[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. Evaluation of efficacy and safety of human insulin (Novo) in the treatment of insulin-dependent diabetes mellitus: a double-blind, multicenter clinical trial. Comparison of the safety and effectiveness of human and bovine long-acting insulins. Comparison of highly purified semi-synthetic insulin and highly purified porcine insulin in the treatment of type I diabetes: interim report of a multi-centre randomised single blind study. A fifteen-month double-blind cross-over study of the efficacy and antigenicity of human and pork insulins. Human insulin: a double-blind clinical study of its effectiveness. Effect of recombinant human insulin-like growth factor-I on progression of ALS. A placebo-controlled study. The North America ALS/IGF-I Study Group. A twelve month double-blind randomized study of the efficacy and immunogenicity of human and porcine insulins in non-insulin-dependent diabetics. A within patient cross over trial of 4 insulin regimens in antibody-negative, C-peptide negative patients. Influence of human insulin on symptoms and awareness of hypoglycaemia: a randomised double blind crossover trial. A long-term, randomized, comparative study of insulin versus sulfonylurea therapy in type 2 diabetes. Insulin versus a combination of insulin and sulfonylurea in the treatment of NIDDM patients with secondary oral failure. Effect of a pharmacist-managed diabetes care program in a free medical clinic. The impact of pharmaceutical care on the clinical outcome of diabetes mellitus among a rural patient population. Comparison of human versus porcine insulin in treatment of diabetes in children. Use of insulin lispro in continuous subcutaneous insulin infusion treatment. Results of a multicenter trial. German Humalog-CSII Study Group. Insulin analogues (insulin detemir and insulin aspart) versus traditional human insulins (NPH insulin and regular human insulin) in basal-bolus therapy for patients with type 1 diabetes. A randomized trial of continuous subcutaneous insulin infusion and intensive injection therapy in type 1 diabetes for patients with long-standing poor glycemic control. Treatment with human insulin (recombinant DNA) in diabetic subjects pretreated with pork or beef insulin: first results of a multicenter study. Biosynthetic human insulin in the treatment of diabetes. A double-blind crossover trial in established diabetic patients. A 2-year pilot trial of continuous subcutaneous insulin infusion versus intensive insulin therapy in patients with newly diagnosed type 1 diabetes (IMDIAB 8). Improved treatment satisfaction but no difference in metabolic control when using continuous subcutaneous insulin infusion vs. multiple daily injections in children at onset of type 1 diabetes mellitus. [Immunogenicity of semisynthetic human insulin Novo--five year prospective studies]. Double blind clinical and laboratory study of hypoglycaemia with human and porcine insulin in diabetic patients reporting hypoglycaemia unawareness after transferring to human insulin. Effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. VII. Mortality and selected nonfatal events with insulin treatment. Comparison of insulin with or without continuation of oral hypoglycemic agents in the treatment of secondary failure in NIDDM patients. Randomized controlled multicentre evaluation of an education programme for insulin-treated diabetic patients: effects on metabolic control, quality of life, and costs of therapy. Metabolic efficacy of preprandial administration of Lys(B28), Pro(B29) human insulin analog in IDDM patients. A comparison with human regular insulin during a three-meal test period. Transfer from porcine insulin to human insulin in insulin-dependent diabetes mellitus: effects on insulin binding to IgG and glycemic control. Long-term improvement in insulin sensitivity by changing lifestyles of people with impaired glucose tolerance: 4-year results from the Finnish Diabetes Prevention Study. Human insulin and porcine insulin in the treatment of diabetic children: comparison of metabolic control and insulin antibody production.
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. The safety and efficacy of human insulin (Novo) were evaluated in a double-blind, parallel, multicenter trial in which 47 insulin-dependent diabetic patients were randomly divided into two equal groups and treated with either purified pork or human insulin (Actrapid and Monotard, Novo) for 12 wk. Mean levels of fasting plasma glucose, glycohemoglobin, and daily insulin dosages showed no statistical differences between the two groups, and there was no significant difference in the incidence of hypoglycemic reactions. The results from this clinical trial indicate that human insulin, prepared by enzymatic transpeptidation of pork insulin, appears to be as safe and efficacious as purified pork insulin in the treatment of insulin-dependent diabetes mellitus. Since ultralente insulin pharmacokinetics suggest faster absorption by human insulin when compared with bovine insulin using the subcutaneous route, the safety and efficacy of human ultralente in the outpatient setting was evaluated. Twenty type I patients participated in a randomized study using a crossover design of four six-week phases: (a) one daily injection of human ultralente; (b) two daily injections of human ultralente; (c) one daily injection of bovine ultralente and (d) two daily injections of bovine ultralente. Pre-meal human regular insulin was used with ultralente insulins and comprised 39 +/- 2% of the total daily insulin dose. Total and ultralente daily insulin doses were lower with human ultralente insulin (51.3 +/- 3.0 total and 30.9 +/- 3.4 ultra lente u/day) when compared to bovine ultralente insulin (57.8 +/- 4.4 and 36.1 +/- 4.4 u/day, p less than 0.01), yet the metabolic control achieved was virtually identical during both phases: (hemoglobin Alc 8.6 +/- 0.2% human vs. 8.4 +/- 0.4 bovine, p = NS). The frequency of mild hypoglycemia was 3.0 +/- 0.5 events per week vs 2.0 +/- 0.3 (p = NS). No severe hypoglycemia occurred. There were no differences between blood glucose daily profiles, insulin doses, hemoglobin Alc (8.6 +/- 0.4% BID vs. 8.4 +/- 0.3% QD injections) and occurrence of hypoglycemia between the single and two-dose long-acting regimens. These data indicate that long-acting semi-synthetic human insulin (a) can be effectively used as a once daily injection, (b) may be more biologically active than bovine, and (c) can be associated with safe and effective diabetes control. This is an interim report of a long term single-blind study of the effects of changing diabetic patients treated with highly purified porcine insulin to semi-synthetic human insulins of identical formulation. Twenty four insulin dependent diabetics were randomly allocated to continue with porcine insulin (n = 11) or human insulin (n = 13). There were no significant changes within the groups nor differences between the groups in mean preprandial