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.
What are other names for prediabetes?
Borderline Diabetes
Impaired Glucose Regulation (IGR)
Non-diabetic hyperglycaemia
Impaired fasting glucose (IFG) together with Impaired Glucose Tolerance (IGT)
What are the symptoms of prediabetes?
Don’t have any symptoms.
If you start to have any symptoms of T2DM it means you have probably already developed it.
List 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 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.
Why implement the NHS diabetes prevention programme?
Many cases of T2DM are preventable.
Strong international evidence that behavioural interventions can significantly reduce risk of developing condition, through reducing weight, increasing physical activity and improving the diet of those at high risk
Diabetes treatment → 10% of annual NHS budget.
What are the aims of the programme?
Long-term:
- Reduce incidence of T2DM
- Reduce incidence of complications associated with diabetes- heart, stroke, kidney, eye and foot problems related to diabetes
- Reduce health inequalities associated with incidence of diabetes
What is the intervention?
NHS DPP has 3 core goals:
- Achieving a healthy weight
- Achievement of dietary recommendations
- Achievement of CMO physical activity
Who is eligible for the NHS DPP?
Individuals eligible for inclusion have ‘non-diabetic hyperglycaemia’ [NDH] defined as → HbA1c 42-47 mmol/mol or a fasting plasma glucose (FPG) of 5.5-6.9 mmol/L.
Blood result indicating NDH must be within the last 12 months to be eligible for referral and only the most recent blood reading can be used.
Only individuals 18+
What are the referral routes into the programme?
- Those who have already been identified as having an appropriately HbA1c 42 – 47 mmol/mol elevated risk level (HbA1c or FPG) in the past and who have been included on a register of patients with high HbA1c or FPG
- The NHS Health Check programme, which is currently available for FPG 5.5 - 6.9 mmol/l individuals between 40 and 74; NHS Health Checks includes a diabetes filter, those identified to be at high risk through stage 1 of the filter are offered a blood test to confirm risk
- Those who are identified with non-diabetic hyperglycaemia through opportunistic assessment as part of routine clinical care
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 all the causes of hyperglycaemia and explain the mechanism of each (check notion)
- Increased glucose Reabsorption
- Decreased glucose Uptake
- Increased Lipolysis
- Inflammation
- NT Dysfunction
- Increased Glucagon secretion
- Increased Hepatic glucose production
- Decreased Insulin secretion
- Vascular insulin resistance
- Decreased insulin Effect
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
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)
What is the primary distribution and function of each GLUT transporter?
- 1
- Primary distributionEndothelium, erythrocytes
- FunctionBasal transport (insulin independent)
- 2
- Primary distributionKidney, SI, liver, pancreatic beta cells
- FunctionLow affinity transport (insulin independent)
- 3
- Primary distributionNeurones, placenta
- FunctionHigh affinity transport (insulin independent)
- 4
- Primary distributionSkeletal muscle, adipose
- FunctionInsulin-regulated glucose transport
What happens if your blood glucose is high, but you are insulin resistant?
- glucose is not taken into skeletal muscle and adipose cells
- glut 1, 2, 3 cells (i.e. endothelium, erythrocytes, kidney, small intestine, liver, pancreatic beta cells, neurones, placenta) will take in lots of glucose
What are the additional functional effect of insulin on the liver, muscle and fat?
- Liver^ Glucose uptake^GlycogenesisDecreased gluconeogenesis and glycogenolysisDecreased lipolysis
- Fat^ Glucose uptake and lipogenesisDecreased lipolysis
- Muscle^ Glucose uptake^ Glycogenesis^ Protein synthesisDecreased 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.
In T2DM liver, fat and 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 (oral glucose tolerance test) - get patient to fast for 8 hrs then give them a 75g oral glucose load, then measure their blood sugar 2 hour after.
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
