Dr Sara Al-Ansari, FY1

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

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

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

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

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.

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

Oral Hypoglycaemic medications

  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

Insulin Regimens

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

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

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

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.

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 - 7-10mmol/kg Chloride - 3-5mmol/kg Potassium - 3-5mmol/kg

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

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

Hyperosmolar Hyperglycaemic State

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

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

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.

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.

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

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

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?