capillary blood glucose, glycosylated haemoglobin or insulin dose during the first 24 weeks of the study. Insulin antibody levels remained low and did not differ between the groups. No local or systemic adverse reactions were observed. In this group of patients conversion to human insulin did not result in a change in diabetic control or insulin dose. The antigenicity and efficacy of semi-synthetic human and pancreatic pork insulins have been compared in a double-blind double cross-over study in 96 insulin-treated diabetic patients. Transfer from pork to human insulin was associated with a 1.2 +/- 0.5 mmol/l deterioration (p less than 0.05) in the fasting blood glucose level, while the opposite change caused a 1.1 +/- 0.5 mmol/l improvement (p less than 0.05). After 4 months treatment, glycosylated haemoglobin levels were lower on pork (11.1 +/- 0.3%) than on human (11.7 +/- 0.3% p less than 0.01) insulin. The incidence of hypoglycaemia was similar with the two insulins. IgG insulin antibody levels were identical after human insulin treatment (5.7 +/- 0.4 micrograms/l) compared to pork insulin treatment (5.9 +/- 0.5 micrograms/l). Patients with high levels of antibodies (greater than 10 micrograms/l) showed a similar reduction in level when switched to either species of highly purified insulin. The deterioration in fasting blood glucose control is consistent with similar reports for biosynthetic human insulin and suggests, in the absence of changes in insulin antibody levels, a small but clinically significant pharmacokinetic difference between human and pork insulin. Over a two-year period, 88 patients were evaluated in a double-blind study of human insulin (recombinant DNA origin) and Iletin II pork insulin. Patient follow-up was done throughout the program by glycohemoglobin assays and self-monitoring of blood glucose levels. The C peptides were studied before and after a test meal of Sustacal. Insulin antibody determinations were made regularly. Dietary management was supervised throughout the study. The objective of this study was to investigate the safety and efficacy of recombinant human insulinlike growth factor-I (rhIGF-I) in the treatment of sporadic ALS. A double-blind, placebo-controlled, randomized study of 266 patients was conducted at eight centers in North America. Placebo or rhIGF-I (0.05 mg/kg/day or 0.10 mg/kg/day) was administered for 9 months. The primary outcome measure was disease symptom progression, assessed by the rate of change (per patient slope) in the Appel ALS rating scale total score. The Sickness Impact Profile (SIP), a patient-perceived, health-related quality of life assessment, was a secondary outcome variable. Progression of functional impairment in patients receiving high-dose (0.10 mg/kg/day) rhIGF-I was 26% slower than in patients receiving placebo (p = 0.01). The high-dose treatment group was less likely to terminate the study due to protocol-defined markers of disease symptom progression, and members in this group exhibited a slower decline in quality of life, as assessed by the SIP. Patients receiving 0.05 mg/kg/day of rhIGF-I exhibited trends similar to those associated with high-dose treatment, suggesting a dose-dependent response. The incidence of clinically significant adverse experiences was comparable among the three treatment groups. Recombinant human insulin-like growth factor-I slowed the progression of functional impairment and the decline in health-related quality of life in patients with ALS with no medically important adverse effects. This study aims to compare the effectiveness and immunogenicity of semisynthetic human insulin (NOVO) and highly purified (monocomponent) porcine insulin over a 12 month period in 16 non-insulin-dependent diabetic subjects not previously exposed to insulin. Sixteen patients were randomly allocated for treatment with either human (n = 9) or monocomponent porcine (n = 7) insulin in a double-blind trial. Both groups were identical with respect to age, sex and measures of metabolic control. Significant insulin antibody was detected in seven of the nine patients (78%) 3 months after the commencement of human insulin therapy whereas it was detected in all patients (100%) in the group treated with monocomponent porcine insulin as early as 2 months after insulin therapy. Besides the delayed rise of insulin antibodies during the first 3 months of human insulin therapy, it tended to have a lower mean insulin antibody titer, though statistically insignificant, at the end of the study. No adverse reaction to either type of insulins was noted. It is concluded that both semisynthetic human and monocomponent porcine insulin were safe and effective. Although human insulin showed a slightly lower immunogenicity than monocomponent porcine insulin of the same formulation and purities, it was not non-immunogenic. Hence, there is no reason to treat all insulin-requiring diabetic subjects with human insulin except those who have developed insulin allergy or those at risk or with a history of allergy. 12 patients entered a within patient cross over trial of 4 insulin regimens:--twice daily semi-synthetic human soluble and insulin zinc suspension (Actrapid/Monotard HM), twice daily porcine soluble and insulin zinc suspension (Actrapid/Monotard), twice daily porcine soluble and isophane insulin (Velosulin/Insulatard), and thrice daily porcine soluble insulin (Actrapid) supplementing once daily bovine ultralente insulin (Ultratard). Each insulin regimen lasted 10 weeks, the order of allocation being determined on a random basis. Patients were encouraged to improve glycaemic control throughout the study by self adjustment of insulin dosage guided by standard algorithms. Metabolic control was assessed by capillary blood glucose series, M-values, HbA1c, and fasting lipids. No significant differences in M-values, mean HbA1c or fasting lipids were found at the end of any of the regimens. Patients achieved significantly (p less than 0.01) lower pre-lunch blood glucose on Velosulin/Insulatard than on any other regimen, but severe hypoglycaemic events were more common (p less than 0.05) on this regimen. A significant fall in HbA1c values from that at recruitment could be demonstrated only by analysing treatment periods in chronological order. Thus at the end of the second study period, mean HbA1c was significantly less than that at recruitment (p less than 0.01), but by the end of the 4 treatment periods of our study, had returned to levels similar to those at recruitment. Similar control is achieved on semi-synthetic human insulin as on other conventional regimens. Day-to-day variability of blood glucose, expressed as a standard deviation, is approximately twice the maximum difference between any 2 regimens at any time point.(ABSTRACT TRUNCATED AT 250 WORDS) To investigate the apparent increased risk of severe hypoglycaemia associated with use of human insulin by comparing the pattern of symptoms of hypoglycaemia with human insulin and porcine insulin.
