1
Q
What is the main indicator of diabetes mellitus?
A
Persistently raised blood sugar levels
2
Q
Liver = producer of glucose and can store glycogen
Pancreas = controller of blood glucose levels (tells liver what to do with glucose) through its specialised cells (detectors)
A
3
Q
Hypoglycaemia leads to… (hormone & location & levels)
A
Glucagon secretion from alpha cells
Typically less than 4mmol/l.
4
Q
Hyperglycaemia leads to… (hormone & location)
A
Insulin secretion from beta cells (negative feedback loop)
5
Q
What does glucagon act on and why (2)?
A
Hepatocytes (liver cells)
- Accelerate conversion of glycogen into glucose
- Promote formation of glucose from lactic acid & amino acids
6
Q
What does this lead to?
A
Liver releases glucose into the blood more rapidly
If blood glucose levels continue to rise, hyperglycaemia inhibits release of glucagon = negative feedback loop to prevent excess glucose release into bloodstream
7
Q
Insulin acts on various cells in the body to increase the uptake of glucose into cells, especially which cells (2)?
A
Skeletal muscle fibres & adipocytes
8
Q
Two storage locations for glycogen:
A
Liver & muscle
9
Q
Other effects of insulin release (4)?
A
- Cells uptake amino acids for protein synthesis
- Enables conversion of fatty acids into triglycerides (stored in adipocytes)
- Slows conversion of glycogen to glucose
- Slows formation of glucose from lactic acid & amino acids
10
Q
Type 1 diabetes is a disease which results from… & potential cause (2)
A
Autoimmune destruction of most of the beta cells in the Islets of Langerhans in the pancreas
Thought to be a combination of genetic predisposition & environmental factors
11
Q
When is T1D often diagnosed?
A
Type 1 diabetes is often diagnosed in childhood.
The vast majority of people under the age of 18 years with diabetes suffer from Type 1 diabetes.
12
Q
Type 2 diabetes occurs when…
A
The body is still capable of producing insulin, but the amount produced is inadequate to control sugar levels
13
Q
Insulin resistance can occur years before T2D diagnosis, what are two signs of this state (pre-diabetic state)?
A
- Raised blood glucose levels between meals
- Reduced ability to clear glucose from circulation quickly and completely (impaired glucose tolerance (IGT))
14
Q
During this time, however, some biochemical changes, particularly abnormal blood glucose levels, can be detected and may be discovered by chance. If individuals change their diet and lifestyle, they can potentially reverse this ‘pre-diabetic stage’ and thus stop the development of Type 2 diabetes.
A
15
Q
What is the ominous octet?
A
Eight factors which play important roles in the development of glucose intolerance in T2D
Glucose intolerance = body is unable to regulate blood glucose properly
16
Q
What are they?
A
- Decreased glucose uptake in muscle
- Decreased insulin secretion in pancreas (beta cell failure)
- Decreased incretin effect in GI tract
- Increased glucose production in liver
- Increased lipolysis in adipose tissue
- Increased glucagon secretion in pancreas (alpha cells)
- Increased glucose reabsorption in kidney
- Adverse effects on neurotransmitter function in brain
17
Q
Incretins are a group of metabolic hormones that decrease blood glucose levels. Incretins are released after eating and augment the secretion of insulin released from pancreatic beta cells of the islets of Langerhans by a blood-glucose–dependent mechanism. GLP-1 & GIP are incretin hormones
A
18
Q
People with insulin resistance frequently have Metabolic Syndrome. What are factors constituting this? (4)
A
- Central (apple-shaped) obesity
- High blood pressure (hypertension)
- Dyslipidaemia (abnormal blood lipid pattern)
- Micro-albuminuria (presence of protein in the urine)
19
Q
What are those with these factors at greater risk of developing?
A
Cardiovascular disease (heart attack or stroke)
20
Q
What is the percentage accountability for both T1D & T2D?
A
T1D = 10%
T2D = 90%
21
Q
Symptoms of diabetes: (6)
A
Thirst (with frequent drinking - polydipsia)
Frequent urination - polyuria
Unexplained weight loss
Fatigue & weakness
Blurred vision
Numbness or tingling in the hands and feet
Symptoms may be slight at first in T2D and not all symptoms may be present
22
Q
What are 2 other symptoms common in T1D?
A
- Muscle cramps
- GI symptoms like nausea, vomiting, abdominal pain and changes in bowel movements
23
Q
Test to determine glucose levels in the urine (hyperglycaemia) & blood glucose levels:
A
Dipstick test
Finger prick test
24
Q
A chemically treated strip is dipped into fresh urine; if glucose is present, it reacts with glucose oxidase on the strip and changes color. Normally, urine contains no glucose, but when blood glucose exceeds the renal threshold (about 10 mmol/L), it spills into the urine.
