Diabetes mellitus Flashcards
1
Q
What is Type 1 Diabetes Mellitus (T1DM)?
A
An autoimmune disorder where the insulin-producing beta cells in the islets of Langerhans in the pancreas are destroyed by the immune system.
2
Q
What results from the destruction of beta cells in T1DM?
A
An absolute deficiency of insulin, leading to raised glucose levels.
3
Q
When do patients typically develop Type 1 Diabetes Mellitus (T1DM)?
A
typically develops in childhood or early adult life.
4
Q
What are common symptoms of Type 1 Diabetes Mellitus (T1DM)?
A
- Weight loss
- Polydipsia
- Polyuria
5
Q
What severe condition may patients with T1DM present with?
A
diabetic ketoacidosis
6
Q
What investigations should be conducted for Type 1 Diabetes Mellitus (T1DM)?
A
- Urine dip for glucose and ketones
- fasting glucose and random glucose
- C-peptide levels and diabetes-specific autoantibodies (not routinely recommended)
7
Q
Why is HbA1c not as useful in diagnosing Type 1 Diabetes Mellitus (T1DM)?
A
HbA1c may not accurately reflect a recent rapid rise in serum glucose in patients with possible or suspected T1DM.
8
Q
What are C-peptide levels typically like in Type 1 Diabetes Mellitus (T1DM)?
A
typically low in patients with T1DM
9
Q
When should further tests, such as C-peptide measurement or diabetes-specific autoantibody titres, be considered for diagnosing T1DM ?
A
If T1DM is suspected but the clinical presentation includes atypical features, such as age 50 years or above, BMI ≥ 25 kg/m², slow evolution of hyperglycaemia, or a long prodrome.
* useful to distinguish between type 1 and type 2 diabetes
10
Q
State 3 diabetes specific autoantibodies
A
- Antibodies to glutamic acid decarboxylase (anti-GAD)
- Islet cell antibodies (ICA, against cytoplasmic proteins in the beta cell)
- Insulin autoantibodies (IAA)
11
Q
What are the diagnostic criteria for Diabetes Mellitus if the patient is symptomatic?
A
Fasting glucose ≥ 7.0 mmol/l or random glucose ≥ 11.1 mmol/l (or after 75g oral glucose tolerance test).
12
Q
What are the diagnostic criteria for Diabetes Mellitus if the patient is asymptomatic?
A
The same criteria as for symptomatic patients, but the glucose levels must be demonstrated on two separate occasions.
13
Q
What is the long term management of T1DM
A
- SC insulin
- monitoring dietary carbohydrate intake
- monitoring blood sugar levels
- monitoring and managing complications
14
Q
What is HbA1c
A
- it measures glycated haemoglobin, which is how much glucose is attached to the Hb molecule
- this reflects the average glucose level over the last 2-3 months
15
Q
How often should HbA1c be monitored in adults with Type 1 Diabetes
A
every 3-6 months.
16
Q
What HbA1c level is diagnostic for adults with Diabetes Mellitus
A
48 mmol/mol (6.5%) or greater
17
Q
What factors should be considered when determining an individual’s HbA1c target?
A
Daily activities, aspirations, likelihood of complications, comorbidities, occupation, and history of hypoglycaemia.
18
Q
How often should people with Type 1 Diabetes Mellitus (T1DM) self-monitor their blood glucose?
A
At least 4 times a day, including before each meal and before bed
19
Q
When should more frequent blood glucose monitoring be done for Type 1 Diabetes Mellitus (T1DM)?
A
- If hypoglycaemic episodes increase
- during illness
- before/during/after sport
- when planning pregnancy and during pregnancy
- while breastfeeding.
20
Q
What are the recommended blood glucose targets for Type 1 Diabetes Mellitus (T1DM)?
A
- 5-7 mmol/l on waking
- 4-7 mmol/l before meals at other times of the day.
21
Q
What insulin regimen is recommended for adults with Type 1 Diabetes Mellitus?
A
A multiple daily injection basal-bolus insulin regimen
* Twice-daily insulin detemir is the regime of choice,
* alternative: once-daily insulin glargine or insulin degludec
* Rapid-acting insulin analogues should be used before meals
22
Q
Side effects of subcutaneous insulin
A
- Hypoglycaemia
- Weight gain
- Lipodystrophy
23
Q
When should metformin be considered for T1DM patients?
