Anxiety Disorder

A blood glucose above 11.1 mmol/L. The clinical task in the emergency setting is not to lower the glucose but to determine which of three states the patient is in, since the management of each is entirely different:

• Uncomplicated hyperglycaemia: no significant ketosis, no acidosis, normal osmolality. Managed by treating the precipitant and optimising oral therapy, generally without insulin in the emergency department and frequently as an outpatient.
• Diabetic ketoacidosis: ketosis with acidosis.
• Hyperosmolar hyperglycaemic state: extreme hyperglycaemia with raised osmolality, without significant ketosis or acidosis.

The rule that governs the first hour: do not give insulin until the patient has been assessed

Insulin given before potassium is known can precipitate fatal hypokalaemia, since insulin drives potassium intracellularly and total body potassium is already profoundly depleted in ketoacidosis despite a normal or high serum value. Insulin given before fluid resuscitation in a hypovolaemic patient causes further intravascular volume shift and circulatory collapse. Insulin given to a patient with uncomplicated hyperglycaemia who is dehydrated and about to be discharged is unnecessary and dangerous. Establish the category, the potassium and the volume status first.

Pathophysiology

Relative or absolute insulin deficiency with counterregulatory hormone excess produces hepatic gluconeogenesis and glycogenolysis, reduced peripheral glucose uptake, and lipolysis with free fatty acid release. Once the renal threshold of around 10 mmol/L is exceeded, osmotic diuresis produces water and electrolyte loss, hypovolaemia, reduced glomerular filtration and a further rise in glucose. Whether ketosis develops depends on the degree of insulin deficiency: even small amounts of residual insulin suppress lipolysis sufficiently to prevent ketogenesis, which is why type 2 diabetes usually produces hyperosmolar states rather than ketoacidosis.

Precipitants, which must be identified in every case

• Infection, which accounts for 30 to 50 percent: urinary tract infection, pneumonia, skin and soft tissue infection, dental sepsis, and in endemic areas malaria, tuberculosis and HIV related infection.
• Non adherence with medication, insulin omission, running out of supply, or insulin storage failure.
• New onset diabetes.
• Acute coronary syndrome, which may be silent in diabetes and which must be actively excluded with an electrocardiogram in older patients.
• Stroke, pancreatitis, trauma, surgery and burns.
• Drugs: corticosteroids, thiazides, atypical antipsychotics, sympathomimetics, and sodium glucose cotransporter 2 inhibitors which cause euglycaemic ketoacidosis.
• Pregnancy.
• Alcohol and substance use.
• Psychosocial factors including depression, eating disorder and inability to afford medication, which are frequent and rarely asked about.

Symptoms of hyperglycaemia

• Polyuria, nocturia and polydipsia.
• Weight loss, which in a newly presenting patient may be substantial.
• Fatigue and lethargy.
• Blurred vision from osmotic lens changes.
• Recurrent infections: candidiasis, balanitis, urinary tract infection, skin sepsis, poor wound healing.
• Polyphagia in early disease.

Symptoms indicating a complicated state

• Nausea, vomiting and abdominal pain, which suggest ketoacidosis. Abdominal pain in ketoacidosis is common and correlates with the severity of the acidosis, but it can also indicate a surgical cause of the ketoacidosis, so pain that persists after the acidosis clears requires surgical assessment.
• Deep sighing Kussmaul respiration and a ketotic breath.
• Altered consciousness, drowsiness and coma, which correlate with osmolality rather than with glucose or acidosis. Coma with a normal osmolality requires a search for another cause.
• Marked dehydration with dry mucous membranes, reduced skin turgor, sunken eyes, tachycardia and hypotension.
• Focal neurological signs and seizures in hyperosmolar states.

Assessment

• Hydration status, including postural blood pressure where the patient can stand.
• A full examination for the precipitant: chest, abdomen, skin including the feet and perineum, dentition, injection sites and any catheters or lines.
• Feet in particular, since a neglected infected foot ulcer is a frequent and easily missed precipitant.

