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I. Bolile metabolice populaionale II.Diabetul zaharat

Conf. Dr. Gabriela Roman


UMF Iuliu Haieganu Centrul Clinic de Diabet, Nutriie, Boli metabolice

De discutat:
Bolile metabolice populaionale

Diabetul zaharat

De discutat:
Bolile metabolice populaionale

Bolile metabolice populaionale

Bolile metabolice populaionale - Impact

2. Impactul epidemiologic: epidemia de obezitate epidemia de prediabet & diabet epidemia de patologie CV 3. Impactul economic, organizatoric, social: costuri crescute ale ngrijirii productivitate sczut discriminare profesional, social
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Bolile metabolice populaionale Etio-Patogeneza

Bolile metabolice populaionale Etio-Patogeneza

Reactivitate aberant la stres

(Atitudine, comportament, relaii)

Stil de via

Decizii zilnice Alimentaie Activitate fizic Consum de alcool Fumat Coabitarea cu stresul Odihna, relaxare,somn Starea de sntate / boal
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Stilul de via Individual

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Stilul de via
Mediu
Reeaua social Comunitatea Condiii generale de mediu Condiii Socio-Economice Condiii de munc, locuit Timp liber Cultur, Tradiii Asisten medical

Ambient
LINDA JONES. Behavioural and environmental influences on health. n Promoting health Knowledge and practice, 11 The Open University, 1997: 1857

Bolile metabolice populaionale Etio-Patogeneza

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Bolile metabolice populaionale Etio-Patogeneza

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Bolile metabolice populaionale Polimorfism clinico-metabolic

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Bolile metabolice populaionale Abordare n practic


Screening programe naionale - cu ocazia diagnosticului unei boli metabolice & CV

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De discutat:

Diabetul zaharat

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DZ - Scurt istoric
1552 B.C. Egipt poliuria I secol D.C. - Areteus prima descriere a DZ 'the melting down of flesh and limbs into urine.' - diabetes sifon, scurgere - mellitus miere (latin)

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De discutat: epidemiologie definiie clasificare diagnostic etiopatogenie aspecte clinice evoluie complicaii acute complicaii cronice aspecte paraclinice management clinic

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2010

2030

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FIGURE 2.1

Prevalence (%) estimates of diabetes (20-79 years) by region, 2010 and 2030

Africa (AFR), Europe (EUR), Middle East and North Africa (MENA), North America and Caribbean (NAC), South and Central America (SACA), South-East Asia (SEA), Western Pacific (WP).

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FIGURE 2.2

Number of people with diabetes by age group, 2010 and 2030

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IGT (STG) / Varsta

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Africa (AFR), Europe (EUR), Middle East and North Africa (MENA), North America and Caribbean (NAC), South and Central America (SACA), South-East Asia (SEA), Western Pacific (WP).

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TABLE 3.1

Regional estimates for diabetes (20-79 years), 2010 and 2030

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Deaths attributable to diabetes as percentage of all deaths (20-79 years) by region, 2010

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European Region

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De discutat: epidemiologie definiie clasificare diagnostic etiopatogenie aspecte clinice evoluie complicaii acute complicaii cronice aspecte paraclinice management clinic

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Diabetul zaharat Definiie & Diagnostic

2006

&
32 www. idf.org

Diabetul zaharat - Definiie


Diabetul zaharat condiia definit primordial prin nivelul hiperglicemiei ce crete riscul de afectare microvascular (retinopatie, nefropatie i neuropatie). Asociat cu : - reducerea speranei de via, - morbiditate semnificativ datorat complicaiilor cronice microvasculare, - risc crescut de complicaii macrovasculare (cardiopatie ischemic, stroke, boal vascular periferic), - reducerea calitii vieii.
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Diabetul zaharat - Definiie

2007

EASD

Dezechilibru metabolic cu etiologie multipl caracterizat prin hiperglicemie cronic cu alterarea metabolismului glucidic, lipidic i proteic, datorat deficitului de insulinosecreie, de aciune a insulinei sau al ambelor. Este asociat pe termen lung cu disfuncii i insuficiene ale diverselor organe, (ochi, rinichi, nervi, inim, vase sanguine) .

