Type 2 diabetes Flashcards
What is the primary cause of type 2 diabetes mellitus (T2DM)?
A combination of insulin resistance and relative insulin deficiency
What percentage of diabetes cases does T2DM account for?
90-95% of diabetes cases
What are the non-modifiable risk factors for T2DM?
(1) Age
= >45 years
(2) Genetics
= polygenic with 400 identified variants
(3) Ethnicity
= higher risk in South Asian, African, and Afro-Caribbean populations
What are the modifiable risk factors for T2DM?
(1) Obesity (BMI >25)
(2) High-fat diet
(3) Physical inactivity
(4) Sedentary behaviours
(5) Raised blood pressure
How does insulin resistance develop in T2DM?
Central obesity increases
(1) plasma-free fatty acids
= impairing insulin-dependent glucose uptake in hepatocytes, myocytes, and adipocytes
How does insulin secretion change in early T2DM?
There is insulin hypersecretion, but it is insufficient to restore glucose homeostasis, leading to persistent hyperglycemia
What happens to pancreatic beta-cells in T2DM?
Hyperglycemia and free fatty acids cause beta-cell damage, reducing insulin production
What are the key hormonal abnormalities in T2DM?
- Increased glucagon secretion (due to reduced intra-islet insulin)
- Reduced incretin effect
What are the common symptoms of T2DM?
Gradual onset is often asymptomatic, but may include;
(1) thirst
(2) polyuria
(3) blurred vision
(4) unintentional weight loss/ or weight gain
(5) recurrent infections
(6) tiredness
What skin condition is associated with T2DM?
Acanthosis nigricans
= insulin-driven epithelial overgrowth in severe insulin resistance
What is the primary diagnostic test for T2DM?
Blood glucose tests
= fasting plasma glucose >7.0 mmol/L or random glucose >11.1 mmol/L)
What is the preferred treatment for T2DM patients with heart failure or chronic kidney disease?
Metformin + SGLT2 inhibitor (first-line) or GLP-1 receptor agonist (second-line)
Why is HbA1c not sufficient for diagnosing T2DM in asymptomatic patients?
Diagnosis should not be based on a single abnormal HbA1c; at least one additional abnormal test is needed
What is the first-line pharmacological treatment for T2DM?
Metformin plus lifestyle modifications
What is the preferred treatment for T2DM patients with atherosclerotic cardiovascular disease?
Metformin + SGLT2 inhibitor
What are additional investigations for T2DM?
(1) Blood pressure
(2) Ketones (if glucose >15 mmol/L)
(3) Cholesterol levels
(4) Possibly pancreatic autoantibodies
When should insulin therapy be initiated in T2DM?
If dual therapy does not control glucose levels
What is the HbA1c target for patients on medications associated with hypoglycemia (e.g., sulfonylureas)?
≤53 mmol/L
What is the HbA1c target for patients managed by diet and lifestyle alone?
≤48 mmol/L
How often should HbA1c levels be monitored in T2DM?
Every 3-6 months until stable
What lifestyle changes can significantly reduce the risk of T2DM?
- Weight loss (especially in individuals with BMI >30)
- Dietary modifications
- Increased physical activity
What defines remission of T2DM?
Maintaining glucose control without the need for exogenous insulin
What is a potential treatment for T2DM remission?
Islet transplantation
What is a common gastrointestinal complication of T2DM?
Gastroparesis
What is the HbA1c cut-off level at the top of the normal (non-diabetic range)?
42 mmol/mol (6.0%)
Novorapid is what type of insulin?
Rapid acting insulin analogue
How does hyperglycaemia exacerbate postural hypotension?
High glucose levels lead to frequent urination which leads to dehydration and a reduction in circulating volume
What is the optimal / target level of HbA1c for a person with type 2 diabetes on single agent therapy such as Metformin?
48 mmol/mol (6.5%)
What are the macrovascular complications of diabetes?
(1) Myocardial infarction
(2) Stroke
(3) Peripheral arterial disease.
Which is more important in the management of type 2 diabetes; blood pressure control or blood glucose control?
Blood pressure control
What drop in blood pressure is required to diagnose postural hypotension?
A fall in systolic BP of 20mmHg or more
What do NICE recommend as the first-line insulin therapy in patients with type 2 diabetes?
Isophane / NPH insulin
A 55-year-old man goes to his general practitioner for a routine follow-up. He has had type 2 diabetes mellitus (T2DM) for 10 years and is currently taking metformin 1 g twice daily and gliclazide 80 mg twice daily.
