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Sample records for basal insulin glargine

  1. Comparison of Insulin Detemir and Insulin Glargine for Hospitalized Patients on a Basal-Bolus Protocol

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    Sondra Davis

    2017-04-01

    Full Text Available BACKGROUND: The primary purpose of this study is to determine whether insulin detemir is equivalent to insulin glargine in controlling hyperglycemia for the adult hospitalized patient on a basal-bolus treatment regimen. METHODS: A retrospective study was conducted at two acute care hospitals within the same health system. Patients from both facilities who were initiated on a basal-bolus subcutaneous insulin regimen were included in the study. The basal-bolus regimen consisted of three components: basal, bolus, and corrective insulin with only the data from the first seven days analyzed. Once the basal-bolus protocol was initiated, all previous glycemic agents were discontinued. The target glycemic goal of the study was 100–180 mg/dL. RESULTS: In both groups, 50% of the patients had achieved the target glycemic control goal (100–180 mg/dL by day 2 (p = 0.3. However, on the seventh or last day of basal-bolus treatment, whichever came first, 36.36% of patients receiving insulin detemir (n = 88 achieved the blood glucose reading goal compared to 52.00% in patients receiving insulin glargine (n = 100 (p = 0.03. This corresponded to an adjusted odds ratio of 2.12 (1.08 to 4.15, p = 0.03. The adjusting variables were provider type, whether the patient was hospitalized within 30 days prior and diagnosis of stroke. The mean blood glucose readings for the insulin glargine and the insulin detemir groups while on basal-bolus therapy were 200 mg/dL and 215 mg/dL, respectively (p = 0.05. The total number of blood glucose readings less than 70 mg/dL and less than 45 mg/dL was very low and there were no differences in number of episodes with hypoglycemia between the two groups. CONCLUSION: There was not a statistical difference between the two groups at 2 days, however there was on the seventh day or the last day of basal-bolus treatment. There were nonsignificant hypoglycemia events between basal insulin groups and the results for the last or seventh day

  2. Insulin glargine overdose

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    Fatma Sari Dogan

    2012-01-01

    Full Text Available Insulin glargine is a long acting novel recombinant human insulin analogue indicated to improve glycemic control, in adults and children with type 1 diabetes mellitus and in adults with type 2 diabetes mellitus. The time course of action of insulins including insulin glargine may vary between individuals and/or within the same individual. Insulin glargine is given as a 24-h dosing regimen and has no documented half-life or peak effect. Hypoglycemia is the most common adverse effect of insulin, including insulin glargine. As with all insulins, the timing of hypoglycemia may differ among various insulin formulations. We present a case of a 76-year-old male insulin-dependent diabetic patient with refractory hypoglycemia secondary to an intentional overdose of insulin glargine. We would like to highlight the necessity of prolonging IV glucose infusion, for a much longer period than expected from pharmacokinetic properties of these insulin analogues after intentional massive overdose.

  3. Modern approach to basal-bolus therapy with glargine and glulisine insulin analoguesin various age groups

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    N N Volevodz

    2013-03-01

    Full Text Available DCCT (Diabetes Control and Complications Trial study established that intensified insulin therapy in multiple daily injections (MDI or continuous insulin infusion (CSII regimens substantially reduce both development and progression of complications in patients with type 1 diabetes mellitus (T1DM as compared to conventional insulin therapy. Insulin analogues possess better pharmacokinetic and pharmacodynamic characteristics than unmodified human insulin agents. These characteristics are beneficial for management of diabetes mellitus, allowing better glycemic outcomes with lower incidence of hypoglycemia.Current review discusses specifics of therapy with glargine (Lantus® and glulisine (Apidra® insulin analogues. Authors analyzed available to date results from corresponding clinical trials in children, adolescents and adults. Pharmacoeconomic aspects and matters of dosage of glargine and glulisine are further addressed.

  4. Cost comparison of insulin glargine with insulin detemir in a basal-bolus regime with mealtime insulin aspart in type 2 diabetes in Germany

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    Dippel, Franz-Werner

    2010-01-01

    Full Text Available Objective: To compare the treatment costs of insulin glargine (IG; Lantus® to detemir (ID; Levemir®, both combined with bolus insulin aspart (NovoRapid® in type 2 diabetes (T2D in Germany. Methods: Cost comparison was based on data of a 1-year randomised controlled trial [1]. IG was administered once daily and ID once (57% of patients or twice daily (43% according to treatment response. At the end of the trial, mean daily basal insulin doses were 0.59 U/kg (IG and 0.82 U/kg (ID. Aspart doses were 0.32 U/kg (IG and 0.36 U/kg (ID. Costs were calculated from the German statutory health insurance (SHI perspective using official 2008 prices. Sensitivity analyses were performed to test robustness of the results. Results: Annual basal and bolus insulin costs per patient were € 1,473 (IG and € 1,940 (ID. The cost of lancets and blood glucose test strips were € 1,125 (IG and € 1,286 (ID. Annual costs for needles were € 393 (IG and € 449 (ID. The total annual cost per patient of administering IG was € 2,991 compared with € 3,675 for ID, translating into a 19% annual cost difference of € 684/patient. Base case results were robust to varying assumptions for insulin dose, insulin price, change in weight and proportion of ID once daily administrations. Conclusion: IG and ID basal-bolus regimes have comparative safety and efficacy, based on the Hollander study, IG however may represent a significantly more cost saving option for T2D patients in Germany requiring basal-bolus insulin analogue therapy with potential annual cost savings of € 684/patient compared to ID.

  5. Clinical Pharmacokinetics and Pharmacodynamics of Insulin Glargine 300 U/mL.

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    Clements, Jennifer N; Threatt, Tiffaney; Ward, Eileen; Shealy, Kayce M

    2016-10-04

    Concentrated insulin analogs have recently been approved and are available for clinical use in the management of diabetes mellitus. One new product is insulin glargine U-300 (Sanofi), a basal concentrated insulin of 300 U/mL. Several studies have been conducted and completed evaluating blood samples for the pharmacokinetics of insulin glargine U-300 and euglycemic clamp procedures for the pharmacodynamics. This concentrated insulin has a low within-day variability and high day-to-day reproducibility, allowing for a more constant and prolonged duration of action, compared with insulin glargine U-100 (100 U/mL). Insulin glargine U-300 is equally effective, when compared with insulin glargine U-100 for glycemic control in patients with type 1 and 2 diabetes mellitus. Insulin glargine U-300 has a similar efficacy profile to insulin glargine U-100 for glycemic control, yet with lower rates of nocturnal and severe hypoglycemia. Insulin glargine U-300 can be considered an acceptable basal insulin for patients with type 1 and 2 diabetes mellitus, and it has a potential role among patients who are naïve to insulin therapy or require titration of basal insulin. Titration of insulin glargine U-300 would result in less volume and a lower risk of hypoglycemia, compared with insulin glargine U-100. This article evaluates and summarizes the pharmacokinetics and pharmacodynamics of insulin glargine U-300, for patients with type 1 or 2 diabetes mellitus, and summarizes its application to clinical practice.

  6. Insulin Glargine 300 U/mL: A Review in Diabetes Mellitus.

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    Blair, Hannah A; Keating, Gillian M

    2016-03-01

    Insulin glargine 300 U/mL (Toujeo(®)) is a long-acting basal insulin analogue approved for the treatment of diabetes mellitus. Insulin glargine 300 U/mL has a more stable and prolonged pharmacokinetic/pharmacodynamic profile than insulin glargine 100 U/mL (Lantus(®)), with a duration of glucose-lowering activity exceeding 24 h. In several 6-month phase III trials, insulin glargine 300 U/mL achieved comparable glycaemic control to that seen with insulin glargine 100 U/mL in patients with type 1 or type 2 diabetes, albeit with consistently higher daily basal insulin requirements. These improvements in glycaemic control were maintained during longer-term (12 months) treatment. Insulin glargine 300 U/mL was generally associated with a lower risk of nocturnal hypoglycaemia than insulin glargine 100 U/mL in insulin-experienced patients with type 2 diabetes, while the risk of nocturnal hypoglycaemia did not significantly differ between treatment groups in insulin-naïve patients with type 2 diabetes or in patients with type 1 diabetes. To conclude, once-daily subcutaneous insulin glargine 300 U/mL is an effective and generally well tolerated basal insulin therapy option for patients with type 1 or type 2 diabetes.

  7. Concentrated insulins: the new basal insulins

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    Lamos EM

    2016-03-01

    Full Text Available Elizabeth M Lamos,1 Lisa M Younk,2 Stephen N Davis3 1Division of Endocrinology, Diabetes and Nutrition, 2Department of Medicine, University of Maryland School of Medicine, 3Department of Medicine, University of Maryland Medical Center, Baltimore, MD, USA Introduction: Insulin therapy plays a critical role in the treatment of type 1 and type 2 diabetes mellitus. However, there is still a need to find basal insulins with 24-hour coverage and reduced risk of hypoglycemia. Additionally, with increasing obesity and insulin resistance, the ability to provide clinically necessary high doses of insulin at low volume is also needed. Areas covered: This review highlights the published reports of the pharmacokinetic (PK and glucodynamic properties of concentrated insulins: Humulin-R U500, insulin degludec U200, and insulin glargine U300, describes the clinical efficacy, risk of hypoglycemic, and metabolic changes observed, and finally, discusses observations about the complexity of introducing a new generation of concentrated insulins to the therapeutic market. Conclusion: Humulin-R U500 has a similar onset but longer duration of action compared with U100 regular insulin. Insulin glargine U300 has differential PK/pharmacodynamic effects when compared with insulin glargine U100. In noninferiority studies, glycemic control with degludec U200 and glargine U300 is similar to insulin glargine U100 and nocturnal hypoglycemia is reduced. Concentrated formulations appear to behave as separate molecular entities when compared with earlier U100 insulin analog compounds. In the review of available published data, newer concentrated basal insulins may offer an advantage in terms of reduced intraindividual variability as well as reducing the injection burden in individuals requiring high-dose and large volume insulin therapy. Understanding the PK and pharmacodynamic properties of this new generation of insulins is critical to safe dosing, dispensing, and administration

  8. Le medicament du mois. Insuline glargine (Lantus).

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    Scheen, André

    2004-01-01

    Insulin glargine (Lantus) is a human insulin analogue produced by recombinant DNA technology and recently launched by Aventis. Modification of the human insulin molecule at position A21 and at the C-terminus of the B-chain results in the formation of a stable compound that is soluble at pH 4.0, but forms amorphous microprecipitates in subcutaneous tissue (pH > 7,4) from which small amounts of insulin glargine are gradually released. The plasma concentration versus time profile of insulin glar...

