T1DM and DKA
Transcript of T1DM and DKA
T1DM and DKA
Endocrinology series
Dr Azeem Alam, MBBS BSc (Hons)Surgical AFPGuy’s and St. Thomas’ HospitalContent reviewed on the 28/04/2020.
Pathophysiology, differentials, investigations and management.
Cases Quiz
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
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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.
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Case 1
Pathophysiology
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Pathophysiology
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Pathophysiology
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Pathophysiology
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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
Pathophysiology
Pathophysiology
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Clinical features
Symptoms Signs
Polyuria Poor wound healing
Polydipsia
Polyphagia
Weight loss
Fatigue
Pathophysiology
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T1DM vs. T2DM
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 acute with DKA
Age > 40 years and gradual onset
Acute manifestation
DKA Usually HHS
Management Insulin Lifestyle à oral medicationà insulin
Pathophysiology
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Primary investigations:• 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/m2
• Autoantibodies: if atypical features are present; e.g. anti-glutamic acid decarboxylase• VBG: if concerned about DKA
Investigations
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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)
Pathophysiology
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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
Monitoring
Pathophysiology
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Complications
System Complication
Cardiovascular • Ischaemic heart disease• Heart failure• PVD
Neurological • Stroke• Carpal tunnel syndrome• Neuropathy
Endocrine • DKARenal • Diabetic nephropathy and
CKDOphthalmology • Diabetic retinopathy
• Macular degeneration• Open-angle glaucoma• Cataracts
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• 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
Diabetic ketoacidosis
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Diabetic ketoacidosis
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Precipitating factor
Net reduction in insulin
Increase in counter hormones
(e.g. cortisol)
Reduced glucose entry into cells
Metabolism of lipids as an alternative energy
source
? FFA to liver ? Ketogenesis
Acidosis
? Gluconeogenesis ? Glycogenolysis
Hyperglycaemia
Osmotic diuresis
Dehydration and electrolyte
abnormalities
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Pathophysiology
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Clinical features
Symptoms Signs
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
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Bedside• Urine dip: glycosuria and ketonuria• Bedside ketone and capillary glucose
Bloods• ABG/VBG: quickest way to ascertain pH and HCO3 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
Investigations
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Triad: hyperglycaemia, acidosis and ketonaemia
Diagnostic criteria
Joint British Diabetes Societies Inpatient Care Group (2013)
Glucose > 11 mmol/L or
known DM
HCO3 < 15 mmol/Land/or
venous pH < 7.30
Ketonaemia (≥ 3 mmol/l) or
2+ ketonuria
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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
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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
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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
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Top decile question
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References
1. Anoel8 / CC BY-SA (https://creativecommons.org/licenses/by-sa/4.0)