Week 23 - Diabetes Type 1 and 2 and all complications! Flashcards
what is type one diabetes
where the pancreas stops being able to produce adequate insulin.
what is the result of not having insulin
the cells of the body cannot absorb glucose from the blood and use it as fuel.
therefore the cells think there is no glucose available, meanwhile the glucose level in the blood keeps rising causing hyperglycaemia
what is the classic triad of symptoms seen in type one diabetes (hyperglycaemia)
- polyuria (excessive urine)
- polydipsia (excessive thirst)
- weight loss (mainly through dehydration)
how else may patients present
with ketoacidosis
the body ideally wants to keep blood glucose concentration at what range
The body ideally wants to keep blood glucose concentration between 4.4 – 6.1 mmol/L.
where is insulin produced and what cell
the beta cells in the islets of langerhans in the pancreas
what are the two ways that insulin acts on the blood sugar levels
Firstly, it causes cells in the body to absorb glucose from the blood and use it as fuel. Secondly, it causes muscle and liver cells to absorb glucose from the blood and store it as glycogen in a process called glycogenesis. Firstly, it causes cells in the body to absorb glucose from the blood and use it as fuel.
Secondly, it causes muscle and liver cells to absorb glucose from the blood and store it as glycogen in a process called glycogenesis.
what is glucagon and what is its role in glucose metabolism
Glucagon is a hormone produced by the alpha cells in the Islets of Langerhans in the pancreas.
It is released in response to low blood sugar levels and stress and works to increase blood sugar levels. It tells the liver to break down stored glycogen and release it into the blood as glucose in a process called glycogenolysis. It also tells the liver to convert proteins and fats into glucose in a process called gluconeogenesis.
when does ketogenesis occur
when there is insufficient glucose supply and glycogen stores are exhausted, such as in prolonged fasting
what is converted to ketones and by what
fatty acids are converted to ketones by the liver
what is the characteristic about ketosis
acetone smell to their breath
what is diabetic ketoacidosis
The kidneys buffer ketone acids (ketones) in healthy people, so the blood does not become acidotic. When type 1 diabetes causes extreme hyperglycaemic ketosis, this results in a life-threatening metabolic acidosis. This is called diabetic ketoacidosis.
when does diabetic ketoacidosis occur
as a consequence of inadequate insulin
what are the three key features of diabetic ketoacidosis
ketoacidosis
dehydration
potassium imbalance
what happens in dehydration
high blood glucose levels overwhelm the kidneys, and glucose leaks into the urine. the glucose in the urine draws water out by osmotic diuresis. this causes increased urine production and resulting in severe dehydration
what does dehydration result in
polydipsia - excessive thirst
what does insulin normally do to potassium
normally drives potassium into cells.
what happens with insulin to potassium and what does this mean for the potassium imbalance
without insulin, potassium is not added to and stored in cells.
the serum potassium can be high or normal as the kidneys balance blood potassium with the potassium excreted into the urine
why is total body potassium low
because no potassium is stored in the cells
what call happen to the potassium imbalance when patients are treated with insulin
patients can develop severe hypokalaemia very quickly leading to severe arrhythmias
what are the symptoms of diabetic ketoacidosis
Polyuria
Polydipsia
Nausea and vomiting
Acetone smell to their breath
Dehydration
Weight loss
Hypotension (low blood pressure)
Altered consciousness
what may diabetic ketoacidosis be triggered by
an underlying infection.
