Diabetes Flashcards
1
Q
Diabetes is the first non-infectious disease that is increasing at epidemic rates. true or false?
A
True
2
Q
What are the 7 types of diabetes?
A
- Type 1
- LADA - latent autoimmune diabetes in adults
- MODY - maturity onset diabetes of the young
- Type 2
- CF related
- Gestational
- Drug induced
3
Q
What is Type 1 diabetes?
A
• Typically develops as a child or young adult • Autoimmune destruction of pancreatic beta cells • Sudden onset usually associated with rapid weight loss
4
Q
What is LADA?
A
1.5
(Latent Autoimmune diabetes in adults) • Gradual autoimmune destruction of pancreatic beta cells • Commonly presents with a slower onset in patients >30 yrs old • NOT linked to insulin resistance
5
Q
What is MODY ?
A
• Hereditary condition - autosomal gene mutation • Ineffective insulin production • Commonly presents with a slow onset in patients < 45 yrs old
6
Q
What is Type 2 diabetes?
A
• Typically affects people > 45 yrs old • Insulin resistance and relative insulin deficiency • Slow onset often associated with patients who are overweight
7
Q
What drugs can induce diabetes?
A
Steroids, thiazides, statins, beta-blockers, atypical antipsychotics
8
Q
Does metformin come with a risk of hypoglycaemia?
A
No as it does not increase insulin
It only increases insulin sensitivity
9
Q
What is polydipsia?
A
Being thirsty
10
Q
If there are basal crackles in the lungs, what could that indicate?
A
Infection
11
Q
What do you want a postprandial blood glucose to be?
A
<10 mmol/L
12
Q
What does glucagon do?
A
The pancreas releases glucagon when the concentration of glucose in the bloodstream falls too low. Glucagon causes the liver to convert stored glycogen into glucose, which is released into the bloodstream
13
Q
Where is insulin made?
A
Beta cells of pancreatic islets
14
Q
What does insulin do?
A
Counteracts high blood glucose by promoting absorption of glucose into liver, fat and skeletal muscles
Inhibits glucose production and secretion from liver
15
Q
What is gluconeogenesis?
A
Production of glucose
16
Q
What is glycogen?
A
Polysaccharide of glucose
Main storage form of glucose in the body
Chains of glucose residues
17
Q
What is glycolysis?
A
Breakdown of glucose
18
Q
What is glycogenolysis?
A
Breakdown of glycogen (chains of glucose residues) into individual glucose
19
Q
What effect do ketones have on the pH or urine and blood?
A
Acidic so decreases pH
20
Q
Do you get DKA in type 2?
A
No- you usually get hyperosmolar hyperglycaemia state
21
Q
What is DKA?
A
Diabetic ketoacidosis (DKA) is a dangerous complication faced by people with diabetes which happens when the body starts running out of insulin.
Medical emergency
Results in:
- Increased glucose production
- Increased glycogen breakdown (to glucose)
- Decreased glucose breakdown
Results in hyperglycaemia
Also results in:
- Increased lipolysis to form free fatty acids
- These go to the liver to form ketones
- Ketones are acidic and lowers pH of urine and blood
22
Q
What is the treatment for DKA?
A
• Fluid replacement
– restoration of circulatory volume
– clearance of ketones
– correction of electrolyte imbalance
• Continuous IV Insulin infusion
– to inhibit gluconeogenesis and lipolysis
– to facilitate the uptake of glucose into cells
• Start SC insulin once out of ketoacidosis
Monitor pH using arterial blood gases
May need intensive care
23
Q
What are the aims of Type 1 diabetes treatment?
What are the complications of this condition?
A
- To replace insulin and mirror natural insulin release profiles
- To prevent DKA
- Want to prevent hypo and hyperglycaemia as we want to reduce the complications: -
- Microvascular (retinopathy, nephropathy, neuropathy- numbess, tingling)
- Macrovascular due to protein glycosylation (cardiovascular disease, CKD, stroke, MI).
The problem is that tight control of diabetes on its own will not reduce macrovascular complications. Lifestyle (diet and weight loss), measuring their QRISK to determine cardiovascular risk so we can then do something about this.
- Diabetic foot
- Increased susceptibility to infection (impaired immune response)
24
Q
What are the two types of neuropathy?
