Hypoglycemia: When Blood Sugar Drops Too Low

How the body controls blood sugar

After a meal, insulin from the pancreas moves glucose into cells and stores the surplus in the liver as glycogen. Between meals, insulin falls and the hormones glucagon, adrenaline, cortisol and growth hormone release glucose from the liver. The brain depends almost entirely on glucose, so the body defends a level above about 70 mg/dL.

Hypoglycemia happens when insulin action is too high for the glucose available, or when the liver cannot release enough glucose.

Levels of hypoglycemia

The American Diabetes Association defines three levels:

Causes in people with diabetes

• Insulin: dose too high, wrong timing, injecting into exercised muscle, or a mix-up between long- and short-acting insulin
• Sulfonylureas (glyburide, glipizide, glimepiride): lows can be prolonged, especially in older people or with kidney disease
• Missed or small meals, vomiting or diarrhea
• Exercise, which increases glucose uptake for up to 24 hours
• Alcohol, which blocks glucose release from the liver for many hours
• Kidney or liver disease, which slows insulin clearance
• Weight loss and improved fitness that reduce insulin needs

Metformin, SGLT2 inhibitors, GLP-1 receptor agonists and DPP-4 inhibitors rarely cause lows when used alone.

Hypoglycemia unawareness

After repeated lows, the body's warning response weakens and people no longer feel shaky or sweaty until they are confused. Strictly avoiding lows for 2 to 3 weeks can restore awareness. CGMs with alarms are especially valuable.

Nocturnal hypoglycemia

Lows during sleep are common in type 1 diabetes. Clues are nightmares, damp sheets, restless sleep and morning headaches. Bedtime glucose checks, CGM alerts, adjusting basal insulin and a bedtime snack when needed reduce the risk.

Causes in people without diabetes

Doctors first separate people who look well from those who are unwell.

In someone who is ill

• critical illness: sepsis, liver failure, kidney failure, severe heart failure
• starvation and eating disorders
• hormone deficiencies: adrenal insufficiency such as Addison's disease, pituitary failure
• alcohol, especially binge drinking without food
• medicines: quinine, pentamidine, some antibiotics (fluoroquinolones), beta-blockers in children

In someone who seems well

• Reactive hypoglycemia: symptoms 2 to 4 hours after a carbohydrate-rich meal. True lows are uncommon; many people have symptoms with normal glucose.
• After stomach surgery: late dumping syndrome and post-bariatric hypoglycemia, often 1 to 3 hours after meals, more than a year after gastric bypass.
• Insulinoma: a rare, usually benign pancreatic tumor that makes insulin, causing fasting and exercise-induced lows.
• Accidental or hidden use of someone else's insulin or diabetes tablets.
• Autoimmune hypoglycemia (antibodies to insulin or its receptor), very rare.

In babies

Newborns of mothers with diabetes, premature or small babies, and babies with rare metabolic or hormone disorders are at risk. Hospitals screen at-risk newborns.

Diagnosis

Whipple's triad

In people without diabetes, true hypoglycemia is confirmed when all three are present:

1. symptoms of hypoglycemia
2. a low plasma glucose measured at the time of symptoms (usually below 55 mg/dL or 3.0 mmol/L)
3. relief of symptoms when glucose is raised

Home glucose meters are less accurate at low levels, so a laboratory sample is preferred.

Further tests

• Blood drawn during a low: glucose, insulin, C-peptide, proinsulin, beta-hydroxybutyrate, a sulfonylurea screen and insulin antibodies. The pattern tells whether too much insulin is the cause and whether it comes from the body or an injection.
• Supervised 72-hour fast in hospital for suspected insulinoma.
• Mixed-meal test for post-meal lows.
• Cortisol and other hormone tests for adrenal or pituitary problems.
• Imaging (CT, MRI, endoscopic ultrasound, specialized PET scans) to find an insulinoma.

Treatment

Immediate treatment is fast-acting sugar (the 15-15 rule) or glucagon. Our low blood sugar symptoms page has the step-by-step first aid.

Long-term treatment targets the cause:

• Diabetes: review insulin doses and timing, switch from sulfonylureas, use CGM or automated insulin delivery systems, and education on exercise and alcohol.
• Reactive or post-surgical hypoglycemia: smaller, frequent meals with protein, fiber and fat; fewer refined carbohydrates; sometimes medicines such as acarbose.
• Insulinoma: surgical removal usually cures it.
• Hormone deficiency: replacement with hydrocortisone or other hormones.
• Medicine-related lows: stop or change the drug.

Complications

• falls, injuries and car crashes
• seizures and, rarely, brain injury or death with prolonged severe lows
• heart rhythm problems in people with heart disease
• fear of hypoglycemia, which can lead to running sugars high
• in older adults, recurrent severe lows are linked to higher dementia risk

Frequently asked questions

What blood sugar level is hypoglycemia?

For people with diabetes, below 70 mg/dL (3.9 mmol/L) is hypoglycemia, and below 54 mg/dL (3.0 mmol/L) is clinically significant. In people without diabetes, doctors usually look for levels below about 55 mg/dL with symptoms that resolve when sugar is raised.

What causes hypoglycemia in non-diabetics?

Causes include reactive hypoglycemia after meals, late dumping after gastric bypass, alcohol, some medicines, severe illness such as liver or kidney failure, adrenal or pituitary hormone deficiency and, rarely, an insulinoma. Many people with post-meal symptoms have normal sugar when tested.

What is Whipple's triad?

Whipple's triad is the standard for confirming hypoglycemia in people without diabetes: typical symptoms, a low glucose level measured at the time, and relief of symptoms when glucose is raised. All three must be present before a cause is searched for.

Can hypoglycemia cause permanent damage?

Most lows cause no lasting harm. Very severe or prolonged hypoglycemia can cause seizures, brain injury, heart rhythm problems or death. Repeated severe lows in older adults are linked to cognitive decline, which is why preventing them is a treatment priority.

What is hypoglycemia unawareness?

It is a loss of the usual early warning symptoms such as shaking and sweating, so the person becomes confused before realizing they are low. It develops after frequent lows. Avoiding lows for a few weeks and using a CGM with alarms help restore safety.