Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

[Lys(B28),Pro(B29)]-human insulin (insulin lispro, CAS 133107-64-9, LY275585, Humalog) is a quick acting insulin analog which is currently undergoing clinical evaluation for the treatment of diabetes. The potential secondary pharmacological activity of insulin lispro was profiled in studies for the evaluation of effects on the central and autonomic nervous system, the cardiovascular system, urine and electrolyte excretion, and gastrointestinal function. In vivo doses ranged from 0.03 to 10 U/kg, administered by the subcutaneous route, while pharmacologic activity in vitro was examined in smooth and cardiac muscle at concentrations of 1 x 10(-9) to 1 x 10(-5) mol/l. Insulin lispro exhibited secondary pharmacological activity in central nervous system tests only at higher doses with the most prominent observations being sedation and decreased responsiveness. Insulin lispro was essentially inactive in tests of autonomic (smooth and cardiac muscle), cardiovascular (mean arterial pressure, heart rate, systolic pressure, diastolic pressure, and pulse pressure), renal (urine and electrolyte excretion) and gastrointestinal (motility) function. In summary, insulin lispro had minimal effect in these pharmacodynamic studies indicating that insulin lispro has minimal potential to produce adverse pharmacological side effects at clinically relevant doses.
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PMID:General pharmacology of insulin lispro in animals. 882 25

For years, it has been recognized that "reasonable" control of blood glucose levels reduces the acute complications of diabetes mellitus. Recent studies have conclusively shown that strict glycemic control reduces the appearance and progression of chronic complications. Thus, strict glycemic control is the most salient goal of insulin therapy. Insulin regimens that closely mimic physiologic insulin secretory patterns have been inadequate because of limitations imposed by the pharmacokinetic profiles of commercially available preparations. The newer insulin analogues, both rapid-acting and long-acting, have more appropriate pharmacokinetic profiles. Lispro (Humalog) is the first human insulin analogue to be approved in the United States. Its pharmacokinetic and pharmacodynamic profile makes it amenable for use before meals. The search for long-acting and hepatospecific analogues continues.
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PMID:Insulin analogues: new agents for improving glycemic control. 904 26

Insulin Lispro is a newly FDA approved analog of human insulin that exhibits rapid absorption and a short duration of action after sc injection. Although Lispro insulin improves immediate postprandial glycemia compared to Regular insulin, long term trials of Lispro insulin have not shown improvement in overall glycemic control, as determined by glycosylated hemoglobin. We hypothesize that this lack of improvement is attributable to the development of late postprandial hyperglycemia secondary to a waning of Lispro insulin's effect in conjunction with continued meal absorption. This study was designed to evaluate the duration of Lispro-induced reductions in plasma glucose after a standardized meal when Lispro insulin is incorporated into a regimen typically employed in insulin-dependent diabetes mellitus. After establishment of euglycemia overnight, 12 healthy IDDM patients received human Ultralente insulin (0.2 U/kg) alone and in combination with each of the following treatments in random sequence immediately before ingesting a 750-Cal American Diabetes Association breakfast: 1) 0.15 U/kg human Regular insulin (Regular 0.15 group), 2) 0.15 U/kg Lispro insulin (Lispro 0.15 group), 3) 0.1 U/kg Lispro insulin (Lispro 0.1 group), and 4) an equimolar (1:1) mixture of Lispro and Regular insulins (0.15 U/kg; 1:1 Mix group). Glucose and hormonal parameters were assessed for 8 h after the meal. Peak postprandial glucose was increased in the Regular insulin group compared to that in all groups that incorporated Lispro insulin (P < 0.001). Glucose area under the curve (AUC) was decreased in the Lispro 0.15 group compared to that in the Lispro 0.1 group, and glucose AUC was decreased in the Lispro 0.15 and 1:1 Mix groups compared to that in the group given Regular insulin (P < 0.001). Mean plasma glucose concentrations during the final hour of study were increased in the Ultralente group compared with those in all other treatment groups and were increased in the Lispro 0.1 group compared with those in the Regular, Lispro 0.15, and 1:1 Mix groups (P < 0.05). Insulin AUC was significantly reduced in the Lispro 0.1 group compared to those in all other short acting insulin groups (P < 0.001), and time to peak insulin was more rapid in the two Lispro groups than those in all other treatment groups (P < 0.01). The glucagon response was significantly greater in the Ultralente group compared to those with all other treatments. There was no difference in the development of hypoglycemia between the groups. This study demonstrates that the reductions in plasma glucose effected by Lispro insulin are consistent and stable for 8 h after meal ingestion when Lispro insulin is used in combination with human Ultralente insulin. These findings suggest that improvement in overall glycemia, as assessed by glycosylated hemoglobin, may be achievable with Lispro insulin if adequate doses are administered.
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PMID:Prolonged efficacy of short acting insulin Lispro in combination with human ultralente in insulin-dependent diabetes mellitus. 906 7

