25. TTiipp 11 ddiijjaabbeetteessaa::
Primarno oštećenje: odsutna ili minimalna
proizvodnja inzulina
Uzrok: Uništenje β-stanica gušterače
(najčešće autoimuna porijekla)
Simptomi se javljaju kad 90% stanica više ne
funkcionira
Presentation title Date Slide no 26
27. ZZaaššttoo jjee ššeeććeerrnnaa bboolleesstt ttiipp 22 ssvvee
uuččeessttaalliijjaa bboolleesstt??
Debljina
Genetska komponenta
DIJABETES TIP 2
Zapadnjački stil
života
International Diabetes Federation. Diabetes Atlas, 2nd Edition, 2003
28. Presentation title Date Slide no 29
AAbbddoommiinnaallnnii ttiipp pprreettiilloossttii
VISCERALNO MASNO TKIVO
metabolički aktivno tkivo
Opseg struka M > 100
cm
Ž > 90 cm
29. Presentation title Date Slide no 30
DDiissttrriibbuucciijjaa vviisscceerraallnnoogg mmaassnnoogg
ttkkiivvaa
normalno tip 2 DM
Courtesy of Wilfred Y. Fujimoto, MD.
31. Patogeneza ššeeććeerrnnee bboolleessttii ttiipp IIII
Toksičnost glukoze
oštećenje β- stanice
lučenje inzulina
potaknuto glukozom
tkivna osjetljivost
na inzulin
mutacije gena
druga oštećenja
okoliš
debljina
mutacije gena
proizvodnja glukoze
u jetri hiperglikemija
Iskorištenje glukoze
hiperinzulinemija
u tkivima
Inzulinski receptori
postreceptorski poremećaji
ciljna tkiva
prijenos glukoze
32. Presentation title Date Slide no 33 PPaattooggeenneezzaa kkrroonniiččnniihh kkoommpplliikkaacciijjaa ––
oossnnoovvnnaa mmeehhaanniizzmmaa
HIPERGLIKEMIJA
glikacija bjelančevina
mikroangiopatija ubrzan razvoj ateroskleroza
ulazak glukoze u stanice neovisno o
inzulinu
nagomilavanje sorbitola i
fruktoze
osmotsko bubrenje stanica
DIJABETIČKA
NEUROPATIJA
KATARAKTA
OČNE LEĆE
DIJABETIČKA
RETINOPATIJA
DIJABETIČKA
NEFROPATIJA
PERIFERNA
ANGIOPATIJA
33. Presentation title Date Slide no 34
MMaakkrrooaannggiiooppaattiijjaa
OOšštteeććeennjjee vveelliikkiihh
kkrrvvnniihh žžiillaa
uuzzrrookkoovvaannoo
aatteerroosskklleerroottsskkiimm
pprroocceessoomm
Naslage kolesterola
Aterosklerotiski plak
35. Presentation title Date Slide no 36
MMiikkrrooaannggiiooppaattiijjaa
OOšštteeććeennjjee
mmaalliihh kkrrvvnniihh
žžiillaa
–RReettiinnooppaattiijjaa
–NNeeffrrooppaattiijjaa
–NNeeuurrooppaattiijjaa
((aauuttoonnoommnnii ii
ppeerriiffeerrnnii
žžiivvccii))
41. Presentation title Date Slide no 42
NNeeffrrooppaattiijjaa
TTrraajjaannjjee ddiijjaabbeetteessaa,, llooššaa rreegguullaacciijjaa
gglliikkeemmiijjee ii kkrrvvnnoogg ttllaakkaa ppoovveeććaavvaajjuu rriizziikk
nneeffrrooppaattiijjee
SSttaaddiijjii::
– nnoorrmmooaallbbuummiinnuurriijjaa
–mmiikkrrooaallbbuummiinnuurriijjaa
–mmaakkrrooaallbbuummiinnuurriijjaa iillii pprrootteeiinnuurriijjaa
– bbuubbrreežžnnoo zzaattaajjeennjjee
42. Presentation title Date Slide no 43
AAkkuuttnnee kkoommpplliikkaacciijjee
ššeeććeerrnnee bboolleessttii::
• dijabetička ketoacidoza
• neketotična hiperosmolarna koma
• hipoglikemija
43. Patogeneza akutnih komplikacija šećerne bolesti
Manjak inzulina
Lipoliza, β –oksidacija
slobodnih masnih kiselina
Katabolizam
bjelančevina Iskorištavanje glukoze
ketonska tijela u krvi glukoneogeneza HIPERGLIKEMIJA
metabolička acidoza osmotička diureza hiperosmolalnost
Izvanstanične tekućine
unutrastanična
dehidracija
HIPEROSMOLARNA
KOMA
DEHIDRACIJA
elektrolitska neravnoteža
KETOACIDOTIČKA
KOMA
Gubitak Na, K
49. MMeettaabboolliizzaamm bbjjeellaannččeevviinnaa
AAmmiinnookkiisseelliinnaa ssee uuggrraađđuujjuu uu
ffuunnkkcciioonnaallnnee pprrootteeiinnee
SSiinntteezzuu bbiiooggeenniihh aammiinnaa
SSiinntteezzaa ppuurriinnsskkiihh ii
ppiirriimmiiddiinnsskkiihh bbaazzaa
GGlluukkoonneeooggeenneezzaa
LLiippooggeenneezzuu
IIzzrraavvnnaa uuppoottrreebbaa zzaa eenneerrggiijjuu From: Summerlin LR (1981) Chemistry for the Life Sciences. New
York: Random House p 563.
The primary defect in type 1 diabetes is absent or minimal insulin secretion. This is due to destruction of the beta-cells. Type 1 diabetes is diagnosed only when extensive destruction of beta-cells occurs (> 90%). The destruction may be due to unknown cause(s), or may be a result of autoimmune destruction (self-destruction).
