Diabetes Mellitis + DKA, HHS, Hypos

Question 1

Compare the patho of Type I vs Type II Diabetes

Answer 1

Type I: Autoimmune destruction of the insulin-producing β cells of the islets of Langerhans in the pancreas

Type II: Relative deficiency of insulin due to an excess of adipose tissue ‘insulin resistance’

Question 2

How does Type I diabetes present

Answer 2

1. Polyuria
2. Polydipsia
3. Weight loss
4. May present with DKA: abdo pain, vomiting, ↓consciousness

Question 3

How does Type II diabetes present

Answer 3

1. Often picked up incidentally on routine blood tests
2. Polydipsia
3. Polyuria

Question 4

What causes polyuria and polydipsia in a diabetes?

Answer 4

Water being ‘dragged’ out of the body due to the osmotic effects of excess blood glucose being excreted in the urine (glycosuria).

Question 5

List 5 ways to check blood glucose

Answer 5

1. Capillary blood glucose - finger-prick glucose monitor
2. One-off blood glucose, fasting or non-fasting
3. HbA1c
4. Glucose tolerance test
5. Flash Glucose Monitoring (e.g. FreeStyle Libre)

Question 6

What does HbA1c tell us?

Answer 6

Measures the amount of glycosylated haemoglobin and represents the average blood glucose over the past 2-3 months

Question 7

Explain the glucose tolerance test

Answer 7

A fasting blood glucose is taken after which a 75g glucose load is taken

After 2 hours a second blood glucose reading is then taken

Question 8

What is the WHO criteria for diagnosing type II diabetes?

Answer 8

If patient is symptomatic:

• fasting glucose ≥ 7.0 mmol/l
• random glucose ≥ 11.1 mmol/l (or after OGTT)

If patient is asymptomatic: above criteria must be demonstrated on two separate occasions

Question 9

Answer the following:

HbA1c ≥ ______% (48 mmol/mol) is diagnostic of diabetes mellitus

But an HbA1c less than this does not exclude diabetes

Answer 9

6.5

Question 10

3 Principals of Diabetes management

Answer 10

1. drug therapy to normalise blood glucose levels
2. monitoring for and treating any complications related to diabetes
3. modifying any other risk factors for other conditions such as CVD

Question 11

Management of Type I diabetes

Answer 11

1. Subcutaneous insulin regimes
2. Monitoring dietary carbohydrate intake
3. Monitoring blood sugar levels on waking, at each meal and before bed
4. Monitoring for and managing complications, both short and long term

Question 12

List 2 S/Es of Insulin

Answer 12

1. Hypoglycaemia
2. Lipodystrophy
3. Weight gain

Question 13

What are the 2 main insulin therapies?

Answer 13

1. Basal Bolus Regimes
2. Insulin Pump

Question 14

Explain the Basal Bolus Regime?

Answer 14

Basal → long acting insulin, typically in the evening, gives a constant background insulin throughout the day

Bolus → short acting insulin, usually 3 times a day before meals. Also injected according to the number of carbohydrates consumed during snacks

Question 15

List 2 examples of Rapid-acting Insulin?

How long do these take to start working and how long do these last?

Answer 15

eg. Novorapid, Humalog, Apidra

Start working after around 10 minutes and last around 4 hours

Question 16

List 2 examples of Short-acting Insulins?

How long do these take to start working and how long do these last?

Answer 16

eg. Actrapid, Humulin S, Insuman Rapid

Start working in around 30 minutes and last around 8 hours

Question 17

List 2 examples of Intermediate-acting Insulin?

How long do these take to start working and how long do these last?

Answer 17

eg. Insulatard, Humulin I, Insuman Basal

Start working in around 1 hour and last around 16 hours

Question 18

List 2 examples of Long-acting Insulins?

How long do these take to start working and how long do these last?

Answer 18

eg. Lantus, Levemir, Degludec (lasts over 40 hours)

Starts working in around 1 hour and lasts around 24 hours

Question 19

What are Combination Insulins?

List 2 examples

Answer 19

Contain a rapid acting and an intermediate acting insulin.

In brackets is the proportion of rapid to intermediate acting insulin

eg.

• Humalog 25 (25:75)
• Humalog 50 (50:50)
• Novomix 30 (30:70)

Question 20

What is an Insulin Pump?

What are the 2 types?

