-
ef.lucr. Dr. Adriana Fodor
UMF Iuliu HaieganuCentrul Clinic de Diabet, Nutriie, Boli
metabolice Bolile metabolice populaionale Diabetul zaharat
-
Obiective curs Obiective generalensuirea de noiuni de baz n
domeniul patologiei metabolico-nutriionale: diabet zaharat,
obezitate, dislipidemii, sindrom metabolic, hiperuricemie,
nutritieObiective specifice cunostinte bolile metabolice
populaionale, impactul acestora, patogeneza i evoluia acestora,
posibilitile de prevenie principii de baz ale abordrii globale a
pacienilor cu diabet zaharat: screening, diagnostic, clasificare,
evaluare, tratamentnoiuni generale despre complicaiile acute i
cronice ale diabetului zaharat: screening, diagnostic, evaluare,
tratamentabordarea persoanelor cu obezitate, dislipidemii, sindrom
metabolic, hiperuricemie: screening, diagnostic, evaluare,
tratamentterapia medical nutriional: definiie, principii
-
Coninutul cursuluiBolile metabolice populaionale: epidemiologie,
impact medical, social, economic Diabetul zaharat: definiie,
clasificare, etiopatogenez, manifestri clinice, complicaii,
management clinicHipoglicemiile Obezitatea: definiie, clasificare,
etiopatogenez, manifestri clinice, complicaii, management
clinicDislipidemiile: definiie, clasificare, etiopatogenez,
manifestri clinice, complicaii, management clinicSindromul
metabolic si riscul cardiovascular: definiie, evaluare, management
clinicHiperuricemia: definiie, evaluare clinic i biochimic,
management clinic Terapia medical nutriional: definiie,
principii
-
BibliografieCatedra de DNBM. Diabet, Nutriie, Boli
metabolice-Curs pentru studeni, Editura Medical Universitar Iuliu
Haieganu, Cluj-Napoca, 2009Hncu N., Roman G., Veresiu I.A.
(editori). Diabetul zaharat, nutritie, bolile metabolice- Tratat,
vol 1 si 2, Editura Echinox Cluj-Napoca, 2010Hncu N., Roman G.,
Veresiu I.A. (editori). Farmacoterapia diabetului zaharat. Editura
Echinox Cluj-Napoca, 2008Vereiu I.A., Hncu N, Roman G. (editori)
Insulina i tratamentul cu insulin. Editura Echinox Cluj-Napoca,
2004
-
De discutat:Bolile metabolice populaionaleDiabetul zaharat
-
Bolile metabolice populaionale
DIABETUL ZAHARAT OBEZITATEA DISLIPIDEMIILE SINDROMUL
METABOLIC
-
Bolile metabolice populaionaleNoncommunicable diseases (NCDs)
kill more than 36 million people each year (63% of all deaths) ~
80% of NCD deaths occur in low- and middle-income countries. >
25% of deaths attributed to NCDs occur before the age of 60; 90% of
these "premature" deaths occurred in low- and middle-income
countries. Cardiovascular diseases - most NCD deaths (48%)Cancers
(21%), respiratory diseases (12%), and diabetes (3%). These 4
groups of diseases account for around 80% of all NCD deaths. They
share four risk factors: tobacco use, physical inactivity, the
harmful use of alcohol and unhealthy diets. WHO 2011
-
Bolile metabolice populaionaleSe definesc prin: determinism
predominant metabolico-nutriional evoluie cronic nsoit de severe
complicaii care: scad calitatea vieii cresc mortalitatea la nivel
populaional
-
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
-
BMP Etio-Patogeneza
-
*BMP Etio-Patogeneza
-
Stil de via(Atitudine, comportament, relaii)Alimentaie
Activitate fizicConsum de alcoolFumatCoabitarea cu stresulOdihna,
relaxare,somnStarea de sntate / boalDecizii zilnice
-
*Stilul de via Individual
-
*Reeaua socialComunitateaCondiii generale de mediuCondiii
socio-economiceCondiii de munc, locuit Timp liberCultur,
TradiiiAsisten medical
Mediu Ambient Stilul de via
-
Factorii cu impact asupra seleciei alimentelor Contento IR.
