[Insulin transference in 198 patients from 6 Latin American countries]. Human (semisynthetic) insulin and porcine insulin in the treatment of non-insulin-dependent diabetes. A double-blind, comparative clinical trial. Transfer from animal insulins to semisynthetic human insulin: a study in four centres. Effects of insulin pump vs. injection treatment on quality of life and impact of disease in children with type 1 diabetes mellitus in a randomized, prospective comparison. [Comparative multicenter study of bovine insulin with forms more purified of swine and human insulin in the treatment of type 1 diabetes mellitus]. Comparative double-blind trial of the effectiveness and antigenicity of semisynthetic human insulin and purified porcine insulin in newly treated diabetic subjects. Effect of the rapid-acting insulin analogue insulin aspart on quality of life and treatment satisfaction in patients with Type 1 diabetes. Immunological and metabolic responses of patients with history of antibody-induced beef insulin resistance to treatment with beef, pork, human, and sulfated beef insulin. Randomized trial of human versus animal species insulin in diabetic pregnant women: improved glycemic control, not fewer antibodies to insulin, influences birth weight.
A multicentric, comparative, single-blind, randomized, prospective study was designed to evaluate the efficacy and safety of the transference from animal source insulins to rDNA human insulin in Latinamerican insulin-requiring diabetic patients. All the patients were on animal insulin for at least two months before inclusion. The patients were evaluated at the beginning, and at two and six weeks after inclusion. A total 198 patients completed the study and were considered evaluable: 94 were assigned to the animal insulin group, and 104 to the human insulin group. There were no statistically significant baseline differences between groups. The only statistically significant difference, detected at the end of the study, was a reduction in fasting blood glucose level in the human insulin group (animal insulin 212 +/- 95.3 initial vs 193 +/- 78.3 mg/dL final, p = 0.18; human insulin 198 +/- 86.8 vs 169 +/- 71.7, p = 0.025). There were no statistically significant initial-final changes in the rest of the parameters evaluated although a trend of reduction in glycohemoglobin levels was observed in both groups. There were more episodes of mild hipoglycemia in the human insulin group, and only one episode of severe unwarned hypoglycemia in the same group. We conclude that the transference of insulins in Latinamerican diabetic patients is effective and reasonably safe (with a dose adjustment when the change is made). Twenty-one patients with non-insulin-dependent diabetes, who had not previously received insulin therapy, participated in a double-blind comparative trial of six months' duration to evaluate the efficacy of human (semisynthetic) insulin. Patients were allocated at random to treatment either with human (semisynthetic) insulin (10 patients) or with an equivalent porcine insulin regimen (11 patients). Sex ratio, age, body mass index, duration of diabetes, C-peptide concentrations, baseline metabolic control and initial insulin requirements were similar in both groups. After six months, no significant differences between the treatment effects of human (semisynthetic) insulin and porcine insulin, as assessed by measurements of fasting and postprandial plasma glucose levels, the concentration of glycosylated haemoglobin, serum lipid levels, insulin dose, and body weight, were found. No adverse reactions, injection-site anomalies, or drug-related biochemical abnormalities were noted in either group. It was concluded that human (semisynthetic) insulin is as effective as porcine insulin in initiating the treatment of patients with non-insulin-dependent diabetes who require insulin therapy. The effects of transfer from animal insulin to semisynthetic human insulin on glycaemic control, insulin dose and anti-insulin antibodies were investigated in a total of 108 patients at four centres in a double-blind controlled study of eight months duration. Six months after transfer from porcine to human insulin there was a mean (+/- SE) increase in pre-breakfast blood glucose of 1.1 +/- 0.6 mmol l-1 (vs a reduction of 1.6 +/- 0.7 mmol l-1 in controls) (p less than 0.01), and a mean increase of pre-lunch blood glucose of 0.9 +/- 0.7 mmol l-1 (vs a reduction of 1.14 +/- 0.7 mmol l-1 in controls) (p less than 0.05). Six months after transfer from bovine to human insulin, there were no significant changes in blood glucose. Glycated haemoglobin showed no significant change six months after transfer from either bovine or porcine to human insulin. Hypoglycaemic symptoms, the total daily insulin dose, and the ratio of short- to intermediate-acting insulin did not change significantly after transfer from either bovine or porcine to human insulin. Transfer from bovine to human insulin resulted in a significant decline in anti-human insulin antibodies (mean (range): 50.5(14.8-125)% of initial levels), vs controls (113(43.4-234)% of initial levels; p = 0.034), and a non-significant decline in anti-bovine insulin antibodies (52.2(25.8-111)% vs 81.7(42.5-128)%; p = 0.082). Effects of pump treatment vs. four times daily injections were explored in children with diabetes with regard to quality of life and impact of disease as well as adverse effects and parameters of metabolic control.