                Randomised controlled double blind crossover trial of treatment with human insulin and porcine insulin, with two treatment periods of six weeks.
                Diabetes outpatient department of a university teaching hospital in Berne, Switzerland.
                44 patients (25 men, 19 women) aged 14 to 60 years, with insulin dependent diabetes mellitus. All patients met the following criteria: receiving treatment with fast acting soluble insulin and long acting protamine insulin; performing multiple daily fingerstick blood glucose self measurements; and had stable glycaemic control with about one mild hypoglycaemic episode a week during the preceding two months.
                Patients were randomised to receive either human or porcine insulin for six weeks and were then changed over to the other type of insulin for a further six weeks.
                Questionnaire recording "autonomic" and "neuroglycopenic" symptoms that occurred during hypoglycaemic episodes confirmed by a blood glucose concentration less than or equal to 2.8 mmol/l.
                Insulin doses and blood glucose, glycated haemoglobin A1c, and fructosamine concentrations were similar during the two treatment periods. 493 questionnaires on hypoglycaemia (234 during treatment with human insulin and 259 during treatment with porcine insulin) were analysed. With human insulin patients were more likely to report lack of concentration (52% v 35%, p = 0.0003) and restlessness (53% v 45%, p = 0.004) and less likely to report hunger (33% v 42%, p = 0.016) than during treatment with porcine insulin. The difference in the pattern of symptoms during the two treatments was similar to that between the 12 patients with a history of recurrent hypoglycaemic coma and the 32 patients without such a history.
                The pattern of symptoms associated with human insulin could impair patients' ability to take appropriate steps to avoid severe hypoglycaemia. Caution should be exercised when transferring patients from animal insulin to human insulin, and a large scale randomised trial of the two types of insulin may be justified. To study the effect of insulin and sulfonylurea (SU) therapy on glycaemic control, insulin resistance and cardiovascular risk factors in type 2 diabetic subjects.
                A prospective, parallel, randomized, controlled, long-term study.
                Outpatient clinic in tertiary referral centre.
                Thirty-six type 2 diabetic subjects treated with diet and SU, aged 44-69 years and a duration of diabetes of between 2 and 14 years.
                Individually adjusted doses of insulin and glibenclamide.
                Glycosylated haemoglobin (HbA1c), insulin resistance (euglycaemic glucose clamp), levels of lipids, lipoproteins and blood pressure.
                Glycaemic control improved during insulin treatment, but deteriorated on SU; HbA1c levels differed significantly between groups after 12 months of therapy (mean +/- SEM 7.9 +/- 0.3 vs. 9.5 +/- 0.4%, P = 0.004). Body mass index increased significantly during insulin treatment (26.4 +/- 0.7 to 27.8 +/- 0.7 kg/m2, P = 0.0001) and 30% of this increase was a result of an increase in lean body mass. The total glucose disposal rate showed a small increase in the insulin group. Levels of triglycerides and apolipoprotein B were significantly reduced during insulin treatment (1.8 +/- 0.2 to 1.5 +/- 0.2 mmol L-1, P = 0.03 and 1.58 +/- 0.1 to 1.40 +/- 0.08 g L-1, P = 0.003), and insulin prevented a reduction in the levels of high-density lipoprotein (HDL) cholesterol and apolipoprotein A-1 and an increase in Lp(a) lipoprotein observed in the SU group. Blood pressure levels did not change during therapy.
                Insulin therapy was superior to SU treatment in achieving good metabolic control. Despite a modest improvement in cardiovascular risk factors in the insulin-treated group, no significant differences were observed between the groups after 1 year's treatment. Comparison of the effectiveness of combined therapy vs. an insulin regimen in NIDDM patients with secondary failure of oral hypoglycemic agents. RESEARCH DESIGN, PATIENTS AND METHODS: 27 NIDDM patients were randomly allocated to Group A (n = 14, insulin) and Group B (n = 13, insulin and sulfonylurea) with crossover after 3 months. After the next 3 months a decision was made about the further treatment according to the metabolic control. The patients were then treated for another year with the more successful regimen. Metabolic control, residual beta-cell secretory capacity, degree of peripheral insulin resistance (clamp) and insulin dose were followed during the whole study.
