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Importanta problemei
Background fiziopatologic
Definitia diabetului zaharat si a altor categorii de
intoleranta la glucoza
Diagnosticul diabetului
Tipurile de diabet zaharat: definitie, etiopatogeneza, istorie
naturala
Tratamentul diabetului zaharat
Complicatiile acute specifice ale DZ
Complicatiile cronice
Obezitatea
Dislipidemiile
Hiperuricemiile
Sd. metabolic
2010 diabetul zaharat
Prima cauza de orbire
Source: Diabetes Atlas 3rd Edition. www.eatlas.idf.org. Last accessed 25 January 2007
~90% dintre persoanele
cu diabet zaharat de tip 2
sunt supraponderale sau
obeze
0
10,025 61 6629 279 631 24
(Patient Numbers)
Whitehall Paris Helsinki
Study Prospective Study Policemen Study
Balkau. Lancet 1997; 350: 1680.
Diabetul zaharat de tip 2 cauza majora
de mortalitate
Fifth leading cause of death after infections,
CVD, cancer, and accidents
10
9 8.6 8.8
attributable to diabetes (%)
Men
8 Women
Excess mortality
6.9
7 6.6
6.0 6.1
6 5.4
5.1
5 4.8
4 3.4
3 2.5
2.2
2
0
Africa Americas Eastern Europe Southeast Western
Mediterranean Asia Pacific
110
100
90
80
70
60
1980 1982 1984 1986 1988 1990 1992 1994 1996
Anul
Diabetici
Non-diabetici
100 Brbai 100 Femei
% supravieuitorilor
% supravieuitorilor
90 90
80 80
n=1628 n=568
70 70
60 60
50 50
40 n=228 40 n=15
6
0 10 20 30 40 50 60 0 10 20 30 40 50 60
Luni Post-IM
Sprafka et al. Diabetes Care. 1991; 14: 537-543.
Riscul coronarian este echivalent pentru diabetici
i pentru nediabeticii cu un IM in antecedente
Incidena IM fatal i non-fatal de-a lungul a 7 ani de urmrire
ntr-o cohort finlandez
P < 0.001
P < 0.001
50% 45.0%
40%
Incidena n %
P < 0.001
30%
18.8% 20.2%
20%
10%
3.5%
0%
Cu IM Fr IM Cu IM Fr IM
Fr Diabet Cu Diabet
Pulsatorie
Bifazic
Insulinosecreia fiziologic profil 24 ore
Pancreasul endocrin - noiuni de anatomie i
fiziologie
Insulele Langerhans
800.000 1.500.000
1 2 % din masa
pancreatic total
Celule: A, B, C, D
ROLUL CENTRAL AL CANALELOR
KATP IN INSULINOSECRETIE
Secretia de insulina dupa adm glucozei intraduodenal
si intravenos
200
oral
intravenous
90
D INSULIN (mU/L)
D GLUCOSE (mg/100ml)
150
70
50
100
30
10 50
-10
-30 0
0 15 30 45 60 75 90 0 15 30 45 60 75 90
TIME (min) TIME (min)
Gut factors termed incretins
McIntyre et al 1964
Actiunea insulinotropa a GLP1 si GIP
asupra cel beta pancreatice
insulina
Rc. Insul.
IRS MAPK
In cazuri de IR sau
scazut crescut
insulino defic.
King GL, 1999
Type-2 Diabetes - A Question of
Balance -
Non-Diabetic State
Diabetic State
Adapted from Kahn SE, Prigeon RL, McCulloch DK, Boyko EJ, Bergman RN, Schwartz MW, Neifing JL, Ward WK, Beard JC, Palmer JP et al. Quantification of the relationship between
insulin sensitivity and beta cell function in human subjects. Evidence for a hyperbolic function. Diabetes 1993, 42: 1663-72. Bergman RN, Ader M. Huecking K, Van Citters G. Accurate
assessment of beta-cell function: the hyperbolic correction. Diabetes 2002, 51 Suppl. 1: S212-20. Bergman RN. Pathogenesis and prediction of diabetes mellitus: lessons from integrative
physiology. Mt Sinai J Med. 2002, 69: 280-90.
