diabetes type 1 Flashcards
what is LADA and what it stand for
Autoimmune diabetes leading to insulin deficiency can present later in life
latent autoimmune diabetes in adults
6 stages of T1Diabetes development
- genetic predisposition
2.triggering event
- immunological activation +development of single autoantibody
-normal insulin release - progressive loss of insulin release-glucose normal
- overt diabetes-c-peptide present
- no c-peptide present (0 b-cell mass)
4 stages of type 1 diabetes
all 2+ autoantibodies
stage 1=normal blood sugar
stage 2=abnormal blood sugar
stage 3=clinical diagnosis
stage 4=long standing T1D
Defect in innate and adaptive immune system
what happens:T1D
- auto-antigen present to autoreactive CD4+ T(helper) lymphocytes
2.CD4+ cells activate CD8+ T lymphocytes
3.CD8+ (cytotoxic) cells travel to islets and lyse beta-cells expressing auto-antigen
4.Exacerbated by release of pro-inflammatory cytokines
5.regulatory T-cells defect= fail to supress autoimmunity
genetic susceptibility
HLA-DR allele
risk level-protective
DR2
DR6-protective/neutral
DR7- but risk to africans
genetic susceptibility
HLA-DR allele
risk level-sig. risk.
DR3
DR4
DR8=neutral/risk
DR9-RISK in chinese, japanese, korean
potential environmental factors- not causation though
Enteroviral infections
Cow’s milk protein exposure
Seasonal change
Changes in microbiota
pancreatic auto-antibodies detectable in the sera of Type 1 diabetics. To make the diagnosis->
Insulin auto antibodies (IAA)
Glutamic acid decarboxylase (GAD-65) – widespread neurotransmitter
Insulinoma-associated-2 autoantibodies (IA-2)
Zinc-transporter 8 (ZnT8)
effects of insulin deficiency - T1D and how ketones are formed
proteinolysis
HGO
Lipolysis (gly+NEFA)
formation of ketone bodies
insulin inhibits fatty acyl-CoA
->ketone bodies
hyperglycaemia complication - acute
DKA
types of insulin treatment
with meals (TDS)
-human insulin-actrapid
-insulin analogue-lispro
background (once daily)
-bound to zinc
-insulin analogue-glargine
intermediate acting insulin=twice daily
Physiological insulin profile
basal insulin =flat profile
prandial peak = 2 phases
insulin never completely suppressed
what is insulin pump therapy and how it works
Continuous delivery of short-acting insulin analogue (e.g. novorapid) via pump
Delivery of insulin into subcutaneous space
Programme the device to deliver fixed units / hour throughout the day (basal)
Actively bolus for meals-Dose adjustment for carbohydrate content
dietary advice
Training for carbohydrate counting
Substitute refined carbohydrate(sugary) with complex carbohydrates (starchy /low glycaemic index)
transplantation- what it available, complications, how
- islet cell transplant- transplant into hepatic portal vein
- simultaneous pancreas and kidney transplant-better survival of pancreas graft
both need life-long immunosuppresssion