A
if the BMI is ≥ 25 kg/m²
24
Q
Explain the pathophysiology of diabetic ketoacidosis
A
caused by uncontrolled lipolysis which results in an excess of free fatty acids that are ultimately converted to ketone bodies
25
Give 3 common precipitating factors of DKA
* infection
* missed insulin doses
* myocardial infarction
26
Features of DKA
* abdominal pain
* polyuria, polydipsia, dehydration
* Kussmaul respiration (deep hyperventilation)
* Acetone-smelling breath ('pear drops' smell)
27
How is DKA diagnosed
* glucose > 11 mmol/l or known DM
* pH < 7.3
* blood ketones > 3 mmol/l or urine ketones ++ on dipstick
28
What investigation should be done to support the diagnosis of DKA
* venous blood gas - metabolic acidosis with a raised anion gap
* blood ketones
* blood glucose
* U & Es
* FBC
29
What electrolyte imbalances are common in DKA
* Hyponatraemia
* hyperkalaemia
* hypokalaemia
30
Explain the potassium imbalance often present in DKA
* serum potassium is often high on admission despite total body potassium being low
* Hyperkalaemia is due to an extracellular shift of potassium caused by insulin insufficiency and acidosis
* Hypokalaemia on arrival indicates severe total-body potassium deficit and is an indicator of severe DKA
31
What are the main principles of management for DKA
* Fluid replacement
* Insulin
* correction of electrolyte disturbance
32
What is the main principle of fluid replacement in the management of DKA?
* isotonic saline is used initially, even if the patient is severely acidotic
* most patients with DKA are deplete around 5-8 litres
33
What is the initial insulin infusion rate for DKA and when should dextrose be introduced?
* Start an IV insulin infusion at 0.1 unit/kg/hour
* Once blood glucose falls below 14 mmol/l, introduce a 10% dextrose infusion at 125 mls/hr, alongside the 0.9% sodium chloride solution.
34
What is the issue with serum potassium in DKA, and how should it be managed?
* serum potassium may fall quickly following insulin treatment, resulting in hypokalaemia
* Potassium may need to be added to the replacement fluids.
35
DKA: How much potassium should be added to 1L of saline if the potassium is within 3.5-5.5mmol/L
40 mmol
36
What monitoring is required when potassium infusion rate exceeds 20 mmol/hour?
Cardiac monitoring may be required
37
What should be done with the insulin regimen once DKA is being treated?
Long-acting insulin should be continued, while short-acting insulin should be stopped
38
What defines the resolution of DKA?
* pH > 7.3
* Blood ketones < 0.6 mmol/L
* Bicarbonate > 15.0 mmol/L
39
What should happen if the resolution criteria for DKA are not met?
If ketonaemia and acidosis are not resolved within 24 hours, the patient requires senior review by an endocrinologist.
40
When can a patient with DKA be switched to subcutaneous insulin?
If the resolution criteria are met and the patient is eating and drinking, they can be switched to subcutaneous insulin.
41
What are some potential complications of Diabetic Ketoacidosis?
* gastric stasis
* thromboembolism
* arrhythmias secondary to hyperkalaemia/iatrogenic hypokalaemia
* iatrogenic due to incorrect fluid therapy: cerebral oedema, hypokalaemia, hypoglycaemia
* acute respiratory distress syndrome
* acute kidney injury
42
What is a major concern in children/young adults during DKA treatment and why?
* Children and young adults are particularly vulnerable to cerebral oedema following fluid resuscitation in DKA
* It can present 4-12 hours after treatment but may occur at any time
43
What is type 2 diabetes mellitus
a chronic condition where a combination of insulin resistance and reduced insulin production cause persistently high blood sugar levels
44
Explain the pathophysiology of T2DM
* repeated exposure to glucose and insulin makes the cells in the body resistant to the effects of insulin
* over time, the pancreas becomes fatigued and damaged leading to a relative deficiency of insulin
45
RFs for T2DM
* Non-modifiable: older age, ethnicity, FHx
* Modifiable: obesity, sedentary, high carb diet
46
How may T2DM present
* asymptomatic and Often picked up incidentally on routine blood tests
* skin infections
* candida infections
* fatigue
* blurred vision
* UTI
47
Give 5 conditions where HbA1c may not be used for diagnosis
* haemoglobinopathies
* haemolytic anaemia
* untreated iron deficiency anaemia
* suspected gestational diabetes
* children
* HIV
* chronic kidney disease
48
What dietary advice should be given to patients with Type 2 Diabetes Mellitus
* Encourage high-fibre, low glycaemic index carbohydrates.
