insulin-glulisine and Diabetes-Mellitus--Type-1

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.

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetes, Gestational; Dose-Response Relationship, Drug; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Pregnancy; Pregnancy in Diabetics; Randomized Controlled Trials as Topic; Treatment Outcome

We review and summarize the literature on the safety and stability of rapid-acting insulin analogs used for continuous subcutaneous insulin infusion (CSII) in patients with diabetes.. Two predefined search strategies were systematically implemented to search Medline and the Cochrane Register of Clinical Trials for publications between 1996 and 2012.. Twenty studies were included in the review: 13 in vitro studies and 7 clinical studies. In vitro studies investigated the effects of extreme CSII conditions (high temperature and mechanical agitation) on the risk of catheter occlusions and insulin stability factors, such as potency, purity, high molecular weight protein content, pH stability, and preservative content (m-cresol, phenol). Under these conditions, the overall stability of rapid-acting insulin analogs was similar for insulin lispro, insulin aspart, and insulin glulisine, although insulin glulisine showed greater susceptibility to insulin precipitation and catheter occlusions. A limited number of clinical trials were identified; this evidence-based information suggests that the rate of catheter occlusions in patients with type 1 diabetes using CSII treatment may vary depending on the rapid-acting analog used.. Based on a limited amount of available data, the safety, stability, and performance of the three available rapid-acting insulin analogs available for use with CSII were similar. However, there is limited evidence suggesting that the risk of occlusion may vary with the insulin preparation under certain circumstances.

Topics: Amino Acid Sequence; Diabetes Mellitus, Type 1; Drug Stability; Humans; Infusions, Subcutaneous; Insulin; Insulin Aspart; Insulin Infusion Systems; Insulin Lispro; Insulin, Short-Acting; Molecular Sequence Data; Risk Factors; Treatment Outcome

Postprandial glucose excursions can inhibit achievement of good glycaemic control, and possibly have a specific effect on the risk of vascular comorbidities. Rapid-acting analogues control these excursions better than human insulin because their pharmacokinetic/pharmacodynamic (PK/PD) profile is closer to that of meal-time endogenous insulin secretion. Review of the findings of PK/PD studies and clinical trials suggests that the three marketed rapid-acting analogues--insulin lispro, insulin aspart and insulin glulisine--are equally efficacious and safe. In comparison with human insulin when using the same basal insulin, they provide comparable glycaemic control with a reduced risk of hypoglycaemia, although the combination of rapid-acting and basal analogues reduces glycated haemoglobin (HbA(1c)) more than human meal-time insulin combined with neutral protamine Hagedorn (NPH) insulin. Some studies have suggested that insulin glulisine has a slightly faster onset of action compared with insulin lispro or insulin aspart, but this has not been translated into demonstrable clinical benefit. Treatment satisfaction in patients with diabetes has been higher when therapy with a rapid-acting analogue is used instead of human insulin, perhaps due to differences in advised timing of injection. The largest benefits in efficacy, hypoglycaemia incidence, treatment satisfaction and quality of life have occurred when patients receive an all-analogue meal-time plus basal regimen as compared with an all-human insulin regimen. No new safety issues have been identified with the marketed rapid-acting analogues, and their insulin-like growth factor 1 receptor affinity and mitogenic activity are comparable to human insulin.

Topics: Area Under Curve; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Lispro; Randomized Controlled Trials as Topic; Treatment Outcome

Since insulin is the unique and life-long therapy in type 1 diabetes and classical insulin preparations have certain limitations due to their pharmacokinetic and pharmacodynamic properties, the new insulin analogues aim to eliminate these limitations. Five insulin analogues are commercially available and approved for individuals with type 1 diabetes: three rapid-acting (insulin lispro, insulin aspart and insulin glulisine) and two long-acting insulin analogues (insulin glargine and insulin detemir). According to several studies conducted in children with type 1 diabetes, insulin analogues, due to their structural alterations, offer flexibility, reduction of nocturnal hypoglycemic episodes and decrease in postprandial hyperglycemic events, resulting in improved quality of life for diabetic children and their families. However, diabetes control measured with glycosylated hemoglobin A1c has been reported to be similar to conventional insulin preparations. Evidence-based medical reports indicate that insulin analogues are safe and effective, and therefore approved for children even from the age of 2 years. Moreover, suspicions and reports on the association of insulin analogues with carcinogenesis have not been established, requiring further investigation. This review reports the properties and characteristics of insulin analogues, as well as the results of current studies concerning pediatric patients with type 1 diabetes.

Topics: Adolescent; Child; Diabetes Mellitus, Type 1; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting

The prevalence of diabetes mellitus continues to increase throughout the world with an expected doubling of documented cases between 2006 and 2030, diabetes deaths are expected to increase by more than 50% from 2006 to 2015. Therapeutic interventions should be based on scientific evidence, including earlier insulin initiation and use of a basal-bolus approach that better mimics normal physiology.. This review focuses on insulin glulisine in the basal-bolus approach. It details pharmacological data, clinical efficacy, safety and tolerability, and potential effects on current treatment regimens.. Insulin glulisine offers a more rapid onset of action and shorter duration of action compared with regular human insulin. These characteristics result in an action profile that closely mimics the normal postmeal endogenous insulin response, thus fulfilling the prandial insulin requirement and making the basal-bolus treatment approach clinically achieveable.

Topics: Animals; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin

Insulin glulisine (Apidra) is a human insulin analogue approved for the improvement of glycaemic control in adults, adolescents and children with diabetes mellitus. It has similar binding properties, and is associated with a faster onset but similar level of glucose disposal, to regular human insulin (RHI). Insulin glulisine and insulin lispro have similar effects on glucose levels. Insulin glulisine is effective when compared to other short- and rapid-acting insulins, demonstrating either noninferiority, no significant difference, or superiority in primary endpoints in studies involving patients with type 1 and type 2 diabetes. It is more effective and has a faster onset and shorter duration of activity than RHI. Insulin glulisine is as effective as insulin lispro in patients with type 1 diabetes; however, there is a need for further, well designed head-to-head comparisons with insulin lispro in patients with type 2 diabetes and with insulin aspart in patients with type 1 or type 2 diabetes to fully establish the place of insulin glulisine in the management of diabetes. Insulin glulisine has a flexible administration period, as it can be administered immediately before or after meals. Hypoglycaemia, a common risk with insulins, occurs at a similar rate among recipients of insulin glulisine to that seen with other insulins. Thus, insulin glulisine is an effective and well tolerated option for the treatment of patients with type 1 and type 2 diabetes.

