T1DM Flashcards
What is T1DM?
Autoimmune condition that destroys pancreatic beta cells, leading to a reduced or no production of insulin
What is the key difference between T1DM and T2DM?
T1DM is autoimmune destruction of islets leading to total insulin insufficiency,
T2DM is insulin resistance leading to relative insulin deficiency (however some overlap)
What is it called when T1DM presents later in life?
LADA - latent autoimmune diabetes in adults
What is an example of monogenic diabetes?
MODY - maturity onset of diabetes of the young
What are the stages of T1DM development?
Genetic predisposition,
environment trigger leading to immune abnormalities (production of autoantibodies),
decreased insulin release,
decreased C-peptide
Why is insulin not used as a marker for assessing T1DM?
Shorter half life than C-peptide (hepatic metabolism) // insulin medication will affect readings
How will you be able to observe immune infiltration of the islets on a microscope?
Macrophages surrounding islets, low density of cells within islets (destruction)
What immune cells are involved in T1DM immune destruction?
CD4 T cells and CD8 T cells
Do patients with T1DM lose all beta cells?
No - some continue to make small amounts of insulin just insufficient levels
Which alleles are responsible for genetic susceptibility to T1DM?
HLA-DR allele: DR3 and DR4 (human leukocyte allele)
What are 4 environmental triggers that can cause T1DM?
Enteroviral infections,
gut microbiota,
seasonal variation,
cow milk protein
What are 4 autoantibodies in the pancreas and how are they detected?
Sera is used for detection -
Insulin Autoantibodies (IAA) ,
Glutamic acid decarboxylase (GAD-65) , (widespread NT)
insulinoma - associated 2 autoantibodies (IA-2A) ,
Zinc-transporter 8 (ZnT8)
Measure antibodies at diagnosis as that is when they are most likely to be positive.
What are 7 symptoms of T1DM?
Polyuria, Nocturia, Polydipsia, Blurred Vision, Recurrent Infections, Weight Loss, Fatigue
Why would you get blurring of vision in T1DM?
Glucose in the aqueous humour, water pulled in, the eye swells distorting light, blurry
What are 6 signs of T1DM?
Dehydration,
Cachexia (muscle wasting),
Hyperventilation,
Ketone Smell,
Glycosuria,
Ketonuria
Why do you get cachexia in T1DM?
Lower insulin stimulates proteinolysis (for amino acids and energy), so muscle wasting occurs
What is the effect of T1DM on lipolysis?
Lipolysis is inhibited by insulin, as insulin is low, lipolysis will increase
What is lipolysis and what is the consequential effect of it?
Non-esterified fatty acids go through beta-oxidation pathway leading to the production of ketone bodies (higher ketone levels in blood)
What is the impact of insulin deficiency in the liver?
Increased hepatic glucose output (gluconeogenesis) - because low insulin usually means more glucose needed
What are the 4 therapeutic objectives of T1DM?
Maintain glucose levels without excessive hypoglycaemia, restore physiological insulin profile,
prevent acute metabolic decompensation,
prevent microvascular and macrovascular complications
What is the best treatment method for T1DM? (with examples)
Individualised plans (insulin injections, insulin pump, islet cell transplantation)
What are three acute complications of T1DM?
Diabetic Ketoacidosis, Uncontrolled Hyperglycaemia, Hypoglycaemia
What are the two groups of chronic complications of T1DM?
Microvascular and Macrovascular
Microvascular complications examples
Retinopathy
Neuropathy
Nephropathy
Macrovascular complications examples
Ischaemic heart disease
stroke - cerebrovascular disease
peripheral vascular disease
What is the limitation of all T1DM managements?
Self-managed condition, regardless of treatment type it will require 24 hour awareness from patient
Describe a physiological insulin profile
Basal insulin is flat but never 0, after food there will be a prandial peak (two phases of insulin release)
If insulin reaches 0 this will lead to DKA
When is short-acting insulin given and name two examples?
With meals, prandial peak
Human insulin (exact molecular replicate - actrapid) ,
Insulin analogue (recombinant - Lispro)
When is long-acting insulin given and name two examples
For background basal levels
Bound to zinc or protamine (NPH) ,
Insulin Analogue (glargine)
What is insulin pump therapy?
Continuous delivery of short acting insulin analogue via a pump into subcutaneous space. Can programme levels to give extra for bolus (meals)
can vary the basal rate
What is a closed loop and how does it work?
Artificial Pancreas - real-time glucose sensor placed in interstitial fluid of subcutaneous fat. Algorithm detects change in glucose and calculates insulin dose required, and administers without human assistance
reduces risk of hypoglycaemia
What are the two types of transplantation used in T1DM?
Islet cell transplants
Pancreas & Kidney Transplant
How does islet cell transplantation work?
Isolate human islet cells from donor and transplant to hepatic portal vein.
Requires lifelong immunosuppression
How does pancreas and kidney transplantation work and why do you need to remove the kidneys?
Remove both pancreas and kidney to lower the chnace of rejection
life-long immunosuppression
What blood tests helps us monitor diabetes?
Glycated Haemoglobin (HbA1c)
Why is this test used?
Reflects the last 3 months of glycaemia. This is glycated not glycosylated (which requires enzymes), and hence a linear relationship. It is also irreversible
When can HbA1c not be used?
Affected erythropoiesis (iron deficiency or excess)
Altered Haemoglobin (genetic)
Glycation from other causes (alcoholism, chronic renal failure)
Erythrocyte destruction (splenomegaly or opposite splenectomy)
Not useful in identifying hypos
Why is the HbA1c test not perfect?
The variation in mean glucose and mean HbA can vary greatly between patients
How can we monitor glucose levels?
Capillary finger prick test // Continuous glucose monitoring machine
What is the presentation of DKA?
Blurred vision, vomiting/nausea, weight loss, recurrent UTI (T1DM specifically)
Why is recurrent UTI associated with DKA?
High glucose concentration in renal areas breeds a better survival environment for bacteria
DKA diagnosis
pH <7.3
Increased ketones
HCO3 <15
glucose > 11
How can hypoglycaemia occur in T1DM and what is the consequence of this?
Tightly controlled glucose intake
Recurrent - adrenergic receptors build up insensitivity to hypoglycaemia
May need to contact the DVLA as it can impact driving
Hypoglycaemia triad
Low glucose - <3.5
Relief of symptoms with glucose administration
Symptoms
Hypoglycaemia symptoms
Adrenergic - tremors, palpitations, sweating, hunger
Neuroglycopenic - confusion, seizures, coma, incoordination, somnolence
Problematic hypoglycaemia
Excessive frq
Impaired awareness (unable to detect low glucose)
Nocturnal hypo
Recurrrent severe hypo
What are 5 impacts of hypoglycaemia?
Seizure/Coma/Death in Bed
Emotional effects
Driving impacted
Day to Day affected
cognition effects
What are the risk factors for hypoglycaemia in T1DM?
Exercise, missed meals, inappropriate insulin dose, alcohol
How do you manage hypoglycaemia in alert & orientated patients?
Oral carbohydrates or sweets/juice
How do you manage hypoglycaemia in drowsy but swallowing patients?
Buccal glucose or glucogel
How do you manage hypoglycaemia in unconscious and non-swallowing patients?
Intravenous 20% glucose & saline
How do you manage hypoglycaemia in deteriorating patients without IV access?
Intramuscular glucagon
