Type 1 Diabetes Flashcards
What is type 1 diabetes
Autoimmune disease
Beta cells affected in pancreas causing partial/complete deficiency in insulin thus hyperglycemia
Difference in type 2
Acquired insulin resistance
What is MODY
mature onset diabetes of the young
Usually monogenic diabetes
What is LADA
latent autoimmune diabetes in adults
When does type 1 DM develop
Usually in youth
Cleavage product with insulin
Proinsulin cleaved into c peptide and insulin
- steps of type I DM development?
genetic predisposition → environmental trigger → immune abnormalities but normal insulin → progressive loss of insulin release → overt diabetes with c-peptide → no c-peptide
- stage I: normal blood sugar, more than one autoantibodystage II: abnormal blood sugarstage III: clinical diagnosisstage IV: long standing type 1 diabetes
Stages of type 1 dm
stage I: normal blood sugar, more than one autoantibody
stage II: abnormal blood sugar
stage III: clinical diagnosis
stage IV: long standing type 1 diabetes
Where are beta cells located
Pancreatic islets of langerhanss, cytological changes after immune infiltration
- clinical relevance of immune basis of disease?
other autoimmune conditions more common in self + relatives
more complete destruction of beta cells
possible immune modulation treatment in the future
Risk of autoimmunity in relatives
Primary step in immune deficiency
autoantigen presented to autoreactive CD4+ T-lymphocytes
- CD4+ → activate CD8+ → lyse beta cells expressing auto-antigen
Exacerbated by pro inflammatory cytokines
Underpinned also by defects in T regulatory cells
What happens after the autoantigen is presented to auto reactive CD4+ T lymphocytes
CD4+ → activate CD8+ → lyse beta cells expressing auto-antigen
what aids this process?
Pro inflammatory cytokines expression and defects in T reg cells
Some beta cells can be ,left thus some insufficient insulin made
What is the HLA-DR gene responsible for
MHC II
Significance of different alleles
associated with different risk levels for diabetes, some dependent also on ethnicity
possible environmental factors?
enteroviral infection, cow’s milk protein exposure, seasonal variation, microbiota changes
what is the significance of pancreatic autoantibodies?
detectable in sera of those with type I at diagnosis. recommended as diagnostic tool
Different types of autoantibodies include
insulin antibodies IAA
GAD-65 glutamic acid decarboxylase
IA-2 insulinoma associated 2 antibodies ZnT8 zinc transporter 8
what is the diagnosis of diabetes based on?
presence of clinical features + ketones
various effects of insulin deficiency?
protein lysis in muscles → amino acid metabolism
increased hepatic glucose output
lipolysis in adipocytes → glycerol + non-esterified fatty acids
- how and where are ketone bodies usually formed?
from fatty acyl-CoAs in liver e.g. → acetyl-CoA, acetoacetyl-CoA
hormonal regulation how?
upregulated by glucagon and suppressed by insulin usually
Principal aims of diabetes treatments
maintain glucose levels, avoid excessive hypoglycaemia
restore physiological insulin profile or close
avoid micro and macrovascular complications
prevent acute metabolic decompensation
acute complications of diabetes?
diabetic ketoacidosis
hypoglycaemia from treatment
chronic complications?
microvascular → retinopathy, nephropathy, neuropathy
macrovascular → ischaemic heart disease, cerebrovascular disease, peripheral vascular disease
physiological insulin profile characteristics?
prandial peak (i.e. after meals) with two phases (peak and mini peak)
baseline insulin steady but not zero. This prevents ketoacidosis
different types of insulin?
human insulin (actrapid), insulin analogues e.g. Lispro, Aspart, Glulisine → short acting, take with meals
zinc or protamine bound e.g. NPH, insulin analogues e.g. Glargine, Determir, Degludec → long acting, background/basal
- short-acting = 3x a day after mealslong acting - 1x a day
When to take different types of insulin
short-acting = 3x a day after meals
long acting - 1x a day
Or twice daily intermediate acting insulin
What do insulin pumps do
continuous delivery of short acting insulin into subcutaneous space
principles of dietary education in diabetes?
carb counting, adjusting dosage based on food carbohydrate content, try sub refined carb foods with complex carb foods
- insulin pump that can detect glucose intake → calculate and adjust insulin dose
what are closed loop systems?
insulin pump that can detect glucose intake → calculate and adjust insulin dose
- how does transplantation work as a treatment option?
islet cell transplants → islets isolated from deceased donor → transplant into hepatic portal vein
simultaneous pancreas and kidney transplants
However require lifelong immunosuppresion
How are glucose levels monitored
capillary blood glucose
continuous glucose monitoring via pump
HbA1c
What is HbA1C
glycated haemoglobin → reflects last 3 months of glycaemia
what factors can throw off HbA1c accuracy?
altered erythropoiesis e.g. increased in iron/B12 deficiency. Decrease in high epo,iron,b12,reticulocytosis
haemoglobinopathies/altered haemoglobin may increase/decrease
variable glycation e.g. increased in excess alcohol,chronic renal failure and decreased Intra erythrocyte pH variable in genetic factors, and low in aspirin, vit C/E,certain haemoglobinopathies
erythrocyte destruction increased HbA1c in splenectomy and increased erythrocyte life span, decreased in haemoglobinopathies,splenimegaly,drugs such as antiretroviral ribavirin and dapsone
how is diabetic ketoacidosis diagnosed?
blood pH < 7.3, ketones (urinary or capillary) increased, HCO3- < 15 mmol/L, glucose > 11 mmol/L
numerical definition of hypoglycaemia?
glucose less than 3.6 mmol/L
what defines severe hypoglycaemia?
situation requires 3rd party assistance
When can severe hypoglycemia become a problem
excessive frequency (can get worse), impaired awareness, nocturnal/recurrent severe hypoglycaemia
Leads to seizures/coma/death
Impacts cognition,driving,day to day function and emotional wellbeing
Who is at risk of hypoglycemia
everyone with type I DM, especially if:
meals missed, exercise too much, alcohol, inappropriate insulin regime/dose adjustment
- how is hypoglycaemia acutely managed?
- if concerned about swallow?IV access → 20% glucose
If unable to give via iv then subcutaneous injection of glucagon - if swallow intact?oral carbs → buccal glucoserapid acting e.g. hypostop, glucogellonger acting → complex carbs
If aware and swallow intact
Rapid acting give sweets or juice
Long acting give sandwiches
