Diabetes And Hypoglycaemia Flashcards
What are blood glucose levels maintained by?
Dietary carbohydrate
Glycogenolysis
Gluconeogenesis
What happens in the body in a fed state?
Glucose increases -> insulin release
Decrease in glycogenolysis and increase of liver nutrient uptake
Increase in peripheral uptake and decrease in peripheral catabolism
What happens in the body in a fasting state?
Decrease in insulin secretion -> increase in gluconeogenesis
Peripheral glucose uptake decreases and increased lipolysis and proteolysis
What is the function of insulin?
Promotes storage and growth
What is the function of glucagon?
Mobilises fuel
Maintains blood glucose in fasting
What is the function of epinephrine?
Mobilises fuel in acute stress
What is the function of cortisol?
Long term change
What is the function of growth hormone?
Inhibits insulin action
What are the major metabolic pathways involving insulin?
Glucose storage in muscle and liver
Protein and fatty acid synthesis
What are the major metabolic pathways involving glucagon?
Activates gluconeogenesis, glycogenolysis and fatty acid release
What are the major metabolic pathways involving epinephrine?
Stimulates glycogenolysis and fatty acid release
What are the major metabolic pathways involving cortisol?
Amino acid mobilisation and gluconeogenesis
What are the major metabolic pathways involving growth hormone?
Stimulates lipolysis
What is diabetes mellitus characterised by?
Chronic hypoglycaemia, glycosuria and associated abnormalities of lipid and protein metabolism
What are the classifications of diabetes mellitus?
Type 1
Type 2
Secondary
Gestational
What happens in type 1 diabetes?
Deficiency in insulin secretion
What happens in type 2 diabetes?
Normal insulin secretion but there is target organ insulin resistance
What causes secondary diabetes?
Chronic pancreatitis
Pancreatic surgery
Antagonist secretion
What differentiates gestational diabetes?
It occurs for the first time in pregnancy
When does type 1 diabetes first present?
Children and young adults but can present at any time
What may symptom appearance be preceded by?
Pre-diabetic period of several months
What is the most common cause of type 1 diabetes?
Autoimmune destruction of beta cells
What is the pathogenesis of type 1 diabetes?
Autoantigens presented to T lymphocytes initiate an autoimmune response
Circulating autoantibodies to various cell antigens against glutamic acid decarboxylase
What is the most commonly detected antibody associated with type 1 diabetes?
Islet cell antibody
What does the destruction of pancreatic beta cells cause?
Hyperglycaemia
Why does the destruction of pancreatic beta cells cause hyperglycaemia?
Absolute deficiency of insulin and amylin
What is amylin?
Glucoregulatory peptide hormone co-secreted with insulin
What does amylin do?
Lowers blood glucose by slowing down gastric emptying and supressing glucagon output from pancreatic beta cells
How does type 2 diabetes present?
Slow onset
Patients middle aged/elderly
Strong familial incidence
What causes a hyperglycaemic hyperosmolar nonketotic state?
Low insulin -> inc gluconeogenesis and glycolysis
- > hyperglycaemia
- > glycosuria and increased plasma osmolarity
What does an increased plasma osmolarity lead to?
Cerebral dehydration and impaired consciousness
What does hyperglycaemia cause?
Glycosuria
What does glycosuria cause?
Osmotic diuresis and loss of water and electrolytes
What does loss of water and electrolytes cause?
Dehydration
Increased blood viscosity
Thrombosis
How do you diagnose diabetes when there are no symptoms present?
Test blood sampled on two different days
How do you diagnose diabetes when symptoms are present?
Random plasma glucose >11.1mmol/L Or Fasting plasma glucose >7mmol/L Or Oral glucose tolerance where plasma glucose >11.1mmol/L
What are the symptoms that would cause you to test for diabetes?
Polyuria
Polydipsia
Weight loss (type 1 only)
What does fasting mean when testing for diabetes?
No caloric intake for at least 8 hrs
What is pre-diabetes?
Impaired glucose tolerance
What is the threshold for impaired glucose tolerance?