A
- Sensory neuropathy - numbness, tingling, neuropathic pain
* Autonomic neuropathy – impotence (inability to get an erection), GI disturbance, postural hypotension
25
What can lead to a diabetic foot?
Peripheral vascular disease
Neuropathy
26
What are the HbA1c level targets for Type 1 diabetes?
Support adults with T1DM to aim for a target HbA1c level of 48 mmol/mol (6.5%) or lower, to minimise the risk of long-term vascular complications.
27
What are some factors to take into account when agreeing with a patient their HbA1c levels?
Agree an individualised HbA1c target with each adult with T1DM,
taking into account factors such as, the patient’s daily activities,
aspirations, likelihood of complications, comorbidities, occupation &
history of hypoglycaemia
28
What do you need to ensure in Type 1 diabetics when aiming for a HbA1c target?
That it is not accompanied by problematic hypoglycaemia (have a balance)
29
What are the target blood glucose values for Type 2 (before and after meals)
4-7 mmol/L fasting
<8.5 mmol/L post prandial
30
What is post prandrial blood glucose according to NICE? (time)
At least 90 minutes after meals
31
What are the target blood glucose values for adult Type 1 (waking, before and after meals)
5-7 mmol/L upon waking
4-7 mmol/L fasting
5-9 mmol/L post prandrial
32
What are the target blood glucose values for < 18 years Type 1 (waking, before and after meals)
4-7 mmol/L upon waking
4-7 mmol/L fasting
5-9 mmol/L post prandrial
33
What are the two forms of insulin?
Human insulin
Analogues
34
What are the advantages of analogues over human insulin?
- More reliable absorption rates
- Less variability
- Can be injected immediately before food.
- Less risk of nocturnal hypoglycaemia
- Post prandrial glucose control is more effective
35
When would a patient need to inject human insulin when they want to eat?
What is the risk of this?
15-20 minutes before food
If they decide they are not hungry, the patient can get hypoglycaemia
36
What do NICE guidelines say about choosing analogue or human insulin?
Human insulins should be used first, however if the patient struggles and condition is not being controlled, use an analogue
In practice, you use a lot more analogues
37
What do you want from an insulin regimen?
Mix of short and long acting together
You want a profile that mimics a healthy person's endogenous insulin profile
e.g. short acting for meals and long acting at night to mimic background insulin
38
What are most insulin preparation strengths and why are some now available in higher strengths?
Most are 100 units/mL
However due to insulin resistance, the amount of insulin needed is higher
39
1. What are insulin analogues?
2. What is the structure change for lispro?
3. What is the structure change for aspart?
1. Structure of insulin is modified to change the PK of insulin.
VERY FAST ACTING :
2. Lysine and proline at positions 28 and 29 of the beta chain are reversed
3. Aspartate REPLACES proline at position 28 of beta chain
40
Name the fast acting human insulins
Actrapid
Humulin Soluble
41
Name the intermediate acting human insulins
Insulatard
Humulin Isophane
42
Name the very fast acting analogue insulins
Lispro
Aspart (Novorapid)
43
Name the long acting analogue insulins
Glargine (lantus)
Detemir
44
Name the very long acting analogue insulin
Degludec
45
What is the mix of a short acting and intermediate/long acting insulin regimen called?
Basal bolus
46
What education is necessary for Type 1 diabetics?
* Blood glucose monitoring- signs of hypoglycaemia and DKA
* Lifestyle
* Diet - carbohydrate counting
* Exercising and insulin requirements
* Driving, other occupations
* Insulin passport and sharps disposal
* Travelling and storing insulin
* How they manage their condition. How to administer insulin, when to measure their blood glucose, symptoms of hypoglycaemia and what to do.
* Should inject thigh or stomach (stomach is faster). Rotate injection site to prevent fat accumulation- if fat builds up in that area, absorption would not be good. It takes 2-3 months to recover from that fat build up.
* Make sure you know what brand insulin they are on
* - DAFNE or other structured education programmes
47
What are the counselling points for a patient injecting insulin?
– Rotating sites to prevent lipohypertrophy which can
affect the absorption of insulin
- Can take 2-3 months to recover from fat build up
– Abdomen is fastest absorption, arms intermediate
absorption, thighs low absorption
- Injected at 90 degree angle
- Change needle each time you inject
48
What is carbohydrate counting?
