Type 1 diabetes mellitus Flashcards
What is type 1 diabetes?
An autoimmune condition in which insulin-producing beta-cells in the pancreas are attacked and destroyed by the immune system
The result is a partial or complete deficiency of insulin production, which results in hyperglycaemia
The resultant hyperglycaemia requires life-long insulin treatment
Why is the dichotomy of diabetes untrue?
There is significant overlap in the ways of presentation e.g Monogenic diabetes can present phenotypically as Type 1 or Type 2 diabetes (eg. MODY, mitochondrial diabetes)
When does type 1 diabetes present?
Traditionally thought to be childhood/ early adu;thoos but it can present at any age.
How does Type 1 diabetes develop?
Genetic predisposition
Immune Activation - Potential precipitating event ( e.g viral infection)
Immune Response - Development of single autoantibody
beta-cell mass degradation
progressive loss of insulin release
Overt diabetes; C-peptide present
No C-Peptide present
Why is the 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
Describe the immunology in Type 1 diabetes?
Defect in both innate and active immune system.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
Can people with type 1 Diabetes produce insulin?
Some have been found to be able to produce a small amount, but not enough to substitute the need for insulin therapy.
What mediates genetic susceptibility for type 1 diabetes?
HLA-DR Allele
What are possible environmental factors for Type 1 diabetes precipitation?
Enteroviral infections
Cow’s milk protein exposure
Seasonal variation
Changes in microbiota
What Pancreatic autoantibodies can you measure to confirm type 1 diabetes?
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)
What are the symptoms of type 1 diabetes?
polyuria nocturia polydipsia Blurring of vision Recurrent infections Weight loss Fatigue
What are the signs of type 1 diabetes?
dehydration cachexia hyperventilation smell of ketones glycosuria ketonuria
What affects the diagnosis of type 1 diabetes?
Diagnosis is based on clinical features and presence of ketones.
What happens when you don’t have enough insulin?
Breakdown of muscle protein
Increase glucose output from the liver
Break down fat cells (lipolysis)
What ketone bodies can lead to diabetic ketoacidosis?
Acetyl CoA
Acetoacetate
Acetone + 3OH-B
What are the main aims of treatment in type 1 diabetes
Maintain glucose levels without excessive hypoglycaemia
Restore a close to physiological insulin profile
Prevent acute metabolic decompensation
Prevent microvascular and macrovascular complications
Why do you lose weight in type 1 diabetes?
Osmotic diuresis
become dehydrated
anything you eat cant be used due to lack of insulin
Is type 1 diabetes monogenic or polygenic?
Polygenic - susceptibility spread amongst many genes
Why do you get blurred vision in type 1 diabetes?
High glucose in the eyeball, water moves in to dilute increased solute concentration.
What are the acute complications of type 1 diabetes?
Diabetes ketoacidosis
Uncontrolled Hyperglycaemia
Hypoglycaemia
What are the chronic microvascular complications of type 1 diabetes?
Retinopathy
Neuropathy
Nephropathy
What are the chronic macrovascular complications of type 1 diabetes?
Ischaemic heart disease
Cerebrovascular disease
Peripheral vascular disease
What are the 4 tenets of type 1 diabetes treatment?
Insulin Treatment
Dietary support / structured educations
Technology
Transplantation
What are the 3 features of insulins physiological profile?
Basal insulin has a flat profile
Insulin is never completely supressed
Prandial peak has two phases
What are the short acting types of insulin?
Human insulin – exact molecular replicate of human insulin (actrapid) Insulin analogue (Lispro, Aspart, Glulisine)
What are the long-acting types of insulin?
Bound to zinc or protamine (Neutral Protamine Hagedorn, NPH) Insulin analogue (Glargine, Determir, Degludec)
Describe Insulin pump therapy?
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
What are the dietary principles for patients with type 1 diabetes?
Where possible, substitute refined carbohydrate containing foods (sugary / high glycemic index) with complex carbohydrates (starchy / low glycemic index)
What is the artificial pancreas?
Real time glucose sensor, with an algorithm to use glucose value to calculate insulin requirement.
What are the two types of transplantation?
Islet cell transplants
Isolate human islets from pancreas of deceased donor
Transplant into hepatic portal vein
Requires life-long immunosuppression
Simultaneous pancreas and kidney transplantBetter
survival of pancreas graft when transplanted with kidneys
Requires life-long immunosuppression
How do we monitor glucose levels?
HbA1c
Why do we measure Hb1Ac?
Reflect last 3 months (red blood cell lifespan) of glycaemia
Biased to the 30 days preceding measurement
Glycated NOT glycosylated (enzymatic)
Therefore linear relationship
Irreversible reaction
Glycated haemoglobin
What guides insulin doses?
Using self-monitoring of blood glucose results at home and HbA1c results every 3-4 months
Based on results, increase or decrease insulin doses
What is the diagnosis for diabetic ketoacidosis?
pH <7.3, ketones increased (urine or capillary blood), HCO3- <15 mmol/L and glucose >11 mmol/L
What is the threshold hold for hypoglycaemia?
<3.6 mmol/L
When does hypoglycaemia become a problem?
Excessive frequency
Impaired awareness (unable to detect low blood glucose)
Nocturnal hypoglycaemia
Recurrent severe hypoglycaemia
What are the risks of hypoglycaemia?
Seizure / coma/ death (dead in bed) Impacts on emotional well-being Impacts on driving Impacts on day to day function Impacts on cognition
What are risk factors for hypoglycaemia?
Exercise Missed meals Inappropriate insulin regime Alcohol intake Lower HbA1c Lack of training around dose-adjustment for meals
What is the acute management for hypoglycaemia?
Alert - Oral Carbs
Drowsy - Buccal glucose
Unconscious - IV glucose
What is the treatment for Diabetic ketoacidosis?
Antiemetic
IV fluids for dehydration through a drip
Insulin to supress ketogenesis
