diabetes Flashcards
what is diabetes
Diabetes is a disease of the pancreas that sits underneath the stomach and the liver.
- When you eat something and it hits your stomach, the pancreas detects these changes in glucose level and will secret insulin to bring the level back down if the concentration is high
- If blood glucose goes down the pancreas secretes glucagon, which increases endogenous blood glucose levels through glycogenolysis.
what are the complications associated with diabetes
- The leading cause of heart disease- is heart attack from a patient who has uncontrolled diabetes to avoid this need to have tight glycaemic control.
- Leading cause of blindness in ageing people- here you have retinopathy and the hardening of capillaries
- Also, the leading cause of renal failure is- the disruption of amyloid and the destruction of kidney function.
- Ulceration and amputation
what are the alpha and beta cells
Within the pancreas, there are alpha and beta cells
- There is a single islet of Langerhans and within these cells are a ball of red cells which is the insulin-producing beta cells
- The beta cells are insulin-producing and the alpha cells produce glucagon so when your blood glucose drops, glucagon is released and tells your liver to release glucose
- When your blood glucose increase, insulin is produced in the beta cells
- The alpha and beta cells are sensitive to glucose
- In patients who have type 1 diabetes the beta cells are destroyed
what is T1D
- The islet of Langerhans is almost undetectable, you don’t see any of the red cells which make insulin.
- The black dots are the cells of that patient’s immune system
- They are moved through the body and moved through all the other cells in the pancreas and they have targeted the insulin-producing cells
- Destroying the insulin-producing cells in an autoimmune manner
- Don’t understand what are the exact triggers of T1D but once triggered then it doesn’t stop and you get a destruction of the insulin-producing cells and it is lifelong.
what is T2D
- The beta cells are still there but they are usually struggling against insulin resistance, obesity, and high circulating levels of fat that affect the production of insulin from the pancreas.
- The structure of the islets is disrupted
- In patients who have uncontrolled T2D the pancreas will try to make more insulin to try and get it to get into the healthy range
what is the difference between t1D and t2D
Both types of diabetes are the destruction of beta cells in Type 1 it occurs quickly wheras I type 2 it happens over a period of time
Type 1 need to manage by educating patients how to inject themselves and in type 2 if discovered early enough can try and get the beta cells back by educating with lifestyle intervention or drugs such as metformin
what are the characteristics of T1D
- Insulin-dependent diabetes mellitus (IDDM)
- Early/juvenile onset, 5-10% of diabetes
- Autoimmune destruction of b-cells.
- Dependent on insulin injections from an early age.
- WHO 422 Million, ~10% with Type 1 Diabetes.
how do you test your blood glucose level
Done by measuring blood glucose by finger pricking, calculating carbohydrates, injecting insulin, need to see if you need to make any adjustments. If not cautious can get hypo/hyperglycaemia which can produce complications if not controlled.
Can be frustrating because lots of fingerpicking (it hurts) and there is an increased risk of infection.
what is the basal-bolus regime
- Basal-bolus regime is a combination of insulin injections which will help give the best chance of a normal, healthy blood glucose range.
- Short-acting insulin injections are administered with mealtimes and the long-acting which you inject that last up to 12-24 hrs
- Not easy to master trial and error to try to mimic the blood glucose level of a healthy pancreas
what are the criteria of the basal-bolus regime and when is this an exception for young children
Basal Bolus Regime
- All children and young people should be offered a basal-bolus regime from the time they are diagnosed
Except:
- If a child needs such a small dose of insulin that it is too difficult to get the dosing right
- If it is felt inappropriate to expect a child <5yrs to have 4 or more injections a day
what are the advantages of the basal-bolus regime
flexible
freedom
tighter control
what are the disadvantages of basal bolus regime
more injections
commitment
young children
what is carbscount
Carbscount is a book which allows patients to understand how much insulin they need depending on what they have eaten
- Done by giving them a book or putting them in a structured education programme
what is mysugr
digital technologies which are easy to access as it is done through your phone and don’t need to see HCP all the time and you can just record everything on your phone
-aimed at younger people
what is glucose buddy
Ones that mimic structured programmes
E.g. Glucose Buddy
Available on your phone and it is about peer support, talking with other people about your experience, struggles etc
Informal way to connect with people eg putting up recipes which are low carb
what is the new technologies of measuring glucose level
Finger prick testing but more and more patients are able to use new technologies instead of having to do a finger prick testing and getting test strips etc
For example:
Dexcom G6 is a glucose sensor which goes into your abdomen and you have a little PDA that will tell you what your blood glucose levels are but now you attach it and sync it with your phone/smartwatch. Improves quality of life and has alarms which will tell you if you are hypoglycaemic. Removes worry from parents if the child is hypoglycaemic as it sets off an alarm so no need to worry whether or not a child will go into a diabetic coma.