Per CP, how many units of insulin does a person start off with to reduce hyperglycaemia risk?
```
• Patients are taught to do carbohydrate
counting
• 10grams of carbohydrate = 1CP
• Most people start using 1 unit of insulin for
every CP to reduce chances of
hyperglycaemia.
• But can vary from 0.5-4units / 10gram of
carbohydrate
```
49
What are structured education programmes for T1DM?
DAFNE (dose-adjustment for normal eating) or DESMOND.
Offer this programme 6-12 months after diagnosis. If they have not done this within a year, offer it at any time that is clinically appropriate
Gives patients the skills to administer right amount of insulin for the amount of carbs you eat
50
How is insulin therapy started in Type 1 DM?
What is the honeymoon phase and how does that affect insulin dose?
What about in illness?
* Approx 0.5 units kg/day to work out how many units and then split it depending on percentages
* Basal bolus regime (2 short acting dose, 1 long acting dose)
* 30-50% basal insulin
* Rest is divided over meals
* Honeymoon phase where pancreas produced some insulin, and the dose can be reduced to 0.2-0.5 units/kg. However, this is only short term.
* During illness and adolescents in growth phase, this may increase to 1-1.5 units/kg
51
How much does 1 unit of insulin decrease the glucose levels?
What does this depend on?
By 2-3 mmol/L
But this depends on sensitivity
52
What do you need to consider when making insulin adjustments?
Adjust insulin by 10-20% each time
Should base it on patterns that develop over 2-3 days, not just by one reading
53
When do you adjust short and long acting insulins?
Depends on the situation. If fasting glucose is high, need to adjust long-acting as basal insulin is not being controlled. If glucose levels are high before a meal, you increase short acting.
54
What usually happens to people's weight when they go on insulin?
Increases
55
How is insulin stored before and during use?
Unopened insulin must be stored in the fridge
Insulin in use can be kept at room temperature for up to one month
56
What are the signs and symptoms of hypoglycaemia (in two classes)?
1. Autonomic symptoms
• Tremor, sweating, palpitations, hunger
2. Neuroglycopenic symptoms
• Atypical behaviour, visual disturbances, speech
difficulty, drowsiness
57
How do you avoid hypoglycaemia?
- Don't miss meals
- Take insulin at recommended doses
- Moderate alcohol intake and do not drink on an empty stomach
- Always carry glucose, snacks and meter
- May need to reduce insulin doses before and after exercise
- Do not drive if blood glucose < 5 mmol/L
58
How often should a type 1 get their HbA1c measured?
Every 3-6 months
59
How often should a patient with type 1 measure their blood glucose?
At least 4 times a day - before meals and bedtime
60
How often should a type 1 get checked for complications of diabetes e.g. diabetic food and retinopathy?
Annually
61
What are the potential issues in managing type 1 diabetes in terms of the patient?
- Fitting in with lifestyle e.g. at school, sports
- Adherence
- May not like the weight gain
- Eating habits can vary
62
What are insulin pumps and the advantages of them?
* Battery-driven syringe pump
* Fine plastic cannula terminates in sub.cut. implanted catheter
* Short-acting analogues
* Continuous basal insulin infusion & patient-activated bolus doses at meal times
Don't have to carry around needles all the time and is discrete
Reduces need for injection
Can modify doses on the device
Good for children
63
What kind of patients are insulin pumps appropriate for?
▫ Recurrent hypoglycaemia
▫ Marked morning glucose rise despite optimum multi-injection
regimen
▫ Repeated/unpredictable hypos despite optimum multiinjection
regimen
▫ HbA1c levels have remained high (>69 mmol/mol) despite
MDI therapy and a high level of care.
64
What form of risk assessment should you do in Type 2?
QRISK - prediction risk for CVD OVER NEXT 10 YEARS
> 10 % - Primary prevention with a statin is indicated
65
What is the aim of therapy in Type 2?
- Control of hyperglycaemia without hypoglycaemia
Tighter control means fewer complications
- Reducing risk of micro and macrovascular complications
- Maintaining BP and cholesterol - adding in a statin
66
What is the HbA1c targets in Type 2?