                (median, interquartile range, in brackets; *, statistically significant difference at P < 0.05): the combined therapy was better than insulin alone in 2/3 of patients. Glycemic control was better (HbA1c at 3 months: Group A = 7.9(1.1)% vs. Group B = 7.0(0.5)%*; HbA1c at 6 months: Group A = 7.4(1.5)% vs. Group B = 8.1(1.5)%. Insulin dose was lower during the combined therapy in the first 3 months: Group A = 0.62(0.18) U/kg body weight vs. Group B = 0.39(0.16) U/kg body weight*. Combined treatment was associated with increased C-peptide excretion both fasting and postprandially. No significant differences in peripheral insulin resistance were noted between the two groups. The combined treatment remained successful even after one year. The two groups of patients with different effective treatment did not differ significantly in any of the observed parameters.
                the combined therapy was more effective than insulin alone. Its favourable effect persisted after treatment for a year. It seems better to start the treatment of the oral failure with combined therapy compared with insulin first and later followed by combined therapy. On the basis of the observed parameters it is impossible to determine in advance which kind of treatment is more suitable for the individual patient. Diabetes care, morbidity, and mortality are usually worse in poor minority populations compared with non-minority ones. This report evaluates evidence-based process and outcome measures of diabetes care in diabetic patients followed in a free medical clinic and compares them to published results. The following process measures compared favorably with measures of the general population: dilated eye and foot exams and measurements of glycated hemoglobin levels; concentrations of total cholesterol; fasting triglycerides and low density lipoprotein (LDL) cholesterol; and proteinuria (by dipstick). Process and outcome measures in 89 diabetic patients referred to a Diabetes Management Program in which diabetes care was delivered by pharmacists following detailed algorithms (experimental group) were compared with measures in 92 diabetic patients who received diabetes care in the general clinic setting (control group). The patients in the experimental group had a slightly longer duration of diabetes and more microvascular and neuropathic complications, and more diabetic patients were taking insulin than were patients in the control group. All of the process measures listed above were more frequent in the experimental group. Compared with the control group, the initial glycated hemoglobin level (% +/- SE) in the experimental group was significantly (P < .001) higher (8.8 +/- 0.2 versus 7.9 +/- 0.2) but fell significantly (P < .03) more (-0.8 +/- 0.2 versus -0.05 +/- 0.3). The lack of a greater decrease in the glycated hemoglobin levels in the experimental group was not related to the inability of the pharmacists to follow the algorithms, the patients' refusal to follow the recommended medication adjustments, or the lack of appropriate self-monitoring of blood glucose in insulin-requiring patients. It was inversely related (r = -0.36, P < .03) to the number of missed visits, i.e., the greater the number of broken appointments, the less the glycated hemoglobin fell. In conclusion, diabetes care for a poor minority population in a free clinic setting can compare favorably to care in the general population. Pharmacists following detailed algorithms can enhance this care further. Administrative and support system changes that minimize the number of missed visits might further improve diabetes care in this population. To evaluate the impact of pharmaceutical care on the clinical outcomes of patients enrolled in a pharmacist-coordinated diabetes management program in a rural health setup.
                Patients were registered into 'control' and 'intervention' groups by randomization at three primary health centers. The study was an open-label parallel study.
                Medical records were prospectively reviewed. Capillary blood glucose level, blood pressure and demographic data were collected at baseline and at the follow-up visits. Pharmacists gave counseling to the intervention group during every visit and their health-related quality of life (HRQoL) was assessed with the Ferrans and Powers questionnaire.
                Single factor ANOVA and the t-test were used to compare the results using SPSS version 0.9 software and MS Excel worksheets.
                The intervention group (n = 104) showed well-controlled BMI, whereas the control group (n = 50) showed significant increase in the BMI. Mean blood glucose level in the intervention group reduced to 25 units from baseline (P = 0.0001) but was significantly increased in the control group (P = 0.0001). ANOVA showed that from the second follow-up onward there was significant decrease in blood glucose levels. Overall, the HRQoL scores increased by 45% in the intervention group and decreased by 2% in the control group.
                The pharmaceutical care program was effective in improving the clinical outcome and HRQoL of diabetes patients in rural India. Such 'pharmaceutical care' models should be fine-tuned and implemented widely. The blood glucose control obtained when using semi-synthetic monocomponent human insulin (insulin A) was compared with that using standard monocomponent porcine insulin (insulin B) in 14 children in a double blind crossover study. At the start of the study age, duration of diabetes, insulin dose, and daily carbohydrate intake were the same in both groups. After a one month run in period of standard treatment with porcine insulin the children were randomly divided into group 1 (three months of insulin A followed by three months of insulin B) and group 2 (three months of insulin B followed by three months of insulin A). During each treatment period blood glucose control was assessed by clinical symptoms, glycosylated haemoglobin, and home blood glucose monitoring. Although a significant difference in the period after lunch during 24 hour blood glucose profiles suggested a shorter onset time and faster peak action time of human insulin, no significant difference in the overall diabetic control was seen between the two types of insulin. There was a trend towards improved blood glucose control (irrespective of insulin) as the trial progressed. No clinical reactions to human insulin occurred, and there was no significant difference in the daily insulin dose between porcine and human insulin. Insulin lispro is an analog of human insulin with a faster onset and a shorter duration of action than regular human insulin. Efficacy and tolerability of insulin lispro in continuous subcutaneous insulin infusion (CSII) treatment were assessed in an open randomized crossover trial comparing insulin lispro and regular human insulin, both applied with insulin pumps.
                A total of 113 type 1 patients (60 male, 53 female, age [mean +/- SD] 37 +/- 12 years, duration of diabetes 19 +/- 9 years) participated in this open, randomized crossover study. Both insulins were applied for 4 months each with the appropriate intervals between the prandial insulin bolus and the meal (human insulin: 30 min; lispro: 0 min). Observation parameters were HbA1c, daily and postprandial blood glucose profiles, adverse events, rate of hypoglycemic and hyperglycemic events, number of catheter obstructions, and treatment satisfaction as assessed with an international validated questionnaire.
