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

Abstract

We tested the hypothesis that transfer from porcine to human insulin causes a fall in nocturnal blood glucose and an increase in the frequency of hypoglycaemic episodes. Twenty IDDM patients (age 19–55, duration 3–36 years) used Velosulin and Insulatard twice daily for 12 weeks, double‐blinded to species (human (H) or porcine (P)) in a randomized crossover study. Species was changed after 4 weeks’ run‐in and 4 weeks later, with insulin doses unchanged on transfer. Ten patients underwent each sequence (H/P/H or P/H/P) and were admitted on the first and eighth night after transfer for hourly blood glucose measurement (22.00–07.00). Biochemical hypoglycaemia (<3.5 mmol l−1) was observed on 39 of the 80 patient‐nights studied (48.75 %). The number of episodes were similar during each night (H1 8, H8 10, P1 10, P8 11, p = 0.83). Total reported symptomatic episodes (H 51 vs P 73, p = 0.85), total HbA1 (H 9.8 ± 0.3 %, P 10.0 ± 0.3 %, p = 0.32) and daily insulin doses (H 0.63 ± 0.04 units kg−1 day−1 vs P 0.63 ± 0.05 units kg−1 day−1, p = 0.54) were not different. Despite an apparent fall in blood glucose levels from night 1 to 8 on transfer to human (AUC 82.3 ± 7.8 vs 61.4 ± 5.3 mmol.h l−1, p < 0.05) but not porcine insulin (AUC 70.7 ± 7.2 vs 70.1 ± 7.5 mmol.h l−1, p = 0.74), there was no difference when all 4 nights were considered together (p = 0.30). We conclude that dose for dose transfer to human insulin does not increase numbers of episodes of nocturnal or reported hypoglycaemia. © 1997 by John Wiley & Sons, Ltd.

Hypoglycaemia induced by exogenous insulin –‘human’ and animal insulin compared

“…Two of the studies[11–12] described in Table 1 have only appeared in abstract form to date. Two reports[12–13] in Table 1 and one report[14] in Table 2 also appear in Tables 3 and 4, respectively, as the data they contain pertains to both the population and laboratory settings. The reports by MacLeod[15–16], in Tables 1 and 3, respectively, studied the same subjects in both population and laboratory settings.…”

“…All but one[61] provided data on hypoglycaemic events, this study simply reporting no events during the investigation. Four studies found no differences in the frequency of hypoglycaemia[2–64]. Two studies reported a statistically insignificantly increased frequency of hypoglycaemia in subjects on ‘human’ insulin as compared to those on insulin of animal origin[65–66].…”

“…Nineteen publications[6–92] compare a period of animal insulin treatment to one of ‘human’ insulin treatment in the same subject. Nine of these studies[75–77,81–83,85–86,88–91] reported no difference between insulin species while a further three[78–79,92] found fewer hypogycaemic episodes with ‘human’ insulin and/or greater awareness of hypoglycaemia.…”

Hypoglycaemia unawareness: a reversible problem?

“…It is likely that glucose sensing neurones alter their hypoglycaemia sensitivity in response to recent previous glucose experience[10]. The neurohumoral responses to hypoglycaemia during sleep are much less vigorous than in the awake state[11], so nocturnal hypoglycaemia is often unsuspected[12,13]. A single episode of nocturnal hypoglycaemia can diminish the reaction to hypoglycaemia the next day, increasing the risk of another severe episode[6].…”

“…Strict hypoglycaemia avoidance is not easy as it involves the patient in frequent glucose monitoring to discover times of asymptomatic hypoglycaemia. Nocturnal hypoglycaemia should always be thought of, as hypoglycaemia during the night is often asymptomatic and may reduce the patient's ability to recognize hypoglycaemia in time the next day[6,11–13].…”