1. ANTIBODIES VARIABILITY IN TYPE 1 DIABETES-Clinical implications? Dr M A LAMKI Senior Consult. Endocrinologist Royal hosp.Oman
2. Introduction <ul><li>Autoantibodies directed to the 65-kDa isoform of glutamate decarboxylase (GAD65), insulin, and a protein tyrosine phosphatase-like islet cell antigen (IA-2) predict the disease). Whereas insulin autoantibodies and IA-2Ab are negatively associated with age at onset, autoantibodies directed against GAD65 (GAD65Ab) are directly associated with age at onset. </li></ul>
3. DIABETES KETOACID. TYPE 1 ? INVEST? R/X INSULIN!!
4. DKA TYPE 1 TYPE 2 DM KETOSIS -PRONE DIABETES MELLITUS FOUR SUB-GROUPS Based on the presence Or absence of antibodies plus the via. Beta cells!
5. DIABETES KETOACIDOSIS <ul><li>DKA is defined by the presence of all of the following: anion gap 15 or greater, blood pH less than 7.30, serum bicarbonate 17 mmol/liter or less, serum glucose greater than 200 mg/dl(>11.1mmol), serum ketone s 5.2 mmol/liter or greater, or urine ketone s moderate to large. </li></ul><ul><li>J Clin Endocrinol Metab 88:5090 ﾐ 5 098  </li></ul>
7. <ul><li>B- Cell secretory capacity was measured at the time of the initial presentation with DKA (within 1 wk after resolution of ketoacidosis) and again after 12 months of follow-up by the following tests: fasting serum C-peptide concentration and C-peptide response to glucagon. B - cell functional reserve was defined as preserved (B+) if the peak C-peptide response to glucagon was at least 1.5 ng/dl (0.5 nmol/liter) or fasting C-peptide concentration was at least 1 ng/dl (0.33 nmol/liter). B - Cell functional reserve was defined as absent (B- ) if the glucagon-stimulated or fasting C-peptide concentrations did not meet these CRITERIA. JCEM 88:5090 2003-MALDONADO M et al. </li></ul>
8. <ul><li>The Journal of Clinical Endocrinology & Metabolism Vol. 88, No. 10 4768-4775Copyright ｩ 2003 by The Endocrine Society Unique Epitopes of Glutamic Acid Decarboxylase Autoantibodies in Slowly Progressive Type 1 DiabetesTetsuro Kobayashi, Shoichiro Tanaka, Minoru Okubo, Koji Nakanishi, Toshio Murase and 〔 e Lernmark </li></ul>
9. <ul><li>IT WAS NOTED THAT THE EPITOPE SPECIFICITY IS MORE SPECIFIC AS AN INDICATOR TO THE DEGREE OF UNDERLYING BETA-CELL DESTRUCTION AND ASSOCIATED CLINICAL EFFECTS THAN GAD 65AB TITRES ALONE. </li></ul><ul><li>Balasubramanyam A, Garza G, Rodriguez L, Hampe C, Gaur L, Lernmark A, Maldonado M 2006 Accuracy and predictive value of classification schemes for ketosis- prone diabetes . Diabetes Care 29:2575 ﾐ 2 579 </li></ul>
10. <ul><li>GAD65 Antibody Epitope Patterns of Type 1.5 Diabetic Patients Are Consistent With Slow-Onset Autoimmune Diabetes:DIABETES CARE 25 02 </li></ul>
11. <ul><li>GAD antibody negative NIDDM in adult black subjects with diabetic ketoacidosis and increased frequency of human leukocyte antigen DR3 and DR4. Flatbush diabetesMA Banerji, RL Chaiken, H Huey, T Tuomi, AJ Norin, IR Mackay, MJ Rowley, PZ Zimmet and HE Lebovitz </li></ul>
12. PAX4 gene variations predispose to ketosis-prone diabetes <ul><li>Ketosis-prone diabetes (KPD) is a rare form of type 2 diabetes, mostly observed in subjects of west African origin (west Africans and African-Americans), characterized by fulminant and phasic insulin dependence, but lacking markers of autoimmunity observed in type 1 diabetes. PAX4 is a transcription factor essential for the development of insulin-producing pancreatic B - cell. </li></ul><ul><li>H.mole.gene vol 13 ,24 .04 </li></ul>
13. <ul><li>expectations </li></ul>
17. CHANGE AND APPROACH TO THE CLINICAL SETTINGS? <ul><li>COUNSELING WITH PATIENT AND PARENTS ON DIAGNOSIS </li></ul><ul><li>DO WE REQUIRE DEFINITE SPECIALISED INVESTIGATIONS OR STREAMLINED? </li></ul><ul><li>WOULD IT OFFER LEAN THERAPEUTIC MODALITIES? </li></ul><ul><li>THANK YOU. </li></ul>