                The patients were well controlled with a mean HBA1c of 7.24 +/- 1.0% at baseline. HbA1c decreased in both treatment periods, but it was better during insulin lispro treatment (insulin lispro: 6.8 +/- 0.9%, regular human insulin: 6.9 +/- 1.0%, Friedman's rank-sum test: P < 0.02). In addition, the 1-h and 2-h postprandial rises in blood glucose were significantly lower (P < 0.001 for each meal) with insulin lispro, resulting in smoother daily glucose profiles as compared with regular human insulin. No significant differences were reported for the rate of hypoglycemia (mean +/- SD [median]: insulin lispro 12.4 +/- 13.9 [8], regular human insulin 11.0 +/- 11.2 [8]), for the rate of catheter obstructions (42 events in each treatment arm), and for the number and type of adverse events. No severe case of ketoacidosis was seen during insulin lispro treatment, whereas one case was reported during therapy with regular human insulin. Treatment satisfaction was better when patients were treated with insulin lispro.
                Insulin lispro is a suitable and very convenient pump insulin that may result in an improvement of long-term glucose control during CSII treatment. Its safety profile does not differ from that of regular human insulin. The aim of the trial was to compare the efficacy and tolerability of two types of basal-bolus therapy, using either the soluble long-acting basal insulin analogue, insulin detemir, in combination with the rapid-acting analogue, insulin aspart, or NPH insulin in combination with mealtime regular human insulin.
                In this 18-week, 1:1 randomised, open-labelled, parallel trial, 595 patients with Type 1 diabetes mellitus received insulin detemir or NPH insulin in the morning and at bedtime in combination with mealtime insulin aspart or regular human insulin respectively.
                Glycaemic control with insulin detemir/insulin aspart was improved in comparison with NPH insulin/regular human insulin (HbA1c: 7.88% vs 8.11%; mean difference: -0.22% point [95% CI: -0.34 to -0.10]; p<0.001). Self-measured 8-point plasma glucose profiles differed between the groups (p<0.001), with lower postprandial plasma glucose levels in the insulin detemir/insulin aspart group. Within-person day-to-day variation in plasma glucose was lower with insulin detemir/insulin aspart than with NPH insulin/regular human insulin (SD: 2.88 vs 3.12 mmol/l; p<0.001). Risk of overall and nocturnal hypoglycaemia (23.00-06.00 hours) was, respectively, 21% (p=0.036) and 55% (p<0.001) lower in the insulin detemir/insulin aspart group than in the NPH insulin/regular human insulin group. Body weight (adjusted for baseline and change in HbA1c) was 1 kg lower with insulin detemir/insulin aspart than with NPH insulin/regular human insulin (p<0.001).
                Basal-bolus therapy using insulin detemir/insulin aspart offers a better balance of control and tolerability than with NPH insulin/regular human insulin. The low variability and more physiological action profiles generated with these insulin analogues resulted in improved glycaemic control with lower risk of hypoglycaemia and no concomitant body weight increase. To assess in a randomized crossover trial the efficacy of continuous subcutaneous insulin infusion in improving glycemic control and health-related quality of life in type 1 diabetic patients with long-standing poor glycemic control.
                A total of 79 patients in 11 Dutch centers were randomized to 16 weeks of continuous subcutaneous insulin infusion followed by 16 weeks intensive injection therapy or the reverse order. Glycemic control was assessed by HbA(1c), self-reported hypoglycemic events, and blood glucose memory meter read outs. Changes in quality of life were assessed by self-report questionnaires administered at baseline and 16 weeks.
                As the drop-out rate after crossover was high (17 of 79 patients [22%]), we analyzed the trial as a parallel clinical trial, using data of the first half of the crossover phase only. At 16 weeks, mean HbA(1c) was 0.84% (95% CI -1.31 to -0.36) lower in the continuous subcutaneous insulin infusion group compared with the insulin injection group (P = 0.002). Stability of blood glucose self-measurement values, expressed as SD of the nine-point blood glucose profiles, improved in the insulin pump group by 29.3 +/- 41.1 vs. 8.2 +/- 36.5% in the injection group (P = 0.039). The number of mild hypoglycemic episodes per patient-week was 0.99 (95% CI 0.11-1.87) higher in the insulin pump group (P = 0.028). Weight gain was similar in both groups. Scores on the Short-Form 36-Item subscales 'general health' and 'mental health' improved in the continuous subcutaneous insulin infusion group, compared with stable values in the injection group (P = 0.048 and 0.050, respectively).
