CSI 5: Diabetes Flashcards
What is prediabetes?
Blood sugars are higher than usual, but not high enough to be diagnosed with T2DM.
Are at a high risk of developing T2DM.
(Not a clinical term recognised by WHO → Starting to be used more by healthcare professionals and in the media to describe people who are at high risk of T2DM.
4 other names for prediabetes
Borderline Diabetes
Impaired Glucose Regulation (IGR)
Non-diabetic hyperglycaemia
Impaired fasting glucose (IFG) together with Impaired Glucose Tolerance (IGT)
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List 5 modifiable factors that increase risk of diabetes
Smoking
History of high BP
Being overweight, especially with centripetal obesity
Sedentary lifestyle (physically inactive → Not doing enough physical activity; sedentary → sitting or lying down for long periods).
Alcohol
List 5 non-modifiable factors that increase risk of diabetes
Older age; more at risk of white and over 40 OR over 25 and Afro-Caribbean, Black African or South Asian.
Having a parent, brother, sister or child with diabetes
Polycystic Ovary Syndrome (PCOS associated with insulin resistance)
Mental health conditions (e.g. schizophrenia, bipolar disorder, depression)
Antipsychotic medication (risk is quite low)
Roughly what % of people who have diabetes have T2D?
90%
(Can come on slowly (Insidious onset), usually over the age of 40. Signs may not be obvious or there may be no signs at all, therefore it might be up to 10 years before diagnosis
What is the NHS diabetes prevention programme?
Joint commitment from NHS England, Public Health England and Diabetes UK, to deliver at scale, evidence based behavioural interventions for individuals identified as being at high risk of developing T2MD.
What are the long term aims of the NHS diabetes programme
Reduce T2DM
Reduce incidence of complications associated
Reduce health inequalities
Which cells release insulin and which release glucagon?
Beta-cells → Insulin → Converts glucose into glycogen.
Alpha-cells → Glucagon → Converts glycogen into glucose.
What are the core defects in T2DM?
Insulin resistance in muscle and liver
Impaired insulin secretion by the pancreatic Beta-cells
List the 10 causes of hyperglycaemia (RULING HIVE)
Increased glucose reabsorption
Decreased glucose uptake
Increased lipolysis
Inflammation
NT dysfunction
Increased glucagon secretions
Increased hepatic glucose production
Decreased insulin secretion
Vascular insulin resistance
Decreased incretin effect
Mechanism of increased glucose reabsorption
Increased renal glucose reabsorption by sodium/glucose co-transporter 2 (SGLT2) and the ^ed threshold for glucose spillage in the urine contribute to the maintenance of hyperglycaemia.
Mechanism of decreased glucose uptake
Beta-cell failure → less insulin is secreted
Mechanism of increased lipolysis
Insulin resistance in adipocytes results in accelerated lipolysis and ^ed plasma FFA levels, both of which aggravate the insulin resistance in muscle and the liver and contribute to Beta-cell failure.
Mechanism of inflammation
Activates and ^ expression of several proteins that suppress insulin-signalling pathways making the body less responsive to insulin and increasing the risk for insulin resistance.
Mechanism of NT dysfunction
Resistance to appetite-suppressive effect of a number of hormones + low brain dopamine + increased brain serotonin level contribute to weight gain, which exacerbates the underlying resistance.
Mechanism of increased glucagon secretion
insulin inhibits glucagon secretion from alpha cells-over time after lots of insulin is being produced, alpha cells become insulin resistant→ glucagon secretion increases→blood glucose increases
Mechanism of increased hepatic glucose production
increased glucagon levels and enhanced hepatic sensitivity to glucagon contribute to the excessive glucose production by the liver
Mechanism of decreased insulin secretion
Beta-cell failure due to:
- GLP resistance
- Insulin resistant adipose, muscle and liver tissue.
Mechanism of vascular insulin resistance
prolonged exposure to high levels of insulin causes increased vasculature resistance
Mechanism of decreased incretin effect
the incretin ‘glucagon-like peptide 1’ (GLP1) stimulates β-cells to secrete insulin
How is insulin involved in glucose metabolism?
Insulin from the blood binds to insulin receptor on skeletal muscle/adipose cell this induces blood glucose to be transported through the Glut-4 receptor via facilitated diffusion into the skeletal muscle/adipose cell glucose is converted to pyruvate via glycolysis pyruvate is converted to acetyl CoA via the link reaction/pyruvate oxidation acetyl CoA is converted to ATP (C) via the Krebs cycle and oxidative phosphorylation when inside the cell, 1 molecule of glucose can gene rate ~30ATP
Where are GLUT-receptors not found?