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RCV RMetab

Glicemia

Definirea strilor glicemice: - normoglicemie - hiperglicemie intermediar: glicemie bazal modificat scderea toleranei la glucoz - diabet zaharat
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2006

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Hiperglicemia intermediar
Scderea toleranei la glucoz
(Impaired Glucose Tolerance - IGT)

Glicemie bazal (a jeun): < 126 mg/dl (7.0 mmol/l) i Glicemia 2h post TTGO: 140 mg/dl i <200 mg/dl) (7.8 and <11.1mmol/l)

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2006

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Hiperglicemia intermediar
Scderea toleranei la glucoz
(Impaired Glucose Tolerance - IGT)

- Prevalen mai mare la femei - Prevalena crete cu vrsta - DECODE: - 2.9% n grupa de vrst 3039 ani - 15.1% n grupa de vrst 7079 ani - 4.5% n grupa de vrst 3039 ani - 16.9% n grupa de vrst 7079 ani
Brbai

Femei

DECODE Study Group. Age- and sex-specific prevalences of diabetes and impaired glucose regulation 38 in 13 European Cohorts. Diabetes Care 2003; 26: 6169.

2006

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Hiperglicemia intermediar
Glicemia bazal modificat
(Impaired Fasting Glucose - IFG)

Glicemie bazal (a jeun): 110 mg/dl 125 mg/dl (6.1 - 6.9 mmol/l) Si, dac este determinat * Glicemia 2h post TTGO: < 140mg/dl (7.8mmol/)
* Dac glicemia la 2 ore post TTGO nu este determinat, condiia de STG nu poate fi exclus
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2006

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Hiperglicemia intermediar
Glicemia bazal modificat
(Impaired Fasting Glucose - IFG) Mai frecvent la brbai DECODE study: GBM izolat 5.2% la 3039 ani 10.1% la 5059 ani 3.2% la 8089 ani 2.6% la 3039 ani 5.9% la 7079 ani

Brbai

Femei

DECODE Study Group. Age- and sex-specific prevalences of diabetes and impaired glucose regulation 40 in 13 European Cohorts. Diabetes Care 2003; 26: 6169.

Diabetul zaharat - Diagnostic


Glicemie bazal (a jeun) 126 mg/dl (7.0 mmol/l) Sau Glicemia 2h post TTGO 200 mg/dl (11.1 mmol/l) Sau

2006

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Simptome de diabet i o glicemie 200 mg/dl


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Diabetul zaharat - Diagnostic


A1c 6.5% + Confirmare Fr confirmare persoane simptomatice ( 200 mg/dl). A1c = 6% - 6.5% - risc crescut Prevenie +++ A1c < 6% - risc n fc de ali fact de risc pt DZ Prevenie ++

2009 International Expert Committee: - American Diabetes Association, - European Association for the Study of Diabetes, - International Diabetes Federation

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Retinopatia diabetica & hiperglicemia & diagn DZ

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Diagnosticul diabetului zaharat Evaluarea globala


Diagnosticul de boal Diagnosticul riscului cardiovascular: Factori de risc cardiovascular Sindrom metabolic Riscul cardiometabolic Stratificarea riscului Diagnosticul complicaiilor micro- i macrovasculare Diagnosticul comorbiditilor

ADA, 2008. Diabetes Care, 31, suppl 1: S12-S54

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De discutat: epidemiologie definiie diagnostic clasificare etiopatogenie aspecte clinice evoluie complicaii acute complicaii cronice aspecte paraclinice management clinic

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Diabetul zaharat - Clasificare

2007

EASD

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Diabetul zaharat tip 2 Screening


1. Populaia general - evaluarea riscului de DZ* (+) - evaluare glicemic la cei cu risc crescut 2. Populaia cu risc crescut de DZ tip 2 - anual - glicemie bazal (snge venos/capilar)

2007

EASD

3. Populaia cu BCV evaluare glicemic bazal i TTGO


* FINDRISC 2001
Jaakko Tuomilehto, Department of Public Health, University of Helsinki, Jaana Lindstrm, MFS, National Public Health Institute, Finland.

- TTGO

GB 110 - < 126 mg/dl (+)

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1.

Age

< 45 years (0 p.) 554 years (2 p.) 5564 years (3 p.) > 64 years (4 p.) 2. Body mass index < 25 kg/m (0p) 25 30 kg/m (1p) 30 kg/m (3p)

5. How often do you eat vegetables, fruit or berries? Every day (0 p.) Not every day (1 p.) 6. Have you ever taken antihypertensive medication regularly? No (0 p.) Yes (2 p.)