A
25
Normal | Pre-Diabetic | Diabetic
Fasting Plasma Glucose
< 5.6 mmol/L | 5.6–6.9 mmol/L | ≥ 7.0 mmol/L
2‑hr OGTT
< 7.8 mmol/L | 7.8–11.0 mmol/L | ≥ 11.1 mmol/L
Random Plasma Glucose
— — ≥ 11.1 mmol/L + symptoms
HbA1c
< 5.7% | 5.7–6.4% | ≥ 6.5%
26
Above what random venous plasma level indicates that a patient has diabetes (alongside symptoms)?
>11.1mmol/l
same or greater than
27
What is diabetes insipidus and a common symptom of it?
When the body is unable to regulate the body's water balance due to problems with antidiuretic hormone (ADH) resulting in polyuria (excessive urination & thirst).
Those with diabetes insipidus don't have problems with their blood glucose levels.
28
What is the purpose of the oral glucose tolerance test (OGTT)?
Determine how well the body processes sugar
29
What are the two steps for this?
1. Initially, blood glucose levels are determined via the ‘fasting test’, whereby the patient refrains from eating or drinking (apart from water) for at least eight hours.
2. Patients are then given a sugary drink which consists of 75g of glucose in 250–300mls of water which is ingested over five minutes. A venous blood sample is then taken two hours after the drink.
Note: oral glucose tolerance tests are not recommended as a standalone screening test but it is the only way of identifying people with impaired glucose tolerance (IGT).
30
What level of plasma glucose levels two hours after drinking 75g of glucose for OGTT determine diabetes diagnosis?
>11.1mmol/l
31
What are some gastric diabetes symptoms (4)?
Cramps
Constipation - T2D
Nausea - T1D
Vomiting - T1D
32
What is HbA1c?
Haemoglobin joining with glucose in the blood becoming glycosylated.
Higher HbA1c levels = more glucose in bloodstream
% represents % of Haemoglobin in blood which is glycosylated
33
The results of a random venous plasma glucose, or a fasting plasma glucose, or a glucose tolerance test, or an HbA1c test enable a diagnosis to be made when symptoms are present. With no symptoms, diagnosis should not be based on a single glucose determination and requires additional testing.
34
What results from random venous plasma glucose levels and fasting venous plasma glucose levels determine diagnosis of diabetes?
Random venous plasma glucose levels - >11.1mmol/l
Fasting venous plasma glucose levels - >7.0mmol/l
(same or greater than)
1 mmol/L = 1 millimole of glucose per liter of blood
35
HbA1c blood levels for diabetes?
>48mmol/mol (6.5%)
36
A diagnosis of diabetes can be made if HbA1c is ≥ 48 mmol/mol (6.5%), indicating long-term elevated blood sugar, or if random plasma glucose is ≥ 11.1 mmol/L, reflecting a high blood sugar level at a single point in time, especially if symptoms are present.
37
What will some HCPs aim for readings of HbA1c levels?
Typically below 42mmol/mol, or 6%
38
Impaired Glucose Tolerance (IGT) is a prediabetic state and diagnosed through the OGTT. (fasting plasma glucose <7.0mmol/l and OGTT ≥7.8mmol/l but <11.1mmol/l).
These results are saying fasting glucose looks okay, but after eating (or a sugar load), the body struggles to handle the glucose spike — higher risk for developing Type 2 diabetes later on.
39
A value of less than 48mmol/mol does not exclude diabetes, and in patients without symptoms, the HbA1c test should be repeated. If the second sample is <48mmol/mol the patient should be treated as high diabetes risk and repeat-tested in six months or sooner if symptoms develop.
40
Why has Impaired Fasting Glycaemia (IFG) been introduced?
To classify individuals who have fasting glucose values above the normal range but below those diagnostic of diabetes (fasting plasma glucose ≥6.1mmol/l but <7.0mmol/l).
41
What symptoms develop when glucose has been present in the urine for some time?
Itching or a rash in the urogenital area, due to an infection by yeasts
42
What is a test that patients can monitor their blood glucose levels regularly at home?
Traditional home blood glucose monitor involving the prick of a finger with a lancet (very fine needle)
43
Next step?
Drop of blood put onto test strip and placed into a measuring device, a glucose meter to display the patients' blood glucose levels
44
Meters vary in size and cost and also the speed at which they work (some results can be achieved in less than 15 seconds). Information can be stored for future usage and then average blood glucose levels can be calculated over a period of time. Some glucose meters have software kits that can convert the readings into graphs of previous test results.