Topics: Adolescent; Adult; Blood Glucose; Child; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin

Insulin glulisine injection [3(B)-Lys, 29(B)-Glu-human insulin] is the newest human insulin analogue product for the control of mealtime blood sugar. As with insulin aspart and insulin lispro products, the insulin glulisine product displays faster absorption and onset of action, with a shorter duration of action than that of regular human insulin. The modifications of the amino acid sequence at positions 3 and 29 in the B chain of human insulin simultaneously provide stability to the molecular structure and render the insulin glulisine molecule less likely to self-associate, compared with human insulin, while still allowing the formation of dimers at pharmaceutical concentrations. Unlike other insulin analogue products, this allows for a viable drug product in the absence of hexamer-promoting zinc and, thus, provides immediate availability of insulin glulisine molecules at the injection site for absorption. Pharmacokinetic studies with insulin glulisine have shown an absorption profile with a peak insulin concentration approximately twice that of regular human insulin, which is reached in approximately half the time. Dose proportionality in early, maximum and total exposure is observed for insulin glulisine over the therapeutic relevant dose range up to 0.4 U/kg. The pharmacodynamic profile of insulin glulisine reflects the absorption kinetics by demonstrating a greater rate of glucose utilization, which is completed earlier and at equipotency on a molar base compared with regular human insulin. Dose-proportionality in glucose utilization has been established for insulin glulisine in patients with type 1 diabetes mellitus in the dose range of 0.075-0.15 U/kg, and a less than dose-proportional increase above 0.15 U/kg, indicating saturation of insulin action in general. The rapid absorption and action of insulin glulisine show similar low intrasubject variability compared with insulin lispro and regular human insulin when given repeatedly, and have been confirmed in healthy subjects of different body mass indices (BMIs) and ethnic groups, as well as adults and children with type 1 and type 2 diabetes. Furthermore, the early insulin exposure and action of insulin glulisine were slightly -- but consistently -- greater than those of insulin lispro in healthy volunteers across a wide range of BMIs.Meal studies in patients with type 1 diabetes show that insulin glulisine provides better postprandial blood glucose control than regular human insulin when administ

Topics: Amino Acid Sequence; Area Under Curve; Biological Availability; Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Insulin; Molecular Sequence Data; Treatment Outcome

A recent meta-analysis evaluated trials of the rapid-acting analogues insulin lispro and insulin aspart, performed before the introduction of the basal analogues, insulin glargine and insulin detemir. This article reviews the effect of rapid-acting and basal insulin analogues separately and in combination, relative to human insulin. Outcomes evaluated include HbA(1c), hypoglycaemia, postprandial glucose (PPG), and weight changes. Results from trials that matched defined criteria are presented in tables. In type 1 diabetes, compared with human insulin, the rapid-acting analogues generally reduced hypoglycaemia and postprandial glucose, whereas the basal analogues tended to reduce hypoglycaemia -- particularly nocturnal hypoglycaemia. Weight gain may also be reduced with basal analogues, compared with human basal insulin. In type 2 diabetes, premix rapid-acting analogues controlled postprandial glucose better than human insulin mixes; basal analogues used as basal-only therapy reduced hypoglycaemia compared with NPH insulin; and some advantages were apparent with analogues in basal-bolus therapy. Whilst the benefits on individual metabolic and clinical outcomes appear modest, almost all studies report some advantage when using insulin analogues in type 1 and type 2 diabetes. Significant benefits, including PPG lowering with the rapid-acting analogues and the potential for reduction in cardiovascular risk, should be investigated further.

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Administration Schedule; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin; Insulin Aspart; Insulin Detemir; Insulin Glargine; Insulin Lispro; Insulin, Isophane; Insulin, Long-Acting; Postprandial Period; Randomized Controlled Trials as Topic

SoloStar (sanofi-aventis) is a new, disposable insulin pen for the administration of insulin glargine (Lantus, sanofi-aventis) or insulin glulisine (Apidra, sanofi-aventis). SoloStar was developed to address a wide range of patient needs and demonstrates advancement over previous devices, owing to its appropriate combination of ergonomically-tested and mechanically improved features. The authors report the results of key investigations carried out by sanofi-aventis as part of the SoloStar development plan, including dose accuracy and injection force testing. Comparisons between SoloStar and two commonly used pens, FlexPen (Novo Nordisk) and the Humulin/Humalog pen (Eli Lilly) establish SoloStar as a state of the art pen that is suitable for most patients with diabetes.

Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Delivery Systems; Equipment Design; Ergonomics; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin, Long-Acting; Mechanics

Normalization of blood glucose is essential for the prevention of diabetes mellitus (DM)-related microvascular and macrovascular complications. Despite substantial literature to support the benefits of glucose lowering and clear treatment targets, glycemic control remains suboptimal for most people with DM in the United States. Pharmacokinetic limitations of conventional insulins have been a barrier to achieving treatment targets secondary to adverse effects such as hypoglycemia and weight gain. Recombinant DNA technology has allowed modification of the insulin molecule to produce insulin analogues that overcome these pharmacokinetic limitations. With time action profiles that more closely mimic physiologic insulin secretion, rapid acting insulin analogues (RAAs) reduce post-prandial glucose excursions and hypoglycemia when compared to regular human insulin (RHI). Insulin glulisine (Apidra) is a rapid-acting insulin analogue created by substituting lysine for asparagine at position B3 and glutamic acid for lysine at position B29 on the B chain of human insulin. The quick absorption of insulin glulisine more closely reproduces physiologic first-phase insulin secretion and its rapid acting profile is maintained across patient subtypes. Clinical trials have demonstrated comparable or greater efficacy of insulin glulisine versus insulin lispro or RHI, respectively. Efficacy is maintained even when insulin glulisine is administered post-meal. In addition, glulisine appears to have a more rapid time action profile compared with insulin lispro across various body mass indexes (BMIs). The safety and tolerability profile of insulin glulisine is also comparable to that of insulin lispro or RHI in type 1 or 2 DM and it has been shown to be as safe and effective when used in a continuous subcutaneous insulin infusion (CSII). In summary, insulin glulisine is a safe, effective, and well tolerated rapid-acting insulin analogue across all BMIs and a worthy option for prandial glucose control in type 1 or 2 DM.

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Randomized Controlled Trials as Topic

The third one so far. Does it offer any advantage over the other two?

Topics: Clinical Trials as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin

Short acting insulin analogue use for diabetic patients is still controversial, as reflected in many scientific debates.. To assess the effects of short acting insulin analogues versus regular human insulin.. The Cochrane Library (Issue 3, 2005), MEDLINE, EMBASE until September 2005.. Randomised controlled trials with an intervention duration of at least 4 weeks.. Trial selection and evaluation of study quality was done independently by two reviewers.. Altogether 8274 participants took part in 49 randomised controlled studies. Most studies were of poor methodological quality. In patients with type 1 diabetes, the weighted mean difference (WMD) of HbA1c was -0.1% (95% CI: -0.2 to -0.1) in favour of insulin analogue, whereas in patients with type 2 diabetes the WMD was 0.0% (95% CI: -0.1 to 0.0). In subgroup analyses of different types of interventions in type 1 diabetic patients, the WMD in HbA1c was -0.2% (95% CI: -0.3 to -0.1) in favour of insulin analogue in studies using continuous subcutaneous insulin injections (CSII), whereas for conventional intensified insulin therapy (IIT) studies the WMD in HbA1c was -0.1% (95% CI: -0.1 to 0.0). The WMD of the overall mean hypoglycaemic episodes per patient per month was -0.2 (95% CI: -1.1 to 0.7) and -0.2 (95% CI: -0.5 to 0.1) for analogues in comparison to regular insulin in patients with type 1 diabetes and type 2 diabetes, respectively. For studies in type 1 diabetes patients the incidence of severe hypoglycaemia ranged from 0 to 247.3 (median 21.8) episodes per 100 person-years for insulin analogues and from 0 to 544 (median 46.1) for regular insulin, in type 2 the incidence ranged from 0 to 30.3 (median 0.3) episodes per 100 person-years for insulin analogues and from 0 to 50.4 (median 1.4) for regular insulin. No study was designed to investigate possible long term effects (e.g. mortality, diabetic complications), in particular in patients with diabetes related complications.. Our analysis suggests only a minor benefit of short acting insulin analogues in the majority of diabetic patients treated with insulin. Until long term efficacy and safety data are available we suggest a cautious response to the vigorous promotion of insulin analogues. For safety purposes, we need a long-term follow-up of large numbers of patients and well designed studies in pregnant women to determine the safety profile for both the mother and the unborn child.

Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Lispro; Randomized Controlled Trials as Topic

Achieving and maintaining glycemic control (glycated hemoglobin--HbA(1c)< or =7.0% according to American Diabetes Association and < or =6.5% according to International Diabetes Federation) is the primary goal in treating diabetes, which lowers the risk for diabetes-related complications. Insulin therapy is essential for type 1 diabetes treatment. Insulin therapy in type 2 diabetes is initiated when glycemic control is inadequate despite the combination of antihyperglycemic drugs. The type of insulin therapy is selected according to the patient's lifestyle and needs. Multiple insulin injection therapy and premixed insulin therapy are usually administered. In multiple insulin injection therapy, basal insulin is administered one or two times a day, and regular human insulin or rapid-acting insulin analog is administered with each meal. The duration of action of regular insulin is 6-8 hours; therefore, the risk for postprandial hypoglycemia is increased. The action of novel insulin analogs (rapid- and long-acting) closely mimics physiological insulin secretion. Three rapid-acting insulin analogs are currently available: insulin lispro, insulin aspart, and insulin glulisine. Insulin glulisine is the most recently approved rapid-acting insulin analog. It is safe, flexible, and effective in achieving target postprandial glycemic control. Moreover, the pharmacokinetics of insulin glulisine does not depend on the amount of subcutaneous fat. Basal insulins include intermediate-acting human insulins (neutral protamine Hagedorn) and long-acting insulin analogs (insulin glargine, insulin detemir). The latter are the optimal choice covering basal insulin requirement. Compared to neutral protamine Hagedorn insulin, long-acting insulin analogs have no pronounced concentration peak and reduce nocturnal hypoglycemia risk and weight gain.

Topics: Adolescent; Adult; Age Factors; Aged; Algorithms; Blood Glucose; Child; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Detemir; Insulin Glargine; Insulin Secretion; Insulin, Long-Acting; Life Style; Middle Aged; Risk Factors; Time Factors

The use of insulin pump treatment (CSII: continuous subcutaneous insulin infusion) became widely accepted in the last couple of years. A growing body of experiences accumulated in paediatric practice because CSII is preferable for treating young patients with type 1 diabetes. Nevertheless, CSII can be used, if indicated, for treating type 2 diabetic patients as well. Recently, fast acting insulin analogues are exclusively used for CSII. At moment, clinical observations with insulin lispro and insulin aspart are available but experiences with glulisine are still limited. Although some inconsistencies could be observed in the literature, it is widely accepted, that higher reduction in HbA(1c) values could be achieved by CSII as compared to intensive conservative insulin treatment; this could be more pronounced in cases with high initial HbA(1c) values. CSII with short acting insulin analogues could lead to a higher reduction of HbA(1c) values than CSII with human regular insulin. Moreover, the decrease of hypoglycaemic events could be expected in some cases.

Topics: Administration, Cutaneous; Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Infusion Pumps, Implantable; Insulin; Insulin Aspart; Insulin Infusion Systems; Insulin Lispro

Insulin glulisine (Apidra, Sanofi-Aventis), a new and recently approved rapid-acting insulin analogue, mimics the pharmacokinetic and pharmacodynamic profiles of physiological human insulin, but has a rapid onset, peak effect at 1h, and a shorter duration of action (approximately 4 h). Its rapid-action properties are maintained across subject types. Formal clinical evaluations show that insulin glulisine can be administered safely and effectively pre- and postmeal. When injected immediately premeal, insulin glulisine provides superior postprandial blood glucose control compared with regular human insulin (RHI) injected 30 min premeal. These data highlight the flexibility in the dosing schedule with insulin glulisine. Clinical trials have demonstrated that insulin glulisine elicits a greater reduction in glycosylated haemoglobin at end point than RHI, in both type 1 and 2 diabetes mellitus. In addition, the safe administration of insulin glulisine by continuous subcutaneous insulin infusion has been demonstrated in patients with type 1 diabetes. In conclusion, insulin glulisine is an effective, safe and well-tolerated rapid-acting insulin analogue.

Topics: Clinical Trials as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Insulin

In patients with diabetes, the benefit of conventional insulin therapy can be limited due to difficulty in achieving tight glycemic control, which is critical to reducing the risk of long-term diabetes-related complications. The recent development of recombinant analogs of regular human insulin is changing the clinical management of diabetes. One of the newest members of this class of hypoglycemic agents is insulin glulisine, a rapid-acting insulin analog with a pharmacokinetic profile that more closely mimics the natural pattern of insulin secretion than regular human insulin. Subcutaneous administration of insulin glulisine has a faster subcutaneous absorption, a more rapid onset of activity, and a shorter duration of action than regular human insulin. These properties of insulin glulisine allow it to be administered shortly before or soon after meals by subcutaneous injection or by continuous subcutaneous pump infusion. Insulin glulisine effectively controls postprandial glucose excursions in both type 1 and type 2 diabetic patients without increasing the risk of hypoglycemia. One unit of insulin glulisine has the same glucose-lowering effect as one unit of regular human insulin. Insulin glulisine has a favorable safety profile, which is not significantly different from that of regular human insulin. This review summarizes the current data on the clinical efficacy and safety of insulin glulisine in type 1 and type 2 diabetic patients.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin

Aventis Pharma (formerly Hoechst Marion Roussel) is developing insulin glulisine, a fast-acting insulin analog, for the potential treatment of hyperglycemia in both type 1 and 2 diabetes. Aventis has submitted an NDA and an MAA to the FDA and the EMEA, respectively.

Topics: Animals; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Structure-Activity Relationship

To investigate whether zinc-free insulin is an effective treatment option for lipoatrophy.. Controlled, randomized, open-label parallel study in young people with type 1 diabetes, pump treatment and lipoatrophy at injection sites. Participants underwent dermatological examination and evaluation of affected areas using ultrasound and magnetic resonance imaging (MRI). After randomization, half of themswitched to insulin glulisine (intervention group) for 6 months. The control group continued their treatment with zinc-containing insulin and switched to insulin glulisine 6 months later. Both groups were followed-up until month 12. Primary endpoint was the increase of the relative thickness of the subcutaneous fat layer of the most atrophic site at 6 months as documented by MRI.. Fourteen participants were included into the study. While relative thickness of subcutaneous fat tissue was comparable between intervention (-60% [-98.8 - -17.6], n = 7) and control group (-50% [-72.7 - -1.0], P = .511; median (range), n = 7)at baseline, it improved in the intervention (-14.3% [-85.7-83.3] vs -31.3% (-66.7-0), P = .031), but not in the control group (P = .125) after 6 months. At 12 months, relative fat thickness (P = .003), number (P = .015) and size of most atrophic sites (P = .001) were improved in the intervention group. Number (P = .018) and size of most atrophic sites (P = .008) were also reduced in the control group between 6 and 12 months.. Although the present pilot study is based on a small sample, the data give first hint that the use of the zinc-free insulin glulisine may be beneficial in people with diabetes, pump and lipoatrophy.

