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Diabetes
Majority of cases will be primary diabetes (type 1 and type 2), although secondary causes include:
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Pancreatic carcinoma
Haemochromatosis
Liver disease
Internal insulin antagonists (e
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GH, adrenocortical hormones, hyperthyroidism)
Iatrogenic causes (e
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corticosteroids, thiazide diuretics, protease inhibitors, antipsychotics)
Gestational diabetes

Incidence
Type 1 usually appears before 40 years of age, is less common than type 2, and accounts for only
10% of people with diabetes in adults, but if children are included then 15% of total people with
diabetes are type 1
...
(BUT
environmental factors may play a bigger role than genetics; several viruses (mumps), dietary factors
(early exposure to cow’s milk), and the hygiene hypothesis have been put forward for causes)
In type 2 diabetes one is 2-6 times more likely to get if any family member has this; type 2 linked
with being overweight (obesity accounts for 80-85% risk of developing type 2), usually over the age
of 40, but in south Asians may be present from 25 years onwards (6 times more common in SA’s,
and 4 times more common in Africans; Bengalis are the worst); we are even seeing young children at
even 7 years old getting this condition (but type 1 is more common in children and peak age of
diagnosis is between 10-14 years)
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Since 1996 in the UK number of people diagnosed with diabetes has increased from 1
...
9 million;
by 2025 it is estimated that 5 million people will have diabetes
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From the 16-34 age groups, slightly more WOMEN have diabetes (ENGLAND), however for all other
age groups, MEN are more likely to have diabetes and this difference is a substantial amount; overall
6
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3 % women have reported diabetes
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1/3
of people with type 2 diabetes develops overt kidney disease; kidney disease causes 21 % deaths of
type 1 diabetics and 11% deaths in type 2 patients)
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(diabetes is leading cause of blindness in
working population)
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People are twice as likely to suffer from depression if they have diabetes
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Currently £10billion pound spent on diabetes (NHS)
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Diagnosis
Type 1 diabetes (tends to have a faster and severe onset of symptoms):
Patient presenting symptoms of type 1 diabetes are hyperglycaemia (>11 mmol/L), polyuria (in
children bedwetting and nappies can be an indicator), polydipsia, and weight loss (due to breakdown
of fat and protein for energy)
...
The high levels of glucose in urine could
lead to frequent infections of the urogenital system
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Diagnosed by classic symptoms, weight loss and capillary blood glucose level of >11mmol/L
(remember CAN’T use HbA1c for type 1 diabetes)
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Children and young people (under 11 here classed as children, 11-18 years are young people):
Upon presentation of suspected type 1 diabetes, consideration of other types of diabetes (e
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early
onset type 2 diabetes, insulin resistant syndromes, molecular/enzymatic abnormalities etc
...
g
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If child is under 2
years or has social or emotional difficulties, or who live far away from hospital, inpatient initial
management should be offered following diagnosis
...
A structured programme of education should be offered which covers;
aims of insulin therapy; delivery of insulin; self-monitoring of BS; effects of diet, physical activity and
intercurrent illness on glycaemic control; and detection and management of hypoglycaemia
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Adults with type 1 diabetes:

In the presence of classical symptoms, diabetes should be confirmed by a single diagnostic
laboratory glucose measurements, or by further laboratory glucose measurement; diagnosis MAY be
supported by raised HbA1c
...

Tests used to detect specific auto-antibodies or to measure C-peptide deficiency should NOT be
used routinely to confirm diagnosis of type 1 diabetes; their use should be considered when
discriminating between type 1 and type 2 (by predicting the rate of decline of islet B-cell function)
...
(similar to that of the child mentioned above)
Type 2 diabetes:
Tends to have an insidious onset of type 2 diabetes, with few or NO classic symptoms; presence of
recurring infections sometimes lead to the detection of type 2 diabetes, but patients tend to present
when the complications e
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CV or renal disease, have already developed
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Methods of diagnosis (especially of type 2 diabetes; all can be used)
In 2011 the WHO recommended that HbA1c can be used for diagnosis of diabetes in the UK
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These can be used as a diagnostic test provided that:
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Stringent QA tests are in place
Assays are standardised to criteria aligned to the international reference values
There are no conditions present which preclude its accurate measurement
The staff carrying out the test are competent

