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Query: UMLS:C0011849 (diabetes)
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The main therapeutic challenge in the treatment of Type 1 diabetes is maintenance of near-normoglycaemia in order to prevent long-term complications and avoid hypoglycaemia. This goal is relevant from the onset of the disease and is feasible if physiological models of insulin replacement are used and patients are educated in the strategy of intensive insulin therapy. Although the use of available insulins within a multiple injection regimen has improved, metabolic control it is still far from being optimal. The recent introduction of insulin analogues with a short- and long-acting profile seems promising in improving metabolic control and quality of care. Insulin lispro and insulin aspart, the short-acting insulin analogues offer a better post-prandial profile, while insulin glargine the new long-acting insulin analogue might provide better overnight control. In fact, the theoretical combination of an acute prandial insulin peak with a flat interprandial and overnight plasma profile would closely mimic the 24-hr insulin profile of non-diabetic individuals. This would possibly lead to lower post-prandial blood glucose excursion and better fasting blood glucose associated with minimal risk of hypoglycaemia. The possible reduction of hypoglycaemia is especially important in children as recurrent episodes might represent a potential risk for cognitive impairment. However, recent clinical research on the short-acting insulin analogues demonstrates the difficulties of translating these theoretical benefits into clinical relevant advantages. This might happen to other insulin analogues and requires further and larger studies in order to fully exploit the theoretical advantages of insulin analogues in the paediatric population. Safety issues should also be carefully monitored when introducting analogues in long-term therapy.
Diabetes Nutr Metab 2001 Dec
PMID:The potential role of insulin analogues in the treatment of children and adolescents with Type 1 diabetes mellitus. 1185 68

Insulin lispro was compared with regular human insulin with respect to glycaemic control in patients with diabetes mellitus on intensive insulin treatment. Sixty-two patients (55 type 1; 7 type 2) from eight study centres in the Czech Republic, Slovenia and the Slovak Republic participated in a 4-month, open-label, randomized, crossover study. Patients administered insulin lispro immediately before meals or regular human insulin 30 min before meals. A test meal (220-400 kcal), based on local and individual dietary habits and consistent for each patient throughout the study was given at baseline and at the end of each treatment. At each test meal visit HbA1c, fasting blood glucose, 1-hour and 2-hour postprandial blood glucose levels were measured. The level of HbA1c (7.6% +/- 1.5% versus 7.4% +/- 1.5%), incidence of hypoglycaemia (41-66% of patients--versus 39-63%) and daily insulin dose (0.67 +/- 0.11 U/kg versus 0.65 +/- 0.11 U/kg) did not differ between treatment groups at endpoint (insulin lispro versus regular human insulin, respectively). Mean 2-hour postprandial blood glucose excursion for the insulin lispro group (0.0 +/- 3.7 mmol/L) was significantly lower (p = 0.035) when compared with the regular human insulin group (1.3 +/- 3.7 mmol/L) at endpoint. Therapy with insulin lispro was therefore associated with a significant improvement in postprandial blood glucose excursion control when compared with regular human insulin, without an increase in rate of hypoglycaemia.
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PMID:Insulin lispro improves postprandial glucose control in patients with diabetes mellitus. 1244 33

Insulin lispro (IL) possesses characteristics (decreased hypoglycaemia, greater convenience in timing of administration and better post-prandial glucose control) which may favour its use in women with diabetes. We report pregnancy outcomes in seven women with Type I diabetes treated with IL. Mean age was 30 years (2241), duration of diabetes from 3 to 21 years. Two were using IL pre-conception; others transferred at various stages of pregnancy. Mean daily dose of IL within the last month of pregnancy ranged from 0.59 to 1.13 U/kg. Mean HbA1C from 4.4 to 8.5%. Babies were delivered at 3438 weeks' gestation, birth weights from 2900 to 4125 g (mean 3434 g). There were no congenital abnormalities. All patients elected to continue with IL after pregnancy. Our experience suggests that IL is convenient and practical therapy for women with Type I diabetes in pregnancy.
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PMID:Preliminary experience with the use of insulin lispro in pregnant diabetic women. 1252 23

Insulin lispro, the first insulin analogue to be used clinically, was engineered to incorporate the pharmacological advantages of insulin-like growth factor-1 (IGF-1), which has a reduced tendency to self associate, compared to conventional soluble insulin. It is absorbed more quickly following a subcutaneous injection, reaching peak concentrations (approximately twice as much as conventional insulin) and then falls more rapidly. These more physiological insulin profiles are reflected in the results of clinical trials involving patients with Type 1 diabetes, which generally show comparable glycaemic control but reduced rates of hypoglycaemia, particularly at night. The reduction in the rate of hypoglycaemia in the early trials has been generally fairly modest, but more recent publications suggest that increasing experience and more individualised insulin adjustment may lead to a greater impact. Other indications include its use in continuous subcutaneous insulin infusion and postprandially in young children.
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PMID:Insulin lispro: a useful advance in insulin therapy. 1287 47

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.
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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

