Diabetes Flashcards
Ix T1DM (5 things)
urine dip: glucose and ketones
fasting glucose and random glucose
HbA1c: may not accurately reflect a recent rapid rise in serum glucose
C-peptide: low
diabetes-specific autoantibodies: useful to distinguish between type 1 and type 2 diabetes
T1DM autoantibodies
- glutamic acid decarboxylase (anti-GAD)
- insulin (IAA)
- islet cells (ICA)
- insulinoma-associated-2 (IA-2A)
T1DM diagnostic criteria
symptomatic:
- fasting glucose >7.0 mmol/l
- random glucose > 11.1 mmol/l
(or after 75g oral glucose tolerance test)
asymptomatic:
- above criteria demonstrated on two separate occasions.
T1DM
- age
- speed of onset
- features
- < 20 years
- more acute, hours-days
- features of DKA, weight loss, ketonuria
T2DM
- age
- speed of onset
- features
- > 40 years
- slower, weeks-months
- milder symptoms, polyuria, polydipsia, obesity, ketonuria is rare
T2DM diagnostic criteria
symptomatic:
- fasting glucose >7.0 mmol/l
- random glucose >11.1 mmol/l
(or after 75g oral glucose tolerance test)
asymptomatic
- above criteria apply but must be demonstrated on two separate occasions.
HbA1c diagnosis of diabetes
HbA1c >48 mmol/mol (6.5%) = diabetes mellitus
cause of misleading HbA1c results
increased red cell turnover
conditions where HbA1c may not be used for diagnosis:
haemoglobinopathies
haemolytic anaemia, untreated iron deficiency anaemia
suspected gestational diabetes
children
HIV
chronic kidney disease
people taking medication that may cause hyperglycaemia (for example corticosteroids)
fasting glucose
>6.1 but <7.0 mmol/l implies
impaired fasting glucose (IFG)
Impaired glucose tolerance (IGT) is defined as
fasting glucose greater than or equal to 6.1 but less than 7.0 mmol/l implies
OGTT 2-hour value greater than or equal to 7.8 mmol/l but less than 11.1 mmol/l
The main focus of diabetes management now is
reducing incidence of complications:
- macrovascular: ischaemic heart disease, stroke
- microvascular: eye, nerves and kidney damage
T1DM
an autoimmune disorder where insulin-producing beta cells of the islets of Langerhans in the pancreas are destroyed by the immune system
this results in an absolute deficiency of insulin resulting in raised glucose levels
patients tend to develop T1DM in childhood/early adult life and typically present unwell, possibly in diabetic ketoacidosis
T2DM
most common cause of diabetes in the developed world.
relative deficiency of insulin due to an excess of adipose tissue.
in simple terms there isn’t enough insulin to ‘go around’ all the excess fatty tissue, leading to blood glucose creeping up.
prediabetes
patients who don’t yet meet the criteria for a formal diagnosis of T2DM to be made but are likely to develop the condition over the next few years.
they require closer monitoring and lifestyle interventions such as weight loss
gestational diabetes
raised glucose levels during pregnancy.
important to detect as untreated it may lead to adverse outcomes for the mother and baby
maturity onset diabetes of the young (MODY)
group of inherited genetic disorders affecting the production of insulin.
results in younger patients developing symptoms similar to those with T2DM
asymptomatic hyperglycaemia with progression to more severe complications such as diabetic ketoacidosis
latent autoimmune diabetes of adults (LADA)
majority of patients with autoimmune-related diabetes present younger in life.
there are however a small group of patients who develop such problems later in life.
these patients are often misdiagnosed as having T2DM
pathological processes which damage insulin-producing cells of pancreas and cause diabetes to develop.
chronic pancreatitis
haemochromatosis
drugs which cause raised glucose levels
glucocorticoid
polyuria and polydipsia are due to
water being ‘dragged’ out of the body
due to the osmotic effects of excess blood glucose being excreted in the urine (glycosuria).
four main ways to check blood glucose:
finger-prick bedside glucose monitor
one-off blood glucose
- fasting
- non-fasting
HbA1c
- measures amount of glycosylated haemoglobin
- represents average blood glucose over past 2-3 months
glucose tolerance test
- fasting blood glucose is taken - 75g glucose load is taken
- after 2 hours a second blood glucose reading is then taken
principle of managing T1DM
patients always require insulin to control the blood sugar levels.
