UMLS:C0011849 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0011849 (diabetes)
277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is well known that rapid-acting insulin analogues like insulin aspart (B28Asp) show a faster onset and a shorter duration of action than currently available U100 soluble insulin preparations. Since this effect is mainly due to a lower concentration of slow-absorbable hexamers, the metabolic profile of human insulin in lower concentration (e.g. U40 insulin) might be more similar to that of insulin aspart. Therefore, we compared the pharmacodynamic and pharmacokinetic properties of U40 soluble insulin with insulin aspart (U100) and with U100 human insulin. Eight healthy volunteers received on different study days s.c. injection of insulin aspart and U40 insulin (0.2 U/kg body weight) under euglycaemic clamp conditions (blood glucose 5 mmol/l, basal i.v. insulin infusion 0.15 mU/kg/min). In a second study, U40 and U100 soluble insulin was administered to 9 other volunteers under similar conditions. No significant differences were observed between the summary measures of U40 and U100 insulin. Insulin aspart showed a faster onset and a shorter duration of action than U40 insulin. The metabolic activity of human insulin in concentrations of U40 and U100 is comparable. Subcutaneous injection of the insulin analogue insulin aspart leads to a faster onset and a shorter duration of action even in comparison to U40 insulin.
Exp Clin Endocrinol Diabetes 1997
PMID:Comparison of the time-action profiles of U40- and U100-regular human insulin and the rapid-acting insulin analogue B28 Asp. 922 9

Insulin aspart is a novel rapid-acting insulin analogue with improved subcutaneous absorption properties when compared with soluble human insulin. Pharmacokinetic studies show an absorption profile with a time to reach peak concentration (t(max)) about half that of human insulin, a peak plasma drug concentration (Cmax) approximately twice as high and shorter residence time. The potency and bioavailability of insulin aspart are similar to those of human insulin. The pharmacokinetics of insulin aspart have been studied in healthy Caucasian and Asian-Japanese volunteers, in patients with type 1 and 2 diabetes mellitus, and in children with diabetes, with both pre- and postprandial administration and during continuous subcutaneous insulin infusion (CSII). The pharmacokinetic profile was similar to that of another rapid-acting insulin analogue, insulin lispro, on the basis of published information for that agent. Pharmacodynamic studies show a smaller excursion of postprandial glucose with insulin aspart injected subcutaneously just before the meal compared with soluble human insulin injected 30 minutes before the meal in patients with type 1 diabetes mellitus, and an equivalent control in patients with type 2 diabetes displaying residual insulin production. In a treatment study, glucose excursions evaluated from 24-hour glucose profiles showed less variability with insulin aspart compared with human insulin. Adverse events, including hypoglycaemia-induced ventricular repolarisation and hypoglycaemic threshold and awareness, did not differ between insulin aspart and human insulin. The available data suggest that subcutaneous injections of insulin aspart just before meals better mimic the endogenous insulin profile in blood compared with human insulin, resulting in improved glucose control in a meal-related insulin regimen. This review summarises the clinical pharmacokinetics and pharmacodynamics of insulin aspart in relation to human insulin and insulin lispro.
...
PMID:Clinical pharmacokinetics and pharmacodynamics of insulin aspart. 1160 14

