Diabetes Mellitus

Question 1

Describe the physiology of pancreatic beta-cell function.

Answer 1

Glucose uptaken by GLUT2
Glucose undergoes respiration by glucokinase
ATP produced causes closure of K(ATP) channel, depolarising the cell
Depolarisation opens Ca2+ channels, which causes exocytosis of insulin in Zn-insulin-crystal form.
Proinsulin is cleaved to form insulin and C-peptide in equimolar amounts

Question 2

Name the three main types of test for diabetes, and give the ranges of pre-diabetes and diabetes.

Answer 2

Fasting glucose: <6; 6.1 - 6.9; >7
2hr oral glucose tolerance test (OGTT): <7.7; 7.8 - 11.0; >11.1
Hb1Ac: <41; 42 - 47; >48 (mmol/mol)
(normal; pre-diabetes; diabetic)

Question 3

Name the main symptoms and complications of diabetes.

Answer 3

Triad (3P’s): polyuria, polydipsia, polyphagia
Others: blurred vision, genital thrush, fatigue, weight loss, weight gain etc
Macrovascular: cardiovascular (MI, PVD, stroke)
Microvascular: retinopathy, nephropathy, neuropathy

Question 4

Give a brief overview of the main drugs of T2 diabetic treatment.

Answer 4

metformin: inhibits glycolysis, neutral weight, risk acidosis, generally very safe and cheap
SUs: gliplizide, gliclizide, tolbutamide. weight gain, risk hypoglycaemia. very, very cheap
TZDs: pioglitazone (PPARy agonists). weight gain but v potent in obese women. risk cardiac failure/fracture
DDP-4 inhibitors: ‘gliptins. very few s/e (GI, rare pancreatitis), weight neutral
GLP-1 agonists: injection, weight loss. reduce appetite, renal and CV benefit. GI s/e (nausea, vomit)
SGLT2 inhibitors: dapagliflozin prevents reabsorption of glucose in kidney, cause weight loss. cardiac and renal benefit. s/e thrush, Fournier gangrene, hypovolaemia

Question 5

Where should insulin be injected? What are the main side effects? Describe how insulin syringes should be stored.

Answer 5

Abdomen, upper outer thigh or arm, buttocks by patient self at home. Same site should be injected while rotating throughout the day. Risk of lipohypertrophy (very rarely atrophy)
Don’t keep open in-use insulin in ward fridge (risk of cross-contamination) - will be OK for a month at room temp. If unopened, store in fridge

Question 6

Name the three main types of insulin therapy regimens, name the drugs involved, and describe how they would be adjusted if hyper- or hypoglycaemia occurs.

Answer 6

Rapid (humalog, actrapid, novorapid)
Intermediate-long acting (insulatard, lantus)
Basal bolus (both)
Hyper-: increase insulin 10% meal before
Hypo-: decrease insulin 10% meal before

Question 7

Give an overview of IV insulin therapy.

Answer 7

Short half-life, must be co-prescribed with K+ / glucose fluid with hourly monitoring
Daily U&E essential
Transfer to s.c. insulin once stable (able to eat and drink normally); discontinue 30-60 min after s.c. injection

Question 8

Describe the treatment of hypoglycaemia.

Answer 8

If able to swallow: glucojuice, tablets, or fruit juice (avoid latter in renal dysfunction)
Confusion: sublingual glucoboost
Unconscious: IM / IV glucose
Check blood glucose 15min after, then give 50g complex carbs (bread, or IV if nil-by-mouth)

Question 9

Describe the CPR approach for diabetic feet.

Answer 9

Glucose damages nerves (neuropathy) and blood supply (ischaemia, gangrene).
CHECK: all diabetic feet on admission. if feet appear normal, conduct toe touch test (big -> little toe, other big -> little toe, middle toe on each; 6 toes total, score out of 6 for sensation)
PROTECT: ankle or foot orthosis if damaged, or risk from neuropathy / toe touch test
REFER: all active ulcers/gangrene

Question 10

Describe the effects of insulin and glucagon on sugars, fats, and proteins.

Answer 10

Insulin - lipogenesis, glycogenesis, protein synthesis

Glucagon - lipolysis, glycogenolysis, gluconeogenesis, proteolysis

Question 11

Describe what is meant by the ‘polygenic common complex’ nature of diabetes.

Answer 11

Many alleles confer additional risk to development of T2DM (2-4%). Most diabetics are obese (90%), but some are obese with no resistance, and some are slim with high resistance - deficiency in fat storage.

Question 12

Which technique is used to best assess insulin sensitivity?

Answer 12

Hyperinsulinemic-eyglycemic clamp

Question 13

Describe the main aspects of nutrition in both types of diabetes.

Answer 13

T1DM - carbohydrate counting. MDI/CSII most flexible. 1 unit = 5g carbs. Patient uses ratio of carbs in meal to their insulin need (e.g. 1:10)
T2DM - >5% weight loss. Mediterranean, low fat diet recommended, with more fibre and fruit/veg, less fat and sugar. Total diet replacement in intensive need. 75min vigorous/150 min moderate exercise/week. BMI > 30 + condition (e.g. T2DM, asthma, HTN) -> referral to dietician (otherwise BMI > 35).

Question 14

Describe the 5 A’s approach to preventing obesity, and SMART goals.

