Diabetes And Hypoglycaemia Flashcards
How are blood glucose levels maintained?
Dietary carbohydrates
Glycogenolysis
Gluconeogenesis
What is the effect of increased insulin?
Decreased liver production of glucose
Liver nutrients uptake
Increase peripheral uptake + decrease peripheral catabolism
What occurs to the insulin levels in the fasting state?
Insulin levels decrease to try increase glucose production
How does decreased insulin increase glucose production in the fasting state?
Increase liver gluconeogenesis
Decrease peripheral uptake
Increase proteolysis and lipolysis
Why is it important to maintain plasma glucose level?
Enough to fuel the body.
Brain and erythrocytes require a continuous supply of glucose
How is high plasma glucose level regulated in the body?
- High blood sugar levels are detected by beta cells in the pancreas
- Beta cells release insulin into the blood stream
- Insulin stimulates glucosereuptake from the blood into tissues
- Insulin also stimulates glycogen formation in the liver
How is low plasma glucose concerntration maintained?
- Low blood sugar is detected by alpha pancreatic cells
- Glucagon released from alpha cells
- Glucagon breaks down glycogen in the liver
- Increases blood glucose level
What is the role of insulin in the liver?
Decrease Gluconeogenesis
Increase glycogen synthesis
Increase lipogenesis
What is the role insulin the striated muscle?
Increase glucose uptake
Increase glycogen synthesis
Protein synthesis
What is the role of insulin in adipose tissue?
Increase glucose reputake
Increase lipogenesis
Decrease lipolysis
What is the role of epinephrine in controlling blood glucose concerntration?
Mobilises fuels in acute stress
Stimulates glycogenolysis
Stimulates fatty acid release
What is the role of cortisol in controlling plasma glucose concerntration?
Changes long term
Stimulates glyconeogenesis And amino acid mobilisation
What is the role of growth hormone in controlling plasma glucose concerntration?
Inhibits insulin action
Stimulates lipolysis
What is diabetes mellitus?
A metabolic disorder charecterised by chronic hypoglycemia
And often associated with abnormalities of lipid and protein metabolism
What are the 4 types of diabetes patients can be classified into?
Type 1
Type 2
Secondary
Gestational
What is type 1 diabetes?
Deficiency in insulin secretion
Sudden onset (days/weeks)
In young children or young adults.
Appearance of symptoms may be proceeded by a “pre diabetic” period of several months
What is type 2 diabetes?
Insulin secretion is retained but there is target organ resistance to its actions
Slow onset (months/years)
Patients middle aged/elderly
What is secondary diabetes?
Chronic pancreatitis
Pancreatic surgery
Secretion of antagonists
What is gestational diabetes?
Occurs for the first time in pregnancy
What causes type 1 diabetes?
Autoimmune destruction of B cells
Due to interaction between genetic and environmental factors
- strong link with HLA genes on chromosome 6
What is the pathogenisis of type 1 diabetes?
- Auto antigens form on insulin producing beta cells and circulate in the blood stream and lymphatics
- Processing and presentation of auto antigens by antigen presenting cells (T lymphocytes)
- Activation of
- macrophages
- autoantigen specific cytotoxic T cells
- B lymphocytes to product islet cell auto antibodies + antiGADs antibodies
Most commonly detected antibody associated with type 1 is islet cell antibody
- Destruction of beta cells with decreased insulin secretion
What is amylin?
A glucoregulatory peptide hormone co-secreted with insulin
Lowers blood glucose by slowing gastric emptying + suppressing glucagon output from pancreatic cells
What causes hyperglycemia?
Deficiency in insulin and amylin
What is polyphagia?
Excessive eating or appetite
Due to to hyperglycemia
What is polydipsia?
Excessive thirst or drinking
Due to increased volume depletion in urine
How can ketoacidosis occur as a result of insulting deficiency in type 1 DM?
- Increased lipolysis
- Increased fatty acids
- Increased fatty acid oxidation in the liver
- Ketoacidosis (DKA)
What causes type 2 diabetes?
Genetic predisposition and obesity + lifestyle factors
Insulin resistance - Beta cell disfunction
What is the pathophysiology of type 2 diabetes?
- Combination of genetic predisposition and obesity and lifestyle factors cause insulin resistance
- Compensatory beta cell hyperplasia (normoglycaemia)
- Early Beta cell failure (impaired glucose tolerance
- Late Beta cell failure (diabetes)
What are the metabolic complications of type 2 diabetes?
Dehydration
Thrombosis
Cerebral dehydration
Explain how type 2 diabetes can cause dehydration.