what does a diagnosis of diabetic ketoacidosis require
Hyperglycaemia (e.g., blood glucose above 11 mmol/L)
Ketosis (e.g., blood ketones above 3 mmol/L)
Acidosis (e.g., pH below 7.3)
what is the priority treatment in diabetic ketoacidosis
fluid resuscitation to correct dehydration, electrolyte imbalance and acodisosi
what is fluid resuscitation followed by in diabetic ketoacidosis treatment
insulin infusion to get the cells to start taking up and using glucose and stop producing ketones
what is the pneumonic used for diabetic ketoacidosis treatment
FIG PICK
what does FIG PICK stand for
F – Fluids – IV fluid resuscitation with normal saline (e.g., 1 litre in the first hour, followed by 1 litre every 2 hours)
I – Insulin – fixed rate insulin infusion (e.g., Actrapid at 0.1 units/kg/hour)
G – Glucose – closely monitor blood glucose and add a glucose infusion when it is less than 14 mmol/L
P – Potassium – add potassium to IV fluids and monitor closely (e.g., every hour initially)
I – Infection – treat underlying triggers such as infection
C – Chart fluid balance
K – Ketones – monitor blood ketones, pH and bicarbonate
what should happen before stopping the insulin and fluid infusions in diabetic ketoacidosis
Ketosis and acidosis should have resolved
They should be eating and drinking
They should have started their regular subcutaneous insulin
TOM TIP: Remember, under normal circumstances, the rate of potassium infusion should not exceed 10 mmol/hour, as there is a risk of inducing an arrhythmia or cardiac arrest. In DKA, rates up to 20 mmol/hour may be used. Higher rates are only used in specific scenarios under expert supervision with cardiac monitoring and through a central line (rather than a peripheral cannula).
what are the autoantibodies seen in type one diabetes
Anti-islet cell antibodies
Anti-GAD antibodies
Anti-insulin antibodies
what is a measure of insulin production and how does it work
Serum C‑peptide is a measure of insulin production. It is low with low insulin production and high with high insulin production.
what does long term management of type one diabetes involve
Subcutaneous insulin
Monitoring dietary carbohydrate intake
Monitoring blood sugar levels upon waking, at each meal and before bed
Monitoring for and managing complications, both short and long term
what does a basal bolus regime of insulin involve a combination of:
background, long acting insulin injected once a day
short acting insulin injected 30 mins before consuming carbohydrates
what are insulin pumps
small devices that continuously infuse insulin at different rates to control blood sugar levels
what are insulin pumps alternative to
a basal bolus regime
what are the disadvantages of insulin pumps
Difficulties learning to use the pump
Having it attached at all times
Blockages in the infusion set
A small risk of infection
what are tethered pumps
devices with replaceable infusion sets and insulin. they are usually attached to the patient’s belt or around the waist with a tube connecting the pump to the insertion site. the controls for the infusion are on the pump itself
what are patch pumps
Patch pumps sit directly on the skin without any visible tubes. When they run out of insulin, the entire patch pump is disposed of, and a new pump is attached. A separate remote usually controls patch pumps.
what does Hb1AC measure
glycated haemoglobin which is how much glucose is attached to the haemoglobin molecule.
This reflects the average glucose level over the previous 2-3 months (red blood cells have a lifespan of about 4 months). It is measured every 3 to 6 months to track the average sugar levels. It is a lab test.
describe capillary blood glucose
Capillary blood glucose (finger-prick test) can be measured using a blood glucose monitor, giving an immediate result. Patients with type 1 and type 2 diabetes rely on these machines for self-monitoring their sugar levels.
what is continuous glucose monitors
similar to flash glucose monitors in that a sensor on the skin monitors the sugar level in the interstitial fluid
However, continuous glucose monitors send the readings over bluetooth and do not require the patient to scan the sensor.
what is a closed loop system for diabetes type one
also called an artificial pancreas, involves a combination of a continuous glucose monitor and an insulin pump. The devices communicate to automatically adjust the insulin based on the glucose readings. Patients still need to input their carbohydrate intake and adjust the system to account for strenuous exercise.
what are symptoms of hypoglycaemia
Typical symptoms are hunger, tremor, sweating, irritability, dizziness and pallor. More severe hypoglycaemia will lead to reduced consciousness, coma and death unless treated.
what does hypoglycaemia need to be treated initially with
rapid acting glucose
high sugary energy drink
after treating hypoglycaemia with rapid acting glucose, what is the next step
Once the blood glucose improves, they consume slower-acting carbohydrates (e.g., biscuits or toast) to prevent it from dropping again. Options for treating severe hypoglycaemia are IV dextrose and intramuscular glucagon.
