1. Dr Sara Al-Ansari, FY1

2. Session Overview Diabetes Mellitus Aetiology Presentation
Investigations
Diagnosis
Management
Complications
Diabetic ketoacidosis
Hyperosmolar hyperglycaemic state
Hypoglycaemia

3. Diabetes Mellitus
Definition: A metabolic disorder characterised by chronic hyperglycaemia resulting from defects in insulin production, insulin action or both.
Aetiological classification of DM
Type 1 DM: (β cell destruction > insulin deficiency)
Immune mediated
Idiopathic
Type 2 DM: (Characterised by variable degrees of insulin deficiency and resistance).
Gestational DM
Other specific types

4. Presentation
Characteristic symptoms: polyuria, polydipsia, blurring of vision, weight loss, recurrent infections, lethargy. In its most severe forms, ketoacidosis or a non-ketotic hyperosmolar state may develop and lead to stupor, coma and in absence of effective treatment, death. Often symptoms are not severe, or may be absent, and consequently hyperglycaemia sufficient to cause pathological and functional changes may be present for a long time before a diagnosis is made

5. Investigations Bedside tests BM Urine dipstick: ketones + proteinuria
Blood tests
Fasting/Random glucose, HbA1c, FBC, U&E’s, LFTs, cholesterol, Amylase, C-peptide, Autoantibodies.
ABG
Additional tests
ECG
CXR
AXR/CT abdomen
Albumin:creatinine ratio

6. Diagnostic Criteria [WHO Criteria]
Diabetes is diagnosed on the basis of history (ie polyuria, polydipsia and unexplained weight loss) PLUS:
Fasting plasma glucose >= 7.0 mmol/L
Two-hour plasma glucose level concentration >= 11.1 mmol/l after 75g anhydrous glucose in an oral glucose tolerance test (OGTT)
A random venous plasma glucose concentration >= 11.1 mmol/l in a patient with classic symptoms of hyperglycemia or hyperglycemic crisis
HbA1c > 6.5% (48 mmol/mol)
With no symptoms diagnosis should not be based on a single glucose determination but requires confirmatory plasma venous determination.

7. Management of Diabetes
Conservative
Lifestyle – weight reduction, dietician input, regular exercise
Smoking cessation
help and advice
Foot care
Eye checks
Patient Education
Medical
Type 1: Insulin regimes
Type 2: Metformin, Sulphonylureas, Glitazones, DDP4 inhibitors, Insulins
Control BP, cholesterol and other risk factors
Surgical
Islet cell transplants
Complications e.g. amputation

8. Oral Hypoglycaemic medications

9. Onset
Peak
Duration
Example
Short-acting
30 minutes
2-4 hours
8 hours
Actrapid
Humulin S
Intermediate
1-2 hours
4-12 hours
16-24 hours
Insulatard
Humulin I
Long-acting
20-35 hours
Human Ultratard
Humulin Zn
Analogue
0-15 minutes
4-6 hours
24 hours
Humalog (Lispro)
Novorapid (Aspart)
Apidra (Glulisine)
Glargine, Levemir

10. Insulin Regimens

11. Glucose control
Review the person's HbA1c level and agree an appropriate target level:
If managed by diet alone or by one drug, a target HbA1c of 6.5% (48 mmol/mol) is generally recommended.
If the person requires more intensive treatment, a target of less than 7.5% (59 mmol/mol) is generally recommended

12. Complications Emergency DKA HONK Hypoglycaemia Long-term
Macrovascular: Stroke, MI, PVD
Microvascular: Neuropathy, nephropathy, retinopathy

13. Diabetic Ketoacidosis
Precipitating factors
Omitted/inadequate insulin dose:
Inadvertent - malfunction of insulin delivery system.
Intentional - not administering insulin when required.
Infection, e.g. pneumonia, UTI.
Acute illness.
Drugs that alter carbohydrate metabolism, e.g. corticosteroids, thiazides, sympathomimetics, and second-generation (atypical) antipsychotics.
Diabetic Ketoacidosis
Ketonaemia > 3.0mmol/l or significant ketonuria (2+ on standard urine sticks)
Blood glucose > 11.0mmol/l or known DM
Bicarbonate (HCO3) < 15.0mmol/l and/or venous pH <7.3

14. Symptoms: Polyuria, polydipsia, weight loss, D+V, abdo pain, lethargy, confusion.
Examination
Acetone breath.
Kussmaul respiration.
Dehydration — classify as:
Mild (3%) — only just clinically detectable.
Moderate (5%) — dry skin + mucus membranes; reduced skin turgor.
Severe (8%) — sunken eyes, prolonged CRT.
Shock — severely ill with: ↑HR, poor peripheral perfusion & ↓BP, indicates decreased cardiac output. Lethargy, drowsiness, or ↓GCS indicates decreased cerebral perfusion. ↓UO indicates decreased renal perfusion.
Assess the person for conditions in which ketoacidosis can have severe consequences: pregnancy, heart failure, renal failure.

