Hypoglycemia unawareness

It may be that the more rapid diffusion and absorption of insulin lispro in diabetics who achieve tight metabolic control and have hypoglycemia unawareness destabilizes glycemic control. 

Gerich JE, Mokan M, Veneman T, Korytkowski M, Mitrakou A. Hypoglycemia unawareness. Endocr Rev 1991 12(4) 356-71. 

Dagogo-Jack S, Fanelli CG, Cryer PE. Durable reversal of hypoglycemia unawareness in type 1 diabetes. Diabetes Care 1999 22(5) 866-7. 

Bober E, Buyukgebiz A, Verrotti A, Chiarelli F. Hypoglycemia, hypoglycemia unawareness and counterregulation in children and adolescents with type 1 diabetes mellitus. J Pediatr Endocrinol Metab. 2005 18 831-841. 

Recently, however, an unexpected complication has been associated with the use of human insulin. The transfer of patients from porcine insulin to human insulin has been suggested by some investigators to cause the death of diabetics due to a phenomenon named hypoglycemia unawareness , where there is a loss of sensation in the patient due to a drop in the blood glucose to dangerously low levels. This phenomenon is not associated with porcine insulin, probably due to its better penetration of the blood-brain barrier because of the difference in one amino acid. The experimental evidence is controversial at this time, but will lead to a reevaluation of the safety of human insulin (Wolff, 1992). 

A 56-year-old man was given a continuous subcutaneous insulin infusion because of frequent episodes of hypoglycemia of which he was unaware and he had four separate episodes of profound ketoacidosis (194). Multiple daily injections produced less flexibility in his mealtimes, more episodes of hypoglycemia, and the need for more injections. However, injecting 60% of his basal needs as insulin glargine once daily in combination with continuous subcutaneous infusion prevented further episodes of diabetic ketoacidosis. 

A 35-year-old woman transferred from regular insulin to insulin lispro, as she had developed unawareness of hypoglycemia (32). After 23 months she developed a circumscribed area of lipoatrophy about 3 cm in diameter at an injection site on the right thigh. Her antiinsulin antibodies were high (50%). Six months later... 

In addition to autonomic neuropathy, several related syndromes of defective counter-regulation in intensively treated type 1 DM patients contribute to their increased incidence of severe hypoglycemia. These include hypoglycemic unawareness, altered thresholds for release of counter-regulatory hormones, and deficient secretion of counter-regulatory hormones. 

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