Scor FINDRISC

3. Waist circumference measured below the 7. Have you ever been found to have high ribs (usually at the level of the navel) blood glucose (eg in a health examination, during an illness, during pregnancy)? Men Women No (0 p.) Yes (5 p.) < 94 cm 94 - 102 cm > 102 cm < 80 cm 80 88 cm > 88 cm 0p 3p 4p 8. Have any of the members of your immediate family or other relatives been diagnosed with diabetes (type 1 or type 2)? oNo (0 p.) oYes: grandparent, aunt, uncle or first cousin (but no own parent, brother, sister or child) (3 p) oYes: parent, brother, sister or own child (5 p.)

Lower than 7 Low: estimated 1 in 100 will develop disease 711 Slightly elevated: estimated 1 in 25 will develop diasease Moderate: estimated 1 in 6 will develop diasease High: estimated 1 in 3 will develop diasease

1214 1520

4. Do you usually have daily at least 30 minutes of physical activity at work and/or during leisure time (including normal daily activity)? Yes (0 p.) No (2 p.)

Higher than Very high: estimated 1 in 2 20 will develop diasease

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Diabetul zaharat Screening


Persoane aflate la risc crescut pentru DZ 2

2007

EASD

Obezitate HTA Antecedente familiale de DZ Antecedente personale de STG, DG, sau femei care au nscut copii cu greutatea peste 4.5 kg Grupuri etnice cu risc crescut HDL colesterol 35 mg/dl i/sau trigliceride serice 250 mg/dl Ovar polichistic Tineri supraponderali care prezint nc 2 FR - la intervale de 2 ani, ncepnd de la vrsta de 10 ani sau de la debutul pubertii
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Diabetul gestational

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Sarcina i Hiperglicemia
Efectul major al hiperglicemiei cronice: - n primul trimestru al sarcinii - hiperglicemia (peste 150 mg/dl) crete de 3 ori riscul producerii anomaliilor fetale i de 4-8 ori riscul de avort spontan - accelerarea creterii ftului - risc de 9 ori mai mare

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GB > 105 mg/dl GPP -1h > 140 mg/dl GB peste 90 - 95 mg/dl comparativ cu cele de 75 mg/dl, GB > 105 mg/dl.

macrosomia - de 7 ori mai frecvent


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macrosomia - de 14 ori mai frecvent


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malformaiile congenitale - 25 % n cazurile cu diabet zaharat pregestaional (tip 1 sau tip 2) necontrolat glicemic (HbA1c peste 10 %).
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G. Roman, N. Costin. Diabetul zaharat i Sarcina-ndrumar de practic medical. 2005

Sarcina i Hiperglicemia
Mortalitatea peri-natal n DG - rata de 2.6% (OR 2.3) n DG netratat - Glicemia Postprandial < 140 mg/dl reducerea MPN cu 75%. Mortalitatea peri-natal n DZ pre-existent sarcinii - media glicemic = 100 mg/dl MPN 4 % - media glicemic = 100150 mg/dl MPN 15 % - media glicemic = >150 mg/dl MPN 24 % Continua cretere a MPN la glicemii > 100 mg/dl

Moshe Hod M., Yogev Y. Goals of Metabolic Management of Gestational Diabetes. Diabetes Care, 2007, 30

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Screening-ul DG - Persoane cu risc crescut


Istorie familial de diabet sau obezitate Suprapondere sau obezitate (IMC de > 25 kg/m2) pre-sarcin Exces ponderal rapid n primele 6 luni Vrst mai mare a mamei (peste 35 ani) Multiparitate Glicemie bazal modificat sau scderea toleranei la glucoz n antecedente Etnie cu risc crescut pentru diabet gestaional Diabet gestaional Cretere ponderal excesiv Macrosomie & LGA n sarcina curent Copii macrosomi sau hipotrofici n antecedente Mortalitate fetal n antecedente Ovar polichistic
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Screening-ul DG

n cazul gravidelor cu factori de risc prezeni, testul de screening se aplic la prima vizita prenatal (nainte de sptmna 24-a) n cazul unui rezultat negativ, se repet n sptmnile 24 28; n cazul gravidelor cu risc crescut se face direct testul de diagnostic; n cazul gravidelor cu ris moderat, screeningul se face n sptmnile 24 28 de sarcin;

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Screening-ul DG

n cazul gravidelor cu factori de risc prezeni, testul de screening se aplic la prima vizita prenatal (nainte de sptmna 24-a) n cazul unui rezultat negativ, se repet n sptmnile 24 28; n cazul gravidelor cu ris moderat, screeningul se face n sptmnile 24 28 de sarcin;