Initial workup in every hyperglycaemic patient

• Monitor and support airway, breathing and circulation.
• Vital signs including blood pressure, pulse, respiratory rate, oxygen saturation and temperature.
• Oxygen if saturation is below 94 percent, targeting 94 percent or above.
• Establish intravenous access.
• Send simultaneously: capillary or serum ketones, venous blood gas, urea and electrolytes with creatinine, and urinalysis.
• Twelve lead electrocardiogram in older patients, in those with cardiovascular risk factors, and in anyone with chest symptoms or an abnormal potassium.
• Brief targeted history and examination directed at the precipitant.
• Withhold insulin until the potassium and the acid base status are known.

Venous rather than arterial gas

A venous blood gas correlates closely with arterial values for pH, bicarbonate and potassium, differing by around 0.03 pH units and 1 to 2 mmol/L of bicarbonate. It is adequate for the assessment and monitoring of hyperglycaemic emergencies, avoids repeated arterial puncture, and should be the default. An arterial sample is needed only when oxygenation must be measured directly.

Categorising the patient

Uncomplicated hyperglycaemia requires all three of:

• A normal venous blood gas, meaning pH 7.3 or above and bicarbonate 15 mmol/L or above.
• Serum ketones below 3 mmol/L, or urine ketones less than 2 plus.
• Calculated serum osmolality below 300 mOsm/kg.

If any of these is not met, the patient has ketoacidosis or a hyperosmolar state and is managed on that pathway.

Calculations

• Calculated total serum osmolality equals 2 times the sum of sodium and potassium in mmol/L, plus glucose in mmol/L, plus urea in mmol/L. Effective osmolality, which correlates better with conscious level, omits urea since urea crosses cell membranes freely.
• Anion gap equals sodium minus the sum of chloride and bicarbonate. A gap above 12 mmol/L indicates a raised anion gap acidosis.
• Corrected sodium equals measured sodium plus 1.6 times the quantity glucose minus 5.6, divided by 5.6. Hyperglycaemia draws water into the intravascular space and dilutes sodium, so a normal or high measured sodium in the presence of marked hyperglycaemia indicates profound free water deficit.

Further investigations directed at the precipitant

• Full blood count, recognising that a leucocytosis up to around 15 x 10⁹/L occurs with ketoacidosis alone from stress demargination, while counts above this or a left shift suggest infection.
• Blood cultures, urine culture, chest radiography.
• Malaria rapid diagnostic test and blood film in endemic areas.
• Amylase and lipase where pancreatitis is suspected, noting that amylase is frequently mildly raised in ketoacidosis without pancreatitis.
• Troponin and serial electrocardiograms where acute coronary syndrome is possible.
• HbA1c, which distinguishes acute stress hyperglycaemia from established poorly controlled diabetes and which establishes the baseline for ongoing management.
• HIV testing where relevant, and tuberculosis screening in endemic settings.
• Pregnancy test in women of reproductive age.

Distinguishing new type 1 from type 2 diabetes matters for immediate management. Younger age, lean habitus, rapid onset with weight loss, ketosis and family history of autoimmune disease favour type 1. Anti glutamic acid decarboxylase antibodies and C peptide are used where the distinction is unclear, but the acute decision is made clinically and a patient who is ketotic requires insulin regardless of classification.

Uncomplicated hyperglycaemia

The essential steps are to identify and treat the precipitant, optimise glucose lowering therapy, arrange follow up, and educate.

Identify and treat the precipitating illness

This is the first management step and frequently the only one that matters. Treat infection with appropriate antimicrobials, manage acute coronary syndrome on its own pathway, and address whatever else has driven the glucose up. Correcting the glucose without addressing the cause guarantees recurrence within days.