                Continuous subcutaneous insulin infusion improves glycemic control and some aspects of health-related quality of life in patients with a history of long-term poor glycemic control. In two double-blind studies 66 insulin-dependent diabetic subjects pretreated with pork insulin were changed to human insulin (recombinant DNA) or a purified pork insulin preparation (regular and NPH insulin). Sixty-five patients previously pretreated with beef insulin were transferred, in a randomized, double-blind fashion, to human insulin and purified beef insulin of the same preparations (regular and NPH insulin). Patients' metabolic control, as demonstrated by fasting and 1-h postprandial blood glucose, HbA1c, and daily insulin dosage, over 4 mo was unchanged in our four groups compared with the values before changing insulin preparation. No severe hypoglycemic attacks or skin reactions were reported. 94 diabetic patients established on treatment with porcine (n = 47) or bovine (n = 47) insulin took part in a double-blind crossover trial, in which 6-week periods of treatment with the appropriate animal insulin were compared with periods of treatment with biosynthetic human insulin (BHI). 6 patients withdrew during the trial, in 3 cases because of hypoglycaemia while taking BHI. In bovine-insulin-treated patients, the mean glucose level (mean of seven capillary-blood samples over 1 day), the modified M index, and total daily insulin requirement were the same on BHI and bovine-insulin treatment. For porcine-insulin-treated patients, mean glucose level and the modified M index were slightly higher on BHI than on porcine-insulin treatment (9.7 vs 9.0 mmol/l and 79.6 vs 65.0, respectively), despite an average increase of 2.3 units/day of BHI after 6 weeks of such treatment. Hypoglycaemic episodes were not significantly more or less frequent on BHI in either group of patients. In both groups fasting blood glucose was higher during BHI treatment than during animal-insulin treatment (14.2 vs 12.8 mmol/l [bovine group]; 12.1 vs 9.6 mmol/l [porcine group]). In bovine-insulin-treated patients blood glucose before the evening insulin injection was higher on BHI than on bovine insulin (11.6 vs 10.0 mmol/l). BHI appears to be a safe alternative to porcine or bovine insulin. Differences in the pharmacokinetics of BHI may account for the observed differences in blood-glucose responses. In a pilot study, the metabolic effects of continuous subcutaneous insulin infusion (CSII) versus intensive subcutaneous insulin therapy (ISIT) started at diagnosis in patients with Type 1 diabetes and continued for a 2-year period were evaluated and compared. Twenty-three patients (between 12 and 35 years old, mean +/- SD 18.4 +/- 9 years) were randomized into two treatment groups (CSII vs. ISIT), and both received supplemental nicotinamide (NA), 25 mg/kg of body weight. CSII was started immediately after admission to the hospital. Parameters of metabolic control [insulin dose, hemoglobin A1c (HbA1c), and C-peptide] were evaluated for a 2-year follow-up period. Data are presented for a total of 19 patients who remained in the study for its duration. Two years after diagnosis, mean +/- SD HbA1c was 6.3 +/- 0.5% and 6.2 +/- 0.3% for the CSII and ISIT groups, respectively (p=not significant). Compared with baseline values, an increase of baseline C-peptide of 38% for the CSII group and 27% for the ISIT group was observed; however, the difference between the groups was not significant. The insulin requirement for the entire duration of the study, but not at entry and 3 months, was significantly higher in CSII compared with ISIT patients (0.62 +/- 0.4 IU/kg/day vs. 0.3 +/- 0.4 IU/kg/day, respectively; p<0.01). After trial completion patients on CSII continued with this mode of therapy. Implementation of CSII as well as ISIT at diagnosis of Type 1 diabetes and continuation for 2 years thereafter achieved similar and optimal metabolic control, but more insulin was required with the CSII group. Both types of intensive insulin therapy combined with NA are able to preserve C-peptide secretion or even increase baseline levels for up to 2 years after diagnosis. The aim of this study was to compare safety, metabolic control, and treatment satisfaction in children/adolescents at onset of type 1 diabetes mellitus who were treated with either continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI).
                Seventy-two children/adolescents (7-17 yr of age) were enrolled in this open, randomized, parallel, multicenter study. Approximately half of the patients were treated with MDI (natural protamine hagedorn [NPH] insulin twice daily and rapid-acting insulin three to -four times daily, n = 38) by pen, and the other half received CSII (n = 34). The patients were followed for 24 months with clinical visits at the entry of the study and after 1, 6, 12, and 24 months. During these visits, hemoglobin A1c, insulin doses, weight, and height were registered. Severe episodes of hypoglycemia and ketoacidosis as well as technical problems were recorded. In addition, the patients/parents answered the Diabetes Treatment Satisfaction Questionnaire.
                There was no significant difference in metabolic control between the treatment groups. Treatment satisfaction was significantly higher in the group treated with CSII compared with the MDI group (p <or= 0.01 at all screening visits). There were no episodes of ketoacidosis and there was no significant difference regarding severe hypoglycemia between the treatment groups.
                CSII treatment proved to be a safe therapy in children/adolescents followed for 24 months after onset of their diabetes. Treatment satisfaction was higher in the CSII group, although there was no difference in metabolic control compared with the MDI group. The aim of the study was to compare the immunogenicity of semisynthetic human and porcine monocomponent (MC) insulin Novo during--5-year observation. Thirty-one diabetic patients, never previously treated with insulin were randomly allocated to treatment with one of the two coded insulin preparations in a double blind trial. 15 patients aged 20-58 years (mean age--36 years) were treated with human insulin and 16 diabetics aged 19-61 years (mean age--34 years) with MC pork insulin. The insulin was injected twice a day (Actrapid plus Monotard). Serum insulin-binding antibodies were determined according to Christiansen (radioimmunoelectrophoretic method). The development of insulin-binding antibodies during the first year of observation was more rapid in patients treated with MC pork insulin but thereafter it was similar in the two studied groups. After 5 years of treatment with human insulin serum insulin-binding antibodies were found in 14 patients. The level of antibodies was very low (< 0.130 mU/ml) in 5 subjects, low (0.171-0.401 mU/ml) in 6 patients and relatively high (0.885; 1.186; 5, 162 mU/ml) in 3 patients. In the group of diabetics treated with MC pork insulin after 5 years of observation serum insulin-binding antibodies were found in 12 patients. The level of antibodies was low (0.131-0.576 mU/ml) in 9 subjects and relatively high (1.034; 3.954; 5.639 mU/ml) in 3 patients. The results obtained after 2-5 years of the study did not differ significantly (Wilcoxon's test, p > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) To compare awareness of hypoglycaemia and physiological responses to hypoglycaemia with human and porcine insulin in diabetic patients who reported loss of hypoglycaemia awareness after transferring to human insulin.
                Double blind randomised crossover study of clinical experience and physiological responses during slow fall hypoglycaemic clamping with porcine and human insulin.
