15. Type I diabetes mellitus Flashcards
what are the 2 classifications of diabetes and who is affected?
- type 1 diabetes - lean, young individuals
- type 2 diabetes - older, obese individuals
what is LADA?
latent autoimmune diabetes in adults which requires insulin as treatment
what is a feature of T2DM?
diabetic ketoacidosis
what can present phenotypically as type 1/2 diabetes?
monogenic diabetes e.g. MODY, mitochondrial diabetes
how does type 1 diabetes arise?
an environmental trigger and genetic influences lead to the autoimmune destruction of islet cells leading to insulin deficiency which results in hyperglycaemia
how does type 2 diabetes arise?
a stronger genetic influence associated with diabetes leads to insulin resistance which causes B-cell failure, resulting in hyperglycaemia
what is the pathogenesis (development) of type 1 diabetes?
- pre-diabetes followed by overt diabetes as the b-cells start to malfunction
- steady progression of b-cell failure
- patients are admitted as sick from diabetic ketoacidosis
- T1DM is a relapsing remitting disease
which type of diabetes has greater genetic susceptibility?
T2DM
abnormalities in which haplotypes can result in an increased risk of developing T1DM?
DR3 and DR4 of the HLA-DR allele
what suggests there is an environmental influence on T1DM?
- there is a higher prevalence of T1DM in winter
- certain places in the world have a higher prevalence of T1DM
what can be done when a clinician is unsure of whether a patient has T1DM or T2DM?
antibody tests
- measure islet cell antibodies (ICA)
- measure insulin antibodies (IAA)
- measure glutamic acid decarboxylase antibodies (GADA)
- measure insulinoma-associated-2 autoantibodies (IA-2A)
what are the symptoms of diabetes?
- polyuria
- nocturia
- polydipsia
- blurred vision
- thrush
- weight loss
- fatigue
what are the signs of diabetes?
- dehydration
- cachexia
- hyperventilation
- smell of ketones
- glycosuria
- ketonuria
what is the role of insulin?
- reduce hepatic glucose output
- drive uptake of glucose by muscle
- prevent protein destruction in muscle
- prevent fatty acids/glycerol from leaving adipose
what happens in insulin deficiency?
- glucose in the liver is released into the circulation
- glucose in the circulation is not taken up by muscle
- proteins are broken down into amino acids and released from muscle
- amino acids are taken up by the liver and result in glucose production
- fatty acids in adipose tissue are broken down so triglycerides start to release lots of fatty acids
- fatty acids released are taken up by the liver and ketone bodies are produced
LEADS TO HYPERGLYCAEMIA
what are the aims of treatment in T1DM?
- reduce early mortality
- avoid acute metabolic decompensation
- prevent long-term complications (retinopathy, nephropathy, neuropathy, vascular disease)
what is the diet of individuals with T1DM?
- reduce calories as fat
- reduce calories as refined carbohydrates
- increase calories as complex carbohydrates
- increase soluble fibre
- balanced distribution of food over the course of the day with regular meals and snacks
what short-acting insulin treatment is administered?
human insulin, insulin analogues (lispro, aspart, glulisine) taken with meals
what long-acting insulin treatment is administered?
protamine zinc insulin (obtained from cow pancreas), insulin analogues (glargine, determir, degludec)
what is a basal bolus regimen?
taking short acting insulin at meal times, taking long acting insulin to cover the day
what is an insulin pump?
a device that administers continuous insulin
the pump has pre-programmed basal rates and bolus for meals
the pump does not measure glucose
what do islet cell transplants involve?
a transplant team taking some b-cells from a donor pancreas (after death of donor), isolating the cells and injecting them into the liver
through hepatic veins the b-cells migrate around the body and produce insulin
patients need to be on immunosuppressive agents after
(rare)
how can the success of treatment be determined?
- patients can measure capillary glucose levels (though this varies depending on tissue perfusion)
- doctors can monitor glucose levels by taking a blood sample
- use a glucose monitor
how can blood glucose be measured over time?
- continuous glucose monitor
- HBA1C: a blood sample that relies on red cells attaching to the glucose monitor. red cells have a lifespan of approx. 120 days so the test gives an idea of glucose levels over 3 months
in which cases will HBA1C not be as accurate?
- patients with a haemoglobinopathy (SCA, thalassaemia)
- patients with renal failure or blood loss
what is an acute complication of T1DM and how does it occur?
ketoacidosis
- patients are hyperglycaemic: reduced tissue glucose utilisation, increased HGP
- patient therefore has a metabolic acidosis: circulating ketone bodies, osmotic dehydration and poor tissue perfusion
what is hypoglycaemia defined as?
plasma glucose <3.6mmol/l
what are the effects of hypoglycaemia?
- blood glucose <3mmol/l: most mental processes impaired
- blood glucose <2mmol/l: conciousness impaired
- severe hypoglycaemia may contribute to arrhythmia and sudden death
- long-term effects include cognitive problems
who is at risk of hypoglycaemia?
patients with low HBA1C
when do hypoglycaemic episodes happen?
can occur at any time but pre-lunch episodes and nocturnal episodes are common
why does hypoglycaemia occur?
- going to the gym while not changing insulin dose
- missing meals or having inadequate snacks
- drinking lots of alcohol
- inappropriate insuline regime
what are the hypoglycaemic symptoms and signs due to increased autonomic activation?
- palpitations
- tremor
- sweating
- pallor/cold extremities
- anxiety
what are the hypoglycaemic symptoms and signs due to impaired CNS function?
- drowsiness
- confusion
- altered behaviour
- focal neurology
- coma
how is hypoglycaemia treated orally?
- if the patient is conscious feed the patient
- give quick acting glucogels (rapidly absorbed as a solution or as tablets)
- complex carbohydrates to maintain blood glucose after initial treatment
how is hypoglycaemia treated parenterally?
- done if the patient has impaired consciousness
- intravenous dextrose (10%) glucose infusion
- 1mg glucagon (intramuscular)
- avoid concentration solutions as these can cause severe skin reactions