Known diabetic

• Establish adherence directly and without judgement. Ask what the patient actually takes, when, and whether they have run out or cannot afford the medication. Non adherence driven by cost or supply failure is common and is solved by addressing supply rather than by escalating the dose.
• If not adherent: resume the previous regimen, address the barrier to adherence, and reinforce education.
• If adherent: the regimen has failed and requires optimisation. Increase the dose of existing agents, add an additional agent, or initiate insulin depending on the degree of failure and the HbA1c.
• Standard oral escalation: metformin titrated to 1 g twice daily with food as the anchor drug in type 2 diabetes, contraindicated if the estimated glomerular filtration rate is below 30 mL/min/1.73 m squared and to be held during acute illness with volume depletion given the risk of lactic acidosis. Add a sulfonylurea such as glicazide 40 to 160 mg twice daily, or a dipeptidyl peptidase 4 inhibitor, sodium glucose cotransporter 2 inhibitor or glucagon like peptide 1 receptor agonist according to availability, comorbidity and cost. Sodium glucose cotransporter 2 inhibitors and glucagon like peptide 1 receptor agonists carry cardiovascular and renal benefit and are prioritised where cardiovascular or kidney disease coexists.
• Where basal insulin is initiated, start at 10 units or 0.1 to 0.2 units/kg at bedtime and titrate by 2 units every 3 days against the fasting glucose, with clear hypoglycaemia education.
• Lifestyle advice with specific, achievable dietary and activity targets rather than general exhortation.
• Advise daily glucose monitoring at the nearest facility or at home with a written record, since a record is what allows the next clinician to titrate rationally.
• Arrange review in an outpatient medical clinic within around 5 days.
• Refer to a diabetes clinic where control is persistently poor, where insulin is being started, or where complications are present.

Newly diagnosed diabetic

• Lifestyle modification advice: dietary carbohydrate quality and quantity, portion control, weight reduction where appropriate, physical activity of at least 150 minutes weekly, alcohol moderation and smoking cessation.
• Consult a physician regarding initiation of treatment, since the choice depends on classification, HbA1c, comorbidity and the presence of ketosis.
• Refer to a diabetes clinic for structured education, dietitian input, and screening for complications.
• Baseline complication screening: retinal examination, foot examination with monofilament and pedal pulses, urinary albumin to creatinine ratio, renal function, lipid profile and blood pressure.
• Start cardiovascular risk reduction: statin therapy for most adults with diabetes over 40 years, and blood pressure control with a target below 130/80 mmHg using an angiotensin converting enzyme inhibitor or angiotensin receptor blocker as first line, particularly with albuminuria.

When to admit rather than discharge

• Any ketosis, acidosis or raised osmolality, that is any patient who does not meet all three criteria for uncomplicated hyperglycaemia.
• Vomiting or inability to maintain oral intake.
• Significant intercurrent illness requiring inpatient treatment.
• Altered consciousness.
• Haemodynamic instability.
• Newly diagnosed type 1 diabetes.
• Inability to arrange safe follow up, no access to medication, or social circumstances that make outpatient management unsafe.
• Pregnancy.

Sick day rules, which must be given to every patient with diabetes before discharge

• Never stop insulin during illness, even when not eating. Insulin requirements rise during illness.
• Monitor glucose at least every 4 hours, and more often if unwell.
• Check ketones if the glucose is above 15 mmol/L or if unwell, where testing is available.
• Maintain fluid intake, at least 100 mL per hour of sugar free fluid, switching to sugar containing fluid if unable to eat and the glucose is low.
• Continue carbohydrate intake in some form.
• Hold metformin and sodium glucose cotransporter 2 inhibitors during acute illness with dehydration or reduced intake.
• Seek help for persistent vomiting, glucose persistently above 15 mmol/L with ketones, breathlessness, drowsiness, abdominal pain, or inability to keep fluids down.

Follow up

Review the glucose record after 5 days, reassess the precipitant, titrate therapy, and reinforce education. Arrange annual complication screening. Address the psychosocial and financial barriers, since these determine control far more than the choice of agent in most settings.