T1DM and DKA Pathophysiology, differentials, investigations and management. Cases Quiz 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 (1) 5
Pathophysiology 6
Pathophysiology Pathophysiology Definition: a metabolic disorder characterised by high glucose levels due to absolute 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 Polyuria Poor wound healing Polydipsia Polyphagia Weight loss Fatigue 10
T1DM vs. T2DM Pathophysiology T1DM T2DM Frequency 10-20% 80-90% Pathogenesis Absolute insulin deficiency Insulin resistance Genetics HLA association No HLA association; strong genetic predisposition Presentation Age < 20 years old and often Age > 40 years and gradual acute with DKA onset Acute manifestation DKA Usually HHS Management Insulin Lifestyle à oral medication à insulin 11
Investigations Pathophysiology Primary investigations: • Random blood glucose: ≥11.1 mmol/L with clinical features à same-day referral • Fasting blood glucose: ≥7.0 mmol/L is typical • Oral glucose tolerance test: ≥11.1 mmol/L 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: short/rapid-acting insulin analogue with intermediate-acting insulin • Used when unable to tolerate basal-bolus regime • Continuous insulin infusion: disabling hypoglycaemia or persistent hyperglycaemia (HbA1c >69mmol/mol) 15
Monitoring Pathophysiology Glucose 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 • Neurological Stroke • 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
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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
Management 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
Management Serum potassium concentration (mmol/L) Potassium replacement > 5.5 None 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
Complications 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
Top decile question 31
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References 1. Anoel8 / CC BY-SA (https://creativecommons.org/licenses/by-sa/4.0). https://upload.wikimedia.org/wikipedia/commons/1/14/Proinsulin_evolution.png All other images used with permission under Basic License from Shutterstock 35
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