Human insulin and awareness of acute hypoglycaemic symptoms in insulin-dependent diabetes

Further evidence for a high incidence of nocturnal hypoglycaemia in IDDM: no effect of dose for dose transfer between human and porcine insulins

“…16,[18][19][20] In the mid 1980s following the introduction of human insulin, a number of patients reported reduced awareness These investigations have also found no significant differences in the numbers of hypoglycaemic episodes of hypoglycaemia following transfer from their insulin of animal origin. These complaints received support from or physiological responses, even among those who claimed to have particular problems following transfer some patient surveys, 1-3 but studies in other centres detected no change in hypoglycaemic symptoms or to human insulin.…”

Hypoglycaemia unawareness in insulin‐dependent diabetes mellitus

“…However, in a questionnaire of 247 patients on animal insulin and 276 human species insulin users no differences in frequency or symptoms of hypoglycaemia were noted [59]. Moreover, three studies in IDDM patients showed no important differences in hormonal response to human vs. porcine insulin given intravenously [60,61], even in patients with hypoglycaemia unawareness [62].…”

Human Insulin in Hypoglycemia: A New Arena?

“…Alternatively, these patients may be more susceptible to an otherwise trivial effect of altering insulin species. Diminished epinephrine responses with human insulin hypoglycemia have been described in some subjects with longbut not short-duration diabetes, for example (11), although no effect was found in formal studies of patients who reported hypoglycemia unawareness that they themselves had attributed to conversion to human insulin use (15,16). There are pharmacokinetic differences between the different insulins (33) that, while apparently of little overall clinical effect (10), may be problematic in a susceptible patient.…”

“…The critical amino acid that distinguishes human insulin is not located on those parts of the insulin molecule involved in receptor binding and insulin action but may inhibit the aggregation of insulin molecules into polymers (33), which would be expected to speed absorption from subcutaneous injection sites. The human insulin molecule is also less lipid soluble (34), which may affect its ability to enter the brain (35), although there is no evidence of any differential effect of human insulin on cognitive function during hypoglycemia (15,16). Human insulins, injected subcutaneously, have a slightly faster onset and shorter duration of action than their animal equivalents (33).…”

“…They have, in general, been larger and used controlled and reproducible hypoglycemic stimuli in subjects with IDDM. By and large, these more sophisticated studies have found no effect of insulin species on the magnitude of hormonal responses or symptoms during hypoglycemia (11)(12)(13)(14)(15)(16) and accelerated glucose recovery with human insulin (11). It might perhaps be argued that IDDM subjects have a more heterogenous response to hypoglycemia, making identification of small differences in responses difficult to detect, but it is undoubtedly this that is the population at risk and the one where relevant studies eventually had to be done.…”