MET3 Revision: Diabetes I

Question 1

A patient is diagnosed with DMT1 after an admission for DKA.

What is the insulin regime you should start them on post-admission? [1]

Answer 1

Twice-daily basal insulin detemir (long acting), insulin aspart (short acting) bolus with meals

Question 2

Name 4 complications associated with untreated diabetes

Answer 2

 skin infections – staphylococcal skin abcesses, oral or genital candidiasis

 foot problems – ulcers or neuropathic pain

 retinopathy – perhaps found on routine eye test

 acute myocardial infarct / stroke– diagnosed whilst in hospita

Question 3

State 4 methods for diagnosing diabetes [4]

Answer 3

 Fasting plasma glucose (FPG) (note NOT a capillary glucose [ie. a fingerprick test])

 Random plasma glucose (RPG)

 75 gram oral glucose tolerance test (OGTT / 2hr PG)

 Haemoglobin A1c (HbA1c, glycated haemoglobin)

NOTE: One diagnostic test is enough to diagnose diabetes w/ symptom

Question 4

Answer 4

Question 5

Impaired glucose tolerance can only be diagnosed using which diagonostic test?
FPG
2 hr PG
RPG
HbA1c

Answer 5

Impaired glucose tolerance can only be diagnosed using which diagonostic test?
FPG
2 hr PG
RPG
HbA1c

Question 6

Answer 6

Question 7

Which HLA is associated with DMT1? [2]

Answer 7

HLA DR3 & DR4

Question 8

Describe what pancreatic diabetes is [1]

Name 4 causes of pancreatic diabetes [4]

Answer 8

Pancreatic diabetes:
* Severe disease of pancreas causes damage to B cells

Causes:
 Acute / Chronic Pancreatitis
 Trauma / Pancreatectomy
 Neoplasia
 Cystic fibrosis
 Haemochromatosis / Thalassaemia – due to iron overload

Question 9

Name 6 endocrine diseases known to cause diabetes [6]

Answer 9

 Acromegaly (excess growth hormone)
 Cushing’s syndrome (excess cortisol)
 Glucagonoma (excess glucagon)
 Phaechromocytoma (excess adrenaline)
 Hyperthyroidism (excess thyroid hormone)
 Conn’s syndrome (excess aldosterone hormone

Question 10

State 5 causes of drug induced diabetes [5]

Answer 10

 Glucocorticoids

 b-blockers

 Thiazide diuretics

 Tacrolimus (used in transplantation – may cause “New Onset Diabetes after Transplantation” [NODAT])

 Atypical anti-psychotics – eg. olanzapine, risperidone, clozapine

Question 11

Name two congenital viral infections that may cause diabetes [2]

Answer 11

 Congenital rubella
 Cytomegalovirus

Question 12

DMT2 is caused by a combination of which two physiological factors? [2]

Answer 12

Insulin resistance AND B-cell failure

Question 13

Insulin resistance AND B-cell failure are exacerbated by hyperglycaemia:
What is this concept called? [1]
Explain the pathophysiology [2]

Answer 13

Glucose toxicity:

 High levels of glucose lead to poorer b-cell function leading to reduced insulin secretion

 therefore lowering glucose may actually help b-cell function

Question 14

Describe how alpha and beta cell mass changes in diabetic patients [2]

Answer 14

 b-cell mass is relatively preserved (50% at autopsies) - but function declines
 a-cell population increased

Question 15

Which factors contribute to metabolic syndrome? [6]

Answer 15

BMI > 30 kg/m2 , or:
Abdominal Waist Circumference – ethnic specific
Low HDL Concentration
Blood pressure
Fasting glucose
Triglyceride

Question 16

Label the treatment choices for the DM patients with multi-morbidities for patients already on metformin management and HbA1c remains above 53

Answer 16

CVD:
A: SGLT-inhibitor
B: GLP-1

Heart Failure:
C: SGLT-inhibitor
D: GLP-1

CKD
E: SGLT-inhibitor
F: GLP-1

High CV Risk:
G: SGLT-inhibitor
H: GLP-1

Frail / elderly:
I DPP-inhibitor (low hypoglycaemia risk)

Obesity
A: SGLT-inhibitor
B: GLP-1

Question 17

Which drugs are contraindicated for patients with DMT2 who might also be suffering from:

Heart Failure [2]
CKD [1]
Frail / elderly [3]
Obesity [2]

Answer 17

Heart Failure:
- Pioglitazone: causes oedema as an AE
- Saxagliptin: increase risk of HF

CKD [2]
- Caution with SUs

Frail / elderly [3]
- SGLT2i (hypoglycaemia risk)
- GLPs (hypoglycaemia risk)
- Caution with SUs (hypoglycaemia risk)

Obesity
- SUs (weight gain)
- Pioglitzaone (weight gain)

Question 18

When are the following useful / recommended as an additional step to DM patient medication? [3]

Sulfonylurea [1]
Pioglitazone [1]
Repaglinide [1]

Answer 18

Sulfonylurea: (gliclazide, glimepiride): if rapid glucose lowering needed and hypos are not a concern

Pioglitazone: can improve lipids, useful for insulin resistance if no C/Is

Repaglinide: can be useful in shift workers/ irregular meal patterns

Question 19

Sick day rules:

During an acute dehydrating illness, patients with diabetes should be advised to stop the SADMAN drugs, and restart once they have been eating and drinking normally for 24-48 hours.

