Diabetes Immune Mechanism Flashcards
Obesity
Effects Leading to Diabetes
Increased LCFFAs and MCFFAs
Cause increased M1 Macrophages
Release TNFalpha, IL-1, IL-6, IFN-gamma and increase NO
Cause increased Th1, CTLs and Neutrophils
Lean Body Diabetes Protective Factors
Increased SCFFAs, M2 Macrophages, IL10, Th2, Treg and Eosinophils
Type 2 Diabetes Risk Factors
Genetics: 52 high risk alleles, 40% risk if one parent, 70% risk if both parents have them
Environmental: Pesticides, Herbicides and Diesel Car Pollution
Behavioral: Sedentary lifestyle and high fat diet
Type 1 Diabetes Risk Factors
Environmental, Microbiota and Behavioral
Enteroviruses, Mumps, Rubella
Low butyrate-producing microbiota
Early cereal, root vegetable, egg and cow’s milk diet
Type 1 diabetes Protective Factors
Breast milk feeding increases insulin immune tolerance
Omega 3 FAs protective
Class 3 VNTR increases insulin
Type 1 Diabetes Genetic Risk Factors
HLA - DQ2/DQ8 seen in most T1D Pts
HLA - DR3/DR4 increases risk in children
CTLA4 Defect - decreased auto T cell suppression
AIRE Defect - decreases central tolerance (-) selection
Class 1 VNTR - decreases insulin mRNA and central tolerance
Islet Cell Auto Antibodies
Types and Use
GAD65, IA-2, IAA
Used for early Type 1 Diabetes diagnosis
Type 1 Diabetes Microflora Issues
Decreased Bacteriodetes and Firmicutes
Decreases Treg cells and causes defective FOXP3
Type 1 Diabetes Immunopathogenesis
IFN-gamma decreases Th2 and causes Beta cell Ag presentation
Dysregulated T cells activated and produce IFN-gamma, IL-1, TNF-alpha
M1 Macrophages increased