                An open, parallel, randomized controlled prospective comparative study lasting 14 months was completed by 38 type 1 children with diabetes (age 4-16 yr) following a 3.5-months run-in phase. Standardized quality-of-life Pediatric Quality of life Inventory (PedsQL) and impact of disease scores were obtained every 3.5 months as well as regular medical parameters. Parallel treatment group data and longitudinal within-patient data were analysed for each treatment modality.
                Within-patient comparisons of the two treatment modalities showed significant improvement in PedsQL and impact scores after pump treatment. Treatment group comparisons did not show significant improvement. Pump treatment resulted in decreased symptomatic hypoglycaemia and lowered haemoglobin A1c by 0.22% after run in.
                Within-patient comparison suggests that metabolic control, frequency of severe hypoglycaemia (a threefold decrease), quality of life and impact of disease scores are improved by pump treatment in comparison to regular treatment with four daily insulin injections. A multicentric double-blind randomized study was organized to investigate the relationship between insulin antibodies and metabolic control in type I diabetics who changed from bovine insulin to monopic porcine and monocomponent human insulin. Twenty eight type I diabetic patients treated with bovine insulin (proinsulin less than 3,000 ppm) were selected. In a 6 month study, 9 patients maintained bovine insulin, 9 changed to monopic porcine insulin (proinsulin less than 10 ppm) and 10 to human insulin (proinsulin less than 1 ppm). The insulin were a gift from Biobras laboratory. The insulin antibodies (IA) were measured by an ELISA method and the metabolic control assessed by fasting blood sugar (FBS), 24 hour glucosuria and glycated protein (GP) measured by affinity chromatography method. After switching insulin therapy, IA decreased with porcine and human insulin, but increased with bovine insulin. Concerning metabolic control, only an increase of FBS with human insulin was found. In the beginning of study, there was negative correlation between IA and 24h glucosuria (rs = -0.509; p = 0.006). In conclusion, there was no improvement of metabolic control, in spite of a decrease of IA in type I diabetics treated during 6 months with less immunogenic insulin preparations. A double-blind comparative trial of the effectiveness and antigenicity of semisynthetic human insulin (Novo) and highly purified (Monocomponent) porcine insulin was performed over a 12 month period in 20 diabetic subjects newly treated with insulin. Human insulin was shown to be indistinguishable from porcine insulin of comparable purity with respect to plasma glucose and glycosylated hemoglobin levels and insulin dose requirements. Human insulin was no less antigenic than porcine insulin; significant IgG-associated insulin binding activity was detected in six of the ten patients in the human insulin treated group and four of the ten patients in the porcine insulin treated group. In all patients, the binding activity was of low capacity. No adverse reactions to human insulin were noted. It is concluded that semisynthetic human insulin, like purified porcine insulin, is safe and effective. Although there may be advantages for human insulin in the setting of insulin allergy, this study does not indicate that human insulin has advantages over purified porcine insulin with respect to elicitation of antibodies of the IgG class. To compare quality of life (QoL) and treatment satisfaction in patients with Type 1 diabetes receiving the rapid-acting insulin analogue, insulin aspart (IAsp), with that in patients receiving soluble human insulin (HI).
                In this 6-month, multinational, randomized, open-label trial, 424 patients from German-speaking countries were subjected to psychometric assessment before and after randomization (ratio 2 : 1) to basal-bolus treatment with either IAsp (n = 283) or HI (n = 141). Patients on HI were advised to keep an injection-meal interval of 30 min, whereas patients on IAsp were advised to inject immediately before meals. Treatment satisfaction and diabetes-related QoL were assessed using validated instruments to measure the domains of patients' individual treatment goals, physical complaints, worries about the future, social relations, leisure time flexibility, daily hassles, diet restrictions, burdens and fear of hypoglycaemia, blood glucose fluctuations, self-efficacy, and fear of insulin analogues.