45
Purpose of a continuous glucose monitoring system (CGMS)?
A device that will record interstitial fluid glucose levels throughout the day and night.
46
How is this device inserted and who by?
A HCP inserts the glucose-sensing device under the skin of the abdomen. Tape holds the device in place. The sensor measures the glucose in the interstitial fluid every 10 seconds and sends the information to a monitor, which can be attached to the patient’s clothing. The system will monitor glucose levels 24 hours a day.
47
The results of four standard glucose meter readings (finger-prick test) are taken at different times of the day and entered into the monitor to calibrate the machine. Any food eaten, insulin taken and exercise done are also recorded into the monitor and noted.
48
What is the main advantage of a test like CGMS?
Help identify any fluctuations and trends that would otherwise go unnoticed with an HbA1c test or the standard glucose meter (finger-prick) test
49
Which ethnic groups (2) have a higher likelihood of developing diabetes and to what extent for both?
More than 6X more common in south asian descent
Up to 3X more common among people of African & African-Caribbean origin
50
How many genes have been found to have an influence on the likelihood of developing T1D?
More than 100 genes.
There has been a link with the human leukocyte antigen (HLA) gene on chromosome 6 to have the most direct effect.
51
By what percentages, for both parents and combined, does T1D increase if they have it?
Mother = 2-4%
Father = 6-9%
Combined = 30%
52
What about for T2D prevalence in next generations within a family?
People with Type 2 diabetes in the family are 2-6X more likely to have diabetes than people without Type 2 diabetes in the family.
53
What percentage of those with T2D are overweight?
80%. The risk of developing the disease increases progressively as BMI, waist-to-hip ratio, waist circumference, or, more specifically, the amount of deep (visceral) abdominal body fat increases.
54
Which indicator of diabetes has been shown to have a greater accuracy of developing diabetes than BMI & what measurements for both female & males?
Waist circumfrence
Female = more than 88cm
Male = more than 102cm
55
What is central to the development of insulin resistance in obese people (3) & where (3)?
Changes in the number, type, and location of fat cells in the body
fat, muscle, and liver.
56
What blood glucose levels indicate hypoglycaemia?
less than 4mmol/l
If hypoglycaemia is severe, insufficient glucose in the blood to provide the energy that the brain needs results in recognisable symptoms often known as a hypo - loss of consciousness may occur
57
Hypoglycaemia is a recognised side effect of which two treatments?
Insulin and/or sulfonylureas.
During standard insulin therapy for Type 1 diabetes, people may have one or more serious episodes of hypoglycaemia in a year, especially where intensive insulin therapy is used to obtain tight control of blood glucose levels.
58
Patients who have not eaten enough carbohydrates can be at risk of low glucose levels. What three other factors can induce hypoglycaemia?
Effects of exercise, alcohol intake, and other medications.
59
What three factors are important for establishing the right insulin medication for an individual to minimise the risk of hypoglycaemia?
The right insulin type, dose, and timing to minimise the risk of a hypo.
Important to self-monitor blood glucose, adopt regular eating and exercise habits, and developing awareness of the warning signs of a hypo.
60
What symptoms of oncoming hypoglycaemia vary from one person to another?
Sweating
Rapid pulse
Shaking
Blurred vision
Confusion
Hunger
Headache
Feeling tearful or moody
Pallor (pale)
Convulsions (seizures)
Weakness
Loss of consciousness and in more serious cases, coma
Death is very rare.
61
What hormone being released causes sweating, pounding heart, and tremor?
Release of adrenaline
Glucagon is also released to counteract symptoms related to hypoglycaemia
62
Why is adrenaline and glucagon released in response to low blood glucose levels (2)?
1. Inhibit insulin secretion
2. Stimulate liver to increase glucose output
= leading to recovery
63
In some diabetics, there may be very little or no warning sign before the onset of a hypo. In this case, the individual may become confused and eventually unconscious, without recognising other warning signs. What is hypoglycaemia unawareness and what may the individual become?
Hypoglycaemia unawareness = the inability to recognise the onset of a hypo
May become confused and eventually unconscious without recognising other warning signs
64
What can be taken when a developing hypo is recognised?
Taking a small oral dose of sugar (any carb but not chocolate as it does not work quickly enough due to its fat content). It should be followed by taking a longer-acting snack containing complex carbs.
65
If a hypo occurs and the person has become unconscious, what medical attention is needed?