* Include low-fat dairy and oily fish.
* Control intake of saturated fats and trans fatty acids.
* Limit substitution of sucrose-containing foods and avoid excess energy intake.
* Discourage foods marketed specifically for people with diabetes.
* Aim for a 5-10% weight loss in overweight individuals.
49
How often should HbA1c be checked in patients with T2DM
every 3-6 months until stable, then 6 monthly
50
What is the first-line drug for managing Type 2 Diabetes Mellitus ?
Metformin
51
What should be done if a patient cannot tolerate standard-release metformin?
Modified-release metformin should be trialed.
52
T2DM: What should the HbA1c target be for patients on lifestyle treatment or monotherapy with metformin?
The target HbA1c is 48 mmol/mol (6.5%).
53
When should a second drug be added for a patient with Type 2 Diabetes Mellitus ?
if the HbA1c rises to 58 mmol/mol (7.5%).
54
What HbA1c target is recommended for patients who are on metformin combined with a drug that causes hypoglycaemia (e.g., sulfonylurea)?
The target HbA1c is 53 mmol/mol (7.0%).
55
When should SGLT-2 inhibitors be used in the management of Type 2 Diabetes Mellitus?
* The patient has a high risk of cardiovascular disease
* The patient has established CVD.
* The patient has chronic heart failure.
56
What should be done if metformin is contraindicated in a patient with Type 2 Diabetes Mellitus
* If the patient has a risk of CVD, established CVD, or chronic heart failure, use SGLT-2 monotherapy.
* If there is no risk of CVD, use a DPP-4 inhibitor, pioglitazone, or sulfonylurea
57
What are the second-line therapy options if HbA1c is not controlled with metformin?
* Metformin + DPP-4 inhibitor
* Metformin + pioglitazone
* Metformin + sulfonylurea
* Metformin + SGLT-2 inhibitor (if NICE criteria are met).
58
What is the third-line therapy if dual therapy does not control HbA1c in Type 2 Diabetes Mellitus?
* Metformin + DPP-4 inhibitor + sulfonylurea
* Metformin + pioglitazone + sulfonylurea
* Metformin + (pioglitazone, sulfonylurea, or DPP-4 inhibitor) + SGLT-2 inhibitor (if criteria met)
* Insulin-based treatment.
59
When should a GLP-1 mimetic be considered in the treatment of Type 2 Diabetes Mellitus (T2DM)?
If triple therapy is not effective or tolerated consider switching one of the drugs for a GLP-1 mimetic especially if:
* BMI ≥ 35 kg/m² or other medical issues related to obesity
* BMI < 35 kg/m² where insulin therapy has significant occupational implications or weight loss would benefit comorbidities
60
What is the blood pressure target for patients with Type 2 Diabetes Mellitus
same as for patients without T2DM:
* Age < 80 years: Clinic BP < 140/90 mmHg (ABPM/HBPM < 135/85 mmHg).
* Age > 80 years: Clinic BP < 150/90 mmHg (ABPM/HBPM < 145/85 mmHg).
61
What is the first-line treatment for hypertension in patients with Type 2 Diabetes Mellitus (T2DM)?
* ACE inhibitors or angiotensin II receptor blockers (ARB).
* An ARB is preferred for patients of black African or African-Caribbean descent.
62
When should antiplatelet therapy be offered to a patient with Type 2 Diabetes Mellitus
should only be offered to patients with existing cardiovascular disease
63
Who should be offered a statin according to NICE guidelines for lipid management in Type 2 Diabetes Mellitus
Patients with a 10-year cardiovascular risk > 10% (using QRISK2) should be offered a statin, with atorvastatin 20mg being the first-line choice.
64
What is the mechanism of action of Metformin in the treatment of Type 2 Diabetes Mellitus?
