CSI - Diabetes Flashcards
What is meant by prediabetes?
- blood sugars are higher than usual, but not high enough to be diagnosed with Type 2 diabetes
- patients are at high risk of developing Type 2 diabetes
- Not a clinical term recognised by WHO, but it’s starting to be used more by healthcare professionals and in the media to describe people who are at high risk of
Type 2 diabetes
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?
- there are no symptoms of prediabetes
- if you start to have any of the symptoms of Type 2 diabetes it means you have probably already
developed it
What are modifiable factors increasing the risk of diabetes?
Modifiable:
smoking
History of high blood pressure
Being overweight, especially with centripetal obesity
sedentary lifestyle (Being ‘physically inactive’ means not doing enough physical activity. Being
‘sedentary’ means sitting or lying down for long periods.)
alcohol
What are non-modifiable factors increasing the risk of diabetes?
Non-modifiable:
older age; more at risk if white and over 40 or over 25 and Afro-Caribbean, Black African,
or South Asian
having a parent, brother, sister or child with
diabetes
gestational diabetes
Polycystic Ovary Syndrome (PCOS is associated with
insulin resistance)
Mental health conditions e.g. schizophrenia, bipolar
disorder, depression
Antipsychotic medication (risk is quite low)
How does diabetes occur? What % of patients have what type?
About 90% of people with diabetes have Type 2 diabetes. It
can come on slowly (insidious onset), usually over the age of 40.
The 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?
NHS Diabetes Prevention Programme
A 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 Type 2 diabetes
Why is the NHS Diabetes Prevention Programme important?
Why implement it?
many cases of Type 2 diabetes are preventable
there is strong international evidence that behavioural interventions can significantly
reduce the risk of developing the condition, through reducing weight, increasing physical
activity and improving the diet of those at high risk
diabetes treatment currently accounts for around 10% of the annual NHS budget
What are the aims of the NHS Diabetes Prevention Programme important?
Long-term aims:
reduce the incidence of Type 2 diabetes
reduce the 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 of the NHS DPP that they provide?
The NHS DPP has three core goals:
• achieving a healthy weight
• achievement of dietary recommendations
• achievement of CMO physical activity
recommendations
What is the eligibility criteria for the NHS DPP?
Eligibility:
individuals eligible for inclusion have ‘non-diabetic hyperglycaemia’ (NDH), defined as having an HbA1c 42 - 47 mmol/mol (6.0 - 6.4%) or a fasting plasma glucose (FPG) of 5.5 - 6.9 mmol/l
the 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 aged 18 years or over are eligible for the intervention
What is Metformin?
Metformin:
used first-line for treatment of T2DM
reduces the amount of sugar your liver releases into your blood
makes your body respond better to insulin by stimulating GLUT-4 translocation
doesn’t cause weight gain, unlike some other diabetes medicines
lower risk of hypoglycaemia
best to take with a meal to reduce the side effects
most common side effects are feeling and being sick, diarrhoea, stomach-ache and going off your food
What is behaviour insights in terms of treatment?
Behavioural insights:
an approach that uses knowledge of how and why people behave, to encourage positive behaviour change
behavioural insights consider all aspects of behaviour (e.g. psychology, social anthropology, and behavioural economics) and acknowledge the importance of the fast and intuitive automatic system in driving behaviour
behavioural insights are most helpful where individuals want to make positive behaviour changes but struggle to do so
What is the EAST framework for behaviour change?
- Make it easy
- Make it attractive
- Make it social
- Make it timely
What are the 3 primary routes of being referred to the NHS DPP?
Referral routes into the programme:
Referral routes vary according to local finding pathways. Three primary mechanisms for referral are:
1. those who have already been identified as having an appropriately 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 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
What are the core defects that lead to T2DM?
Core defects in type 2 diabetes mellitus (T2DM):
insulin resistance in muscle and the liver
impaired insulin secretion by the pancreatic β-cells
What is the mnemonic to remember the causes of hyperglycaemia?
RULING HIVE
R - increased glucose Reabsorption
U - decreased glucose Uptake
L - increased Lipolysis
I - Inflammation
N - neurotransmitter Dysfunction
G - increased Glucagon secretion
H - increased Hepatic glucose production
I - decreased Insulin secretion
V - Vascular insulin resistance
E - decreased incretin Effect
How is insulin involved in glucose metabolism?