The following situations are whereby the HbA1c test is not appropriate for diagnosing diabetes:
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In children and young people
Patients of ANY age suspected of having type 1 diabetes (due to a rapid change in glycaemic
levels and thus HbA1c may remain normal)
Patients with symptoms of diabetes for less than 2 months (as it takes into account for
previous 2-3 months)
Patients at high risk of diabetes who are ACUTELY ill (i
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those requiring hospital admission)
Patients taking medicines which can cause glucose rise (corticosteroids, thiazide diuretics,
protease inhibitors, antipsychotics)- will provide incorrect information
Patients with acute pancreatic damage including pancreatic surgery
In pregnancy
Presence of genetic, haematologic, and illness-related factors that influence HbA1c and its
measurement

HbA1c of 6
...
5% does NOT exclude diabetes which may have been diagnosed using glucose tests
...
(generally when patients present, a standard finger-prick
glucose test should be carried out and if level is above 11mmol/L, then do an urgent lab glucose test)
A value of 6-6
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g
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In patients without symptoms of diabetes, there should be a repeat of the laboratory HbA1c; if the
value is below 6
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g
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If the glucose
tests have not already been done, they could be done for patients with symptoms or at a high risk of
developing diabetes, however the use of such tests in this situation are not recommended routinely
(i
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an OGTT could be used)
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5%, and for those at an
increased risk of arterial disease below or equal to 6
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Recommendations from 2006 (which still also apply):
This can be split into two methods of approach; diabetes WITH symptoms and WITHOUT symptoms
diagnosis
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e
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1mmol/L (especially if CURRENTLY with
symptoms)
OR
A fasting plasma glucose >7mmol/L
OR
A plasma glucose > 11
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At LEAST one additional glucose test result with a value
within the diabetic range on a DIFFERENT day is essential (unless children; they should be referred
ASAP same day ideally) (the different day should be 4-6 weeks later), either from fasting, a random
sample or as an oral glucose tolerance test
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(so remember, in patients with classic symptoms, one abnormal value of any of the tests listed
above is diagnostic of diabetes; in the absence of symptoms, 2 abnormal values are needed to
confirm the diagnosis i
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on different days)
Impaired glucose tolerance is a stage of impaired glucose regulation whereby the fasting levels are
below 7 mmol/l however the tolerance test values are >7
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1 mmol/L
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1 but <7
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DVLA
Insulin treated diabetes (group 1: car and motorcycle):
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drivers must have an awareness of hypoglycaemia (i
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detect its symptoms)

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must not have had MORE THAN 1 episode of hypo in past 12 months which needed
assistance
2 hours before and every 2 hours while driving blood glucose should be monitored
Must NOT be regarded as likely source of danger to public while driving
The visual standards for acuity and visual field must be met

If standards met 1,2, or 3 years license can be given
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Furthermore there should be no other debarring complications of
diabetes such as visual field defect
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Diabetes managed by diet ALONE (group 1 + 2)
Need NOT to notify DVLA unless develop relevant disabilities, e
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diabetic eye complications
effecting visual acuity or visual field; or if insulin is required
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Diabetes managed by tablets which carry the risk of inducing hypo:
Group 1: - must not have had a hypo needing assistance from someone in past 12 months
-

Must be able to recognise hypo (and other things listed on the document)

Normal licence can be issued
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Group 2: same as that for insulin (see above)

Standard measures for driving; (see diabetes PDF sheet; IMPORTANT)

Preventing type 2 diabetes
A NICE guidance is published on this topic in order to identify people of high risk of developing type
2 diabetes and the provision of clinical and cost-effective interventions for them
...

The following prompts and interventions are recommended:
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Risk assessment: HCP’s should implement a two-stage strategy to identify people at high
risk of developing type 2 diabetes; first a risk assessment(stage 1 below), and second where
necessary a blood test should be offered (stage 2 below)
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Explain that even if feel healthy still should do the
test, and should encourage their family
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If carried out in a CP should refer those at high risk to their
GP; GP’s should ideally have their own tool of identifying and recruiting patients

