Upload File

glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 –...

  • Home
  • Documents
  • Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes
56
Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10 -5 0 5 10 15 20 25 30 Years of diabetes Burger HG, et al. 2001. Diabetes Mellitus, Carbohydrate Metabolism, and Lipid Disorders. In Endocrinology. 4 th ed. Edited by LJ DeGroot and JL Jameson. Philadelphia: W.B. Saunders Co., 2001. Originally published in Type 2 Diabetes BASICS. (International Diabetes Center, Minneapolis, 2000). Relative function (%) Fasting glucose Obesity Obesity IFG IFG Diabetes Diabetes Uncontrolled Uncontrolled hyperglycemia hyperglycemia Insulin resistance Insulin resistance and -cell dysfunction are fundamental to type 2 diabetes Post-prandial glucose Insulin secretion Clinical diagnosis

Upload: azzolino-paoletti

Post on 01-May-2015

247 views

Category:

Documents


1 download

Report

Tags:

TRANSCRIPT

Page 1: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes

Glucose(mg/dl)

50 –

100 –

150 –

200 –

250 –

300 –

350 –

0 –

50 –

100 –

150 –

200 –

250 –

-10 -5 0 5 10 15 20 25 30Years of diabetes

Burger HG, et al. 2001. Diabetes Mellitus, Carbohydrate Metabolism, and Lipid Disorders. In Endocrinology. 4th ed. Edited by LJ DeGroot and JL Jameson. Philadelphia: W.B. Saunders Co., 2001.

Originally published in Type 2 Diabetes BASICS. (International Diabetes Center, Minneapolis, 2000).

Relativefunction

(%)

Fasting glucose

ObesityObesity IFGIFG DiabetesDiabetes UncontrolledUncontrolledhyperglycemiahyperglycemia

Insulin resistance

Insulin resistance and -cell dysfunction are fundamental to type 2 diabetes

Post-prandialglucose

Insulin secretionClinical diagnosis

Page 2: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes

A Century of Diabetes Care

Sulfonylureas

Alpha-glucosidase InhibitorsBiguanide

GlitazonesMeglitinides

Insulin therapy

1920

Type 2

20001900 1950

Diet

Type 1

20001900 19501920

Insulin therapyPump th

erapy

Human insulin

Insulin analogs

First h

uman treated

NPH insulin

Page 3: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes
Page 4: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes

*Lower extremity amputation or fatal peripheral vascular disease

Per

cen

tag

e re

du

ctio

n i

n r

elat

ive

risk

co

rres

po

nd

ing

to

a 1

% f

all

in H

bA

1c

–50

–45

–40

–35

–30

–25

–20

–15

–10

–5

0

21%

P < 0.0001

Any diabetes-related

endpoint

21%

P < 0.0001

Diabetes-related death

14%

P < 0.0001

All cause

mortality

14%

P < 0.0001

Myocardial infarction

12%

P = 0.035

Stroke

43%

P < 0.0001

Peripheral vascular disease*

37%

P < 0.0001

Microvascular disease

19%

P < 0.0001

Cataract extraction

Adapted from Stratton IM, et al. UKPDS 35. BMJ 2000; 321:405–412.

UKPDS: reduced micro- and macrovascular complications for a 1% decrease in HbA1c

Page 5: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes

EPIC-Norfolk study: Risk of CV events or Death Associated with HbA1c Level

Ag

e-ad

just

ed r

elat

ive

risk

Men

0

1

2

3

4

5

6

7

8

CHD events CVD events All-causemortality

CHD events CVD events All-causemortality

Women

5–5.4% 5.5–5.9% 7%6.5–6.9%6.0–6.4%HbA1c level:

P 0.001 for linear trend across HbA1c categories for all endpoints.

Khaw et al. Ann Intern Med 2004; 141: 413–20

Page 6: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes

STENO-2 STUDY

Page 7: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes

SECRETAGOGHI

•Sulfoniluree: Glibenclamide

Gliclazide

Glimepiride

•Glinidi: Repaglinide

Nateglinide

Page 8: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes
Page 9: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes

K+

Ca++Ca++

K+

Precondizionamento ischemico

ATPADP

Cellula muscolarecardiaca o coronarica

Normale

Page 10: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes

K+

Ca++Ca++

K+ ATP

ADP

Ischemia

Cellula muscolarecardiaca o coronarica

ContrattilitàConsumo energia

Rilascio muscoloVasodilatazione

Precondizionamento ischemico

Page 11: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes

K+

Ca++Ca++

K+

SUR2

ATP

ADP

Cellula muscolarecardiaca o coronarica

Ischemia

FARMACO

ContrattilitàConsumo energia

Rilascio muscoloVasodilatazione

Precondizionamento ischemico

Page 12: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes

Sulfaniluree e Preconditioning1: Lee TM, Chou TF. Impairment of myocardial protection in type 2 diabetic patients. J Clin Endocrinol Metab. 2003 Feb;88(2):531-7.

