lada and mody
DESCRIPTION
in this slide i have given a little information about latent autoimmune diabetes in adult and maturity onset diabetes in youngTRANSCRIPT
LADA & MODYPresented By
Sriloy Mohanty
LADA- Latent Onset Diabetes In Adult
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
Diabetes 1.5
History 1980s
San Raffaele Hospital
Milan (patient)
Stiff Mans Syndrome (SMS)
Type 1 DM
Anti GAD antibodies (Glutamic acid
decarboxylase)
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
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
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
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
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)
Maturity-Onset Diabetes of the Young (MODY)
1975 Definition
Type-2 diabetes mellitus in the young plus
Autosomal dominant inheritance
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
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
Heterozygous Gene Mutations Identified in MODY
Name (Year) GeneChromosome
MODY1 (1991) HNF-4a 20qMODY2 (1993) Glucokinase 7pMODY3 (1996) HNF-1a 12qMODY4 (1997) IPF-1 (PDX-1) 13qMODY5 (1997) HNF-1b 17qMODY6 (1999) Neuro-D1 / BETA-2 2q
HNF = Hepatocyte nuclear factorIPF = Insulin promoter factorPDX-1 = Pancreatic duodenal
homeobox-1
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
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.
Transcription factor IPF-1
Rare
Expressed in pancreatic islets
Central role in development of
pancreas.
Mediates glucose-induced
stimulation of insulin-gene
transcription
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
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
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
Rx for MODYRx 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.
Thank you…