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Risk identification (stage 2): here blood glucose tests should be offered (HbA1c or fasting
plasma glucose) to adults with high risk scores from stage 1 OR for those over 25 years from
south Asian or Chinese descent with a BMI over 23; a fasting glucose level of 5
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9 mmol/L
or HbA1c of 6-6
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Possible type 2 diabetes could also be identified using the OGTT
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Matching interventions to risk: patients at low risk- offer brief advice on how things be
improved for future outcomes, including advice on healthy eating etc
Patients at moderate risk (high risk questionnaire score but fasting BS< 5
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5-6
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4% )- tell patient currently at high risk (may not get type 2 diabetes) and lifestyle changes
can help; a referral to a local QA based intensive lifestyle-change programme should be
considered

Patients with possible type 2 diabetes (fasting glucose 7mmol/L or more, or HbA1c 6
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g
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Physical activity: ensure patients understand benefits of exercise and risks of sedentary
lifestyle etc
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g
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Renal function should be checked before starting, and then TWICE yearly or
more often if needed; doses of metformin should be low to start with, and increased
gradually as tolerated
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o

Orlistat: tends to be an option for those with BMI of more than 28 who are still
progressing to type 2 diabetes, in particular if they haven’t benefitted from lifestyle
changes, or are unable to participate in physical activity because of disability or for
medical reasons
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Use should
be reviewed every 12 weeks, and an aim of 5% body fat loss should be made (per 3

months), but can be carried on if not hit this level; use should be reviewed for
continuation after a year
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Surgery considered if BMI 40+ or 35-40 with other comorbidities
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Insulin is a polypeptide hormone which plays a key role in the regulation of carbohydrate, fat, and
protein metabolism
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Insulin may be extracted from pork or beef pancreas by crystallisation however beef is now rarely
used
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No differences in terms of immunogenicity have been shown if human or animal insulin
has been used
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The main problem
caused by SC insulin is localised lipodystrophy which can be minimised by using different injection
sites in rotation (NB such sites will become less-painful so patient will want to use more; however
absorption from them may be erratic); note local allergic reactions are rare
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The requirements may be increased by infection, stress, trauma (surgical or accidental),
and during puberty; requirements may be decreased in certain endocrine disorders e
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Addison’s
disease, or celiac disease
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Pregnant women with type 2 diabetes may be treated with insulin if diet alone fails
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Short-acting: have rapid onset of action but short duration;
e
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SOLUBLE insulin, rapid-acting insulin analogues (insulin aspart, insulin glulisine, and
insulin lispro)
the advantage of rapid-acting vs short-acting is the reduced risk of severe hypoglycaemia
(see box below), and that they can be administered just before a meal rather than the 30
mins needed for short acting insulin
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Time of use: soluble insulin (15-30mins before meals); rapid-acting analogues used at similar
time (or closer to meal time) and can be used IV as an alternative to soluble insulin
Onset of action: soluble insulin (SC: 30-60mins, peak @ 2-4hours; IV: 5mins), rapid-acting
human insulin analogues (SC: 10-20mins, peak @ 1-3 hours)

Duration of action: soluble insulin (SC: 8 hours, IV: 30minutes), rapid-acting human insulin
analogues (SC: 3-5 hours)
2
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5 hours, peak @ 4-12 hours
Duration of action: 24 hours
3
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g
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(insulin deludec; new basal insulin w/ better half-life)
Onset: 1 hour (SC)
Duration of action: 24 hours
4
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Premixed insulin: e
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30% soluble and 70% isophane insulin is the main combination used
Onset: 30mins, peak at 2-8 hours
Duration of action: 24 hours
The duration of action of insulin will vary on a patient-patient basis
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g
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g
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For patients who have difficulty or prefer NOT to use multiple injection regimens a mixture of
premixed short-acting insulin/rapid-acting insulin analogue with an intermediate acting OR longacting insulin (most commonly in a proportion of 30% soluble insulin and 70% isophane insulin) can
be given once or twice daily
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Recommended insulin regimens are as follows:
Insulin 1
Short-acting/rapid-acting

Insulin 2
With intermediate/long acting

Short-acting/rapid-acting

MIXED with intermediate/longacting
With or WITHOUT short/rapidacting
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Intermediate/long-acting
Continuous SC insulin infusion;
has shown to reduce the risk of
severe hypoglycaemic episodes
compared to multiple daily
injections; has shown to
improve QoL and decrease the
use of insulin; needs to be used
in conjunction with motivation,
and carbohydrate counting
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; NICE recommends this
should be used in 12 years +
provided that attempts to
achieve HbA1c with multiple
daily injections has caused
severe hypo