An HCP providing glucagon either intravenously, intramuscularly, or subcutaneously
66
In which patients does diabetic ketoacidosis (DKA) occur usually in?
T1D
It is not uncommon in some patients with T2D
67
What causes DKA and how does it occur?
Consistently high blood glucose levels.
A severe lack of insulin means glucose isn't used for energy. Instead, the body breaks down fatty acids into ketone bodies as an alternative energy source. Ketone bodies building up leads to tissues within the body becoming acidic, causing ketoacidosis.
68
What are some common symptoms of DKA? (8)
1. Polyuria
2. Polydipsia
3. Weight loss
4. Vomiting
5. Dehydration
6. Dyspnea (breathing problems)
7. Confusion
8. Abdominal pain
Coma may occur therefore it is a medical emergency.
69
When does gestational diabetes occur and what % of people have it?
Gestational diabetes occurs during pregnancy in people who have not previously suffered from diabetes.
About 5% of pregnant people have gestational diabetes.
70
Close attention to monitoring and managing blood glucose levels are carried out through 3 essential ways:
1. Diet
2. Exercise
3. Insulin self-treatment (potentially)
71
What are two possibilities if the birthing parent has gestational diabetes?
Miscarriage & stillbirth
72
In which population does Hyperosmolar Hyperglycaemic State (HHS) occur in?
The potentially life-threatening condition occurs in people with T2D who experience very high blood glucose levels (often over 40mmol/l)
73
3 causes of HHS:
It can develop over the course of weeks through a combination of:
1. Illness (infection)
2. Dehydration
3. Rise via the effect of other hormones the body produces during illness
HHS develops when illness causes a rise in stress hormones, which raise blood sugar and reduce insulin’s effectiveness. The result is extremely high glucose, leading to dehydration through excess urination, and eventually severe hyperosmolarity — a dangerous state that worsens brain and organ function.
74
Symptoms early on (5) & late stages (2) of HHS:
Frequent urination, dehydration with marked thirst, nausea, dry skin, disorientation
Later - drowsiness and gradual loss of consciousness
75
Essential treatment: (2)
Urgent hospitalisation and treatment to lower blood glucose by giving replacement fluid and insulin by an intra-venous drip
76
Retinopathy = damage to retina
Nephropathy = damage to kidney
Neuropathy = damage to nerves
Microalbuminuria is a small increase in urinary albumin (30–300 mg/day), while macroalbuminuria is a larger increase (>300 mg/day), indicating more advanced kidney damage.
77
The US Diabetes Control and Complications Trial (DCCT) showed that, over a six and a half year period, intensive insulin treatment aimed at lowering HbA1c levels reduced the risk of new onset of: (3)
Retinopathy by 76%
Neuropathy by 69%
Microalbumia, the first stage of nephropathy (kidney disease) by 34% compared with conventional insulin treatment
78
The United Kingdom Prospective Diabetes Study (UKPDS) followed just over 5,000 people with Type 2 diabetes between 1977 and 1997. It found that tight control of blood glucose through diet, exercise and medication can prevent complications from developing, even after several decades. If blood glucose was controlled adequately, it reduced the risk of: (2)
Microvascular complications (retinopathy and kidney disease) by 37% for each reduction of 1% in HbA1c level
The UKPDS also showed that the risk of macrovascular complications (such as heart attack and stroke) was also reduced.
79
Which population is less likely to have nepthropathy?
T2D population
However, its earlier stages of microalbuminuria and macroalbuminuria are not infrequent.
80
Although microvascular complications – retinopathy, nephropathy and neuropathy – seriously affect the health of many people with diabetes, macrovascular complications are more common. What are these (5)?
Stroke
Angina
Heart attack
Heart failure
Peripheral vascular disease
81
What should be tightly controlled to prevent macrovascular complications?
Tight control of blood pressure
82
There are no diabetes-specific medications being actively developed for macrovascular complications because treatments are the same for people without diabetes. What are these treatments (3)?
1. Anti-hypertensives
2. Aspirin
3. Statins
83
Retinopathy affects both populations and is one of the more common complications, what is it?
A disease of the small blood vessels of the retina at the back of the eye
84
What are two symptoms of retinopathy & its detection?
1. Micro-aneurysms (tiny outgrowths of small blood vessels in the retina)
2. Small haemorrages
Detected by an eye examination
85
What causes retinopathy?
Hyperglycaemic damage that weakens capillaries of the retina
Diabetes also accelerates the formation of cataracts.
86
As retinal capillary damage worsens, what two things form following areas of cell death in the nerve fibre layer of the retina?