Topics: Adolescent; Child; Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Infusion Systems; Lipodystrophy; Male; Pilot Projects; Treatment Outcome

According to current knowledge, glulisine insulin (GLU) has a slightly faster onset of action than aspart (ASP) insulin. Therefore, GLU might lead to a better postprandial profile than ASP following the consumption of high-glycemic index (H-GI) meals. The aim of this study was to assess differences in the action of GLU and ASP after the consumption of a H-GI meal in type 1 diabetic children treated with insulin pumps.. FIFTY-SIX TYPE 1 DIABETIC CHILDREN OF MEAN AGE 14.72.0 YEARS WERE INCLUDED IN A RANDOMIZED, DOUBLE-BLIND, TWO-WAY CROSSOVER STUDY.. GLU-ASP and ASP-GLU. They were given a H-GI breakfast for two subsequent days.. The primary outcome was postprandial glycemia (PPG) based on continuous glucose monitoring system and self monitoring of blood glucose levels during 3 h of follow-up. The secondary outcomes were the frequency of hypoglycemia, glucose area under the curve, mean amplitude of glycemic excursion, and glycemic rise.. THERE WERE NO SIGNIFICANT DIFFERENCES BETWEEN THE GROUPS WITH REGARD TO PPG IN THE DETERMINED TIME INTERVALS AS WELL AS WITH RESPECT TO THE SECONDARY OUTCOMES. BETWEEN 60 AND 120MIN AFTER FOOD CONSUMPTION IN BOTH STUDY GROUPS, BLOOD GLUCOSE LEVELS WERE CLOSE TO OR ABOVE 10.0MMOL/L. GLUCOSE PEAKS WERE HIGHER IN THE GLUASP GROUP THAN IN THE ASPGLU GROUP (90MIN: P=0.065; 120 min: P=0.052). Most of the episodes of hypoglycemia were observed after the second hour of follow-up.. No statistically significant difference was found between GLU and ASP with regard to PPG after the consumption of a H-GI breakfast. Neither GLU nor ASP stabilized the glycemic profile after the consumption of a H-GI meal.

Topics: Adolescent; Blood Glucose; Child; Cross-Over Studies; Diabetes Mellitus, Type 1; Double-Blind Method; Female; Glycemic Index; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Male; Postprandial Period; Treatment Outcome

Basal and bolus insulin therapy is required for strict blood control in diabetic patients, which could lead to prevention of vascular complications in diabetes. However, the optimal combination regimen is not well established.. Fifty-nine diabetic patients (49 type 1 and 10 type 2; 52.9 ± 13.3 years old) whose blood glucose levels were uncontrolled (HbA1c  > 6.2%) by combination treatment of basal insulin glargine with multiple daily pre-meal injections of bolus short-acting insulin [aspart (n = 19), lispro (n = 37) and regular human insulin (n = 3)] for at least 8 weeks were enrolled in this study. We examined whether glycaemic control and vascular injury were improved by replacement of short-acting insulin with glulisine. Patient satisfaction was assessed with Diabetes Treatment Satisfaction Questionnaire.. Although bolus and basal insulin doses were almost unchanged before and after replacement therapy, switching to glulisine insulin for 24 weeks significantly decreased level of HbA1c , advanced glycation end products (AGEs), soluble receptor for AGEs (sRAGE), monocyte chemoattractant protein-1 (MCP-1) and urinary albumin excretion. In multiple stepwise regression analysis, change in MCP-1 values from baseline (ΔMCP-1) was a sole determinant of log urinary albumin excretion. ΔAGEs and ΔsRAGE were independently correlated with each other. The relationship between ΔMCP-1 and ΔsRAGE was marginally significant (p = 0.05). Replacement of short-acting insulin by glulisine significantly increased Diabetes Treatment Satisfaction Questionnaire scores.. Our present study suggests that combination therapy of glargine with multiple daily pre-meal injections of glulisine might show superior efficacy in controlling blood glucose, preventing vascular damage and improving treatment satisfaction in diabetic patients.

Topics: Adult; Aged; Biomarkers; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Drug Administration Schedule; Drug Resistance; Drug Therapy, Combination; Female; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin, Long-Acting; Japan; Male; Middle Aged; Patient Satisfaction

Data on the safety of insulin glulisine for type 1 diabetes are limited in paediatric populations. The European post-marketing Observational prospective Cohort study of children with type 1 diabetes treated with APIDRA(®) (OCAPI) study evaluated the safety of insulin glulisine in children aged 6-12 years in real-life clinical practice, with a particular focus on the 6-8 years age group.. OCAPI was an international, multicentre, observational, non-interventional, prospective cohort study, in which 94 participants with type 1 diabetes (6-8 years age group: n=31; 9-12 years age group: n=63) received insulin glulisine for 6 months under normal, local conditions. The primary objective was the incidence of severe hypoglycaemia in all participants.. Overall incidence of severe hypoglycaemia was 6.6 events per 100 persons/year (7.2 and 6.3 events per 100 persons/year in the 6-8 and 9-12 years age groups, respectively). 12 participants (all aged 9-12 years) experienced transient injection-site reactions. No systematic hypersensitivity reactions were reported. Only 1 participant (9-12 years age group) experienced a serious class-effect risk possibly related to insulin glulisine (severe hypoglycaemia requiring an Emergency Department visit). Glycated haemoglobin levels did not change markedly throughout the study, and were inversely proportional to the risk of hypoglycaemia.. Insulin glulisine has a good safety profile in children with type 1 diabetes aged 6-12 years, with generally low rates of severe hypoglycaemia and few adverse reactions. These results are encouraging for its use in paediatric populations.

Topics: Child; Cohort Studies; Diabetes Mellitus, Type 1; Drug Hypersensitivity; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Incidence; Insulin; Male; Prospective Studies

The effects of glargine/glulisine insulin regimen on exercise blood glucose (BG) and strategies to limit exercise-induced hypoglycemia are not well documented. Intermittent high-intensity exercise has been proposed to prevent hypoglycemia, but its effect in participants with type 1 diabetes using glargine/glulisine is unknown.. The study used a repeated-measures design with three randomly ordered exercise conditions. Eleven participants completed 60 min of moderate-intensity exercise at 50% VO(2peak) for all conditions. These conditions varied as follows: participants ingested 0 g of glucose preexercise (0G + MOD), 30 g of glucose preexercise (30G + MOD), or 0 g of glucose preexercise but performed brief high-intensity intervals interspersed every 2 min (0G + MOD/INT) during exercise. If BG fell <4 mmol·L(-1), a 20% dextrose solution was started to maintain BG between 4 and 5 mmol·L(-1).. Consuming 30 g of glucose before exercise (30G + MOD) resulted in a higher preexercise BG (11.7 ± 2.7 mmol·L(-1)) compared with 0 g of glucose before exercise (0G + MOD, 7.8 ± 4.0, and 0G + MOD/INT, 9.2 ± 3.5mmol·L(-1)), P < 0.05. A dextrose infusion was required in 7/11, 4/11, and 1/11 participants for 0G + MOD, 0G + MOD/INT, 30G + MOD conditions, respectively, P < 0.02. The duration and the quantity of dextrose infused were greatest in the 0G + MOD condition, moderate in the to 0G + MOD/INT condition, and minimal in the 30G + MOD condition, P < 0.01.. Our results suggest that both moderate-intensity exercise with a 30-g preexercise glucose beverage or interspersed with intermittent high-intensity sprints may be safe strategies to prevent hypoglycemia in glargine/glulisine users.