Numerous studies have established a direct relationship between maternal levels of glycemic control and neonatal outcomes for pregnancies complicated by diabetes. The past several years have seen the addition of insulin analogues as well as many new oral agents to the pharmacological armamentarium available to treat diabetes. Insulin analogs (both rapid and long acting) are of potential interest for women with insulin-requiring diabetes because of the improved control reported in non-pregnant individuals. Insulin lispro is the only insulin analog to be systematically studied in pregnancy. At this time, the majority of evidence suggests that insulin lispro does not cross the placenta and does not have adverse maternal or fetal effects during pregnancy in women with diabetes. For women with gestational diabetes mellitus (GDM) and type 2 diabetes, which are characterized by insulin resistance and relatively decreased insulin secretion, treatment with oral hypoglycemic agents is generating much excitement. Most retrospective studies and the published clinical experience have failed to demonstrate an increased risk of neonatal hypoglycemia and other neonatal morbidities with glyburide or metformin. To date there has been only one randomized controlled trial utilizing glyburide, which found it to be safe and effective in the management of GDM. More intensive investigation regarding the safety and feasibility of oral agents in pregnancies complicated by type 2 diabetes is necessary.
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PMID:Insulins and oral hypoglycemic agents in pregnancy. 1712 90

Insulin lispro, alone (Humalog) or as premixture (Humalog Mix25 or Humalog Mix50) is indicated for the treatment of hyperglycaemia in diabetes mellitus in many countries worldwide. It is a recombinant human insulin analogue and, except for the transposition of two amino acids, is identical to endogenous human insulin. Insulin lispro has a faster onset of action and shorter duration of activity than regular human insulin, and the time-action profile of insulin lispro mimics that of the physiological response of endogenous human insulin to food intake. In diabetic patients, from young children to the elderly, it has demonstrated postprandial blood glucose control similar to or better than that achieved with regular human insulin, without an increased risk of hypoglycaemia. In some trials, the risk of hypoglycaemia, including nocturnal episodes, was less in insulin lispro recipients than in regular human insulin recipients. Insulin lispro alone, or as a premixture with the longer-acting insulin neutral protamine lispro, can be administered immediately before or after meals. This convenient and flexible injection schedule may enable patients, including those with a non-routine lifestyle or unpredictable eating or exercising habits, to achieve the tight glycaemic control required to minimise long-term complications of diabetes and contributes to patient satisfaction with treatment.
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PMID:Insulin lispro: a review of its use in the management of diabetes mellitus. 1733 98

The purpose of this review is to provide a brief overview of the safety of antidiabetics in pregnancy. Specifically, concerns over teratogenicity due to the possible placental transfer of antidiabetics as well as maternal and neonatal outcomes are addressed. Several new insulin analogs are currently available for the treatment of diabetes. Due to the improved glycemic control demonstrated in non pregnant patients, these analogs may also prove to be beneficial in pregnancy. Insulin lispro is the only insulin analog that has been systematically studied in pregnancy. Results of these studies show a lack of transfer across the placenta and no adverse fetal and neonatal outcomes. The use of oral hypoglycemic agents in pregnancy is also generating interest. To date, there has been only one randomized controlled trial investigating the use of glyburide which found it to be safe and effective in the management of gestational diabetes mellitus. The lack of randomized controlled trials for antidiabetics in pregnancy highlights the need for more comprehensive investigation regarding their safety and efficacy.
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PMID:Treating the mother--protecting the unborn: the safety of hypoglycemic drugs in pregnancy. 1829 74

Human recombinant synthetic insulin analogs allow better control of blood glucose concentrations while minimizing the risk of hypoglycemic events in diabetic human patients. Little information is available regarding the use of insulin analogs in cats and dogs. Insulin lispro is an ultrashort-acting analog that has been used in the intensive treatment of dogs with diabetic ketoacidosis. Insulin glargine and insulin detemir are long-acting, and are used in people as basal insulin replacement. Both are associated with reduced risk of hypoglycemia, while detemir also is associated with less undesired weight gain. In cats, insulin detemir and insulin glargine have longer durations of action than traditionally used insulin formulations, and both have been used successfully in once-a-day regimens for treatment of diabetes. Insulins detemir and glargine may have shorter durations of action in cats than in people, and more variability in their effects.
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PMID:Synthetic insulin analogs and their use in dogs and cats. 2021 90

Excellent glycaemic control is essential in pregnancy to optimise maternal and foetal outcomes. The aim of this review is to assess the efficacy and safety of insulin analogues in pregnancy. Insulin lispro and insulin aspart are safe in pregnancy and may improve post-prandial glycaemic control in women with type 1 diabetes. However, a lack of data indicating improved foetal outcomes would suggest that there is no imperative to switch to a short-acting analogue where the woman's diabetes is well controlled with human insulin. There are no reports of the use of insulin glulisine in pregnancy and so its use cannot be recommended. Most studies of insulin glargine in pregnancy are small, retrospective and include women with pre-existing diabetes and gestational diabetes. There appear to be no major safety concerns and so it seems reasonable to continue insulin glargine if required to achieve excellent glycaemic control. A head-to-head comparison between insulin detemir and NPH insulin in women with type 1 diabetes showed that while foetal outcomes did not differ, fasting plasma glucose improved with insulin detemir without an increased incidence of hypoglycaemia. The greater evidence base supports the use of insulin detemir as the first line long-acting analogue in pregnancy but the lack of definitive foetal benefits means that there is no strong need to switch a woman who is well controlled on NPH insulin. There seems little justification in using long acting insulin analogues in women with gestational diabetes or type 2 diabetes where the risk of hypoglycaemia is low.
Diabetes Obes Metab 2013 Oct
PMID:The use of insulin analogues in pregnancy. 2348 21


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