what are the macrovascular complications of diabetes type one
Coronary artery disease is a significant cause of death in diabetics
Peripheral ischaemia causes poor skin healing and diabetic foot ulcers
Stroke
Hypertension
what are the microvascular complications of diabetes type one
Peripheral neuropathy
Retinopathy
Kidney disease, particularly glomerulosclerosis
what are the infection-related complications of diabetes type one
Urinary tract infections
Pneumonia
Skin and soft tissue infections, particularly in the feet
Fungal infections, particularly oral and vaginal candidiasis
what is type two diabetes
a condition where there is a combination of insulin resistance and reduced insulin production causing persistently high blood sugar levels
what is the simple pathophysiology behind diabetes type 2
Repeated exposure to glucose and insulin makes the cells in the body resistant to the effects of insulin. More and more insulin is required to stimulate the cells to take up and use glucose. Over time, the pancreas becomes fatigued and damaged by producing so much insulin, and the insulin output is reduced.
A high carbohydrate diet combined with insulin resistance and reduced pancreatic function leads to chronic high blood glucose levels (hyperglycaemia). Chronic hyperglycaemia leads to microvascular, macrovascular and infectious complications, as described in the type 1 diabetes section.
what are the non-modifiable risk factors for type two diabetes
older age
ethnicity - black
family history
what are the modifiable risk factors for type two diabetes
Obesity
Sedentary lifestyle
High carbohydrate (particularly sugar) diet
what is the presentation of diabetes
tiredness, polyuria, polydipsia, unintentional weight loss, opportunistic infections, slow wound healing, glucose in urine
what is acanthosis nigricans characterised by
thickening and darkening of the skin giving a velvety appearance, often at the neck, axilla and groin. it is often associated with insulin resistance
what is pre diabetes
an indication that the patient is heading towards diabetes. they do not fit the full diagnostic criteria but should be educated about the risk of diabetes and lifestyle changes
what Hb1AC reading indicates pre diabetes
An HbA1c of 42 – 47 mmol/mol
what does the Hb1AC rest reflect
the average glucose level over the previous 2-3 months
a Hb1ac of what indicates type 2 diabetes
Hb1Ac of 48mmol/mol
what is the management of type 2 diabetes
A structured education program
Low-glycaemic-index, high-fibre diet
Exercise
Weight loss (if overweight)
Antidiabetic drugs
Monitoring and managing complicationsw
what are the treatment targets for type 2 diabetes
48mmol/mol for new type 2 diabetes
53mmol/mol for patients requiring more than one medication
Hb1Ac is measured how many times
measured every 3 to 6 months until it is under control and stable
what is first line management of type 2 diabetes
metformin
what is added once the patient is settled on metformin if there is co existing heart diease or failure
an SGLT2 inhibitor if the patient has co existing cardiovascular disease or heart failure
what is the normal SGLT2 inhibitor used for diabetes type 2 with metformin
dapagliflozin
what is second line after metformin
Second-line is to add a sulfonylurea, pioglitazone, DPP-4 inhibitor or SGLT-2 inhibitor.
what are the third line options to treat diabetes type 2
triple therapy with metformin and two of the second line drugs
insulin therapy
what is considered where triple therapy fails and the patient’s BMI is above 35kg/m2
Where triple therapy fails, and the patient’s BMI is above 35 kg/m2, there is the option of switching one of the drugs to a GLP-1 mimetic (e.g., liraglutide).
what does metformin do
increases insulin sensitivity and decreases glucose production by the liver
it is biguanide
does metformin cause weight gain and hypoglycaemia
metformin does not cause weight gain and does not cause hypoglycaemia
what are the notable side effects of metformin
Gastrointestinal symptoms, including pain, nausea and diarrhoea (depending on the dose)
Lactic acidosis (e.g., secondary to acute kidney injury)
what can patients with gastrointestinal side effects with standard release metformin try
modified release metformin
what suffix do SGLT2 inhibitors end in
suffix -gliflozin. Examples are empagliflozin, canagliflozin, dapagliflozin and ertugliflozin.
where is the sodium-glucose co-transporter 2 protein found
in the proximal tubules of the kidneys
it acts to reabsorb glucose from the urine back into the blood
SGLT-2 inhibitors block the action of this protein, causing more glucose to be excreted in the urine. Loss of glucose in the urine lowers the HbA1c, reduces the blood pressure, leads to weight loss and improves heart failure.
