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

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T1DM and DKA

Endocrinology series

Dr Azeem Alam, MBBS BSc (Hons) Surgical AFP Guy’s and St. Thomas’ Hospital

Content reviewed on the 28/04/2020.

Pathophysiology, differentials, investigations and management.

Cases Quiz

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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

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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

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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

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Pathophysiology

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Clinical features

Symptoms Signs Polyuria Poor wound healing Polydipsia Polyphagia Weight loss Fatigue

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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

nset

Acute manifestation DKA Usually HHS Management Insulin Lifestyle à oral medication à insulin

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Pathophysiology

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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/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: 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)

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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

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Pathophysiology

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Complications

System Complication 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

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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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21 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

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known DM HCO3 < 15 mmol/L and/or venous pH < 7.30 Ketonaemia (≥ 3 mmol/l)

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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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