DZ tip 2 deficitul insulinosecreiei
postprandiale
800
Persoane nediabetice
insulinosecretie (pmol/min)
DZ tip 2
600
400
200
0
6 am 10 am 2 pm 6 pm 10 pm 2 am 6 am
timp
Poliurie
Polidipsie
Polifagie
Scdere ponderal
Astenie
Indicaiile screening-ului pentru DZ la subiecii
asimptomatici cu ajutorul glicemiei bazale
Diabet zaharat
Pe nemncate sau 110 (6,1) 110 (6,1) 126 (7,0)
La 2 ore dup glucoz 180 (10,9) 200 (11,1) 200 (11,1)
Scderea toleranei la glucoz
Pe nemncate i < 110 (<6,1) i < 110 (<6,1) i < 126 (<7,0) i
La 2 ore dup glucoz 120 (6,7) 140 (7,8) 140 (7,8)
Glicemie bazal modificat
Pe nemncate 100 (5,6) i 100 (5,6) i 110 ( 6,1) i
< 110 (<6,1) < 110 (<6,1) < 126 (<7,0)
CLASIFICAREA DIABETULUI ZAHARAT
Diabetul gestaional
Masa cel in dinamica
proliferare apoptoza
hypertrofie atrofie
Autoimunitate
Progresia distructiei beta celulare
Insuficienta functiei beta celulare
Dependenta de insulina exogena
Risc de ceto acidoza
Etiopatogenia DZ 1 autoimun
Predispoziie genetic
Factor de mediu (viral, toxic, alimentar)
Activare autoimun insulit
Scderea capacitii -secretoare; afectarea fazei secretorii
iniiale, dar insulinemia plasmatic este normal
Diabet clinic manifest; insulinemie plasmatic sczut,
hiperglicemie, apar simptomele
Apariia complicaiilor
Factorii de risc implicai n patologia
diabetului zaharat tip 2
vrst (ani)
20
Normal
30
Gene Insulino-rezisten Ambient
40
Deficienta de secretie
Diabetogene 50
a insulinei Obezitate
primare
secundare Diet
Gene legate de diabet Activitate fizic 60
Diabet tip II
Hyperglycemia
75
50
IFG/IGT DZ tip 2
25
-10 -6 -2 0 2 6 10 14
Ani de la diagnostic
Adapted from Lebovitz. Diabetes Reviews 1999;7(3)
UKPDS Group. Diabetes. 1995; 44:1249-1258.
Cum se combina insulino-rezistenta si disfunctia -
celulara in geneza diabetului zaharat de tip 2?
Insulin Hyperinsulinemia,
secretion then -cell failure
Post-
Abnormal
prandial
glucose tolerance
glucose
Fasting Hyperglycemia
glucose
*IGT = impaired glucose tolerance
Adapted from Type 2 Diabetes BASICS. International Diabetes Center (IDC), Minneapolis, 2000.
Pierderea masei celulare in istoria naturala a DZ2
Boala poligenica
Hiperinsulinemia
Malnutritie fetala formarii celulelor
beta
Copil cu greutate mica la nastere
thrifty gene
7% scaderea celuilelor beta/an
Epidemiologia i riscul CV n diabet
Risc pentru
ochi, rinichi,
Diabet nervi
STG Risc
CV
Limita glicemiei
normale
Gerstein H. 2003
Glicozilarea neenzimatic a proteinelor
TRIADE
HbA1c
Componentele cresterii HbA1c
Uncontrolled Diabetes HbA1c 8%
Basal hyperglycaemia
300 contributes ~2%
Post-prandial
Plasma glucose (mg/dL)
hyperglycaemia
contributes HbA1c ~1%
200 Post-prandial
hyperglycaemia
Fasting
hyperglycaemia
100
Normal
HbA1c ~5%
0
6 B 12 L 18 D 24 6
Time of day (h)
B=breakfast; L=lunch; D=dinner.
Adapted from Riddle MC. Diabetes Care. 1990;13:676-686.
OBIECTIVE BIOMEDICALE PENTRU CONTROLUL
DIABETULUI ZAHARAT
Glicemia (autodeterminare)
pe nemncate/preprandial 80-110 (4,4-6,1) 111-140 (6,2-7,8) > 140 (>7,8)
postprandial [mg/dl (mmol/l)] 100-145 (5,5-8,0) 146-180 (8,1-10,0) > 180 (>10,0)
HbA1c (%) < 6,5 6,5-7,5 > 7,5