How insulin is involved in glucose metabolism
Insulin (protein 1) from the blood binds to insulin receptor (protein 2) on skeletal
muscle/adipose cell
this induces blood glucose to be transported through the Glut-4 receptor (protein 3) via
facilitated diffusion into the skeletal muscle/adipose cell
glucose is converted to pyruvate via glycolysis (A)
pyruvate is converted to acetyl CoA via the link reaction/pyruvate oxidation (B)
acetyl CoA is converted to ATP (C) via the Krebs cycle and oxidative phosphorylation
when inside the cell, 1 molecule of glucose can generate ~30ATP
If your blood glucose is high but you are insulin resistant…
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
Insulin mediates glucose uptake via Glut-4.
RULING HIVE: R
- Increased glucose Reabsorption
-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.
RULING HIVE: U
- Decreased glucose Uptake
-due to beta-cell failure -> less insulin is secreted
RULING HIVE: L
Increased Lipolysis
-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.
RULING HIVE: I
Inflammation
-Inflammation activates and increases the expression of several proteins that suppress insulinsignalling pathways, making the human body less responsive to insulin and increasing the risk
for insulin resistance.
RULING HIVE: N
Neurotransmitter dysfunction
-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
RULING HIVE: G
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
RULING HIVE: H
Increased Hepatic glucose production
-increased glucagon levels and enhanced hepatic sensitivity to glucagon contribute to the
excessive glucose production by the liver
RULING HIVE: I
Decreased Insulin secretion
Beta-cell failure due to:
GLP1 resistance
Insulin resistant adipose, muscle, and liver tissue
RULING HIVE: V
- Vascular insulin resistance
-prolonged exposure to high levels of insulin causes increased vasculature resistance
RULING HIVE: E
Decreased incretin Effect
-the incretin ‘glucagon-like peptide 1’ (GLP1) stimulates β-cells to secrete insulin
What are the 3 Ps of diabetes symptoms?
Diabetes symptoms, the 3 P’s:
Polydipsia: an increase in thirst; when blood glucose levels get high, your kidneys produce more urine in an effort to remove the extra glucose from your body, leaving you feeling dehydrated.
Polyuria: frequent urination; when blood glucose
levels are too high, your body will try to remove some of the excess glucose via urination. This also leads to your kidneys filtering out more water, which leads to an increased need to urinate.
Polyphagia: a rise in appetite; in people with diabetes, glucose can’t enter cells to be used for
energy. This can be due to either low insulin levels or insulin resistance. Because your body can’t
convert this glucose to energy, you’ll begin to feel very hungry
What is a type 2 diabetes diagnosis?
Type 2 diabetes diagnosis:
Symptoms + 1 red glucose range test
No symptoms + multiple red glucose range tests
What is the Renal threshold for glucose?
Renal threshold for glucose (RTG):
The proximal tubule can only reabsorb a
limited amount of glucose (~375 mg/min),
known as the transport maximum.
When the blood glucose level exceeds about
160–180 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 HBA1C?
HbA1c
Haemoglobin A1C (or HbA1C) is haemoglobin that has become glycosylated, i.e. chemically linked
to a sugar
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
Advantages of using HbA1C as a diagnostic
tool for diabetes:
- Cheap
- takes into account blood glucose levels for 2-
3months - easy to measure (fasting is not needed for A1C
assessment and no acute perturbations (e.g.,
stress, diet, exercise) affect A1C)
Disadvantages of using HbA1C as a
diagnostic tool for diabetes:
- only an approximate measure
- not reliable in certain conditions e.g.
Pregnancy (amount of haemoglobin
changes/rapid changes in glucose
management), renal failure, Sickle Cell
What are additional functional effects of insulin on the liver?
liver:
increased glucose uptake
increased glycogenesis
decreased glycogenolysis
decreased gluconeogenesis
decreased lipolysis
What are additional functional effects of insulin on the muscle?
muscle:
increased glucose uptake
increased glycogenesis
increased protein synthesis
decreased protein catabolism
What are additional functional effects of insulin on fat?
increased glucose uptake
increased lipogenesis
decreased lipolysis
What are SGLT1 and SGLT2 responsible for?