Insulin aspart (IAsp), is a rapid-acting analogue of human insulin (HI), for use in the meal related treatment of diabetes mellitus. The degree of glycaemic control achieved by IAsp in comparison with HI after algorithm-driven dose optimisation was tested over 3 months. The prospective, multicentre, randomised, open-label study with parallel groups was performed in 48 centres in 11 countries and included 423 basal-bolus treated patients with Type 1 diabetes. Main outcome measures were blood glucose control assessed by HbA1c, nine-point self-monitored blood glucose profiles, insulin dose, quality of life, hypoglycaemia and adverse events. An algorithm-driven increase occurred in the dose and number of daily injections of basal insulin, particularly in the IAsp group. After 12 weeks of treatment, HbA1c was significantly lower in IAsp compared to HI treated subjects by 0.17 (95% CI 0.30-0.04) (P<0.05). Comparison of the blood glucose profiles showed lower blood glucose levels with IAsp after breakfast (mean 8.4 vs 10.1 mmol/l; P<0.0001) and dinner (8.2 vs 9.3 mmol/l; P<0.01). There were no differences between treatments in the incidence of hypoglycaemic episodes or in the adverse event profiles. The WHO Diabetes Treatment Satisfaction Questionnaire score for perceived hyperglycaemia was lower with Iasp (P=0.005), and patients found the insulin aspart treatment more flexible (P=0.022). The current study underlines the need for optimising the basal insulin regimen in order to take full advantage of the pharmacodynamics of IAsp.
Diabetes Res Clin Pract 2001 Nov
PMID:Glycaemic control in type 1 diabetic patients using optimised insulin aspart or human insulin in a randomised multinational study. 1164 Sep 94

Insulin aspart is a novel rapid-acting human insulin analogue, which structure is almost identical to human insulin, except for the substitution of a single residue in the amino acid sequence of the insulin. The structure of insulin aspart leads to more rapid absorption than human insulin. As a result, insulin aspart provides significantly better postprandial glucose control than human insulin. As mealtime insulin in a basal-bolus regimen, insulin aspart gives stable 24-hour blood glucose control, with lower maximum glucose levels during daytime than with human insulin. The better daily glycaemic profile with insulin aspart gives the better long-term metabolic control estimated by HbA1C. The score of patients' satisfaction in DTSQ(Diabetes Treatment Satisfaction Questionnaire) was greater with insulin aspart treatment. The overall safety of insulin aspart is comparable to human insulin.
...
PMID:[Insulin aspart(NN-X14)]. 1171 99

Numerous studies have demonstrated that tight glycaemic control reduces long-term complications in both Type 1 and Type 2 diabetes. However, current intensive insulin regimens increase the risk of hypoglycaemia, dissuading many attempting this approach. Normal physiological insulin profiles consist of a stable, basal component and meal-related surges in secretion. Conventional insulin regimens cannot mimic this profile accurately due to pharmacokinetic limitations. Human insulin has a slow onset of action, thus patients are advised to inject about 30 min before a meal, ensuring peak insulin concentrations coincide with postprandial glucose excursions. This is clearly impractical for many and can lead to pre-meal hypoglycaemia if the meal is delayed. Furthermore, it only partially overcomes the unphysiological insulin profile and patients experience postprandial hyperglycaemia and are vulnerable to postabsorptive hypoglycaemia. Insulin aspart and insulin lispro are rapid-acting analogues that allow a more physiological replacement of mealtime insulin secretion. They reduce postprandial glucose and usefully reduce the incidence of hypoglycaemia when used in a basal-bolus regimen in tightly controlled patients. Pre-mixed insulins, containing a combination of rapid-acting and intermediate-acting insulin, are widely used, particularly in Type 2 diabetes. They have limitations achieving tight glucose targets but early data suggest that the combination of 30% insulin aspart and 70% protaminated insulin aspart may also reduce severe hypoglycaemia. On-going clinical trials will establish whether they can be used to achieve better glycaemic control with less hypoglycaemia.
...
PMID:Reducing hypoglycaemia with insulin analogues. 1217 21