Metformin increases insulin sensitivity and decreases hepatic gluconeogenesis
65
What are the common side effects of Metformin?
Gastrointestinal upset and lactic acidosis (secondary to AKI)
66
What is a contraindication for using Metformin?
cannot be used in patients with an eGFR of < 30 ml/min.
67
How do Sulfonylureas work in the treatment of Type 2 Diabetes Mellitus?
stimulate pancreatic beta cells to secrete insulin.
68
What are examples of Sulfonylureas used in the treatment of Type 2 Diabetes Mellitus?
* Gliclazide
* glimepiride
* glipizide
69
What are the common side effects of Sulfonylureas?
* Hypoglycaemia
* weight gain
* hyponatraemia
70
What is the mechanism of action of SGLT-2 inhibitors in the treatment of Type 2 Diabetes Mellitus?
inhibit glucose reabsorption in the kidneys.
71
What are examples of SGLT-2 inhibitors used in the treatment of Type 2 Diabetes Mellitus?
* empagliflozin
* canagliflozin
* dapagliflozin
* ertugliflozin
72
What are the common side effects of SGLT-2 inhibitors?
* Urinary tract infections
* weight loss
* DKA
73
What is the mechanism of action of Pioglitazone in the treatment of Type 2 Diabetes Mellitus?
pioglitazone is a Thiazolidinediones: they activate the PPAR-gamma receptor in adipocytes to promote adipogenesis and fatty acid uptake.
74
What are the common side effects of Thiazolidinediones?
* Weight gain
* fluid retention
* fractures
75
How do DPP-4 inhibitors work in the treatment of Type 2 Diabetes Mellitus?
increase levels of incretins (GLP-1 and GIP) by decreasing their peripheral breakdown
76
What are the common side effects of DPP-4 inhibitors?
* low risk of acute pancreatitis
* headaches
77
Give 2 examples of DPP-4 inhibitors
* sitagliptin
* alogliptin
78
How do GLP-1 agonists work in the treatment of Type 2 Diabetes Mellitus?
GLP-1 agonists are incretin mimetics that:
* inhibit glucagon secretion
* increase insulin secretion
79
What are the common side effects of GLP-1 agonists?
* Nausea and vomiting
* pancreatitis
* weight loss and reduced appetite
80
Give 2 examples of GLP-1 agonists
* exenatide
* liraglutide
81
What route are GLP-1 agonists taken
subcutaneous
82
What is Hyperosmolar Hyperglycaemic State?
a medical emergency characterised by hyperglycaemia, osmotic diuresis, severe dehydration, and electrolyte deficiencies, with a significant associated mortality rate
83
What is the pathophysiology of Hyperosmolar Hyperglycaemic State?
Hyperglycaemia increases serum osmolality, leading to osmotic diuresis and severe volume depletion.
84
What are common precipitating factors of Hyperosmolar Hyperglycaemic State?
* intercurrent illness
* dementia
* sedative drugs
85
How does the presentation of Hyperosmolar Hyperglycaemic State differ from Diabetic Ketoacidosis?
HHS develops over many days, causing more severe dehydration and metabolic disturbances compared to DKA, which presents acutely within hours.
86
What are the clinical features of Hyperosmolar Hyperglycaemic State?
* Dehydration: polyuria, polydipsia, clinical signs of dehydration
* Systemic: lethargy, nausea, vomiting
* Neurological: altered level of consciousness, focal neurological deficits
* Haematological: hyperviscosity leading to myocardial infarctions, strokes, and peripheral arterial thrombosis.
87
What are typical diagnostic features of Hyperosmolar Hyperglycaemic State?
* marked hyperglycaemia (>30 mmol/L)
* significantly raised serum osmolarity (> 320 mosmol/kg)
* no significant hyperketonaemia (<3 mmol/L) or no significant acidosis
88
hat is the initial management approach for Hyperosmolar Hyperglycaemic State?
* Fluid replacement: 0.9% sodium chloride solution at 0.5 - 1 L/hour, depending on clinical assessment.
* Potassium monitoring and supplementation: monitored and added to fluids as needed.
* Insulin: Should not be given unless blood glucose stops falling while giving intravenous fluids.
* VTE prophylaxis
