B cell destruction
Type 1 DM
Progressive insulin secretory defect
Type 2 DM
- Beta cells produce what 2 things?
- Alpha cell produce what 1 thing?
- Beta –> insulin & amylin
- Alpha –> glucagon
- Which age/race has highest incidence of T1DM?
- Bimodal: peaks at what 2 ages?
- Is it heritable?
- Non-hispanic WHITE children/adolescents
- 4-6 & 10-14
- Risk increases if relatives have T1DM
What are the 2 types of T1DM?
- Immune mediated (1A)
- Idiopathic (1B)
Which type of T1DM?
- Scandinavia / Northern Europe
- Minnesota
- Genes (HLA DR3-DQ2) & (HLA-DR4)
- Environmental causes
- B cell auto-immunity
Immune Mediated T1DM (1A)
Which type of T1DM?
- Minority of pts have this type
- Asian / African origins
- PAX-4: a transcription factor essential for development of pancreatic islets
Idiopathic T2DM (1B)
Studies of 1st degree relatives of pts w/ type 1 DM show that the persistent presence of two or more ____, is an almost CERTAIN predictor of clinical hyperglycemia & DM.
auto-antibodies
What are the 5 circulating antibodies present at time of dx for T1DM?
- Zinc transporter 8 (ZnT8)
- Islet cells (ICA)
- Glutamic acid decarboxylase 65 (GAD 65)
- Insulin (IAA)
- Tyrosine phosphatase IA2 (ICA-512)
(ZIGIT)
Presence of antibodies in T1DM facilitate the screening of which 2 patients?
◦Siblings of affected child
◦Adults with atypical features of T2DM
6 tests to dx T1DM
- C-peptide
- Glutamic Acid Decarboxylase Autoantibodies (GADA or Anti-GAD)
- Insulin Autoantibodies (IAA)
- Insulinoma-Associated-2 Autoantibodies (IA-2A)
- Islet Cell Cytoplasmic Autoantibodies (ICA)
- Zinc Transporter 8 (ZnT8 Ab)
Which test to dx T1DM?
◦Quantitative blood test for the connecting polypeptide that is cleaved prior to the formation of insulin
◦Levels generally match insulin levels in the body and can indicate how much insulin is being produced
◦Low levels of ______ and insulin usually point to T1DM
◦Level can be checked in the presence of exogenous insulin
C-peptide
- low levels of C-peptide
Which test to dx T1DM?
◦Test for antibodies against a specific enzyme in the pancreatic β cells
Glutamic Acid Decarboxylase Autoantibodies (GADA or Anti-GAD)
Which test to dx T1DM?
◦Test for antibodies targeting insulin
Insulin Autoantibodies (IAA)
Which test to dx T1DM?
◦Test for antibodies against a specific enzyme in β cells
Insulinoma-Associated-2 Autoantibodies (IA-2A)
Which test to dx T1DM?
◦______sense blood glucose levels and express insulin accordingly
◦Test for a reaction between _____ antibodies from humans and a variety of _____ proteins from an animal pancreas
◦Older test not used frequently
Islet Cell Cytoplasmic Autoantibodies (ICA)
- Islet cells (are all of the blanks)
Which test to dx T1DM?
◦Newer test for antibodies targeting an enzyme specific to β cells
Zinc Transporter 8 (ZnT8 Ab)
- A1C test measures average blood glucose of the past ___ months.
- Advantage is no need to fast/drink anything.
- Diagnosis is made of an A1C of ___ or greater.
- 2-3 months
- 6.5 or greater
Should an A1C or blood glucose be used to dx type 1 DM in SYMPTOMATIC individuals?
Blood glucose
Screening for Type 1 DM w/ an antibody panel is recommended in which 2 circumstances?
- Clinical research study
- 1st degree family member of a proband w/ type 1 DM
The American Diabetes Association recommends that children under the age of 19 diagnosed with type 1 diabetes strive to maintain an A1C level < ____.
7.5
What is the dx?
- Fasting Plasma Glucose (FPG): 100-125
- 2 hour plasma glucose: 140-199
- A1C: 5.7 - 6.4
Pre-diabetes
Type 1 DM
- Polyuria, polydipsia, weight loss
- Random plasma glucose of ____ or more
- Plasma glucose of ____ or more AFTER an overnight fast
- HbA1C of ___ or higher
- Random: 200 mg/dL
- Overnight fast: 126 mg/dL
- A1C: 6.5
Type 1 or 2 DM?
- Ketonemia
- Ketonuria
- Islet autoantibodies frequently present
Type 1