1. Hard exudates may form on the retina as a result of leakage from the blood vessels
2. 'Cotton wool spots'
87
Retinopathy may then spread, with the formation of new, small blood vessels over the retina. What can follow this?
Maculopathy (disease of the macula – the central area of the retina that is responsible for detailed central vision) can also follow.
Both can cause severe sight loss.
88
Where does neuropathy most commonly affect and does it lead to?
Legs & feet. Can affect hands.
Produce numbness that may lead to foot problems such as ulceration. Often results in incapacitating, burning nerve pain.
89
What % of individuals are affected by erectile dysfunction and what % of individuals over the age of 70 suffer with it?
75% rising to 95% when over the age of 70
90
What can cause this? (3)
1. Nerve damage
2. Damage to blood vessels
3. Certain medications needed by such patients can also be a contributory factor.
91
What is the cause of death for 80% of people with diabetes?
Coronary heart disease
People with T1D or T2D are at greater risk of developing high blood pressure, stroke, and heart attacks
92
A 2007 report from Diabetes UK estimated that the risk of cardiovascular disease is how many times more likely in middle-aged men & females with diabetes (individual)?
Middle-aged men = 5X
Women = 8X
93
Acute pancreatitis is an inflammatory condition of the pancreas. The incidence of pancreatitis is increasing. The reason for the increased incidence of acute pancreatitis is unknown; however, it is notable that a concurrent trend has been the rapid, worldwide increase in Type 2 diabetes and obesity. The Type 2 diabetic cohort had a 2.83-fold greater risk of pancreatitis than non-diabetics in one study.
94
What can high levels of circulating insulin (hyperinsulinemia) promote?
The growth of tumours
95
Which cancers have double the risk of being developed by T2D (3)?
1. Pancreatic cancer
2. Liver cancer
3. Endometrial cancer (uterine cancer located in tissues lining the uterus)
96
Which cancers have a smaller increased risk of 20% to 50% in T2D (4)?
1. Colorectal cancer
2. Bladder cancer
3. Breast cancer
4. Blood cancers (non-Hodgkin's lymphoma)
97
Which cancer has a lower incidence rate in T2D?
Prostate cancer
98
Which cancers have an increased risk in developing T1D population? (3)
1. Stomach cancer
2. Cervical cancer
3. Endometrial cancer
99
Which bacterial infections can occur in people with diabetes? (6)
Boils
Styes (infections of the glands of the eyelids)
Folliculitis
Carbuncles
Nail infections
Urinary tract infections
100
Which fungus is responsible for infections and when does it occur & treatment?
Candida albicans
Occurs in warmer & moist folds of the skin
Treated with an anti-fungal
101
Itching is often caused by diabetes. It can be caused by a yeast infection or poor circulation (especially in the lower part of the legs). Keeping legs moisturised will help to prevent the itching from occurring.
102
What does diabetic dermopathy look like & location?
Light brown, scaly patches, which can be oval or circular in shape
Located on the front of legs. Harmless and not needed to be treated.
103
Necrobiosis lipoidica is a result of diabetic neuropathy. What characterises it?
This inflammatory skin disorder is characterised by irregularly-shaped calluses with a reddish-brown colour.
Unless lesions break open, no treatment is required.
104
Diabetic blisters occur more often in patients with diabetic neuropathy. Where do they occur and what do they look like & treatment?
Backs of fingers, toes, hands, legs, and forearms. Look like burn blisters.
Main treatment is better blood glucose control.
105
What does eruptive xanthomatosis look like & location?
Yellow pea-like small bumps which have a red-halo around it and may be itchy.
Found on backs of hands, feet, arms, legs, and buttocks.
106
What causes eruptive xanthomatosis and how is it treated?
High cholesterol. Bumps disappear when blood glucose is better controlled.
107
Which population does eruptive xanthomatosis usually occur in?
Young men with T1D
108
When does digital sclerosis occur & location?
Skin thickens and becomes tight & waxy on the backs of hands, sometimes skin on toes & forehead thickens.
Also, known as diabetic stiff skin or diabetic cheiroarthropathy.
109
Treatment for digital sclerosis?
Bringing blood glucose levels under control
110
Characterisation of granuloma annulare?
Red bumps on the skin. Localised granuloma annulare occurs in red raised patches with a definite circular boarder.
111
Characterisation of acanthosis nigricans & location & treatment:
Tan or brown raised areas appear on the sides of the neck, armpits and groin. Sometimes, they will be found on the hands, elbows and knees.
It usually occurs in those who are overweight, so weight loss will diminish the condition. Some creams may be used to help make the spots look better.
112
Diabetes medications aim to do what 5 things?
