Diabetes

Question 1

T2DM: treatment ladder

Answer 1

1. Diet
2. Metformin*
3. Add sulfonylurea OR gliptin (DPP-4 inhibitor) OR pioglitazone OR -flozin (SGLT-2 inhibitor)
4. Triple therapy
5. Insulin or GLP-1 agonist (if BMI >35 or if lower BMI but weight loss would benefit obesity-related comorbidities)

*Add SGLT-2 inhibitor as 1st line if heart failure/CVD/high risk CVD. New guidance from NICE 2022

Question 2

Diabetes antibodies

Answer 2

https://www.southtees.nhs.uk/services/pathology/tests/diabetes-autoantibodies/

Question 3

Differentiating type 1 vs type 2 diabetes
a) Insulin and C-peptide
b) Antibodies
c) Other

Answer 3

a) - Insulin low (<5) in T1DM, high in T2DM
- C-peptide low in T1DM, normal in T2DM (>1)

b) >1 diabetes antibody suggests T1DM
- Anti-islet antigen 2 (IA2) - present in first 6 months of T1DM
- Anti-GAD65 - present for life in T1DM
- Anti-insulin antibodies

c) Suggesting T1DM:
- Weight loss, young age, ketones, insulin requirement within 1 year of onset

Question 4

ExPLAIN hypoglycaemia

Answer 4

EX Exogenous drugs (insulin, oral hypoglycaemics, alcohol, pentamidine, quinine, quinolones)
P Pituitary insufficiency (no GH or cortisol)
L Liver failure (no glycogen stores)
A Adrenal failure (no cortisol)
I Insulinomas/immune hypoglycaemia
N Non-pancreatic malignancy (retroperitoneal sarcoma secreting IGF-2)/ Nurses abusing insulin

Question 5

C-peptide
a) Cause of raised level
b) Cause of deficiency
c) Insulin abuse
d) Where does c-peptide come from?

Answer 5

a) Insulinoma

b) T1DM, alcohol, diuretics

c) Normal c-peptide

d) Proinsulin cleaved into insulin + c-peptide
- This occurs in the golgi apparatus courtesy of 2 endoproteases

Question 6

MODY
a) Common mutation and treatment
b) Most severe MODY type
c) Prevalence of total diabetes
d) Which MODY type generally needs no treatment except in pregnancy? Risk if homozygous?
e) Factors suggesting MODY as a cause
f) Which MODY causes failure of pancreas development if homozygous?

Answer 6

a) MODY 3:
- HNF1-alpha (Ch 12) mutation, causing defective beta cells in the pancreas and defective insulin release
- Rx: sulfonylureas

b) MODY-5 (rare)
- HNF1-beta
- Liver and renal cysts
- Rx: insulin

c) 1-2 %

d) MODY 2:
- Glucokinase mutation (“2-cokinase”)
- If homozygous, causes neonatal persistent hyperglycaemia

e) - Strong FHx - parent or multiple generations affected
- Age of onset <25 without weight loss

f) MODY 4

Question 7

Glucagonoma - presentation

Answer 7

Diabetes
Weight loss
Necrolytic migratory erythema

Question 8

Which medications are good and bad for weight loss in diabetes?

Answer 8

Significant weight loss:
- GLP-1 agonists
- SGLT2 inhibitors

Modest weight loss:
- Metformin

Weight neutral
- DPP-4 inhibitors (gliptins)

Weight gain:
- Sulfonylureas
- Pioglitazone
- Insulin

Question 9

Insulinoma
a) Presentation
b) Best diagnostic test
c) Supporting tests

Answer 9

a) - Recurrent episodes of hypoglycaemia with typical symptoms
- Weight gain

b) 72h inpatient fast with glucose monitoring

c) At time of hypoglycaemic episode:
- Raised insulin
- Raised C-peptide
- Also test for sulfonylureas

Question 10

Diabetes drugs in renal impairment

Answer 10

Metformin - avoid GFR <30 (also if lactate >2)

Sulfonylureas - caution in mild-mod, avoid in severe

DPP-4 - safe to use

Pioglitazone - safe to use (avoid in liver impairment)

SGLT2 - dependent on the type (dapagliflozin can be used up to eGFR 15)

GLP1 agonist - caution GFR 30-50, avoid Saxenda in <30*
Victoza (another brand of liraglutide), can be used in CrCl <30, but avoid in end-stage renal failure

Question 11

HbA1c
a) Who should it not be used in?
b) Who must it be interpreted cautiously in?
c) Targets
d) Threshold for treatment intensification

Answer 11

a) - Symptoms < 2 months or suspected T1DM
- Pregnancy
- ESRF
- Acute pancreatitis
- Patients on steroids
- HIV

b) - Anaemia
- Haemoglobinopathy/haemolysis (HbA1c underestimated as there is less time to become glycosylated)
- Recent transfusion

c) - 48 if managed with diet/lifestyle or if on one diabetic drug not associated with hypoglycaemia
- 53 if on >1 diabetic medication
- Higher targets may be suitable for those at risk of hypoglycaemia, or in the elderly/severe comorbidities

d) 58 or more

Question 12

GLP-1 agonist
a) Indications
b) Treatment target at 6 months

Answer 12

a) - BMI >35 with medical/psychological impact
- BMI 30-34 if good reason to avoid insulin, or if weight loss would benefit other outcomes (e.g. CVD)

b) To continue treatment, they must have achieved by 6 months:
- HbA1c reduced by 11
- Weight loss of 3%