The development and progress of antidiabetic drugs (e.g., insulin preparations and hypoglycemic drugs) are retrospectively investigated in Japan. Their influences on the treatment of diabetes mellitus (DM) and its epidemiological aspects are also discussed. 1) Insulin preparations: Insulin was introduced for DM therapy in 1925, two or three years after its discovery in Canada. The preparations were raw extracts of bovine or porcine pancreas. These did not prevail widely in Japan because of the low incidence of DM before World Wan II. After the war, a shortage of mammalian materials compelled the use of fish pancreatic tissues such as bonito and/or tuna for insulin production. Insulin infection, so-called regular insulin, was first promoted in the 6th "Pharmacopoeia Japonica" (JP6) in 1951 and has been maintained to the present edition (JP14, 2001). Although depot-type insulin preparations were developed in the USA and Europe during the war, the introduction of those preparations to Japan was delayed until 1951, when Protamine zinc insulin appeared. Globin zinc insulin and Isophane insulin were introduced for clinical use in 1952 and 1955, respectively. These were also adopted for JP7 (1961). Biphasic-type insulin, which has a rapid onset and long duration of activity, appeared in 1965. Purified preparations from bovine or porcine sources have been available since 1980, which might be a strong reason for the decrease in insulin allergy. Insulin from animal origin has been supplied for almost 60 years since its discovery. Amino acid sequences of insulins from various species of animals were determined by the pioneering studies of Sanger and his associates. Human insulin, which differs from porcine insulin by only one amino acid, was produced by Novo researchers in 1982 using a semi-synthetic method. Then the Lilly group soon succeeded in obtaining human insulin by recombinant DNA technology in the same year. Both products were introduced to Japan in 1985, and the recombinant products prevailed throughout the 1990s. Human insulin analogues (i.e., Insulin lispro and Insulin aspart) appeared in 2001. These are applied for after-meal glycosmia owing to their ultrarapid onset of activity. Self-injection by DM patients was legalized in 1981. To make the infection technique sure and easy, cartridge (pen-type) and disposable kit-type needles were devised in the 1990s. 2) Oral hypoglycemic drugs: Instead of the exclusive parenteral usage of insulins, there was also demand for oral dosage forms. The first of the sulfonyrlurea (SU) group, BZ-55, was used for DM clinically in 1955 in Germany. But it was soon withdrawn because of its antibacterial action. This led to the development of various SU groups. Tolbutamide (1956), chlorpropamide (1959), acetohexamide (1964) and tolazamide (1961) were introduced to Japan as first-generation SUs. Then glyclopyramide (Kyorin, 1965), glybenclamide (1971), gliclazide (1984) and glimepiride (1999) appeared as the second-generation SUs. These were used orally for Type 2 diabetes. Biguanide (BG) group, phenformin HC1 (1959), metformin HC1 (1961) and buformin HC1 (1961) had also been in use by oral treatment of Type 2 diabetes. SU appears to act by increasing the sensitivity of b-cells, which secrete insulin. BG probably exerts by increasing glucose transport across the membranes of target organs. 3) New types of antidiabetic drugs: a-Glucosidase inhibitors (i.e., acarbose: Bayer, 1993; and voglibose: Takeda, 1994) act on hyperglycemia after meals by decreasing glucose absorption. Thiazolidinedione compounds, such as troglitazone (Sankyo, 1995) and pioglitazone HC1 (Takeda, 1994) act by increasing the insulin sensitivity of the target tissues. These are useful for Type 2 DM patients when SUs are ineffective. Nevertheless, troglitazone was discontinued in 2000 due to severe liver damage. Nateglinide (Ajinomoto Co., 1999), which is a D-phenylalanine derivative acting similar to SUs, is useful orally for after-meal hyperglycemia of Type 2 diabetes. Epalrestat (Ono Yakuhin Co., 1992) is effective for diabetic neuropathy by reducing the formation of sorbitol. These anti-DM drugs were recently studied and developed in Japan. 4) The Japan Diabetes Society proposed a guideline on diagnostic criteria and treatment of diabetes mellitus (DM) in 1999 and revised it in 2002. DM is classified as insulin-dependent DM (Type l) and non-insulin dependent DM (Type 2). Type 1, juvenile onset DM, requires insulin therapy to prevent ketosis and to sustain life. Treatment of type 2, adult onset DM, is recommended as a step-by-step method, starting with dietary-exercise therapy, followed by oral hypoglycemic drugs and then insulin therapy. DM patients with complications should have a therapy devised to match their circumstances. 5) Epidemiological aspects: The mortality rate of DM compared to the time of drug appearance was traced from 1920 to 2000. The curve goes down slowly in the time frame of World War II, but rises from 1950 to 1970. The elevation could not be suppressed by the appearance of SUs, BGs or improved insulin preparations. The curve runs flat from 1980 to 1990, which might be related to the use of purified insulin or human insulin therapy. The mortality rate of DM indicates that death by hyperglycemic coma and other deaths resulting from complications are excluded. The survey of the principal cause of death by DM during the period of 1981-1990 indicates that the death rate due to hyperglycemic coma is only 1.7% of the total deaths caused by DM. The effect of drug therapy on all of the death resulting from DM is not detected. Hospital visitation and admission rates of the DM patients have been recorded since 1952 in Japan. This curve is rising continuously, and none of the antidiabetic drugs has been able to suppress it. These data show that the antidiabetic drugs relieve DM symptoms through their effective hypoglycemic actions, but that they cannot suppress the mortality rate of DM. It is possible that none of the drugs currently available can suppress the increasing tendency of DM patients.
...
PMID:[A 50-year history of new drugs in Japan-the development and progress of anti-diabetic drugs and the epidemiological aspects of diabetes mellitus]. 1457 54