  9. Effectiveness and tolerability of treatment intensification to basal–bolus therapy in patients with type 2 diabetes on previous basal insulin-supported oral therapy with insulin glargine or supplementary insulin therapy with insulin glulisine: the PARTNER observational study

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    Pfohl M

    2015-11-01

    Full Text Available Martin Pfohl,1 Thorsten Siegmund,2 Stefan Pscherer,3 Katrin Pegelow,4 Jochen Seufert5 1Medizinische Klinik I, Evangelisches Bethesda-Klinikum GmbH, Duisburg, Germany; 2Städtisches Klinikum München GmbH, Klinikum Bogenhausen, III. Medizinische Abteilung, München, Germany; 3Klinisches Diabeteszentrum Südostbayern, Innere Medizin – Diabetologie, Traunstein, Germany; 4Sanofi-Aventis Deutschland GmbH, Berlin, Germany; 5Medizinische Universitätsklinik, Klinik für Innere Medizin II, Abteilung für Endokrinologie und Diabetologie, Freiburg, Germany Background: Due to the progressive nature of type 2 diabetes mellitus (T2DM, antidiabetic treatment needs to be continuously intensified to avoid long-term complications. In T2DM patients on either basal insulin-supported oral therapy (BOT or supplementary insulin therapy (SIT presenting with HbA1c values above individual targets for 3–6 months, therapy should be intensified. This study investigated effectiveness and tolerability of an intensification of BOT or SIT to a basal–bolus therapy (BBT regimen in T2DM patients in daily clinical practice. Methods: This noninterventional, 8-month, prospective, multicenter study evaluated parameters of glucose control, occurrence of adverse events (eg, hypoglycemia, and acceptance of devices in daily clinical practice routine after 12 and 24 weeks of intensifying insulin therapy to a BBT regimen starting from either preexisting BOT with insulin glargine (pre-BOT or preexisting SIT with ≥3 daily injections of insulin glulisine (pre-SIT. Results: A total of 1,530 patients were documented in 258 German medical practices. A total of 1,301 patients were included in the full analysis set (55% male, 45% female; age median 64 years; body mass index median 30.8 kg/m2; pre-BOT: n=1,072; pre-SIT: n=229, and 1,515 patients were evaluated for safety. After 12 weeks, HbA1c decreased versus baseline (pre-BOT 8.67%; pre-SIT 8.46% to 7.73% and 7.66%, respectively (Δ mean

  10. Insulin glargine 300 U/ml in the management of diabetes: clinical utility and patient perspectives

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    de Galan BE

    2016-10-01

    Full Text Available Bastiaan E de Galan Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands Abstract: There is ongoing interest in optimizing basal insulin treatment by developing insulins with a flat pharmacological profile, a long duration of action (typically beyond 24 hours and minimum day-to-day variation. Glargine-300 is a modified form of the long-acting insulin analog glargine in that it has been concentrated at 300 units/mL rather than the conventional 100 units/mL. Glargine-300 has a longer duration of action and a flatter pharmacological profile than original glargine-100. This property allows for more flexibility around the timing of administration, when injected once per day. Open-label studies in patients with diabetes have shown that treatment with glargine-300 achieves comparable glycemic control compared to treatment with glargine-100, albeit with consistently higher insulin requirements. These studies also showed that treatment with glargine-300 was associated with lower risks of nocturnal hypoglycemia in patients with type 2 diabetes, particularly those already on insulin, whereas data are mixed in insulin-naïve patients with type 2 diabetes or in patients with type 1 diabetes. Treatment with glargine-300 did not appear to affect the risk of overall hypoglycemia, whereas studies lacked sufficient power to investigate the effect on the risk of severe hypoglycemia. Future studies need to establish the role of glargine-300 in the treatment of diabetes alongside the other new long-acting insulin analog, insulin degludec, which was recently introduced to the market. Keywords: insulin glargine-300, type 1 diabetes, type 2 diabetes, hypoglycemia, HbA1c, patient-reported outcomes

  11. Once-daily basal insulin glargine versus thrice-daily prandial insulin lispro in people with type 2 diabetes on oral hypoglycaemic agents (APOLLO): an open randomised controlled trial

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    Bretzel, R.G.; Nuber, U.; Landgraf, W.

    2008-01-01

    BACKGROUND: As type 2 diabetes mellitus progresses, oral hypoglycaemic agents often fail to maintain blood glucose control and insulin is needed. We investigated whether the addition of once-daily insulin glargine is non-inferior to three-times daily prandial insulin lispro in overall glycaemic c...

  12. Long-term insulin glargine therapy in type 2 diabetes mellitus: a focus on cardiovascular outcomes

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    Joseph JJ

    2015-01-01

    Full Text Available Joshua J Joseph, Thomas W Donner Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA Abstract: Cardiovascular disease is the leading cause of mortality in type 2 diabetes mellitus. Hyperinsulinemia is associated with increased cardiovascular risk, but the effects of exogenous insulin on cardiovascular disease progression have been less well studied. Insulin has been shown to have both cardioprotective and atherosclerosis-promoting effects in laboratory animal studies. Long-term clinical trials using insulin to attain improved diabetes control in younger type 1 and type 2 diabetes patients have shown improved cardiovascular outcomes. Shorter trials of intensive diabetes control with high insulin use in higher risk patients with type 2 diabetes have shown either no cardiovascular benefit or increased all cause and cardiovascular mortality. Glargine insulin is a basal insulin analog widely used to treat patients with type 1 and type 2 diabetes. This review focuses on the effects of glargine on cardiovascular outcomes. Glargine lowers triglycerides, leads to a modest weight gain, causes less hypoglycemia when compared with intermediate-acting insulin, and has a neutral effect on blood pressure. The Outcome Reduction With Initial Glargine Intervention (ORIGIN trial, a 6.2 year dedicated cardiovascular outcomes trial of glargine demonstrated no increased cardiovascular risk. Keywords: glargine, insulin, type 2 diabetes, cardiovascular disease, cardiovascular outcomes

  13. Comparison of insulin glargine and NPH insulin in the treatment of type 2 diabetes: a review of clinical studies.

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    Duckworth, William; Davis, Stephen N

    2007-01-01

    Despite the evidence-based approach to management of Type 2 diabetes outlined in current diabetes practice guidelines, a large proportion of patients are achieving suboptimal glycemic control. A substantial amount of data exists comparing insulin glargine and neutral protamine Hagedorn (NPH) insulin for long-acting basal insulin coverage. The objective of this systematic review was to provide a balanced appraisal of existing clinical evidence and to determine the appropriate step in therapy for insulin glargine or NPH insulin. Relevant English language articles from 1996 to 2005 were identified through searches of the National Center for Biotechnology Information PubMed database. Search terms included neutral protamine Hagedorn, NPH, insulin glargine, insulin therapy, Type 2 diabetes, insulin analogs, HOE901, and HOE-901. Studies were compared regarding designs, primary and secondary efficacy parameters, glycosylated hemoglobin A1c (A1C), fasting plasma glucose (FPG), incidence of hypoglycemia, and other safety assessments. Six original multicenter, randomized, open-label, parallel-group trials conducted in Europe or the United States, ranging in duration from 4 to 52 weeks, met the inclusion criteria. Two additional analyses represented a subanalysis and a study extension. All of the studies compared insulin glargine with NPH insulin given once or twice daily as monotherapy or in conjunction with oral antidiabetic agents in patients with Type 2 diabetes. Based on available evidence, insulin glargine has shown equal clinical efficacy to that of NPH insulin and similar reductions in A1C and is associated with similar or lower FPG levels. Recent studies also have demonstrated that less frequent nocturnal hypoglycemia incidence is associated with insulin glargine compared with NPH insulin. The known pathophysiology of Type 2 diabetes and the need for basal insulin treatment are presented as rationale for comparison of these insulins.

  14. In vitro metabolic and mitogenic signaling of insulin glargine and its metabolites.

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    Mark R Sommerfeld

    Full Text Available BACKGROUND: Insulin glargine (Lantus is a long-acting basal insulin analog that demonstrates effective day-long glycemic control and a lower incidence of hypoglycemia than NPH insulin. After subcutaneous injection insulin glargine is partly converted into the two main metabolites M1 ([Gly(A21]insulin and M2 ([Gly(A21,des-Thr(B30]insulin. The aim of this study was to characterize the glargine metabolites in vitro with regard to their insulin receptor (IR and IGF-1 receptor (IGF1R binding and signaling properties as well as their metabolic and mitogenic activities. METHODS: The affinity of human insulin, insulin glargine and its metabolites to the IR isoforms A and B or IGF1R was analyzed in a competitive binding assay using SPA technology. Receptor autophosphorylation activities were studied via In-Cell Western in CHO and MEF cells overexpressing human IR-A and IR-B or IGF1R, respectively. The metabolic response of the insulins was studied as stimulation of lipid synthesis using primary rat adipocytes. Thymidine incorporation in Saos-2 cells was used to characterize the mitogenic activity. CONCLUSIONS: The binding of insulin glargine and its metabolites M1 and M2 to the IR were similar and correlated well with their corresponding autophosphorylation and metabolic activities in vitro. No differences were found towards the two IR isoforms A or B. Insulin glargine showed a higher affinity for IGF1R than insulin, resulting in a lower EC(50 value for autophosphorylation of the receptor and a more potent stimulation of thymidine incorporation in Saos-2 cells. In contrast, the metabolites M1 and M2 were significantly less active in binding to and activation of the IGF1R and their mitogenicity in Saos-2 cells was equal to human insulin. These findings strongly support the idea that insulin glargine metabolites contribute with the same potency as insulin glargine to blood glucose control but lead to significantly reduced growth-promoting activity.

  15. [INSULIN GLARGINE 300 U/mL (TOUJEO®)].

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    Scheen, A J

    2016-02-01

    This article presents a new formulation of insulin glargine concentrated at 300 U/mL (Gla-300). It is commercialized under the trade name of Toujeo® in an optimized pre-filled SoloStar™ pen for the treatment of type 1 and type 2 diabetes in adults. Besides a threefold higher concentration compared to the classical insulin Lantus® (100 U/mL or Gla-100), both pharmacokinetic and pharmacodynamic profiles of Gla-300 are flatter and longer (more than 24 hours) and have a lesser intra-/inter-variability, which makes them more reproducible. Overall, Toujeo® offers the same hypoglycaemic efficacy and the same safety profile when compared with Lantus®. However, a lower risk of hypoglycaemia, especially at night, a slightly smaller weight gain and a better flexibility in the time of injection have been reported. The two insulin formulations are not bioequivalent and the daily insulin requirement is slightly higher with insulin Gla-300 than with insulin Gla-100. The shift from an already available basal insulin towards Toujeo® may require a dose adjustment and a reinforcement of blood glucose monitoring.

  16. rDNA insulin glargine U300 – a critical appraisal

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    Wang F

    2016-12-01

    Full Text Available Fei Wang,1 Stefanie Zassman,1 Philip A Goldberg2 1Department of Pharmacy Practice, School of Pharmacy, University of Connecticut, Storrs, CT, USA; 2Department of Internal Medicine, Section of Endocrinology, Yale University School of Medicine, New Haven, CT, USA Background: As the first once-daily basal insulin analog, insulin glargine 100 U/mL (Gla‑100; Lantus® rapidly evolved into the most commonly prescribed insulin therapy worldwide. However, this insulin has clinical limitations. The approval of new basal insulin analogs in 2015 has already started to alter the prescribing landscape.Objective: To review the available evidence on the clinical efficacy and safety of a more concentrated insulin glargine (recombinant DNA origin injection 300 U/mL (Gla-300 compared to insulin Gla-100 in patients with type 1 and type 2 diabetes mellitus (T1DM and T2DM.Methods: The following electronic databases were searched: PubMed and MEDLINE (using Ovid platform, Scopus, BIOSIS, and Google Scholar through June 2016. Conference proceedings of the American Diabetes Association (2015–2016 were reviewed. We also manually searched reference lists of pertinent reviews and trials.Results: A total of 6 pivotal Phase III randomized controlled trials known as the EDITION series were reviewed. All of these trials (n=3,500 were head-to-head comparisons evaluating the efficacy and tolerability of Gla-300 vs Gla-100 in a diverse population with T1DM and T2DM. These trials were of 6 months duration with a 6-month safety extension phase.Conclusion: Gla-300 was as effective as Gla-100 for improving glycemic control over 6 months in all studies, with a lower risk of nocturnal hypoglycemia significant only in insulin-experienced patients with T2DM. Overall, patients on Gla-300 required 10%–18% more basal insulin, but with less weight gain compared with Gla-100. Keywords: basal insulin, glargine 300 U/mL, glargine 100 U/mL

  17. Insulin glargine in the management of diabetes mellitus: an evidence-based assessment of its clinical efficacy and economic value