There is a strong family history, with 45–80% of young sufferers having at least one parent with diabetes and 74–100% having a first- or second-degree relative with type 2 diabetes. The increased incidence of type 2 diabetes seems to reflect the growth in urbanization and economic development, and is closely associated with the increase in individuals who are overweight or obese.
International Diabetes Federation, 2003. Diabetes Atlas, 2nd edition. Available at: www.idf.org/e-atlas. Last accessed 25 January 2007.
Development and Progression of Type 2 Diabetes
This conceptual diagram shows a proposed paradigm on the development and progression of pathophysiology in type 2 diabetes.1
The horizontal axis in the figure shows the years before and after diagnosis of diabetes.
Insulin resistance begins years before diagnosis.1 Insulin resistance rises during disease development and continues to rise during impaired glucose tolerance (IGT). Over time, insulin resistance remains stable during the progression of type 2 diabetes.1
The insulin secretion rate increases to compensate for the decrease in insulin effectiveness due to insulin resistance. β-cell function can decrease even as insulin secretion increases. At the time of diagnosis of type 2 diabetes and 6 years afterwards about 50% and 73% of β-cell function has been lost, respectively.2 Over time, β-cell compensatory function deteriorates and insulin secretion decreases. β-cell function progressively fails.1,2
Initially, fasting glucose is maintained in near-normal ranges. The pancreatic β cells compensate by increasing insulin levels, leading to hyperinsulinemia. This compensation keeps glucose levels normalized for a time, but as β cells begin to fail, IGT develops with mild postprandial hyperglycemia. As the disease progresses, the β cells continue to fail, resulting in higher PPG levels. With continued loss of insulin secretory capacity, fasting glucose and hepatic glucose production increase.1
Once β cells cannot secrete sufficient insulin to maintain normal glycemia at the fasting or postprandial stage, type 2 diabetes (hyperglycemia) becomes evident.
Insulin resistance and β-cell dysfunction are established well before type 2 diabetes is diagnosed.1
POLIOLSKI PUT – povećana aktivnost sorbitolskog puta dovodi do intracelularnog nagomilavanja sorbitola i fruktoze. Posljedica toga je ulazak vode u stanicu i stanično bubrenje koje remeti njezinu funkciju i uzrokuje njeno oštećenje. Hiperglikemija s povećanim ulaskom glukoze u stanice koje ne ovise o inzulinu ometa ulazak mioinozitola u stanice. (mioinozitol je preteča inozitol-fosfatnih spojeva koji imaju ulogu unutarstaničnih kemijskih posrednika).
GLIKACIJA BJELANČEVINA=proces u kojem se glukoza (zbog suviška) kemijski veže za proteine, bez posredovanja enzima
With macroangiopathy, fat and blood clots build up in the large blood vessels (atheroma formation), stick to the vessel walls, and block the flow of blood. Types of macroangiopathy include: coronary artery disease (in the heart), cerebrovascular disease (in the brain), and peripheral vascular disease (affecting, for example, vessels in the legs).
Persistent hyperglycaemia in people with diabetes cause damage to the microvascular circulation and to cells that are not dependent upon insulin for their glucose uptake. Excessive levels of glucose cause permanent damage to the eyes (retinopathy), kidneys (nephropathy) and autonomic and peripheral nerves (neuropathy). The chronic microvascular complications are rarely seen before 5–7 years’ duration of diabetes in type 1 diabetes. In contrast, type 2 diabetes patients often present at diagnosis with retinopathy, neuropathy or foot ulceration, as many of them have been living for years with mildly elevated blood glucose before they are diagnosed. Hypertension additionally contributes to the severity of microvascular complications,
Diabetic retinopathy develops, to some degree, in nearly all patients with diabetes, and is the most common cause of new cases of blindness among adults. The most predominant causes of vision loss are clinically significant macular edema (CSME) and proliferative diabetic retinopathy (PDR). Vision loss can be avoided or minimized with proper ophthalmic care and examination to identify retinopathy in its early stages.
There are several stages of retinopathy. The earliest clinical stage of diabetic retinopathy is identified as mild nonproliferative diabetic retinopathy (NPDR). Progression of disease from NPDR to proliferative diabetic retinopathy (PDR) is related to the level or severity of NPDR, and therefore the severity of NPDR should determine follow-up and management of diabetic retinopathy.
The next four slides will review the clinical findings and management of each stage of retinopathy.
Different patterns of neuropathy exist (see figure).
The ‘classic’ diabetic peripheral neuropathy affect symmetrically the sensor and motor nerves. It is the commonest neuropathy and is due to distal dying back of axons affecting the long nerves, and therefore the feet are often affected in a stocking distribution. Symptoms include numbness, altered sensation and pain. Loss of pain sensation is an important cause of foot ulcerations.
Other peripheral neuropathies include mononeuropathies (probably ischaemic in origin), pressure palsies and acute painful neuropathy.
Autonomic neuropathy may affect the cardiovascular, gastrointestinal, genitourinary and other systems. The most common conditions related to autonomic neuropathy are postural hypotension, palpitations, gastroparesis and erectile dysfunction. The latter can also be a result of psychological and vascular factors.
Diabetic complications can be divided into acute and long-term complications. The acute complications are associated with untreated type 1 diabetes (diabetic ketoacidosis) and the over-treatment of diabetes with either insulin or insulin secretagogues (hypoglycaemia).
The long-term microvascular complications of diabetes are related to the degree and duration of hyperglycaemia. Long-term complications are not an inevitable consequence of diabetes and much can be done to minimize their effects by encouraging patients to maintain tight blood glucose control and to make lifestyle changes to reduce their cardiovascular risk factors.