Humalog is the first analog of human insulin to be evaluated on a large scale in clinical conditions by discontinuous subcutaneous administration. Eight international multicentric studies have investigated the efficacy and tolerance of Humalog in protocols with 3 daily insulin injections (3 preprandial injections of Humalog associated with 1 or 2 injections of Umuline NPH or Umuline Zinc). A total of 2834 patients participated in these studies, including 2,277 who used Humalog. In addition to these trials, more than 5,000 patients had used Humalog by 1996, in some cases for more than 3 years. In insulin-dependent diabetes (IDDM), glycaemic control at the time of inclusion of patients in these protocols, as evaluated by HbA1C, was generally moderate (8 to 9%) despite 3 daily injections. This did not constitute intensive care since basal insulin for half of these patients was ensured by only a single daily injection. In these conditions, the results obtained showing significant postprandial improvement in glycaemic control and a significant reduction of the number of hypoglycaemic episodes, particularly at night, are important even though HbA1C levels were not significantly decreased. In a more recent crossover study (1996), 199 well-controlled IDDM patients (HbA1C = 7.3%) were treated intensively by multiple injections. The number of severe hypoglycaemic episodes with coma was only one-fifth that of the group treated by Humalog (equivalent to a reduction of 26 comas per 100 patients/year) in the absence of any significant modification of HbA1C. No differences were noted for lipids, adverse side effects or severe events (except hypoglycaemic episodes) and immunogenicity. In non-insulin-dependent diabetes, the results were similar but less impressive concerning the improvement in postprandial glycaemic control and the reduction in hypoglycaemic episodes. In addition to the significant results obtained in these studies, Humalog was favoured by the vast majority of patients. It is likely that Humalog will allow intensified treatment of diabetes in very favourable conditions, and that more patients will achieve the difficult goal of normalising glycaemia. However, a single injection of NPH or prolonged insulin is not sufficient for that purpose. Two daily injections will generally be necessary.
Diabetes Metab 1997 Sep
PMID:[The insulin analog, Humalog, in discontinuous: from pharmacology to clinical use]. 941 May 53