Another example is the freestyle libre
- Are a glucose sensor and syncs it to a phone
give an example of an artificial pancreas
New technologies
For example, Medtronic is like an artificial pancreas
Links together the glucose sensor on an insulin pump to give patients a completely free pancreas. The pump adapts to insulin and avoids complications
what are some of the procedures for diabetes
- Thinking of ways to replace insulin-producing cells
- Islet transplants and the challenges of immunosuppressants. In the syringe, there are isolated human islets of Langerhans from a donor and they’re injected into the patient.
- Viacyte- little pouches you can put cells into and transplant them into the abdomen. No need for immunosuppressants because the cells are protected from the immune system.
o You have your little pouch and you’ve got your insulin-producing cells. Some of these are stem cells some of them are donated cells
o They can release insulin out and glucose can come in.
o There is newer tech that allows the cells to be modified so that the blood supply can go inside the little pouch
o So you get a replacement pancreas in the form of a little pouch that’s vascularised and will be able to respond to changes in your blood glucose - This tech is used in the form of CRISPR tech- Gene editing. Being able to modify the contents of the cells by slicing tiny sections of DNA. The aim is to try and avoid the immune response in T1D that destroys the insulin-producing cells
what are some of the Challenges to understanding the immunology of T1D
- Monoclonal antibodies- the first drug to treat the immunology of T1D
- In T1D, the islet doesn’t show a lot of insulin-producing cells
- The green cells are the alpha cells (glucagon-producing cells) and there is a hollow bowl where the insulin-producing cells used to be
- Once the beta cells started to die there was no way of slowing the process down
how to overcome these challenges of the immunology of T1D
- Monoclonal antibody Tzeild: Teplizumab which slows down the progression of T1D
- When the disease starts there is a period where you see the loss of beta cell function and you start to see a loss of first phase insulin release-like pre-diabetic (hard to detect it)
- Now we know there are which antibodies to test for and make a monoclonal antibody to slow down the process.
- Helps slow down the beta loss of insulin-producing cells.
list the signs and symptoms of diabetes
- Polydipsia- an increased thirst to try to flush out high glucose
- Polyuria- increased urination caused by hyperglycaemia
- Polyphagia- Increased hunger. Not getting the energy from what you are eating. If you don’t have insulin can use the glucose which becomes stored as energy
- Blurred vision- can be one or both eyes occurs by changes in osmotic pressure in the eye from living in high concentrations of glucose
- Dizziness- dehydrated and low bp due to high level of glucose
- Fatigue- lack of energy if you don’t have insulin working properly don’t have energy, you can’t, burn glucose as energy it can take up into your muscles you as cant store glycogen in the liver don’t have the energy to complete tasks
Symptoms that are more common in adults
- Genital itchiness from yeast infections and general infections and thrush in a short period of time as you are peeing out high glucose levels
- Slow wound healing- nerve damage, infections
what are the 3 diagnostic tests for diabetes
- A random plasma glucose concentration of >11.1mmol/l should be around 4-6mmol/l
- Fasting plasma glucose concentration of >7mmol/l should be around 4mmol/l
- The plasma glucose concentration of >11.1mmol/l 2 hours after oral glucose tolerance. Should be around 4-6mmol/l after 2 hours
how do you do the random blood glucose test
- Can do them at your GP/hospital/pharmacy
- Can come in and do a finger prick test or draw blood and have a full analysis of them
- If it comes over 11.1mmol/l = diabetic
how do you do the fasting plasma glucose test
- No food or drink 8-12 hours
- Take a blood test sample again
- If over 7mmol/l the = diabetic
how do you do The plasma glucose concentration of >11.1mmol/l 2 hours after oral glucose tolerance.
- No food or drink 8-12 hours prior to the test
- Have a glucose drink of 75g of glucose
- Take a blood test 2 hours later if still above 11.1mmol/l = diabetic
what is the final diagnostic test and what does it show us
HbA1c level (glycosylated haemoglobin)
If it has a lot of sugar molecules stuck to the haemoglobin then diabetic
- Tells us how your glucose regulation over the last 3 months
what are the steps you need to do before insulin injecting
Everyone’s journey is different because the metabolism is different
Have to manage your metabolism by injecting insulin if not controlled then get complications
finger prick test
calculate carb count
inject insulin
what is insulin
- All insulin in UK is 100iu/ml
- Human – genetically engineered in yeast or E.coli you know how active it is so there is stability
- Range of activities, different combinations
what are the different regimens of insulin
Once daily injection – a mixture of very long and very short-acting analogues
- Twice daily injections – a mix of short and long-acting insulins (morning and evening)
- Multiple daily injections (before meals) of short-acting insulin and one daily injection of long-acting insulin (Basal Bolus)
-Insulin pump – short-acting insulin only
list the different types of insulin injections
- Short Acting – Lispro, Aspart, Novorapid, Glulisine
- Intermediate – NPH/isophane (pre-mix of NPH/regular)
- Long acting – Glargine, Detemir, Lantus, Levimir
what are the two factors when considering which injection to give to someone
speed of onset and duration are the key factors to consider when giving insulin
what is Tresibar
Smooth onset of action
Approx. 25 hours half life
42 hours duration of action
what do you have to consider when injecting insulin
When you are injecting insulin your body doesn’t know that the insulin is already there
Have to consider how long the long-acting insulin before injecting short-acting because might give too much insulin and get hypoglycaemia which means that blood glucose is low and can drop into a diabetic coma
what type of regimen do you start when you are first diagnosed with diabetes
When first diagnosed with diabetes get onto the basal-bolus regimen
what conditions should a child/young person not be offered the basal bolus regimen
- All children and young people should be offered a basal-bolus regime from the time they are diagnosed
Except:
- If a child needs such a small dose of insulin that it is too difficult to get the dosing right
- If it is felt inappropriate to expect a child <5yrs to have 4 or more injections a day
how do you calculate how much insulin to give
Insulin Injections: How much insulin?