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    Rhian Clissold

    2007-11-01

    Full Text Available Rhian Clissold1, Steve Clissold21Endocrinology Department, Frenchay Hospital, Bristol, UK; 2Content Ed Net Communications S.L., Madrid, SpainIntroduction: Diabetes is a chronic disease associated with high morbidity and mortality, which represents a major public health concern. Interventions that can enhance patient care and reduce clinic visits will not only relieve some of this burden, they will also improve patient QOL and wellbeing.Aims: This review assesses the evidence for the use of insulin glargine in type 1 and type 2 diabetes mellitus.Evidence review: Once-daily insulin glargine has a prolonged, peakless activity profile, making it a candidate as a long-acting (basal insulin. In combination with bolus insulin to cover prandial glucose surges, it facilitates a more physiologic approach to patient management. Evidence from large, randomized, controlled clinical trials in patients with type 1 diabetes has confirmed its effectiveness and tolerability relative to neutral protamine hagedorn (NPH insulin, with a tendency toward causing less hypoglycemia. In patients with type 2 diabetes requiring insulin therapy, once-daily insulin glargine has proven to be clinically superior to NPH insulin in terms of providing at least as effective glycemic control, but with significantly fewer episodes of nocturnal hypoglycemia. A variety of economic analyses have confirmed the cost effectiveness of insulin glargine in type 1 and type 2 diabetes and in particular it was shown to be significantly superior to NPH insulin.Clinical value: Insulin glargine has established itself as a first-line choice in patients with type 1 diabetes, including children (>6 years and adolescents, and is a recommended treatment option. In patients with type 2 diabetes it is clearly associated with less hypoglycemia than NPH insulin, and this may help overcome one of the major barriers to starting insulin therapy in this class of patient. Thus, insulin glargine is a valuable

  18. Switching from basal or basal-bolus insulin to biphasic insulin aspart 30: Results from the Indian cohort of the A 1 chieve study

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    Arpandev Bhattacharyya

    2014-01-01

    Full Text Available Aim: To determine the safety and efficacy of biphasic insulin aspart 30 (BIAsp 30 therapy in the Indian patients with type 2 diabetes previously on basal or basal-bolus insulin therapies. Materials and Methods: Patients switching from insulin glargine, neutral protamine Hagedorn (NPH insulin, or basal-bolus insulin to BIAsp 30 in the Indian cohort of the A 1 chieve study were included. Safety and efficacy of treatment was evaluated over 24 weeks. Results: A total of 422 patients (pre-study basal-bolus insulin, 49; NPH insulin, 157; insulin glargine, 216 switched to BIAsp 30. Pre-study insulin doses were 0.61 ± 0.26 U/kg, 0.34 ± 0.2 U/kg and 0.40 ± 0.21 U/kg and the mean week 24 BIAsp 30 doses were 0.50 ± 0.21 U/kg, 0.35 ± 0.15 U/kg and 0.42 ± 0.16 U/kg in the prior basal-bolus insulin, NPH insulin and insulin glargine groups, respectively. No serious adverse drug reactions, major or nocturnal hypoglycemia were reported. The proportion of patients experiencing overall hypoglycemia was significantly lower from baseline (5.6% to week 24 (1.0% in the pre-study insulin-glargine group and appeared to be lower in pre-study NPH insulin and basal-bolus insulin groups. Glycemic control improved significantly from baseline week 24 in the pre-study NPH insulin and insulin-glargine groups (P < 0.001, while it appeared to improve in the pre-study basal-bolus group. Quality of life was positively impacted after 24 weeks in all 3 groups. Conclusion: The switch from basal or basal-bolus insulin to BIAsp 30 was safe, well tolerated and improved the glycemic control in this Indian cohort.

  19. Switching from basal or basal-bolus insulin to biphasic insulin aspart 30: Results from the Indian cohort of the A1 chieve study

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    Bhattacharyya, Arpandev; Shetty, Raman; Rajkumar, C; Bantwal, Ganapathi

    2014-01-01

    Aim: To determine the safety and efficacy of biphasic insulin aspart 30 (BIAsp 30) therapy in the Indian patients with type 2 diabetes previously on basal or basal-bolus insulin therapies. Materials and Methods: Patients switching from insulin glargine, neutral protamine Hagedorn (NPH) insulin, or basal-bolus insulin to BIAsp 30 in the Indian cohort of the A1 chieve study were included. Safety and efficacy of treatment was evaluated over 24 weeks. Results: A total of 422 patients (pre-study basal-bolus insulin, 49; NPH insulin, 157; insulin glargine, 216) switched to BIAsp 30. Pre-study insulin doses were 0.61 ± 0.26 U/kg, 0.34 ± 0.2 U/kg and 0.40 ± 0.21 U/kg and the mean week 24 BIAsp 30 doses were 0.50 ± 0.21 U/kg, 0.35 ± 0.15 U/kg and 0.42 ± 0.16 U/kg in the prior basal-bolus insulin, NPH insulin and insulin glargine groups, respectively. No serious adverse drug reactions, major or nocturnal hypoglycemia were reported. The proportion of patients experiencing overall hypoglycemia was significantly lower from baseline (5.6%) to week 24 (1.0%) in the pre-study insulin-glargine group and appeared to be lower in pre-study NPH insulin and basal-bolus insulin groups. Glycemic control improved significantly from baseline week 24 in the pre-study NPH insulin and insulin-glargine groups (P < 0.001), while it appeared to improve in the pre-study basal-bolus group. Quality of life was positively impacted after 24 weeks in all 3 groups. Conclusion: The switch from basal or basal-bolus insulin to BIAsp 30 was safe, well tolerated and improved the glycemic control in this Indian cohort. PMID:25143902

  20. Glycemic control with insulin glargine plus insulin glulisine versus premixed insulin analogues in real-world practices: a cost-effectiveness study with a randomized pragmatic trial design.

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    Levin, Philip A; Zhang, Quanwu; Mersey, James H; Lee, Francis Y; Bromberger, Lee A; Bhushan, Madhu; Bhushan, Rajat

    2011-07-01

    Cost can be an important consideration, along with safety and efficacy, in deciding the most appropriate treatment for patients with type 2 diabetes. Both basal-bolus and premixed insulin analogue regimens are widely used in clinical practice; however, limited information is available regarding cost-effectiveness. The goal of this study was to compare glycemic control, cost-effectiveness, and quality of life effects of insulin glargine plus insulin glulisine (glargine/glulisine) versus premixed insulin analogues in real-world clinical practice. Adults with type 2 diabetes (glycosylated hemoglobin [HbA(1c)] ≥7.0%) at 3 US endocrinology centers were randomly assigned to receive either glargine/glulisine or premixed insulin analogues and continued treatment following the centers' usual practice. HbA(1c), weight, insulin dose, concomitant oral antidiabetic drug (OAD) usage, and hypoglycemia were evaluated at baseline and 3, 6, and 9 months. Medication costs, including costs for all insulin or OAD regimens, were estimated using published wholesale acquisition costs. A total of 197 patients were randomized to receive glargine/glulisine therapy (n = 106) or premixed analogue therapy (n = 91). Overall, the mean age was 56 years, the mean duration of diabetes was 13 years, with a mean HbA(1c) of 9.25% and mean BMI of 35.8 kg/m(2) at baseline. Patients randomized to receive glargine/glulisine had a greater mean HbA(1c) reduction from baseline (-2.3%) than patients receiving a premixed analogue regimen (-1.7%). Adjusted mean follow-up HbA(1c) was 6.9% versus 7.5%, respectively (difference, -0.59%; P < 0.01). The glargine/glulisine group also used a lower mean number of OADs (0.86 vs 1.14; difference, -0.28; P = 0.04) but had a higher weight (240 vs 235 lb; difference, 4.55 lb; P = 0.03) than the premixed analogue group at follow-up. There were no significant differences in daily insulin dose and rates of hypoglycemia. Overall medication costs per 1.0% reduction in HbA(1c

  1. The cost-effectiveness of exenatide twice daily (BID) vs insulin lispro three times daily (TID) as add-on therapy to titrated insulin glargine in patients with type 2 diabetes

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    Gordon, J.; McEwan, P.; Sabale, U.; Kartman, B.; Wolffenbuttel, B. H. R.

    2016-01-01

    Objective: To evaluate the cost-effectiveness of exenatide twice daily (BID) vs bolus insulin lispro three times daily (TID) as add-on therapy when glycemic control is sub-optimal with titrated basal insulin glargine and metformin. Methods: The analysis was based on the recent 4B Study, which compar

  2. Potential formula for the calculation of starting and incremental insulin glargine doses: ALOHA subanalysis.

    Directory of Open Access Journals (Sweden)

    Takashi Kadowaki

    Full Text Available BACKGROUND: Pragmatic methods for dose optimization are required for the successful basal management in daily clinical practice. To derive a useful formula for calculating recommended glargine doses, we analyzed data from the Add-on Lantus® to Oral Hypoglycemic Agents (ALOHA study, a 24-week observation of Japanese type 2 diabetes patients. METHODOLOGY/PRINCIPAL FINDINGS: The patients who initiated insulin glargine in basal-supported oral therapy (BOT regimen (n = 3506 were analyzed. The correlations between average changes in glargine dose and HbA1c were calculated, and its regression formula was estimated from grouped data categorized by baseline HbA1c levels. Starting doses of the background-subgroup achieving the HbA1c target with a last-observed dose above the average were compared to an assumed optimal starting dose of 0.15 U/kg/day. The difference in regression lines between background-subgroups was examined. A formula for determining the optimal starting and titration doses was thereby derived. The correlation coefficient between changes in dose and HbA1c was -0.9043. The estimated regression line formula was -0.964 × change in HbA1c+2.000. A starting dose of 0.15 U/kg/day was applicable to all background-subgroups except for patients with retinopathy (0.120 U/kg/day and/or with eGFR<60 mL/min/1.73 m(2 (0.114 U/kg/day. Additionally, women (0.135 U/kg/day and patients with sulfonylureas (0.132 U/kg/day received a slightly decreased starting dose. CONCLUSIONS/SIGNIFICANCE: We suggest a simplified and pragmatic dose calculation formula for type 2 diabetes patients starting glargine BOT optimal daily dose at 24 weeks  =  starting dose (0.15×weight + incremental dose (baseline HbA1c - target HbA1c+2. This formula should be further validated using other samples in a prospective follow-up, especially since several patient groups required lower starting doses.

  3. Meta-Analysis of Maternal and Neonatal Outcomes Associated with the Use of Insulin Glargine versus NPH Insulin during Pregnancy

    Directory of Open Access Journals (Sweden)

    Jacques Lepercq

    2012-01-01

    Full Text Available As glargine, an analog of human insulin, is increasingly used during pregnancy, a meta-analysis assessed its safety in this population. A systematic literature search identified studies of gestational or pregestational diabetes comparing use of insulin glargine with human NPH insulin, with at least 15 women in both arms. Data was extracted for maternal outcomes (weight at delivery, weight gain, 1st/3rd trimester HbA1c, severe hypoglycemia, gestation/new-onset hypertension, preeclampsia, and cesarean section and neonatal outcomes (congenital malformations, gestational age at delivery, birth weight, macrosomia, LGA, 5 minute Apgar score >7, NICU admissions, respiratory distress syndrome, neonatal hypoglycemia, and hyperbilirubinemia. Relative risk ratios and weighted mean differences were determined using a random effect model. Eight studies of women using glargine (331 or NPH (371 were analyzed. No significant differences in the efficacy and safety-related outcomes were found between glargine and NPH use during pregnancy.

  4. Translating structure to clinical properties of an ideal basal insulin.

    Science.gov (United States)

    Unnikrishnan, A G; Bantwal, Ganapathi; Sahay, R K

    2014-01-01

    There is a need for ideal basal insulin which can overcome the unmet need of a truly once daily insulin, with a flat peakless profile. Useful for all types of patients Insulin degludec is next generation insulin with a unique mode of protraction of forming soluble multi-hexamers and slow continuous absorption giving it a flat profile compared to the existing basal insulin. In patients with type 1 diabetes or with type 2 diabetes, at steady-state, the mean terminal half-life of insulin degludec was 25 hours, i.e., approximately twice as long as for insulin glargine (half-life of 12.1 hours). In once-daily dosing regimen it reaches steady state after approximately 3 days. The duration of action of insulin degludec was estimated to be beyond 42 hours in euglycaemic clamp studies and this gives the unique opportunity of flexible time dosing which is not an available option with the existing basal insulin. The glucose-lowering effect is evenly distributed across a 24-hour dosing interval with insulin degludec having 4 times lower variability than insulin glargine. This is an important attribute given the narrow therapeutic window of insulin and the goal of achieving night time and inter-prandial glycaemic control without increasing the risk for hypoglycaemia, a goal that is challenging given the variability of absorption and lower PK half-lives of current basal insulin products. The combination of the ultra-long, flat and stable profile with an improved hour-to-hour and day-to-day variability could present an improved risk-benefit trade-off with the lower risk of hypoglycaemia, allowing for targeting improved levels of glycaemic control.