                Clinical investigation unit of teaching hospital recruiting from diabetes clinics of five teaching hospitals and one district general hospital.
                17 patients with insulin dependent diabetes mellitus of more than five years' duration who had reported altered hypoglycaemia awareness within three months of transferring to human insulin.
                Glycaemic control and frequency of hypoglycaemic episodes during two months' treatment with each insulin. Glucose thresholds for physiological and symptomatic responses during clamping.
                Glycaemic control did not change with either insulin. 136 hypoglycaemic episodes (eight severe) were reported with human insulin and 149 (nine severe) with porcine insulin (95% confidence interval -4 to 2.5, p = 0.63). 20 episodes of biochemical hypoglycaemia occurred with human insulin versus 18 with porcine insulin (-0.8 to 1, p = 0.78). During controlled hypoglycaemia the mean adrenaline response was 138 nmol/l/240 min for both insulins; neurohormonal responses were triggered at 3.0 (SE 0.2) versus 3.1 (0.2) mmol/l of glucose for adrenaline and 2.5 (0.1) versus 2.5 (0.1) mmol/l for subjective awareness.
                These data suggest that human insulin per se does not affect the presentation of hypoglycaemia or the neurohumoral, symptomatic, and cognitive function responses to hypoglycaemia in insulin dependent diabetic patients with a history of hypoglycaemia unawareness. The University Group Diabetes Program is a long-term prospective clinical trial designed to evaluate the effects of various hypoglycemic agents on vascular complications in patients with asymptomatic adult-onset diabetes. Mortality and blood glucose levels were determined as well as certain nonfatal events for patients assigned to diet alone or to either of two insulin treatment regimens. Lower levels of blood glucose with mean values close to normoglycemia were achieved in the treatment group in which the insulin dosage was adjusted to achieve normoglycemia compared with the levels achieved in patients treated with diet alone or with a fixed dose of insulin. In spite of differences in blood glucose levels among the treatment groups, there were only minor differences in the occurrence of fatal or nonfatal events. Optimal insulin regimens for non-insulin-dependent diabetes mellitus (NIDDM) patients with secondary failure are controversial. We evaluated the efficacy, side effects, and quality of life of patients receiving insulin either alone or in combination with their previous oral hypoglycemic agents (OHAs).
                Fifty-three Chinese patients with NIDDM (mean age 53.9 +/- 12.6 years, duration of diabetes 9.0 +/- 4.9 years, body wt 60.4 +/- 13.3 kg with corresponding body mass index 24.2 +/- 4.3 kg/m2, receiving the maximum dose of sulfonylurea and/or metformin) were confirmed to have OHA failure. Twenty-seven patients were randomized to continue OHAs and were given additional bedtime insulin (combination group); 26 patients were randomized to insulin therapy alone with twice-daily insulin (insulin group). Insulin doses were increased incrementally, aiming at fasting plasma glucose (FPG) < 7.8 mmol/l during a stabilization period of up to 8 weeks. Insulin dosage, body weight, glycemic control, and quality of life were assessed before and at 3 and 6 months after stabilization.
                Both groups showed similar improvement of glycemic control. For the combination group, FPG decreased from 13.5 +/- 2.7 to 8.9 +/- 3.0 mmol/l at 3 months (P < 0.0001) and to 8.6 +/- 2.5 mmol/l at 6 months (P < 0.0001). For the insulin group, FPG decreased from 13.5 +/- 3.6 to 7.5 +/-3.0 mmol/l at 3 months (P < 0.0001) and to 9.8 +/- 3.5 mmol/l at 6 months (P < 0.0001). No significant differences were observed between the groups. Similarly, both groups had significant improvement of fructosamine and glycosylated hemoglobin (HbA1c). Fructosamine fell from a mean of 458 to 365 mumol/l at 3 months (P < 0.0001) and to 371 mumol/l at 6 months (P < 0.0001) and from 484 to 325 mumol/l at 3 months (P < 0.0001) and to 350 mumol/l at 6 months (P < 0.0001) for the combination and insulin groups, respectively. HbA1c decreased from 10.2 to 8.4% at 3 months (P < 0.0001) and to 8.7% at 6 months (P < 0.0001) in the combination group and from 10.7 to 7.8% at 3 months (P < 0.0001) and to 8.4% at 6 months (P < 0.0001) in the insulin group. Despite similar improvement of glycemia, insulin requirements were very different. At 3 months, the combination group was receiving a mean of 14.4 U/day compared with 57.5 U/day in the insulin group (P < 0.0001). Similar findings were observed at 6 months (15.0 vs 57.2 U/day, P < 0>0001). Both groups gained weight. However, for the combination group, weight gain was 1.6 +/- 1.8 kg at 3 months and 2.1 +/- 2.5% kg at 6 months (both P < 0.0001 vs baseline), whereas for the insulin group, weight gain was 3.5 +/- 4.3 and 5.2 +/- 4.1 kg, respectively (both P < 0.0001 vs baseline). Weight gain was significantly greater in the insulin group (P < 0.05 at 3 months, and P < 0.005 at 6 months). Fasting plasma triglyceride decreased in the insulin group (1.8 +/- 1.0 to 1.4 +/- 0.8 mmol/l at 3 months [P < 0.005] and to 1.4 +/ 0.7 mmol/l at 6 months [P < 0.02] but not in the combination group. No changes were observed in total and high-density lipoprotein cholesterol. No severe hypoglycemic reactions were recorded in either group. Mild reactions occurred with similar frequency in both groups. Well-being and quality of life improved significantly in both groups. The majority of patients (82.7%) wanted to continue insulin beyond 6 months, irrespective of the treatment group.