2011. Jones and Bartlett Publishers, 40 Tall Pine Drive, Sudbury,MA
01776Comportamente cu determinism biologic: gust/plcere
foame/saietate mecanisme cerebraleExperiena alimentar: condiionarea
de asociere
Condiionarea psihologic: sigurana/familiaritate preferine
alimentare saietate
Condiionarea social: modele recompense contextul social
afectivFactori intra-personali: percepii atitudini convingeri
motivaie/valori cunotine/abiliti norme sociale norme culturale
Factori inter-pesonali: reeau social i familialFactori de
mediu:Ambientul fizic: disponibilitatea alimentelor resurse pentru
micareAmbientul social: influene sociale practici culturale
structuri sociale politici Ambientul economic: resurse preuri
timpAmbientul informaional: publicitate educaie mediaPreferine/
factori senzoriali-afectiviConvingeri, atitudini,
normeDisponibilitate, influene
-
BMP Polimorfism clinico-metabolic
-
BMP-Triada ngrijirii Abordare n practicScreening programe
naionale - cu ocazia diagnosticului unei boli metabolice &
CV
-
Obiectivele abordrii n BMP Optimizarea parametrilor
clinico-metabolici i nutriionali, prin care se realizeaz
Prevenirea i controlul complicaiilor i asociaiilor morbide, ceea
ce contribuie la
mbuntirea calitii vieii i a adaptrii familiale, profesionale i
sociale, creterea speranei de via.
-
Profilaxia BMPExposure to the four main behavioural risk factors
that contribute to NCDs - tobacco use, physical inactivity, harmful
use of alcohol and unhealthy diets - remains high worldwide and is
increasing in the majority of low- and middle-income countries- WHO
2011 RR: Diabet zaharat tip 2 (58%) Cardiopatie ischemic (80%)
Cancer (30%)
-
De discutat:Diabetul zaharat
-
1552 B.C. Egipt poliuriaI secol D.C. - Areteus prima descriere a
DZ'the melting down of flesh and limbs into urine.' - diabetes
sifon, scurgere - mellitus miere (latin)
DZ - Scurt istoric
-
De discutat:
epidemiologie definiie clasificare diagnostic screening
etiopatogenie aspecte clinice tablou clinic,evoluie complicaii
acute complicaii cronice aspecte paraclinice management clinic
-
Idf.org Epidemiologie DZ
-
The global burden of diabetesDiabetes is a huge and growing
problem
-
80% of people with diabetes live in low- and middle-income
countries The greatest number of people with diabetes are between
40 to 59 years of age 175 million people (46%) with diabetes are
undiagnosed Diabetes caused 5.1 million deaths in 2013 Diabetes
caused 11% of total health spending on USA adults in 2013 .
-
Predicie 2005-2020 - EURODIAB (Epidemiology and Prevention of
Diabetes) -dublarea numrului de cazuri noi de DZ1 la copii < 5
ani - cretere a prevalenei cazurilor la grupa de vrsta < 15 ani,
cu 70% Patterson CC, Dahlquist GG, Gyurus E, et al. Incidence
trends for childhood type 1 diabetes in Europe during 1989-2003 and
predicted new cases 2005-2020: a multicentre prospective
registration study. Lancet 2009; 373: 2027-33.
-
*Impact Economic
- productivitate scazuta- pierdere zile de munca, - restrictie
la anumite activitati, - mortalitate si disabilitate prin
diabet
-
*De discutat: epidemiologie definiie clasificare diagnostic
screening etiopatogenie aspecte clinice evoluie complicaii acute
complicaii cronice aspecte paraclinice management clinic
-
Grup de boli metabolice caracterizate prin: Hiperglicemie cronic
indus de defecte n secreia i/sau aciunea insulineiModificri n
metabolismul lipidic i proteicConsecine pe termen lung - apariia
complicaiilor cronice: Retinopatia Nefropatia Neuropatia
Cardiopatia ischemic Arteriopatia periferic Boala cerebrovascular
Aceste complicaii pot fi prevenite printr-un control
multifactorial, intensiv, instituit precoce. Definiia diabetului
zaharatADA, 2013. Diabetes Care, 36, suppl 1: S67-S74
-
Societi tiinifice Federatia Internationala de Diabet
www.idf.orgAsociatia Europeana pentru Studiul Diabetului EASD (www.
