Normal fasting subjects received regular insulin and mixtures of regular with NPH or lente to assess the effects of the combinations on serum insulin concentrations (SIC) and blood glucose responses (BGR). In addition, the influence of concentration, depth, and method and site of administration was investigated. In studies of mixtures of regular with NPH and with lente, it was observed that the regular: lente ratio needed to achieve peak SIC was higher than with the regular: NPH combination. Increased SIC, including either the peak and/or the time interval required to achieve the peak, were related to the depth and site (deltoid and abdominal greater than anterior thigh or buttocks). Assuming linear kinetics of absorption, significant quantities of insulin fail to reach the serum. Marked intra- and intersubject variations in SIC and BGR to regular, NPH, and lente insulins were observed.

Biological Availability↗

PubMedDate not supplied

Effect of premixed nph and regular insulin on glucose control and health-related quality of life in patients with type 2 diabetes mellitus.

OBJECTIVE: To compare the effect of the addition of regular insulin as a premixed 70/30 insulin to the treatment regimen of patients with type 2 diabetes who had used NPH insulin alone relative to overall glycemic control (postprandial blood glucose), patient satisfaction, and health-related quality of life. METHODS: We studied 90 patients with type 2 diabetes in a 10-week, randomized, double-blind, crossover trial involving 9 clinical investigators. Patients previously treated with NPH insulin alone were transferred to 30% regular insulin added to 70% NPH as a premixed insulin (70/30) administered twice daily. Patients in one sequence group received NPH insulin twice daily for 4 weeks followed by 70/30 insulin for 4 weeks; in the second sequence group, the order was reversed. RESULTS: The magnitude of the 1.5- and 2-hour postprandial glucose excursion was reduced with 70/30 insulin in comparison with NPH insulin, and patients treated with 70/30 insulin experienced fewer hypoglycemic events than with NPH insulin. With regard to health-related quality of life, patients treated with 70/30 insulin rated their physical functioning as better; rated their ability to be spontaneous, follow the meal plan, and interact socially to be less difficult; and had less fear of hypoglycemia and perceived their diabetes to be better controlled than when treated with NPH insulin alone. CONCLUSION: In patients with type 2 diabetes mellitus, premixed 70/30 insulin improved postprandial glycemic control and health-related quality of life without increasing the frequency of hypoglycemic events and without any additional cost.

Clinical Trial↗

PubMedDate not supplied

New advances in insulin treatment of diabetes: overcoming barriers.

OBJECTIVE: To discuss the optimal role of insulin in the treatment of patients with diabetes mellitus. METHODS: We review the complications of diabetes, highlight the attempts to improve control of plasma glucose, and summarize current recommendations for use of insulin in clinical practice. RESULTS: With the strict new guidelines for the diagnosis of diabetes issued by the American Diabetes Association in July 1997--a plasma glucose level of 126 mg/dL (7 mmol/L) rather than 140 mg/dL (7.8 mmol/L)--an additional 8 million persons will be diagnosed this year, and diabetes and its complications will be at the forefront of public health concerns. Strong evidence indicates that with reduction of plasma glucose levels and tight control of glycohemoglobin, the rate of complications can be considerably decreased. Although insulin replacement therapy is well known to be both the best and the most cost-effective way to control glucose levels in patients with type 1 diabetes, studies have no shown that those with type 2 diabetes can likewise benefit from appropriate insulin therapy. Other investigations have indicated that coronary events are as likely to occur in patients with recently discovered impaired glucose tolerance as in patients with known diabetes (at a 2-hour postprandial glucose threshold of 96 mg/dL [5.3 mmol/L]). Such finding suggest that there may be no such thing as "borderline diabetes" and give impetus to the search for improved types of insulin to treat all patients with diabetes. A recent candidate is the new insulin analogue lispro, which was developed by recombinant DNA techniques, with its design influenced by the structural analogy to another endogenous hormone, insulin-like growth factor I. Lispro is a fast-acting, rapidly dissipating insulin formulation. This profile allows lispro to be given less than 15 minutes before a meal, yet with little risk of postprandial hypoglycemia because its high mealtime peak is followed by rapid disappearance from the bloodstream. CONCLUSION: Lispro has been shown to improve postprandial control of plasma glucose and to decrease the occurrence of hypoglycemia episodes in comparison with regular insulin. Because of its stability and pharmacokinetic properties, lispro can also be used in insulin pump therapy.

Journal Article↗

PubMedDate not supplied

Transfer of patients with diabetes from semisynthetic human insulin to human insulin prepared by recombinant DNA technology using baker's yeast: a double-blind, randomized study.