What do the SADMAN drugs refer to? [6]
State why need to stop each of the SADMAN drugs [6]

Answer 19

SGLT2 inhibitors: (risk of DKA)
ACE inhibitors: (risk of AKI)
Diuretics (risk of AKI)
Metformin (risk of lactic acidosis)
ARBs (risk of AKI)
NSAIDs (risk of AKI)

Question 20

DPP4 inhibitors have a risk of causing which pathology? [1]

Answer 20

Pancreatitis

Question 21

What BP in DM patients would indicate BP treatment? [1]
What BP for a diabetic patient would indicate BP treatment if they have kidney, eye or CV disease ? [1]

Answer 21

BP persistantly over 140 / 90 mmHG

BP persistantly over 130 / 80 mmHG & kidney, eye or CV disease

Question 22

What drug, dose and administration would you give to DMT2 patients with no CVD, but Qrisk score of greater than 10% to modify their lipid levels? [1]

What drug, dose and administration would you give to DMT2 patients with known CVD modify their lipid levels? [1]

If not achieving target, which drugs should be prescribed modify their lipid levels? [2]

Answer 22

Diabetic patients with no CVD, but Qrisk score of greater than 10%:
- Arvostatin, 20mg daily

Diabetic patients with known CVD:
- Arvostatin, 80mg daily

No response:
- Ezetimibe
- PCSK9 inhibitors

Question 23

When should you provide statins for DMT1 patients? [2]

Answer 23

• Anyone who has has DMT1 for over 10 years
• Statins for anyone with complications (eyes / neuro etc

Question 24

Describe the physiological effect for long term diabetic management of having tight glycaemic control [2]

Answer 24

Microvascular complications reduced

Macrovascular complications has no effect

Question 25

Which conditions are HbA1c may be invalid for when assessing diabetic conditions? [2]

Answer 25

May be invalid in **haemoglobinopathy** or **anaemia** (reduced red blood cell survival)

Question 26

How can patients using insulin therapy assess their glycaemic control? [1] What are pre-prandial and post-prandial glucose level aims? [2]

Answer 26

Self monitoring of blood glucose (SMBG): Pre-prandial aim: **4-7 mmol/L** Post-prandial aim: **5-9 mmol/L**

Question 27

Name this [1] Which Ptx populations can use it? [4]

Answer 27

**Intermittently Scanned Continuous Glucose Monitoring (Freestyle Libre)** ▪ Can be used in most people with T1D ▪ Consider in people with T2D if they are on twice daily or more insulin therapy ▪ AND have recurrent hypos or severe hypos or hypo unawareness ▪ OrLearningdisability/Cognitiveimpairment

Question 28

DMT2 Management: - MoA of Metformin? [3]

Answer 28

* Acts by activation of the AMP-activated protein kinase (AMPK) * **Increases insulin sensitivity / improving insulin resistance** * **Decreases hepatic gluconeogenesis** - **inhibits glucose absorption in the gut**

Question 29

State 2 advantages of sulfonylureas State 3 disadvantages of sulfonylureas

Answer 29

Advantage: **Oral** **Cheap** Disadvantage **Hypoglycaemia** **Weight gain** **Testing glucose if driving**

Question 30

Describe the MoA of Acarbose [2]

Answer 30

 Blocks disaccharidase in the GI tract  Reduces absorption of glucose }

Question 31

Name 3 advantages of glitazones for diabetic control

Answer 31

Generally well tolerated Oral / once daily Cheap - ~ £2.00 per month HbA1c reduction 10-15 mmol/mol Little hypoglycaemia

Question 32

Name 4 disadvantages of glitazones (thiazolidinediones) [4]

Answer 32

**Oedema** (avoid in HF) **Weight gain** 3-5 kg **Fractures** in **post menopausal women** Query around cause of bladder cancer **ELBOW** Edema Liver failure Bladder cancer Osteoporosis Weight gain

Question 33

Describe the physiological effect of GLP-1 [4]