easd.org)Asociatia Americana de Diabet ADA -
www.diabetes.orgFederatia Romana de Diabet, Nutritie, Boli
metabolice www.federatiaromanadiabet.roSocietatea Romana de Diabet,
Nutritie, Boli metabolice - www.societate-diabet.ro
-
*Definirea strilor glicemice:- normoglicemie- hiperglicemie
intermediar: glicemie bazal modificat scderea toleranei la glucoz -
diabet zaharat
- Hiperglicemia intermediar Glicemie bazal (a jeun): 110 mg/dl
125 mg/dl (6.1 - 6.9 mmol/l)Glicemia bazal modificat (Impaired
Fasting Glucose - IFG)Glicemia 2h post TTGO: 140 mg/dl i
-
ADA. I. Classification and Diagnosis. Diabetes Care
2013;36(suppl 1)Categorii la risc crescut pentru diabetul zaharat
(prediabet)1.Glicemia bazal modificat (GBM)2.Scderea toleranei la
glucoz (STG)3. HbA1c: 5,7-6,4%
-
*Diabetul zaharat - Diagnostic Glicemie bazal (a jeun) 126 mg/dl
(7.0 mmol/l)SauGlicemia 2h post TTGO 200 mg/dl (11.1
mmol/l)SauSimptome de diabet i o glicemie 200 mg/dl SauHbA1c
6,5%
-
Retinopatia diabetica & hiperglicemia & diagn DZ
-
*
Diagnosticul de boalStratificarea riscului
cardiovascularDiagnosticul complicaiilor micro- i
macrovasculareDiagnosticul comorbiditilor ADA, 2008. Diabetes Care,
31, suppl 1: S12-S54Diagnosticul diabetului zaharatEvaluarea
global
-
De discutat: epidemiologie definiie diagnostic clasificare
etiopatogenie screening aspecte clinice evoluie complicaii acute
complicaii cronice aspecte paraclinice management clinic
-
I. DZ tip 1: produs prin deficit absolut de insulin, ca urmare a
distruciei celulelor beta pancreatice dou subtipuri: autoimun
idiopatic
II. DZ tip 2: 90-95% din cazuri consecin a unui de defect n
secreia de insulin pe fond de insulinorezistena Etiopatogeneza:
factori genetici & ctigaiClasificarea etiopatogenetic a DZ
-
III. Tipuri specifice de diabet: Defecte genetice ale celulelor
beta pancreatice (MODY) Defecte genetice ale mecanismului de aciune
a insulinei Pancreatopatii exocrine (pancreatite, tumori,
pancreatectomii, hemocromatoza) Endocrinopatii (sindrom Cushing,
feocromocitom, acromegalie) Medicamente sau substane chimice (acid
nicotinic, glucocorticoizi, hormoni tiroidieni, agonisti
adrenergici, tiazide, alfa interferon) Infecii (rubeola
congenitala, virus citomegalic) Sindroame genetice
IV. DZ gestaional: apare n timpul sarcinii i este produs prin
mecanismele tipului 1 sau 2Clasificarea diabetului zaharat
-
Evoluia stadial
-
Diabetul zaharat tip 2 Screening 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) GB 110 - < 126 mg/dl (+)- TTGO3. Populaia cu BCV
evaluare glicemic bazal i TTGO* FINDRISC 2001Jaakko Tuomilehto,
Department of Public Health, University of Helsinki, Jaana
Lindstrm, MFS, National Public Health Institute, Finland.
-
Scor FINDRISC
Age < 45 years (0 p.)554 years (2 p.)5564 years (3 p.)> 64
years (4 p.) 5. How often do you eat vegetables, fruit or berries?
Every day (0 p.) Not every day (1 p.)2. Body mass index< 25 kg/m
(0p)25 30 kg/m (1p) 30 kg/m (3p)6. Have you ever taken
antihypertensive medication regularly?No (0 p.) Yes (2 p.)3. Waist
circumference measured below the ribs (usually at the level of the
navel)7. Have you ever been found to have high blood glucose (eg in
a health examination, during an illness, during pregnancy)?No (0
p.) Yes (5 p.)Men Women < 94 cm< 80 cm0 p94 - 102 cm80 88 cm3
p> 102 cm > 88 cm4 p4. 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.)8. Have any
of the members of your immediate family or other relatives been
diagnosed with diabetes (type 1 or type 2)?No (0 p.)Yes:
grandparent, aunt, uncle or first cousin (but no own parent,
brother, sister or child) (3 p)Yes: parent, brother, sister or own
child (5 p.)