Answer 20

Small devices that continuously infuse insulin at different rates to control blood sugar levels

Types:

• Tethered pump
• Patch pump

Question 21

What is needed to qualify for an insulin pump funded by the NHS?

Answer 21

Child needs to be over 12 and have difficulty controlling their HbA1c

Question 22

List 3 advantages and 3 disadvantages of an insulin pump over a basal-bolus regime?

Answer 22

Advantages:

• Better blood sugar control
• More flexibility with eating
• Less injections

Disadvantages

• Difficulties learning to use the pump
• Having it attached at all times
• Blockages in the infusion set
• Small risk of infection

Question 23

Medical management of Type II Diabetes?

In order of stepping up

Answer 23

1. Initial drug treatment → Metformin
2. Dual therapy → Metformin + pioglitazone or DPP‑4 inhibitor or sulphonylurea
3. Triple therapy → using above medications OR insulin therapy
4. metformin + sulfonylurea + GLP1 memetic

Question 24

Medical management of Type II diabetes if Metformin is not tolerated?

In order of stepping up

Answer 24

1. Gliptin or Sulfonylurea or Pioglitazone
2. (Gliptin + Pioglitazone) or (Gliptin + Sulfonylurea) or (Pioglitazone + Sulfonylurea)
3. Insulin

Question 25

List 4 drug classes use to treat Type II Diabetes

Answer 25

1. Biguanides 2. Sulfonylureas 3. SGLT-2 inhibitors 4. DPP-4 inhibitors 5. Thiazolidinediones 6. GLP-1 analogues 7. Intestinal Alpha-Glucosidase Inhibitors

Question 26

Example of a Biguanide Mechanism of action?

Answer 26

Eg. Metformin (first line) MoA: Increases peripheral insulin sensitivity, decreases hepatic gluconeogenesis

Question 27

Side effects of Metformin? Contraindications?

Answer 27

S/E: diarrhoea, abdo pain, lactic acidosis Contraindications: eGFR \< 30 ml/min

Question 28

Example of a Sulfonylureas Mechanism of Action? S/E

Answer 28

Eg. Gliclazide MoA: Stimulate pancreatic beta cells to secrete insulin S/E: Hypoglycaemia, weight gain, hyponatraemia

Question 29

Example of a SGLT2 Inhibitor? Mechanism of action? S/E

Answer 29

Eg. Dapgliflozin MoA: Increase urinary glucose loss S/E: Glucoseuria, UTIs, Weight loss, DKA

Question 30

Example of a DPP4-Inhibitor? Mechanism of action? S/E?

Answer 30

Eg. Sitagliptin MoA: inhibits DPP-4, this increases GLP-1 activity S/E: GI upset, symptoms of URTI, pancreatitis

Question 31

What diabetic medication is contraindicated in heart failure?

Answer 31

Pioglitazone

Question 32

List the 3 main short term complications of diabetes

Answer 32

1. Hypoglycaemia 2. Hyperglycaemia (and DKA) 3. Hyperosmolar Hyperglycaemic state (HHS) - rare

Question 33

List 4 causes of hypoglycaemia

Answer 33

1. Insulin/sulphonylureas 2. Liver failure 3. Addison's disease 4. Alcohol 5. Insulinoma

Question 34

How are symptoms of hypoglycaemia divided? Why does each occur?

Answer 34

**\< 3.3** mmol/L → **autonomic** symptoms due to release of glucagon and adrenaline **\< 2.8** mmol/L → **neuroglycopenic** symptoms due to inadequate glucose supply to the brain

Question 35

Features of hypoglycaemia \< 3.3 mmol/L

Answer 35

1. Hunger 2. Irritability 3. Sweating and Tremors 4. Dizziness 5. Pallor

Question 36

Features of hypoglycaemia \< 2.8 mmol/L

Answer 36

1. Weakness 2. Vision changes 3. Confusion 4. Dizziness

Question 37

Pathophysiology of cardiac complications in diabetes?

Answer 37

Hyperglycaemia + free FA's in blood can cause the lining of BVs to become thicker → impair blood flow MI is commonly caused by a clot preventing supply to the heart

Question 38

Management of hypoglycaemia if patient is altert

Answer 38

15-20g fast acting carbohydrate ie. GlucoGel or Dextrogel, sweets or fruit juice Eat some slower acting carbohydrate afterwards (e.g. toast)

Question 39

Management of hypoglycaemia if patient is unconscious or unable to swallow

Answer 39

1mg/kg IM glucagon or alternativly 200ml 10% dextrose IV Treat seizure if prolonged or repeated

Question 40

What is DKA?