Basal-bolus regimen (preferred method): where a long or intermediate-acting insulin is injected
once or twice a day (basal), PLUS a bolus injection of a short-acting insulin before each meal
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Additional bolus injections may be required if high carbohydrate
snacks are eaten between meals
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An NPSA alert has identified that the use of IU or U for an abbreviation of units is not acceptable and
that non-insulin syringes (typically IV syringes) should NOT be used to administer SC insulin; if IV
insulin is given 50ml syringes or larger bags should be used to differentiate
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In 2011 NPSA also suggested
that all patients should have an insulin passport for the correct identification of regimen
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5% seems to be the threshold before such treatment is
considered
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NPH (intermediate-acting insulin) is recommended first-line in addition with the existing oral hypo
agents due to its cost-effectiveness; HbA1c should be checked after 3 months and this regimen
continued if under control
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If the HbA1c is >9%, a twice daily pre-mixed insulin could be considered, and HbA1c checked after 3
months; if BS are controlled this regimen can continue otherwise a basal-bolus regimen should be
issued (oral treatment would be stopped)
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5mmol/L)
Patients should monitor their own BS’s when necessary as this will differ on a patient-to-patient
basis; driving status, patient preference, risk of hypo etc should be taken into account
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(optimal targets of BS are 4-7 pre-prandial, and below 9 postprandial)
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Current recommendations on treatment of hypo are; 15-20g (BNF 10-20g; see BNF page 463) of
short acting-carbohydrate (120ml of non diet soft drink; five or more glucose tabs; five sweets;
glucose gel; 3-4 heaped teaspoons of sugar in water); if necessary should be repeated 10-15 mins
and after initial treatment offer a snack
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This increases plasma glucose by
mobilising glycogen stored in the liver
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If glucagon is not effective in 10 minutes IV
glucose should be given
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Oral anti-diabetic drugs (read NICE type 2 diabetes qrg in line with this):
These are used for the treatment of type 2 diabetes, and should ONLY be prescribed if patient fails
to respond adequately to AT LEAST 3 months’ restriction of energy and carbohydrate intake and
increase in physical activity
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If
insulin is added this is done so during bedtime (usually isophane or long-acting insulin (which can
cause nocturnal hypo in type 1)) or if insulin has replaced oral therapy, can be given as twice daily of
a biphasic insulin, or a multiple injection regimen
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ONLY GLIBENCLAMIDE AND METFORMIN CAN BE USED IN PREGNANCY AND BREASTFEEDING
Sulphonylureas: glibenclamide, gliclazide, glimepiride, glipizide, tolbutamide
Several sulphonylureas are available and choice is determined by side-effects, duration of action,
patients age, and renal function
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Considered for patients who are NOT overweight, or in whom metformin is contra-indicated
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Mode of action: augment insulin secretion (thus only effective when there is some residual
pancreatic beta-cell activity)
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Glibenclamide; long-acting but associated with greater risk of hypo thus avoided in elderly and short
acting alternatives used instead
Gliclzide and tolbutamide; short-acting
Usual dose: single dose normally taken after breakfast; glipizide can be given before lunch or
breakfast
Cautions and contra-indications: cause weight gain (should only px if there is poor control and
symptoms when dieting); use with caution in elderly and those with G6PD deficiency; AVOID in acute
porphyria and presence of DKA
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If necessary the short-acting tolbutamide or
gliclizide can be used in renal impairment
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Side effects: hypoglycaemia (uncommon, but may persist for a few hours and needs hospital
attention); other side effects tend to be mild-moderate and include N+V+D and constipation;
hyponatremia (glipizide and glimepiride); can cause a disturbance in liver function
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Can again
be used with the same combo’s as those listed for sulfonylurea, with the additional option of
combination with repaglinide or nateglinide (see above)
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ADVANTAGES: causes weight loss and rarely causes a hypo
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Can also be used in pregnancy and breastfeeding alone or in combo with insulin
where DM prior to pregnancy or gestational diabetes
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Works only in presence of endogenous insulin therefore some residual function
of pancreatic islet cells must be apparent
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Usual dose: usually 500mg with meals; (counselling; take with or after food)
Cautions and contra-indications: can provoke lactic acidosis in renal impairment (determine renal fx
before treatment initiated and annually (or at least twice annually in those with additional risk
factors for renal impairment)
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DO NOT USE IN;
ketoacidosis and in surgery, NB: IV iodinated contrast agents can cause renal failure  lactic
acidosis, therefore if iodine is used metformin should be suspended prior to the test and started no
earlier than 48 hours after the test if renal function has returned to baseline
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Taste disturbance and ab pain can also occur
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Post-prandial hyperglycaemia in type 1 diabetes can be reduced by acarbose, but it has been used
little for this purpose
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Usual dose: 50-200mg TDS; counselling: chew with first mouthful of food, or swallow whole with a
little liquid IMMEDIATELY before food; risk of hypo higher when taken with insulin or sulfonylurea so
patient should carry GLUCOSE (not sucrose as acarbose interferes with its absorption)
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Side effects: flatulence (reduced over time)
Interactions: avoid with orlistat

