Type 1 Diabetes Flashcards
What usually causes the inception of type 1 diabetes?
An environmental trigger in a genetically susceptible individual leading to an autoimmune process involving pancreatic beta cell destruction
The days of patients frequently dying from ketoacidosis induced comas are gone. What are patients with type 1 diabetes most likely to ultimately die from now?
Cardiovascular or renal disease
Histologically how do the islet cells appear in type 1 diabetes?
The islet cells are filled with lymphocytes
Histologically how do the islet cells look with type 2 diabetes?
There is amyloid deposition around the islet cells
Which genotypes are associated with increased type 1 diabetes risk?
- HLA DR3-DQ2
- HLA DR4-DQ8
- Insulin gene (on chromosome 11)
Incidence rates for type 1 diabetes are worse at which time of the year?
Winter
Which islet cell antibodies may be detected in type 1 diabetes?
- IA2
- IAA
- GAD65
- ZnT8
Which antibodies for T1DM are more commonly sensitive for younger patients?
- IA2
- IAA
Which antibodies for T1DM are more commonly sensitive for older patients?
- GAD65
- ZnT8
Clinical type 1 diabetes can be accelerated by which factors?
- Infection
- Insulin resistance
- Puberty
- Diet/weight
- Stress
What are the foetal risk factors which cause there to be an increased chance of developing diabetes?
- Infection
- Older mother
- ABO mismatch
- Birth order (1st child more suseptible)
- Stress
If a patient is prediabetic, what are the risk factors which could cause them to beome clinical diabetics?
- Viral infection
- Vitamin D deficiency
- Diet
- Environmental toxins
What is the typical triad of symptoms in T1DM?
- Polyuria
- Polydipsia
- Weight loss
How does polyuria manifest in children?
As enuresis - inability to control urination e.g. wetting the bed
As well as the classic triad of T1DM symptoms, which other symptoms may be experienced?
- Fatigue
- Blurred vision
- Candidal infection
- Ketoacidosis
Candidal infection may cause which conditions in males and females with T1DM?
- Pruritis vulvae
- Balanitis
What are the key features of clinical diabetes?
- Raised glucose
- Ketones
- Decreased insulin secretion
- Decreased beta cell mass
- Decreased C-peptide
An annual review assessment for someone with T1DM should include which tests?
- Weight
- BP
- Bloods - HbA1c, renal function, lipids
- Retinal screening
- Foot risk assessment
Children are more likely to develop type 1 diabetes if their __________ has the condition
Children are more likely to develop type 1 diabetes if their father has the condition
What are the microvascular complications of chronic poor glycaemic control?
- Retinopathy
- Nephropathy
- Neuropathy
At which age is type 1 diabetes diagnosed most often?
5-15 years
Describe the onset of T1DM
Short with severe symptoms
At presentation with T1DM, there are ________ complications
At presentation with T1DM, there are rarely complications
Type 1 diabetes is associated with weight ______
Type 1 diabetes is associated with weight loss
What is LADA?
Latent onset diabetes of adulthood
Type 2 diabetes is usually diagnosed at which age?
>25years
Describe the onset of type 2 diabetes
Insidious onset with (initially) mild symptoms
At presentation with T2DM there are __________ complications
At presentation with T2DM there are commonly complications
Which factors are most associated with LADA?
- Male
- 25-40 years
- Non-obese
- AA +ve
- Other autoimmune conditions
- Not requiring insulin at presentation
In which autoimmune condition is there a very high chance of also suffering from type 1 diabetes?
Cystic fibrosis
In those with cystic fibrosis, which screening test can aid in picking up T1DM?
OGTT from the age of 10
Which autoimmune conditions can be commonly associated with T1DM?
- Thyroid disease
- Coeliac disease
- Pernicious anaemia
- Addison’s disease
- IgA deficiency
- Cystic fibrosis
Which rare auto-immune conditions may be implicated in those with T1DM?