Answer 40

A state of severe, uncontrolled diabetes due to insulin deficiency Complication of existing **T1DM** or may be the first presentation (Rarely in T2DM)

Question 41

Pathophysiology of DKA

Answer 41

Uncontrolled **lipolysis** which results in an excess of FFAs that are ultimately converted to ketones

Question 42

List 3 of the most common precipitating factors of DKA

Answer 42

1. Infection 2. Missed insulin doses 3. Myocardial infarction

Question 43

List 4 symptoms of DKA

Answer 43

1. abdominal pain 2. vomiting/ nausea 3. lethargy, weakness, drowsiness 4. polyuria, polydipsia 5. leg cramps 6. blurred vision 7. Reduced consciousness ⇒ COMA

Question 44

List 4 clinical signs of DKA

Answer 44

1. Kussmaul respiration (deep hyperventilation) 2. Acetone-smelling breath ('pear drops' smell) 3. Dehydration 4. Electrolyte imbalance and Acidosis 5. Hypotension ⇒ Shock 6. Tachycardia 7. Ketonaemia/ ketonuria 8. Hyperglycaemia/ glycosuria

Question 45

Diagnostic criteria for DKA "Joint British Diabetes Societies (2013)"

Answer 45

1. Glucose \> 11 mmol/l or known DM 2. pH \< 7.3 3. Bicarbonate \< 15 mmol/l 4. Ketones \> 3 mmol/l or urine ketones ++ on dipstick

Question 46

Management of DKA

Answer 46

1. Fluid replacement: **Isotonic saline** used initially 2. **Fixed rate Insulin** IVI, 5% dextrose infusion once BG is \< 15 mmol/l 3. Correct electrolyte disturbances: **add K+** to replacement fluids 4. Continue long-acting insulin, STOP short acting insulin

Question 47

What defines resolution of DKA?

Answer 47

1. pH \> 7.3 and 2. blood ketones \< 0.6 mmol/L and 3. bicarbonate \> 15.0mmol/L

Question 48

Complications of DKA or treatment itself?

Answer 48

1. cerebral oedema 2. hypoxaemia – pulmonary oedema 3. fluid overload 4. respiratory failure 5. thromboembolism 6. arrhythmias – cardiac arrest 7. shock 8. renal insufficiency – AKI 9. hypoglycaemia 10. coma

Question 49

Monitoring of DKA

Answer 49

1. Glucose hourly for first 15 hours 2. Finger prick ketones hourly until stable 3. Blood gases/venous bicarbonate and electrolytes - 2, 4, 8 and 12 hourly 4. Pulse, BP, temperature, neuro obs 5. Urine output

Question 50

What is Hyperosmolar Hyperglycaemic state (HHS)

Answer 50

Hyperglycaemia in T2 diabetes Results in osmotic diuresis, severe dehydration, and electrolyte deficiencies - Medical emergency

Question 51

In which popultion is HHS most common?

Answer 51

Typically presents in the elderly with T2DM Note: increasing incidence in younger adults, can be the initial presentation of T2DM

Question 52

Pathophysiology of HHS

Answer 52

Hyperglycaemia results in **osmotic diuresis** with associated **loss of Na+ and K+** Severe volume depletion results in a significant **↑ serum osmolarity**, resulting in hyperviscosity of blood Despite these, the typical patient may not look as dehydrated as they are, because hypertonicity leads to preservation of intravascular volume

Question 53

Diagnostic criteria for HHS

Answer 53

1. Hypovolaemia and hypotension 2. Severe **Hyperglycaemia** (≥ 30 mmol/L) without significant ketonaemia or acidosis 3. Significant **Hyperosmolality** (\> 320 mosmol/kg)

Question 54

How do we differentiate DKA from HHS

Answer 54

In HHS the hyperglycaemia is not accompanied by significant acidosis or ketosis (as it is in DKA) In T2DM endogenous insulin production is sufficient to 'switch off' ketone production and prevent DKA

Question 55

Management of HHS

Answer 55

1. **Fluid resuscitation** 0.9% saline → correction of osmolality and fluid and electrolyte losses (gradually) 2. **Insulin** at 0.05 units/kg/hour → correction of hyperglycaemia (gradually) 3. **VTE prophylaxis** - patients are high risk due to dehydration

Question 56

List the main long term complications of diabetes Incl 2 macro and 2 microvascular complications

Answer 56

Macro: IHD, Stroke, CVD Micro: retinopathy, nephropathy, and neuropathy

Question 57

What is the BP target in a person with type 2 diabetes? Why is this important?