1. Provide insulin that is missing
2. Increase insulin production by the pancreas
3. Increase insulin sensitivity (improve efficiency in working)
4. Reduce blood glucose levels
5. Prevent the development of complications by reducing other risk factors (e.g. high blood pressure)
113
Three rapid-acting insulins & duration (bolus):
Lispro
Aspart
Glulisine
2-5hrs
114
Three long-acting insulins & duration (basal):
Glargine
Detemir
Degludec
16-24hrs
115
Short acting insulin & duration:
Soluble insulin
4-8hrs
116
When is a short-/long-acting insulin injected & how & why?
Injected subcutaneously shortly before each main meal to prevent hyperglycaemia
117
Both the rate of release of insulin from its subcutaneous injection site into the circulation and the metabolic need for blood glucose vary between one person and another and from one day to another, depending on diet, exercise and other factors. It is therefore necessary to fine-tune the type, amount and timing of insulin injections for each individual. Learning to make appropriate adjustments from day to day is part of the self-care process for those with diabetes, especially those with Type 1 diabetes. Diet, lifestyle and monitoring blood glucose levels are key to maintaining health as a diabetic.
118
What was the first rapid-acting insulin analogue available in the UK?
Insulin lispro
119
How does its structure differ from human insulin and what does this lead to (2)?
Same structure as human insulin but has the order of two amino acids reversed.
= diffuse more rapidly out of the injection site
1. Has a faster onset of action
2. Shorter duration of action
than unmodified human insulin.
120
Rapid-acting analogues can be taken immediately before or just after eating to reduce post-meal hyperglycaemia
121
When was the first long-acting insulin analogue introduced and what was it?
Insulin glargine in 2000 - once daily at the same time each day. In T2D, it may be used in combination with oral hypoglycaemic agents.
122
Which was the second long-acting analogue insulin to be made available?
Insulin detemir. Given once or twice daily depending on insulin requirements. In T2D, it may be used in combination with oral hypoglycaemic agents in certain circumstances.
123
Which is an ultra-long acting analogue insulin and has a duration of action twice that of insulin glargine, and provides a lower risk of night-time hypoglycaemia?
Insulin degludec
124
How are insulins typically supplied (in what form) (3)?
Cartridges, vials, or pre-loaded pens
125
What is an alternative to deliver insulin and why as opposed to multiple injection regimens?
Continuous infusion pumps for intensive control of glycaemia as it can reduce the number of hypoglycaemic episodes
126
Two large studies, the Finnish Diabetes Prevention Study and the US Diabetes Prevention Program, have both shown that overweight people with IGT (pre-diabetes) can reduce their risk of going on to develop diabetes by % & how (3)?
By 58% through increasing their physical activity, reducing calorie intake, and improving diet quality
127
In the same Diabetes Prevention Programs, they had a comparative arm. What was this and what was the % reduction instead?
Metformin. Reduced their risk by 31%.
128
What are the 9 classes of medicines authorised in the UK for the treatment of hyperglycaemia in T2D?
Metformin (biguanide)
Sulfonylureas
Meglitinides
Glitazones
Acarbose
DPP4 inhibitors (dipeptidyl peptidase 4 gliptins)
GLP1 agonists
SGLT2 inhbitors (sodium glucose co-transporter-2)
Insulin
129
What is considered the first choice ('gold standard') in patients where dieting has 'failed' to control diabetes & since when in UK?
Metformin since late 1950s
Metformin is the preferred choice in those who are overweight - it is also the only biguanide oral anti-diabetic medicine
130
What is the generic name and class for metformin?
Metformin hydrochloride
Biguanide class
131
MOA of metformin (2):
1. Acts on liver, inhibiting glucose production
2. Increases insulin-mediated peripheral glucose uptake (helps muscle & fat cells absorb glucose)
peripheral = tissues outside of the liver
132
Metformin has positive effects on lipid metabolism also. What are these two ways?
1. Decreased hepatic glucose production
2. Increased insulin-mediated peripheral glucose uptake
133
Which two chemical reactions are implied by the term decreased hepatic glucose production?
1. Gluconeogenesis (glucose from non-carb sources like pyruvate/AAs/glycerol)
2. Glycogenolysis
134
How often is metformin usually administered and 2 common side effects?
Usually twice or three times daily
May lead to GI problems like nausea & diarrhoea especially in higher doses.
A prolonged release form is available as a once daily tablet with few side effects than formulations taken 2-3 times.
135
When would the other medications be used in conjunction with metformin or as dual/triple therapies (3)?
When metformin is contraindicated or not tolerated
Or if HbA1c levels were not controlled on metformin alone.