SGLT1 and SGLT2
active transport
glucose transported into luminal epithelial cells in the kidney and small intestine
How many GLUT transporters are there?
4
GLUT-1, GLUT-2, GLUT-3, GLUT-4
What is the primary distribution and function of each Glut transporter? : GLUT-1
GLUT -1
primary distribution: endothelium, erythrocytes
function: basal transport (insulin independent)
What is the primary distribution and function of each Glut transporter? : GLUT-2
Primary distribution: kidney, small intestine, liver,
pancreatic beta cells
function: low affinity transport (insulin independent)
What is the primary distribution and function of each Glut transporter? : GLUT-3
primary distribution: neurones, placenta
function: high affinity transport (insulin independent)
What is the primary distribution and function of each Glut transporter? : GLUT-4
primary distribution: skeletal muscle, adipose
function: insulin-regulated glucose transport
if your blood glucose is high but you are insulin resistant, 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
**Insulin mediates glucose uptake via Glut-4. **
What happens to blood glucose levels and FFA?
increases
What is the difference in pathogenesis between TYPE 1 and TYPE 2 diabetes?
Type 1: very little/no insulin produced at all
Type 2: little insulin produced + insulin resistant cells
What is the difference between impaired fasting glucose and impaired glucose tolerance?
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 postprandial insulin release results in poor cellular glucose uptake
Impaired fasting glucose and impaired glucose tolerance can occur together or separately, one could occur first
EAST Framework for behavioural change: How do you make it easy?
uptake: default referrals
simplify invitation
letters
offer taster session
retention: sessions at
convenient times
identify barriers to
ongoing attendance
behaviour change:
challenging but
realistic goals
manageable written
materials
tell people ‘how’
rather than ‘what’
EAST Framework for behavioural change: How do you make it attractive?
uptake: offer incentives
highlight benefits
retention: add an element of
competition
make sessions a
‘game
behavioural change: emphasise
immediate/
short-term
benefits
tailor to audience
EAST Framework for behavioural change: How do you make it social?
uptake: normalise
attendance
testimonies from a
range of patients
use commitment
devices/apps
retention: delivery in group
sessions
use of commitment contracts
behavioural change: include social
support aspect
consider different
messengers (not
just doctors but
other figures)
EAST Framework for behavioural change: How do you make it timely?
uptake:
provide a deadline for
signing up
send a text saying
that their invite letter
will follow (‘priming’)
retention:
text reminders to
attend sessions
behavioural change:
time-orientated goals
select the optimal
time for each patient
(consider
personal/religious/cultural aspects)
What is the normal, impaired and diabetes range?
Normal
metabolism
- Fasting
glucose
<6.1 mmol/
Post prandial
glucose*
<7.8 mmol/l
Random
<11.1 mmol/l
What are the implications of smoking cessation treatments?
Smoking cessation treatments
reduces the risk of developing or worsening of smoking-related illnesses
benefits begin as soon as a person stops smoking
may be associated with temporary withdrawal symptoms caused by nicotine dependence,
making it difficult for people to stop
symptoms include nicotine cravings, irritability, depression, restlessness, poor concentration,
light-headedness, sleep disturbances, and increased appetite
weight gain is a concern for many people who stop smoking, but is less likely to occur when
drug treatment is used to aid smoking cessation
What are non-drug treatments to stop smoking?
Non-drug treatment
all smokers (including e-cigarettes smokers), should be advised to stop and be offered
support to facilitate smoking cessation
stopping in one step (‘abrupt quitting’) offers the best chance of
lasting success, and that a combination of drug treatment and
behavioural support is likely to be the most effective approach
‘abrupt quitting’ is when a smoker makes a commitment to stop
smoking on or before a particular date (the quit date), rather than
by gradually reducing their smoking
smokers who wish to stop smoking should be referred to their local
NHS Stop Smoking Services, where they will be provided with
advice, drug treatment, and behavioural support options such as individual counselling or
group meetings.
smokers who decline to attend their local NHS Stop Smoking Services should be referred to a
suitable healthcare professional who can also offer drug treatment and practical advice
What are drug treatments to stop smoking?