Answer 57

\< 140/90 mmHg BP control needs to be strict in diabetes because they are at higher risk of macro and microvascular complications

Question 58

How may physicians prevent CVD in diabetes? Explain?

Answer 58

Lipid lowering through use of Statins For T2DM use **QRISK2** → \>10% offer 20 mg **Atorvastatin**

Question 59

What is a recognised gastrointestinal complication of diabetes? How/why does this occur

Answer 59

Gastroparesis - due to poor glycaemic control Results in Autonomic Neuropathy - nerve damage to the ANS, specifcally to the vagus nerve (controls gastric muscles)

Question 60

How does Gastroparesis present?

Answer 60

Damage to vagus nerve leads to delayed gastric emptying and abnormal stomach wall movements. Presents as: 1. offensive egg smelling burps due to bacterial overgrowth 2. early satiety 3. morning nausea 4. fluctuations in blood glucose (mismatch between glucose absorbed in food and insulin injected)

Question 61

Treatment of Gastroparesis

Answer 61

1. Motility agents ie. metoclopramide, domperidone 2. Tight glycaemic control 3. Antibiotics ie Erythromycin (bacterial overgrowth) 4. Botox injections to relax the gastric outflow obstruction 5. Gastric pacemakers if all else fails

Question 62

List a clinical feature of autonomic neuropathy in diabetics How is this defined?

Answer 62

Postural/ orthostatic hypotension Defined as a fall in **systolic** BP by **20mmHg** or more after changing position or posture, typically lying to standing

Question 63

What is a consequence of orthostatic hypotension

Answer 63

Drop in BP on movement can lead to dizziness, falls and loss of consciousness Can be exacerbated by dehydration (ie. if a patient has hyperglycaemia and consequent polyuria)

Question 64

Management of Autonomic Neuropathy in diabetes

Answer 64

1. ↑ dietary salt 2. salt retaining hormones ie. Fludrocortisone or Midodrine 3. raising the head of the bed to retrain body's baroreceptors 4. wearing elasticated stockings to overcome venous pooling in peripheries 5. sitting or standing slowly may help with light headedness

Question 65

How do we prevent Peripheral Arterial Disease in diabetics

Answer 65

1. Patients and carers shold be educated about good foot self surveillance and care strategies 2. Feet should be reviewed on a regular basis

Question 66

How may Peripheral Arterial Disease present?

Answer 66

If circulation is compromised, it can manifest in several ways: * foot discolouration * gangrene * intermittent claudication * rest pain * night pain * absent peripheral pulses (confirmed on doppler)

Question 67

What is the treatment for PAD based upon?

Answer 67

managing cardiovascular risk factors

Question 68

A patient with Type II diabetes presents with critical ischaemia on their left foot. a) what is the biggest risk? b) what is your first immediate step in management

Answer 68

a) at risk of losing their foot b) need to be urgently seen by a multi-disciplinary specialist diabetic foot team which includes a vascular surgeon

Question 69

Most common causative organisms in diabetic ulcers?

Answer 69

Gram (+) → Staphylococcus aureus and Enterococcus Gram (-) → Escherichia coli, Klebsiella species, Proteus species, Pseudomonas aeruginosa and anaerobes.

Question 70

Management of diabetic foot infections

Answer 70

1. Good glycaemic and BP control 2. Stopping smoking 3. Improving the circulation (potentially with angioplasty or bypass surgery), 4. Debridement of the wound and use of larvae therapy and antibiotics

Question 71

What is the risk if an ulcer is deep and probes down to bone tissue? How do we diagnose this?

Answer 71

Osteomyelitis Diagnosed by MRI (does not reliably show up on plain X-rays)

Question 72

What is the commonest cause of death for diabetics?

Answer 72

Heart and circulation problems (75% of all deaths), with heart attacks accounting for 30% of all deaths