Diabetes Flashcards
Prediabetes
Blood surgery are higher than usual but not high enough to be diagnosed with type 2 diabetes
O only checks HbA1C
Risk factors
Age
Family history
High bp
Weight
Diet
Physical inactivity
Prevention
Manage weight
Eat healthy and balanced diet
Exercise
Pathogenesis of impaired glucose metabolism
Insulin resistance in muscle and the liver, and impaired insulin secretion by the pancreatic β-cells are the core defects in type 2 diabetes mellitus (T2DM).
β-cell resistance to the incretin ‘glucagon-like peptide 1’ (GLP1) contributes to progressive failure in the function of β-cells, whereas increased glucagon levels and enhanced hepatic sensitivity to glucagon contribute to the excessive glucose production by the liver.
Insulin resistance in adipocytes results in accelerated lipolysis and increased plasma free fatty acid (FFA) levels, both of which aggravate the insulin resistance in muscle and the liver and contribute to β-cell failure.
Increased renal glucose reabsorption by the sodium/glucose co-transporter 2 (SGLT2) and the increased threshold for glucose spillage in the urine contribute to the maintenance of hyperglycaemia.
Resistance to the appetite-suppressive effects of a number of hormones, as well as low brain dopamine and increased brain serotonin levels contribute to weight gain, which exacerbates the underlying resistance.
How much atp does glucose generate when inside cell
30 atp
How does glucose become metabolized
Insulin binds to insulin receptor. This results in GLUT4 being translocated to the cell surface membrane. GLUT4 transports glucose into the cell. In the cell, glucose can be metabolized to produce ATP.
Glucose transporters
GLUT 1-endothelium and erythrocyte,insulin independant,has baseline affinity. Important for glucose transport across blood brain barrier
GLIT 2-kidney and small intestine ,liver,pancreatic beta cells,insulin independent,low glucose affinity
GLUT 3-neurones,placenta,insulin independent,high glucose affinity
GLUT 4-skeletal muscle and adipose tissue,insulin dependent,high glucose affinity
T2DM cause
There is insulin resistance: a problem with the translocation of GLUT4 to the cell surface membrane once the insulin has bound to the receptor.
This results in less glucose being taken up by the cell, leading to hyperglycaemia.
Beta cell dysfunction
Pancreatic B-cells have GLUT-2 receptors. The B-cells take up more glucose (as there is hyperglycaemia), and hence secrete more insulin.
The increased glucose uptake and increased insulin secretion together result in beta cell dysfunction: ability of the beta cells to secrete insulin decreases.
There is a gradient in this pathophysiology.
HbA1c
HbA1c is a type of glycated haemoglobin, a subtype of HbA. It is easier to detect than other subtypes.
HbA1c levels are linked blood glucose levels. Hence HbA1c can be used to measure blood glucose levels.
HbA1c gives an 8 to 12 week idea of mean blood glucose.
Capillary blood glucose test using a lancet.
If > 48 mmol / L , it suggests T2DM.
If between 42 - 47 mmol / L , classed as prediabetes.
Advantages of HbA1C
Good way of assessing mean blood glucose over 2-3 months.
Fasting is not necessary.
Convenient: only a blood sample is required.
Cheap
Disadvantages -If HbA1c is above cut-off, but patient is asymptomatic, patient cannot at that point be diagnosed with diabetes. Having an HbA1c above 48 mmol / mol is only diagnostic if there are symptoms. Symptoms have been present for more than 2 months.
If HbA1c is below cut-off but patient has symptoms, other tests must be conducted.
Cannot be used in patients with abnormal RBC turnover. High RBC turnover will lead to RBCs not accumulating as much glucose on Hb, so can lead to low HbA1c resulting in false negative.
If haemoglobin is dysfunctional, it will not pick up the glucose in the same way, so different values may be obtained.
Does not work well in some groups, such as young children.
Certain medications and conditions (eg: HIV, pregnancy) may interfere with this process.
Metformin
It stimulates AMPK (adenosine monophosphate kinase), which is involved in the translocation of GLUT-4 to the cell surface membrane of myocytes. Therefore there will be greater translocation of GLUT-4 by the myocyte cell membranes, resolving some of the insulin resistance.
Metformin also decreases hepatic glucose output by inhibiting hepatic gluconeogenesis.
However it is not very selective: has many targets and acts on many different tissues.
Main side effects: gastrointestinal. eg: diarrhea
Why is metformin a first line medicine
Broad-target: MPK is present in most tissues, so Metformin has positive effects on the liver, adipose, etc.
May cause modest weight loss: probably due to **gastrointestinal disturbances that occur as a side effect which lead to eating less
May have protective effect against kidney cancer and pancreatic cancer: AMPK has tumour suppressive activity
Glucose metabolism
Glucose converted to Pyruvate by glycolysis
Pyruvate converted to Acetyl coa via link reaction or pyruvate oxidation