Type 2 diabetes is characterized by progressive beta-cell failure. Indications for exogenous insulin therapy in patients with this condition include acute illness or surgery, pregnancy, glucose toxicity, contraindications to or failure to achieve goals with oral antidiabetic medications, and a need for flexible therapy. Augmentation therapy with basal insulin is useful if some beta-cell function remains. Replacement therapy with basal-bolus insulin is required for beta-cell exhaustion. Rescue therapy using replacement regimens for several weeks may reverse glucose toxicity. Replacement insulin therapy should mimic normal release patterns. Basal insulin, using long-acting insulins (i.e., neutral protamine Hagedorn [NPH], ultralente, glargine) is injected once or twice a day and continued on sick days. Bolus (or mealtime) insulin, using short-acting or rapid-acting insulins (i.e., regular, aspart, lispro) covers mealtime carbohydrates and corrects the current glucose level. The starting dose of 0.15 units per kg per day for augmentation or 0.5 units per kg per day for replacement can be increased several times as needed. About 50 to 60 percent of the total daily insulin requirement should be a basal type, and 40 to 50 percent should be a bolus type. The mealtime dose is the sum of the corrective dose plus the anticipated requirements for the meal and exercise. Adjustments should be made systematically, starting with the fasting, then the preprandial and, finally, the postprandial glucose levels. Basal therapy with glargine insulin provides similar to lower A1C levels with less hypoglycemia than NPH insulin. Insulin aspart and insulin lispro provide similar A1C levels and quality of life, but lower postprandial glucose levels than regular insulin.
...
PMID:Insulin therapy for type 2 diabetes: rescue, augmentation, and replacement of beta-cell function. 1560 55

Insulin aspart (NovoRapid, NovoLog) is a short-acting insulin analogue, which has a faster onset and shorter duration of action than regular human insulin. Insulin aspart administered immediately before meals provided significantly greater improvements in glycosylated haemoglobin and better postprandial glycaemic control than regular human insulin administered 30 minutes before meals, when used in a basal-bolus regimen with neutral protamine Hagedorn (NPH) insulin, in randomised, nonblind studies in patients with type 1 diabetes mellitus. In patients with type 2 diabetes, insulin aspart provided similar glycaemic control to regular human insulin, administered in a basal-bolus regimen with NPH insulin. Small studies suggest that the use of insulin aspart in combination with oral hypoglycaemic agents may be beneficial. Insulin aspart, administered by continuous subcutaneous insulin infusion (CSII) provided better glycaemic control than insulin aspart multiple daily injection regimens in patients with type 1 (but not type 2) diabetes, and had similar efficacy to CSII with insulin lispro or regular human insulin in type 1 diabetes. Limited studies show insulin aspart to be effective in children, adolescents and young adults with type 1 diabetes. Insulin aspart had a tolerability profile similar to that of regular human insulin in clinical trials. The incidence of major or nocturnal hypoglycaemic events reported in patients receiving insulin aspart was lower than that of regular human insulin in several studies. In conclusion, insulin aspart, administered immediately before meals in a basal-bolus regimen with NPH insulin, provided better long-term glycaemic control than regular human insulin administered 30 minutes before meals in patients with type 1 diabetes, and was as effective as regular human insulin in patients with type 2 diabetes. A significantly lower risk of hypoglycaemia was seen in several trials. Insulin aspart CSII provided better glycaemic control than insulin aspart multiple daily subcutaneous injection (MDI) in patients with type 1 (but not type 2) diabetes and had similar efficacy to CSII with insulin lispro or regular human insulin in type 1 diabetes. Insulin aspart is an effective and well tolerated alternative to regular human insulin and insulin lispro for the maintenance of glycaemic control in patients with type 1 or 2 diabetes.
...
PMID:Insulin aspart: a review of its use in the management of type 1 or 2 diabetes mellitus. 1532 46

