Mechanisms of hypoglycemia unawareness and implications in diabetic patients

Table 1 Treatment options for the management of hypoglycemia unawareness and mechanisms of action

Treatments options	Mechanism of action
Optimizing insulin treatment	Avoidance of hypoglycemia
Pharmacological therapy
β2-adrenergic agents	Enhancement of adrenaline effect
Methylxanthine derivates (caffeine, theophylline)	Central nervous system stimulation
Serotonin reuptake inhibitors (fluoxetine, sertraline, paroxetine)	Unknown. It has been hypothesized that the effect could be mediated by an atypical presentation of serotonin syndrome that will lead to autonomic dysfunction
KATP channel modulators	Modulation of hypoglycemia sensing
Other treatments
Islet cell transplantation	Improving metabolic control
Fructose	Modulation of hypoglycemia sensing