In diabetic patients, low glucagon levels (undetectable or in the lower quartile of the normal range) in the presence of hypoglycemia (where your blood glucose level is lower than the standard range) indicate impairment of hypoglycemic counterregulation.

Glucose counterregulation is the sum of processes that protect against development of hypoglycemia and that restore euglycemia if hypoglycemia should occur. In order of importance, the key counterregulatory factors are glucagon, epinephrine, growth hormone, cortisol, and hepatic autoregulation.

These patients may be particularly prone to recurrent hypoglycemia. This can be a permanent problem due to islet alpha-cell destruction or other, less well understood processes (eg, autonomous neuropathy - when there is damage to the nerves that control automatic body functions). It can also be functional, most often due to over-tight blood glucose control and may be reversible after decreasing insulin doses.

Elevated glucagon levels in the absence of hypoglycemia may indicate the presence of a glucagon-secreting tumor. Successful treatment of a glucagon-secreting tumor is associated with normalization of glucagon levels.

Inappropriate elevations in glucagon levels in hyperglycemic type I diabetic patients indicate that paradoxical glucagon release may contribute to disease severity. This can be observed if insulin treatment is inadequate and patients are ketotic. However, glucagon measurement plays little, if any, role in the diagnostic workup of diabetic ketoacidosis, which is based on demonstrating significantly elevated plasma or serum glucose (>250 mg/dL), circulating ketones (beta-hydroxy butyrate), and acidosis (typically with increased anion gap).