2: Riddle MC. Editorial: sulfonylureas differ in effects on ischemic preconditioning--is it time to retire glyburide? J Clin Endocrinol Metab. 2003 Feb;88(2):528-30.

3: Scognamiglio R, Avogaro A, Vigili de Kreutzenberg S, Negut C, Palisi M, Bagolin E, Tiengo A. Effects of treatment with sulfonylurea drugs or insulin on ischemia-induced myocardial dysfunction in type 2 diabetes. Diabetes. 2002 Mar;51(3):808-12.

4: Lee TM, Su SF, Chou TF, Lee YT, Tsai CH. Loss of preconditioning by attenuated activation of myocardial ATP-sensitive potassium channels in elderly patients undergoing coronary angioplasty. Circulation. 2002 Jan 22;105(3):334-40.

5: Ghosh S, Standen NB, Galinianes M. Failure to precondition pathological human myocardium. J Am Coll Cardiol. 2001 Mar 1;37(3):711-8.

6: Ovunc K. Effects of glibenclamide, a K(ATP) channel blocker, on warm-up phenomenon in type II diabetic patients with chronic stable angina pectoris.Clin Cardiol. 2000 Jul;23:535-9.

7: Tomai F, Danesi A, Ghini AS, Crea F, Perino M, Gaspardone A, Ruggeri G, Chiariello L, Gioffre PA. Effects of K(ATP) channel blockade by glibenclamide on the warm-up phenomenon. Eur Heart J. 1999 Feb;20(3):196-202.

Page 13: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes

B D

437

Glibenclam.

p<0.05

3712

Insulin

p= NS

468 451

1

B DB D

Page 14: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes
Page 15: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes

Impairment of Myocardial Protection in Type

2 Diabetic Patients: ST segment shift (mV)

0

0,2

0,4

0,6

0,8

1

1,2

Glibenclamide Glimepiride

Page 16: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes

• Metformina

• (Fenformina)

BIGUANIDI

Page 17: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes
Page 18: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes

a

c

b

Glucose 5 mM

Glucose 20 mM

Glucose 20 mM+Metformin

Page 19: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes
Page 20: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes

UKPDS 34. Lancet 1998;352:854-865.

EFFECT OF METFORMIN IN OVERWEIGHT PATIENTS

Page 21: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes

Is Metformin cardioprotective?

Diabetes Care 2002

Page 22: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes

Risk of Fatal and Nonfatal Lactic Acidosis With Metformin Use in Type 2 Diabetes Mellitus: Systematic Review and Meta-

analysisSalpeter SR, Greyber E, Pasternak GA, Salpeter EE

There is no evidence to date that metformin therapy is associated with an increased risk of lactic acidosis or with increased levels of lactate compared with other antihyperglycemic treatments if the drugs are prescribed under study conditions, taking into account contraindications.

Arch Intern Med 2003;163(21):2594-602

Page 23: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes

CONTROINDICAZIONI E LINEE-GUIDA PER LA SOSPENSIONE DELLA METFORMINA

BMJ, 326, 2003

• Sospendere se la creatininemia è >150 mol/l*• Sospendere durante i periodi di sospetta ipossia tissutale (peres. durante infarto del miocardio, sepsi, etc.)• Sospendere per 3 giorni dopo somministrazione di mezzo dicontrasto contenente iodio e ripristinare solo dopo controllodei parametri di funzionalità renale• Sospendere 2 giorni prima di un’anestesia generale e ripristinare quando la funzionalità renale è stabile

*Qualsiasi concentrazione di creatinina venga scelta come livello cut-off perinsuficienza renale sarà arbitrario in considerazione della massa muscolaredell’individuo e del turnover proteico; precauzione nel paziente anziano.

Page 24: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes

Condizioni associate Condizioni associate (% pazienti)(% pazienti)

Phillips, Phillips, BMJ BMJ 1:239, 19781:239, 1978

Metformina ed Acidosi LatticaMetformina ed Acidosi Lattica

0

20

40

60

80

100

I R Epat. CHF No

23 casi riportati in letteratura fino al 197823 casi riportati in letteratura fino al 1978

Page 25: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes

Conclusions. Metformin was the only antidiabetic agent not associated with harm in patients with heart failure and diabetes. It was associatedwith reduced all cause mortality in two of the three studies.