what can SGLT2 inhibitors cause
hypoglycaemia when used with insulin or sulfonylureas
which SGLT2 inhibitors are licensed for heart failure
Empagliflozin and dapagliflozin
what is licensed for chronic kidney disease
Dapagliflozin
what are the notable side effects of SGLT2 inhibtors
Glycosuria (glucose in the urine)
Increased urine output and frequency
Genital and urinary tract infections (e.g., thrush)
Weight loss
Diabetic ketoacidosis, notably with only moderately raised glucose
Lower-limb amputation may be more common in patients on canagliflozin (unclear if this applies to the others)
Fournier’s gangrene (rare but severe infection of the genitals or perineum)
TOM TIP: Remember two side effects of SGLT-2 inhibitors. Firstly, an increased frequency of urinary tract infections and genital thrush due to lots of sugar passing through the urinary tract. Secondly, diabetic ketoacidosis. Patients starting SGLT-2 inhibitors are counselled about the features of DKA and when to seek emergency medical input.
what is pioglitazone
a thiazolidinedione
what is the mode of action of Pioglitazone
it increases insulin sensitivity and decreases liver production of glucose. it does not typically cause hypoglycaemia
what are the notable side effects of Pioglitazone
weight gain
heart failure
increased risk of bone fractures
small increase in risk of bladder cancer
what is the most common sulfonylurea
Gliclazide is the most common sulfonylurea. Sulfonylureas stimulate insulin release from the pancreas.
what are the notable side effects of sulfonylureas
weight gain
hypoglycaemia
what are incretins
hormones produced by the GI tract
incretins are secreted in response to large meals and acts to reduce blood sugar by what actions:
increasing insulin secretion
inhibiting glucagon production
slowing absorption by the GI tract
what is the main incretin
The main incretin is glucagon-like peptide-1 (GLP-1).
what are incretins inhibited by
an enzyme called dipeptidyl peptidase-4 (DPP-4).
what do DPP4 inhibitors do
block the action of DPP-4, allowing increased incretin activity. Examples of DPP-4 inhibitors are sitagliptin and alogliptin. They do not cause hypoglycaemia.
what are the notable side effects of DPP4 inhibitors
headaches
low risk of acute pancreatitis
give two examples of GLP1 mimetics
exenatide and liraglutide
what are the notable side effects of GLP1 mimetics
reduced appetite
weight loss
gastrointestinal symptoms
give an example of a rapid acting insulin
novorapid
how does novorapid work
start working after around 10 minutes and last about 4 hours.
give an example of short acting insulins
actrapid
how does actrapid work
start working in around 30 minutes and last about 8 hours.
give an example of intermediate acting insulins
humulin 1
how does humulin 1 work
start working in around 1 hour and last about 16 hours.
give 2 examples of long acting insulins
Levemir and Lantus
how do long acting insulins work
start working in around 1 hour and last about 24 hours or longer.
what do combination insulins contain
Combinations insulins contain a rapid-acting and intermediate-acting insulin. In brackets is the ratio of rapid-acting to intermediate-acting insulin:
Humalog 25 (25:75)
Humalog 50 (50:50)
Novomix 30 (30:70)
what is used first line to manage hypertension in patients with type 2 diabetes
ACE inhibitors
when are ACE inhibitors started in type 2 diabetics with chronic kidney disease
when the albumin-to-creatinine ratio (ACR) is above 3 mg/mmol (as opposed to 30 mg/mmol in patients without diabetes).
when are SGLT2 inhibitors started in type 2 diabetics with chronic kidney disease
when the albumin-to-creatinine ratio (ACR) is above 30 mg/mmol (in addition to the ACE inhibitor).
what may be used for erectile dysfunction in type 2 diabetics
Phosphodiesterase‑5 inhibitors (e.g., sildenafil or tadalafil) may be used for erectile dysfunction.
