Professional Documents
Culture Documents
Dr Muries
Barham
Diabetes
Diabetes mellitus may present with
characteristic symptoms such as thirst,
polyuria, blurring of vision, and weight loss.
In its most severe forms, ketoacidosis or a
nonketotic hyperosmolar state, in absence of
effective treatment, death.
Often symptoms are not severe, or may be
absent, and consequently hyperglycaemia
sufficient to cause pathological and functional
changes may be present for a long time
before the diagnosis is made.
Glucose Tolerance
Categories
FPG
Plasma glucose
(mg/dL)
h PPG (OGTT)-2
240
Diabetes
Mellitus
220
200
180
Diabetes
Mellitus
160
14
0
126
120
IFG
100
80
IGT
Normal
Normal
60
American Diabetes Association. Diabetes Care. 2004;27(suppl 1):S5-S10
Type 2
Gestational
D. Endocrinopathies
Acromegaly, Cushing's
syndrome, glucagonoma,
pheochromocytoma,
hyperthyroidism,
somatostatinoma,
aldosteronoma
E. Drug- or chemicalinduced
F. Infections
congenital rubella,
cytomegalovirus,
coxsackie
G. Uncommon forms of
immune-mediated diabetes
"stiff-person" syndrome,
anti-insulin receptor antibodies
Gestational
Diabetes
Hyperglycemia during pregnancy
usually resolves
after birth
Complicates ~4% of all
pregnancies in the United States
High risk of perinatal morbidity
and mortality
Gestational
Diabetes
Etiologies of diabetes/hyperglycemia
in childhood
1- Type 1 DM.
2- Type 2DM.
3- Other specific types of DM:
Genetic defects in beta-cell and
in insulin receptor.
ANTIBODIES:
ISLET CELLS
DURATION OF DIABETES
% POSITIVE
1-4 WEEKS
60-95 % *
3-9 MONTHS
50 %
1-10 YEARS
< 25 %
AntiGADAntibodies
Present in 75- 84 % of
recent onset DM type 1.
Pathogenesis of Type 1
Diabetes : One Defect
No hepatic
insulin effect
Unrestrained
glucose production
Absent
insulin
secretion
Hyperglycemia
No muscle/fat
insulin effect
Impaired glucose
clearance
Glycosuria
D.M. Type 1
Epidemiology in US in < 19 yr of age
population:
1. Incidence: 16/100,000/yr.
2. Prevalence: 140/100,000.
3. Mean age of onset: 11 yr in F / 12.5 yr in M.
4. Incidence by gender:
< 5 yr: increased in males;
5-10 yr: increased in females;
11-19 yr: equal in males and females.
D.M. Type 1
Pathogenesis
1. Genetic factors:
1) Major histocompatibility complex
(MHC) predisposing genes HLA-DR3,
DQB1*0201 or DR4,DQB1*0302.
protective: DQB1*0602.
2) Non- MHC genes: At least 19 genes
have been identified, 3 of them
mapped to chromosomes: 11, 15, 2.
D.M. Type 1
2. Environmental factors: e.g. Coxakie virus
infection.
3. Autoimmune:
A) T- lymphocyte- mediated destruction
(inslinitis).
B) Markers, not causative: Autoantibodies
( ICA, IAA, GAD).
D.M. Type 1
The combination of all those factors
ultimately leads to - cell destruction,
which is an insidious process that may
take up to 10 yrs before completion;
once the - cell mass is <5-10% of its
original amount, symptoms of diabetes
become manifest.
Late-Onset Type 1
Diabetes
About half of patients with type 1
diabetes are diagnosed after age 18
Autoimmune process may differ and is
slower
Often mistaken for type 2 diabetesmay
make up 10%30% of individuals
diagnosed with type 2 diabetes
Can be identified by ICA or GAD
antibodies
Oral agents are usually ineffective
insulin therapy is eventually required
called:
1. Characterized by evidence of
recovery of
endogenous insulin secretion.
[ presence of C-peptide in serum ]
Insulin requirements become less
and less, sometimes none.
Type 1.5 DM
Begins as Type 1 with DKA.
Later becomes non-insulin dependent.
No HLA predisposition.
No autoimmunity.
Occurs in certain ethnic groups, e.g.
African- Americans.
Pathogenesis of Type 2
Diabetes : Two Defects
Hepatic
insulin
resistance
Excessive
glucose production
Impaired
insulin
secretion
Hyperglycemia
Glycosuri
Muscle/fat
insulin
resistance
Impaired glucose
clearance
120
100
Normal
20
glucose
80
60
40
20
0
30 0 30 60 90 120
Time )minutes(
Type 2 diabetes
Plasma insulin )U/ml(
120
100
20 g glucose
80
60
40
20
0
30 0 30 60 90 120
Time )minutes(
MODY
MODY is non-insulin requiring form
of diabetes,occurring in children and
young adults,resulting from genetic
defect in beta-cell function,and
inherited in autosomal dominant
trait(AD)
MODY
MATURITY ONSET
YOUNG (MODY)
DIABETES
OF
THE
Clinical Features
Obesity
Type 1
No
No
Yes
Type 2
Yes
Yes
No
MODY
No
No
No
MODY
Type
Mody1
Gene
HNF-4
Mody2
Glucokinase
Mody3
HNF-1
Mody4
Mody5
IPF-1
HNF-1
.Diabetes
Diabetes;renal cysts and renal dysfunction,internal
genital . abnormalities
Mody6
NeuroD1,OR
BETA2
.Diabetes
h PPG (OGTT)-2
240
Diabetes
Mellitus
220
200
180
Diabetes
Mellitus
160
140
126
120
IFG
100
80
IGT
Normal
Normal
60
American Diabetes Association. Diabetes Care. 2004;27(suppl 1):S5-S10