10g of carbohydrate = 1 unit of insulin
10g of carbohydrate
= 1 carbohydrate portion (CP)
= 1 unit of insulin
Carb count- a handbook which guides new diagnosed T1D how to calculate their carb count
what is DAFNE
Online
- Helps us see patterns over the course of weeks and then can do trial and error
- Need to use a mixture of long and short to try and adjust the blood glucose level
what is mysugr
- Helps the user also keep a record of the glucose blood sugar level concentration
- Has got a gamification element as it allows users to collect points and set personal goals
what is glucose buddy
- A network where you talk with other types 1 diabetic to share their experience and they can come up with recipes or what things that they are doing that works/ doesn’t work for them
Finger Prick BG Monitoring
38 meters on the market
-Minimum of 5 tests per day
-More frequent testing with exercise or illness
If you are on the basal-bolus regime then you may have to take more finger-prick tests approx. 10-15 finger pricks
Finger pricks BGM: Advantages
- Helps determine which foods are best for individual control
- Helps inform patients and doctors re injection regimes
- Increases understanding and reduces anxiety about hypos
- Vitally important for undertaking dangerous tasks (driving, operating machinery etc)
Finger pricks BGM: Disadvantages
Requires willingness and commitment
- It hurts
- Expense to the NHS
- Anxiety about blood glucose control and general health
- can cause higher risks of infection
Continuous Glucose Monitoring Systems
There are 3 type of continuous blood glucose monitoring
- Real time Continuous Glucose Monitors
- Retrospective Continuous Glucose Monitors
- Flash Glucose Monitors
Continuous Glucose Monitoring Systems
- Originally to PDA but now to a phone/smartwatch
- Shows you continuous reading
- When you are in the red zone will alarm you and will let you know you are hypo
- The trend arrows move all the time showing where your glucose is going either up/down. - - Want the arrow flat
- Can link to other people’s phones eg useful for parents w a child
An Example is Dexcom G6
No PDA
- Done on your phone
- Painless procedure
- Work for 10 days and gives reading every 5 mins
- Abdomen back of your arm or lower back region
- Can get it on prescription
Simple Auto-applicator
Slim, water proof 10 day sensor
High, low and “Urgent, low soon” alerts
3 options for sensor placement
Use in pregnancy
Indicated for two years or older
CGMS: Advantages
- All the advantages of SMBG, without the pain!
- Hypo alarms for safety
- Linked to parents’ phones/devices for safety
- Downloadable data for both patients & health teams
Continuous glucose monitoring systems
Recommended for children and young T1D who have
- Frequent severe hypoglycaemia
- Impaired awareness of hypoglycaemia
- Inability to recognise, or communicate about, symptoms of hypoglycaemia
Symptoms of hypoglycaemia include:
- Dizzy
- Clammy
- Confused
If you have had hypoglycaemia for a long time you may become desensitized to the symptoms so there is a risk of you falling into a diabetic coma so it may be strongly advised to get continuous glucose blood monitoring
When would you consider to go on Consider ongoing real-time CGMS for:
- Neonates, infants and pre-school children
- Children or young people undertaking high levels of physical activity
- Children and young people with comorbidities (e.g anorexia), or receiving treatments e.g. corticosteroids) that can make BG control difficult
What are the challenges of CGMS:
Not currently funded by the NHS for most patients
- Expensive to buy privately
- Time delay between interstitial and blood glucose levels
- Provides large amounts of data
what is flash glucose monitoring
- A sensor that goes into your phone and syncs it to your phone
- Scan the phone on the patch area and will give you the reading
An example of flash glucose monitoring
Abbot Freestyle Libre sensor
- 14-day sensor, scanned by a handheld reader
- Partial funding support in some areas of the NHS
- Does not have hypo alarms
The latest flash glucose monitoring is freestyle libre 3
- Linked to smartphones
- Reading every minute (CGMS)
- More affordable
- Smallest, thinnest sensor
- Accurate 14-day sensor life
- Now has hypo alarms
Insulin pump therapy
Adults and children >12 yrs provided that
- Attempts to achieve target HbA1c with MDI (basal/bolus) result in disabling hypoglycaemia
- If HbA1c levels remain greater than 8.5% (69 mmol/mol) on MDI despite a high level of care
When is the insulin pump advised
Children under the age of 12 yrs when:
- MDI therapy is considered impractical or inappropriate
- Young children on pumps would be expected to trial MDI Between the ages of 12-18yrs.