Page 26: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes

Nathan DM, Buse JB, Davidson MB, et al. Management of hyperglycaemia in type 2 diabetes: a consensus algorithm

for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of

Diabetes. Diabetologia 2006;49:1711-21.

Page 27: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes

TIAZOLIDINEDIONI (GLITAZONI)

• Pioglitazone

• Rosiglitazone

Page 28: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes
Page 29: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes

Adipocyte

Thiazolidinediones: mechanism of action

Thiazolidinedione (rosiglitazone, pioglitazone)

DNA

Nucleus

GLUT 4RNA

GLUT 4

Insulin

Glucose

Thiazolidinedione

Storage granule

Transcription

Translation

PPAR

Cytoplasm

GLUT 4+

Page 30: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes
Page 31: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes
Page 32: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes
Page 33: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes
Page 34: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes
Page 35: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes
Page 36: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes
Page 37: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes

GLITAZONI - EFFETTI INDESIDERATI

Edema

Anemia (da diluizione)

Ipercolesterolemia

Incremento ponderale

Epatopatia

Insufficienza Cardiaca

ALTRI: trombocitopenia, ipoglicemia, sonnolenza, vertigini, cefalea, parestesie, dolori addome, flatulenza, nausea, alopecia, rash, astenia

Page 38: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes

ADA-AHA 2006

Prima di iniziare la terapia verificare la presenza di cardiopatia, edema, dispnea

Page 39: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes

STOP-NIDDM trial

Effect of acarbose and placebo on cumulative probability of remaning free of diabetes over

timeLancet, 2002

Page 40: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes
Page 41: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes

Insulina

Page 42: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes

Le insuline nella storia Insulina porcina: non piu’ in commercio differiva da quella umana per un aminoacido Insulina bovina: non piu’ in commercio differiva da quella umana per tre aminoacidi Insulina umana: disponibile, in produzione dagli anni ‘80 non differisce da quella umana e viene prodotta con la tecnica del DNA ricombinante: piu’ pura

Insulina analogo: disponibile, in produzione dal ‘96 differisce dall’umana: miglior farmacocinetica

Page 43: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes

Comparison of Human Insulins / Analogues

Regular 30–60 min 2–4 h 6–10 h

Lispro/aspart 5–15 min 1–2 h 4–6 h

NPH/Lente 1–2 h 4–8 h 10–20 h

Ultralente 2–4 h Unpredictable 16–20 h

Glargine 1–2 h Flat ~24 h

Insulin Onset of action PeakDuration of action

Page 44: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes

4:00 16:00 20:00 24:00 4:00

Breakfast Lunch Dinner

8:0012:008:00

Time

Glargineor

Detemir

Lispro Lispro Lispro

Aspart Aspart Aspartor oror

Pla

sma

insu

lin

Basal/Bolus Treatment Program withRapid-acting and Long-acting Analogs

Page 45: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes

• Mantenere la normoglicemia

• Evitare le complicanze acute

• Evitare o arrestare la progressione delle complicanze croniche

• Migliorare la qualità di vita

Scopi del trattamento insulinico intensivo

Page 46: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes
Page 47: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes
Page 48: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes

Dandona P et al, Am J Cardiol 2007;99[suppl]15B-26B.

Page 49: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes

GLP-1

• “Incretin” hormone secreted by jejunal and ileal L cells in response to a meal

• Stimulates insulin secretion

• Decreases glucagon secretion

• Slows gastric emptying

• Reduces fuel intake (increases satiety)

• Improves insulin sensitivity

• Increases -cell mass and improves -cell function (animal studies)

Page 50: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes

ProGIP GIP (1-42)

Cellule K – tratto GI prossimale(duodeno e digiuno prossimale)

Proglucagone GLP 1(7-37) GLP 1(7-36)NH2

Cellule L – tratto GI distale(ileo e colon)

GIP = polipeptide insulinotropico glucosio-dipendenteGLP 1 = peptide 1 glucagone-simile

Stimola la secrezione di insulina in

maniera glucosio-dipendente

Promuove la proliferazione e la

sopravvivenza delle cellule beta in

colture di isole pancreatiche

Adattato da Drucker DJ Diabetes Care 2003;26:2929–2940; Ahrén B Curr Diab Rep 2003;3:365–372; Drucker DJ Gastroenterology 2002;122:531–544; Farilla L et al Endocrinology 2003;144:5149–5158; Trümper A et al Mol Endocrinol 2001;15:1559–1570; Trümper A et al J Endocrinol 2002;174:233–246.