A multicenter, double-blind, randomized, parallel-group, 12-month study was conducted to determine if patients with diabetes could be transferred safely and effectively from semisynthetic human insulin (ssHI) to human insulin produced by recombinant DNA technology using baker's yeast as the host cell [rDNA HI (BY)]. Sixty-five patients who ranged in age from 19 to 67 years and who had been on a stable dose of NPH or Lente ssHI with or without Regular ssHI participated. Forty-three were transferred randomly to rDNA HI (BY) and 22 continued on ssHI. Evaluation at both six and 12 months of treatment indicated no statistically or clinically significant differences between the ssHI and rDNA HI (BY) groups with regard to the mean changes from baseline in glycosylated hemoglobin, total daily insulin dose, or body weight. In addition, the proportions of patients who had episodes of mild or moderate hypoglycemia, severe hypoglycemia, hyperglycemia, or other clinical experiences related to diabetes or treatment were similar in the ssHI and rDNA HI (BY) groups. No pattern of unexpected retinal changes occurred, nor were there any remarkable changes in human insulin antibody binding or in mean or individual yeast antibody values in either group. These results show that patients with diabetes can be safely and effectively transferred from semisynthetic human insulin to human insulin produced by rDNA technology from baker's yeast with no change expected in the insulin dose.

Adult↗

PubMedDate not supplied

Impact of transfer from animal-source insulins to biosynthetic human insulin (rDNA E coli) in patients with diabetes mellitus.

Six hundred forty-eight patients (50.5% men; 49.5% women) with diabetes mellitus on animal-source insulin therapy for at least five years were studied. In this patient population, approximately 68.7% had Type I insulin-dependent diabetes mellitus and 31.3% had Type II noninsulin-dependent diabetes mellitus, nonetheless requiring insulin therapy. Patients were voluntarily transferred from animal-source insulin to biosynthetic human insulin derived by recombinant DNA technology from genetically altered Escherichia coli [human insulin (rDNAE coli)] and were monitored regularly thereafter. At a mean interval of 14 months after transfer to human insulin (rDNAE coli), these patients had gained 0.8 kg in body weight (P less than 0.01). There was a significant decline in systolic (P less than 0.01) but not in diastolic blood pressure. Insulin requirements while on animal-source insulin averaged 47.6 +/- 22.9 U/day (mean +/- SD); this requirement was not significantly different after transfer to human insulin (rDNAE coli) (47.0 +/- 21.2 U/day). The distribution of regular and modified insulin types prescribed did not change after patients were transferred from animal-source insulin to human insulin (rDNAE coli). However, a significant increase in the number of insulin injections from 1.79 +/- 0.59 to 1.96 +/- 0.61 injections/day was observed (P less than 0.001). Fasting glucose levels declined significantly from 202 +/- 87 mg/dl on animal-source insulin to 178 +/- 66 mg/dl on human insulin (rDNAE coli) (P less than 0.001). Postprandial glucose levels (at two hours) also declined from 227 +/- 83 mg/dl to 212 +/- 80 mg/dl. Glycosylated hemoglobin (HbA1c) decreased from 9.57 +/- 2.01% while taking animal insulin to 8.97 +/- 2.00% on human insulin (rDNAE coli) (P less than 0.001) Serum cholesterol and triglyceride levels insulin (rDNAE coli). Serum high-density lipoprotein cholesterol (HDL-cholesterol) levels increased from 54.2 +/- 15.1 mg/dl on animal insulin to 57.2 +/- 15.5 mg/dl on human insulin (rDNAE coli) (P less than 0.001). These data demonstrate that transfer of patients from animal-source insulins to human insulin (rDNAE coli) was associated with: (1) an improvement in glycemic control parameters; (2) a slight increase in the number of insulin injections in some patients, but no overall alteration in insulin requirements; and (3) no adverse trends in indicators of cardiovascular risks, such as serum lipids. Indeed, overall cardiovascular risk may have declined not only as a result of improvement in glycemic control, but also owing to a reduction in systolic blood pressure and an elevation in HDL-cholesterol levels.

Animals↗

PubMedDate not supplied

Comparison of fixed-ratio versus variable-ratio regular and NPH semisynthetic human insulin in insulin-requiring diabetic patients.

The efficacy and safety of a fixed combination of semisynthetic human insulin (Novolin) providing a 70:30 ratio of NPH to regular insulin versus a varying ratio of semisynthetic human insulin, regular and NPH (control group), were compared in adult insulin-dependent and noninsulin-dependent diabetic patients whose glycemic control had been stable on customized split-mix regimens of animal insulin. Seventy-eight patients were enrolled, of whom 72 were evaluated for efficacy of the respective regimens. Although the baseline fasting serum glucose concentrations were significantly higher in the fixed-ratio group than in the control group, mean serum glucose and glycosylated hemoglobin values throughout the 12 weeks of experimental treatment were not significantly different between groups. The mean serum glucose and glycosylated hemoglobin values in the fixed-ratio group also did not differ significantly from baseline; however, statistically significant increases were observed in the control group at weeks 4 and 8, but not at week 12. Total daily insulin dosages were comparable between the two groups, and body weight did not change significantly in either group. At the end of the study, the investigators judged 90% of the patients in the fixed-ratio group and 88% of the patients in the control group to be either improved or unchanged with respect to glycemic control. The frequency of hypoglycemic episodes and other clinical events did not change significantly from baseline in either group or differ significantly between the two groups at any time. The results of this study suggest that stable diabetic patients receiving animal insulin can safely be transferred to semisynthetic human insulin and that the majority of patients can maintain acceptable glycemic control with a fixed 70:30 ratio of NPH to regular semisynthetic human insulin.

Adult↗

PubMedDate not supplied

Proplast reconstruction of soft tissue defects: the effects of preoperative and postoperative radiation on fibrous ingrowth.

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Animals↗