T1DM and DKA Pathophysiology, differentials, investigations and - PowerPoint PPT Presentation

T1DM and DKA Pathophysiology, differentials, investigations and management. Quiz Cases Dr Azeem Alam, MBBS BSc (Hons) Surgical AFP Guy’s and St. Thomas’ Hospital Endocrinology series Content reviewed on the 28/04/2020.

Case 1 History An 11-year-old boy presents to the emergency department with abdominal pain and vomiting. He reports an ongoing history of frequent urination and extreme thirst. BM levels are unrecordable and ketones are 4 mmol/L. You notice a fruity smell on his breath. Observations HR 125, BP 92/65 mmHg, RR 28, SpO2 97%, Temp 38.0 2

Case 1 History An 11-year-old boy presents to the emergency department with abdominal pain and vomiting. He reports an ongoing history of frequent urination and extreme thirst. BM levels are unrecordable and ketones are 4 mmol/L. You notice a fruity smell on his breath. Observations HR 125, BP 92/65 mmHg, RR 28, SpO2 97%, Temp 38.0. 4

Pathophysiology Pathophysiology (2) (1) 5

Pathophysiology 6

Pathophysiology Definition: a metabolic disorder characterised by high glucose levels due to absolute Pathophysiology insulin deficiency . Epidemiology • 10-20% of all diabetic patients • Most common form of diabetes in <20 years of age • Highest incidence at 10-14 years old Risk factors • HLA risk profile: HLA-DR3 and HLA-DR4 • Personal / family history of autoimmune disease: e.g Hashimoto’s 9

Clinical features Pathophysiology Symptoms Signs Poor wound healing Polyuria Polydipsia Polyphagia Weight loss Fatigue 10

T1DM vs. T2DM T1DM T2DM Pathophysiology 10-20% 80-90% Frequency Pathogenesis Absolute insulin Insulin resistance deficiency HLA association No HLA association; Genetics strong genetic predisposition Age < 20 years old and Age > 40 years and Presentation often acute with DKA gradual onset DKA Usually HHS Acute manifestation Lifestyle à oral Management Insulin medication 11 à insulin

Investigations Primary investigations: Pathophysiology • Random blood glucose: >11mmol/mol with clinical features à same-day referral • Fasting blood glucose: ≥7.0 mmol/L is typical • Oral glucose tolerance test: >11mmol/mol two hours after a 75g oral glucose load • HbA1c: >48 mmol/mol suggests hyperglycaemia over 3 months. Use for monitoring Investigations to consider: C-peptide: if atypical features are present e.g. age > 50, or BMI > 25kg/m 2 • Autoantibodies: if atypical features are present; e.g. anti-glutamic acid decarboxylase • VBG: if concerned about DKA • 13

Management Urgent referral to diabetes specialist team Lifestyle • Diet high in fibre and low in fat, sugar, and salt • Educate regarding carbohydrate counting; allows insulin dose to be matched to intake Insulin therapy • Basal-bolus: first-line, long-acting regularly (basal) with rapid-acting insulin before meals (bolus) • Basal : Levemir (Detemir) given twice daily . Lantus (Glargine) once-daily is an alternative • Bolus : Insulin Lispro (Humalog), Insulin Aspart (Novorapid) • Mixed insulin regimen: mixed insulin comprises a short-acting and long-acting insulin, BD. • Used when unable to tolerate basal-bolus regime • Continuous insulin infusion: disabling hypoglycaemia or persistent hyperglycaemia (HbA1c >69mmol/mol) 15

Monitoring Glucose Pathophysiology HbA1c: measured every 3-6 months with a target of ≤48 mmol/mol • Self-monitoring: check blood glucose levels at least 4 times a day. Targets as follows: • On waking: 5-7 mmol/L • Before meals and other times of the day: 4-7 mmol/L • Retinopathy Immediate ophthalmology referral upon diagnosis and annually thereafter • Arrange urgent review thereafter if: • Acute reduction in acuity • Pre proliferative or proliferative retinopathy • Diabetic maculopathy • Diabetic foot • Should be assessed at least annually; refer urgently to foot protection service if at risk (e.g. ulceration) Diabetic nephropathy Annual measurement of eGFR and urinary albumin:creatinine ratio • 16