Insulin secretagogues; nateglinide and repaglinide:
Both drugs have a RAPID-ONSET of action, and a short-duration of activity, thus should be
administered shortly before each main meal
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Netaglinide is ONLY licensed to be used with metformin
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Usual dose: normally taken 30 minutes before meals, and adjusted according to response
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Change to
insulin during intercurrent illness or surgery, and recommence when eating and drinking normally
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The combo of pioglitazone + metformin is preffered (especially for obese patients)
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Pioglitazone can also be used with insulin, when insulin alone is not good and metformin is
inappropriate (NB: incident of HF may be increased especially in those with predisposing factors e
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previous MI; if there is any deterioration in CV then stop treatment; do NOT use in current or history
of HF)
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NICE recommends that treatment with pioglitazone should ONLY be continued if HbA1c
concentration is reduced by 0
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Mode of action: reduces peripheral insulin resistance, therefore reducing blood glucose
concentration
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Advise
patients to seek immediate attention if N/V, ab pain, fatigue or dark urine develop; STOP if jaundice
occurs (all due to liver toxicity)
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Liver function should be monitored (AVOID in hepatic impairment)
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Side effects: GI disturbances, WEIGHT GAIN, oedema, anaemia, headache
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Saxagliptin, sitagliptin and
vildagliptin can be used in type 2 diabetes in combo with metformin or a sulfonylurea or
pioglitazone
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(read BNF for full combinations list)
Treatment with sitagliptin or vildagliptin should only be continued if HbA1c concentration is reduced
by at least 0
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May be preferable to pioglitazone if further weight gain will cause problems, or if it is
contraindicated
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Usual dose: used once daily (vildagliptin used twice daily)

Cautions and contraindications: discontinue if there are symptoms of pancreatitis (e
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persistent
severe abdominal pain)
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medical
attention should be sought promptly)
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Side effects: GI disturbances, peripheral oedema, headache, dizziness
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Glucagon-like peptide-1 agonist (GLP-1 agonists); exenatide, liraglutide, and lixisenatide
(Exenatide is used as a third-line option in type 2 diabetes):
Treatment has been associated with the PREVENTION of weight gain and possible promotion of
WEIGHT loss which can be beneficial in overweight patients
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(same for Liraglutide)
Standard release Exenatide combos: + basal insulin; + basal insulin and metformin; + basal insulin
with pioglitazone; + basal insulin, pioglitazone and metformin
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Treatment with standard release Exenatide (and Liraglutide) ONLY continued if there is 1% reduction
in HbA1c and 3% body weight within 6 months of initiation (in triple therapy)
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Lixisenatide to be used with oral hypo’s or basal insulin, or both; should not be used with basal
insulin and sulfonylurea due to increased risk of hypo
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Usual dose: given by SC injection; NB Liraglutide 1
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Exenatide and lixisenatide (once daily): Use twice daily before main meals  do NOT administer
after main meals if dose missed then carry on without; some oral medicines may need to be taken 1
hr before or 4 hours after
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Pancreatitis has been reported, therefore in
presence of signs such as ab pain, N + V etc seek medical attention and discontinue permanently if
diagnosed with pancreatitis
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Sodium-glucose co-transporter 2 inhibitor (SGLT2); dapagliflozin
Combos include; alone; + insulin; + other antidiabetics
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e
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Usual dose: 10mg once daily
Cautions and contraindications: determine renal function before treatment and at least annually
thereafter (avoid if eGFR is less than 60ml/min)
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AVOID in DKA

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