His recent HbA1c is 8.5% (69 mmol/mol), and he is finding it difficult to lose weight despite making dietary modifications and exercising regularly. During the examination, his BMI is 32 kg/m², and his blood pressure is 140/85 mmHg. No other abnormalities are noted.
What is the most appropriate next step in the management of this patient?
Addition of an SGLT2-inhibitor
A 65-year-old woman presents to her GP for a review of her long-term conditions. She has hypertension and type 2 diabetes mellitus, and she takes amlodipine and metformin.
What should her target blood pressure be?
<140/90mmHg
A 65-year-old man with diabetes has developed painful peripheral diabetic neuropathy.
What are suitable first-line treatments?
Tricyclic anti-depressants
A 65-year-old man with a past medical history of hypertension and poorly controlled type 2 diabetes mellitus presents to his GP with nausea which he has been experiencing every morning for several weeks. He also reports feeling full after eating only a small amount of food and has offensive burps that smell like eggs. He denies dysphagia, diarrhoea and bleeding.
What is the most likely diagnosis?
Gastroparesis
A 73-year-old man with diabetes and learning difficulties attends the Podiatrist for review. He has not been looking after himself and the podiatrist contacts the hospital to arrange an urgent review.
What would constitute a ‘high-risk foot’ and would need urgent referral?
- ulceration with limb ischaemia
- ulceration with fever/sepsis
- clinical concern of deep tissue or bone infection
- gangrene
A 49-year-old man is referred to the diabetic foot clinic following an unsuccessful in-growing toenail amputation by his GP. He was found to have peripheral neuropathy and an infection of his nail bed. On examination, he was also found to have an infected heel ulcer of which the patient was not previously aware. He was poorly compliant with his oral hypoglycaemic medication and had an HbA1C of 89 mmol/mol.
What organism is commonly found in diabetic foot ulcers?
Pseudomonas aeruginosa > chronic ulcers
+ potentially E.coli and in really rare cases bacillus cereus too
A 42 year old male with longstanding type 2 diabetes is referred to the renal clinic due to ongoing proteinuria. He is currently taking metformin, ramipril and gliclazide at optimised doses.
He has the following investigation results:
Albumin: Creatinine Ratio (Urine)
35 mg Alb/mmol
(F) 0-3.5; (M) 0-2.5
What is the most appropriate management? and why is this your answer?
SGLT2 inhibitors
=Dapagliflozin
(1) This patient has type 2 diabetes with evidence of diabetic nephropathy, as indicated by a raised albumin: creatinine ratio (ACR) of 35 mg/mmol
(2) NICE guidelines recommend SGLT2 inhibitors, such as dapagliflozin, in patients with type 2 diabetes and chronic kidney disease (CKD) to slow disease progression, reduce proteinuria, and provide cardiovascular and renal benefits
If symptomatic, one of the following results is sufficient for diagnosis of type 2 diabetes
(1) Random blood glucose ≥ 11.1mmol/l
(2) Fasting plasma glucose ≥ 7mmol/l
(3) 2-hour glucose tolerance ≥ 11.1mmol/l
(4) HbA1C ≥ 48mmol/mol (6.5%)
if the patient with type 2 diabetes is asymptomatic, what test results are required for a diagnosis?
two results are required from different days
A 39 year old woman with longstanding type 2 diabetes presents to the clinic. She has multiple complications of diabetes including retinopathy, renal disease and peripheral neuropathy. She has a background history of hypothyroidism and she has had 2 previous miscarriages which were thought to be due to poorly controlled diabetes. She phones the diabetes specialist nurse to say that she has just found out that she is pregnant for the third time - she estimates that she is only 5 weeks pregnant. She wants to know if she needs to stop or change any of her current medications.
Which medication should be stopped in this scenario?
ACE ihibitors -Perindopril
= potentially teratogenic
A 62-year-old man has type 2 diabetes mellitus which is usually well-controlled on metformin. He has recently noted worsening blood sugars after starting a new medication.
Which medication is the likely cause of his increased blood sugar? and why?
Bendroflumethiazide
= (1) works on the distal convoluted tubule to reduce both sodium and potassium reabsorption
(2) Insulin release from Beta cells is mediated in part by membrane ATP-sensitive potassium channels
(3) Due to low serum potassium, there is decreased insulin release and therefore worsening blood sugars
A 78-year-old woman with T2DM has autonomic neuropathy and her most significant symptom is dizziness on standing which has led to several distressing falls.
What are useful treatments for this particular complication?
Patients with postural hypotension can benefit from additional salt intake
A 46-year-old woman has been diagnosed with type 2 diabetes. Her HbA1c is 62mmol/mol. She has polyuria and polydipsia, but no other symptoms. She is commenced on treatment
What monitoring actions are most appropriate?
