Lada and mody

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

1. LADA & MODY Presented By Sriloy Mohanty

2. LADA- Latent Onset Diabetes In Adult

3. 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

4. Diabetes 1.5

5. History 1980s San Raffaele Hospital Milan (patient) Stiff Mans Syndrome (SMS) Type 1 DM Anti GAD antibodies (Glutamic acid decarboxylase)

6. 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

7. Adults who should be considered for antibody testing*: age of onset <50 years acute symptoms BMI <25 kg/m 2 personal or family history of autoimmune disease C-Peptide test is positive

8. 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

9. 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

10. 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)

11. Maturity-Onset Diabetes of the Young (MODY) 1975 Definition Type-2 diabetes mellitus in the young plus Autosomal dominant inheritance

12. 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

13. 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

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

15. 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

16. Liver-enriched transcription factors HNF-1 a , HNF-1 b , and HNF-4 a 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.

17. Transcription factor IPF-1 Rare Expressed in pancreatic islets Central role in development of pancreas. Mediates glucose-induced stimulation of insulin-gene transcription

18. 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

19. 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

20. 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

21. 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.

22. Thank you…