                After 6 months, IAsp was associated with significantly greater improvement in treatment satisfaction than HI in two different scales (P < 0.01), and in QoL with respect to diet restrictions (P < 0.01). Improved satisfaction was mainly due to increased dietary and leisure time flexibility (P < 0.0001). Twenty-three percent of the IAsp group vs. 14% of the HI group achieved small but important improvements of total QoL (between-group difference, P < 0.06). The number needed to treat (NNT) with IAsp for an important increase in QoL was calculated to be 10. Regression analyses of potential predictors of improvement in QoL highlighted patients intensely striving for physical strength (P < 0.01; NNT = 7) and patients feeling less protected against hypoglycaemia (P < 0.005; NNT = 8) as being the most likely to benefit from IAsp.
                Under these study conditions, IAsp improved treatment satisfaction and quality of life regarding diet restrictions when compared with human insulin. The 'numbers needed to treat' for important quality of life benefits indicate that the effect of IAsp in this regard is not trivial. We evaluated immunological and metabolic responses during therapy with beef (B), pork (P), human (H, rDNA), and sulfated beef (SB) insulins in patients with insulin-antibody-mediated insulin resistance.
                A randomized double-blind sequential crossover study was performed with each insulin administered for 56 days unless dose reached 200 U/day or allergy developed. Participants were 26 individuals with history of B-P insulin dosage greater than or equal to 200 U/day and insulin binding capacities greater than 0.216 nM (30 mU/ml serum). Twenty-one participants completed the study. Insulin dosage/day, fasting plasma glucose, percentage HbA1, insulin antibody binding capacity (IABC), bound insulin (BI), percentage binding of 125I-labeled B, P, and H insulins, and receptor inhibition factor (RIF) were assessed.
                Mean insulin dosage (U/day) was significantly greater on B (88.9) than on P (29.2), H (29.4), or SB (29.6). On B, dosage increased in 12 individuals and reached 200 U/day in 6 individuals. Mean fasting plasma glucose (12.1 mM) and HbA1 (11%) were significantly higher on B than on P, H, and SB. Mean IABC, bound insulin, RIF, and percentage of B, P, and H bound were significantly higher on B than on P, H, and SB. Prolonged treatment with SB before entry into the study (greater than 5 wk) resulted in a blunted anamnestic response to B insulin.
                Rechallenge with B results in anamnestic immunological response and deterioration of metabolic control. SB, H, and P insulins have equivalent effects in patients with insulin antibody-mediated immunologic resistance. Macrosomia occurs in infants of diabetic mothers in spite of "nearly normal maternal blood glucose levels" with insulin treatment. Insulin antibodies may carry bound insulin into the fetal blood and thus may be associated with fetal hyperinsulinemia and macrosomia in these infants. Our objective was to test the hypothesis that human insulin is associated with lower insulin antibody levels and less macrosomia than is animal species insulin.
                Forty-three insulin-requiring pregnant (< 20 weeks' gestation) women, previously treated with animal insulin, were randomized to human and animal insulins and studied at weeks 10 through 20, 24, 28, 32, 36, and 38, at delivery, and at 3 months post partum. Infant blood was drawn at delivery (cord) and at 1 day and 3 months post partum 1 hour after a glucose-amino acid challenge.
                Women receiving human insulin required significantly less insulin per kilogram of body weight and showed significant dampening of glucose excursions (p < 0.05 for each comparison). Infants born to mothers receiving human insulin weighed 2880 +/- 877 gm compared with 3340 +/- 598 gm for infants of women treated with animal insulin (p < 0.05). There was no difference in insulin antibody levels between groups for either mothers or infants. Infants born to mothers receiving human insulin had a 1 hour C-peptide level after the glucose-amino acid challenge at 3 months of age of 0.21 +/- 0.13 pmol/ml compared with 0.32 +/- 0.13 pmol/ml (p = 0.01).
                Administration of human insulin to pregnant diabetic women has a therapeutic advantage over animal insulin, with less maternal hyperglycemia or hypoglycemia, fewer larger-for-gestational-age infants, and less neonatal hyperinsulinemia. Our data do not support the hypothesis that maternal antibodies to insulin influence infant birth weight.
A comparison of the effects of human and animal insulin as well as of the adverse reaction profile did not show clinically relevant differences. Many patient-oriented outcomes like health-related quality of life or diabetes complications and mortality were never investigated in high-quality randomised clinical trials. The story of the introduction of human insulin might be repeated by contemporary launching campaigns to introduce pharmaceutical and technological innovations that are not backed up by sufficient proof of their advantages and safety.