Lower than 7Low: estimated 1 in 100 will develop
disease711Slightly elevated: estimated 1 in 25 will develop
diasease1214Moderate: estimated 1 in 6 will develop
diasease1520High: estimated 1 in 3 will develop diaseaseHigher than
20Very high: estimated 1 in 2 will develop diasease
-
Persoane aflate la risc crescut pentru DZ 2Diabetul zaharat tip
2 Screening
-
Diabetul gestational
-
Sarcina i HiperglicemiaEfectele majore 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 - macrosomia - de 7 ori mai frecvent -
GB peste 90 - 95 mg/dl comparativ cu cele de 75 mg/dl,- macrosomia
- de 14 ori mai frecvent- GB 105 mg/dl.- malformaiile congenitale -
25 % n cazurile cu diabet zaharat pregestaional (tip 1 sau tip 2)
necontrolat glicemic (HbA1c peste 10%). G. Roman, N. Costin.
Diabetul zaharat i Sarcina-ndrumar de practic medical. 2005
-
*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/dlMPN 4 %- media glicemic = 100150 mg/dlMPN 15 %-
media glicemic = >150 mg/dlMPN 24 % Continua cretere a MPN la
glicemii > 100 mg/dl
Sarcina i HiperglicemiaMoshe Hod M., Yogev Y. Goals of Metabolic
Management of Gestational Diabetes. Diabetes Care, 2007, 30
-
Screening-ul DG - Persoane cu risc crescut Istorie familial de
diabet sau obezitate Suprapondere sau obezitate pre-sarcin Exces
ponderal rapid n primele 6 luniVrst mai mare a mamei (peste 35
ani)Multiparitate GBM sau STG sau Diabet Gestaional n
antecedenteEtnie cu risc crescut pentru diabet gestaional
Macrosomie & hipotrofie fetal n sarcina curent /
antecedenteMortalitate fetal n antecedente Ovar polichistic
-
*n cazul gravidelor cu factori de risc prezeni, cu risc crescut,
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;Screening-ul DG
-
Diagnostic Testul de screening i 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 cu 75
g glucoz i este pozitiv la cel putin o valoare peste : ADA, 2013.
Diabetes Care, 36, suppl 1: S67-S74
-
De discutat:
epidemiologie definiie clasificare diagnostic screening
etiopatogenie aspecte clinice evoluie complicaii acute complicaii
cronice aspecte paraclinice management clinic
-
Patogeneza DZ tip 1 autoimun Boal autoimun cu etiologie
multifactorial - Interaciune factori genetici + factori mediu Minim
/ absent secreie de insulin prin distrucia autoimun selectiv a
celulelor pancreatice.Markerii auto-imuni atc anti-insulari IAA atc
anti-insulinaIA-2/ICA-512 (tirozin-fosfataza) Atc anti-GAD
(decarboxilaza ac glutamic) antitransportor de Zn (ZnT8) Asociere
cu alte boli autoimune
-
Patogeneza DZ 1- Predispoziia genetic Asociere puternic cu HLA
DQA, DQB, DRBRisc de transmitere familial: Risc crescut pentru
rudele de gradul 1 ale pacienilor cu DZ (36% comparativ cu 0.21% n
populaia general european). 2-3% pe linie matern, 5-6% pe linie
patern, 30% dac ambii prini au diabet Rata de concordan la gemenii
monozigoi (30-50%)
-
Susceptibilitatea genetic nu e suficient pentru a face boala.~
80 90% din pacieni cu DZ1 nu au rude cu DZ1Peste 50% din gemenii
monozigoi nu fac boala10% din persoanele susceptibile HLA fac
boalaVariaia sezonier i geografic a incideneiAsocierea cu infecii
virale
Patogeneza DZ - Factori de mediu
-
Istoria natural a DZ tip 1
-
Autoanticorpi anti antigene insulare - rol ?
Susceptibilitate Pierderea toleranei genetic imunologice(DR3 -
DQ2, DR4 - DQ8)
Infiltrarea insulelor pancreatice: macrofage, linfocite T CD4+,
CD8+ (insulit)
Distrucia autoimun a celulelor ???
-
Mecanisme patofiziologiceDou etape la persoanele susceptibile
genetic:1. Declanarea procesului autoimun duce la apariia unuia sau
mai multor autoanticorpi i la distrugerea treptat a celulelor 2.
Pierderea funciei secretorii a celulelor manifestat prin dispariia
primei faze de secreie a insulinei, reducerea peptidului C, scderea
toleranei la glucoz, iar n final hiperglicemia.Inducerea procesului
autoimun insular la persoane susceptibile genetic i apariia
autoanticorpilor mpotriva antigenelor insulare pot preceda debutul
clinic cu luni de zile sau chiar ani.