Complications System Complication Pathophysiology • Cardiovascular Ischaemic heart disease • Heart failure • PVD • Stroke Neurological • Carpal tunnel syndrome • Neuropathy • Endocrine DKA • Renal Diabetic nephropathy and CKD • Ophthalmology Diabetic retinopathy • Macular degeneration • Open-angle glaucoma • Cataracts 17

Diabetic ketoacidosis • Metabolic state as a complication of T1DM (predominantly) • Medical emergency : dehydration and electrolyte imbalances • Triad : hyperglycaemia, acidosis and ketonaemia • Mortality rate < 1% in UK • May be a first presentation of T1DM • Often a precipitating factor : infection , trauma, surgery, corticosteroid use 18

Diabetic ketoacidosis 20

Precipitating factor Increase in Net reduction in counter hormones insulin (e.g. cortisol) Reduced glucose entry ? Gluconeogenesis into cells ? Glycogenolysis Metabolism of lipids as Hyperglycaemia an alternative energy source ? FFA to liver Osmotic diuresis ? Ketogenesis Dehydration and Acidosis electrolyte abnormalities 21

Clinical features Symptoms Signs Pathophysiology Abdominal pain Fruity ‘pear drop’ smell of acetone on the breath Nausea and vomiting Dehydration : Mild : only just detectable • Moderate : dry skin and mucus membranes; reduced skin • turgor Shock : tachycardia, hypotension (late), drowsiness, • reduced urine output Polyuria and polydipsia Kussmaul respiration : deep, laboured breathing Weight loss Inability to tolerate oral fluids Lethargy and confusion 24

Investigations Bedside • Urine dip: glycosuria and ketonuria • Bedside ketone and capillary glucose Bloods • ABG/VBG: quickest way to ascertain pH and HCO 3 levels • U&Es: electrolyte derangement and acute kidney injury due to dehydration • FBC and CRP: raised inflammatory markers may suggest underlying infection as a precipitant • Infection screen : if an infection is the suspected trigger 25

Diagnostic criteria Triad : hyperglycaemia, acidosis and ketonaemia Joint British Diabetes Societies Inpatient Care Group (2013) Glucose > 11 mmol/L or known DM HCO3 < 15 mmol/L and/or venous pH < 7.30 Ketonaemia (≥ 3 mmol/l) or 2+ ketonuria 26

Manageme nt Treatment Further information IV fluid SBP < 90 mmHg 1 litre 0.9% NaCl over 15 mins • Call for senior help as required • SBP > 90 mmHg : typical regimen • 1 litre 0.9% NaCl over 1 hour • 1 litre 0.9% NaCl with KCl over next 2 hours • 1 litre 0.9% NaCl with KCl over next 2 hours 1 litre 0.9% NaCl with KCl over next 4 hours • 1 litre 0.9% NaCl with KCl over next 4 hours • 1 litre 0.9% NaCl with KCl over next 6 hours • Insulin Fixed-rate insulin infusion : Commence at 0.1 U/kg/h • Add in 10% glucose once glucose levels drop below 14.0 mmol/L • Do not stop long-acting insulin • 28

Manageme nt Serum potassium concentration (mmol/L) Potassium replacement None > 5.5 3.5-5.5 40 mmol/L < 3.5 Consider HDU/ITU for replacement via central line • Potassium replacement • Total body potassium is low and correction of acidosis causes further reduction in potassium • Anticoagulation: patients are at increased risk of VTE • Glucose, pH, bicarbonate, ketone levels, and electrolytes should be closely monitored throughout, 1-2 hourly 29

Complicatio ns Hypokalaemia and hyperkalaemia • Potentially life-threatening • Hyperkalaemia: extracellular shift of K + due to acidosis • Hypokalaemia: due to correction of acidosis Hypoglycaemia • Due to rapid correction of ketoacidosis • May result in rebound ketosis Cerebral oedema • More common in children (70-80% of diabetes-related deaths) • Likely to be iatrogenic 30

T1DM and DKA Pathophysiology, differentials, investigations and - PowerPoint PPT Presentation

T1DM and DKA Pathophysiology, differentials, investigations and management. Quiz Cases Dr Azeem Alam, MBBS BSc (Hons) Surgical AFP Guys and St. Thomas Hospital Endocrinology series Content reviewed on the 28/04/2020. Case 1 History

T1DM and DKA Pathophysiology, differentials, investigations and management. Cases Quiz Dr

Introduction People with T1DM are usually in basal-bolus therapy Timely and accurate