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

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antibodies variability in type 1 diabetes clinical implications

ANTIBODIES VARIABILITY IN TYPE 1 DIABETES-Clinical implications?

Dr M A LAMKI

Senior Consult. Endocrinologist

Royal hosp.Oman

introduction
Introduction
  • Autoantibodies directed to the 65-kDa isoform of glutamate decarboxylase(GAD65), insulin, and a protein tyrosine phosphatase-like isletcell antigen (IA-2) predict the disease). Whereas insulinautoantibodies and IA-2Ab are negatively associated with ageat onset, autoantibodies directed against GAD65 (GAD65Ab) aredirectly associated with age at onset.
slide3

DIABETES KETOACID.

TYPE 1 ?

R/X

INSULIN!!

INVEST?

slide4

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

diabetes ketoacidosis
DIABETES KETOACIDOSIS
  • DKA is defined by the presence of all of the following: aniongap 15 or greater, blood pH less than 7.30, serum bicarbonate17 mmol/liter or less, serum glucose greater than 200 mg/dl(>11.1mmol),serum ketones 5.2 mmol/liter or greater, or urine ketones moderateto large.
  • J Clin Endocrinol Metab 88:5090ミ5098[2003]
ketosis prone diab mell
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S67-2005
slide7
B-Cell secretory capacity was measured at the timeof the initial presentation with DKA (within 1 wk after resolutionof ketoacidosis) and again after 12 months of follow-up by thefollowing tests: fasting serum C-peptide concentration and C-peptideresponse to glucagon. B-cell functional reserve was defined as preserved(B+) if the peak C-peptide response to glucagon was at least1.5 ng/dl (0.5 nmol/liter) or fasting C-peptide concentrationwas at least 1 ng/dl (0.33 nmol/liter). B-Cell functionalreserve was defined as absent (B-) if the glucagon-stimulatedor fasting C-peptide concentrations did not meet these CRITERIA. JCEM 88:5090 2003-MALDONADO M et al.
slide8
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
slide9
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-pronediabetes. Diabetes Care 29:2575ミ2579
slide10
GAD65 Antibody Epitope Patterns of Type 1.5 Diabetic Patients Are Consistent With Slow-Onset Autoimmune Diabetes:DIABETES CARE 25 02
slide11
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
pax4 gene variations predispose to ketosis prone diabetes
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 Africansand African-Americans), characterized by fulminant and phasicinsulin dependence, but lacking markers of autoimmunity observedin type 1 diabetes. PAX4 is a transcription factor essentialfor the development of insulin-producing pancreatic B-cell.
  • H.mole.gene vol 13 ,24 .04
change and approach to the clinical settings
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.