Diabetes & Hypoglycaemia Flashcards
How are blood glucose levels maintained
- Dietary carbohydrates
- Glycogenolysis
- Gluconeogenesis
Explain the FED state
When we eat there is an increase in blood glucose levels.
There is a rise in insulin levels to counter that increase.
There is less liver glucose production and increased liver nutrient uptake
- Increased peripheral uptake
- Decreased peripheral catabolism
Explain the fasting state
- Decreased insulin production
- Increased liver gluconeogenesis
- decreased peripheral uptake and increased lipolysis and proteolysis
- Increased glucose production
What is the mechanism for when there is high blood sugar
- Increased insulin release from the pancreas
- Insulin stimulates glucose uptake from blood
- Stimulates glycogen formation in the liver and glucose uptake in muscle and tissue cells
- Lowers blood sugar
What is the mechanism for when there is low blood sugar
- Increased glucagon release from the pancreas
- Glucagon stimulates glucose release into the blood
- Stimulates glycogen breakdown in the liver
- Increases blood sugar
What are the effects of insulin on adipose tissue
- Increased glucose uptake
- Increased lipogenesis
- Deceased lipolysis
What are the effects of insulin on striated muscle
- Increased glucose uptake
- Increased glycogen synthesis
- Increased protein synthesis
What are the effects of insulin on the liver
- Decreased gluconeogenesis
- Increased glycogen synthesis
- Increased lipogenesis
What is the function of insulin and what are its major metabolic pathways
- Promotes storage - stimulates glucose storage in muscle, liver
- Promotes growth - Stimulates protein and fatty acid synthesis
What is the function of glucagon and what are its major metabolic pathways
- Mobilises fuel - activates gluconeogenesis and glycogenolysis
- Maintains blood glucose in fasting - activates fatty acid release
What is the function of Adrenalin and what are its major metabolic pathways
- Mobilises fuels in
stimulates - glycogenolysis; acute stress, stimulates fatty acid release
What is the function of cortisol and what are its major metabolic pathways
- Changing long term - amino acid mobilization gluconeogenesis
What is the function of growth hormone and what are its major metabolic pathways
- Inhibits insulin action - stimulates lipolysis
What is diabetes mellitus
A metabolic disorder characterised by chronic
hyperglycaemia, glycosuria and associated abnormalities of lipid and protein metabolism
What is the prevalence of DM
- Globally 422 million people have diabetes (WHO, 2014); estimated to increase by 2035
- In UK 2018 ~ 3.8 million diagnosed with DM.
What are the types of diabetes
- Type 1: deficiency in insulin secretion
- Type 2: Insulin secretion is retained but there is target organ resistance to its action
- Secondary: chronic pancreatitis, pancreatic surgery, secretion of antagonist
- Gestational: Occurs for first time in pregnancy
What are the characteristics of type 1 DM
Predominantly in children and young adults; but other
ages as well.
Sudden onset (days/weeks)
Appearance of symptoms may be preceded by
‘prediabetic’ period of several months
Commonest cause is autoimmune destruction of B-cells:
- interaction between genetic and environment factors.
- strong link with HLA genes within the MHC region on
chromosome 6.
What is the pathogenesis of type 1 DM?
Destruction of B-cells starts with autoantigen formation
Autoantigens are presented to T-lymphocytes to initiate
autoimmune response
There would be circulating autoantibodies to various -cell
antigens against glutamic acid decarboxylase:
- tyrosine-phosphatase-like molecule
- Islet auto-antigen
The most commonly detected antibody associated with type 1
DM is the islet cell antibody
What is the role of amylin in diabetes
More than 90% of newly diagnosed persons with type 1 DM have one or another of these antibodies.
Destruction of pancreatic ß-cell causes hyperglycaemia
due to absolute deficiency of both insulin & amylin:
- Amylin, a glucoregulatory peptide hormone co-secreted
with insulin. - lowers blood glucose by slowing gastric emptying, & suppressing glucagon output from pancreatic cells.
Describe how insulin deficiency can cause Diabetic coma
- Even with high blood sugar there is still a feeling of hunger therefore we eat more - Polyphagia
- High blood glucose causes it to leak into urine in the kidneys - Glycosuria
- Increased glucose concentration draws more water into the urine in the nephron causing more ruin and more frequent urination - Polyuria
- Water leaving causes volume depletion and causes feelings of thirst and drinking more water to compensate - Polydipsia
- If not able to keep up with volume depletion with drinking more water can lead to diabetic coma
Describe how insulin deficiency can cause Ketoacidosis
- Increased lipolysis to make glucose within cells
- There is an increase in free fatty acids
- Increased free fatty acid oxidation in the liver
- Increased production of ketone bodies leading to ketoacidosis
What are the characteristics of type 2 DM
- Slow onset (months/years)
- Patients middle-aged/elderly – prevalence increases
with age - Strong familiar incidence
- Pathogenesis uncertain - insulin resistance; β-cell dysfunction
what is the pathophysiology of type 2 DM
- Both genetic predisposition and Obesity lifestyle factors can cause Insulin resistance
- Beta cells compensate by producing more insulin which results in temporary normoglycemia
- When there is beta cell failure there is impaired glucose tolerance
- Full beta cell failure leads to diabetes
- Primary beta cell failure can cause diabetes straight away
How do we diagnose diabetes
In the presence of symptoms: (polyuria, polydipsia & weight loss for Type I):
- Random plasma glucose ≥ 11.1mmol/l (200 mg/dl ).
OR - Fasting plasma glucose ≥ 7.0 mmol/l (126 mg/dl) Fasting is
defined as no caloric intake for at least 8 h OR - Oral glucose tolerance test (OGTT) - plasma glu ≥ 11.1 mmol/l
In the absence of symptoms:
- test blood samples on 2 separate days
