The diagnosis of a hypoglycemic disorder requires a high level of suspicion, careful assessment of the patient for the presence of mediating drugs or a predisposing illness, and, where indicated, methodical evaluation on the basis of well-defined diagnostic criteria.

The diagnostic burden is heaviest for healthy-appearing persons with episodes of confirmed neuroglycopenia. Our criteria for insulin mediation of hypoglycemia are: plasma insulin >=18 pmol (ICMA [immunochemiluminometric assay]), C-peptide >=200pmol/L (ICMA), proinsulin >=5pmol/L (ICMA), ßOH butyrate, <=2.7mmol/L and generous (1.4mmol/L) response of plasma glucose to IV glucagon administered when the patient is hypoglycemic. Sulfonylureas, meglitinides and insulin antibodies should be sought in the plasma of any hypoglycemic patient.