  5. Health economic evaluations comparing insulin glargine with NPH insulin in patients with type 1 diabetes: a systematic review

    Directory of Open Access Journals (Sweden)

    Dippel Franz-Werner

    2011-10-01

    Full Text Available Abstract Background Compared to conventional human basal insulin (neutral protamine Hagedorn; NPH the long-acting analogue insulin glargine (GLA is associated with a number of advantages regarding metabolic control, hypoglycaemic events and convenience. However, the unit costs of GLA exceed those of NPH. This study aims to systematically review the economic evidence comparing GLA with NPH in basal-bolus treatment (intensified conventional therapy; ICT of type 1 diabetes in order to facilitate informed decision making in clinical practice and health policy. Methods A systematic literature search was performed for the period of January 1st 2000 to December 1st 2009 via Embase, Medline, the Cochrane Library, the databases GMS (German Medical Science and DAHTA (Deutsche Agentur für Health Technology Assessment, and the abstract books of relevant international scientific congresses. Retrieved studies were reviewed based on predefined inclusion criteria, methodological and quality aspects. In order to allow comparison between studies, currencies were converted using purchasing power parities (PPP. Results A total of 7 health economic evaluations from 4 different countries fulfilled the predefined criteria: 6 modelling studies, all of them cost-utility analyses, and one claims data analysis with a cost-minimisation design. One cost-utility analysis showed dominance of GLA over NPH. The other 5 cost-utility analyses resulted in additional costs per quality adjusted life year (QALY gained for GLA, ranging from € 3,859 to € 57,002 (incremental cost effectiveness ratio; ICER. The cost-minimisation analysis revealed lower annual diabetes-specific costs in favour of NPH from the perspective of the German Statutory Health Insurance (SHI. Conclusions The incremental cost-utility-ratios (ICER show favourable values for GLA with considerable variation. If a willingness-to-pay threshold of £ 30,000 (National Institute of Clinical Excellence, UK is adopted

  6. Comparison of the Efficacy and Safety of Insulin Glargine and Insulin Detemir with NPH Insulin in Children and Adolescents with Type 1 Diabetes Mellitus Receiving Intensive Insulin Therapy

    OpenAIRE

    Dündar, Bumin Nuri; Dündar, Nihal; Eren, Erdal

    2010-01-01

    Objective: The purpose of this study was to compare the efficacy and safety of insulin glargine and detemir with NPH insulin in children and adolescents with type 1 diabetes mellitus (DM). Methods: Thirty four children and adolescents with type 1 DM (mean age 12.7 ± 3.4 years, diabetes duration 5.4 ± 3.0 years) were included in the study. All patients had been receiving intensive insulin therapy with insulin aspart and NPH for at least 6 months before switching from NPH to insulin glargine (G...

  7. Treatment with the long-acting insulin analogues detemir or glargine during pregnancy in women with type 1 diabetes

    DEFF Research Database (Denmark)

    Callesen, Nicoline F; Mathiesen, Jonathan Michael; Ringholm, Lene

    2013-01-01

    .046). No perinatal deaths were observed. One offspring in each group was born with a major congenital malformation. Conclusions: Glycaemic control and pregnancy outcome were comparable in women using insulin detemir or glargine, except for a lower prevalence of large for gestational age infants in women on glargine...

  8. Effect of insulin glargine on glycemic control in adolescents with type 1-diabetes

    Directory of Open Access Journals (Sweden)

    Hassan M. Mona

    2015-06-01

    Conclusion: The present study encourages the use of insulin glargine in the presence of significant hypoglycemia and glucose variability, with close monitoring of diet and weight. Cost effectiveness and effect on HbA1c and quality of life need further longitudinal studies with larger numbers.

  9. 口服降糖药联合甘精胰岛素及餐前一次门冬胰岛素的治疗达标研究——1+1研究%Efficacy of the addition of a single bolus of insulin glulisine in combination with basal insulin glargine and oral antidiabetic drugs

    Institute of Scientific and Technical Information of China (English)

    天津市"1+1研究"协作组

    2011-01-01

    目的 观察2型糖尿病患者经口服降糖药联合甘精胰岛素治疗仍未达标时,于餐前增加1次门冬胰岛素的有效性、安全性和可行性.方法 采用多中心、开放、自身对照的方法.59例经口服降糖药及甘精胰岛素治疗而糖化血红蛋白(Hb)A1c>6.5%但<9%的患者,于主餐前加用门冬胰岛素治疗16周.结果 16周后,患者HbA1c由治疗前的(8.04±0.58)%降至(6.78±0.30)%(P<0.01),其中13例(22.03%)达到≤6.5%,43例(72.88%)达到<7.0%.早餐前、午餐前及晚餐前注射门冬胰岛素组3餐后血糖均较前明显降低,HbA1c分别为(6.70±0.29)%,(6.80±0.32)%及(6.90±0.21)%.患者低血糖发生率为0.38次/(患者·年),无夜间低血糖和严重低血糖事件发生.患者平均体重及体重指数均明显下降.结论 对于口服降糖药联合甘精胰岛素治疗血糖控制欠佳的2型糖尿病患者,于主餐前增加1次门冬胰岛素可以有效、安全地降低患者血糖,提高达标率,且具有较高可行性.%Objective To investigate the efficacy,safety and feasibility of the addition of a single bolus of insulin glulisine before meal, in combination with basal insulin glargine and oral antidiabetic drugs (OADs) in the treatment of patients with type 2 diabetes. Methods 59 patients with type 2 diabetes who were suboptimally controlled (HbA1c 6.5%-9.0% )on their previous glargine and OADs regimen were included in this 16 weeks, multicentre, open-label and self-control study. A single injection of glulisine was added,at main mealtime,to their existing therapy. Results HbA1c was decreased from (8.04 ±0.58)% to (6.78 ±0.30) % after 16 weeks(P <0.01 ). 13 patients(22.03% ) obtained the target of HbA1c ≤6.5%,43 patients (72.88%)obtained the target of HbA1c <7.0%. Glulisine given at breakfast,lunch or dinner was equally effective in controlling plasma glucose level, and the HbA1c was ( 6.70 ± 0.29 ) %, ( 6.80 ±0.32 ) %, (6.90 ± 0.21 ) % separately. The

  10. Low within- and between-day variability in exposure to new insulin glargine 300 U/ml.

    Science.gov (United States)

    Becker, R H A; Nowotny, I; Teichert, L; Bergmann, K; Kapitza, C

    2015-03-01

    To characterize the variability in exposure and metabolic effect of insulin glargine 300 U/ml (Gla-300) at steady state in people with type 1 diabetes (T1DM). A total of 50 participants with T1DM underwent two 24-h euglycaemic clamps in steady-state conditions after six once-daily administrations of 0.4 U/kg Gla-300 in a double-blind, randomized, two-treatment, two-period, crossover clamp study. Participants were randomized to receive Gla-300 as a standard cartridge formulation in the first treatment period, and as a formulation with enhanced stability through polysorbate-20 addition in the second treatment period, or vice versa. This design allowed the assessment of bioequivalence between formulations and, subsequently, within- and between-day variability. The cumulative exposure and effect of Gla-300 developed linearly over 24 h, and were evenly distributed across 6- and 12-h intervals. Diurnal fluctuation in exposure (within-day variability) was low; the peak-to-trough ratio of insulin concentration profiles was swing and peak-to-trough fluctuation were high: the between-day within-subject coefficients of variation for total systemic exposure (area under the serum insulin glargine concentration time curve from time 0 to 24 h after dosing) and maximum insulin concentration were 17.4% [95% confidence interval (CI) 15-21] and 33.4% (95% CI 28-41), respectively. Reproducibility of the metabolic effect was lower than that of exposure. Gla-300 provides predictable, evenly distributed 24-h coverage as a result of low fluctuation and high reproducibility in insulin exposure, and appears suitable for effective basal insulin use. © 2014 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

  11. Exposure to excess insulin (glargine) induces type 2 diabetes mellitus in mice fed on a chow diet.

    Science.gov (United States)

    Yang, Xuefeng; Mei, Shuang; Gu, Haihua; Guo, Huailan; Zha, Longying; Cai, Junwei; Li, Xuefeng; Liu, Zhenqi; Cao, Wenhong

    2014-06-01

    We have previously shown that insulin plays an important role in the nutrient-induced insulin resistance. In this study, we tested the hypothesis that chronic exposure to excess long-acting insulin (glargine) can cause typical type 2 diabetes mellitus (T2DM) in normal mice fed on a chow diet. C57BL/6 mice were treated with glargine once a day for 8 weeks, followed by evaluations of food intake, body weight, blood levels of glucose, insulin, lipids, and cytokines, insulin signaling, histology of pancreas, ectopic fat accumulation, oxidative stress level, and cholesterol content in mitochondria in tissues. Cholesterol content in mitochondria and its association with oxidative stress in cultured hepatocytes and β-cells were also examined. Results show that chronic exposure to glargine caused insulin resistance, hyperinsulinemia, and relative insulin deficiency (T2DM). Treatment with excess glargine led to loss of pancreatic islets, ectopic fat accumulation in liver, oxidative stress in liver and pancreas, and increased cholesterol content in mitochondria of liver and pancreas. Prolonged exposure of cultured primary hepatocytes and HIT-TI5 β-cells to insulin induced oxidative stress in a cholesterol synthesis-dependent manner. Together, our results show that chronic exposure to excess insulin can induce typical T2DM in normal mice fed on a chow diet.

  12. Addition of insulin glargine or NPH insulin to metformin monotherapy in poorly controlled type 2 diabetic patients decreases IGF-I bioactivity similarly

    NARCIS (Netherlands)

    A.J. Varewijck (Aimee); J.A.M.J.L. Janssen (Joseph); M. Vähätalo (M.); L.J. Hofland (Leo); S.W.J. Lamberts (Steven); H. Yki-Jarvinen (Hannele)

    2012-01-01

    textabstractAims/hypothesis The aim of this study was to compare IGFI bioactivity 36 weeks after the addition of insulin glargine (A21Gly,B31Arg,B32Arg human insulin) or NPH insulin to metformin therapy in type 2 diabetic patients who had poor glucose control under metformin monotherapy. Methods In

  13. Disruption of KEX1 gene reduces the proteolytic degradation of secreted two-chain Insulin glargine in Pichia pastoris.

    Science.gov (United States)

    Sreenivas, Suma; Krishnaiah, Sateesh M; Shyam Mohan, Anil H; Mallikarjun, Niveditha; Govindappa, Nagaraja; Chatterjee, Amarnath; Sastry, Kedarnath N

    2016-02-01

    Insulin glargine is a slow acting analog of insulin used in diabetes therapy. It is produced by recombinant DNA technology in different hosts namely E. coli and Pichia pastoris. In our previous study, we have described the secretion of fully folded two-chain Insulin glargine into the medium by over-expression of Kex2 protease. The enhanced levels of the Kex2 protease was responsible for the processing of the glargine precursor with in the host. Apart from the two-chain glargine product we observed a small proportion of arginine clipped species. This might be due to the clipping of arginine present at the C-terminus of the B-chain as it is exposed upon Kex2 cleavage. The carboxypeptidase precursor Kex1 is known to be responsible for clipping of C-terminal lysine or arginine of the proteins or peptides. In order to address this issue we created a Kex1 knock out in the host using Cre/loxP mechanism of targeted gene deletion. When two-chain glargine was expressed in the Kex1 knock out host of P. pastoris GS115 the C-terminal clipped species reduced by ∼80%. This modification further improved the process by reducing the levels of product related impurities.

