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Query: UMLS:C0011849 (diabetes)
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The study included 16 patients with diabetes mellitus (DM) type 1 and 15 healthy controls. By the moment of examination the patients had achieved subcompensation. 10 patients developed diabetic vascular complications. The patients received biosynthetic insulins Humulin S, Humulin I, Humulin M3. Pretreatment glycemia in the patients surpassed that in the controls, MDA red cell levels per ml of hemolysate were higher by 121% and 130% per protein 1 mg. MDA measured equal both in angiopathy patients and those without it. The activity of the antioxidant enzymes in DM patients was similar to control indices. Human insulin administration reduced red cell MDA levels both in angiopathy and free of it patients, though in the former MDA remained higher than normal, while in the latter normal levels are obtained. The parameters of the antioxidant defense enzymes changed on the treatment week 12: catalase activity rose by 41%, that of superoxide dismutase and glutathione peroxidase lowered by 35 and 65%, respectively. Variations in these enzymes activity showed no dependence on vascular complications.
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PMID:[Lipid peroxidation and the antioxidant protection of the erythrocytes in diabetes mellitus patients]. 829 27

This paper provides some historical aspects on the research and development of Humulin (rDNA origin), the first human health-care product derived from rDNA technology more than a decade ago. Also referred to as biosynthetic human insulin, Humulin is currently produced via the human proinsulin route, using an Escherichia coli fermentation process. The authenticity, high purity, and safety of BHI has been investigated and verified by a complex battery of analytical and physicochemical methods. The daily treatment of more than two million diabetic patients worldwide with this rDNA human insulin not only demonstrates the value of rDNA technology in providing an important medical product, it is assurance that diabetic patients will have unlimited supplies of this vital hormone as well as potential analogue refinements.
Diabetes Care 1993 Dec
PMID:Research, development, production, and safety of biosynthetic human insulin. 829 70

To test whether the binding of insulin to an endogenous serum protein can be used to extend the time action of insulin, human insulin was acylated at the epsilon-amino group of Lys(B29) with palmitic acid to promote binding to serum albumin. Size-exclusion chromatography was used to demonstrate specific binding of the resulting analog, [N(epsilon)-palmitoyl Lys(B29)] human insulin, to serum albumin in vitro, and the time action and activity of the analog were determined in vivo using overnight-fasted, insulin-withdrawn diabetic dogs. In the diabetic animal model, the duration of action of [N(epsilon)-palmitoyl Lys(B29)] human insulin administered intravenously was nearly twice that of unmodified human insulin, and the plasma half-life was nearly sevenfold that of the unmodified protein. Administered subcutaneously, [N(epsilon)-palmitoyl Lys(B29)] human insulin had a longer duration of action; a flatter more basal plasma insulin profile; and a lower intersubject variability of response than the intermediate-acting insulin suspension Humulin L (Lilly, Indianapolis, IN). These studies support the concept that modification of insulin to promote binding to an existing serum protein can be used to extend the time action of human insulin. In addition, the time action, pattern, and decreased variability of response to [N(epsilon)-palmitoyl Lys(B29)] human insulin support the development and further testing of this soluble insulin analog as a basal insulin to increase the safety of intensive insulin therapy.
Diabetes 1997 Apr
PMID:Acylation of human insulin with palmitic acid extends the time action of human insulin in diabetic dogs. 907 4

Management of very high insulin requirements in rare extreme insulin resistance syndromes is difficult and poorly documented. We report a case of a type B insulin-resistant patient requiring approximately 10,000 units of insulin per day, i.e. beyond the possibilities of current insulin formulations and delivery devices. Only the Panomat C10 portable pump model (Disetronic) and U500 Humulin (Lilly) allowed the required rate of 400 units per hour to be attained only when the reservoir was changed twice daily and the site and catheter were changed once daily. Three months after discharge, the patient was in good general and local condition, but with only fair diabetes control (glycated haemoglobin 9.5%).
Diabetes Metab 1997 Dec
PMID:Extreme insulin resistance: clinical management by external subcutaneous insulin infusion. 949 61