Answer 14

Ask - permission to enquire - don’t make assumptions, the patient may already be dieting/losing weight
Assess - current behaviour and diet
Advise - tailored advice
Agree - identify and agree on goals
Assist - support gains in knowledge, progress. point to support networks
SMART goals - specific, measurable, achievable, realistic, timely

Question 15

Give the values for healthy, high, and very high risk waist circumference; and values for healthy cholesterol panel.

Answer 15

Men - <94 / 94-102 / >102
Women - <80 / 80-88 / >88
Cholesterol profile - total <5
HDL: >1 (male), >1.2 (female)
LDL <3, non-HDL <4
Triglycerides <2.3

Question 16

Describe the epidemiology of T1DM, stages of progression, treatment, and monitoring.

Answer 16

75% diagnosed as children, peak at 15yrs
HLA genes in 50%, DR3-DQ2 / DR4-DQ8
Seasonality higher in winter - may be due to viral infection, weight gain, or vitamin D deficiency triggers in genetic susceptibility
————
S1: normoglycaemic pre-symptomatic
S2: dysglycaemic pre-symptomatic
S3: hypoglycaemic acute symptoms
————
Aims of Mx: prevent hypo-, avoid hyper- reduce risk of complications (micro-, macrovascular)
Monitoring, MDI/CSII - note Hb1Ac may ‘mask’ hypo/hyper. Train in DAFNE/BERTIE

Question 17

Which autoimmune diseases are associated with T1DM?

Answer 17

Thyroid, coeliac’s, pernicious anaemia, Addison’s, IgA deficiency, cystic fibrosis (CFRDM).

Question 18

Name the main types of monogenic diabetes, their mechanism, and how they are treated.

Answer 18

MODY2 - glucokinase (GCK) - treated with diet only
MODY1, 3 - genetic factors (e.g. HNFa) - treated with sulfonylureas.
Neonatal - defect to K-channel proteins (Kir6/SU). Treatment with SUs.

Question 19

Describe how the three main microvascular complications of diabetes arise.

Answer 19

Excess glucose causes formation of mitochondrial ROS by shunting to alternative pathways, including

• polyl pathway
• pentose phosphate
• hexosamine
• diacyl glycerol
• AGE/RAGE

Question 20

Give an overview of diabetic retinopathy.

Answer 20

Glucose causes damage to the vessels in the eye. Bleeding causes haemorrhage (small: dot, large: blot, very large: flame; DH, BH, FH). These can lead to IRMAs and venous beading, then neovascularisation, which have risk of huge haemorrhage
- R1: mild background
- R2: >4 BH - 6month
- R3: IRMAs, beading - refer
- R4: NVD, NVE, vitreous haemorrhage, retinal detachment - urgent referral
- M1: hard exudate - 6month
- M2: hard exudate/BH within 1 circumference of macula - refer
Treatment with optical coherance tomography (OCT), or intravitrial VEGF.

Question 21

Give an overview of diabetic nephropathy and neuropathy.

Answer 21

Nodular glomerulosclerosis, with hypertension and decline in renal function (1ml/mol/month), meaning the glomeruli are more leaky and lose protein.
Normal ASR <3.5 female, <2.5 male
Insipid DN: ACR<30, PCR<50
Overt DN: ACR>30, PCR>50
Treat with ACEi/ARBs and SGLT2i.
————
Neuropathy can be peripheral (gloves and stocking), proximal, autonomic, or focal. May lead to charcot foot, which needs an aircast boot or total contact cast. Treatment with pain relief (e.g. amitryptiline, gabapentin etc.)

Question 22

Describe the basics of ethics of consent.

Answer 22

Battery - unlawful touching (patient does not need to be harmed to claim damages)
Consent - may be retracted at any time
Contract - may be withdrawn, but subject to consequences
Consent is assumed at 16, unless treatment immediately needed to save a life, someone could be hurt (mental health), or public health (e.g. TB, COVID-19)
Capacity is assumed if a patient can understand, retain, and use information to make a decision.

Question 23

What is DKA? What are the main causes? Describe the key symptoms, biochemical markers, and treatment.

Answer 23

Absolute/relative insulin deficiency, plus increase in counter-regulatory hormones (e.g. glucagon, cortisol).
5 I’s: infection (pneumonia, UTI), inflammation (pancreatitis), intoxication (alcohol, drugs), infarction (MI, stroke), iatrogenic (steroids, surgery).
Ketonaemia >3mmol/L
Ketonuria >2 ++
Bicarbonate < 12mmol/L
pH <7.1
Hypokalaemia <3.5mmol/L
Osmotic symptoms (thirst, polyuria), ketones (nausea, vomiting, flush, Kussmaul breathing, fruity smell)
Replace fluid loss (0.9% saline, replace with dextrose when glucose <15mmol/L, monitor K+, consider an NG tube, give LMWH
Inform of sick-day rules and give ketone meter

Question 24

Describe the hyperglycaemic hyperosmolar state, its main causes, treatments, and considerations.

Answer 24

Relative insulin deficiency + counter-regulatory hormones - enough insulin to stop ketogenesis.
Osmolality > 320mOsm/kg, where osmo = 2xNa + urea + glucose
Main causes are IHD (MI, stroke), sepsis, steroids, thiazide diuretics
Main concern is fluid loss, much less insulin. Give 0.45% saline (about 12l), but be careful for fluid overload.
Patients are older, so screen for co-morbidities, such as silent MI. check feet.