Type 1 Diabetes Mellitus Flashcards
What is type 1 diabetes?
Autoimmune disease where beta cells in pancreas are attacked and destroyed by immune system.
Partial or complete insulin deficiency causing hyperglycemia.
Requires life long insulin treatment.
What is the best treatment for type 1 Diabetes
Individualize to clinical status and preferences
What is autoimmune diabetes presenting later in life called
Latent autoimmune diabetes in adults (LADA)
Can T2DM present in childhood ?
Yes
Can ketoacidosis be a feature of T2DM
Yes
What can monogenic diabetes present as?
Type 1 or type 2 e.g MODY , mitcohondiral diabetes
Can diabetes present following pancreatic damage or other endocrine disease.
Yes
What is a challenge for clinicians with diabetes in adults
differentiating between adult onset Type 1 and much larger cases of diabetes type 2
Stages of Development of Type 1 Diabetes
Genetic predisposition -> potential precipitating event -> overt immunological abnormalities, normal insulin release –> progressive loss of insulin -> overt diabetes c peptide still present -> no c-peptide present
Why is C-peptide used as a marker for insulin
Has a longer half-life as insulin goes though hepatic first pass metabolism.
If on insulin treatment don’t know if insulin is from pancreas or injection
stages of T1DM autoimmune
after immune activation beta cells attacked.
Development of single autoantibody.
Normal blood sugar –> abnormal blood sugar ( >/ 2 autoantibodies–> clinical diagnosis –> Long standing T1DM
Why is immune basis important
Increased prevalence of other autoimmune disease
Risk of autoimmunity in relatives
More complete destruction of B-cells
Auto antibodies can be useful clinically
Immune modulation offers the possibility of novel treatments
Not there yet
Overview of immunology
Primary step is the presentation of auto-antigen to autoreactive CD4+ T lymphocytes
CD4+ cells activate CD8+ T lymphocytes
CD8+ cells travel to islets and lyse beta-cells expressing auto-antigen
Exacerbated by release of pro-inflammatory cytokines
Underpinned also, by defects in regulatory T-cells that fail to supress autoimmunity
Why is it good that sometimes not all beta cells are destroyed
If heading towards hypo then pancreas can buffer insulin production.
Less likely to have vascular problems in future
Which HLA-Dr allele have the highest risk
DR3 and DR4
What factors may be implicated (no causality established)
Enteroviral infections
Cow’s milk protein exposure
Seasonal variation
Changes in microbiota
What are pancreatic auto-antibodies
Detectable in the sera of people with Type 1 diabetes at diagnosis.
Not generally needed for diagnosis in most cases
Insulin antibodies (IAA)
Glutamic acid decarboxylase (GADA) – widespread neurotransmitter
Insulinoma-associated-2 autoantibodies (IA-2A)-Zinc-transporter 8 (ZnT8)
Presentation of type 1 diabetes
SYMPTOMS
Excessive urination (polyuria)
Nocturia
Excessive thirst (polydipsia)
Blurring of vision
Recurrent infections eg thrush
Weight loss
Fatigue
SIGNS
dehydration
cachexia
hyperventilation
smell of ketones
glycosuria
ketonuria
Effects of insulin deficiency
Proteinolysis
increased HGO
increased lipolysis –> glycerol and NEFA
how are Ketone bodies made
Acetyl coA –> acetoacetate –> acetone + 3OH B – > ketone bodies
What causes smelly breath
acetone
treatment of type 1
People with type 1 diabetes, require insulin FOR LIFE
Aims:
Maintain glucose levels without excessive hypoglycaemia
Restore a close to physiological insulin profile
Prevent acute metabolic decompensation
Prevent microvascular and macrovascular complications
Management of type 1 diabetes
Insulin Treatment
Dietary support / structured educations
Technology
Transplantation
Type 1 diabetes is a condition that is ‘self-managed’
complication of hypergycaemia
Acute
Diabetic ketoacidosis
Chronic
Microvascular
Retinopathy
Neuropathy
Nephropathy
Macrovascular
Ischaemic heart disease
Cerebrovascular disease
Peripheral vascular disease
short acting insulin
With meals (short / quick-acting insulin)
Human insulin – exact molecular replicate of human insulin (actrapid)
Insulin analogue (Lispro, Aspart, Glulisine)
Background insulin
Background (long-acting / basal)
Bound to zinc or protamine (Neutral Protamine Hagedorn, NPH)
Insulin analogue (Glargine, Determir, Degludec)