Topics: Adult; Biomarkers; Blood Glucose; Diabetes Mellitus, Type 1; Exercise; Exercise Test; Female; Glucose; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Treatment Outcome

In patients with diabetes, intraday glucose variability might predict health outcomes independently from glycosylated hemoglobin (HbA1c).. Our objective was to evaluate patient satisfaction (PS), quality of life (QoL), glycemic control, and variability during insulin intensification to HbA1c below 7.0%.. Eighty-two type 1 and 306 insulin-treated type 2 diabetes patients (47% male; age 54±11 yr; HbA1c=7.8±0.7%) participated in this multicenter, randomized, crossover trial at 52 U.S. centers.. Interventions included insulin glargine plus premeal glulisine (n=192) vs. twice-daily premix 75/25 or 70/30 analog insulin (n=196) for 12 wk and crossed to the alternate arm for 12 wk.. Main outcome measures included PS and QoL questionnaires, 3-d continuous glucose monitoring (CGM), and HbA1c every 4-8 wk.. Mean±se HbA1c change was -0.39±0.09% for glargine-glulisine and -0.05±0.09% for premix (P<0.0001). The PS net benefit scale (0-100) improved from 51.1 to 60.5±1.2 for glargine-glulisine and worsened to 45.4±1.2 for premix (P<0.0001). The PS regimen acceptance scale was comparable (P=0.33). Overall QoL favored glargine-glulisine (P<0.001), as did perceived health (P<0.0001), symptom distress (P<0.0001), general health perceptions (P<0.01), and psychosocial (P<0.02). CGM daily glucose mean, daily glucose sd (glycemic variability), and percent time over 140 mg/dl were lower for glargine-glulisine by 13.1±2.7 mg/dl, 5.9±1.4 mg/dl, and 7.3±1.6%, respectively (all P<0.0001), with no difference in CGM percent time below 70 mg/dl (P=0.09). Symptomatic hypoglycemia rates were comparable. HbA1c, mean CGM daily glucose, and glycemic variability were independent predictors of PS net benefit.. Patient satisfaction was impacted more positively by improved QoL, reduced glucose variability, and better glycemic control with a basal-bolus regimen than negatively by the burden of additional injections, thereby facilitating insulin intensification and the ability to achieve HbA1c below 7.0%.

Topics: Adult; Aged; Blood Glucose; Body Weight; Cross-Over Studies; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Patient Satisfaction; Quality of Life; Surveys and Questionnaires

We compared the efficacy and safety of insulin glulisine with insulin lispro as part of a basal-bolus regimen in children and adolescents with type 1 diabetes.. Overall, 572 children and adolescents (4-17 years old) using insulin glargine or neutral protamine Hagedorn insulin as basal insulin were enrolled in a 26-week, multicenter, open, centrally randomized, parallel-group, noninferiority study. Subjects were randomized to receive glulisine (n = 277) or lispro (n= 295) 0-15 min premeal.. Baseline-to-endpoint hemoglobin A1c changes were similar between the two insulins: adjusted mean change (glulisine vs. lispro), 0.10% versus 0.16%; between-treatment difference (glulisine-lispro), &minsu;0.06, 95% confidence interval (-0.24; 0.12); and prespecified noninferiority margin, 0.4%. Overall, for all age groups together, the percentage of patients achieving American Diabetes Association age-specific A1c targets at endpoint was significantly higher (P = 0.039) with glulisine (38.4%) versus lispro (32.0%). From Month 4 to endpoint, both "all" and "severe" symptomatic hypoglycemia rates were similar (3.10 vs. 2.91 and 0.06 vs. 0.07 events/patient-month, respectively). Frequency and type of adverse events, serious adverse events, or hypoglycemia reported as serious adverse events were similar between both groups.. Glulisine was as effective as lispro in baseline-to-endpoint A1c change, and both treatments were similarly well tolerated.

Topics: Adolescent; Child; Child, Preschool; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Lispro; Logistic Models; Male

In a previous pilot study comparing insulin glulisine (GLU) with insulin aspart (ASP) administered by continuous subcutaneous insulin infusion (CSII), GLU-treated patients did show a trend toward fewer catheter occlusions compared with ASP-treated patients. Here we performed a randomized open-label, three-way crossover, controlled multicenter study comparing GLU with ASP and insulin lispro (LIS).. Subjects with type 1 diabetes were allocated to one of three treatment orders-GLU-ASP-LIS, ASP-LIS-GLU, or LIS-GLU-ASP-with each insulin used for 13 weeks. The study was designed to demonstrate the superiority of GLU over ASP and LIS on unexplained hyperglycemia and/or perceived infusion set occlusion. A prespecified P value of 0.025 was considered significant to correct for multiple testing.. Percentages of subjects with at least one unexplained hyperglycemia and/or infusion set occlusion were not significantly different between GLU and ASP (68.4% [62.7-74.1%] vs. 62.1% [56.2-68.1%], P = 0.04) and GLU and LIS (68.4% [62.7-74.1%] vs. 61.3% [55.4-67.3%], P = 0.03). No differences were seen in hemoglobin A1c at end point, most points of the seven-point glucose curves, severe hypoglycemia, and symptomatic ketoacidosis. The overall rate of hypoglycemia with a plasma glucose level below 70 mg/dL per patient-year was significantly different between GLU and ASP (73.84 vs. 65.01, P = 0.008) and GLU and LIS (73.84 vs. 62.69, P < 0.001). Insulin doses remained unchanged during the trial.. GLU was not superior to ASP and LIS with no significant difference seen among GLU, ASP, and LIS in CSII use with respect to unexplained hyperglycemia and/or perceived catheter set occlusion. GLU was associated with a higher frequency of symptomatic hypoglycemia, possibly because of slight overdosing, as previous trials suggested lower insulin requirements when GLU is initiated in type 1 diabetes.