  14. Evaluation of the cost effectiveness of exenatide versus insulin glargine in patients with sub-optimally controlled Type 2 diabetes in the United Kingdom

    Directory of Open Access Journals (Sweden)

    Tetlow Anthony P

    2008-08-01

    Full Text Available Abstract Objective Exenatide belongs to a new therapeutic class in the treatment of diabetes (incretin mimetics, allowing glucose-dependent glycaemic control in Type 2 diabetes. Randomised controlled trial data suggest that exenatide is as effective as insulin glargine at reducing HbA1c in combination therapy with metformin and sulphonylureas; with reduced weight but higher incidence of adverse gastrointestinal events. The objective of this study is to evaluate the cost effectiveness of exenatide versus insulin glargine using RCT data and a previously published model of Type 2 diabetes disease progression that is based on the United Kingdom Prospective Diabetes Study; the perspective of the health-payer of the United Kingdom National Health Service. Methods The study used a discrete event simulation model designed to forecast the costs and health outcome of a cohort of 1,000 subjects aged over 40 years with sub-optimally-controlled Type 2 diabetes, following initiation of either exenatide, or insulin glargine, in addition to oral hypoglycaemic agents. Sensitivity analysis for a higher treatment discontinuation rate in exenatide patients was applied to the cohort in three different scenarios; (1 either ignored or (2 exenatide-failures excluded or (3 exenatide-failures switched to insulin glargine. Analyses were undertaken to evaluate the price sensitivity of exenatide in terms of relative cost effectiveness. Baseline cohort profiles and effectiveness data were taken from a published randomised controlled trial. Results The relative cost-effectiveness of exenatide and insulin glargine was tested under a variety of conditions, in which insulin glargine was dominant in all cases. Using the most conservative of assumptions, the cost-effectiveness ratio of exenatide vs. insulin glargine at the current UK NHS price was -£29,149/QALY (insulin glargine dominant and thus exenatide is not cost-effective when compared with insulin glargine, at the current

  15. Incidence and predictors of hypoglycemia in Japanese patients with type 2 diabetes treated by insulin glargine and oral antidiabetic drugs in real-life: ALOHA post-marketing surveillance study sub-analysis.

    Science.gov (United States)

    Odawara, Masato; Kadowaki, Takashi; Naito, Yusuke

    2014-02-15

    Add-on Lantus® to Oral Hypoglycemic Agents (ALOHA), an observational, non-interventional, 24-week post-marketing surveillance study in Japanese patients with type 2 diabetes (T2DM) having uncontrolled glycemic control, demonstrated that basal supported oral therapy (BOT) with insulin glargine was an effective and safe treatment in real-life clinical practice. We performed subgroup analysis to identify incidence and predictors associated with risk of hypoglycemia. Among 4219 patients with T2DM, 3732 patients were insulin-naïve and 487 patients were insulin non-naïve who switched from other insulin to insulin glargine. All hypoglycemic episodes were counted by physicians' documentation based on patients' reports. Relationships between baseline patient characteristics and glargine-related hypoglycemic episodes were examined by univariate and multivariate analysis. Among 4219 patients, 44 (1.0%) patients experienced hypoglycemic episodes (41 insulin-naïve patients; 3 insulin non-naïve patients), with a rate of incidence 0.035 episodes/patient-years. Majority of patients with hypoglycemia (37 of 44) had just one hypoglycemic episode during study period. Among insulin-naïve patients, incidence of hypoglycemia differed significantly depending on age, diabetic complications, estimated glomerular filtration rate (eGFR), and postprandial plasma glucose (P multivariate adjusted model, poor renal function (eGFR <60 mL/min/1.73 m2) was a statistically significant risk factor (P < 0.05). Our results suggest that BOT using insulin glargine is an option of insulin therapy with 1% risk of hypoglycemia in patients with T2DM with inadequate glycemic control. Patients with low renal function might need a careful follow-up.

  16. Insulin pumps: Beyond basal-bolus

    National Research Council Canada - National Science Library

    Millstein, Richard; Becerra, Nancy Mora; Shubrook, Jay H

    2015-01-01

    Insulin pumps are a major advance in diabetes management, making insulin dosing easier and more accurate and providing great flexibility, safety, and efficacy for people who need basal-bolus insulin therapy...

  17. Concentrations of insulin glargine and its metabolites during long-term insulin therapy in type 2 diabetic patients and comparison of effects of insulin glargine, its metabolites, IGF-I, and human insulin on insulin and IGF-I receptor signaling

    NARCIS (Netherlands)

    A.J. Varewijck (Aimee); H. Yki-Jarvinen (Hannele); R. Schmidt (Reinhold); N. Tennagels (Norbert); J.A.M.J.L. Janssen (Joseph)

    2013-01-01

    textabstractWe investigated 1) the ability of purified glargine (GLA), metabolites 1 (M1) and 2 (M2), IGF-I, and NPH insulin to activate the insulin receptor (IR)-A and IR-B and IGF-I receptor (IGF-IR) in vitro; 2) plasma concentrations of GLA, M1, and M2 during longterm insulin therapy in type 2

  18. The Effect of Basal Analog Insulin on the Glycemic Variability in Type 2 Diabetics

    Directory of Open Access Journals (Sweden)

    Soner Cander

    2014-06-01

    Full Text Available Purpose: The aim of this study was to investigate the effect of insulin detemir and glargine on glycemic variability as determined by capillary blood glucose measurements in Type 2 diabetics treated with oral antidiabetic drugs. Material and Method: A total of 64 insulin-naive type 2 diabetics with a HbA1c level of 7.5%-10% were included in the study. The patients were randomized into 3 groups according to the basal insulin analog started; Group 1 (n=22 was started on once-daily detemir, Group 2 (n=22 twice-daily detemir, and Group 3 (n=20 insulin glargine. Basal insulin doses were titrated according to the morning/evening fasting capillary blood glucose levels. Standard deviations of the 8-point intraday fasting and postprandial blood glucose values were compared. Results: The fasting blood glucose intraday standard deviation values showed an improvement of 22.4% in Group 1, 21.4% in Group 2, and 26.4% in Group 3, while the intraday standard deviation for the postprandial values showed an improvement of 14.4%, 15.2%, and 38.7%, respectively (p>0.05. The standard deviation values did not show statistical significance when the groups were compared with each other. Baseline HbA1c values and insulin doses negatively correlated with the glycemic variability. Dicussion: Basal insulin added to treatment in Type 2 diabetics provided an improvement of 14.4% to 38.7% in glycemic variability. There was no significant difference between insulin glargine and detemir regarding this effect. Turk Jem 2014; 2: 33-38

  19. Insulin Detemir Causes Lesser Weight Gain in Comparison to Insulin Glargine: Role on Hypothalamic NPY and Galanin

    Directory of Open Access Journals (Sweden)

    Mohammad Ishraq Zafar

    2014-01-01

    Full Text Available Objective. Compared with other insulin analogues, insulin detemir induces less weight gain. This study investigated whether this effect was achieved by influencing the hypothalamic appetite regulators neuropeptide Y (NPY and galanin (GAL. Methods. Type  2 diabetic rat models were established with a high-fat diet and intraperitoneal injection of STZ. All rats were divided into NC, DM, DM+DE and DM+GLA groups. Glycemic levels of all study groups were checked at study onset and after 4 weeks of insulin treatment. Food intake and body weight were monitored during treatment. After 4 weeks, the hypothalamus of rats was examined for NPY and GAL mRNA and protein expression. Results. After 4 weeks of treatment, compared with the DM+GLA group, the DM+DE group exhibited less food intake (P<0.05 and less weight gain (P<0.05, but showed similar glycemic control. The expression of hypothalamic NPY and GAL at both mRNA and protein level were significantly lower (P<0.05 in the DM+DE group. Conclusion. Insulin detemir decreased food intake in type 2 diabetic rats, which led to reduced weight gain when compared to insulin glargine treatment. This effect is likely due to downregulation of hypothalamic NPY and GAL.

  20. Cost effectiveness of insulin glargine plus oral antidiabetes drugs compared with premixed insulin alone in patients with type 2 diabetes mellitus in Canada.

    Science.gov (United States)

    Tunis, Sandra L; Sauriol, Luc; Minshall, Michael E

    2010-01-01

    Several treatment options are available for patients with type 2 diabetes mellitus who are making the transition from oral antidiabetes drugs (OADs) to insulin. Two options currently recommended by the Canadian Diabetes Association for initiating insulin therapy in patients with type 2 diabetes who are no longer responsive to OADs alone are insulin glargine plus OADs, and premixed insulin therapy only. Because of differences in efficacy, adverse events (such as hypoglycaemia) and acquisition costs, these two treatment options may lead to different long-term clinical and economic outcomes. To determine the cost effectiveness of insulin glargine plus OADs compared with premixed insulin without OADs in insulin-naive patients with type 2 diabetes in Canada. Using treatment effects taken from a published clinical trial, the validated IMS-CORE Diabetes Model was used to simulate the long-term cost effectiveness of insulin glargine with OADs, versus premixed insulin. Input treatment effects for the two therapeutic approaches were based on changes in glycosylated haemoglobin A(1c) (HbA(1c)) at clinical trial endpoint, and hypoglycaemia rates. The analysis was conducted from the perspective of the Canadian Provincial payer. Direct treatment and complication costs were obtained from published sources (primarily from Ontario) and reported in $Can, year 2008 values. All base-case costs and outcomes were discounted at 5% per year. Sensitivity analyses were conducted around key parameters and assumptions used in the study. Outcomes included direct medical costs associated with both treatment and diabetes-related complications. Cost-effectiveness outcomes included total average lifetime (35 years) costs, life expectancy (LE), QALYs and incremental cost-effectiveness ratios (ICERs). Base-case analyses showed that, compared with premixed insulin only, insulin glargine in combination with OADs was associated with a 0.051-year increase in LE and a 0.043 increase in QALYs. Insulin

  1. Comparison between the therapeutic effect of metformin, glimepiride and their combination as an add-on treatment to insulin glargine in uncontrolled patients with type 2 diabetes.

    Directory of Open Access Journals (Sweden)

    Cheol-Young Park

    Full Text Available To compare the commonly prescribed oral anti-diabetic drug (OAD combinations to use as an add-on therapy with insulin glargine in patients with uncontrolled type 2 diabetes despite submaximal doses of OADs.People with inadequately controlled type 2 diabetes (n = 99 were randomly assigned on a 1∶1∶1 basis to receive insulin glargin, with fixed doses of glimepiride, metformin, and glimepiride plus metformin. Outcomes assessed included HbA1c, the changes in fasting glucose levels, body weight, serum lipids values, insulin dose and symptomatic hypoglycemia.After 24 weeks, HbA1C levels improved from (mean ± SD 8.5±0.9% to 7.7±0.8% (69.0±10.0 mmol/mol to 60.8±8.6 mmol/mol with insulin glargine plus metformin, from 8.4±1.0% to 7.7±1.3% (68.8±10.6 mmol/mol to 61.1±14.4 mmol/mol with insulin glargine plus glimepiride and from 8.7±0.9% to 7.3±0.6% (71.7±9.8 mmol/mol to 56.2±6.7 mmol/mol with insulin glargine plus glimepirde plus metformin. The decrease in HbA1c was more pronounced with insulin glargine plus glimepiride plus metformin than with insulin glargine plus metformin (0.49% [CI, 0.16% to 0.82%]; P = 0.005 (5.10 mmol/mol [CI, 1.64 to 8.61]; P = 0.005 and insulin glargine plus glimepiride (0.59% [CI, 0.13% to 1.05%]; P = 0.012 (5.87 mmol/mol [CI, 1.10 to 10.64]; P = 0.012 (overall P = 0.02. Weight gain and the risk of hypoglycemia of any type did not significantly differ among the treatment groups.The combination therapy of metformin and glimepiride plus glargine insulin resulted in a significant improvement in overall glycemic control as compared with the other combinations.ClinicalTrials.gov, NCT00708578. The approval number of Kangbuk Samsung hospital's institutional review board (IRB: C0825.