- Glycosuria due to hyperglycemia
- Osmotic diuresis
- Loss of water and electrolytes
Explain how type 2 diabetes can cause thrombosis
Increased blood viscosity due to the increased plasma osmolarity
Explain how type 2 diabetes causes cerebral dehydration.
Increased plasma osmarity due to hyperglycemia
How diabetes diagnosed?
When symptoms are present:
Random plasma glucose > 11.1 mmol/l
Fasting plasma glucose > 7.0 mmol/l
Oral glucose tolerance test (OGTT) - plasma Glu > 11.1 mmol/l
In abscense of symptoms:
Test blood samples on 2 separate days
How can glycated Haemoglobin (HbA1c) be used to detect diabetes?
Reflects the average plasma glucose over 8 to 12 weeks
Performed any time of the day
Initially used as glycaemic control, but now used for diagnosis
> 6.5% is diabetic
HOWEVER, may be effected by a variety of genetic, haematologic disorders
How is impaired glucose tolerance (IGT) diagnosed in pre-diabetes?
Fasting plasma glucose > 7 mmol/L
OGTT value of 7.8 - 11.1 mmol
How is impaired fasting Glycaemia (IFG)?
Fasting plasma glucose 6.1 to 6.9 mmol/L
OGTT value of < 7.8 mmol/L
What is the use of the oral glucose tolerance test?
To check the body’s ability of metabolising glucose
- in patients with IFG
- in unexplained glycosuria
- in clinical features of diabetes with normal plasma glucose values
How is the oral glucose tolerance test carried out?
75g oral glucose and test after 2 hour
Blood samples collection at 0 and 120 mins after glucose
What are the treatments of type 2 diabetes?
- Diet and exercise
- Oral monotherapy (metformin)
- Oral combination
- insulin injection and oral agents
What drugs are used to treat type 2 diabetes?
Metformin
Sulfonylureas
Thiazolifinediones
SGLT2 inhibitors
Incretin targeting drugs:
- DPP-4 inhibitors (prevent breakdown of natural incretins)
- GLP-1 agonist
What is the aim of monitoring glycaemic control?
To prevent complications or avoid hypoglycaemia
What are ways to monitor glycaemic control?
Self monitoring to be encouraged: using analysis and capillary blood measurement
2-3 months: blood HbA1c
Others: urinary albumin
What are long term complications of type 1 and 2 diabetes?
Micro vascular disease
- retinopathy, neuropathy, nephhropathy
Macro vascular disease
- related to atherosclerosis heart attack/stroke
MECHANISMS OF COMPLICATIONS UNCLEAR
What is hypoglycaemia?
Plasma glucose level < 2.5 mmol
What are the causes of hypoglycaemia?
Drugs are the most common cause
- common in type 1 diabetes
- less common in type 2 diabetes taking insulin
Tumour in the pancrease
What are some sulfonylureas that cause hypoglycaemia?
Glyburide
Glipzide
Glimepiride
How can hypoglycaemia occur in patients without diabetes?
Drugs such as alcohol
Endocrine diseases eg. Cortisol disorder
Inherited metabolic disorders eg. Hereditary fructose intolerance
Insulinoma - tumour in beta cells
What is the role of ethanol in hypoglycaemia?
Inhibit Gluconeogenesis but not glycogeolysis
Hypoglycaemia will typically follow several days alcohol binge with limited food intake
What is the role of sepsis in hypoglycaemia?
Cytokines acceleration glucose utilisation
nduced inhibition of gluconeogenesis in the setting of glycogen depletion.
What is the role of CDK in hypoglycaemia?
Mechanism not clear - impared Gluconeogenesis
Reduced renal clearance of insulin
Reduce renal glucose production
What is reactive hypoglycaemia (hypo after eating)?
Drop sin blood sugar level usually reccurant and occur within four hours after eating
What is the cause of reactive hypoglycaemia?
CAUSE UNCLEAR
Possibly a benign tumour in the pancreas may cause overproduction of insulin
Too much glucose may be used by the tumour itself
Deficiency’s in counter regulatory hormones eg. Glucagon
What are the NEUROGENIC (autonomic) signs and symptoms of hypoglycaemia?
Mediated by sympathoadrenal release of catecholamines and ACh
Mood changes
Paleness
Trembling
Sweating
Dizziness
Blurred vision
Headache
Extreme tiredness
Hunger
What are the NEUROGLYCOPAENIA signs and symptoms of hypoglycaemia?
Due to neuronal glucose deprivation
Confusion
Difficulty speaking
Ataxia
Parenthesia
Seizures
Coma
Death