Topics: Adult; Cross-Over Studies; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Infusion Systems; Insulin Lispro; Male; Middle Aged; Statistics as Topic; Time Factors

Evaluation of a new disposable insulin pen and injection habits of diabetes patients in everyday clinical practice. Injection devices (pens) for insulin application play a major role in treatment acceptance and adherence in insulin-treated diabetes patients. The mechanical disposable pen SoloStar containing the insulin analogs glargine or glulisine (each 100 IE/ml) provides modern design with user-friendly handling features.. In two independent, non-interventional, observational studies conducted nation-wide between April and December 2007 in outpatient practices, patients with diabetes newly instructed on how to use the pen were interviewed by their trainers (physicians, diabetes consultants) after approx. 6-8 weeks of pen use to give feedback on technical deficiencies, handling problems with the pen, injection habits, as well as on pen properties. Trainers were also asked to assess pen properties and particularly to document the time required for pen training. The evaluation applied a grading system similar to that used in German schools (1: very good; 6: very insufficient/failed). Furthermore, trainers were asked to retrospectively record any adverse events occurring during the observational period.. A total of 2,412 trainers from 1,626 centres and 8,428 patients (80% type 2) participated in the studies. In each study 0.5% of patients reported 41 and 19 technical problems with the pen, respectively. Similarly 3% of patients from each study reported handling problems. Recommended changes of needles and safety checks of the pen before each injection were performed by 40% and max. 25% of the patients, respectively. The features of the new disposable pen were all rated "very good" to "good" by the majority of patients and trainers. The best rated features were usability, dose adjustment and the low effort for the dose release. Pen training of patients were rated as "very simple" or "simple" by the training staff and average instruction time was reported not to exceed more than 10 minutes for the majority of patients. In 19 patients (0.2%) a total of 34 adverse events were documented.. The results of these two observational studies showed no relevant technical deficiencies and handling problems associated with the new disposable pen in everyday clinical practice. Ease of use and little time required for pen training may contribute to a high acceptance and satisfaction by the patients and training staff. Injection habits, however, indicated that patients did not well comply with recommendations given for needle changes and safety tests.

Topics: Adult; Aged; Attitude of Health Personnel; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Disposable Equipment; Equipment Failure; Female; General Practice; Germany; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Patient Education as Topic; Patient Satisfaction; Surveys and Questionnaires

The rapid-acting insulin analogue insulin glulisine (glulisine) was compared with insulin lispro (lispro) for efficacy and safety in Japanese patients with type 1 diabetes mellitus (T1DM), using insulin glargine (glargine) as basal insulin.. This was an open, randomized, parallel-group, comparative non-inferiority study. The primary efficacy measure was change in adjusted mean haemoglobin A1c (HbA1c) from baseline to endpoint. Safety and treatment satisfaction using the Diabetes Treatment Satisfaction Questionnaire (DTSQ) were also assessed. Patients were treated for 28 weeks with either glulisine or lispro administered 0-15 min before a meal. Doses were titrated to obtain 2-h postprandial plasma glucose (2h-PPG) of 7.11-9.55 mmol/l (128-172 mg/dl). All patients were concomitantly treated with glargine at bedtime, titrated to obtain a fasting (prebreakfast) plasma glucose level of 5.27-7.11 mmol/l (95-128 mg/dl).. Baseline mean HbA1c values were similar for the glulisine (n = 132) and lispro (n = 135) groups (7.44 and 7.50% respectively). From baseline to endpoint, adjusted mean HbA1c increased by 0.10% in the glulisine group and by 0.04% in the lispro group. Non-inferiority of glulisine compared with lispro was shown. There were no significant differences between glulisine and lispro in adjusted mean 2h-PPG [glulisine, 9.06 mmol/l (163 mg/dl) vs. lispro, 8.13 mmol/l (146 mg/dl); p = 0.065] and change in adjusted mean daily rapid-acting insulin dose (glulisine, 0.26 U vs. lispro, 0.26 U; p = 0.994) at study endpoint. There was a significant difference for change in adjusted mean daily basal insulin dose from baseline to study endpoint (glulisine, -0.54 U vs. lispro, 0.26 U; p = 0.013). The most common serious adverse events were hypoglycaemia-related events (hypoglycaemia, hypoglycaemic seizure and hypoglycaemic coma) with no difference observed between the two groups [glulisine, 6.8% (9/132) vs. lispro, 4.4% (6/135); p = 0.437]. No noteworthy differences were observed for change in insulin antibodies from baseline to endpoint. Assessment of treatment satisfaction score and perceived frequency of hyperglycaemia and hypoglycaemia by DTSQ showed no changes from baseline in either group.. Glulisine was as effective as lispro with respect to change in HbA1c and was well tolerated when used in combination with glargine in Japanese patients with T1DM.

Topics: Adult; Aged; Asian People; Blood Glucose; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Japan; Male; Middle Aged; Patient Satisfaction; Young Adult

To compare the end-organ metabolic effects of insulin glulisine (glulisine), insulin lispro (lispro) and regular human insulin (RHI) in patients with type 1 diabetes mellitus.. Eighteen patients with type 1 diabetes mellitus (mean age 36.9 +/- 8.6 years, BMI 23.6 +/- 2.8 kg/m(2), haemoglobin A(1c) 7.4 +/- 0.9%) were randomized in this single-centre, double-blind, three-period cross-over, standard Latin-square, euglycaemic glucose clamp trial. Patients received sequential, primed stepwise intravenous infusions of glulisine, lispro or RHI (infusion rates were increased in a stepwise manner from an initial rate of 0.33 [180 min] to 0.66 [180 min] and 1.00 [180 min] mU/kg/min). The primary variables were the suppression of endogenous glucose production (S(EGP)) and glucose uptake (GU).. Mean basal endogenous glucose production (EGP) was 1.88, 2.12 and 2.12 mg/kg/min for glulisine, lispro and RHI respectively. Mean (+/-s.e.) maximum absolute S(EGP) (adjusted for basal EGP) was -1.64 +/- 0.06, -1.72 +/- 0.05 and -1.56 +/- 0.05 mg/kg/min respectively. Mean (+/-s.e.) maximum absolute increase in GU (adjusted for basal GU) was 6.46 +/- 0.26, 6.23 +/- 0.24 and 6.72 +/- 0.24 mg/kg/min respectively. There were no clinically relevant differences between the three insulin treatments with respect to serum insulin, free fatty acid (FFA), glycerol or lactate levels. No serious adverse events and no episodes of severe hypoglycaemia were reported.. This study shows that glulisine, lispro and RHI have similar effects on S(EGP), GU, FFA, glycerol and lactate levels, providing evidence for similar end-organ metabolic effects.

Topics: Adolescent; Adult; Aged; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 1; Double-Blind Method; Fatty Acids, Nonesterified; Female; Glucose Clamp Technique; Glycerol; Humans; Hypoglycemic Agents; Infusions, Intravenous; Insulin; Insulin Lispro; Lactic Acid; Male; Middle Aged

Topics: Adult; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Glucose Clamp Technique; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Kinetics; Male; Metabolic Clearance Rate

This twelve-week, European, multicenter, controlled, open-label, randomized (1 : 1), parallel-group trial compared the safety of insulin glulisine with insulin as part used in continuous subcutaneous insulin infusion. Patients with type 1 diabetes (n=59) and continuous subcutaneous insulin infusion experience (mean values: HbA1c 6.9 % [insulin glulisine: 6.8 % VS. insulin as part: 7.1 %]; age 45.8 years; body mass index 26.0 kg/m2) were enrolled. HbA1c levels at endpoint (insulin glulisine: 7.0 % VS. insulin as part: 7.2 %), daily insulin doses, blood glucose profiles and adverse event rates were similar in both groups. The median (minimum-maximum) catheter occlusion rate was low for insulin glulisine and insulin as part (0 [0 - 0.7] VS. 0 [0 - 1.1] occlusions/month. Unexplained hyperglycemia occurred in six insulin glulisine-treated patients and twelve insulin as part-treated patients. Patients were expected to change their catheters every 2 days (15 changes/month); the catheter change rate was similar for insulin glulisine and insulin as part (14.1 VS. 14.8 changes/month). The frequency of infusion site reactions and hypoglycemia, and the time between catheter changes were similar for both insulin forms. Diabetic ketoacidosis was not reported. This study supports the safety of insulin glulisine in continuous subcutaneous insulin infusion administered via an external pump in type 1 diabetes.