  2. Use of basal insulin and the associated clinical outcomes among elderly nursing home residents with type 2 diabetes mellitus: a retrospective chart review study

    Directory of Open Access Journals (Sweden)

    Davis KL

    2014-10-01

    Full Text Available Keith L Davis,1 Wenhui Wei,2 Juliana L Meyers,1 Brett S Kilpatrick,3 Naushira Pandya4 1RTI Health Solutions, Research Triangle Park, NC, USA; 2Sanofi US, Inc, Bridgewater, NJ, USA; 3AnalytiCare, LLC, Glenview, IL, USA; 4Nova Southeastern University College of Osteopathic Medicine, Fort Lauderdale, FL, USA Background: The management of type 2 diabetes mellitus in long-term care (LTC settings can be complex as a result of age-related complications. Despite guideline recommendations, sliding scale insulin remains commonplace in the LTC setting and data on basal insulin use are lacking.Methods: This retrospective study used medical chart data and the Minimum Data Set from elderly LTC facility patients who received basal insulin (insulin glargine, insulin detemir, or neutral protamine Hagedorn insulin for the treatment of diabetes, to investigate the practice patterns and associated clinical outcomes.Results: A total of 2,096 elderly, insulin-treated patients in LTC were identified, with 59.5% of them (N=1,247 receiving basal insulin. Of these, more than 50% of patients received sliding scale insulin in co-administration with basal insulin. Despite its ease of use, insulin pen use was very low, at 14.6%. Significant differences were observed between the basal insulin groups for glycated hemoglobin level and dosing frequency. Hypoglycemia was uncommon -17.2% of patients experienced at least one event, and there was no significant difference in the prevalence of hypoglycemia between the groups.Conclusion: These data suggest the underutilization of basal insulin in the LTC setting and worryingly high combinational use with sliding scale insulin. Differences in glycated hemoglobin and dosing frequencies between types of basal insulin warrant further comparative effectiveness studies. Keywords: long-term care, nursing homes, type 2 diabetes mellitus, insulin detemir, insulin glargine, NPH insulin

  3. Effect of insulin analogues on insulin/IGF1 hybrid receptors: increased activation by glargine but not by its metabolites M1 and M2.

    Directory of Open Access Journals (Sweden)

    Cécile Pierre-Eugene

    Full Text Available BACKGROUND: In diabetic patients, the pharmacokinetics of injected human insulin does not permit optimal control of glycemia. Fast and slow acting insulin analogues have been developed, but they may have adverse properties, such as increased mitogenic or anti-apoptotic signaling. Insulin/IGF1 hybrid receptors (IR/IGF1R, present in most tissues, have been proposed to transmit biological effects close to those of IGF1R. However, the study of hybrid receptors is difficult because of the presence of IR and IGF1R homodimers. Our objective was to perform the first study on the pharmacological properties of the five marketed insulin analogues towards IR/IGF1R hybrids. METHODOLOGY: To study the effect of insulin analogues on IR/IGF1R hybrids, we used our previously developed Bioluminescence Resonance Energy Transfer (BRET assay that permits specific analysis of the pharmacological properties of hybrid receptors. Moreover, we have developed a new, highly sensitive BRET-based assay to monitor phophatidylinositol-3 phosphate (PIP(3 production in living cells. Using this assay, we performed a detailed pharmacological analysis of PIP(3 production induced by IGF1, insulin and insulin analogues in living breast cancer-derived MCF-7 and MDA-MB231 cells. RESULTS: Among the five insulin analogues tested, only glargine stimulated IR/IGF1R hybrids with an EC50 that was significantly lower than insulin and close to that of IGF1. Glargine more efficiently stimulated PIP(3 production in MCF-7 cells but not in MDA-MB231 cells as compared to insulin. In contrast, glargine metabolites M1 and M2 showed lower potency for hybrid receptors stimulation, PIP(3 production, Akt and Erk1/2 phosphorylation and DNA synthesis in MCF-7 cells, compared to insulin. CONCLUSION: Glargine, possibly acting through IR/IGF1R hybrids, displays higher potency, whereas its metabolites M1 and M2 display lower potency than insulin for the stimulation of proliferative/anti-apoptotic pathways in

  4. Insulin degludec as an ultralong-acting basal insulin once a day: a systematic review

    Directory of Open Access Journals (Sweden)

    Wang F

    2012-07-01

    Full Text Available Fei Wang,1 Justine Surh,1 Manmeet Kaur21University of Connecticut School of Pharmacy, Department of Pharmacy Practice, Storrs, 2Joslin Diabetes Center Affiliate, Hospital of Central Connecticut, New Britain, CT, USABackground: Insulin degludec (IDeg is a neutral, ultralong-acting new generation basal insulin analog developed by NovoNordisk currently in Phase III clinical development. IDeg offers a duration of action of more than 42 hours in adults, much longer than current basal insulin formulations.Objective: The aim of this review is to assess the efficacy and safety data of IDeg in the treatment of type 1 and type 2 diabetes mellitus.Methods: Relevant English language articles from 2010 to 2012 were identified through MEDLINE, PubMed, EMBASE, Scopus, BIOSIS, and Google Scholar. Online conference proceedings of the 71st ADA Scientific Sessions and the 47th EASD Annual Meeting were reviewed. Studies were compared in terms of their study designs, primary and secondary efficacy parameters, and tolerability data.Results: There are a total of nine published trials investigating the clinical efficacy and safety of IDeg in over 3000 subjects with type 1 and 2 diabetes. Only three trials were published in full. All were open-label, randomized multicenter trials with durations of 16 to 52 weeks. IDeg and coformulations of IDeg with insulin aspart (IAsp were compared to insulin glargine (IGlar, detemir, and biphasic IAsp 30 (BIAsp 30.Conclusion: Based upon the available evidence, there appear to be no reported differences between IDeg and IGlar, detemir, or BIAsp 30 in the reduction of the primary efficacy end-points of HbA1c and mean fasting plasma glucose (FPG concentrations. Only flexible dosing of IDeg provided a significant reduction in FPG compared to IGlar. IDeg demonstrated a significant reduction in nocturnal hypoglycemia in type 1 diabetes. In type 2 diabetes, IDeg reduced the incidence of hypoglycemia by 18% and 58% compared to IGlar and

  5. Improving treatment satisfaction and other patient-reported outcomes in people with type 2 diabetes: the role of once-daily insulin glargine.

    Science.gov (United States)

    Bradley, C; Gilbride, C J B

    2008-07-01

    Insulin therapy becomes essential for many people with type 2 diabetes. After starting insulin, people with diabetes that is poorly controlled with oral agents typically report improved well-being and treatment satisfaction. However, healthcare professionals and people with type 2 diabetes are often reluctant to begin insulin treatment, citing concerns such as time/resources needed to educate patients, increased risks of hypoglycaemia and fear of injections, which lead them to focus on intensifying conventional oral therapy. Insulin glargine, which offers people with diabetes a once-a-day injection regimen with low risk of hypoglycaemia, is more likely to overcome such initial barriers than other more complex insulin regimens. Once-daily insulin glargine, in combination with modern glucose-dependent oral agents that do not need to be chased with food to prevent hypoglycaemia, does not require the fixed mealtimes and set amounts of carbohydrates necessary with twice-daily injection mixes and older sulphonylureas. We know that it is such dietary restrictions that cause the most damage to quality of life (QoL). To avoid damaging QoL unnecessarily and to ensure optimal satisfaction with treatment, it is important to evaluate the effects of treatment on QoL, treatment satisfaction and other patient-reported outcomes (PROs) using questionnaires validated for this purpose, such as the widely used Diabetes Treatment Satisfaction Questionnaire and the Audit of Diabetes-Dependent Quality of Life measure. A systematic electronic literature search identified reports of studies evaluating PROs associated with insulin glargine in comparison with other treatments. The studies show that insulin glargine is usually associated with greater improvements in treatment satisfaction and other PROs compared with intensifying oral therapy or alternative insulin regimens.

  6. Insulin degludec, a long-acting once-daily basal analogue for type 1 and type 2 diabetes mellitus.

    Science.gov (United States)

    Berard, Lori; MacNeill, Gail

    2015-02-01

    Here, we discuss certain practical issues related to use of insulin degludec, a new long-acting basal insulin analogue. Degludec provides uniform ("peakless") action that extends over more than 24 hours and is highly consistent from dose to dose. Like the 2 previously available basal analogues (detemir and glargine), degludec is expected to simplify dose adjustment and enable patients to reach their glycemic targets with reduced risk of hypoglycemia. Phase 3 clinical trials involving type 1 and type 2 diabetes have demonstrated that degludec was noninferior to glargine in allowing patients to reach a target glycated hemoglobin (A1C) of 7%, and nocturnal hypoglycemia occurred significantly less frequently with degludec. In addition, when dosing intervals vary substantially from day to day, degludec continues to be effective and to maintain a low rate of nocturnal hypoglycemia. Degludec thus has the potential to reduce risk of nocturnal hypoglycemia, to enhance the flexibility of the dosing schedule and to improve patient and caregiver confidence in the stability of glycemic control. A dedicated injector, the FlexTouch prefilled pen, containing degludec 200 units/mL, will be recommended for most patients with type 2 diabetes. Degludec will also be available as 100 units/mL cartridges, to be used in the NovoPen 4 by patients requiring smaller basal insulin doses, including most patients with type 1 diabetes.

  7. Treatment of Abnormal Glucose Regulation and Huge Ovarian Cysts with High Dose Insulin Glargine in an Infant with Leprechaunism - Case Report

    Directory of Open Access Journals (Sweden)

    Ayşe Yasemin Çelik

    2010-12-01

    Full Text Available Introduction: Leprechaunism is a rare autosomal recessive disorder caused by mutations in the insulin receptor gene. In this report; we present a 75 days old infant with leprecahunism treated by high dose insulin glargine.Case Report: Yetmiş day old girl was diagnosed as leprechaunism because of the hyperglycemia, ketoacidosis and dysmorphic appearance. Huge cysts with multiple septa were determined in her ovaries. High dose insulin glargine were adjusted to achieve target blood glucose regulation. Huge ovarian cysts resolved by this treatment.Conclusion: Leprechaunism is characterized by intra-uterine and postnatal growth restriction, lipo-atrophy, characteristic facial features, severe acanthosis nigricans, abnormal glucose homeostasis, clitoromegaly and hirsutism. It is usually fatal within the 1st year of life because of diabetic ketoacidosis or recurrent infections. (Journal of Current Pediatrics 2010; 8: 119-22

  8. Comparison of three algorithms for initiation and titration of insulin glargine in insulin-naive patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Dailey, George; Aurand, Lisa; Stewart, John; Ameer, Barbara; Zhou, Rong

    2014-03-01

    Several titration algorithms can be used to adjust insulin dose and attain blood glucose targets. We compared clinical outcomes using three initiation and titration algorithms for insulin glargine in insulin-naive patients with type 2 diabetes mellitus (T2DM); focusing on those receiving both metformin and sulfonylurea (SU) at baseline. This was a pooled analysis of patient-level data from prospective, randomized, controlled 24-week trials. Patients received algorithm 1 (1 IU increase once daily, if fasting plasma glucose [FPG] > target), algorithm 2 (2 IU increase every 3 days, if FPG > target), or algorithm 3 (treat-to-target, generally 2-8 IU increase weekly based on 2-day mean FPG levels). Glycemic control, insulin dose, and hypoglycemic events were compared between algorithms. Overall, 1380 patients were included. In patients receiving metformin and SU at baseline, there were no significant differences in glycemic control between algorithms. Weight-adjusted dose was higher for algorithm 2 vs algorithms 1 and 3 (P = 0.0037 and P algorithms 1, 2, and 3, respectively). Yearly hypoglycemic event rates (confirmed blood glucose algorithm 3 than algorithms 1 (P = 0.0003) and 2 (P algorithms for initiation and titration of insulin glargine in patients with T2DM resulted in similar levels of glycemic control, with lower rates of hypoglycemia for patients treated using simpler algorithms 1 and 2. © 2013 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  9. Efficacy and Safety of LixiLan, a Titratable Fixed-Ratio Combination of Lixisenatide and Insulin Glargine, Versus Insulin Glargine in Type 2 Diabetes Inadequately Controlled on Metformin Monotherapy: The LixiLan Proof-of-Concept Randomized Trial.