The safety of insulin lispro was compared with that of regular human insulin of recombinant DNA origin (Humulin R, Lilly), with special emphasis on the development and progression of the chronic complications of diabetes mellitus in relation to insulin therapy. Ten clinical trials of 3634 patients with type 1 and type 2 diabetes mellitus were analyzed. The primary focus was treatment-emergent adverse events, and the secondary focus was the development and progression of the chronic complications of diabetes. The evaluations were based on pertinent laboratory values, predetermined disease-specific COSTART (coding symbol and thesaurus for adverse event terminology) terms, physician evaluations of patients, and physical examinations. There were no clinically or statistically significant differences in the frequency of treatment-emergent adverse events or progression of retinopathy, neuropathy, or cardiovascular disease reported with each therapy. There was no difference between insulin lispro and Humulin R in the occurrence and progression of kidney disease as measured by changes in serum creatinine levels. Pooled data from clinical studies show that insulin lispro has a safety profile comparable to that of Humulin R.
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PMID:Safety of insulin lispro: pooled data from clinical trials. 1019 89

To compare the postprandial glucodynamics of Humalog Mix25, (Humalog Mix75/25 in the US; Mix25), to human insulin 30/70 (Humulin 70/30 in the US; 30/70) in patients with type 1 or type 2 diabetes. Ninety-three patients with type 1 diabetes and 84 patients with type 2 diabetes were evaluated in two separate but identical protocols using a randomized, multicenter, double-blind, crossover design. Patients consumed test meals 5 minutes after equal doses of Mix25 or 30/70. Plasma glucose was measured at baseline and 15 minute intervals for 4 hours after the meal. Two-hour postprandial glucose (2pp), 2-hour glucose excursion (2pp(ex) ), glucose versus time area under the curve 0 to 4 hours (AUC(0-4) ) and glucose excursion area under the curve 0 to 2 and 0 to 4 hours (AUCex(0-2), AUCex(0-4) ) were calculated. For the combined patient population, Mix25 resulted in significantly lower 2pp (12.45 +/- 3.59 vs. 13.47 +/- 3.62 mmol/L; p <0.001), AUC(0-4) (44.45 +/- 12.20 vs. 47.25 +/- 11.97 mmol x h/L; p <0.001), and glucose excursion parameters: 2pp(ex) (3.20 +/- 2.72 vs. 4.40 +/- 2.81 mmol/L; p <0.001), AUCex(0-2) (5.45 +/- 3.15 vs 6.60 +/- 3.13 mmol x h/L; p <0.001), and AUCex(0-4) (7.57 +/- 8.37 vs. 11.02 +/- 8.47 mmol x h/L; p <0.001) compared to 30/70. Further analysis of the treatment by type of diabetes indicated that Mix25 provided nearly identical glucose excursion responses in type 1 and type 2 diabetes up to 2 hours after the test meal, in contrast to 30/70. Pre-meal injection of Mix25 resulted in lower postprandial blood glucose levels compared to 30/70. The postprandial blood glucose response following Mix25 was similar in patients with either type 1 or type 2 diabetes.
Diabetes Metab 2000 Dec
PMID:Humalog Mix25 offers better mealtime glycemic control in patients with type 1 or type 2 diabetes. 1117 19

The purpose of this study was to (1) develop consistent definitions to report time-activity profiles of insulin formulations, (2) determine human insulin time-activity profiles based on all available pharmacokinetic studies of biosynthetic human insulin rDNA(E. coli) (Humulin), and (3) create graphs that accurately and usefully represent human insulin time-activity profiles (TAPs). Standard definitions of onset, peak, duration, and time of 50% maximal activity were developed for human insulin. Results from all pharmacokinetic and pharmacodynamic studies available on human insulin from searches of both published literature and unpublished work were analyzed by these standard methods. Data obtained using these definitions were used to construct diagrams of the time-activity relationships for each formulation. Sixty-three insulin tests utilizing a variety of methodologies and data analysis techniques were located. Time-activity curves generated by application of standardized definitions varied depending on methodology, and on whether glucose, insulin and/or glucose infusion rates were used as the measure of insulin activity. A method of standard analysis is required for evaluating insulin pharmacokinetic studies due to the wide variation in design of these studies. Graphic representation of ranges obtained by standard analysis of onset, peak, duration, and 50% maximal activity increase the information transmitted when compared to currently used tables of time-activity data. The time of 50% maximal activity during increasing and decreasing phases may be a better marker of clinically significant activity than the classically defined parameters of onset and duration.
Diabetes Technol Ther 2001
PMID:Graphical human insulin time-activity profiles using standardized definitions. 1176 21