Topics: Adult; Catheters, Indwelling; Diabetes Mellitus, Type 1; Drug Administration Routes; Equipment Failure; Female; Humans; Hyperglycemia; Hypoglycemia; Infusion Pumps; Insulin; Insulin Aspart; Insulin Infusion Systems; Male; Middle Aged

The aim of this study was to investigate the pharmacokinetics, postprandial blood glucose excursions, and safety of insulin glulisine as compared with regular human insulin (RHI), both administered immediately before meals in pediatric patients with type 1 diabetes.. A total of 10 children (aged 5-11 years) and 10 adolescents (aged 12-17 years) were enrolled in a randomized, single-center, single-dose, double-blind, cross-over study. The blood glucose of fasting patients was stabilized with intravenous insulin, following which patients received 0.15 IU/kg of subcutaneously injected insulin glulisine or RHI 2 min before a weight-adjusted standardized liquid meal.. For insulin glulisine versus RHI, maximum insulin concentrations (58 vs. 33 microIU/ml, P < 0.05) and initial insulin concentrations (insulin [area under the curve] AUC(0-2h) 5,232 vs. 2,994 microIU.min(-1).ml(-1), P < 0.05; data are geometric means) were higher after insulin glulisine than RHI. Both time to maximum insulin concentration (54 vs. 66 min) and mean residence time (88 vs. 137 min, P < 0.05) were shorter with insulin glulisine versus RHI. Postprandial glucose excursions after insulin glulisine were lower than after RHI (glucose AUC(0-6h) 641 vs. 801 mg.h(-1).dl(-1), P < 0.05). The pharmacokinetic profile for insulin glulisine was similar for children and adolescents, whereas the pharmacokinetic profile for RHI demonstrated a 64% higher concentration in adolescents. Insulin glulisine was safe and well tolerated.. The rapid-acting properties of insulin glulisine that have been previously demonstrated in adults are also observed in children and adolescents with type 1 diabetes. Further, these initial data indicate that insulin glulisine is safe and well tolerated in this patient population.

Topics: Adolescent; Area Under Curve; Child; Child, Preschool; Cross-Over Studies; Diabetes Mellitus, Type 1; Double-Blind Method; Female; Humans; Hypoglycemic Agents; Insulin; Male

Insulin glulisine (glulisine), a human insulin analogue with a rapid-acting time-action profile, has been developed to fulfil the mealtime (bolus) insulin requirement in patients with diabetes. The aim of this multinational, multi-centre, controlled, open-label, randomized, parallel-group study was to compare the efficacy and safety of insulin glulisine (glulisine) to that of insulin lispro (lispro) in adults diagnosed with Type 1 diabetes. Of the 683 patients randomized, 672 received treatment (339 patients received glulisine, 333 patients received lispro). Over the 26-week study, a similar reduction in mean HbA1c occurred in both groups (adjusted mean change from baseline -0.14% in both groups). The basal insulin dose was relatively unchanged from baseline in the glulisine group but increased in the lispro group (glulisine: 0.12 IU vs. lispro: 1.82 IU; p = 0.0001). As a consequence, total daily insulin dose decreased in the glulisine group but increased in the lispro group (glulisine: -0.86 IU vs. lispro: 1.01 IU; p = 0.0123). There was no relevant difference between the two groups in the reporting of symptomatic hypoglycaemia (overall, nocturnal and severe). This study demonstrates that glulisine provides equivalent glycaemic control to lispro. The clinical relevance of any difference in total daily insulin dose remains to be established.

Topics: Adult; Antibodies, Bacterial; Blood Glucose; Diabetes Mellitus, Type 1; Drug Hypersensitivity; Escherichia coli; Female; Humans; Insulin; Insulin Antibodies; Male; Middle Aged

The patient was 82-year-old man with type 1 diabetes mellitus. He had been using insulin degludec (IDeg) and insulin glulisine (IGlu) for treatment. He was admitted to our hospital due to diabetic ketoacidosis. As he started eating after recovery, we restarted intensive insulin therapy for glycemic control. Although he had eaten almost whole meals, his fasting blood glucose was extremely low, and the existence of nocturnal hypoglycemia was apparent. We reduced the dose and changed the injection time (evening→morning) of IDeg. We also stopped the evening IGlu injection; however, his nocturnal hypoglycemia did not improve. We decided to switch IDeg to insulin glargine U300 and to attach an intermittently scanned continuous glucose monitor (isCGM). His nocturnal hypoglycemia improved three days later. Since he had chronic heart failure and premature ventricular contractions, we used a Holter electrocardiogram to investigate the difference in arrythmia during hypoglycemia and non-hypoglycemia. As a result, the number of premature ventricular contractions was apparently high during hypoglycemia. In the present case, which involved an elderly patient with type 1 diabetes mellitus, chronic heart failure and nocturnal hypoglycemia, switching IDeg to insulin glargine U300 improved nocturnal hypoglycemia. IDeg differs from insulin glargine U300 in that it has a fatty acid side chain, which leads IDeg to combine with serum albumin. We thought that the increased level of free fatty acid due to hypoglycemia was competing against albumin combined IDeg, which increased free IDeg, and as a result, encouraged hypoglycemia.

Topics: Aged; Aged, 80 and over; Chronic Disease; Diabetes Mellitus, Type 1; Heart Failure; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Ventricular Premature Complexes

Glycogenic hepatopathy (GH) is a rare complication of poorly controlled type 1 diabetes mellitus (T1DM). We present a 19-year-old woman with T1DM and autoimmune thyroiditis who admitted to our department because of abrupt onset intermittent abdominal pain in the right upper quadrant accompanied by laboratory evidence of acute anicteric hepatitis. Physical examination revealed significant hepatomegaly but the common imagining studies were negative. Following exclusion of common causes of acute hepatitis and because of the presence of smooth muscle antibodies in a young female patient with already established two autoimmune diseases, a liver biopsy was performed in order to exclude the potential presence of autoimmune hepatitis. However, liver histology showed typical findings of GH. Intense treatment targeting strict glycemic control resulted in normalisation of liver biochemistry. This case underlines that GH should be considered as a rare cause of acute hepatitis in T1DM patients with poor glycemic control.

Topics: Diabetes Mellitus, Type 1; Female; Glycogen; Hepatomegaly; Humans; Hypoglycemic Agents; Infusions, Subcutaneous; Insulin; Liver Function Tests; Young Adult

We evaluated the efficacy and safety of insulin glulisine (GLU) used for continuous s.c. insulin infusion (CSII) in 20 children with type 1 diabetes after 1 year of GLU treatment. There were no significant differences in mean plasma glucose before breakfast and before dinner between before and after using GLU, but the levels after breakfast and after dinner significantly improved, from 192.5 ± 31.7 to 162.0 ± 27.3 mg/dL for breakfast, and from 191.1 ± 33.3 to 161.1 ± 24.5 mg/dL for dinner (P < 0.01). Mean hemoglobin A1c significantly decreased (from 8.0 ± 0.8 to 7.7 ± 0.8%, P < 0.05), and the mean frequency of hypoglycemia significantly reduced after using GLU (from 8.3 ± 4.9 to 6.0 ± 3.4/month, P < 0.05). In conclusion, the use of GLU rather than other rapid-acting analogues for CSII might be an effective treatment option in children with type 1 diabetes.