Insulin Lispro (IL) is a short-acting insulin analog that better reproduces the physiological postprandial insulin profile. The aim of this study was to compare the effects of intensive insulin therapy on lipid metabolism using preprandial IL and regular insulin (RI) in 10 insulin-dependent diabetes mellitus (IDDM) subjects. The mean hemoglobin A1c (HbA1c) at baseline was 7.13% +/- 1.2% and did not change after both treatments. In IDDM patients, total cholesterol and triglyceride levels appeared lower after RI than after IL. The low-density lipoprotein (LDL) to high-density lipoprotein (HDL) ratio significantly decreased only after RI (baseline, 2.01 +/- 0.6; IL, 1.88 +/- 0.6; RI, 1.71 +/- 0.5, P < .05). Although no very-low-density lipoprotein (VLDL) composition abnormalities were observed at baseline, the protein content was lower (P < .05) after IL (8.13% +/- 2.93%) than after RI (11.93% +/- 3.41%). Intermediate-density lipoprotein (IDL) protein depletion at baseline (6.14% +/- 6.84%) was normalized after both treatments (IL, 11.09% +/- 12.14%; RI, 10.38% +/- 16.68%, P < .05). LDL, HDL, HDL2, and HDL3 composition abnormalities were similar after both treatments and did not normalize. IDDM and control subjects showed similar LDL subfraction distribution at baseline and after both treatments. Two-hour postprandial VLDL composition alterations, although improved after RI, completely normalized after IL (P < .05). Lipoprotein lipase (LPL) and cholesteryl ester transfer protein (CETP) activities were similar to the control group and did not change after both treatments. Hepatic lipase (HL) activity was lower in diabetic patients (39.6 +/- 35.2 v 87.0 +/- 27.1 U/L, P < .01) and remained lower after both treatments. In conclusion, in IDDM patients, IL (injected immediately before the meal) may offer small different effects on lipoprotein metabolism versus RI (injected 30 minutes before the meal) that, taken together, do not seem relevant.
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PMID:Effects of a short-acting insulin analog (Insulin Lispro) versus regular insulin on lipid metabolism in insulin-dependent diabetes mellitus. 958 Feb 47

The results of a clinical trial comprising 162 type 1 and 2 diabetics who took for 12 weeks Humalog in cartridges revealed that administration of this insulin before or 20 minutes after a meal does not affect the blood sugar level in a major way. None of the patients developed after Humalog administration local or general allergic manifestations. Hypoglycaemic episodes grade I and II were not more frequent during treatment with human insulins. The mean compensation of diabetes (HbA1c) remained unchanged. 80% of the diabetics are statistically significantly satisfied with Humalog treatment as compared with Humulinem R administration.
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PMID:[The short-acting insulin analog Lispro (Humalog) in the treatment of diabetes--comparison of preprandial and postprandial administration and comparison with treatment using Humulin R]. 974 77

Seven obese Type 2 diabetic patients were studied for two 4-h periods after ingestion of a glucose load to determine the effects of preprandial subcutaneous injection of Insulin Lispro (5 min before the meal) or regular insulin (20 min before the meal) on glucose metabolism. Glucose production and utilisation were measured using a dual isotope method. After Lispro, the mean postprandial increase in plasma glucose was 29% lower and the increase in insulin concentration 25% higher than after regular insulin (p < 0.05). Suppression of endogenous glucose production was similar with both types of insulin. Thus, preprandial injection of Lispro reduced postprandial glucose increments in Type 2 diabetic patients as compared to regular insulin. This effect is best explained by the increased postprandial bioavailability of Lispro.
Diabetes Metab 1998 Dec
PMID:Effects of regular insulin or insulin LISPRO on glucose metabolism after an oral glucose load in patients with type 2 diabetes mellitus. 993 19

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 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

Poly(isobutylcyanoacrylate) nanocapsules have been shown to decrease the blood glucose level after oral administration to streptozotocin-induced diabetic fasted rats after 2 days [Diabetes 37 (1988) 246]. Yet, the absorption of insulin in the blood of rats has not been characterised. The aim of this work was to evaluate the biological activity of insulin given orally as nanocapsules. Humalog-loaded nanocapsules (50 IU/kg) were administered by gavage to streptozotocin-induced diabetic rats. Thirty minutes to 1 h after oral administration, significant levels of human insulin were detected in rat plasma. However, the concentrations were very heterogenous from one rat to another and no decrease of glycemia could be observed. In addition, parenteral injection of insulin in solution showed that high levels of the protein are necessary to decrease blood glucose concentration in diabetic rats. These concentrations were not reached after oral administration. The same dose of insulin decreased glycemia by 50% in normal rats and by only 25% in diabetics. This suggested that an insulino-resistance was developed by streptozotocin-induced diabetic rats.
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PMID:Absorption and efficiency of insulin after oral administration of insulin-loaded nanocapsules in diabetic rats. 1217 72


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