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DIABETUL ZAHARAT
Diabetul zaharat
Curs 1
Introduced the
term diabetes -Established the relationship
Defined: between pancreas and
- normal values of blood glucose, diabetes.
-renal threshold for glucose, -Made the distinction
- glycogenic function of the liver between Type 1 and Type 2
diabetes
Mota M, Popa SG, Mota E, Mitrea A, Catrinoiu D. et al. Prevalence of Diabetes Mellitus and Prediabetes in the Adult
Romanian Population: PREDATORR Study. J Diabetes. 2015. doi: 10.1111/1753-0407.12297. [Epub ahead of print]
Complications and mortality
Standards of Medical Care in Diabetes2015, Diabetes Care Volume 38, Supplement 1, January 2015
Metzger BE, Gabbe SG, Persson B, et al.; International Association of Diabetes and Pregnancy Study Groups Consensus Panel.
International Association of Diabetes and Pregnancy Study Groups recommendations on the diagnosis and classification of
hyperglycemia in pregnancy. Diabetes Care 2010;33:676682
Diabetul zaharat tip 1
Standards of Medical Care in Diabetes2015, Diabetes Care Volume 38, Supplement 1, January 2015
Diabetul zaharat tip 2 (anterior non
insulino-dependent)
Standards of Medical Care in Diabetes2015, Diabetes Care Volume 38, Supplement 1, January 2015
Alte tipuri specifice de DZ - diagnostic
A. Defecte genetice ale functiei celulelor beta
Diagnosticul DZ monogenic (DZ neonatal si MODY -
Maturity-Onset Diabetes of the Young) trebuie luat n
considerare la copiii la care se constat:
DZ diagnosticat n primele 6 luni de via
AHC puternice de DZ, dar far caracteristicile DZ tip 2
(non-obez, etnie cu risc sczut)
Glicemie a jeun medie (100150 mg/dL [5.5
8.5mmol/L])
Autoanticorpi negativi i far obezitate sau insulino-
rezisten.
Standards of Medical Care in Diabetes2015, Diabetes Care Volume 38, Supplement 1, January 2015
Standards of Medical Care in Diabetes, Diabetes Care Volume 37, Supplement 1, January 2014
http://monogenicdiabetes.uchicago.edu/what-is-monogenic-diabetes/mody-maturity-onset-diabetes-of-the-young/types-of-mody/
Alte tipuri specifice de DZ - diagnostic
B. Defecte genetice in actiunea insulinei
Insulinorezistenta tip A
Leprechaunism
Sindromul Rabson-Mendenhall
Diabetul lipoatrofic
C. Bolile pancreasului exocrin
Pancreatitele
Trauma/pancreatectomie
Neoplasm/ Fibroza chistica
Hemocromatoza
Talasemie/ Pancreatopatie fibrocalculoasa.
Standards of Medical Care in Diabetes, Diabetes Care Volume 37, Supplement 1, January 2014
DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012
Alte tipuri specifice de DZ - diagnostic
D. Endocrinopatii
Acromegalie
Hipertiroidism
Sindrom Cushing
Feocromocitom
Glucagonom
Somatostatinom
Aldosteronom.
Standards of Medical Care in Diabetes, Diabetes Care Volume 37, Supplement 1, January 2014
DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012
Alte tipuri specifice de DZ - diagnostic
Standards of Medical Care in Diabetes, Diabetes Care Volume 37, Supplement 1, January 2014
DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012
Alte tipuri specifice de DZ - diagnostic
I. Alte sindroame genetice, deseori asociate cu diabet
Sindromul Down
Sindromul Klinefelter
Sindromul Turner
Sindromul Wolfram
Porfiria
Ataxia Friedreich
Corea Huntington
Sindromul Laurence-Moon-Biedl
Distrofia miotonica
Sindromul Prader-Willi.