    Science.gov (United States)

    Rosenstock, Julio; Diamant, Michaela; Aroda, Vanita R; Silvestre, Louise; Souhami, Elisabeth; Zhou, Tianyue; Perfetti, Riccardo; Fonseca, Vivian

    2016-09-01

    This study assessed the efficacy and safety of LixiLan, a fixed-ratio, titratable, combination of 2 units insulin glargine (Gla-100) and 1 μg lixisenatide administered once daily via a single pen, versus Gla-100 in insulin-naïve type 2 diabetes on metformin. Participants were randomized to once-daily LixiLan (n = 161) or Gla-100 (n = 162) for 24 weeks, while continuing metformin. LixiLan and Gla-100 were started at 10 units/5 μg and 10 units, respectively, and titrated based on the Gla-100 requirement according to fasting plasma glucose levels. The primary objective was to test noninferiority (upper bound of the 95% CI ≤0.4%) of LixiLan in reducing HbA1c; if met, statistical superiority was tested. Secondary objectives included body weight changes, hypoglycemia, and safety. Baseline characteristics (mean age 57 years, diabetes duration 6-7 years, BMI 32 kg/m(2)) were similar between groups. At week 24, mean HbA1c was reduced from 8.0% (64 mmol/mol) at baseline to 6.3% (45 mmol/mol) and 6.5% (48 mmol/mol) with LixiLan and Gla-100, respectively, establishing statistical noninferiority and superiority of LixiLan (least-squared mean [95% CI] difference: -0.17% [-0.31, -0.04] {-1.9 mmol/mol [-3.4, -0.4]}; P = 0.01). HbA1c <7.0% (<53 mmol/mol) was achieved in 84% and 78% of participants (nonsignificant), respectively. LixiLan improved 2-h postmeal plasma glucose versus Gla-100 (least-squared mean difference: -3.17 mmol/L [-57 mg/dL]; P < 0.0001). Body weight was reduced with LixiLan (-1 kg) and increased with Gla-100 (+0.5 kg; P < 0.0001), with no increase in hypoglycemic events (∼25% in each group). The incidence of nausea (7.5%) and vomiting (2.5%) was low with LixiLan. LixiLan achieved statistically significant reductions to near-normal HbA1c levels with weight loss and no increased hypoglycemic risk, compared with insulin glargine alone, and a low incidence of gastrointestinal adverse events in type 2 diabetes inadequately controlled on metformin. © 2016 by

  10. Enhancement in production of recombinant two-chain Insulin Glargine by over-expression of Kex2 protease in Pichia pastoris.

    Science.gov (United States)

    Sreenivas, Suma; Krishnaiah, Sateesh M; Govindappa, Nagaraja; Basavaraju, Yogesh; Kanojia, Komal; Mallikarjun, Niveditha; Natarajan, Jayaprakash; Chatterjee, Amarnath; Sastry, Kedarnath N

    2015-01-01

    Glargine is an analog of Insulin currently being produced by recombinant DNA technology using two different hosts namely Escherichia coli and Pichia pastoris. Production from E. coli involves the steps of extraction of inclusion bodies by cell lysis, refolding, proteolytic cleavage and purification. In P. pastoris, a single-chain precursor with appropriate disulfide bonding is secreted to the medium. Downstream processing currently involves use of trypsin which converts the precursor into two-chain final product. The use of trypsin in the process generates additional impurities due to presence of Lys and Arg residues in the Glargine molecule. In this study, we describe an alternate approach involving over-expression of endogenous Kex2 proprotein convertase, taking advantage of dibasic amino acid sequence (Arg-Arg) at the end of B-chain of Glargine. KEX2 gene over-expression in Pichia was accomplished by using promoters of varying strengths to ensure production of greater levels of fully functional two-chain Glargine product, confirmed by HPLC and mass analysis. In conclusion, this new production process involving Kex2 protease over-expression improves the downstream process efficiency, reduces the levels of impurities generated and decreases the use of raw materials.

  11. Régimen con insulina lispro mix 25 versus insulina glargina para la diabetes tipo 2 Starting an insulin regimen with insulin lispro mix 25 versus glargine insulin for type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Laura Fernández Landó

    2012-06-01

    Full Text Available La información sobre el inicio de regímenes de insulina en poblaciones específicas con diabetes tipo 2 (DT2 es limitada. Se comparó eficacia y seguridad de dos regímenes de inicio: insulina lispro mix 25 (LM25 e insulina glargina basal (GL. Se evaluaron 193 pacientes no tratados previamente con insulina, en la fase de iniciación de 24 semanas del ensayo DURABLE; edades: 30-79 años, DT2 controlada inadecuadamente (HbA1c > 7.0% con = 2 medicaciones orales antidiabéticas (MOAs, aleatorizados para LM25 (25% de insulina lispro, 75% de insulina lispro protamina en suspensión dos veces/día, o GL (insulina glargina basal una vez/ día, a las MOAs previas. La eficacia primaria se midió por HbA1c a las 24 semanas. Se midió eficacia secundaria por: proporción de pacientes que alcanzaron HbA1c= 6.5% y= 7.0%, cambio en peso corporal, valores de automonitoreo glucémico e índices de hipoglucemia. LM25 demostró mayor reducción de la HbA1c (- 2.4% ± 0.16 vs. -2.0% ± 0.16, P = 0.002, mayor proporción de pacientes alcanzaron HbA1c= 7.0% (P = 0.012 y niveles de glucemia menores después del desayuno (P = 0.028 y de la cena (P = 0.011, y a las 3 a.m. (P = 0.005 comparada con GL. La glucemia en ayunas (GA y la proporción de pacientes que alcanzaron una HbA1c= 6.5% fueron similares. En ambos grupos hubo aumento del peso corporal, mayor en la valoración final con LM25 (6.35 kg vs. 4.23 kg, P Information on starting insulin regimens in specific populations with type 2 diabetes (T2D is limited. This analysis compared efficacy and safety of two starter insulin regimens: insulin lispro mix 25 (LM25 and basal insulin glargine (GL in patients from Argentina. This post-hoc analysis evaluated 193 insulin-naïve patients who participated in the DURABLE trial 24-week initiation phase. Patients 30-79 years with T2D inadequately controlled (HbA1c > 7.0% with = 2 oral antihyperglycemic medications (OAMs, were randomized to add LM25 (25% insulin lispro, 75

  12. Nonclinical pharmacology and toxicology of the first biosimilar insulin glargine drug product (BASAGLAR(®)/ABASAGLAR(®)) approved in the European Union.

    Science.gov (United States)

    Byrd, Richard A; Owens, Rebecca A; Blackbourne, Jamie L; Coutant, David E; Farmen, Mark W; Michael, M Dodson; Moyers, Julie S; Schultze, A Eric; Sievert, Michael K; Tripathi, Niraj K; Vahle, John L

    2017-08-01

    Basaglar(®)/Abasaglar(®) (Lilly insulin glargine [LY IGlar]) is a long-acting human insulin analogue drug product granted marketing authorisation as a biosimilar to Lantus(®) (Sanofi insulin glargine [SA IGlar]) by the European Medicines Agency. We assessed the similarity of LY IGlar to the reference drug product, European Union-sourced SA IGlar (EU-SA IGlar), using nonclinical in vitro and in vivo studies. No biologically relevant differences were observed for receptor binding affinity at either the insulin or insulin-like growth factor-1 (IGF-1) receptors, or in assays of functional or de novo lipogenic activity. The mitogenic potential of LY IGlar and EU-SA IGlar was similar when tested in both insulin- and IGF-1 receptor dominant cell systems. Repeated subcutaneous daily dosing of rats for 4 weeks with 0, 0.3, 1.0, or 2.0 mg/kg LY IGlar and EU-SA IGlar produced mortalities and clinical signs consistent with severe hypoglycaemia. Glucodynamic profiles of LY IGlar and EU-SA IGlar in satellite animals showed comparable dose-related hypoglycaemia. Severe hypoglycaemia was associated with axonal degeneration of the sciatic nerve; the incidence and severity were low and did not differ between LY IGlar and EU-SA IGlar. These results demonstrated no biologically relevant differences in toxicity between LY IGlar and EU-SA IGlar. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Basal insulin and cardiovascular and other outcomes in dysglycemia

    DEFF Research Database (Denmark)

    Gerstein, Hertzel C; Bosch, Jackie; Dagenais, Gilles R

    2012-01-01

    The provision of sufficient basal insulin to normalize fasting plasma glucose levels may reduce cardiovascular events, but such a possibility has not been formally tested.......The provision of sufficient basal insulin to normalize fasting plasma glucose levels may reduce cardiovascular events, but such a possibility has not been formally tested....

  14. Effect of pioglitazone versus insulin glargine on cardiac size, function, and measures of fluid retention in patients with type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Groop Leif

    2009-03-01

    Full Text Available Abstract Background Both insulin and thiazolidinediones (TZDs are effective in the treatment of hyperglycaemia and amelioration of insulin resistance in type 2 diabetes but have side effects including weight gain and fluid retention. The use of TZDs has been further hampered by the risk of adverse cardiovascular events including heart failure. The present study evaluated the effect of pioglitazone or insulin glargine on cardiac function and size as well as on surrogate markers of fluid retention such as weight, haemoglobin and natriuretic peptides. Methods Thirty patients with inadequate glycaemic control on metformin and sulfonylurea were randomised to receive add-on therapy with insulin glargine or pioglitazone for 26 weeks. Echocardiographic data and blood samples were collected from the two groups before the start of the treatment and after 26 weeks. Left ventricular end-diastolic and left atrial end-systolic volumes were quantified, weight measured and blood samples analyzed. Results After 26 weeks of treatment, the changes in HbA1c, weight and haemoglobin were similar between the two groups. HDL increased significantly in the pioglitazone group. While there was an increase in natriuretic peptides in the pioglitazone group (NT-proBNP 11.4 ± 19.6 to 22.8 ± 44.0, p = 0.046, the difference between the treatment groups was not significant. Left ventricular end-diastolic volume increased by 11% and left atrial end-systolic volume by 17% in the pioglitazone group (Both, p Conclusion This randomised pilot-study showed that six-month treatment with pioglitazone induced significant increases in natriuretic peptides and alterations of cardiac size. These changes were not observed with insulin glargine, which also is known to induce fluid retention. Larger randomised trials are warranted to confirm these findings.

  15. Sitagliptin/Metformin Versus Insulin Glargine Combined With Metformin in Obese Subjects With Newly Diagnosed Type 2 Diabetes.