NICE recommends checking HbA1c at 3-6 monthly intervals
A 56-year-old male visits his GP for advice. He intends to fast during Ramadan, but he has type -2 diabetes mellitus managed with metformin, three times a day. His diabetes is well controlled.
What should the GP advise him to do?
Continue on 500mg
(1) Take the morning dose before Suhoor (pre-sunrise meal)
(2) Combine the afternoon dose with the dose taken at Iftar (after sunset meal)
A 45-year-old man presents with increased thirst, frequent urination and blurred vision. He has a history of hypertension, obesity and chronic pancreatitis
What is the most likely cause of his symptoms?
Secondary diabetes
What are fasting glucose and 2h glucose normal levels?
(1) Fasting = 3.9–5.5 mmol/L
(2) 2hr = <7.8 mmol/L
What are the fasting blood glucose levels for Impaired Fasting Glucose (IFG)?
6.1–6.9 mmol/L
What are the 2-hour glucose values for Impaired Glucose Tolerance (IGT)?
7.8–11.1 mmol/L
What is required for a diagnosis of type 2 diabetes?
(1) If symptomatic, one result is enough:
Random blood glucose ≥ 11.1 mmol/L
Fasting plasma glucose ≥ 7 mmol/L
2-hour glucose tolerance ≥ 11.1 mmol/L
HbA1c ≥ 48 mmol/mol (6.5%)
(2) If asymptomatic, two results from different days are required
<150/90mmHg target blood pressure for who?
Those over the age of 80
130/80mmHg target blood pressure for who?
If there are known renal, eye or cerebrovascular complications in patients with Type 1 diabetes
When would you add exenatide?
GLP-1 mimetic
= It promotes weight loss and may be helpful for a patient with a large BMI
However, it is only recommended (NICE guidelines) in patients with a BMI greater than 35 who have failed THREE oral hypoglycaemic agents
If two oral hypoglycaemic agents fail to meet the HbA1c target in T2DM, NICE guidelines recommend the addition of what?
Weight loss - DPP-4 inhibitor
SGLT-2 inhibitor
Weight gain - Pioglitazone, sulfonylurea or insulin
What are first-line drugs to reduce blood pressure in a diabetic?
ACE or ARB
You are reviewing a 63-year-old female patient with hypertension and type 2 diabetes in her annual health check. She takes ramipril in the morning and metformin twice a day. She follows all the lifestyle advice given to her and has modified her diet. He HbA1C level is 53 mmol/mol.
At what point should a second drug (in combination with metformin) be added to lower this patient’s HbA1c?
If the HbA1c is greater than 58 mmol/mol
The Hba1c target for patients on a drug which may cause hypoglycaemia (eg sulfonylurea) is what?
53
You are reviewing a 57-year-old man who was diagnosed with type 2 diabetes mellitus around four months ago. At the time of diagnosis his HbA1c was 54 mmol/mol (7.1%). He was started on metformin and the dose was titrated up. At what threshold should you consider adding a second agent?
58
What is the stepwise approach for managing Type 2 diabetes, from first-line to fifth-line treatment?
Exercise and lifestyle changes
- Metformin
- SGLT-2 inhibitors
= (….flozin)
GLP-1 receptor agonists
= (…lutide) + Metformin - Continue metformin and remove one of the 2nd line drugs then add
(1) DPP-4 inhibitors
= (…liptin)
OR
(2) Sulfonylureas
(glimepiride, gliclazide)
- Add Thiazolidinediones
(pioglitazone) or start insulin therapy - combination therapy / Dual
= Insulin (basal or bolus) combined with oral agents like metformin or GLP-1 agonists
In patients with T2DM, SGLT-2 should be introduced at any point they develop what?
CVD, a high risk of CVD or chronic heart failure
When should DPP-4 inhibitors be used to replace sulfonylureas instead of a 2nd line drug like GLP-1 receptor agonists?
(1) DPP-4 inhibitors should be used when the patient has contraindications or is unable to tolerate GLP-1 receptor agonists
(2) such as in cases of gastrointestinal issues or when weight loss is not a primary concern. STOMACH ISSUES + BMI NORMAL use this drug
If a patient with Type 2 diabetes is on metformin, SGLT-2 inhibitors, and sulfonylureas, but wants to lose weight due to a high BMI, what medication should replace the sulfonylureas?
Replace sulfonylureas with a GLP-1 receptor agonist
(eg, liraglutide, semaglutide) as it promotes weight loss
When is metformin contraindicated?