15. Management of DKA Rapid ABC
Large bore IV canula and commence IV fluid replacement
Full clinical assessment and initial investigation
Blood ketones
CBG
Venous plasma glucose
FBC + U&Es
Blood cultures
ECG
CXR
Urinalysis and culture
Urinary catheterisation if patient is incontinent and anuric
Fixed Rate insulin infusion - This is made of 50 units of human soluble insulin
(Actrapid®, Humulin S®) made up to 50ml with 0.9% sodium chloride solution [0.1 units/kg/hr]
Continue long-acting insulin analogues
Potassium replacement
Reassess the patient
Review biochemical and metabolic parameters: Monitor hourly blood glucose and ketones. Monitor serum K and bicarbonate 2-hourly for the first 6 hours.
Diabetes specialist team
Typical deficits in adult
Water - 100ml/kg
Sodium mmol/kg
Chloride - 3-5mmol/kg
Potassium - 3-5mmol/kg

17. Assessment of severity, the presence of one or more of the following may indicate severe DKA:
Blood ketones > 6mmol/L
Bicarbonate level < 5mmol/L
Venous/arterial pH < 7.0
Hypokalaemia on admission (<3.5mmol/L)
GCS <12 or abnormal AVPU scale
O2 sats <92% on RA (assuming
normal baseline resp function)
SBP <90mmHg
Tachy/bradycardic
Anion gap above 16 [Anion Gap = (Na+ + K+) – (Cl- + HCO3-) ]
Metabolic treatment targets:
↓ blood ketone by 0.5 mmol/L/hour
↑ venous bicarb by 3 mmol/L/hour
↓ CBG by 3 mmol/L/hour
Maintain potassium between 4.0 and 5.5mmol/L
If these rates are not achieved, then the FRIII rate should be increased

18. Serious complications of DKA and their treatment
Hypokalaemia & Hyperkalaemia
Hypoglycaemia
Cerebral oedema
Pulmonary oedema

19. Hyperosmolar Hyperglycaemic State

20. Goals of treatment
The goals of treatment of HHS are to treat the underlying cause and to gradually and safely: • Normalise the osmolality • Replace fluid and electrolyte losses • Normalise blood glucose Other goals include prevention of: • Arterial or venous thrombosis • Other potential complications e.g. cerebral oedema/ central pontine myelinolysis • Foot ulceration

21. Management Rapid ABC IV access and commence fluid replacement
Full clinical assessment and investigation
FRII – 0.05units/kg/hr if significant ketonaemia/ketonuria
Potassium replacement
Prophylactic LMWH

22. Hypoglycaemia
Definition: Blood glucose levels decrease to less than 4.0 mmol/L. Adrenergic effects (early symptoms): sweating, tachycardia, palpitations, pallor, hunger, and restlessness. Apart from sweating, these effects may be suppressed in people taking non-cardioselective beta-blockers (such as propranolol). Neuroglycopenic effects (late symptoms): confusion, slurred speech, drowsiness, frequent yawning, anxiety, blurred vision, diplopia, and numbness of nose, lips, and fingers. In more serious cases, this can lead to loss of consciousness, seizures, and death. Hunger, headache, nausea, and tiredness are non-specific symptoms which can be associated with low, high or normal blood glucose.

23. Mild & Moderate hypoglycaemia is when the person is aware of, responds to and self-treats the hypoglycaemia. They can swallow safely.
Three to six glucose tablets.
90–180 mL of fizzy drink or squash.
50–100 mL of Lucozade Energy® (contains 26% glucose syrup/100mL).
2-4 spoonfuls of sugar added to a cup of drink (for example, water).
Sweets such as four large jelly babies, or seven large jelly beans.
A glass of fruit juice.
Glucose gel (GlucoGel® or Dextrogel®; both contain 10 g of glucose)
The patient should immediately eat some long-acting, starchy carbohydrate (such as a sandwich or some biscuits). Around 10–20 g is recommended but the exact amount will vary from person to person.

24. Severe hypoglycaemia is when the person is semi-conscious or unconscious or in a coma with or without convulsions and will require parenteral therapy (glucagon or intravenous glucose). These people are unable to swallow safely.
Protect Airway
15L O2
IV access
50ml 50% glucose STAT
(100ml of 20%, 200ml of 10%)
For large insulin OD give 1mg
of glucagon SC/IM/IV
Should respond in 10 min
1L 10% glucose over 4-8h
Aim for BM > 5

25. Case Scenario
A 52 year old man presents to his GP as he has been feeling lethargic and tired for the last few months.  He has over the last 2 weeks also become very thirsty and is drinking more than normal.  He reports no other significant symptoms.  He suffers from hypertension which is managed with ramipril and has no known allergies.  He works as a librarian and drinks socially and doesn’t smoke.  On examination he has a BMI of 32 and full systems examinations are unremarkable. His urine dip shows glucose ++ and a BM done in the surgery registers as 13.  à Diabetes Mellitus type 2

26. What are your differentials for this gentleman
What are your differentials for this gentleman? (make sure these include all important differentials that must be ruled out)
How would you investigate this man?
How would you manage this gentleman?
What are the diagnostic criteria for diabetes?
What are impaired fasting glucose and impaired glucose tolerance?
What are the micro and macrovascular complications of diabetes?
How does diabetes cause peripheral neuropathy?
What drugs are used to manage type 2?
What insulin regimes are used to manage type 1?