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