<48mmol/mol (< 6.5%) for patients on
lifestyle or monotherapy with a medication
with a low risk of hypoglycemia e.g.
metformin
<53 mmol/mol (<7.0%) for patients on a
monotherapy associated with the risk of
hypoglycaemia e.g. gliclazide
67
At what HbA1c level in Type 2 would lead to intensification of treatment?
> 58mmol/mol (>7.5%)
68
What tests and monitoring should you do in Type 2?
* Blood glucose
* Lipid levels
* HR
* Diabetic foot test and nerve response test
* 24-hour blood pressure monitoring. Should be <140 (or more aggressive 130 systolic if kidney/eye/cerebrovascular damage). NICE says to repeat BP in 1 month if higher than 150/90
* LFTs
* FBC (Us+Es), albumin in the urine as the patient may have microalbuminuria (sign of reduced kidney function)- no need to test for ketones because it is Type 2
* QRISK
Especially important to monitor renal function if patient is on antihypertensive treatment e.g. ramipril
Monitoring needs to be done after each increase of dose
69
What is first line in Type 2?
Standard release metformin
70
What are the alternative first line treatments if metformin is not tolerated/contraindicated?
- DPP-4 inhibitor
- Pioglitazone
- Sulphonylurea
71
When would blood glucose monitoring be recommended in Type 2?
Self monitoring is not routinely offered unless patient is on insulin/ if recurrent hypoglycaemic/if at risk of low blood sugars whilst driving or operating machinery.
Or if pregnant/planning on getting pregnant
72
What is the treatment pathway for Type 2?
1. Lifestyle and diet
2. When HbA1c rises to 48mmol/mol - metformin/alternative if needed
3. First intensification:
When HbA1c rises to 58mmol/mol - add DPP-4 inhibitor, pioglitazone, sulphonylurea or SGLT-2 inhibitor (Aim for HbA1c < 53 mmol/mol)
4. Second intensification:
When HbA1c rises to 58mmol/mol - start insulin
5. Third intensification:
When HbA1c rises to 58mmol/mol - Start GLP-1 mimetic
73
In what cases would you relax the HbA1c target?
▫ who are unlikely to achieve longer-term risk-reduction benefits, e.g.
have a reduced life expectancy
▫ for whom tight blood glucose control poses a high risk such as,
hypoglycaemia, e.g. people at risk of falling, have impaired awareness
of hypoglycaemia and who drive or operate machinery as part of their
job
▫ for whom intensive management would not be appropriate e.g. those
with significant co-morbidities.
74
What are the side effects of metformin?
Lactic acidosis
GI upset
75
How does metformin work?
Increases insulin sensitivity to increase glucose uptake out of the bloodstream
Increases peripheral utilisation of glucose
Reduces hepatic glucose production
Decreases glycogenolysis (so stops glycogen breaking down into individual glucose)
76
How do sulphonylureas work?
Increases insulin secretion from beta cells so is dependent on beta cell function
Blocks ATP dependent potassium channels in beta cells - potassium cannot leave causing depolarisation of the cell and insulin secretion
77
True or false. Sulphonylureas lower blood glucose faster than metformin.
True
78
What are the advantages of metformin?
No weight gain
No hypoglycaemia
Decreases MI stroke and associated mortality
79
What are the disadvantages of sulphonylureas?
Hypoglycaemia
Weight gain
Stops working over time
You need residual pancreatic function in order for them to work
80
Give an example of a sulphonylurea
Gliclazide
81
Give an example of a biguanide
Metformin
82
How do meglitinides work?
Similar to sulphonylureas but have a weaker binding affinity
Very short acting
83
What is an advantage of meglitinides?
Less chance of hypoglycaemia
84
What is the cardiovascular risk in both types of diabetes?
• High risk of hypertension (both type 1 and 2
diabetes patients)
– Increase CV risk
– Increase nephropathy risk
– Increase retinal damage
• Very important to manage blood pressure
85
What education points are important for Type 2?
• Exercise
• Reducing weight – have a target
– Reduce the portion size
• What type of diet should the patient have?
– Glycaemic index
– How much carbohydrate – reduce this
– Increase the amount of fruits and vegetables, wholegrains,
pulses
– Low salt, sugar, saturated fats in diet
• Not to have diabetic diets
– High amount of fat
86
What increases the risk of hypoglycaemia (drugs and non-drug stuff)?