-
Autoanticorpii-rol ? importan !Dg. alte forme de diabet Prevenia
bolii !!! -preced debutul clinic cu luni sau ani de zile.
Autoanticorpi multipli n 6-12 luni dup primul Autonticorpii
tranzitori, unul singur rar (haplotip protectiv HLA DR15 DQ6).
-
Istoria natural a DZ 2
-
Insulino-rezisten Disfuncie -celularSusceptibilitatea genetic,
obezitatea, sedentarismul Ficat Producia hepatic a glucozei
Muchi i esut adipos Utilizrii glucozei prin mecanisme dependente
de insulin Reducerea secreiei -celulare de insulin
Imposibilitatea celulelorbeta de a compensa IRPatogeneza DZ tip
2 - Mecanisme
-
Reducerea utilizrii glucozei n muchi i tes. adipos Creterea
produciei hepatice de glucozglucotoxicitatelipotoxicitateInsulino
rezistenDisfuncie -celularHiperglicemieCreterea lipolizei i a
fluxului de AGLCreterea AGLNecesar crescut de insulin Obezitate
abdominalPatogeneza DZ tip 2
-
*Adipozitate intra-abdominal Obezitate IR DZ 2
Sindrom metabolic cardiovascularPatogeneza DZ tip 2
-
*
-
*HOMA=homeostasis model assessment.UKPDS Group. Diabetes
1995;44:124958. Adapted from Holman RR. Diabetes Res Clin Pract
1998;40(suppl 1):S215.Declinul funciei -celulare evoluia progresiv
a DZ 2-cell function (% of normal by HOMA)Time
(years)0204060801001086420246Time of diagnosis?Pancreatic function=
50% of normal
-
*Celula beta insulinosecreia dependent de glucoz Sensor" glucoz
Activarea Glut 2 la o glicemie de 90 mg/dl nchiderea canalelor de
K+ - ATP dependente,Deschiderea canalelor de Ca2+ dependente de
voltaj12Declansarea depolarizarii345Influxul de Ca2+ i exocitoza
insulinei
-
*Pierderea primei faze de secreie a insulinei
-
*Glicemie(mg/dl)50 100 150 200 250 300 350 0 50 100 150 200 250
-10-5051015202530Ani DZAdaptat dup Bergenstal RM, et al. Diabetes
mellitus, carbohydrate metabolism and lipid disorders. In
Endocrinology. 4th ed. 2001.Funcierelativ (%)Glic.
bazalObezitateSTGDZ 2Hiperglicemie
Insulino-rezistenGlic.PostprandialInsulino-secretieDiagnostic
clinicFiziopatologia DZ 2 - Evoluie126200
-
*
-
Obezitate abdominalInsulino-rezisten Cauze genetice, Alim.
Hipercaloric, Sedentarism Muscle Liver Arteries Other mechanisms
Blood Blood glucose -cellDyslipidemia: TG HDL Small & dense LDL
Chol/HDL ratio apo B PP HLPPro-Thrombotic Pro-InflammatoryState:
PAI-1 t-PA FVII, F XII FibrinogenHBPLVHCHF-cell failure Ins.
Ins.Genetic, acquired causesG & L toxicity Stiffness
EndothelialDysfunction Atherothrombotic Arterial diseaseCVDT2
DMModified after H. Yki-Jarvinen. Textbook of diabetes, JC
Pickup&G. Williams (eds),2003 Alb-uriaSindromul
cardio-metabolic Adipose T FFA
*trebuie s subliniem c, de fapt, riscul nutriional pentru BMP i
bolile cronice n general, ncepe nc din perioada dezvoltrii fetale.
El se continu apoi n copilrie, accentundu-se la aduli i vrstnici. n
felul acesta BMP pot s apar la orice vrst, chiar i n copilrie,
fenomen epidemiologic aflat ntr-o alarmant cretere. Dar indiferent
de vrsta apariiei lor pe plan clinc, BMP reprezint i efectul
intergeneraii al factorilor de risc. Cu alte cuvinte, prezena
riscului la mam devine un risc i pentru copil. Aa este cazul
malnutriiei gravidei, urmat de naterea unui ft subponderal care va
dezvolta la vrsta adult sindromul metabolic *In 1997 and 203, The
Expert Committee on the Diagnosis and Classification of Diabetes
Mellitus1,2 recognized an intermediate group of individuals whose
glucose levels, although not meeting criteria for diabetes, are
nevertheless too high to be considered normalThis group was defined
as having impaired fasting glucose (IFG) or impaired glucose
tolerance (IGT)IFG: fasting plasma glucose (FPG) of 100125 mg/dL
(5.65.9 mmol/L)*IGT: 2-hour plasma glucose (2-h PG) on the 75-g
oral glucose tolerance test (OGTT) of 140199 mg/dL (7.811.0
mmol/L)Individuals with IFG and/or IGT have been referred to as
having prediabetes, indicating a relatively high risk for future
development of diabetesIFG and IGT should not be viewed as clinical
entities in their own right but rather risk factors for diabetes as
well as cardiovascular disease (CVD)IFG and IGT are associated with
obesity (especially abdominal or visceral obesity), dyslipidemia
with high triglycerides and/or low HDL cholesterol, and
hypertensionIndividuals with an A1C of 5.76.4% should be informed
of their increased risk for diabetes as well as CVD and counseled
about effective strategies to lower their risks (see Section IV.