The primary purpose of the study was to determine whether pen users would challenge the insufficient remaining dose (IRD) stop mechanism with sufficient force to affect the dose accuracy of the final dose. The secondary purpose was to determine the participant's positive and negative impressions of the Humalog/Humulin pen and the likelihood of using the new prefilled pen. Three different modifications to the prefilled pen's IRD stop feature were made. These three pen models then underwent environmental dose accuracy testing at various temperatures and humidities, and user dose accuracy testing by 64 patients with diabetes. Evaluation also involved challenging the IRD stop at various dialing torques. Thirty pens from each model were tested to failure of the IRD stop. A model of the prefilled pen was selected for commercialization that met the dose accuracy targets of +/- 1 unit (U) for insulin doses less than 20 U and +/- 5% of dose volume for doses equal to or over 20 U. The selected pen model was superior at the minimum (1 unit), median (30 unit) and maximum (60 unit) dose volumes. Also 92% (n = 59) of patients interviewed felt that the stop mechanism for the final dose was clear. Extensive testing in the development of a prefilled insulin delivery device demonstrates an accurate and reliable medical device.
Diabetes Technol Ther 2001
PMID:Dose accuracy testing of the humalog/ humulin insulin pen device. 1191 Nov 76

The purpose of this study was to determine the feasibility of a flexible multiple daily insulin (FMDI) regimen in routine pediatric diabetes care by comparing HbA(1c), body mass index (BMI), and episodes of severe hypoglycemia (SH) before and after initiation of FMDI therapy. Data from 44 patients (2-16 years old), on a conventional insulin (CI) regimen, were collected during quarterly diabetes clinic visits. These patients were transitioned from CI to FMDI regimen: pre-meal lispro (bolus) and once or twice daily Humulin Ultralente with or without bedtime Humulin NPH as the basal insulin. There was a significant improvement in HbA(1c) in prepubertal (9.3%+/-1.3% vs. 8.0%+/-1.1%, p<0.002) and pubertal subjects (9.2%+/-1.0% vs. 8.2%+/-0.9%, p<0.001). Pubertal subgroup demonstrated an increase in BMI (21.3+/-3.1 vs. 22.7+/-3.2 kg/m(2), p<0.0001) after one year. The rate of SH was decreased in both prepubertal ( p<0.01) and pubertal ( p<0.05) groups of patients on FMDI therapy. The use of FMDI in a general pediatric diabetic population is a feasible therapeutic option for maintenance and possible improvement of glycemic control. It may effectively decrease the HbA(1c), and reduce hypoglycemic episodes, without producing an abnormal increase in BMI.
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PMID:Beneficial effects of flexible insulin therapy in children and adolescents with type 1 diabetes mellitus. 1460 70

We investigated the use, in a short period, of Humalog Mix25 (Mix25) in a twice-daily administration regimen compared to a twice-daily injection therapy with Humulin 30/70 (30/70) in diabetic patients with Italian dietary habits. We studied 33 type 2 diabetic patients aged 59.1 +/- 8.1 years, BMI 29.8 +/- 2.7 kg/m2, duration of diabetes and insulin therapy of 14.4 +/- 9.8 and 4.2 +/- 4.6 years, respectively. After a 4-day lead-in period of twice-daily human insulin 30/70 treatment, patients were randomized to one of two treatment sequences: (1) a twice-daily regimen with Mix25 just 5 minutes before the morning and evening meals for 12 days, followed by a twice-daily therapy with human insulin 30/70 given 30 minutes before the morning and evening meals for an additional 12 days; or (2) the alternate sequence. Each patient underwent a mixed meal test: Humulin 30/70 was administered 30 minutes before the meal, while Mix25 was given 5 minutes before. The 2-hour post-prandial glucose concentration after breakfast was significantly lower during treatment with Mix25 than with Humulin 30/70 (157 +/- 43.2 vs. 180 +/- 43.2 mg/dl, p<0.05). The glycemic excursion after dinner on Mix25 treatment was significantly lower than with Humulin 30/70 (12.2 +/- 48.01 vs. 35.5 +/- 36.92 mg/dl, p<0.05). AUCglucose after Mix25 was lower than after Humulin 30/70. Glycemia after test meal was significantly lower with Mix25 than with Humulin 30/70. Insulin and free insulin concentrations after the test meal were significantly higher with Mix25 in comparison to Humulin 30/70. AUC serum insulin and free insulin curves after Mix25 were significantly higher than after Humulin 30/70 (p=0.028 and p=0.005, respectively). Twice-daily injections of Humalog Mix25, compared to human insulin 30/70 in type 2 diabetic patients with Italian dietary habits, provide improved and lasting post-prandial glycemic control, with the great convenience of the injection just before the meal.
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PMID:Importance of premeal injection time in insulin therapy: Humalog Mix25 is convenient for improved post-prandial glycemic control in type 2 diabetic patients with Italian dietary habits. 1474 Feb 79


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