tipo 2
Fattori ereditati/acquisiti
Uptake di
glucosio
Carenza di insulina Insulino resistenza
Iperglicemia
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Altre conseguenze dell’ insulino resistenza
Arterie
Insulino resistenza
PiastrineAlterazioni
procoagulanti
Produzione diTG nel fegato
TG=trigliceridi.Adattata da Yki-Järvinen H. In: Textbook of Diabetes 1. 3rd ed. Oxford, UK: Blackwell; 2003:22.122.19.
Malattia ateromatosa delle arterie
Dislipidemia
diabetica
Aumentata rigidità, ipertensione,disfunzione endoteliale
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HOMA=homeostasis model assessment.UKPDS Group. Diabetes 1995;44:1249―58. Adattata da Holman RR. Diabetes Res Clin Pract 1998;40(suppl 1):S21―5.
Il declino della funzione della -cellula determina la natura progressiva del DMT2
Fu
nzi
on
e d
ella
-cellu
la
(% d
el n
orm
ale
con
HO
MA
)
Tempo (anni)
0
20
40
60
80
100
―10 ―8 ―6 ―4 ―2 0 2 4 6
Momento della diagnosi
?
Funzione pancreatica= 50% del normale
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SCOPI DELLA TERAPIA
EVITARE LE COMPLICANZE
- ACUTE
- CRONICHE
MIGLIORARE LA QUALITA’ DI VITA
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Il signor Giulio
• 58 anni
• Insegnante di economia
• Sposato con due figli
• Ex fumatore.
• Sedentario
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BARRIERS TO INSULIN THERAPYIn realtà…….
…Nel DM di tipo 2, la terapia insulinica:
• Aumenta la sensibilità all’insulina attraverso la riduzione della
glucotossicità
• Probabilmente, riduce il rischio CV
• L’incremento ponderale è modesto
• L’ipoglicemia severa è rara
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Standard di cura SID - AMD - Diabete Italia
5.1 Utilizzare una insulina basale come detemir, glargine o NPH (con NPH il rischio di ipoglicemia è tuttavia maggiore).oppure5.2 Utilizzare un analogo rapido ai pasti.oppure5.3 Utilizzare direttamente uno schema basal-bolus.oppure5.4 In presenza di gravi ed evidenti problemi di compliance, utilizzare una doppia somministrazione di insulina pre-miscelata (bifasica), tentando comunque di educare il paziente verso uno schema basal-bolus.
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NPL 14-18 hours
6-20
20-24
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Profilo farmacodinamico delle insuline Lispro e Umana Regolare
RCP Humalog
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Vantaggi della farmacocinetica di Lispro
• Ripristino della prima fase secretoria• Miglioramento dell’efficienza secretoria della
beta-cellula• Riduzione della produzione epatica di glucosio• Riduzione del rischio di ipoglicemie tardive
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HumalogHumalog®® Reduces Postprandial Blood Reduces Postprandial Blood Glucose Excursions in Type 2 DiabetesGlucose Excursions in Type 2 Diabetes
Anderson JH et al. Arch Internal Med 1997;157:1249-1255.
6 month cross-over study: mealtime Humalog or regular human insulin for 3 months, then switch to other treatment
Humulin® R
Humalog
*p<0.001
Postprandial time (h)
Ris
e in
Se
rum
G
luc
os
e (
mm
ol/L
)
*
N= 722 T2DM
*
0
1
2
3
4
0 1 2
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HumalogHumalog®® Reduces Overall and Nocturnal Reduces Overall and Nocturnal Hypoglycemia in Patients with Type 2 DiabetesHypoglycemia in Patients with Type 2 Diabetes
Combined treatment periods (episodes/patient/30 days)
Anderson JH et al. Arch Internal Med 1997;157:1249-1255.
All Episodes (overall) Episodes from Midnight to 6AM
P=0.02
P<0.001
0.
0.2
0.4
0.6
0.8
1.0
0
1
2
3
4
Humulin® R
Humalog
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61
InsulinInsulin(µU/mL)(µU/mL)
GlucoseGlucose(mg/dL)(mg/dL)
Physiologic Insulin Secretion: 24-Hour Profile
150150
100100
5050
0077 88 99 1010 1111 1212 11 22 33 44 55 66 77 88 99
A.M.A.M. P.M.P.M.
Basal GlucoseBasal Glucose
Time of DayTime of Day
5050
2525
00 Basal InsulinBasal Insulin
Breakfast Lunch dinnerBreakfast Lunch dinner
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