A variety of abnormalities of metabolic, haemostatic and endothelial markers are associated with Type 2 diabetes. Evidence suggests that poor post-prandial blood glucose control may contribute to vascular risk. We aimed to examine whether the restoration of a more physiological insulin profile post-prandially would improve these abnormalities. Twenty-one patients with insulin-treated Type 2 diabetes were recruited into a single centre, crossover, double-blind study. Patients were randomized to unmodified human insulin or insulin aspart before main meals for 6-week study periods, both together with NPH insulin. At the end of each study period, pre-breakfast levels of markers of vascular risk were assessed and a test meal performed. There was no significant difference in HbA(1c) (7.04 +/- 0.13% (+/-S.E.) versus 7.15 +/- 0.11%, P = 0.060) with insulin aspart compared to human insulin at the end of each study period. The mean post-prandial blood glucose concentration at 90 min from self-monitored results was lower with insulin aspart than with human insulin (7.9 +/- 0.4 mmol/l versus 9.3 +/- 0.4 mmol/l, P = 0.011) as was study day post-prandial blood glucose at 90 min (8.4 +/- 0.5 mmol/l versus 9.2 +/- 0.6 mmol/l, P = 0.046). No significant differences were found in fasting lipid profile, apolipoproteins, fibrinogen, plasminogen activator inhibitor-1, E-selectin, or homocysteine between the two study periods. Insulin aspart resulted in improved post-prandial glycaemic control when compared to human insulin in Type 2 diabetic patients, but this was not associated with changes in markers of vascular risk.
Diabetes Res Clin Pract 2005 Mar
PMID:The effect of improved post-prandial blood glucose control on post-prandial metabolism and markers of vascular risk in people with Type 2 diabetes. 1571 51

Synthetic insulins such as Humalog Lispro, Novolog Aspart, or Lantus Glargine, are commonly employed for the treatment of insulin-dependent diabetes mellitus owing to convenient handling and fast or prolonged bioavailability. However, the misuse of insulin in sports has been reported often, and the international doping control system requires a reliable and robust assay to determine the presence or absence of related drugs prohibited by the World Anti-Doping Agency. Qualitative evidence of administered substances, which is preferably obtained by mass spectrometry, is of utmost importance. Plasma specimens of 2 mL were fortified with three synthetic insulin analogues and purified by immunoaffinity chromatography, and extracts were analyzed by microbore liquid chromatography and tandem mass spectrometry. Product ion scan experiments of intact proteins enabled the differentiation between endogenously produced insulin and its synthetic analogues by collisionally activated dissociation of multiply charged precursor ions. This top-down sequencing-based assay allows the assignment of individual fragment ions, in particular, of those comprising modifications that are originating from C-termini of B-chains. Recoveries of synthetic insulins from plasma aliquots ranged from 91 to 98%, and detection limits were accomplished at 0.5 ng/mL for all target analytes.
...
PMID:Qualitative determination of synthetic analogues of insulin in human plasma by immunoaffinity purification and liquid chromatography-tandem mass spectrometry for doping control purposes. 1592 92

1 2 3 Next >>