What are the advantages of insulin pump
Avoiding insulin injections
- Greater freedom and flexibility
- Fewer large swings in blood glucose
- Improvements in HBA1c
Insulin pump disadvantages
Checking blood glucose every 3-4 h
- Changing infusion site every 48-72 h
- Know your carbs!
- May take several months to optimise
An example of an insulin pump is Medtronic (minimed 670G System) features
Artificial pancreas system
-Advanced insulin pump
- Sensor talks to the pump
Features of smart guard tech
- Variable personalised rate of insulin 24 hours a day
- Automatically adjust insulin delivery and corrects blood glucose levels every 5 minutes
- Automatically corrects highs and suspends when low
- Anticipates blood glucose changes and adjusts insulin delivery automatically
- Advanced Bolus WizardTM
Features of guardian 4 tech
- Seven-day continuous wear
- No finger pricks required
- 94% of users prefer this system to their previous device
name other devices of insulin pump
Other examples are tandem, camdiab, CamAPD FX, omnipod
what are the follow-ups after a pancreas transplant
>
90% are simultaneous pancreas and kidney transplant Lifelong immunosuppressant therapy Cyclosporine/tacrolimus/sirolimus, Azathioprine/mycophenolate mofetil Corticosteroids- to dampen down the immune system to avoid rejection
what is islet transplantation and what do you need
Lifelong immunosuppressant therapy
- Steroid free immunosuppression to allow beta cell to function
- tacrolimus/sirolimus
- Alemtuzumab, monoclonal antibodies
Islet transplantation advantages:
- Improved HbA1c
- Improved quality of life
- Loss of fear of hypoglycaemia
- Zero instances of hypoglycaemia
Islet transplant Disadvantages
- Islets are in desperately short supply
o New sources of insulin-producing cells are required. - Transplanted cells run out of steam
o Enhance and protect the function of transplanted cells
what is viacyte
Is like a pouch where it keeps the islet cells which contain the beta cells which are insulin-producing cells which are implanted near the abdomen underneath the surface of the skin and this device allows it to act like a normal pancreas. It is kept in a pouch to avoid the immune system from attacking the beta cells containing the insulin.
what is viacyte mad up of
A key component of ViaCyte’s devices is composed of a medical-grade plastic called expanded polytetrafluoroethylene (ePTFE)
- it is a polymer that can control the pore size at a molecular level and the insulin-producing cells are stored in a semi-permeable membrane and the blood vessels sit outside if the pouch
what are the three type of viacyte pouches available
- PEC-ENCAP is for T1D
- PEC-Direct is for uncontrolled high risk T1D
- PEC-QT is for insulin-dependent diabetes
what is the features of PEC-ENCAP- ALL TYPE 1 DIABETES
- Semi-permeable barrier- just small molecules such as insulin, oxygen, exchange gases can go through the pouch not blood vessel as it is too big
- No immunosuppressants
- Stem cell-derived
- Pancreatic precursors
what are the features of PEC-DIRECT- Type 1 patients with the highest risk of acute, life-threatening complications
- Permeable barrier
- Allows blood vessels to enter
- Improved, rapid engraftment
- Requires immunosuppressants
- Quicker then PEC-ENCAP
what People who are suitable for PEC-DIRECT
those who are:
- Hypoglycaemic unawareness
- Extreme glycaemic lability
- 140,000 USA and Canada waiting
- Unlimited, consistent supply-strength
what are the features of PEC-QT- All patients with Type 1 and insulin-dependent Type 2 Diabetes
-Experimental technology
-CRISPR-modified cells
- Permeable barrier
- Immune Evasive
PEC-QT Patients:
- T1D
- Insulin-dependent Type 2
- CRISPR technology
CRISPR Technology: Gene Editing
- Changes the original stem cells
- Uses Cas9 enzyme to find the sequence and uses gene editing
what are the features of PEC-QT
- Gene-edited pluripotent human stem cell line
- Differentiated into pancreatic endoderm cells
- Specifically engineered to avoid destruction by the patient’s immune system
- The same type of device is used for PEC-Direct
