case

1

• ??? ??? ??? ???
• ??? ? ? ??? ???

2
Case

• Wang Ming, male, 6 years old .He was sent to
  hospital for cold ,headache ,felt unusual
  thirsty,so he drinks very much and urinate
  frequently day and night .Eat much,but weight
  loss, abdomenal pain,No fever, sweating, visual
  blurring or edema on lower limb.
• Blood routine and urine routine have been
  carried out. which show that blood glucose
  (after fasting for 8 hrs) gt27.8mmol/l, WBC gt 17.2
  109 L, Urinary glucose ,ketone body
• Immunological tests show that ICA is positive

3
DIAGNOSIS

• drink much, polyuria, more food, weight loss
• blood glucose (after fasting for 8 hrs
  )gt27.8mmol/l, Urinary glucose 4 ,

Diabetes
4
Complications of diabetes

• Keto acidosis
• pathological changes of heart heart failure,
  angina, miocardial infarction
• pathological changes of eyes iritis, glaucoma,
  cataract
• pathological changes of foot Gangrene
• pathological changes of nerve, kidney

5
Classification of diabetes
Diabetes
others
type2
GDM
type1
Immune mediated
Idiopathic
6

• apparent keto acidosis
• Immunological tests show that ICAs(selfAb) is
  positive

• Autoimmune type1 diabetes mellitus

7
Autoimmue type1 diabetes mellitus

• Clinical manifestation
• Cause and Mechanism
• Prevention and treatment

8
Clinical manifestation

• Two types
• Adolescent type1
  LADA
• 
  (latent-onset diabetes in adult)
• Onset Acute
  chronic
• Classical syndromapparent
  hidden
• Keto acidosis yes under
  infection/stress
• both lack of insulin absolutely
• treatmentinsulin
• selfAb(ICA, GAD-Ab ,IA-2,IAA)

9
Cause

• Function of heredity

• Environmental factor

10
Function of heredity

• Consistent rate of type1 diabetes in monozygotic
  twins is 30----50
• The probability that relatives of patients
  suffer type 1 diabetes is 5----10,while the
  probability of common people is 0.4

• Statistics indicate that type1 diabetes is
  highly related to heredity ,so far many
  susceptible genes of the disease have been
  discovered

11
Susceptible genes of type1 diabetes
Susceptible genes chromosome Link marker
IDDM1 6P21 HLA-DQB
IDDM2 11P15 Insulin VNTR
IDDM3 15q26 Insulin VNTR
IDDM4 11q13 FGF3,D11S1337
IDDM5 6q25 D6S476-ESR-D6S448
IDDM6 2q31 D2S152
IDDM7 6q27 D6S281
IDDM8 14q24,3-q31 D14S67
IDDM11 2q33 CTLA-4
IDDM12 7q34 IGFBP-2,-5
12

• HLA-DR and HLA-DQ linked with IDDM1 are closely
  related to type1 diabetes
• The 57th aa residue on the product of DQßchain
• Asp resistance
• Ala ,vla susceptible
• The mutation of the genes can change the
  specificity of MHC-?binding with self/non-self Ag

13
Environmental factors

• Virus ???B4 ??, ????, ?????

• Chemical substance Vacor(?????????)

• Milk albumin

• Cytotoxic substance ????????

14
Autoimmune trigger mechanism

• Molecular mimicry ( cross reaction )

• Abnormal expression of HLA-?

15
Molecular mimicry (cross reaction)

• Basis of cross reaction
  common antigen determinant
• ???B4???GAD(??????)
• ??????P69??(???ß??????)

16
Activated T cell
Nonself antigen
CTL
TH1
M?
Isletß cells
B ____ TH2 cell cell
Ab
17
Abnormal expression of HLA-?
Islet ßcell
MHC-?
CD4T

TH1?
CKs
CD8T
TH2?
macrophage
18
Fas-fasL
Activated T cell
IFN-r
Fas
FasL
CTL
ßcell
IL-1
macrophage
Isletßcell apoptosis
19

• lymphocytes infiltration in pancreas (rat)

20
characteristic

• Autoimmune type1 diabetes mellitus is caused by
  destruction of islet ß cell mediated by
  autoimmune response

• The marker of Autoimmune destruction of cells
  includeICA GAD-Ab IA-2

• Patients often have family history of Autoimmune
  diseases

• Polygenic susceptibility tendency
• Closely related to the HLA genes

21
Therapy and prevention
22

• Now the Insulin therapy is the most effective.
  Once the Type I diabetics is diagnosed, they
  will have to rely on insulin all the life, or
  else their lives will be endangered.

1978?,?????W????(?1980??????????????????)???????,
????DNA?????????????????
23

• But nowadays, the most effective way in
  confronting diabetes is still healthy and proper
  diet and doing proper amount of physical
  exercises.

24
Sugar or not?

• A diet with a strict limitation on sugar is
  not suggest for type 1 diabetes. Yes, that means
  the patient is allowed to take food with sugar
  but just in case that insulin is injected
  regularly, and still, the intake of refined sugar
  should still be limited. Food rich in protein is
  suggested.

25

• Breast feed is very important to prevent
  autoimmune type1 diabetes.since milk albumin can
  probably induce the disease

26
TRPV1 sensory neurons control beta cell stress
and islet inflammation in autoimmune diabetes

• In type 1 diabetes, T
  cell-mediated death of pancreatic beta cells
  produces insulin deficiency. However, what
  attracts or restricts broadly autoreactive
  lymphocyte pools to the pancreas remains unclear.
  We report that TRPV1() pancreatic sensory
  neurons control islet inflammation and insulin
  resistance. Eliminating these neurons in
  diabetes-prone NOD mice prevents insulitis and
  diabetes, despite systemic persistence of
  pathogenic T cell pools. Insulin resistance and
  beta cell stress of prediabetic NOD mice are
  prevented when TRPV1() neurons are eliminated.
  TRPV1(NOD), localized to the Idd4.1 diabetes-risk
  locus, is a hypofunctional mutant, mediating
  depressed neurogenic inflammation. Delivering the
  neuropeptide substance P by intra-arterial
  injection into the NOD pancreas reverses abnormal
  insulin resistance, insulitis, and diabetes for
  weeks. Concordantly, insulin sensitivity is
  enhanced in trpv1(-/-) mice, whereas
  insulitis/diabetes-resistant NODxB6Idd4-congenic
  mice, carrying wild-type TRPV1, show restored
  TRPV1 function and insulin sensitivity. Our data
  uncover a fundamental role for insulin-responsive
  TRPV1() sensory neurons in beta cell function
  and diabetes pathoetiology.

27
Thank you so much!
28

• The complication of diabetes also costs the
  sights of many patients, leaving them in
  the world of darkness for ever.

29

• Recently, there is data demonstrating that 70 of
  the patients that suffer from amputation are due
  to the complication of diabetes.