Standards of Medical Care in Diabetes, Diabetes Care Volume 37, Supplement 1, January 2014
DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012
Criterii de screening pentru diabet la
indivizii aduli asimptomatici
Adultii cu IMC >25kg/mp* + factori de risc aditionali:
o Sedentarism
o Rude grad 1 cu DZ
o Prediabet testari anterioare
o Rase/etnii cu risc crescut (african-americanii, latinii)
o Femei care au nascut macrosomi (G >4 kg la nastere) sau DZG
o HTA, istoric de boala cardio-vascular
o HDL-Col <35mg/dL (0.90mmol/L) si/sau TG>250mg/dL
(2.82mmol/L)
o IR (obezitate severa, femei cu sindrom de ovar polichistic
acantosis nigricans)
In absenta criteriilor (1): testarea va incepe la 45 ani.
Standards of Medical Care in Diabetes2015, Diabetes Care Volume 38, Supplement 1, January 2015
Araneta MR, Gandinetti A, Chang HK. Optimum BMI cut points to screen Asian American for type 2 diabetes: the UCSD
Filipino Health Study and the North Kohala Study. Diabetes 2014;63(Suppl. 1):A20
Criterii de screening pentru DZ tip 2 la
adulii asimptomatici
Standards of Medical Care in Diabetes2015, Diabetes Care Volume 38, Supplement 1, January 2015
American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2014;37(Suppl. 1):S81S90
Screening i diagnostic pentru DZG
Standards of Medical Care in Diabetes2015, Diabetes Care Volume 38, Supplement 1, January 2015
Agenda
unused glucose
glucose
requirement
Fasted-state metabolism
Morfopatologia pancreasului n DZ tip 1
Insulinorezistenta
Raspuns compensator -
Stimulare cronica -celulara
celular
Disfunctie -celulara
Hiperinsulinism compensator
Insuficienta compensatorie -celulara
Diabet
zaharat
R.Pannala et al. New-onset diabetes: a potential clue to the early diagnosis of pancreatic cancer Lancet Oncol 2009; 10: 8895
Evoluia naturala a DZ tip 2
Adaptat dup: Mazze R, et al. Part two: The treatment of diabetes. In: Mazze R, Strock ES, Simonson G, Bergenstal RM, eds. Staged Diabetes
Management: A Systematic Approach. 2nd ed. rev. 2006:78-154. Int J Clin Pract. Dec 2012; 66(12): 11471157
H. Bosch, Lcomia, c. 1480
Echilibrul secretor ntre insulin i glucagon
menine controlul normal postprandial al glicemiei
140 Masa Glicemie
Insulin
mg%
120 Glucagon
Dup mas
100
160
120 Insulin Glucagon
mU/ml
80
40
Acest echilibru controleaz
strict creterile glicemice care
130
120
apar dup ingestia de alimente
110
pg/ml
100
90 n condiii normale, controlul
0 glicemic se auto-regleaz
-60 0 60 120 180 240
Timp (min)
18
Glucoz (mmol/L)
12
0
0600 1000 1400 1800 2200 0200 0600
Timp (ore)
M. Mota, M. Dinca, S.Popa si col. Patologia Nutritional Metabolica, ed Medicala Universitara Craiova, 2010
Agenda
*Goals should be individualized based on duration of diabetes, age/life expectancy, comorbid conditions,
known CVD or advanced microvascular complications, hypoglycemia unawareness.
Postprandial glucose measurements should be made 12 h after the beginning of the meal.
Diabetes Care Volume 39, Supplement 1, January 2016.
Lipid Targets for Pacients with Type 2 DM
1. Endocr Pract. 2015;21(Suppl 1); 2. European Heart Journal Advance Access, May,
2016; 3. European Heart Journal Advance Access published
August 27, 2016.
Hypertension and diabetes
Systolic targets/ Diastolic targets
Assess
Underlying causes, Co-morbidities, Assess effects on co-
Weight loss history morbidities, weight,
maintenance and weight
Set goals and propose realistic, individualized and regain.
sustainable lifestyle changes at the log term
Weight loss goal
5-15% of body weight or 0,5-1.0 kg/week
- CH ~ 45 -55%
- L ~ 25-36%
- P ~ 16-20%
Diabetes Care 2014;37(suppl.1):120-143.