Fasting plasma glucose >7mmol/L
Oral glucose tolerance of 7.8-11.1mmol/L
What is the threshold for impaired fasting glycaemia?
Fasting plasma glucose 6.1-6.9mmol/L
Oral glucose tolerance value of <7.8mmol/L
When do you do an oral glucose tolerance test?
In patients with:
impaired fasting glycaemia
Unexplained glycosuria
Clinical features of diabetes with normal plasma glucose values
Why do you carry out an oral glucose tolerance test?
To check the bodys ability to metabolise glucose
How do you do an oral glucose tolerance test?
75g oral glucose tolerance and blood tests at 0 and 120 mins after glucose
How do you treat type two diabetes?
Diet and exercise -> oral monotherapy -> oral combination -> insulin with/without oral agents
What drug is used in oral monotherapy for type 2 diabetes?
Metformin
What drug is used in oral combination therapy for type 2 diabetes?
Sulphonylureas
gliptins
GLP-1 analogues
What do thiazolidinediones do?
Reduced insulin resistance
How do SGLT2 inhibitors work?
Prevent glucose reabsorption and increase excretion
How do incretin targeting drugs work?
Help the body to increase glucose when needed
Why do you monitor glycaemic control?
To prevent complications or avoid hypoglycaemia
How do you monitor glycaemic control?
Capillary blood measurement
urine analysis
Blood HbA1c
Urinary albumin
What does glucose in urine give an indication of?
Blood glucose concentration above renal threshold
What is blood HbA1c?
Glycated Hb; covalent linkage of glucose to residue in Hb
What are the long term complications of (badly managed) diabetes?
Micro and macro vascular disease
What are the examples of microvascular disease?
Retinopathy, nephropathy, neuropathy
What are some examples of macrovascular disease?
Atherosclerosis heart attack/ stroke
What is hypoglycaemia defined as?
Plasma glucose <2.5 mmol/L
What are the causes of hypoglycaemia?
Drugs
More common in type 2 diabetes (when taking insulin and inslin secretagogues)
What is the treatment for hypoglycaemia?
Exogenous insulin and insulin secretagogues
What are some examples of insulin secretagogues?
Glyburide
Glipizide
Glimepiride
What can cause hypoglycaemia in patients without diabetes?
Alcohol and pharma drugs (Beta blockers, ACE inhibitors, IGF-1 etc) Endocrine disease Insulinoma Inherited metabolic disorders Sepsis Chronic kidney disease
What does ethanol inhibit?
Gluconeogenesis
What happens if you have a several day long alcohol binge with limited food intake?
Hepatic depletion of glycogen
What happens in sepsis?
Cytokine accelerated glucose utilisation and induced inhibition of gluconeogenesis in the setting of glycogen depletion
Why does chronic kidney disease cause hypoglycaemia?
Involve impaired gluconeogenesis, reduced renal clearance of insulin and reduced renal glucose production
What is another name for reactive hypoglycaemia?
Postprandial hypoglycaemia
What is reactive hypoglycaemia?
Drops in blood sugar are usually recurrent and occur within four hours of eating
What causes reactive hypoglycaemia?
Possibly a benign tumour in the pancreas overproducing insulin
Too much glucose used up by the tumour itself
Deficiencies in the counter-regulatory hormones
What are the categories for signs of hypoglycaemia?
Neurogenic
Neuroglycopaenic
What are the neurogenic symptoms of hypoglycaemia triggered by?
Falling glucose levels
What are the neurogenic symptoms of hypoglycaemia activated by?
Autonomic nervous system
What are the neurogenic symptoms of hypoglycaemia mediated by?
Sympathoadrenal release of catecholamines and ACh
What are the neurogenic symptoms of hypoglycaemia?
Mood changes Trembling Paleness Sweating Dizziness Blurred vision Hunger Headaches Extreme tiredness
What is neuroglycopaenia caused by?
Neuronal glucose deprivation
What are the symptoms of neuroglycopaenia?
Confusion Difficulty speaking Ataxia Paresthesia Seizures Coma Death