                In NIDDM patients with secondary OHA failure, therapy with a combination of OHAs and insulin and with insulin alone was equally effective and well tolerated. However, combination therapy was associated with a lower insulin dose and less weight gain. Combination treatment may be considered when OHA failure occurs as a potential intermediate stage before full insulin replacement. A multicentre controlled randomized education study was performed to evaluate an education programme for insulin-treated diabetic patients. The main objective of the education programme, which took place on an out-patient basis, was to improve the level of self-care of the participants. Fifteen randomly recruited hospitals (558 patients) were equally divided into three groups: two experimental groups who completed the programme under the guidance of a health care professional or a fellow patient, and a control group. Patients in the experimental group were evaluated four times and those in the control group twice, with an intervening period of 6 to 7 months. The effect of the programme on metabolic control, quality of life, and costs of therapy was assessed. No significant effect of education of any one of these variables could be found.(ABSTRACT TRUNCATED AT 250 WORDS) The objective of this study was to compare the efficacy of the rapid-acting Lys(B28), Pro(B29) human insulin analog, insulin lispro, with currently available short-acting human insulin in a multiple injection therapy (MIT) regimen with respect to blood glucose and plasma insulin profiles and to serum metabolites (lactate, free fatty acids, glycerol, and beta-hydroxybutyrate) in 12 well-controlled type 1 diabetic subjects (8 male, HbA1c 6.8 +/- 0.9% [mean +/- SD]).
                After a run-in period of 4 weeks, patients were treated with either lispro at mealtime or human insulin 30 min before the meal for two periods of 4 weeks in a randomized open-label crossover study. Intermediate-acting insulin (NPH insulin) was given at bedtime. At the end of both study periods, metabolic profiles were assessed from 10:00 P.M. to 7:00 P.M. the next day.
                During the treatment periods, glycemic control was stable during lispro but improved during human insulin (delta HbA1c lispro 0.1 +/- 0.48, NS; human insulin -0.41 +/- 0.34%, P < 0.05). Glucose excursions, as measured by the incremental AUC, during the day and for the 2-h postprandial periods, were lower, although not significantly, for lispro. Insulin profiles demonstrated a faster rise after administration of lispro as compared with human insulin, peaking at 61 +/- 11.9 and 111 +/- 48.1 min (P < 0.01). Glycerol levels showed a slight increase before lunch and dinner, suggestive of enhanced lipolytic activity and compatible with the lower insulin levels.
                Lispro insulin applied in an MIT regimen creates more physiologic insulin profiles and tends to lower the glycemic excursions during the day compared with short-acting insulin. The analog can be applied safely in an MIT regimen, with mealtime intervals up to 5 h. Thirty type I diabetic patients who were treated for at least 2 years with a combination of regular and lente monocomponent porcine insulins were allocated in a double-blind study to either continued porcine insulin treatment or a transfer to the corresponding semi-synthetic human insulins. Insulin binding to IgG measured by an immunoelectrophoretic method, was followed at 3-month intervals for 1 year, and did not change after the transfer. The glycemic control, as assessed by hemoglobin A1 levels, tended to deteriorate in the human insulin group during the first 3 months of the trial and then return to the baseline level. It is concluded that a transfer from highly purified porcine insulin to human insulin apparently does not change the insulin binding to IgG in already sensitized patients. Lifestyle interventions reduce the incidence of type 2 diabetes among individuals with impaired glucose tolerance (IGT). However, it is unknown whether this is due to improved insulin sensitivity or insulin secretion. We investigated at baseline insulin sensitivity and insulin secretion applying frequently sampled intravenous glucose tolerance test (FSIGT) in 87 of 101 obese middle-aged subjects with IGT randomized into an intervention or a control group in the Finnish Diabetes Prevention Study. FSIGT was repeated after 4 years in 52 people. There were no significant differences in any of the baseline anthropometric or metabolic characteristics between the groups. The 4-year weight and waist circumference decreases were greater in the intervention than in the control group (P = 0.043 and P = 0.025, respectively). At 4-year examination, insulin sensitivity (Si) tended to be higher in the intervention group (the difference between the mean values 36%; P = 0.067, and P = 0.136 after adjustment for age, sex, BMI, and baseline Si value). There was strong correlation between the 4-year changes in Si and weight (r = -0.628 and r = -0.710, for intervention and control groups; P < 0.001 for both). In the entire group, Si improved by 64% in the highest tertile of weight loss but deteriorated by 24% in those who gained weight (lowest tertile). Acute insulin response declined significantly in the control group. In conclusion, Si markedly improved by weight reduction during the 4-year follow-up of individuals with IGT. Insulin secretion remained constant for years in individuals with IGT who were able to lose weight. Semisynthetic human insulin and highly purified porcine insulin were compared in a double blind crossover study in 21 diabetic children. Glycosylated haemoglobin values at the end of four month treatment periods were higher after treatment with human insulin than after treatment with porcine insulin (mean 15.7% (SD 2.3%) v 14.2% (2.3%); p less than 0.01). Higher fasting blood glucose concentrations occurred during treatment with human insulin than with porcine insulin (mean 12.0 (SD 2.1) v 11.0 (2.4) mmol/1; mean 216 (SD 38) v 198 (43) mg/100 ml; p less than 0.05), but there were no significant differences at other time points during the day. The incidence of hypoglycaemia was similar for both treatment groups. Concentrations of antibody reactive with porcine and human insulins were similar for the two treatment groups, although greater fluctuation was observed in the amount of antibody reactive with human insulin. Semisynthetic human insulin is safe and effective in diabetic children, although further work is needed to devise regimens which achieve optimal blood glucose control.
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.