Hypoglycemia diagnostic criteria

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Mohammed Abdelwahed M.D[2]


Diagnostic criteria of hypoglycemia include symptoms of hypoglycemia, a low plasma glucose concentration correlated with symptoms, and correction of glucose level relieves symptoms. These criteria called Whipple's triad. Neonatal hypoglycemia can be diagnosed by measuring multiple metabolic panels include plasma insulin, plasma C-peptide, beta-hydroxybutyrate, blood pH, bicarbonate, lactate, Free fatty acidsacylcarnitine profile, plasma free and total carnitine levels.

Hypoglycemia diagnostic criteria

The following 3 characteristics should be present to diagnose hypoglycemia, which is called Whipple's triad and includes:[1][2]

The strategy is to seek Whipple's triad under conditions in which hypoglycemia would be expected:[3][4]

  • If the symptoms occur in the fasting state, that evaluation should be performed during fasting.
  • If there is a compelling history of postprandial symptoms, it is reasonable to seek Whipple's triad with frequent, timed plasma glucose measurements and recording of any symptoms after a mixed meal.

Identifying the cause

After confirmation of hypoglycemia. Physicians should have history, signs and laboratory results sufficient to help them to identify the cause of hypoglycemia:[5]

Plasma insulin[6] C-peptide proinsulin Sulfonylurea in plasma insulin or insulin receptor antibodies Postprandial symptoms Fating symptoms
Insulinoma high high high - - - +
Oral hypoglycemics high high high + - - -
Autoimmune hypoglycemia high high high - + - -
NIPHS* high high high - - + -
Exogenous insulin high low low - - - -
Non-islet cell tumors low low low - - - -

*(NIPHS) non-insulinoma pancreatogenous hypoglycemia syndrome

Neonatal hypoglycemia:


  1. Guettier JM, Gorden P (2006). "Hypoglycemia". Endocrinol Metab Clin North Am. 35 (4): 753–66, viii–ix. doi:10.1016/j.ecl.2006.09.005. PMID 17127144.
  2. Landau BR, Wahren J, Chandramouli V, Schumann WC, Ekberg K, Kalhan SC (1996). "Contributions of gluconeogenesis to glucose production in the fasted state". J Clin Invest. 98 (2): 378–85. doi:10.1172/JCI118803. PMC 507441. PMID 8755648.
  3. Service FJ, O'Brien PC (2005). "Increasing serum betahydroxybutyrate concentrations during the 72-hour fast: evidence against hyperinsulinemic hypoglycemia". J Clin Endocrinol Metab. 90 (8): 4555–8. doi:10.1210/jc.2005-0033. PMID 15886243.
  4. Hogan MJ, Service FJ, Sharbrough FW, Gerich JE (1983). "Oral glucose tolerance test compared with a mixed meal in the diagnosis of reactive hypoglycemia. A caveat on stimulation". Mayo Clin Proc. 58 (8): 491–6. PMID 6876881.
  5. Service FJ, Natt N (2000). "The prolonged fast". J Clin Endocrinol Metab. 85 (11): 3973–4. doi:10.1210/jcem.85.11.6934. PMID 11095416.
  6. Cryer PE, Axelrod L, Grossman AB, Heller SR, Montori VM, Seaquist ER; et al. (2009). "Evaluation and management of adult hypoglycemic disorders: an Endocrine Society Clinical Practice Guideline". J Clin Endocrinol Metab. 94 (3): 709–28. doi:10.1210/jc.2008-1410. PMID 19088155.