What is diabetes? Flashcards
What are the primary sources of glucose to the body?
Glucose absorbed from gut (dietary glucose)
The Liver - through Gluconeogenesis & glycogenolysis
What is the role of insulin in our bodies
It is the only hormone that acts to lower blood glucose levels
It (and other enzymes) are used to maintain our blood glucose levels
What is the effect of insulin on these:
a) adipose tissue
b) the liver
c) muscle
Insulin release causes:
a) Adipose tissue - Reduced lipolysis
b) The liver - Reduced glucose production
c) Muscle - Increased glucose uptake into cells
What is the definition of diabetes?
a group of metabolic diseases of multiple aetiologies
characterised by hyperglycaemia together with disturbances of carbohydrate, fat and protein metabolism
resulting from defects in insulin secretion, insulin action, or both
What are the symptoms of hyperglycaemia (and diabetes)?
Polydipsia (excessive thirst)
Polyuria (excessive urine passage)
Blurred vision
Weight loss
Infections
What are the potential complications of diabetes arising from metabolic decompensation?
Diabetic Ketoacidosis (DKA) - usually type 1 diabetes
Hyperosmolar hyperglycaemic state (HHS) - type 2 diabetes
What are the long term complications of Diabetes?
Microvascular:
- Retinopathy
- Neuropathy
- Nephropathy
Macrovascular:
- Stroke
- MI
- PVD, diabetic foot etc
What is the approach to diagnosing diabetes?
Diabetes can be diagnosed when overt symptoms are present and random blood glucose measurement.
In absence of clear symptoms - diagnosis can be made using any 1 of 3 measurements of glucose metabolism
How is diabetes with overt symptoms diagnosed?
*Random plasma glucose* >11 mmol/L
other options:
Fasting plasma glucose > 7 mmol/L
2 hour OGTT (glucose tolerance test) value > 11
HbA1c > 48.00 mmol/mol
(Symptoms + 1 diagnostic test +ve)
How is diabetes with less clear symptoms diagnosed?
Same options for tests but requires 2 positives…
*Random blood glucose > 11
Fasting blood glucose > 7
2 hour OGTT > 11
HbA1c > 48
(no symptoms diagnosis = 2 diagnostic test +ves)
What is intermediate hyperglycaemia?
Its like a btec version of Diabetes. Blood tests show impairment - but not to the degree of diabetes.
- Impaired fasting glucose 6.1-7 mmol/L
- Impaired glucose tolerance 2h glucose ≥7.8 and <11mmol/l
- HbA1c 42-47mmol/mol
The diagnostic criteria for diabetes means that a lot of people tested will have impaired glucose metabolism (Intermediate hyperglycaemia) - but fail to be diagnosed with diabetes.
Why is this?
Diabetes diagnostic criteria identify patients who have significant enough risk of premature mortality and micro/macrovascular complications
Intermediate hyperglycaemia does not place you at a significant enough risk basically
What does intermediate hyperglycaemia indicate about a patients future?
Intermediate hyperglycaemia (IGT and IFG) identifies a group at higher risk of future diabetes and adverse outcomes such as cardiovascular disease
What does normoglycaemic mean?
For glucose levels associated with a low-risk of developing diabetes or CVD
What is the significance/meaning of HbA1c?
HbA1c - part of Haemoglobin which is bound to irreversibly to glucose
The higher the HbA1c - the higher the glucose levels
HbA1c circulates for the lifespan of the red blood cell, so reflects the prevailing blood glucose levels over the preceding 2-3 months (ie more long term measurement)
What are the contraindications to using HbA1c for the diagnosis of diabetes?
Children/young people
Pregnancy
Short duration of diabetes symptoms
If illness/presentation is very acute
Medications - corticosteroids, antipsychotics
Pancreatic damage or surgery
Renal failure
HIV infection
What are all of the types of diabetes?