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Screening
La prima vizita prenatal

Glicemie bazal

92 mg/dl

Risc crescut DG

TTGO 75 mg glucoz
Pozitiv Negativ

TTGO 75 mg glucoz
Spt. 24 28 de sarcin

Diagnostic

Tratament
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Diagnostic DG Metode TTGO


Diagnostic

Testul de diagnostic trebuie efectuat dimineaa, dup o perioad de 814 ore de repaus digestiv i consum minimum de 150 g hidrai de carbon n zilele precedente;

Diagnosticul se face prin determinarea glicemiei plasmatice n cadrul TTGO (test de toleran la glucoz oral), cu 75 g glucoz:

1 sau mai multe valori peste


GB >/= 92 mg/dL G 1 ora >/= 180 mg/dL G 2 ore >/= 153 mg/dL
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De discutat: epidemiologie definiie clasificare diagnostic etiopatogenie aspecte clinice evoluie complicaii acute complicaii cronice aspecte paraclinice management clinic

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Mecanisme diabetogene: - Distrucia celulelor beta - Defect n secreia i/sau aciunea insulinei - Combinarea

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Istoria natural a DZ

Toleran normal la glucoz


25 %

Prediabet (Hiperglicemie intermediar)


25 %

50 %

DZ

DZ 2

DZ 2

DG

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Semnificaia prediabetului

Risc pentru diabet zaharat

Risc pentru complicaii cardiovasculare

Prediabetul este o boal, nu o pre-boal!


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Patogeneza DZ tip 1

Boal autoimun cu etiologie multifactorial - Interaciune factori genetici + factori mediu Reacie auto-imun fa de celulele beta din insulele Langerhans Markerii auto-imuni atc anti-insulari

IAA atc anti-insulina IA-2/ICA-512 (tirozin-fosfataza) Atc anti-GAD (decarboxilaza ac glutamic)

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Patogeneza DZ tip 1

Factori declanatori:

infecii virale,(rubeola congenital) anticorpi mpotriva laptelui de vac, mediu

Fundament genetic fenotip HLA: alele DR3 and DR4 Risc de transmitere familial:

2-3% pe linie matern, 5-6% pe linie patern, 30% dac ambii prini au diabet

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DZ tip 1

Predispozitie genetica + Factori declanatori:


Distrucia progresiv a celulelor beta Deficit absolut de insulin endogen

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Patogeneza DZ tip 2 - Mecanisme


Insulino-rezisten Disfuncie -celular
Reducerea secreiei celulare de insulin

Ficat Producia hepatic a glucozei Muchi i esut adipos Utilizrii glucozei prin mecanisme dependente de insulin

Imposibilitatea celulelor beta de a compensa IR

Susceptibilitatea genetic, obezitatea, sedentarismul

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Patogeneza DZ tip 2
Insulino rezisten

educerea utilizrii glucozei n muchi i tes. adipos Obezitate Creterea produciei hepatice abdominal de glucoz

Creterea lipolizei i a fluxului de AGL

Necesar crescut de insulin

Hiperglicemie
glucotoxicitate lipotoxicitate

Creterea AGL

Disfuncie -celular

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Patogeneza DZ tip 2
Adipozitate intra-abdominal

Obezitate IR DZ 2 Sindrom metabolic cardiovascular

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Declinul funciei -celulare evoluia progresiv a DZ 2


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-cell function (% of normal by HOMA)

Time of diagnosis

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60

40

Pancreatic function = 50% of normal

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0 10

Time (years)
HOMA=homeostasis model assessment. UKPDS Group. Diabetes 1995;44:124958. Adapted from Holman RR. Diabetes Res Clin Pract 1998;40(suppl 1):S215.