```
• Increasing age
• Insulin and sulphonylureas
• Rigid glycaemic control
• Poor eating habits
• Impaired renal function
• Alcohol intake
• Accelerated absorption e.g. exercise, injecting to
muscle by mistake, changing site of injection
• Medication errors
```
87
What increases the risk of hypoglycaemia (drugs and non-drug stuff)?
* Increasing age
* Insulin and sulphonylureas
* Rigid glycaemic control
* Poor eating habits e.g. skipping meals
* Impaired renal function
* Alcohol intake
•Exercise (up to 12 hours after so have a snack before)
• Accelerated absorption e.g. exercise, injecting to
muscle by mistake, changing site of injection
• Medication errors e.g. wrong number of units/wrong insulin type
88
What drug can mask the symptoms of hypoglycaemia?
Beta blockers
89
How would you manage hypoglycaemia?
Giving carbohydrates
Short or long acting
90
Name a few short and long acting carbohydrates that you could give in hypoglycaemia
• Short-acting carbohydrates
– 120ml glass of non-diet soft drink, eg, cola or lemonade
– Four or more glucose tablets
– Five sweets, eg, jelly babies
– 150–200ml glass or carton of fruit juice
– Three or four heaped teaspoons of sugar dissolved in water
– Glucose gel
– Glucagon injection IM or SC 1mg if unconscious
```
• Long-acting carbohydrate
– half a sandwich
– fruit
– small bowl of cereal
– biscuits and milk
```
91
What do you give to a hypoglycaemic patient if they are unconscious and why?
Glucagon injection IM/SC 1mg
As it converts glycogen to glucose in the liver
92
If a diabetic patient was on ramipril and had declining kidney function, what would you do to manage their hypertension?
Stop ramipril and add CCB
Also think about holding their metformin if they were on it until renal function had improved
93
Why are diabetic sweets not recommended?
They are high in saturated fats
94
What is the blood pressure target in Type 2?
Would this change if they had kidney/eye/cerebrovascular damage?
Target BP 140/80 mmHg
| – 130/80mmHg if kidney, eye or cerebrovascular damage
95
What are the complications of untreated hypertension in Type 2?
- Renal impairment
- Stroke
- Increased CVD risk
96
What are the treatment guidelines for hypertension in Type 2?
• ACE inhibitors first line
• ACE inhibitors and angiotensin 2 inhibitors
– Reduce microalbuminaemia, renal disease, CV risk
• Other antihypertensive agents can also be used
• For Afro-Carribeans, use combination of ACE inhibitor
and another antihypertensive agent
BP monthly until target reached
97
Hypoglycaemia can last longer if on a sulphonylurea. True or false?
True
98
What is the DVLA advice for patients who have
| diabetes and are taxi drivers?
– Check BG no more than 2 hours before driving
– Check glucose every 2 hrs
– BG must be > 5mmol/l (no hypoglycaemia)
– For taxi drivers, lorry and bus drivers need to
ensure that the monitors record the readings for
the past 3 months.
– If hypoglycaemia a problem then the patient may
not be able to drive
99
What is the maximum dose in CKD patients for metformin?
1g a day
100
If a diabetic patient comes into the Pharmacy with an infection on their foot e.g. athletes foot, what should you look out for?
* Signs of necrosis
* Loss of sensation
* Discolouration
* Signs of ulceration
* Cold to touch
101
Why do steroids induce hyperglycaemia?
– Reduce insulin secretion
– Increase gluconeogenesis
– Reduces glycogen synthesis in muscle
– Reduces glucose uptake into muscle
102
How would you manage steroid induced hyperglycaemia?
Sulphonylurea
Can use pioglitazone but this takes time to work
Insulin
No evidence for other drugs
103
What tests do you do before starting statins?
- Thyroid due to increased muscle side effects if thyroid function is abnormal and left untreated (alongside muscle myopathy risk with statins)
- Renal and liver function
- Creatine kinase levels
- Lipid profile
104
Give an example of a thiazolidedione. How many are licensed?
Only 1- Pioglitazone
105
How does thiazolidinediones work?