this is because there is an absolute deficiency of insulin with no pancreatic tissue left to stimulate with drugs
different types of insulin are available according to their duration of action
principle of managing T2DM
first-line: metformin
second-line: sulfonylureas, gliptins and pioglitazone.
if oral medication is not controlling the blood glucose to a sufficient degree then insulin is used
Insulin
Mechanism:
Route:
Main side effects:
Direct replacement for endogenous insulin
Subcutaneous
Hypoglycaemia, Weight gain, Lipodystrophy
Used in all patients with T1DM and some patients with poorly controlled T2DM
What is first line in T2DM?
Metformin
Metformin
Mechanism:
Route:
Main side effects & considerations?
Increases insulin sensitivity & Decreases hepatic gluconeogenesis
Oral
Gastrointestinal upset, Lactic acidosis
Cannot be used in patients with an eGFR of < 30 ml/min
Sulfonylureas Mechanism: Route: Main side effects: Examples:
Stimulate pancreatic beta cells to secrete insulin Oral
Hypoglycaemia, Weight gain, Hyponatraemia
Examples include gliclazide and glimepiride
Thiazolidinediones Mechanism: Route: Main side effects: Examples:
Activate PPAR-gamma receptor in adipocytes to promote adipogenesis and fatty acid uptake
Oral
Weight gain, Fluid retention
Only currently available thiazolidinedione is pioglitazone
DPP-4 inhibitors Mechanism: Route: Main side effects: Examples:
Increases incretin levels which inhibit glucagon secretion Oral Generally well tolerated but increased risk of pancreatitis
(-gliptins)
SGLT-2 inhibitors Mechanism: Route: Main side effects: Examples:
Inhibits reabsorption of glucose in the kidney Oral Urinary tract infection
(-gliflozins)
GLP-1 agonists (-tides) Mechanism: Route: Main side effects: Examples:
Incretin mimetic which inhibits glucagon secretion
Subcutaneous
Nausea and vomiting, Pancreatitis
(-tides)
Which diabetes meds result in weight loss
SGLT-2 inhibitors (-gliflozins)
GLP-1 agonists (-tides)
What is glucagon-like peptide-1 (GLP-1),
hormone released by the small intestine in response to an oral glucose load
Increasing GLP-1 levels, either by the administration of an analogue (glucagon-like peptide-1, GLP-1 mimetics, e.g. exenatide) or inhibiting its breakdown (dipeptidyl peptidase-4 ,DPP-4 inhibitors - the gliptins), is therefore the target of two recent classes of drug.
What is the incretin effect
In normal physiology an oral glucose load results in a greater release of insulin than if the same load is given intravenously - this known as the incretin effect. This effect is largely mediated by GLP-1 and is known to be decreased in T2DM.
in t2dm insulin resistance and insufficient B-cell compensation occur
example of a glucagon-like peptide-1 (GLP-1) mimetic.
exenatide
Liraglutide
Examples of Dipeptidyl peptidase-4 (DPP-4) inhibitors
Vildagliptin, sitagliptin
Key points of GLP-1 mimetics?
ne of the major advances of GLP-1 mimetics is that they typically result in weight loss, in contrast to many medications such as insulin, sulfonylureas and thiazolidinediones. They are sometimes used in combination with insulin in T2DM to minimise weight gain.
Exenatide must be given by subcutaneous injection within 60 minutes before the morning and evening meals. It should not be given after a meal.
Liraglutide is the other GLP-1 mimetic currently available. One the main advantages of liraglutide over exenatide is that it only needs to be given once a day.
Both exenatide and liraglutide may be combined with metformin and a sulfonylurea. Standard release exenatide is also licensed to be used with basal insulin alone or with metformin. Please see the BNF for a more complete list of licensed indications.
Consider adding exenatide to metformin and a sulfonylurea if:
BMI >= 35 kg/m² in people of European descent and there are problems associated with high weight, or
BMI < 35 kg/m² and insulin is unacceptable because of occupational implications or weight loss would benefit other comorbidities.
NICE like patients to have achieved a > 11 mmol/mol (1%) reduction in HbA1c and ?% weight loss after 6 months to justify the ongoing prescription of GLP-1 mimetics.
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