- Polyglandular endicrinopathy syndromes (types 1 and 2)
- AIRE mutations
- IPEX syndrome
By which other name is Wolfram syndrome known?
DIDMOAD
What is Wolfram syndrome?
An autosomal recessive disorder encompassing:
- Diabetes insipidius
- Diabetes mellitus
- Optic atrophy
- Deafness
- Neurological abnormalites
What is Bardet-Biedl syndrome?
A ciliopathic human genetic disorder associated with:
- Obesity
- Polydactyly
- Hypogonadal
- Visual impairment
- Hearing
- Mental retardation
- Diabetes
On which continent is type 1 diabetes most common?
Europe
Which viruses have the strongest association as triggers for T1DM?
- Congenital rubella syndrome
- Human enteroviruses
Coeliac disease shares which genotype with T1DM?
HLA-DQ2
What is insulitis?
Inflammation of the beta cell
At which stage will hypeglycaemia develop in type 1 diabetes?
When 80-90% of the pancreatic beta cells are destroyed
Why is it that patients with type 1 diabetes present with hyperglycaemia and ketoacidosis?
Patients cannot utilise glucose in peripheral glucose and adipose tissues
There is no insulin to allow this storage to happen
Instead, the secretion of counter-regulatory hormones increases
Examples include glucagon, adrenaline, cortisol and growth hormone
These hormones can induce gluconeogenesis, glycogenolysis and ketogenesis in the liver
This means patients will have increased blood glucose levels and a metabolic acidosis due to the by products of glucose production in this way
Long term hyperglycaemia can lead to what type of complications?
Vascular complications
Why do vascular complications occur with chronic hyperglycaemia?
- Glycosylation of proteins in tissue and serum
- Production of sorbitol (reduced glucose)
- Free radical damage
What are macrovascular complications of chronic hyperglycaemia?
- Cardiovascular disease
- Cerebrovascular disease
- PVD
Why is it that chronic hyperglycaemia causes atheroma formation and PVD?
Hyperglycaemia causes oxidative stress by neutralising nitric oxide
This results in dysfunctional endothelium which allows LDL entry into the vessel wall
This induces a slow inflammatory process which results in atheroma formation
What are the two types of type 1 diabetes?
- Autoimmune/classical
- Idiopathic
How common is idiopathic type 1 diabetes, which population is it most common in and how is it characterised?
Not common
Asians
Abscence of antibodies, yet beta cell destruction
Why is early diagnosis possible in type 1 diabetes?
Glucose and HbA1c rise well before symptoms commence
If a patient presents with ketoacidosis, how will you know?
Smell of ketones on breath like pear drops
Dehydration and acidotic symptoms:
- Nausea and vomiting
- Abdominal pain
- Tachypnoea
- Tachycardia
- Lethargy
In a symptomatic patient, in which 4 ways can T1 diabetes be confirmed?
- Random plasma glucose >11mmol/l
- Fasting plasma glucose >6.9mmol/l
- 2hr OGTT (75mg glucose) >11mmol/l
- HbA1c > 48mmol/mol
In type 1 diabetes, what can there be autoantibodies for?
- Glutamic acid decarboxylase (GAD)
- Insulin (IAA)
- Islet antigens (IA2)
- Zinc transporter ZnT8
John, an obese teenager with a family history of T2DM has high blood glucose. How do you differentiate between type 1 and 2 diabetes?
- Low C-peptide levels
- Anti-GAD antibodies
Both of these indicate T1DM
What is the typical age of presentation for T1DM?
5 - 15 years
Which genes are considered susceptibilty genes?
- DR4-DQ8
- DR3-DQ2
Which infectious agents have beens associated with triggering T1DM?
Congenital rubella and human enteroviruses
How is fasting defined?
No calorific intake for at least 8 hours
What value of random plasma glucose is diagnostic of T1DM?
11mmol/l
What value of fasting plasma glucose is diagnostic for T1DM?
>6.9mmol/l