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Celula beta Insulinosecreia dependent de glucoz


Sensor" glucoz Legatur metabolic cu canalele de K pentru controlul potenialului de membran plasmatic Canal de voltaje dependent de Ca++ Granule coninnd insulin rezervor - rezervor de urgen (eliberare imediat)
Transportor de glucoz

Glicoliza

Activat la o glicemie de 90 mg/dl

4 declansarea depolarizarii 3 deschiderea canalelor de Ca2+ dependente de voltaj 2 nchiderea canalelor de K+ - ATP dependente,
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Celula beta Insulinosecreia dependent de glucoz

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Pierderea primei faze de secreie a insulinei

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Celula beta Insulinosecreia DZ 2

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Transportul intracelular de glucoz, Sinteza proteic Sinteza lipidelor n esutul adipos

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Fiziopatologia DZ 2 - Evoluie
Obezitate
350 300 250 200 150 100 50 250 200 150 100 50 0 -10 -5 0 5 10 15 20 25 30 Diagnostic clinic

STG

DZ 2

Hiperglicemie
Glic. Postprandial

Glicemie (mg/dl)

200 126

Glic. bazal

Funcie relativ (%)

Insulino-rezisten

Insulino-secretie

Ani DZ
Adaptat dup Bergenstal RM, et al. Diabetes mellitus, carbohydrate metabolism and lipid disorders. In Endocrinology. 4th ed. 2001.

Fiziopatologia DZ 2 - Evoluie

Glucose (mg/dl)

Relative function (%)

S.N. Braunstein, J. P. Palmer. Medscape, 2006

Sindromul cardio-metabolic
Cauze genetice, alim. Hipercaloric, Sedentarism Obezitate abdominal Insulino-rezisten
FFA Adipose T

Muscle

Liver

Arteries

Other mechanisms

Blood
Pro-Thrombotic Pro-Inflammatory State: PAI-1 t-PA FVII, F XII Fibrinogen

Blood glucose

-cell

Ins.

Ins.

Dyslipidemia: TG HDL Small & dense LDL Chol/HDL ratio apo B PP HLP

Stiffness Endothelial Dysfunction

HBP LVH CHF

-cell failure
Genetic, acquired causes G & L toxicity

T2 DM

Atherothrombotic Arterial disease CVD

Alb-uria

80 Modified after H. Yki-Jarvinen. Textbook of diabetes, JC Pickup&G. Williams (eds),2003

De discutat: epidemiologie definiie clasificare diagnostic etiopatogenie aspecte clinice tablou clinic, evoluie complicaii acute complicaii cronice aspecte paraclinice management clinic

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Tablou clinic Debut 3 P poliurie - polidipsie - polifagie scdere ponderal astenie iritabilitate, insomnie greuri, vrsturi cetoacidoz prin complicaii infecii, candidoze

Simptomatologia Hiperglicemiei

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Tablou clinic Cetoacidoza Deshidratare sever Miros caract. Cetone Respiraie acidozic Kussmaul Dureri epigastrice Greuri, vrsturi Cetonurie, acidoz sanguin Stare general alterat, com

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Tablou clinic Evoluie asimptomatic control glicemic adecvat simptome de hiperglicemie simptome de hipoglicemie (tratament?) simptome ale complicaiilor cronice simptome ale co-morbiditii deces
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Tabloul clinic al DZ tip 1


Semne i simptome datorate diurezei osmotice: poliurie, nicturie sete, polidipsie vedere nceoat deshidratare Semne i simptome datorate deficitului insulinic: hiperglicemie i glicozurie important oboseal extrem epuizare muscular scdere n greutate - lipsa insulinei gluconeogenez grsimile utilizate ca surs de energie cetoz, cetoacidoz Simptome asociate cu scderea rezistenei la infecii: infecii tegumentare prurit genital Simptome asociate cu deficitul balanei calorice: creterea apetitului scdere n greutate

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Tablou paraclinic DZ tip 1


Peptidul C Markerii distruciei autoimune a celulelor : atc. Anticelulari (ICAs), atc. Anti-insulin (IAAs), atc. Anti glutamic acid decarboxylase (GAD65), atc. Anti tyrosine phosphatases IA-2 and IA-2 Glicemii bazale (a jeun) - postprandiale (90 120 minute) - nocturn (ora 3) Hemoglobina glicat A1c Creatinina seric Microalbuminuria / proteinuria Profilul lipidic: colesterol total, LDL-colesterol, HDL-colesterol, TG Hemo-leucograma Hormonii tiroidieni Alti biomarkeri de boli autoimune 86

Tablou paraclinic DZ tip 2


Glicemii bazale (a jeun) - postprandiale (90 120 minute) - nocturn (ora 3) Hemoglobina glicat A1c Creatinina seric Microalbuminuria / proteinuria Profilul lipidic: colesterol total, LDL-colesterol, HDL-colesterol, TG Hemo-leucograma Proteina C reactiv Fibrinogen Enzimele hepatice: transaminazele, gama-GT, Ac. Uric
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Riscul cardiovascular

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ntrebri Discuii

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