Page 51: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes

ProGIP GIP (1-42)

Cellule K – tratto GI prossimale(duodeno e digiuno prossimale)

Proglucagone GLP 1(7-37) GLP 1(7-36)NH2

Cellule L – tratto GI distale(ileo e colon)

GIP = polipeptide insulinotropico glucosio-dipendenteGLP 1 = peptide 1 glucagone-simile

Stimola la secrezione di insulina in

maniera glucosio-dipendente

Sopprime la produzione epatica di

glucosio attraverso l’inibizione glucosio-

dipendente della secrezione di glucagone

Promuove la proliferazione e la

sopravvivenza delle cellule beta in

modelli animali ed in colture di isole

pancreatiche umane

Adattato da Drucker DJ Diabetes Care 2003;26:2929–2940; Ahrén B Curr Diab Rep 2003;3:365–372; Drucker DJ Gastroenterology 2002;122:531–544; Farilla L et al Endocrinology 2003;144:5149–5158; Trümper A et al Mol Endocrinol 2001;15:1559–1570; Trümper A et al J Endocrinol 2002;174:233–246.

Page 52: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes

GLP-1 GIP

Secreto dalle cellule L dell’intestino distale (ileo e colon)

Secreto dalle cellule K dell’intestino prossimale (duodeno)

Stimola la secrezione insulinica in modo glucosio dipendente

Stimola la secrezione insulinica in modo glucosio dipendente

Sopprime la produzione epatica di glucosio inibendo la secrezione di glucagone in modo glucosio dipendente

Migliora la proliferazione e la sopravvivenza delle beta cellule (modelli animali e colture di cellule umane)

Migliora la proliferazione e la sopravvivenza delle beta cellule in linee di colture cellulari

GLP-1 e GIP

Adapted from Drucker DJ Diabetes Care 2003;26:2929–2940; Ahrén B Curr Diab Rep 2003;3:365–372; Drucker DJ Gastroenterology 2002;122:531–544; Farilla L et al Endocrinology 2003;144:5149–5158; Trümper A et al Mol Endocrinol 2001;15:1559–1570; Trümper A et al J Endocrinol 2002;174:233–246.

Page 53: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes

Biosynthesis & Regulation of GLP-1

Page 54: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes
Page 55: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes

Aumento del GLP-1

Adattato da: Drucker. Curr Pharm Des. 2001; Drucker. Mol Endocrinol. 2003

Secrezione GLP-1 è ridotta in diabete di Tipo 2

GLP-1 naturale ha una emivita estremamente breve

Aggiungere GLP-1 analoghi con emivita più lunga:

• exenatide

• liraglutide

Iniettivi

Bloccare DPP-4, l’enzima che degrada GLP-1:• sitagliptin• vildagliptin

Orali

- Sitagliptin- FDA approvato- EMEA approvato

-Vildagliptin -FDA non approvato -EMEA approvato

- Exenatide - FDA approvata- EMEA approvata

- Liraglutide- Phase III

Page 56: Glucose (mg/dl) 50 – 100 – 150 – 200 – 250 – 300 – 350 – 0 – 50 – 100 – 150 – 200 – 250 – -10-5051015202530 Years of diabetes Burger HG, et al. 2001. Diabetes

Future Century of Diabetes Care: A new Paradigm

Sulfonylureas

Alpha-glucosidase Inhibitors

Metformin

Glitazones

Human insulin

Insulin analogs

First human treated

NPH insulin

Exendin

Cardiovascular protection

Metabolic control

?


150 / 250 / 350 - johannus.com...User Manual Vivaldi 150/250/350 7 Main screen Vivaldi 250/350 and Vivaldi 150 with optional LIVEreverb Main screen Vivaldi 150 2.2 Switch on Switch

RODIACUT 150 - 250

DF SERIES 150 AND 250 • TRANSMISSION - … series 150 and 250...FUNK MANUFACTURING COMPANY SubsidiaryofDeere &Company • • DF SERIES 150 AND 250 • TRANSMISSION ASSEMBLYIOISASSEMBLY

material.eng.usm.my · 2020. 9. 8. · 400/ 3 magnifications 180 150, 200 (with IA 200 150 400 250 250 150 20/hr 150 150 100 280/run 30 300 300/hr 125 250/hr 250/hr 300/cycle run

200.232.30.99200.232.30.99/download.asp?file=3303016.pdf · 150 500 280 315 250 150 600 500 750 600 250 500 200 600 150 150 100 Notas: Previsäo para 1.800 motores/ dia. Investimento