nicotine replacement therapy (NRT), varenicline and bupropion hydrochloride, are
effective drug treatments to aid smoking cessation
choice of drug treatment should take into consideration the smoker’s age, likely adherence,
preferences, whether they’re pregnant or breastfeeding, medical conditions, and previous
experience of smoking-cessation aids, as well as contra-indications and side-effects of each
preparation
varenicline, or a combination of long-acting NRT (transdermal patch) and short-acting NRT
(lozenges, gum, sublingual tablets, inhalator, nasal spray and oral spray), are the most
effective treatment options and thus the preferred choices
if the combination option is not appropriate, bupropion hydrochloride or single therapy
NRT should be considered instead
there is no evidence that one form of NRT is more effective than another
any combination of NRT, varenicline, and bupropion hydrochloride should not be
prescribed together
a quit date should be agreed when drug treatment is prescribed for smoking cessation, and
treatment should be available before the person stops smoking
smokers should be prescribed enough treatment to last 2 weeks after their agreed quit date and be reassessed shortly before their supply finishes
What are e-cigarettes?
E-cigarettes
electronic device that delivers vapour composed of nicotine without the toxins found in
tobacco smoke e.g. tar or CO
evidence suggests that e-cigarettes are substantially less harmful to health than tobacco
smoking, but long-term effects are still largely unknown
some smokers have found e-cigarettes useful for smoking cessation,
however they cannot be prescribed or supplied by smoking cessation
services (you have to buy them)
people who wish to use e-cigarettes should be advised that although
these products are not licensed drugs, they are regulated by the Tobacco
and Related Products Regulations 2016
are most effective if used with support from an NHS stop smoking service
in the UK, sale of e-cigarettes is prohibited in children under 18 years of age
What are concomitant drugs?
Concomitant drugs
polycyclic aromatic hydrocarbons found in tobacco smoke increase the
metabolism of some drugs by inducing hepatic enzymes, often requiring an increase in dose
Why is smoking during pregnancy something to be aware about?
Pregnancy
pregnant females should be advised to stop smoking completely, and be informed about the
risks to the unborn child of smoking during pregnancy, and the harmful effects of exposure to
second-hand smoke for both mother and baby
all pregnant females who smoke or have stopped smoking in the last 2 weeks should be
referred to their local NHS Stop Smoking Services, and ongoing support should be offered during and following pregnancy
smoking cessation should also be encouraged for all members of the household
pregnant females who smoke should be advised to contact the NHS Pregnancy Smoking Helpline for further information
NRT should only be used in pregnant females if non-drug treatment options have failed
clinical judgement should be used when deciding whether to prescribe NRT following a discussion about its risks and benefits
subsequent prescriptions should only be given to pregnant females who have demonstrated
they are still not smoking
Inhaled medicines for COPD: bronchodilator:
rescue therapy - what is the mechanism and give examples
mechanism:
beta-2 agonists; sympathetic nervous system dilates airways through beta adrenergic receptors
muscarinic antagonists; antagonistically works
against parasympathetic nervous system that keeps airways constricted
both come in long acting and short acting forms
examples:
short acting beta
agonists (SABA)
Salbutamol
(Ventolin)
short acting
muscarinic antagonists
(SAMA)
Ipratropium
bromide
(Atrovent)
Inhaled medicines for COPD: long acting bronchodilator:
maintenance therapy - what is the mechanism and give examples
mechanism:
beta-2 agonists; sympathetic nervous system dilates airways through beta adrenergic receptors
muscarinic antagonists; antagonistically works
against parasympathetic nervous system that keeps airways constricted
both come in long acting and short acting forms
examples:
long acting beta agonists
(LABA)
Formoterol,
Salmeterol (Serevent)
long acting muscarinic
antagonists (LAMA)
Tiotropium (Spiriva),
Glycopyrronium
Inhaled medicines for COPD: inhaled corticosteroids (ICS) - what is the mechanism and give examples?