Prevention/Delay of Type 2 Diabetes)*The World Health Organization
(WHO) and a number of other diabetes organizations define the
cutoff for IFG at 110 mg/dL (6.1 mmol/L)
*ReferencesExpert Committee on the Diagnosis and Classification
of Diabetes Mellitus. Report of the Expert Committee on the
Diagnosis and Classification of Diabetes Mellitus. Diabetes Care
1997;20:1183-1197. Genuth S, Alberti KG, Bennett P, et al., for the
Expert Committee on the Diagnosis and Classification of Diabetes
Mellitus. Follow-up report on the diagnosis of diabetes mellitus.
Diabetes Care 2003;26:3160-3167.American Diabetes Association.
Standards of medical care in diabetes2012. Diabetes Care
2012;35(suppl 1):S13. Table 3.
Autoanticorpi anti antigene insulare pot fi prezeni naintea
insulitei, nu sunt o consecin a acesteia. Nu se coreleaza cu
intensitatea distruciei celulelor Att imunitatea celular ct i cea
umoral sunt implicate n distrucia celulelor . Infiltrarea cu celule
mononucleare, limfocite T CD8+, CD4+ (insulit) distruge selectiv
celulele . Rolul limfocitelor B este evident doar n studiile
animale (NOD mice) Intensitatea si durata distruciei celulelor
variaza i pare a fi legata de prezenta haplotipurilor HLA cu risc
crescut, in special DR3 - DQ2, DR4 - DQ8 . Moleculele HLA clasa II
sunt prezente pe suprafata celulelor de prezentare a antigenului
(APC) ca dendritic cells and macrophages but also on activated B
and T lymphocytes or even activated endothelialcells. Moleculele cu
risc crescut HLA de pe APC se pare ca faciliteaza activarea
limfocitelor t CD+8 de catre CD+4. Islet autoimmunity (single or
multiple autoantibodies persistent for 3 6 months) proved to be
useful in differentiating T1DM from other forms of diabetes.One or
more of these autoantibodies can be detected months up to years
before clinical onset in more than 95% of newly diagnosed patients
with T1DM, even as early as in the perinatal period.Multiple islet
autoantibodies( 2) usually appear within 6 12 months following the
appearance of the fi rst autoantibody (Figure 9.2 )Some individuals
develop transient islet autoantibodies but they are usually
solitary and associated with lower risk, possibly because of the
presence of protective genes such as HLA DR15 DQ6 Multiple islet
autoantibodies ( 2) usually appear within 6 12 months following the
appearance of the fi rst autoantibody (Figure 9.2 )Detection of of
the four main autoantibodies may predict the disease by as much as
98%*Six-year follow-up data from the United Kingdom Prospective
Diabetes Study (UKPDS) demonstrated the decline in -cell function
with T2DM over time.At the time of diagnosis, -cell function is
already reduced by about 50% and continues to decline regardless of
therapy.
Holman RR. Diabetes Res Clin Pract 1998;40(suppl 1):S215.UKPDS
Group. Diabetes 1995;44:124958.
*There is a temporal relationship between insulin resistance,
insulin secretion and the development of diabetes.In the early
stages, as insulin resistance rises, there is a compensatory
increase in insulin secretion and the individual remains
normoglycemic.In the long term, as the -cells begin to fail,
insulin secretion falls, hyperglycemia becomes apparent and frank
type 2 diabetes develops.
Adapted from Bergenstal RM, et al. Diabetes mellitus,
carbohydrate metabolism and lipid disorders. In Endocrinology. 4th
ed. 2001. *T-PA tissue-type plasminogen activator antigen