136
Which medication was first oral agents used to treat T2D?
Sulfonylureas (SUs)
137
1st generation & X4 2nd generation sulfonylureas:
1st - tolbutamide
2nd - glipizide, gliclazide, glimepiride, glibenclamide
Second generation more commonly used.
138
How do they work?
Increase insulin secretion when some beta cell activity is present by binding to receptors on beta cells
139
What two factors separate sulfonylureas?
Length of action & how they're eliminated from the body
140
Because beta cell function declines progressively as diabetes progresses, the anti-hyperglycaemic effect of these medicines declines as well, making it necessary to add another agent of a different type in order to maintain long-term control.
141
What are the mild side effects (3)?
1. GI disturbances
2. Hypoglycaemia
3. Weight gain.
They can occasionally cause a disturbance in liver function and hypersensitivity reactions can occur as well (dermatitis).
142
How do meglitinides work?
Stimulate insulin release from beta cells
143
One similarity & difference for meglitinides compared with sulfonylureas:
Both stimulate beta cells to secrete insulin
They act on different receptor sites
144
Meglitinides, like other insulin secretagogues, can cause hypoglycaemia. When can they have a greater risk of causing hypos & why?
Used together with metformin as they are rapidly absorbed and have a fast onset of action
145
Acting faster than short-acting sulfonylureas, meglitinides are taken 15–30 minutes before main meals. Acting more quickly than the short-acting sulfonylureas, they have a relatively short duration of action.
146
Two types of meglitinides (generics):
Nateglinide
Repaglinide
147
What is acarbose and what does acarbose do & why?
It is an alpha glucosidase inhibitor acting on the enzyme which breaks down complex carbohydrates in the intestine into simple sugars like glucose.
Therefore, slows down absorption & reduces the blood glucose peak following a meal.
148
When is acarbose taken (specific)?
Taken at each meal, with the first mouthful of food
149
Why does acarbose not affect the release of insulin from the pancreas?
It almost entirely acts locally at the intestine. Very small amounts of it are absorbed also.
150
What side effects are caused by acarbose & why?
Complex carbohydrates move down the intestine, past the small intestine, where digestions may give rise to flatulence, abdominal pain, and diarrhoea
151
Acarbose does not directly affect the release of insulin from the pancreas or the production of glucose by the liver. The improvement in HbA1c level seen with acarbose is generally less than following sulfonylurea or metformin treatment.
152
Because acarbose inhibits the breakdown of complex carbohydrates in the small intestine, these pass further down the intestine, where their digestion may give rise to symptoms. How can you reduce the symptoms & what are these symptoms (3)?
Start at a lower dose and then titrating the dose upwards
1. Flatulence
2. Abdominal pain
3. Diarrhoea
These are common symptoms at first and can be worsened due to certain dietary choices
153
Acarbose does not itself cause hypoglycaemia, but can increase the risk when taken together with sulfonylureas or insulin.
154
Which is the only glitazone class available in the UK?
Pioglitazone
155
Pioglitazone can be used either singly or, as recommended by NICE and SIGN guidance, in combination with a sulfonylurea and/or metformin. It can also be used in combination with insulin, where patients have not achieved adequate glycaemic control.
156
It does not affect insulin secretion by the pancreas, and thus has a
low risk of hypoglycaemia. How does pioglitazone reduce blood glucose levels? (2 ways)
1. Reduces glucose output from the liver
2. Increases glucose uptake into fat cells and skeletal muscle cells
157
How does pioglitazone work on a cellular level?
Acts on receptors in the nucleus of fat, liver, and muscle cells causing changes that enhance action of insulin on these cells
Increasing GLUT4 receptor production so more glucose is uptaken and also increasing insulin receptors (increasing insulin sensitivity)
Pioglitazone binds to PPAR-γ in the nucleus →
Alters transcription of genes →
↑ GLUT4, ↑ insulin receptor activity, ↓ inflammation, ↓ fatty acid buildup in liver/muscle
158
DPP4 inhibitors (gliptins) inhibit which enzyme?
dipeptidyl peptidase 4 (DPP4)
159
What does DPP4 usually do (2)?
Responsible for rapid inactivation of incretin hormones GLP1 & glucose-dependent insulinotropic polypeptide (GIP)
160
What are GLP1 & GIP enzymes needed for?
Both incretin hormones are involved in the physiological regulation of glucose homeostasis. Incretins are secreted at a low basal level throughout the day and levels rise immediately after meal intake. GLP-1 and GIP increase insulin secretion from pancreatic beta cells and GLP-1 also reduces glucagon secretion from pancreatic alpha cells.
