Diabetes Flashcards
What type of insulin does an insulin pump have?
Short acting insulin
What regime are insulin injections given in and why?
Basal bolus regime to try and mimic the body’s normal response
How long have islet transplantations been done for?
~20 years
Limitations of islet transplantations
Requires cadaveric islets
Patients need to go on immunosuppressants
Reserved for those with severe hypoglycaemia
Risk factors for diabetes
HLA type
Family history
Levels of anti-islet antibodies in the blood
What is a closed-loop system in treatment of diabetes and what does it involve?
It is basically an artificial pancreas
It uses real time glucose data to affect the insulin administration from the insulin pump, but is not licensed at the moment
Why does T1D develop?
Immune based disease on a background of susceptibility factors
Can T1D be predicted?
Partially
Can sometimes predict whether or not someone will develop diabetes but can’t predict when
Epidemiology of T1D
Highest incidence in individuals of European descent and rates increasing in Europe
Peaks at age 5-7 and again at puberty
Highest incidence in Scandinavian and Northern European cohorts
Genetic risk factors for T1D
Polygenic
HLA genes on chromosome 6 lead to 50% increased risk (HLA class II)
>40 genes identified
Environmental risk factors for T1D
Viral infection
North/South hypothesis - vitamin A/vitamin D exposure
What is currently the only available marker of islet autoimmunity in T1D?
Islet autoantibodies
What percentage of individuals with T1D will have islet autoantibodies?
93%
What is Type 1 diabetes?
An autoimmune disorder of beta cell destruction which results in a state of absolute insulin deficiency
Commonest autoantibody in T1D
Anti-GAD
Diagnosis of T1D
Fasting blood glucose ≥7mmol/L
Random blood glucose ≥11.1mmol/L and symptoms
Often the type of diabetes diagnosed on symptoms alone but if in doubt check autoantibodies
What is T2D due to?
Progressive loss of beta-cell insulin secretion frequented on the background of insulin resistance
What is gestational diabetes?
Diabetes diagnosed in the second or third trimester of pregnancy that was not clearly overt diabetes prior to gestation
What is idiopathic T1D?
When patients have permanent insulinopenia and are prone to DKA but there is no evidence of beta cell autoimmunity
What HbA1c level is diabetes diagnosed at?
≥48mmol
Aims of therapy in T1D
Prevent hyperglycaemia
Prevent hypoglycaemia
Reduce chronic complications
Aims of therapy in T1D
Prevent hyperglycaemia
Avoid hypoglycaemia
Reduce chronic complications
Hyperglycaemia symptoms
Thirst
Tiredness
Blurred vision
Weight loss
Polyuria
Nocturia
Fungal infections
Altered cognitive function, mood state, information processing and memory
Hypoglycaemia symptoms
Pallor
Sweating
Tremor
Palpitations
Nausea
Hunger
Confusion
Coma
What is done in a diabetes annual review assessment?
Weight
Blood pressure
HbA1c
Renal function
Lipids
Retinal screening
Diabetic foot assessment
Devices to administer insulin
Syringe
Disposable pen
Re-usable cartridge pen
Continuous subcutaneous insulin infusion pump
Prandial insulin analogues:
Examples
Onset
Peak action
Duration
Examples - Novorapid, Humalog, Apidra
Onset of action - 10-15 minutes
Peak action - 60-90 minutes
Duration - 4-5 hours
Prandial soluble insulin:
Examples
Onset
Peak action
Duration
Examples - Humulin S, Actarapid
Onset of action - 30-60 minutes
Peak action - 2-4 hours
Duration - 5-8 hours
Isophane basal insulins:
Examples
How long do they act?
What is the peak action?
Examples - Insulatard, Humulin I
Intermediate/long acting
Peak activity 4-6 hours after administration
Analogue basal insulins:
Examples
How often should they be given?
Examples - Lantus, Levemir
May be given once or twice a day
True or false:
People with cystic fibrosis can develop their own cystic fibrosis form of diabetes
True - usually found in severe mutations
Autoimmune conditions that may be associated with diabetes
Thyroid disease
Coeliac disease
Pernicious anaemia
Addison’s disease
IgA deficiency
Indications for pancreas transplantation in a patient with diabetes
Imminent or ESRD due to receive or with kidney transplant
Severe hypoglycaemia/metabolic complications
Incapacitating clinical or emotional problems
4 key steps in islet transplantation
Pancreas donation and retrieval
Islet isolation
Islet culture
Islet transplantation
What causes monogenic diabetes?
Mutations in a single gene - they are Mendelian disorders
Is monogenic diabetes autosomal or recessive?
Can be either
What is the most common form monogenic diabetes?
MODY - mature onset diabetes of the young
Is MODY autosomal dominant or autosomal recessive?
Dominant
Is MODY insulin dependent?
No
What is the age of onset in MODY?
Usually <25 years
Clinical diagnosis of MODY
3 generation FH
One family member diabetes <25
Non-insulin dependent
What are the three groups of MODY?
Those with mutations in glucokinase gene
Those with mutations in transcription factors
Those with MODY but we do not know the gene
What is the function of glucokinase?
Converts glucose into glucose-6-phosphate
When does MODY with glucokinase mutations present?
Birth
Describe insulins secretion in someone with glucokinase mutation
There is a right shift of the insulin sensing curve
They will sense normal glucose as e.g. 7 compared to 5
They produce just as much insulin as someone who doesn’t have diabetes, no defect in beta cell function
When does MODY with transcription factor mutations present?
Teenage years or early adulthood
True or false:
Transcription factor MODY is a progressive disease?
True
In glucokinase MODY, there is stable/unstable hyperglycaemia
Stable
How is glucokinase MODY treated?
Diet treatment
Where are the mutations in transcription factor MODY?
HNF-1alpha, HNF-1beta, HNF4-alpha
How is transcription factor MODY treated?
1/3 diet, 1/3 OHA, 1/3 insulin
Which diabetes drugs do patients with transcription factor MODY respond well do?
Sulphonylureas
Mutations present in neonatal diabetes
KCNJ11, ABCC9
How do the mutations present in neonatal diabetes affect the body?
Causes K channels to be unresponsive to ATP, leading to them remaining open and the beta cell remains hyper polarised and there is no insulin secretion
True or false:
Neonatal diabetes is insulin dependent?
False - not necessarily. Can use sulphonylureas to close the channel
Lipids and liver fat biochemical biomarkers that are increased and decreased in T2DM
Increased - ALT, TG (triglycerides)
Decreased - HDL
Inflammatory biochemical biomarkers that are increased in T2DM
CRP
IL-1
IL-6
IL-18
MCP-1
Ferritin is increased/decreased in T2DM
Increased
Adiponectin is increased/decreased in T2DM
Decreased
What percentage of diabetes is T2D?
90-95%
Aims of management in T2DM?
Treat symptoms
Prevent microvascular complications
Prevent cardiovascular complications
How much weight loss can result in remission of T2DM?
10-15%
Advice on healthy eating for T2DM
Normal intake of unrefined carbs, reduced intake of unrefined sugars
Reduce fat intake
Increase fruit and veg intake
Reduce salt
Safe and sensible alcohol consumption
Factors leading to failure to reach glycemic targets in T2DM
Female
Younger
Obese
Not at lipid or BP targets
Poor adherence to meds, lifestyle
Reluctance to intensify treatment