Market 150 -100 -150 25 25 20 10 250 200 150 -50 -100 -150

 · Technical specifications Technical specifications TX 150 200 250 Nominal heat output kW 150 199 250 Heat output range kW 45-150 59-199 75-250

R Cookbook · temperature temperature 000000000000 350 0 50 150 250 350 0 50 150 250 Scatter Plot Line Plot

PGO BR 50-150-250 Manuel Utilisateur

2004 F-150 5.4L Engine, 2005 F-150, 250, 350 5.4L Engine

NS250N ; 250 A SIRCOVER 250 IMW 150/5 E 72 ; 0-150/250 A E-72 ; 0-500 V 0

ACOPLES INDSTRIALES - Dayflex Corporation · tipo “c” acople hembra -vastago manguera en aluminio, polipropileno, acero inox. 304, bronce 250 250 250 250 250 150 150 125 100 75

Eta Line 150-250

CHP column series - diaion.com · 20×150 20×250 4.6×150 4.6×250 10×150 20×150 20×250 CHP20/C04 4 4.6×150 CHPOD/C04 20×200 CHP20/C10 CHP07/C04 CHP07/C10 CHK40/C04 4 4.6×150

Telemetrele cu laser GLM 150 şi GLM 250 VF · 2021. 3. 11. · GLM 150 / 250 VF: G L M 150 / 250 VF Professional Bosch Albastru Professional “Lenght Measurer” – măsurare cu

 · 115" Altu ra Longitudes 150 200 150 200 150 200 150 250 250 250 El apoyo mínimo de los dinteles debe ser de 15 cm de cada lado del vano para tabiques diviso-

ABSTRACT (150 to 250 words)

Maintenance Manual GS 42 GS 51 GS 150 SV 150 GS 200 SV 200 ... 000950002 J... · Maintenance Manual GS 42 GS 51 GS 150 SV 150 GS 200 SV 200 GS 250 SV 250 GS 250 L SV 250 L GS 200/66

1 150 200 250 500 100 150 200 250 500 100 150 200 250 500 100 150 200 250 500 100 150 200 250 500 100 The Sun And The Earth And The Moon The Planets Potpourri

SIS. ECOTECH 150 - 200 - 250

P1001-290-150/125 P1001-300-200-150 P1001-360-250-250

EPIDEMIOLOGIA DE LA DIABETES · PDF fileLIMA CUSCO PUCALLPA PIURA CIUDADES PREVALENCIA INTOLERENCIA DIABETES. 0 50 100 150 200 250 NUM ERO < 20 20 a 40 41 a 60 61 a

P RivièreYama BROMONT P ska Psentiersbromont.org/wp-content/uploads/2016/01/Fev2017... · 2017. 2. 15. · 150 150 150 200 250 250 350 250 250 350 300 300 300 400 450 500 400 400

Салаты 150 г. Супы 250 г....Веселые «Осьминожки» Пельмешки «Детские» 160 150 160 250 г. 250 г. 250 г. (куриное филе,

Diabetes 2004 Palmer 250 64

ZPrinter 150 and 250 User Manual

Características clínicas de la diabetes mellitus en 250

Jugar Salir. 150 250 400 300 200 300 400 250 100 150 450 350 200 450 350 450 300 100 250 150 200 400 SALIR

Precautions taken n = 250 against Diabetes Mellitus

Diabetes: Diagnóstico y manejo actual - SMS CHILE · 250 200 150 100 50 0 1997 2000 2010 AÑO 300 2025 120 280 333 177 150 “La prevalencia de la diabetes en el mundo: 5.1% y aumentando...”

太陽コンクリート工業株式会社｜群馬県 ... · 300 400 150 250 120 250 250 00 x 200 g 276 126 150 150 H 150 400 x

Каталог применяемости аккумуляторовD ELTA CT · 150 250 250 250 250 250 600 50 100 250 50 50 50 50 50 125 125 150 150 200 250 250 300 400 500 2010

Diabetes Mellitus Diabetes Mellitus. Diabetes Mellitus Diabetes Mellitus epidemiology World WHO 2004 > 150 millionWorld WHO 2004 > 150 million China at

2210_95009 ZPrinter 150 and 250 QSG.pdf

List 1List 2List 3List 4List 5 $50 $100 $150 $200 $250 $500 $750 $1000 $1500 $50 $100 $150 $200 $250 $500 $750 $1000 $1500 $50 $100 $150 $200 $250 $500