161
Which 5 gliptins are currently licensed in the UK?
Sitagliptin
Saxagliptin
Vildagliptin
Alogliptin
Linagliptin
162
DPP-4 inhibition by the gliptins leads to an increase in the endogenous levels of these incretin hormones, resulting in glucose-dependent increase in insulin secretion and lower glucagon.
163
Gliptins can be used as standalone treatments, but appear to work well in combination with other Type 2 diabetes medicines. DPP-4 inhibitors are generally regarded as weight-neutral medicines with a low risk of hypoglycaemia. However, when used in combination with insulin or a sulfonylurea, a lower dose of the insulin or sulfonylurea may be required to reduce the risk of hypoglycaemia.
The risk of cardiovascular complications with DPP-4 inhibitors has been investigated through two large trials – SAVOR–TIMI 53.
164
How do GLP1 agonists (incretin mimemics) work to reduce blood glucose levels? (3)
1. Increase insulin secretion
2. Decrease glucagon secretion
3. Slow gastric emptying
165
4 examples of GLP1 RAs:
Semaglutide
Liraglutide
Exanatide
Lixisenatide
166
How do SGLT2 inhibitors work to reduce blood glucose levels?
They lower blood glucose levels by blocking a protein in the kidneys that is responsible for the reabsorption of glucose into the bloodstream, thereby increasing the excretion of glucose in the urine.
167
Therefore, SGLT2 inhbitors lower blood glucose levels independent of insulin
168
3 side effects & 2 SGLT2 inhbitors:
Weight loss, urinary tract infections, candidiasis (thrush)
Dapagliflozin & canagliflozin
169
How does retinopathy initially start in both populations of diabetes and over a longer period of time when taking insulin?
Worsening of retinopathy in the short term but is followed by the benefit over the longer time (1yr onwards). Significant worsening unlikely unless in those with pre-existing retinopathy in T2D.
Duration of diabetes and high HbA1c levels are predictors of the risk of progression over time.
170
Two treatments for retinopathy:
1. Laser treatment late in the progress of the disease to prevent blindness
2. anti-VEGF injections often used to treat age-related macular degeneration (AMD)
The long term effectiveness is not known, as it is a relatively new treatment. More research is needed to compare this to laser treatment.
171
Neuropathic pain is treated with conventional analgesics (painkillers) but these may not be sufficient. What are two other treatments used for neuropathy?
1. Pregabalin
2. Duloxetine (serotonin/noradrenaline reuptake inhibitor)
172
When the renin-angiotensin-aldosterone (RAA) system is overactive, it can damage the small blood vessels in the kidneys. What medicines can be used to slow the progression of kidney deterioration? (4)
Angiotensin-converting enzyme (ACE) inhibitors:
T1D - captopril
T2D - lisinopril
Angiotensin receptor blockers (ARBs)
T2D - losartan
T2D - irbesartan
173
Since many people with Type 2 diabetes also have high blood pressure, and as these medicines are used for controlling it, it is likely that the benefit of slowing progression of kidney complications will be obtained without needing to add additional medication.
174
When may these medicines, RAA inhibitors, not be adequate?
When the patients have advance nephropathy. Late-stage kidney disease is expensive and burdensome for the patient as it requires dialysis, and then kidney transplantation.
175
The UKPDS, DCCT and other studies have also shown that controlling blood pressure using anti-hypertensive medication is also important, as it protects against cardiovascular events (heart attack, stroke, heart failure) which are not eliminated by tight glycaemic control. In addition, controlling blood pressure also has a positive effect on microvascular complications such as retinopathy and nephropathy.
176
What are two physical therapies for T1D to reduce the amount of injectable insulin required?
Pancreas & islet cell transplantation
177
However, in this case, immunosuppressive medicines must be taken for the rest of the person’s life to prevent rejection, which occurs in about half of all cases. Islet cell transplantation is still a highly experimental procedure.
178
Why is islet transplantation considered inappropriate for T2D?
Due to insulin resistance being the dominant feature of T2D
ABPI Exam
flashcards
Decks in class (13)
# Cards
-
Dermatology Pt1179
-
Dermatology Pt232
-
Diabetes178
-
Respiratory197
-
Human Body Systems Pt1361
-
Human Body Systems Pt2 - Nervous System117
-
Human Body Systems Pt2 - Endocrine System39
-
Human Body Systems Pt2 - Reproductive System96
-
Human Body Systems Pt2 - Urinary System58
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NHS Structure & Function22
-
Dev & Use of Medicines107
-
Operating in Pharma1
-
ABPI4
