Diabetes & obesity Flashcards
Glucose is the main energy source for the brain. How much glucose is used by the brain in comparison to other tissues at rest?
The brain uses ~80mg glucose/minute.
Other tissues use ~50mg glucose/minute at rest
*this can increase with exercise / stress
Glucose cannot diffuse across cells so GLUT transporters provide facilitated transport across cell membranes. What is the difference between GLUT-1 & 3, vs. GLUT- 4 transporters?
GLUT-1 and GLUT-3 : not insulin-dependent, passes into brain and neuronal cells for function.
GLUT-4: insulin-dependent, muscle and fat cells (peripheral tissues).
*Lock and key mechanism where SGLT is the lock and insulin is the key.
What is the role of sodium in glucose transport?
Sodium is the co-transporter required for the GLUT transporters to carry out facilitated transport
When sufficient sources of glucose not present, e.g. starvation, increased need – extreme exercise / stress, F____________ cells broken down into K___________.
Fatty cells
ketones.
Why would ketones need to be synthesised from fatty acids?
To maintain brain function when glucose can not be accessed e.g. starvation or times of increased need (extreme exercise/stress).
Ketones can cross the blood-brain barrier – it’s an energy source as an adjunct AND alternative to glucose.
What happens when we eat food/drinks containing sugar?
Food/drink intake causes glucose levels to rise in the blood.
Insulin (secreted by the pancreas in the anabolic pathway) allows blood glucose to enter cells by attaching to insulin receptors.
When not being used, the rise in blood glucose signals the liver to absorb glucose and convert it to glycogen.
What happens when we need energy between meals or at times of stress/exercise?
In normal circumstances, glucagon from the liver is used to breakdown the glycogen into glucose within cells, and export back into the blood stream.
Glucagon (made in the pancreas), cortisol, adrenaline & growth hormone are used in the catabolic pathway to release energy.
At times of stress, in addition to glucagon breakdown into glycogen -> glucose, Cortisol & adrenaline also have a major role in blood glucose (make fat/muscle cells resistant to insulin) - involved in the Flight or fight response.
When there is not enough glycogen stores, or we need glucose quickly,
Fatty acids are broken down into triglycerides, then into glycerol, and finally blood glucose. Where does this take place?
In the liver.
So the anabolic pathway from blood to tissue is i______.
The catabolic pathway to release glucose from tissues into blood includes g_______, c_______ & a_________.
Gluconeogenesis runs alongside this
Insulin.
Glucagon, cortisol and adrenaline
Glycogen is also found in the ________. But this cannot be mobilised into the bloodstream, and only used at this site.
Muscles.
What happens during glycolysis?
During glycolysis, energy is released as glucose is broken down into 2x pyruvate, ATP, NADH & water. Takes place in the cytoplasm of muscles. Doesn’t require O2. Occurs in aerobic & anaerobic state.
Pyruvate is built up into glucose during g_____________, when dietary intake is insufficient or absent.
It takes place in the liver, and glucose can be stored as glycogen.
gluconeogenesis.
Patients with diabetes may be under the care of a multi-disciplinary team. Give examples.
Pts are supported by GP, diabetic nurse, ophthalmic team, hospital diabetes team if needed.
Define diabetes mellitus
A group of disorders with many causes which are characterised by a persistently raised blood glucose level.
Usually due to - A lack of insulin and/or - An inability to respond to insulin
What happens in the body in T1 DM?
Autoimmune – T cell mediated – the body attacks the B cells that sit within Islets of Langerhans in the pancreas. The B cells are essential in the production of insulin, their destruction (~90%) results in a lack of insulin. Without replacement insulin, people would die within days/weeks.
- Often diagnosed early childhood / early adolescence.
What is the classification of diabetes mellitus
E.g. T1 DM, T2 DM, gestational DM
Other types: · Monogenic diabetes (single gene defect or associated with genetic conditions like Down’s or Turner’s)
· Diabetes secondary to pathological conditions such as pancreatitis, trauma or pancreatic surgery
· Drug-induced (long-term corticosteroid treatment).
· Malignant tumours of pancreas - rare
What happens in T2 DM?
· Metabolic disorder
· Inability to produce enough vol of insulin that is required due to dysfunction of β-cells in pancreas.
· Insulin that is produced is not used correctly in the body, or there is resistance to insulin by the cells. (failure of the intracellular signalling pathways).
· Insidious onset, evolving over months/years. ~50% of cases are undiagnosed. Often diagnosed in middle & elderly ages.
What causes blood glucose levels to rise in T2 DM
- Reduced ability of muscle & fat cells to take up glucose
- Reduced ability to suppress liver glucose production after eating (so glycogen is broken down into glucose = increased blood glucose)
- Together with the dysfunction of B cells and deregulation of insulin production means that it is inappropriately produced both when eating and fasting.
Why do some T2 DM pts need to supplement with insulin
There is a period of excessive insulin production as more is produced to counteract the insulin resistance, later on the beta cells fail and there is a lack of insulin production.
What are the risk factors of T2 DM?
-Obesity – 80x more likely to develop T2 DM. Adipocytes release pro-inflammatory cytokines.
-Family History – 2-6x more likely if first degree relative has T2 DM
-Ethnicity - Asian, African and Black communities are 2-4x more likely
-Hx of gestational diabetes - 7x increased risk, the children are 6x more likely to develop it later in life.
-Poor diet - low fibre, high GI diet increases risk of obesity which increases risk of T2 DM
-Other: medications, Polycystic ovary syndrome, metabolic syndrome, low birth weight for gestational age
What is gestational DM?
· High glucose levels throughout pregnancy. Can have delivery complications but this type of DM resolves following birth of baby.
· Requires close monitoring & scans by consultant obstetrician throughout and shortly after birth.
What is the difference in pathogenesis of DM1 and DM2?
T1 DM - Autoimmune - B cells that produce insulin are destroyed.
T2 DM - Metabolic - not enough insulin produced due to dysfunction of B cells, or insulin resistance due to failure of the intracellular signalling pathways in cells.
What is diabetes insipidus?
A lack of ADH causing excessive urination and then excessive thirst. Nothing to do with insulin or hyperglycaemia.
What are the symptoms of T1 DM & why?
· Polyuria – excess urination. Glucose in urine causes osmotic diuresis (inhibition of the reabsorption of water) as urine osmotic pressure increases, so kidneys can’t retain the water and the patient becomes fluid depleted.
· Polydipsia – extreme thirst due to fluid depletion
· Weight loss -despite an increase in appetite. The insulin isn’t present to do the anabolic pathway, so the catabolic pathways are used to generate energy and use up the fat stores.
· Fatigue, weakness, dehydration & tiredness.
What is a diabetic ketoacidosis?
Where the body runs out of insulin so the liver begins to break down fats leading to ketone production.
- Increased production of ketones accumulate in the blood so metabolic acidosis leads to a fall in blood pH.
- Can also happen in pts with significant hyperglycaemia (over 11mmol)
Diabetic ketoacidosis is a medical emergency with a 5-10% mortality and is fatal if untreated. What are the symptoms? How is it managed at the hospital?
Symptoms: rapid deterioration, hyperventilation- Kussmail breathing – gasping for air, fruity breath, confusion, loss of consciousness, abdominal pain, nausea, shaking, polyuria, polydipsia.
Tx: insulin given IV, fluids with electrolytes for dehydration.
How is blood glucose monitored?
HbA1c blood test carried out every 3 months to check glycated haemoglobin. (Average lifespan of RBC is 120 days- so 3/12 for accurate diabetic control).
- Ideally below 48mmol/mol or 6.5%
