What labs are used to diagnose and manage hypoglycemia (low blood sugar)?

Laboratory Tests for Diagnosing and Managing Hypoglycemia

The essential laboratory tests for diagnosing and managing hypoglycemia include blood glucose measurement, HbA1c, and specific diagnostic tests when hypoglycemia etiology is unclear, with continuous glucose monitoring being the most effective tool for ongoing hypoglycemia detection and prevention.

Definition and Diagnostic Criteria

• Hypoglycemia is defined by the American Diabetes Association as blood glucose ≤70 mg/dL (3.9 mmol/L) for level 1 hypoglycemia or <54 mg/dL (3.0 mmol/L) for level 2 (clinically significant) hypoglycemia 1
• Diagnosis requires both laboratory confirmation of low blood glucose and presence of hypoglycemic symptoms that resolve with glucose administration 2
• Blood glucose <54 mg/dL (3.0 mmol/L) detected by self-monitoring of blood glucose (SMBG), continuous glucose monitoring (CGM), or laboratory measurement is considered clinically significant hypoglycemia that should be reported in clinical trials 3

Primary Laboratory Tests for Hypoglycemia

• Blood glucose testing via laboratory methods or fingerstick glucose monitoring is the fundamental test for diagnosing hypoglycemia 3
• Continuous glucose monitoring (CGM) devices that measure interstitial glucose every 5-15 minutes are recommended for patients at risk of hypoglycemia, especially those with hypoglycemia unawareness 3
• Real-time CGM should be used in conjunction with insulin therapy to reduce hypoglycemia in teens and adults with type 1 diabetes who have hypoglycemia unawareness or episodes of hypoglycemia (high-quality evidence) 3
• Intermittently scanned CGM should be considered for adults with type 1 diabetes to reduce hypoglycemia (moderate-quality evidence) 3

Laboratory Tests for Evaluating Hypoglycemia Etiology

• When investigating unexplained hypoglycemia, measurement of insulin, C-peptide, and other related compounds may be necessary to identify causes such as insulinoma or surreptitious insulin use 2
• In ambiguous cases where type 1 and type 2 diabetes need to be distinguished, C-peptide measurement is recommended, particularly in individuals with type 2 phenotype who present in ketoacidosis 4
• For patients with suspected non-islet cell tumors causing hypoglycemia, imaging studies such as CT scan or MRI of chest, abdomen, and pelvis may be indicated 1

Monitoring and Prevention Strategies

• HbA1c should be measured routinely every 3 months until acceptable targets are reached, then at least every 6 months to assess long-term glycemic control 4
• Comparison between patient self-testing results and simultaneous laboratory testing is useful to assess the accuracy of patient results and detect pseudohypoglycemia 3, 5
• For patients with impaired hypoglycemia awareness, more frequent glucose monitoring is essential, with CGM being particularly beneficial for detecting nocturnal hypoglycemia and preventing severe episodes 6
• Professional CGM data coupled with diabetes self-management education and medication dose adjustment should be considered to identify and address patterns of hypoglycemia 3

Special Considerations for Laboratory Testing

• To minimize glycolysis in fasting plasma glucose samples, tubes containing granulated citrate buffer should be used or the sample should be placed immediately in ice-water slurry and centrifuged within 15-30 minutes 4
• For patients with suspected hypoglycemia but normal glucose readings, consider the possibility of pseudohypoglycemia, which represents falsely low blood glucose readings 5
• Patients with impaired awareness of hypoglycemia should undergo screening at least yearly using validated questionnaires such as the single-question Pedersen-Bjergaard or Gold tools 3

Management Based on Laboratory Results

• When blood glucose is ≤70 mg/dL (3.9 mmol/L), treatment with 15-20g of glucose or carbohydrate-containing food is recommended, followed by glucose rechecking after 15 minutes 1, 3
• For severe hypoglycemia, glucagon should be administered: 1 mg for adults and children >25 kg or ≥6 years with unknown weight; 0.5 mg for children <25 kg or <6 years with unknown weight 7
• If hypoglycemia persists after 15 minutes, the treatment should be repeated; once glucose normalizes, the patient should consume a meal or snack to prevent recurrence 3
• For patients with recurrent hypoglycemia, especially those with impaired awareness, glycemic targets should be temporarily raised to strictly avoid hypoglycemia for several weeks to help reverse hypoglycemia unawareness 3

Pitfalls and Caveats in Laboratory Testing

• Laboratory blood glucose testing by healthcare providers should not be used routinely to assess glycemic control except to supplement information from other testing methods or to verify accuracy of SMBG 3
• Relying solely on symptoms without laboratory confirmation can lead to misdiagnosis, as symptoms may occur at higher blood glucose levels in individuals with poor glycemic control 6
• The relief of symptoms by glucose administration alone is not sufficient to establish a diagnosis of hypoglycemia without laboratory confirmation 2, 8
• When using portable capillary blood testing devices rather than standard laboratory methods, rigorous quality control procedures should be employed 3