Effect of human proinsulin on blood glucose control and metabolic instability in type 1 diabetes mellitus.
The effect of human biosynthetic proinsulin (PRO) on blood glucose (BG) control and glucose excursions was studied in a nonrandomized design in eight patients with unstable type 1 diabetes mellitus and compared with that of human NPH insulin. Both preparations were injected subcutaneously twice daily for three days each in combination with small doses of regular insulin. All patients were kept in metabolic control during PRO treatment. Mean BG (mean of three days, 18 samples per day) was lower during PRO (mean +/- SE: 14.4 +/- 4.0 versus 11.4 +/- 3.0 mmol/l, p = 0.079). Inspection of individual data showed that four patients had similar BG profiles and mean daily BG concentrations with both preparations (12.3 +/- 1.1 vs 12.1 +/- 1.0 mmol/l), while the other four had significantly lower values during PRO (16.5 +/- 1.0 vs 10.1 +/- 1.1 mmol/l, p = 0.003). Metabolic instability (MAGE values) was similar during NPH and PRO (7.5 +/- 0.5 versus 7.0 +/- 0.5 mmol/l, H = 0.011, p = 0.88) when calculated for the entire group of patients. However, all patients with similar BG profiles during NPH and PRO treatment had smaller daily BG excursions on PRO (8.1 +/- 0.8 versus 6.6 +/- 0.6 mmol/l, p = 0.104, Wilcoxon test). The counterregulatory hormones, growth hormone and cortisol were not different between the two treatment periods or between the two groups. Plasma PRO concentrations (as determined through crossreaction in a C-peptide assay) did not correlate with the PRO dose (rxy = 0.508, p = 0.20), but correlated negatively with BG (rxy = 0.841, p = 0.009).


CONCLUSIONS
(1) Patients with type 1 mellitus can be kept in metabolic control during treatment with human PRO. (2) The dose of PRO considered equipotent to NPH insulin must be determined for each patient individually in order to avoid hypoglycemic attacks. (3) Although there was a tendency towards improved metabolic stability during PRO in some patients, this requires further investigations.
Bock
E
E
Department of Internal Medicine, Klinikum Steglitz, Freie Universität Berlin, FRG.
Quabbe
H J
HJ
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D002096:C-Peptide / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D005260:Female; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D011384:Proinsulin / Q000097:blood / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D011994:Recombinant Proteins; D013006:Growth Hormone; D011384:Proinsulin; D006854:Hydrocortisone