Introduction To Diabetes 07.12.23 Flashcards
In the fasting state, what happens in regulation of CHO metabolism in non diabetic humans
In the fasting state
all glucose comes from liver (and a bit from kidney)
Breakdown of glycogen
Gluconeogenesis (utilises 3 carbon precursors to synthesise glucose including lactate, alanine and glycerol)
Glucose is delivered to insulin independent tissues, brain and red blood cells
Insulin levels are low
Muscle uses FFA for fuel
Some processes are very sensitive to insulin, even low insulin levels prevent unrestrained breakdown of fat
After feeding, what happens in regulation of CHO metabolism in non diabetic humans
After feeding (post prandial) - physiological need to dispose of a nutrient load
Rising glucose (5-10 min after eating) stimulates insulin secretion and suppresses glucagon
40% of ingested glucose goes to liver and 60% to periphery, mostly muscle
Ingested glucose helps to replenish glycogen stores both in liver and muscle
High insulin and glucose levels suppress lipolysis and levels of non-esterified fatty acids (NEFA or FFA) fall
Microstructure of islets of langerhans
Slide 7
How does insulin secretion occur in the beta cells?
Slide 8
How does insulin act in muscle and fat cells
Slide 9
What are the key hormonal regulators of carbohydrate metabolism
Insulin
Glucagon
Adrenaline
Cortisol
Growth hormone
What does insulin do?
Supresses hepatic glucose output
Glycogenolysis
Gluconeogenesis
Increases glucose uptake into insulin sensitive tissues (muscle, fat)
Suppresses
Lipolysis
Breakdown of muscle
What does glucagon do?
Increases hepatic glucose output
Glycogenolysis
Gluconeogenesis
Reduce peripheral glucose uptake
Stimulate peripheral release of gluconeogenic precursors (glycerol, AAs)
Lipolysis
Muscle glycogenolysis and breakdown
Define diabetes mellitus
A disorder of carbohydrate metabolism characterised by hyperglycaemia
How does diabetes mellitus cause mortality and morbidity
Acute hyperglycaemia which if untreated leads to acute metabolic emergencies diabetic ketoacidosis (DKA) and hyperosmolar coma (Hyperosmolar Hyperglycaemic State )
Chronic hyperglycaemia leading to tissue complications (macrovascular and microvascular)
Side effects of treatment- hypoglycaemia
What complications are diabetes associated with?
Diabetic retinopathy
Diabetic nephropathy
Stroke
Cardiovascular disease
Diabetic neuropathy
What are the types of diabetes?
Type 1
Type 2 (inc. gestational and medication induced diabetes)
MODY (Maturity onset diabetes of youth)/monogenic diabetes
Pancreatic diabetes
Endocrine diabetes (acromegaly/cushings)
Malnutrition related diabetes
Define diabetes
Symptoms and random plasma glucose > 11 mmol/l
Fasting plasma glucose > 7 mmol/l
No symptoms - GTT (75g glucose) fasting > 7 or 2h value > 11 mmol/l (repeated on 2 occasions)
HbA1c of > 48mmol/mol (6.5%)
Define type 1 diabetes
An insulin deficiency disease characterised by loss of beta cells due to autoimmune destruction
How does type 1 diabetes occur?
Beta cells express antigens of HLA histocompatability system perhaps in response to an environmental event (?virus)
Activates a chronic cell mediated immune process leading to chronic ‘insulitis’