4. Introduction
Latent Autoimmune Diabetes in Adults (LADA) is a
form of autoimmune (type 1 diabetes) which is
diagnosed in individuals who are older than the
usual age of onset of type 1 diabetes.
Often, patients with LADA are mistakenly thought to
have type 2 diabetes, based on their age at the
time of diagnosis.
Progress to insulin requirement within 6 years
6. History
1980s
San Raffaele Hospital
Milan (patient)
Stiff Mans Syndrome (SMS)
Type 1 DM
Anti GAD antibodies (Glutamic acid decarboxylase)
7. GAD
Glutamic acid decarboxylase
Present in cytoplasm of the human beta cells
Catalyses the Conversion of glutamic acid to GABA
GABA is involved in release of insulin from secretory
granules
8. Adults who should be considered for
antibody testing*:
age of onset <50 years
acute symptoms
BMI <25 kg/m2
personal or family history of autoimmune
disease
C-Peptide test is positive
9. Symptoms
Unusual thirst
Frequent urination
Weight loss despite an increase in appetite
Blurred vision
Nausea and vomiting
Extreme weakness and fatigue
Irritability and mood changes
Frequent bladder and skin infections that don't heal
easily
High levels of sugar in the blood when tested
High levels of sugar in the urine when tested
Dry, itchy skin
Tingling or loss of feeling in the hands or feet
10. Diagnosis
C-peptide test (a measure of endogenous insulin)
If positive then….
GAD antibody test
Islet cell antibodies (ICA) are also common
HDL to triglyceride ratio- it exceeds 4 then insulin
resistance
If IR then no LADA
11. Rx for LADA
LADA often does not require insulin at the
time of diagnosis and may be managed
with diet and exercise
the avoidance of using metformin
treatment
May require multiple daily Insulin
injections(after 6 months)
12.
13.
14. Maturity-Onset Diabetes of the Young
(MODY)
1975 Definition
Type-2 diabetes mellitus in the young
plus
Autosomal dominant inheritance
15. Understanding MODY
Mutations in one of the 6 different genes
Onset of diabetes type 2 early in life:
childhood, adolescence or young
adulthood
Primary defect in insulin secretion, and
IR
16. Maturity Onset diabetes of the young
(MODY)
MODY 1 - Mutation in HNF-4-alpha (transcription factor),
chromosome 20
MODY 2 - Mutation in glucokinase gene, chromosome 7
MODY 3 - Mutation in HNF-1-alpha (transcription factor),
chromosome 12 (most common form)
MODY 4 - Mutation in insulin promoter factor-1 (IPF-1),
chromosome 13
MODY 5 - Mutation in HNF-1-beta, chromosome 17
MODY 6 - Mutation in Neurogenic Differentiation Factor-1
(NEUROD1) , chromosome 2
19. MODY-Related Proteins
Glucokinase
Expressed in b-cells and liver
GSK catalyzes the formation of glucose-6-phosphate from
glucose.
Liver – Helps in storage of glucose as glycogen
Mutation causes problem in conversion
20. Liver-enriched transcription factors
HNF-1a, HNF-1b, and HNF-4a
Expressed in liver, pancreatic islets, kidneys and
genitalia.
In Beta cells they regulate
The expression of the insulin gene
Proteins involved in glucose transport and metabolism.
Mutations results in defect of insulin secretion response to
glucose, leading to progressive decline in glycemic
control.
21. Transcription factor IPF-1
Rare
Expressed in pancreatic islets
Central role in development of pancreas.
Mediates glucose-induced stimulation of
insulin-gene transcription
22. Transcription factor Neuro-D1
(BETA2)
Rare
Expressed in pancreatic islets
Activates the transcription of the insulin
gene
Required for normal development of the
pancreatic islets
23. Recognition at young age
1.Mild, asymptomatic increase in blood glucose in
a child, adolescent or young adult(<25 years)
2. Prominent family history of diabetes in 2-3
generations
3. Usually not associated with obesity
24. When to suspect MODY
a “type 1″ diabetes patient who has negative blood
testing for autoantibodies.
a “type 1″ diabetes patient who generates a significant
amount of insulin for years beyond diagnosis (detectable
blood levels of c-peptide, proinsulin, and/ or insulin)
a “type 2″ diabetes patient who is normal weight and
shows no signs of insulin resistance.
a diabetes with family history of early onset diabetes for
2-3 generations.
Diabetes paired with pancreatic insufficiency
Individual or family history of diabetes paired with
developmental kidney disease or kidney cysts
25. Rx for MODY
Rx depends on the involved gene and other factors
MODY 3 and 1 can be treated initially with
sulfonylureas, prompts the body to produce
insulin.
Usually GCK-MODY requires no treatment at all.
Other type of MODY Rx is unclear may require
multiple daily Insulin injections.