in this slide i have given a little information about latent autoimmune diabetes in adult and maturity onset diabetes in young

2. LADA & MODY
Presented By
Sriloy Mohanty

3. LADA- Latent Onset Diabetes In Adult

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

5. Diabetes 1.5

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)

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

17. Heterozygous Gene Mutations
Identified in MODY
Name (Year) Gene Chromosome
MODY1 (1991) HNF-4a 20q
MODY2 (1993) Glucokinase 7p
MODY3 (1996) HNF-1a 12q
MODY4 (1997) IPF-1 (PDX-1) 13q
MODY5 (1997) HNF-1b 17q
MODY6 (1999) Neuro-D1 / BETA-2 2q
HNF = Hepatocyte nuclear factor
IPF = Insulin promoter factor
PDX-1 = Pancreatic duodenal homeobox-1

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.

26. Thank you…