Mechanism:
anti-inflammatory for airways
reduces the risk of flare-ups or
exacerbations
useful for people whose condition is
an overlap of asthma and COPD
numerous different inhaler devices
exist
numerous drug combinations exist
within a single inhaler
examples:
alone - not licensed in COPD
Beciomestasone, Fluticasone (Flixotide)
in combination e.g. with a LABA
Fluticasone + Vilaterol (together = Relvar)
What is NRT?
the main reason people smoke is
because they’re addicted to
nicotine
the amount of nicotine in NRT is
much lower and less addictive
than in smoking tobacco, and does
not contain the poisonous
chemicals e.g. tar, CO, present in
tobacco
NRT can help with unpleasant
withdrawal symptom
What is varenicline? aka Champix?
works in 2 ways:
1) reduces cravings for
nicotine like NRT
2) blocks the rewarding
and reinforcing effects of
smoking
Evidence suggests it’s the
most effective medicine
for helping people stop
smoking
What is bupropion hydrochloride?
aka zyban
- originally used to treat depression, has since been found to help people quit smoking
it’s not clear exactly how it works, but it’s thought to have an effect on the parts of the brain involved in addictive behaviour
Where can you get and how do you use NRT?
Nicotine replacement therapy
can be bought from pharmacies and
some shops
is available on prescription from a
doctor or NHS stop smoking service
It’s available as:
skin patches
chewing gum
inhalators (which look like plastic
cigarettes)
tablets, oral strips and lozenges
nasal and mouth spray
patches release nicotine slowly
nicotine transdermal patches are
applied for 16 hours, with the patch
removed overnight
if smokers experience strong
nicotine cravings upon waking, a
24-hour patch can be used instead
short-acting nicotine
preparations e.g. inhalators, gum,
and sprays are used whenever the
urge to smoke occurs or to
prevent cravings
using a combination of long and
short acting NRT is more effective
treatment usually lasts 8-12 weeks
before gradually reducing the
dose and eventually stopping
Where can you get and how do you use varenicline (champix)?
only available on
prescription; usually
need to see GP or
contact an NHS stop
smoking service to
get it
taken as 1-2 tablets a
day
start taking it a week
or 2 before trying to
quit
a course of treatment
usually lasts 12 weeks,
but can be continued
for longer if
necessar
Where can you get and how do you use bupropion (zyban)?
only available on
prescription;
usually need to see
GP or contact an
NHS stop smoking
service to get it
taken as 1-2 tablets
a day
start taking it a
week or 2 before
trying to quit
a course of
treatment usually
lasts 7-9 weeks
Who can use NRT?
smokers who are unwilling or not
ready to stop smoking may benefit
from the use of NRT as part of a
‘harm reduction approach’
harm reduction approaches include
stopping smoking whilst using
NRT to prevent relapse, and
smoking reduction or temporary
abstinence with or without the
use of NRT
NRT will make it easier to reduce
how much they smoke and
improve their chance of stopping
smoking in the long-term
Most people are able to use NRT,
including:
adults and children over 12 years of
age; children under 18 should not
use the lozenges without getting
medical advice first
pregnant women
breastfeeding women
get medical advice first e.g. if you
have kidney or liver problems, or
you’ve recently had a heart attack OR stroke
What are possible side effects of NRT?
skin irritation when using patches
irritation of nose, throat or eyes
when using a nasal spray
difficulty sleeping (insomnia),
sometimes with vivid dreams
an upset stomach
dizziness
headaches
Any side effects are usually mild. But if
troublesome, contact GP as dose or
type may need to be changed
What are side effects of varenicline?
feeling and being sick
difficulty sleeping
(insomnia), sometimes
with vivid dreams
dry mouth
constipation or
diarrhoea
headaches
drowsiness
dizziness
Contact GP if side-effects
are troublesome.
Who can use varenicline?
safe for most people to
take, although there are
some situations when it’s
not recommended, e.g.
children under 18
years of age
women who are pregnant or breastfeeding
- people with severe kidney problems
What are side effects of bupropion?
dry mouth
difficulty sleeping
(insomnia
headaches
feeling and being
sick
constipation
difficulty
concentrating
dizziness
Contact GP if sideeffects are troublesome
Who can take bupropion?
safe for most people to
take, although there are
some situations when
it’s not recommended,
e.g.
children under 18
years of age
women who are breastfeeding or pregant
people with epilepsy, bipolar disorder, eating disorders