Terapia nutriional n diabet
Macronutrieni - glucide
- Cantitate individualizat
- Aportul de CH glicemia postprandial
- Monitorizarea cantitativ a aportului de CH
strategie cheie n obinerea controlului glicemic
- Surse recomandate
- Legume i vegetale
- Fructe
- Cereale integrale
- Produse lactate
Diabetes Care 2014;37(suppl.1):120-143.
Exerciiul fizic
Se recomand EF
aerob, 30 min /zi,
5 zile/ sptmn
Tratamentul medicamentos n DZ
INSULINA totdeauna,
imediat dupa stabilirea diagnosticului
Tipuri de tratament insulinic
Clasic
- Convenional (1-2 injecii/zi)
- Intensiv (3-5 injecii/zi)
Modern
- intensiv: pompa de insulina
- Pancreas artificial
Insulinoterapia
Administrare:
- Subcutanat
- Intravenos
- Intramuscular
Aspect:
- Toate au aspect limpede.
Administrarea iv a insulinelor cu
ac. scurt
Tipuri de insulin:
- Mixtard 10%, 20%, 30%, 40%, 50%
- Humulin M1 (10%), M2 (20%), M3 (30%) etc,
- Insuman Comb 25, 50.
Aspect: tulbure.
Insulin types
Rapid-acting - Humalog ,
Novolog , Apidra
Short-acting - Regular
Intermediate - NPH
Long-acting - Glargine
(Lantus), Detemir (Levemir)
79
Tratamentul intensiv modern
Pancreasul artificial
- folosit de necesitate: gravida cu DZ n travaliu,
intervenii chirurgicale, coma diabetic
-printr-un mecanism de feed-back el injecteaz
glucoz sau insulin iv, n funcie de glicemie.
Pompele de insulin
- administreaz continuu, aproximativ 1u insulin pe or
sc, iv sau intraperitoneal i cte un bolus de insulin la
fiecare mas, funcie de glicemii (pe care le efectueaz
bolnavul), doze pe care le stabilete bolnavul.
Continuous subcutaneous insulin infusion
(CSII) pumps
External, programmable pump connected to a subcutaneous
catheter to deliver rapid acting insulin as a basal rate and prandial
boluses in oreder to mimick the physiological insulin secretion
Pompe de insulin
Hipoglicemia
Cresterea ponderala
Abcese locale
Alergia la insulina
Lipodistrofia atrofic sau hipertrofic
Dureri la locul injectrii
Tulburri de vedere
Edeme insulinice
Insulinorezistena
Declansarea unui episod de neuropatie hiperalgica
Tratament n diabetul zaharat
de tip 2
Locuri de aciune ale medicaiei
antidiabetice
Metformin
Mecanism de actiune
Metformin controleaz IR; nu stimuleaz insulinosecreia
- Suprim producia hepatic de glucoz
- Crete captarea muscular a glucozei mediat de insulin
Metformin scade n principal hiperglicemia a jeun in DZ tip 2
Monoterapia cu metformin nu causeaz hipoglicemie
Aciunea antidiabetic a metformin necesit insulin n circulaie
Metforminul nu cauzeaz cretere ponderal
Metformin amelioreaz profilul lipidic.
Metforminul poate ameliora ali factori de risc cardiovascular.
Indicaii ale Metformin
Indicaii - Ca monoterapie, sau n combinaie cu alte
antidiabetice orale sau insulin n DZ tip 2
Utilizare - Se va lua dup mas
- Se va crete doza progresiv, maxim 3 g/zi
Contraindicaii - Boli renale i hepatice
i atenionri - Insuficien cardiac i respiratorie
- Infecii severe, abuz de alcool, istorie de
acidoz lactic, sarcin
- n explorrile cu substane de contrast iv
Efecte - Simptome gastrointestinale, gust metalic
secundare - Poate altera absorbia vitaminei B 12 i a
acidului folic
- Risc de acidoz lactic, dar sczut.