Type juan
Type 2 - most common
MODY - rare
Secondary diabetes - rare
Note Type 2 diabetes overlaps with all other types to a certain degree
What age is type 1 diabetes most prevalent in?
Most common in young people (10-19)
How does familial risk for type 1 diabetes translate?
If father has T1DM - 6% risk
If mother has T1DM - 1% risk
If both parents have T1DM - 30% risk
Increased risks translate when comparing siblings
For the development of Type 1 diabetes to occur - what must happen?
Genetic predisposition and
A trigger event (viral infection?) which leads to autoimmunity
What abnormality of insulin characterises Type 1 diabetes?
T1DM characterised by Insulin deficiency
Which leads to - increased lipolysis in fat, Increased glucose production in liver and reduced glucose uptake by muscle cells
Describe the clinical presentation of symptomatic Type 1 diabetes
Symptoms:
- Polydipsia
- Polyuria / nocturia
- Blurred vision
Signs:
- Ketone smell on breath (peardrop)
- Dehydration (cap refill etc)
- Maybe - Increased resp rate, tachycardia, hypotension
- May have low-grade infection - thrush etc
What is the familial risk associated with type 2 diabetes?
T2DM has much stronger familial risks than T1DM
If both parents have it - 75% risk for child
How does insulin production change as type 2 diabetes is developed?
May initially be hyperinsulinaemia
However, T2DM characterised by progressive decrease in insulin production
What is the effect of decreased insulin production on adipose, liver & Muscle
Adipose tissue - altered lipolysis
Liver - Increased glucose production
Muscle - reduced glucose uptake
What are the symptoms of type 2 diabetes?
*May have no symptoms*
Polydipsia (thirst)
Polyuria
Blurred vision
Tiredness
Sometimes weight loss
Sx of complications
What are the signs of type 2 diabetes?
Not ketotic
Overweightness (sometimes not)
Low-grade infections - such as thrush
Signs of complications
What groups of people should be screened for diabetes? (asymptomatic)
Age >/= 40
NOT pregnant women
Aged 25–39 of South Asian, Chinese, African- Caribbean, black African and other high-risk black and minority ethnic groups
Adults with conditions that increase risk of T2DM
What conditions increase the risk of developing type 2 diabetes?
Cardiovascular disease, hypertension, stroke
Obesity
Mental health problems
Polycystic ovary syndrome
History of gestational diabetes
What is MODY?
Maturity Onset Diabetes in the Young
Caused by autosomal dominant single gene defect
Mutations involving which genes cause Mody?
Glucokinase gene mutations (onset at birth)
or
Transcription factor mutations (Adolescence/young adult-onset)
What are the differences between MODY caused by Glucokinase gene mutations or transcription factor gene mutations?
Glucokinase mutations:
- Onset at birth
- Stable hyperglycaemia
- Complications rare
- Diet treatment
Transcription factor mutations:
- teenager/young adult onest
- Progressive hyperglycaemia
- 1/3 diet, 1/3 Oral Hypo Agents (OHA), 1/3 Insulin
- Complications frequent
What specific transcription factor genes are mutated in this type of MODY?
HNF-1a
HNF-1b
HNF-4a
a = alpha, b = beta
What is gestational diabetes?
Diabetes (hyperglycaemia) that happens during pregnancy
Features:
Increasing insulin resistance during 2nd/3rd trimester of pregnancy
Family history of type 2 diabetes
More common if overweight, inactive
What does gestational diabetes risk for the child?
Neonatal problems such as:
Macrosomia (big baby)
Respiratory distress (possible IRDS)
Neonatal hypoglycaemia
What is secondary diabetes?
diabetes that results as a consequence of another medical condition
What can cause secondary diabetes?
Major disease of the exocrine pancreas:
- Chronic pancreatitis
- Haemochromatosis
- Cystic fibrosis
Endocrinopathies:
- Acromegaly
- Cushing’s
- Glucagonoma
- Pheochromocytoma
Drug/Chemical induced diabetes:
- Steroids