Question 13

Gastroparesis
a) Cause
b) Treatment
c) Investigations
d) Presentation

Answer 13

a) Microvascular neuropathy

b) Domperidone* - prokinetic antiemetic

• Caution in those aged >60 (risk of ventricular arrhythmia), contraindicated in cardiac disease/arrhythmia, mechanical obstruction. Can be used in PD for GI symptoms as doesn’t cross BBB (however, caution on CV risk - consider baseline ECG; possible increased risk of SUDPAR)

c) Gastric emptying studies

d) Nausea, vomiting, early satiety, abdominal pain

Question 14

Charcot joint:
a) Causes
b) Presentation
c) Management

Answer 14

a) Neuropathy, then trauma/infection/ulcers cause remodelling

b) - Red, warm, swollen foot/joint (with or without pain)
- Changes to foot shape

c) Immobilisation boot for 3-6 months to prevent further joint destruction
Bisphosphonates
Surgery as last resort

Question 15

Gestational diabetes
a) Management

Answer 15

a) If fasting glucose <7:
- 2 week trial diet/exercise
- If this fails, metformin
- If this fails, insulin +/- metformin

If fasting glucose >7 (or any current macrosomia/hydramnios):
- Insulin +/- metformin

Question 16

Somatostatinomas
a) Most are found where?
b) Common presentation

Answer 16

a) Head of the pancreas

b) Diabetes (as somatostatin prevents insulin release)
Diarrhoea
Gallstones

Question 17

Diabetic amyotrophy
a) Presentation
b) Risk factors
c) Management

Answer 17

a) Pain and weakness in the thighs (femoral nerve distribution)

b) - Poor diabetic control
- Rapid change in glucose (e.g. period of poor glycaemic control and rapid improvement after starting insulin)

c) Physiotherapy, neuropathic agents

Question 18

Reducing hypoglycaemia
a) T2DM
b) T1DM

Answer 18

a) Avoid sulfonylureas and insulin (promote GLP-1 agonists instead)

b) - DAFNE - training insulin dosing to food and exercise
- Avoid alcohol
- Allow higher BMs - to regain hypoglycaemic awareness
- Insulin pumps
- Continuous glucose monitoring (e.g. Libre)
- Islet cell transplant/ whole pancreas transplant

Question 19

HHS
a) Diagnostic criteria
b) Calculating osmolality
c) Management

Answer 19

a) “Hyperosmolar” – raised serum osmolality, usually Osm >320

“Hyperglycaemic” – very raised glucose, usually CBG >30 (often >50)

“State” – they’re in a right state – very hypovolaemic

No significant ketones (urine <2+, serum <3) or acidosis (pH >7.30, bicarb >15 mmol/L)

b) Osmolality = (2 x Na) + urea + glucose

c) - IV fluid replacement - 0.9% NaCl
- After 6h, start IV insulin
- Maintain BM 10-14 (add 10% dextrose when BM <14)
- Monitor electrolytes, osmolality and glucose (don’t expect as rapid a correction as with DKA)

Question 20

DKA
a) Diagnostic criteria
b) Criteria for ‘severe’ DKA
c) Management
d) Goals of treatment
e) ‘Resolution’ of DKA - define. What next in management?

Answer 20

a) “Diabetic” - BM >11 or known diabetes

“Keto-“ - Urine ketones 2+, or serum ketones >3.0

“Acidosis” - serum pH < 7.30 or bicarb <15

b) Severe DKA with need for HDU/ICU support if any of…
- Biochemical: any of ketones >6, pH <7.1 or bicarb <5, anion gap >16
- Vitals: HR >100 or <60, Systolic BP <90, SpO2 <92%
- GCS <12
- Hypokalaemia (K <3.5) on admission

c) - IV fluids - treat shock, replace losses, should contain 40mmol/L potassium unless K >5.5 or anuric (if K <3.5, may need higher concentration K+ and HDU/ICU)
- After 1 hour, start insulin (usually FRII at 0.1 units/kg/hr)
- When BM <14, add dextrose and consider reducing insulin to 0.05 units/kg/hr
- Monitor BM and ketones hourly
- Monitor venous pH and potassium (VBG) 2-hourly, then less frequently
- Monitor U&E 4-hourly then less frequently
- Continuous cardiac monitoring, monitor vitals and GCS regularly
- Assess need for NG - reduced GCS or vomiting
- Should have VTE prophylaxis
- Treat any precipitating factors
- Ensure referral made to the diabetes team

d) Aims of treatment:
• Rate of fall of:
- ketones of at least 0.5 mmol/L per hour
- bicarbonate rise 3 mmol/L per hour
- blood glucose fall 3 mmol/L per hour (Avoid hypoglycaemia)
• Maintain serum potassium in normal range

e) Resolution defined as:
- Serum ketones <0.6 mmol/L
- Venous pH >7.3 and/or venous bicarbonate >18 mmol/L

Once DKA resolved biochemically:
- If E+D –> switch to SC insulin (stop FRII 30 mins after SC insulin dose given)
- If not E+D –> switch to VRII
- Diabetes team review with plan for discharge etc.