Answer 33

**Glucose-dependently stimulates insulin secretion and decreases glucagon secretion**:  Delays gastric emptying  Decreases food intake and induces satiety  Stimulates B-cell function and preserves or increases B-cell mass in animal models (stimulating insulin release)

Question 34

Name a daily [1] & weekly [2] injectable GLP-1 drug

Answer 34

 **Liraglutide** – daily injection  **Dulaglutide** – weekly injection  **Semaglutide** – weekly injection or oral tablet

Question 35

Name 4 advantages of GLP-1 analogues [3]

Answer 35

**Weight loss** Reduce CV risk HbA1c reduction 10 / 30 mmol/mol One weekly injection

Question 36

Name 4 disadvantages of GLP-1 analogues [4]

Answer 36

Injection Cost ~ £73.00 per month Needs some nursing GI side effects ?? Pancreatitis risk

Question 37

Name 4 disadvantages of using SGLT-2 inhibitors [4]

Answer 37

**- UTIs / Thrush** - Euglycaemic DKA (rare) - get DKA but at normal glucose levels - Care in acute illness - £ 36

Question 38

Describe an overview of the drug pathway for glycaemic management of DMT2

Answer 38

- HbA1c above 48 at diet and lifestyle alone: condiser Ptx CV risk or CV disease - If Ptx has low CV risk: **metformin first line** - If Ptx has high CV risk or CV disease: **metformin AND gliflozin** - If HbA1c continued not to be controlled: **dual oral therapy** - If HbA1c continued not to be controlled: **triple oral therapy**

Question 39

What is rescue therapy prescribed for symptomatic hyperglycaemia? [2]

Answer 39

- Consider **insulin or sulfonylurea** - Review when glucose control achieved

Question 40

How do you chose between GLP-1 analogue versus insulin for DMT2 after triple oral therapy has not controlled HbA1c? [1]

Answer 40

**GLP-1:** - BMI > 35 **Insulin:** - BMI < 35

Question 41

Describe when insulin is released in a normal person [2]

Answer 41

**Biphasic**: - Short-lived, rapidly generated meal-related insulin peaks - Low, steady, basal insulin profile

Question 42

Name indications for insulin therapy for DMT2 patients [5]

Answer 42

▪ inadequate glycaemic control on tablets ▪ contraindications to tablets ▪ symptomatic hyperglycaemia ▪ pregnancy ▪ infection / foot ulcers }

Question 43

State the three different types of insulin regimens

Answer 43

 Once-daily / twice-daily intermediate- or long-acting (basal) insulin  Once-/ twice-/ three-times daily premixed insulin  Basal–bolus therapy

Question 44

Describe the dosing regimen of twice daily insulin [2]

Answer 44

**Two injections:** **First injection** (contains both): - Short acting acts on breakfast - Long acting works on lunch **Second injection:** - Short acting acts on dinner - Long acting works in background

Question 45

Describe basal bolus therapy regime for insulin

Answer 45

3 injections of rapid acting, 1 injection of long acting: mimics normal physiology

Question 46

A man sees his GP for a review of his type 2 diabetes. He is on metformin at the maximum tolerated dose. His latest HbA1c is 64 mmol/mol. His GP starts him on gliclazide and plans to repeat the HbA1c in 3 months' time. What is the patient's new target HbA1c? [1]

Answer 46

The Hba1c target for patients on a drug which may cause hypoglycaemia (eg sulfonylurea) is **53** mmol/mol

Question 47

Pioglitazone is contraindicated in which type of cancer? [1]

Answer 47

Bladder cancer

Question 48

Name three anti-VEGF medications used to treat diabetic retinopathy [3]

Answer 48

**ranibizumab**, **bevacizumab** & **Aflibercept**

Question 49

Name two corticosteroids used to treat diabetic retinopathy [2] Which

Answer 49

**Triamcinolone** **Dexamethasone implant** can also be used, particularly in **refractory DME**

Question 50

Describe how you would treat mild-moderate hypokalaemia (2.5-3.4) and severe hypokalaemia (< 2.5) [2]

Answer 50

**Mild to moderate hypokalaemia 2.5 - 3.4** mmol/l: - **oral potassium** provided the patient is not symptomatic and there are no ECG changes. **Severe hypokalaemia (< 2.5mmol/l) or symptomatic hypokalaemia**: - should be **managed with IV replacement.** - If there are no contraindications to fluid therapy (e.g. volume overload, heart failure) potassium should be diluted to low concentrations as higher concentrations can be phlebitic. - **The infusion rate should not exceed 20mmol/hr**

Question 51

A second drug should be added in type 2 diabetes mellitus if the HbA1c is > **[]** mmol/mol

Answer 51

A second drug should be added in type 2 diabetes mellitus if the HbA1c is **> 58 mmol/mol**