Kidney and SI
How do GLUT and SGLT receptors transport glucose into our body cells, respectively?
GLUT - Facilitated diffusion
SGLT - Active Transport (glucose transported into luminal epithelial cells in the kidney and small intestine)
Primary distribution and function of GLUT1
Endothelium and erythrocytes
Basal transport (insulin independent)
Primary distribution and function of GLUT2
Kidney, SI, liver, pancreatic beta cells
Low affinity transport (insulin independent)
Primary distribution and function of GLUT3
Neurones and placenta
High affinity transport (insulin independent)
Primary distribution and function of GLUT4
Skeletal muscle, adipose
Insulin-regulated glucose transport
What happens if your blood glucose is high, but you are insulin resistant?
Glucose not taken into skeletal muscle and adipose cells
GLUT 1/2/3 cells take in lots of glucose
What are the functional effects of insulin on the liver
Increases glucose uptake
Increases glycogenesis
Decreased gluconeogenesis and glycogenolysis
Decreased lipolysis
Functional effect of insulin on fat
Increased glucose uptake and lipogenesis
Decreased lipolysis
Functional effect of insulin on muscle
Increased glucose uptake
Increased glycogenesis
Increased P. Synthesis
Decreased protein catabolism
What are the core impairments of T2DM?
Insulin resistance: Liver, fat and muscle don’t respond to insulin as well. This could cause a stage where lots of insulin is produced (hyperinsulinemia).
Beta-cells eventually become worn down, so they don’t produce as much insulin.
There isn’t enough insulin produced to overcome the resistance, so person becomes diabetic.
Fat, liver, muscle tissue become insulin resistant and beta-cells are unable to produce enough insulin to compensate so increased BG AND FFAs
What are the differences in pathogenesis between T1DM and T2DM?
T1DM → Very little/no insulin produced at all
T2DM → Little insulin produced + insulin resistant cells.
How is post-prandial glucose tested?
OGTT - get patient to fast for 8 hrs then give them a 75g oral glucose load, then measure their blood sugar 2 hour after.
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What is the difference between impaired fasting glucose vs. impaired glucose tolerance?
Impaired fasting glucose: predominantly hepatic insulin resistance leads to continuous glucose output from the liver
Impaired glucose tolerance: predominantly muscle insulin resistance plus impaired post-prandial insulin release results in poor cellular glucose uptake.
Impaired fasting glucose and impaired glucose tolerance can occur together or separately,
one could occur first
What are the 3 symptoms of T2DM (can also be T1DM)?
Polydipsia- increase in thirst
Polyurethane - frequent urination
Polyphasic - rise in appetite
How can you diagnose T2DM?
Symptoms + 1 red glucose range test
OR
No symptoms + multiple red glucose range tests
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What is the renal threshold for glucose (RTG)?
The proximal tubule can only reabsorb alimited amount of glucose (~375 mg/min),
known as the transport maximum.
When the blood glucose level exceeds about 60–180 mg/dL, the proximal tubule becomes overwhelmed and begins to excrete glucose in the urine. This point is called the renal threshold for glucose (RTG).
What is the HbA1c test?
HbA1c → Hb that has been glycosylated.
- this process occurs non-enzymatically and can occur with the monosaccharides glucose,
fructose, and galactose (although glucose least easily) - formation of HbA1C occurs proportionately to plasma glucose levels
- therefore, HbA1C levels can be used to diagnose and monitor diabetes
What are the advantages of the HbA1c test
Takes into account blood glucose for 2-3 months
Easy to measure (fasting is not needed for A1C assessment and no acute perturbations (e.g., stress, diet, exercise) affect A1C)
Cheap
What are the disadvantages of the HbA1c test
Only an approximate measure.
Not reliable in certain conditions e.g. Pregnancy (amount of Hb changes/rapid changes in glucose management) → Renal failure + Sickle cell
What is used for first-line treatment of T2DM and how does it work?
Metformin
Reduces the amount of sugar your liver releases into your blood. It makes your body respond better to insulin by stimulating GLUT-4 translocation
It doesn’t cause weight gain, unlike some other diabetes medicines
Lower risk to hypoglycaemia
Best to take with a meal to reduce the side effects
What are the most common side effects of Metformin?
Sick, diarrhoea, stomach-ache and going off your food.
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What is the behavioural insight approach?
Approach that uses knowledge of how and why people behave, to encourage positive behaviour change.
Behavioural insights consider all aspect of behaviour (e.g. psychology, social anthropology and behavioural economics) and acknowledge the importance of the fast and intuitive automatic system driving behaviour.
Behavioural insights are most helpful where individuals want to make positive behaviour changes but struggle to do so.
- EAST Framework for behavioural change:Untitled Database