Topics: Child; Child, Preschool; Diabetes Mellitus, Type 1; Drug Administration Schedule; Female; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Male; Treatment Outcome

Several studies have found improved glycemic control with continuous subcutaneous insulin infusion compared with multiple daily insulin injections for patients with type 1 diabetes, albeit for a relatively short-period of follow-up. This prospective study presents for the first time the optimization of glycemic control with insulin pumps in a cohort of Greek patients with type 1 diabetes for a 3-year follow-up period during the socioeconomic crisis in Greece.. Ninety-four patients, previously on intensified basal-bolus insulin therapy with poor glycemic control, were initially recruited. Glycosylated hemoglobin (HbA1c), hypoglycemic and diabetic ketoacidosis episodes, pump-related side effects, lipidemic profile, 24-h urine albumin excretion, body mass index, blood pressure, and total daily insulin requirements (bolus and basal) were recorded during the 3-year follow-up. Statistical analysis was initially conducted for the entire study population and after body mass index and gender stratification.. Seventy-nine patients completed the study. A statistically significant decrease of HbA1c level (P < 0.0001) was observed at the end of Year 1 and was retained for the following years for the whole population. Similarly, significantly fewer hypoglycemic episodes occurred during the follow-up period (P < 0.0001) compared with study entry. Insulin pump treatment was not accompanied with weight changes across all body mass index strata.. Continuous subcutaneous insulin infusion achieved almost optimal glycemic control, reduced the number of hypoglycemic episodes without weight gain, and was well tolerated for the whole study period. Finally, this therapeutic approach was accompanied with lower daily insulin requirements.

Topics: Adult; Cohort Studies; Diabetes Complications; Diabetes Mellitus, Type 1; Drug Monitoring; Female; Follow-Up Studies; Glycated Hemoglobin; Greece; Hospitals, Urban; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Infusion Systems; Insulin Lispro; Male; Middle Aged; Outpatient Clinics, Hospital; Prospective Studies

Topics: Adolescent; Diabetes Mellitus, Type 1; Female; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Lipodystrophy

This study determined the optimal timing of insulin bolus administration in relation to meal consumption in adolescents and adults with type 1 diabetes.. Twenty-three subjects participated in this crossover study consisting of three treatment arms: delivering an insulin glulisine bolus by insulin pump 20 min prior to a meal ("PRE"), immediately before the meal ("START"), and 20 min after meal initiation ("POST"). Blood glucose levels were measured every 30 min for a total of 240 min post-meal initiation. Mean blood glucose levels at 1 and 2 h after meal initiation, blood glucose area under the curve (AUC), and maximum blood glucose levels were analyzed.. At both 60 and 120 min after meal initiation, the PRE arm showed significantly lower glycemic excursions than the START arm (P = 0.0029 and 0.0294, respectively) and the POST arm (P = 0.001 and 0.0408, respectively). Glycemic AUC was significantly less in the PRE arm versus both the START and POST arms (159.5 +/- 58.9 mg/dL vs. 187.0 +/- 43.1 mg/dL [P = 0.0297] and 184.5 +/- 33.2 mg/dL [P = 0.0463], respectively). Peak blood glucose levels were significantly lower in the PRE arm compared to the START arm (P = 0.0039) and the POST arm (P = 0.0027).. A bolus of rapid-acting insulin 20 min prior to a meal results in significantly better postprandial glucose control than when the meal insulin bolus is given just prior to the meal or 20 min after meal initiation.

Topics: Adolescent; Adult; Blood Glucose; Child; Colorado; Cross-Over Studies; Diabetes Mellitus, Type 1; Drug Administration Schedule; Female; Humans; Hyperglycemia; Insulin; Insulin Infusion Systems; Male; Self Care; Young Adult

Topics: Adult; Diabetes Mellitus, Type 1; Drug Hypersensitivity; Humans; Immune Tolerance; Insulin; Male

SoloSTAR (SR) is a new pre-filled insulin pen device for administration of insulin glargine and insulin glulisine. This article reports on the usability of SR, as reported by healthcare professionals (HCPs) and participants, in clinical practice in Australia.. Individuals with Type 1 or Type 2 diabetes were eligible for this 3-month observational survey. Participants were supplied with the insulin glargine SR pens, the instruction leaflet and a toll-free helpline number. Training was offered to all participants. Independent telephone interviews were conducted with participants and HCPs after 6-10 weeks of use of SR.. Overall, 150 HCPs across 93 sites supported this survey. Of these, 65 HCPs (14 doctors; 51 diabetes educators, covering 1669 patients) provided feedback, with the remaining 85 HCPs not responding. All HCPs rated participant training as 'very easy' or 'easy', and most reported that SR had, in their opinion, made training easier (85%) and quicker (98%). Most of the 536 participants reported that ease of learning to use (98%), ease of using (98%) and features (> or = 89%) of SR were 'excellent' or 'good'. SR had positive impacts on various psychological aspects for people with diabetes, including helping overcome reluctance to use insulin, and increasing confidence in their ability to manage their diabetes using insulin.. In this non-randomized, non-interventional, open-label, observational survey of clinical practice, HCPs reported that SR was easy to teach and easy to use for people with diabetes. People with diabetes reported that SR was easy to use and rated specific features of SR highly. Further follow-up surveys and comparative studies in clinical practice are needed to confirm these findings and to determine the impact of SR in diabetes management.

Topics: Adult; Aged; Australia; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Equipment Design; Equipment Safety; Female; Health Educators; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Interviews as Topic; Male; Middle Aged; Physicians; Syringes

Insulin glulisine is a rapid-acting human insulin analogue that has a faster onset of action and shorter duration of action than regular human insulin (RHI) in patients with type 1 or 2 diabetes mellitus and is efficacious in controlling prandial blood glucose levels in these patients. In large, well designed trials in patients with type 1 diabetes, insulin glulisine demonstrated a similar degree of glycaemic control, as measured by glycosylated haemoglobin (HbA(1c)) levels, to RHI after 12 weeks and insulin lispro after 26 weeks. Pre-meal insulin glulisine was also more effective than RHI at controlling 2-hour post-prandial glucose excursions in patients with type 1 or 2 diabetes over a period of 12 weeks. In patients with type 2 diabetes, insulin glulisine induced significantly greater reductions in HbA(1c) levels and 2-hour post-breakfast and post-dinner blood glucose levels than RHI over a period of 26 weeks. Insulin glulisine was generally well tolerated by patients with type 1 or 2 diabetes and had a similar safety profile to insulin lispro or RHI. Severe hypoglycaemia was experienced by similar proportions of insulin glulisine or comparator insulin (insulin lispro or RHI) recipients with type 1 or type 2 diabetes.

Topics: Adult; Area Under Curve; Clinical Trials as Topic; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Middle Aged; Molecular Sequence Data; Recombinant Proteins; Treatment Outcome

Topics: Blood Glucose; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting; Time Factors; Weight Loss

Topics: Administration, Oral; Blood Glucose; Clinical Trials, Phase III as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Injections, Intravenous; Insulin; Quality of Life; Time Factors