Reactive Hypoglycaemia

Reactive (postprandial) hypoglycaemia is a fall in blood glucose below normal within 1 to 5 hours of eating, causing adrenergic and neuroglycopenic symptoms that settle with food. A true diagnosis needs documented low glucose at the time of symptoms and relief when glucose is restored. Most people with these symptoms have normal glucose at the time, and are treated with dietary measures and reassurance.

• Definition of hypoglycaemia: venous plasma glucose below 3.0 mmol/L (54 mg/dL) with symptoms that resolve when glucose is raised. A level below 3.9 mmol/L (70 mg/dL) is the alert threshold.
• Causes: late dumping syndrome after gastric, oesophageal or bariatric surgery (exaggerated insulin and GLP-1 response 1 to 3 hours after meals); early type 2 diabetes or insulin resistance with delayed insulin release; idiopathic reactive hypoglycaemia; alcohol (especially with mixers on an empty stomach); hereditary fructose intolerance and galactosaemia in childhood; insulin autoimmune syndrome (anti-insulin antibodies, linked to drugs containing a sulfhydryl group such as methimazole, alpha lipoic acid); non-insulinoma pancreatogenous hypoglycaemia; and rarely insulinoma.
• Fasting hypoglycaemia is a separate and more serious pattern, requiring urgent evaluation for insulinoma, adrenal insufficiency, hepatic failure, sepsis, drugs and hormone deficiency.
• Benign course in most; the symptoms are unpleasant but rarely dangerous.

• Symptoms 2 to 5 hours after a meal: sweating, tremor, palpitations, anxiety, hunger, irritability, pallor, nausea, light headedness, and in some confusion, difficulty concentrating, headache, blurred vision, weakness, and rarely seizures or loss of consciousness.
• Relief within 10 to 15 minutes of eating carbohydrate.
• Triggers: high refined carbohydrate meals, alcohol, long gaps between meals, exercise, previous gastric surgery.
• Red flags for pathological hypoglycaemia: symptoms during fasting or overnight, weight gain, seizures or collapse, glucose lowering drugs or insulin at home (including another person's), neuroglycopenia without warning, children with failure to thrive, liver disease, renal failure, adrenal insufficiency features (pigmentation, hypotension), hypopituitarism.

• Document the Whipple triad: symptoms of hypoglycaemia, a low plasma glucose measured at the time (venous sample in a fluoride tube, processed rapidly, or capillary glucose confirmed by laboratory), and relief when glucose rises.
• Capillary glucose measurement when symptoms occur (home meter or continuous glucose monitor for 10 to 14 days).
• Mixed meal test under specialist supervision (a meal that provokes symptoms, with glucose at 0, 30, 60, 90, 120, 180, 240 and 300 minutes). A 75 g oral glucose tolerance test is not used because it may cause hypoglycaemia in healthy people.
• When glucose is below 3.0 mmol/L: insulin, C-peptide, proinsulin, beta hydroxybutyrate, sulfonylurea and meglitinide screen, insulin antibodies, cortisol, liver and kidney function, and consider a supervised prolonged fast (up to 72 hours) if fasting hypoglycaemia is suspected.
• Imaging (endoscopic ultrasound, CT, MRI) only if biochemistry shows endogenous hyperinsulinism.
• Differentials: panic disorder, anxiety, thyrotoxicosis, phaeochromocytoma, postural orthostatic tachycardia syndrome, menopause, arrhythmia, epilepsy, alcohol effects, medicines (insulin, sulfonylureas, quinine, beta blockers masking symptoms).

Acute episode

• Conscious: 15 to 20 g of fast acting carbohydrate (150 to 200 mL of fruit juice or non-diet soft drink, 4 to 5 glucose tablets, or 3 to 4 teaspoons of sugar), recheck glucose after 15 minutes, repeat if below 4 mmol/L, then give a snack containing starch or protein.
• Unconscious or unable to swallow: glucagon 1 mg intramuscularly or subcutaneously (children under 25 kg or under 8 years: 0.5 mg), or intravenous glucose 10 percent 150 to 200 mL (20 g) over 15 minutes in hospital; call emergency help.

Dietary management (first line)

• Eat 5 to 6 small meals or snacks every 3 hours rather than 3 large meals.
• Choose low glycaemic index foods (whole grains, legumes, vegetables, nuts), with protein and healthy fat at every meal and snack; limit refined carbohydrate, sweets, sugary drinks, fruit juice and white bread.
• Avoid alcohol on an empty stomach, and take it with food only.
• Regular exercise but with a carbohydrate snack beforehand if exercise is prolonged.
• Weight loss in overweight people with insulin resistance.
• Keep a symptom, meal and glucose diary.

Drug treatment (persistent symptoms after dietary change; specialist initiated)

• Acarbose 25 mg orally with the first mouthful of each main meal, increased weekly to 50 mg and then 100 mg three times daily; side effects are flatulence, bloating and diarrhoea, which are reduced by slow titration. Do not use with inflammatory bowel disease or advanced renal impairment. Treat hypoglycaemia with glucose (not sucrose) while on acarbose.
• Metformin 500 mg daily, increasing to 500 mg twice daily, may help in insulin resistance.
• Calcium channel blocker (verapamil modified release 120 to 240 mg once daily or nifedipine) and diazoxide 50 to 100 mg three times daily are options after specialist assessment; octreotide 25 to 50 micrograms subcutaneously 30 minutes before meals for severe dumping syndrome.
• Late dumping syndrome after surgery: dietary measures, acarbose, and sometimes octreotide, with surgical revision for severe disease.

Cause directed treatment

• Insulinoma: surgery; autoimmune hypoglycaemia: stop the triggering drug, may need glucocorticoids and immunosuppression.
• Adrenal or pituitary insufficiency: hydrocortisone 15 to 25 mg daily in divided doses.
• Hereditary fructose intolerance and galactosaemia: dietary exclusion by a specialist.

Safety advice

• Carry glucose, do not drive when symptomatic, test glucose before driving in those with documented hypoglycaemia, and inform family members and colleagues how to help.

Follow up

• Review in 4 to 6 weeks and refer to endocrinology when hypoglycaemia is documented below 3.0 mmol/L, fasting hypoglycaemia occurs, or symptoms persist despite diet.