what drugs may be used for gastroparesis in type 2 diabetics
Prokinetic drugs (e.g., domperidone or metoclopramide) may be used for gastroparesis (slow emptying of the stomach). These medications are used with caution due to cardiac side effects.
what are the four options of drugs for neuropathic pain diabetic neuropathy
Amitriptyline – a tricyclic antidepressant
Duloxetine – an SNRI antidepressant
Gabapentin – an anticonvulsant
Pregabalin – an anticonvulsant
what is a hyperosmolar hyperglycaemic state
a rare but potentially fatal complication of type 2 diabetes
how is HHS characterised
hyperosmolality (water loss leads to very concentrated blood), high sugar levels (hyperglycaemia) and the absence of ketones, distinguishing it from ketoacidosis.
how does HHS present
with polyuria, polydipsia, weight loss, dehydration, tachycardia, hypotension and confusion.
what is the treatment of HHS
It is a medical emergency with high mortality. Involve experienced seniors early. Treatment is with IV fluids and careful monitoring.
what are the three mechanisms via which the kidney can be damaged due to diabetes
glomerular damage
ischaemia caused by damage to efferent and afferent arterioles
ascending infection
what kind of disease is diabetic nephropathy primarily
a disease of younger diabetics, and the incidence is lower in older patients.
what does renal hypertrophy lead to
leads to glomerular sclerosis.
there is thickening of the basement membrane and disruptions in the linkages between cells - ultimately means that larger molecules are allowed to be filtered that normally wouldnt be so
what is the first detectable marker of diabetic nephropathy
albuminurea
what are two things patients with nephropathy tend to have
normocytic normochromic anaemia and be hypertensive
what can the risk of progression of diabetic nephropathy be reduced by
aggressively tackling cardiovascular risk factors
giving ACE inhibitor therapy
strictly controlling glucose
what is usually present with nephropathy
diabetic retinopathy
what diabetic treatment do you need to avoid in diabetic nephropathy
glibenclamide
what is diabetic neuropathy directly related to
the duration and degree of abnormal metabolic control
what is diabetic neuropathy thought to be due to
metabolic disturbances. one of the most common theories is that the Schwann cells are affected. it is thought that the accumulation of fructose and sorbitol in schwann cells leads to their degradation
what is the first sign in diabetic neuropathy
delayed nerve signal transit time
this is a direct result of demyelination, as a result of damage to Schwann cells
what are the five types of neuropathy in diabetes
Symmetrical, mainly sensory neuropathy in distal regions
Acute painful neuropathy
Mononeuropathy and mononeuritis multiplex. This can occur either to cranial nerves, or to individual peripheral nerves
Diabetic amyotrophy – this is progressive wasting of muscle tissues
Autonomic neuropathy
what are the first signs of symmetrical mainly sensory neuropathy
loss of pain, temperature and vibration feelings
in what pattern is sensation lost in diabetic neuropathy
in a stocking and glove pattern
what is the classic foot shape of a diabetic and what is this a result of
motor neurones to the interosseous muscles of the foot can also be involved. this leads to wasting of the muscles, and this then alters how other muscles act on the foot.
this gives rise to the classic foot shape of a high arch and clawing toes. this alters the weight distribution on the foot, and can lead to calluses and ulcer formation
when may acute painful neuropathy develop
after sudden improvement in glycaemic control (the patient starts on insulin)
what can be given for acute painful neuropathy
Gabapentin, carbamezipine and tricyclic antidepressants can reduce the pain, but often not as much as the patient would like.
what are the most common nerves involved with mononeuritis and mononeuritis multiplex
3rd and 6th cranial nerves, this resulting in reduced ocular movement
what syndrome is very common in diabetics
carpal tunnel syndrome
in who is diabetic amyotrophy seen in and what is the presentation
tends to be seen in older men with diabetes. presentation tends to be with painful wasting of the quadriceps muscles
why dont diabetics feel a heart attack
due to autonomic neuropathy of the vagus nerves
what can vagal damage lead to
gastroparesis
what agents are known to be effective against neuropathic pain
Amitriptyline – a tricyclic antidepressant. Should be used first line
Pregabalin (Lyrica®) – may be considered in cases resistant to amitriptyline
Gabapentin