(1) Severe renal impairment
= eGFR < 30 mL/min/1.73m²
(2) Acute or chronic metabolic acidosis = diabetic ketoacidosis, lactic acidosis
(3) Severe liver impairment
(4) Severe respiratory or cardiovascular failure
(5) Acute dehydration, shock, or sepsis
What are the criteria for using GLP-1 receptor agonists like semaglutide in diabetes management?
(1) Obesity (BMI ≥ 30 kg/m²)
(2) Overweight with comorbidities such as cardiovascular disease or high cardiovascular risk
considered 2nd/ 3rd line
A 78-year-old man with type 2 diabetes mellitus is reviewed in the diabetes clinic. He is currently taking metformin 1g bd. He also has a history of hypertension and hypothyroidism. His HbA1c one year ago was 44 mmol/mol (6.2%). The most recent test is reported as 46 mmol/mol (6.4%).
What is the most appropriate next step in management?
Make no changes
Correct Order for Type 2 Diabetes Treatment
(0) Lifestyle changes and exercise
(2) Metformin
(first-line unless contraindicated, such as in severe renal impairment)
(2) Second-line treatment:
SGLT-2 inhibitors
(eg, empagliflozin, dapagliflozin)
OR
GLP-1 receptor agonists
(eg, liraglutide, semaglutide)
ONLY if the patient has obesity (BMI ≥ 30) or cardiovascular disease
(3) Third-line:
Add one more drug while continuing metformin =
DPP-4 inhibitors
(eg, sitagliptin, linagliptin)
OR
Sulfonylureas
(eg, glimepiride, gliclazide)
(4) Fourth-line:
Thiazolidinediones (eg, pioglitazone) or insulin therapy
(5) Fifth-line:
Combination therapy with insulin and other oral agents
(eg, metformin or GLP-1 receptor agonists)
A 62-year-old gentleman with a background of myocardial infarction, congestive heart failure and chronic obstructive pulmonary disease attends for a diabetes review at his GP. He has recently been diagnosed with type 2 diabetes mellitus and despite a trial of lifestyle modifications, his HbA1c is 56 mmol/mol. His GP decides to commence drug treatment.
What drug would be contraindicated for this patient? and why?
Pioglitazone
= can cause fluid retention and is therefore contraindicated in patients with heart failur
You are reviewing the blood test results for a 42-year-old woman with type II diabetes mellitus who commenced on gliclazide three months ago. She was initially trialled on metformin including modified release, however, she had intolerable GI side effects including nausea, abdominal discomfort, and diarrhoea. Results showed an HbA1c of 52 mmol/mol.
What should be the next step in your management?
Repeat HbA1c in 3-6 months as The Hba1c target for patients on a drug which may cause hypoglycaemia (eg sulfonylurea) is 53 mmol/mol
A 50-year-old man presents to the GP for his diabetes review. He was diagnosed with type 2 diabetes one year ago and managed initially with lifestyle measures alone. However, his HbA1c remained high and he was subsequently started on metformin 500mg BD.
Today his HbA1c is 51 mmol/mol with his target being 48 mmol/mol.
What is the next step in managing this patient’s diabetes?
Titrate up metformin then add a SGLT-2 inhibitor to the regime
What drug should be avoided in active foot disease (such as skin ulceration, osteomyelitis, or gangrene) due to the possible increased risk of lower limb amputation (mainly toes)?
SGLT2-inhibitors
You are planning to treat a 63-year-old man with type 2 diabetes with
metformin.
Which is the most common side effect that the patient should be advised about?
GI upset
A diabetic patient with type 2 diabetes is having a medication review
Which drug used to treat Type 2 Diabetes works by inhibiting a brush border enzyme in the small intestine responsible for the absorption of disaccharides?
Alpha-glucosidase inhibitor e.g acarbose
A 45-year-old man with a BMI of 37kg/m2 has poorly controlled type 2 diabetes associated with a chronic diabetic foot ulcer. His HbA1c of 68mmol/mol (8.4%). His glycaemic control did not respond to a recent trial of adding alogliptin, which has subsequently been stopped. He continues to take metformin and glimepiride.
What’s the next step?
Exenatide / GLP-1 receptor
= SGL2 inhibitors are contradicted since foot disease
Bernard is a 62-year-old man who comes to see you with a 3-day history of sore throat, cough and muscle ache. He has a past medical history of type 2 diabetes and hypertension. He takes a twice-daily insulin regimen.
After a full assessment, you explain to Bernard that he has likely got the flu and advise rest, regular paracetamol and plenty of fluids.
What is the most appropriate advice to give Bernard with regards to his insulin whilst he is unwell?
Continue his normal insulin regime and check blood sugars frequently. Up fluid intake
