1. ANTIBODIES VARIABILITY IN TYPE 1 DIABETES-Clinical implications?
Dr M A LAMKI
Senior Consult. Endocrinologist
Royal hosp.Oman

2. Introduction
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.

3. DIABETES KETOACID.
TYPE 1 ?
R/X
INSULIN!!
INVEST?

4. TYPE 1
TYPE 2 DM
DKA
Based on the presence
Or absence of antibodies plus the via. Beta cells!
KETOSIS -PRONE DIABETES
MELLITUS
FOUR SUB-GROUPS

5. DIABETES KETOACIDOSIS
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 ketones 5.2 mmol/liter or greater, or urine ketones moderate to large.
J Clin Endocrinol Metab 88:5090ﾐ5098[2003]

6. Ketosis -prone DIAB-MELL
4-TYPES:
A+ OR A-
B+ OR B-
A+ B- ---> CLASSICAL T1DM
A+ B+ ---->OLDER,OVERWEIGHT,insulin depend/or independency- LADA,SPDM,
TYPE 1.5 DIABETES
Diabetes 54(Suppl 2):S62ﾐS

7. 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: MALDONADO M et al.

8. The Journal of Clinical Endocrinology & Metabolism Vol. 88, No
The Journal of Clinical Endocrinology & Metabolism Vol. 88, No Copyright 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

9. 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.
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2579

10. GAD65 Antibody Epitope Patterns of Type 1
GAD65 Antibody Epitope Patterns of Type 1.5 Diabetic Patients Are Consistent With Slow-Onset Autoimmune Diabetes:DIABETES CARE 25 02

11. 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

12. PAX4 gene variations predispose to ketosis-prone diabetes
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.
H.mole.gene vol 13 ,24 .04

13. expectations

17. CHANGE AND APPROACH TO THE CLINICAL SETTINGS?
COUNSELING WITH PATIENT AND PARENTS ON DIAGNOSIS
DO WE REQUIRE DEFINITE SPECIALISED INVESTIGATIONS OR STREAMLINED?
WOULD IT OFFER LEAN THERAPEUTIC MODALITIES?
THANK YOU.