Diabetes Mellitus and related disorders, Forth edition, Harold Lebovitz, 2004
Derivaii de sulfoniluree (SU)
Mecanism de aciune
Contraindicaii
DZ tip 1
Pacieni cu boli hepatice
Sarcin
Insuficien cardiac
Boli cardio vasculare
Inhibitorii de alfa-glucozidaz
Mecanism de aciune: inhib alfa-glucozidaza
intestinal => scade digestia glucidelor, care vor fi
eliminate n scaun
Reprezentani:
Acarboza (GLUCOBAY) de 50mg i 100mg
Miglitol
Reacii adverse:
meteorism, flatulen
insuficien hepatic.
Tratamentul incretinic
Efectul incretinic asigur ~60-70% din eliberarea de insulin pp
Glucagon-like peptide 1 (GLP-1)
Sintetizat i eliberat de celulele endocrine L, n ileon i colon
Locuri multiple de aciune:
celulele pancreatice i ,
tractul GI,
SNC,
Cord
Glucose-dependent insulinotropic polypeptide (GIP)
Sintetizat i eliberat de celulele endocrine K, n duoden i
jejun
Locul de aciune:
predominant celulele pancreatice;
Adipocite
Efectele GLP1 i GIP sunt mediate de receptori specifici
Drucker DJ. Diabetes Care. 2003;26:2929-2940; Thorens B. Diabetes Metab. 1995;21:311-318; Baggio LL, Drucker DJ.
Gastroenterology. 2007;132:2131-2157; Nyberg J, et al. J Neurosci. 2005;25:1816-1825.
Rolul Incretinelor n homeostazia glicemic
Captarea
Pancreas Insulina Glucozei de
Ingestia de (GLP-1 i GIP) esuturile
hran Glucozo periferice
dependent
cells
Tract
GI
Eliberare de
Incretine cells
active GLP-1 i GIP Glucoza
Glucozo sanguin a jeun
dependent
DPP-4 i pp
enzyme
Glucagon
(GLP-1)
GLP-1 GIP
Inactiv Inactiv Producia
Hepatic de
glucoz
Concentrations of the active intact hormones are increased by JANUVIA, thereby increasing and prolonging the actions
of these hormones. Trademark of Merck & Co., Inc., Whitehouse Station, NJ, USA
Agoniti de receptori de GLP
Exenatide (Byetta) / injectabil, sc
- 2 injecii/zi de 5 microgr
Sau
- 2 injecii/zi de 10 microgr
Se recomand n DZ tip 2, cnd medicaia oral maxim
nu mai este eficient/ mai devreme chiar
Se adm nainte de mas, cu maxim 60 min
Durata ntre prize va fi mai mare de 6 ore
Bydureon 2mg form cu aciune prelugit: durata 7 zile.
Administrare injectabil, sc.
Inhibitorii de DPP4
Januvia (Sitagliptin)
Saxagliptin - recent
1tb de 100 mg se adm nainte de mas
Crete GLP 1 prin scderea catabolismului,
inhibnd DPP 4.
JANUVIA (sitagliptin)
Mecanism de aciune
Captarea
Pancreas Insulina Glucozei de
Ingestia de (GLP-1 i GIP) esuturile
hran Glucozo periferice
dependent
cells
Tract
GI
Eliberare de
Incretine cells
active GLP-1 i GIP Glucoza
Glucozo sanguin a jeun
dependent
i pp
JANUVIA
(DPP-4 X DPP-4
enzyme Glucagon
(GLP-1)
inhibitor)
GLP-1 GIP
Inactiv Inactiv Producia
Hepatic de
glucoz
Concentrations of the active intact hormones are increased by JANUVIA, thereby increasing and prolonging the actions
of these hormones. Trademark of Merck & Co., Inc., Whitehouse Station, NJ, USA
Inhibitori ai SGLT 2 (transportori de Na-
glucoza)
Hiperglicamie a - biguanide
jeun - glitazone
- sulfoniluree cu aciune lung
- insuline sau analogi de insulin cu aciune lung
Insulino - biguanide
rezisten - glitazone
- inhibitori de alfa-glucozidaz
Deficit de - sulfoniluree
insulin - glinide
- insulin