Decreases gluconeogenesis and increases the peripheral utilisation of glucose
It decreases free fatty acids
Decreases insulin resistance
106
What are the disadvantages of pioglitazone?
When do you need to have a review?
– Weight gain
– Fluid retention – worsens heart failure
– Cardiovascular safety is an issue - CHF
– Increased risk of fracture?
– Risk of bladder cancer and bone fractures
– Takes time to have maximum effect
Review after 3-6 months
107
What are the two classes of incretin based therapy?
GLP-1 analogues and DPP-4 inhibitors
108
What are incretins?
Group of metabolic hormones that stimulate a decrease in blood glucose levels
109
How do GLP-1 analogues work?
Glucagon like peptide
- Mimics antihyperglycaemic effect of GLP 1
110
GLP-1 analogues and DPP-4 inhibitors overall have the same effect in the bodyas they are both incretin based therapies. What are these effects?
What effect do they have on appetite?
- Increases insulin secretion
- Increases beta cell mass
- Inhibits postprandrial glucagon secretion (alpha cells)
- Reduces food uptake, slows gastric emptying and reduces appetite
111
What are the two classes of GLP-1 analogues and give examples
1. Short acting:
Exenatide (BD) and Lixisenatide
2. Long-acting
Liraglutide, dulaglutide, exenatide once weekly
112
What are the short acting GLP-1 analogues more effective on?
Postprandrial plasma glucose
113
What are the long acting GLP-analogues more effective on?
Fasting plasma glucose
114
What are the advantages of GLP-1 analogues?
- Can aid weight loss as it reduces appetite
| - Very low risk of hypoglycaemia
115
What are the disadvantages and side effects of GLP-1 analogues?
- Nausea but should wear off within 2 weeks
- Appetite suppression
- Headaches and dizziness
- Monitor risk for pancreatitis
- Only available as SC fixed dose injection
116
What is a counselling point for GLP-1 analogues?
Other medicines should be taken either:
- 1 hour before
- 4 hours after
Immediate release should not be administered after a meal
117
When would you consider GLP-1 analogues?
– have a BMI of 35 kg/m2 or higher and specific
psychological or other medical problems associated
with obesity or
– have a BMI lower than 35 kg/m2 and:
• for whom insulin therapy would have significant
occupational implications or weight loss would benefit other
significant obesity-related comorbidities.
118
When should you only continue GLP-1 therapy?
If there is a reduction in HbA1c by 1% AND a weight loss of at least 3% of initial body weight within 6 months
119
Give an example of a DPP-4 inhibitor
Sitagliptin
120
What is the MOA of DPP-4 inhibitors?
Blocks DPP-4 which increases levels of GLP-1
Increase pancreatic insulin production and decreases release of glucose from liver
121
When should you only continue DPP-4 therapy and SGLT-2 inhibitor?
HbA1C reduction of 0.5% in 6 months
122
What are the advantages of DPP-4 inhibitors?
- Weight neutral
| - Low risk of hypoglycaemia
123
What is a serious side effect of DPP-4 inhibitors?
Pancreatitis - stop treatment if persistent severe abdominal pain occurs
124
What class of drugs reduces HbA1c the most?
Sulphonylureas
125
How do SGLT-2 inhibitors work?
Blocks sodium glucose co-transporter
```
• ~ 90% of the glucose
reabsorption in the kidney
• Blocking this transporter
causes blood glucose to be
eliminated through the urine.
```
126
Name some examples of SGLT-2 inhibitors?
Dapagliflozin
Canagliflozin
Empagliflozin
127
What are the advantages of SGLT-2 inhibitors?
- No risk of hypoglycaemia
| - Reduces weight
128
What are the side effects of SGLT-2 inhibitors?
- UTIs and thrush (genitourinary fungal infections)
- Causes osmotic effects that may lead to hypotension and dehydration (particularly in patients taking diuretics)
- May cause hyperkalaemia so need to be careful with those taking ACEi as well
- Efficacy is dependent on renal function
129
What have been the two MRHA warnings in SGLT-2 inhibitors?
- Increased risk of toe amputation with canagliflozin - stop if foot complications develop
- DKA has been reported even if plasma glucose is near normal (look out for DKA)
130
Give an example of a meglitinide
Repaglinide