    Science.gov (United States)

    Ji, Ming; Xia, Libin; Cao, Jingzhu; Zou, Dajin

    2016-03-01

    To compare the therapeutic effects of different regimens in Chinese obese type 2 diabetic mellitus (T2DM) patients. From October 2013 to July 2014, a total of 166 T2DM outpatients who attended the Shanghai Changhai Hospital and the Yijishan Hospital of Wannan Medical College were randomly assigned into an experimental sitagliptin/metformin combined with low caloric diet group (n = 115) and an insulin glargine combined with metformin control group (n = 51). Inclusion criteria were body mass index (BMI) ≥ 25 kg/m and diagnosed with T2DM with glycosylated hemoglobin (glycated hemoglobin A1C [HbA1c]) >9%. Main outcome parameters were fasting plasma glucose, postprandial plasma glucose, BMI, HbA1c, fasting C-peptide, 2-h postprandial C-peptide, triglyceride (TG), total cholesterol (TC), high-density cholesterol (HDL-C), and low-density cholesterol (LDL-C), which were determined by the 75 g steamed-bun meal tolerance test before and 4, 8, 12, and 24 weeks after the treatment started. Treatment costs and life quality were also assessed. BMI, HbA1C, TG, TC, and LDL were significantly more reduced (P 9%, oral sitagliptin/metformin combined with a low caloric diet effectively and economically maintained glycemic control and significantly improved life quality.

  16. The Evolution of Insulin Glargine and its Continuing Contribution to Diabetes Care

    OpenAIRE

    Hilgenfeld, Rolf; Seipke, Gerhard; Berchtold, Harald; Owens, David R.

    2014-01-01

    The epoch-making discovery of insulin heralded a new dawn in the management of diabetes. However, the earliest, unmodified soluble insulin preparations were limited by their short duration of action, necessitating multiple daily injections. Initial attempts to protract the duration of action of insulin involved the use of various additives, including vasoconstrictor substances, which met with limited success. The subsequent elucidation of the chemical and three-dimensional structure of insuli...

  17. Factors associated with reaching or not reaching target HbA1c after initiation of basal or premixed insulin in patients with type 2 diabetes.

    Science.gov (United States)

    Scheen, A J; Schmitt, H; Jiang, H H; Ivanyi, T

    2017-02-01

    To evaluate factors associated with reaching or not reaching target glycated haemoglobin (HbA1c) levels by analysing the respective contributions of fasting hyperglycaemia (FHG), also referred to as basal hyperglycaemia, vs postprandial hyperglycaemia (PHG) before and after initiation of a basal or premixed insulin regimen in patients with type 2 diabetes. This post-hoc analysis of insulin-naïve patients in the DURABLE study randomised to receive either insulin glargine or insulin lispro mix 25 evaluated the percentages of patients achieving a target HbA1c of reached the target HbA1c. The higher the HbA1c quartile, the greater was the decrease in HbA1c, but also the smaller the percentage of patients achieving the target HbA1c. HbA1c and FHG decreased more in patients reaching the target, resulting in significantly lower values at endpoint in all baseline HbA1c quartiles with either insulin treatment. Patients not achieving the target HbA1c had slightly higher insulin doses, but lower total hypoglycaemia rates. Smaller decreases in FHG were associated with not reaching the target HbA1c, suggesting a need to increase basal or premixed insulin doses to achieve targeted fasting plasma glucose and improve patient response before introducing more intensive prandial insulin regimens. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  18. Efficacy and Safety of Once-Daily Insulin Degludec/Insulin Aspart versus Insulin Glargine (U100) for 52 Weeks in Insulin-Naïve Patients with Type 2 Diabetes: A Randomized Controlled Trial

    Science.gov (United States)

    Kumar, Ajay; Franek, Edward; Wise, Jonathan; Niemeyer, Marcus; Mersebach, Henriette; Simó, Rafael

    2016-01-01

    Purpose The efficacy and safety of insulin degludec/insulin aspart (IDegAsp) once daily (OD) compared with insulin glargine U100 (IGlar) OD over 52 weeks in insulin-naïve adults with type 2 diabetes mellitus (T2DM) was investigated. Methods In this open-label, parallel-group treat-to-target trial, participants were randomized (1:1) to receive IDegAsp OD (breakfast, n = 266) or IGlar OD (as per label, n = 264). Participants then entered a 26-week extension phase (IDegAsp OD, n = 192; IGlar OD, n = 221). The primary endpoint was change from baseline to Week 26 in HbA1c. Results After 26 and 52 weeks, mean HbA1c decreased to similar levels in both groups. After 52 weeks, the mean estimated treatment difference was –0.08% (–0.26, 0.09 95%CI), confirming the non-inferiority of IDegAsp OD versus IGlar OD evaluated at Week 26. After 52 weeks, there was a similar reduction in mean fasting plasma glucose in both treatment groups. The rate of confirmed hypoglycemic episodes was 86% higher (p administration of IDegAsp with the main meal of the day, tailored to the individual patient’s needs. Trial Registration ClinicalTrials.gov: NCT01045707 [core]) and NCT01169766 [ext] PMID:27760129

  19. Switching to basal-bolus insulin therapy is effective and safe in long-term type 2 diabetes patients inadequately controlled with other insulin regimens.

    Science.gov (United States)

    Vinagre, Irene; Sánchez-Hernández, Juan; Sánchez-Quesada, José Luis; María, Miguel Ángel; de Leiva, Alberto; Pérez, Antonio

    2013-05-01

    To assess in standard clinical practice the feasibility, efficacy, and safety of switching patients with long-standing type 2 diabetes (T2DM) and poor or unstable blood glucose control to basal-bolus insulin therapy. This was a prospective, single center study including 37 patients with T2DM (age 65±8 years, 62.2% men, body mass index 28.8±6.2 kg/m2, diabetes duration 18±8 years) with poor or unstable glycemic control, who were switched to a basal-bolus insulin regimen with glargine and rapid-acting insulin analogue at the discretion of their physicians. After a group-structured outpatient diabetes training program, patients were followed in a clinical practice setting for 6 months. Clinical and biochemical variables were collected before switching and at 3 and 6 months. After switching to basal-bolus therapy, glycosylated hemoglobin (HbA1c) decreased from 9±1.2% to 8.1±1.2% (p<0.001) at 3 months and to 8.0±1.2% at 6 months (p<0.001) without changing total daily insulin dose. The proportion of patients with HbA1c ≥ 9% decreased from 51% to 13.8% at 3 months and to 18.9% at 6 months respectively. There was a single episode of severe hypoglycemia. No changes were seen in body weight and quality of life. The size of LDL (low density lipoprotein) particles significantly increased at 3 and 6 months, while all other lipid parameters remained unchanged. Our study confirmed that basal-bolus insulin therapy is feasible, effective, and safe in patients with long-standing T2DM, and does not impair their quality of life. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

  20. Initiation of insulin glargine in patients with Type 2 diabetes in suboptimal glycaemic control positively impacts health-related quality of life. A prospective cohort study in primary care

    DEFF Research Database (Denmark)

    Hajós, Tibor R S; Pouwer, F; de Grooth, R

    2011-01-01

    control (HbA(1c) > 53 mmol/mol; 7%) on maximum dose of oral glucose-lowering medications were included from 363 primary care practices (n = 911). Patients started insulin glargine and were followed up for 6 months. At baseline (start insulin therapy), 3 and 6 months, HbA(1c) was measured and patients......AIMS: To study prospectively the impact of initiating insulin glargine in suboptimally controlled insulin-naïve patients with Type 2 diabetes on health-related quality of life in relation to glycaemic control. METHODS: Insulin-naïve Dutch patients with Type 2 diabetes in suboptimal glycaemic......-revised score decreased from 15 ± 14 to 10 ± 12 and 10 ± 13 (P up and 67 ± 21.8 at 6-month follow-up (P

  1. Insulin glargine provides greater improvements in glycaemic control vs. intensifying lifestyle management for people with type 2 diabetes treated with OADs and 7-8% A1c levels. The TULIP study.

    Science.gov (United States)

    Blicklé, J-F; Hancu, N; Piletic, M; Profozic, V; Shestakova, M; Dain, M-P; Jacqueminet, S; Grimaldi, A

    2009-04-01

    To determine whether earlier administration of insulin glargine (glargine) vs. the intensification of lifestyle management (LM) improves glycaemic control in type 2 diabetes patients with A1c 7-8% treated with oral therapy. TULIP [Testing the Usefulness of gLargine when Initiated Promptly in type 2 diabetes mellitus (T2DM)] was a 9-month, 12-visit, open-label, multinational, multicentre, randomized study to evaluate starting glargine or intensifying LM in T2DM patients aged 40-75 years, body mass index (BMI) 24-35 kg/m2 and A1c 7-8%, treated with maximum doses of metformin and sulphonylurea for > or = 2 years. Glargine was injected once daily (evening) and titrated to fasting blood glucose 0.7-1.0 g/l. In the LM arm, dietary and physical activity counselling recommended stable weight for people with BMI or = 27 kg/m2. A total of 215 patients were randomized to glargine (n = 106) or LM (n = 109). The primary objective was patients achieving A1c < 7% at endpoint. Secondary endpoints included changes in A1c, in fasting plasma glucose (FPG), body weight and hypoglycaemia incidence. Two hundred and eleven (52.6% male) patients were randomized and treated; mean (+/- s.d.) age 60.7 +/- 7.9 years, weight 84.5 +/- 13.1 kg, BMI 29.9 +/- 3.5 kg/m2 and A1c 7.6 +/- 0.4%. More patients reached A1c < 7% (66 vs. 38%; p < 0.0001) or < 6.5% (34 vs. 11%; p = 0.0001) with glargine vs. LM. The change in FPG from baseline to study endpoint was significantly greater in the glargine vs. the LM arm (-0.50 +/- 0.47 vs. -0.05 +/- 0.39 g/l respectively; p < 0.0001). Compared with the glargine group, the LM group showed a decrease in weight (+0.9 +/- 2.9 vs. -2.5 +/- 3.2 kg; p < 0.0001), as well as the expected lower symptomatic hypoglycaemia (55.3 vs. 25.0%; p < 0.0001) and nocturnal hypoglycaemia (20.4 vs. 5.6%; p = 0.0016). No significant changes were observed from baseline to study endpoint in any of the lipid parameters tested. In patients with T2DM with A1c 7-8%, who were previously

  2. Internalization and localization of basal insulin peglispro in cells.

    Science.gov (United States)

    Moyers, Julie S; Volk, Catherine B; Cao, Julia X C; Zhang, Chen; Ding, Liyun; Kiselyov, Vladislav V; Michael, M Dodson

    2017-10-15

    Basal insulin peglispro (BIL) is a novel, PEGylated insulin lispro that has a large hydrodynamic size compared with insulin lispro. It has a prolonged duration of action, which is related to a delay in insulin absorption and a reduction in clearance. Given the different physical properties of BIL compared with native insulin and insulin lispro, it is important to assess the cellular internalization characteristics of the molecule. Using immunofluorescent confocal imaging, we compared the cellular internalization and localization patterns of BIL, biosynthetic human insulin, and insulin lispro. We assessed the effects of BIL on internalization of the insulin receptor (IR) and studied cellular clearance of BIL. Co-localization studies using antibodies to either insulin or PEG, and the early endosomal marker EEA1 showed that the overall internalization and subcellular localization pattern of BIL was similar to that of human insulin and insulin lispro; all were rapidly internalized and co-localized with EEA1. During ligand washout for 4 h, concomitant loss of insulin, PEG methoxy group, and PEG backbone immunostaining was observed for BIL, similar to the loss of insulin immunostaining observed for insulin lispro and human insulin. Co-localization studies using an antibody to the lysosomal marker LAMP1 did not reveal evidence of lysosomal localization for insulin lispro, human insulin, BIL, or PEG using either insulin or PEG immunostaining reagents. BIL and human insulin both induced rapid phosphorylation and internalization of human IR. Our findings show that treatment of cells with BIL stimulates internalization and localization of IR to early endosomes. Both the insulin and PEG moieties of BIL undergo a dynamic cellular process of rapid internalization and transport to early endosomes followed by loss of cellular immunostaining in a manner similar to that of insulin lispro and human insulin. The rate of clearance for the insulin lispro portion of BIL was slower than

  3. Comparison of the influence of oral antidiabetic drug and combined with basal insulin treatment on diabetic control and micro-inflammatory state in type 2 diabetes mellitus patients

    Institute of Scientific and Technical Information of China (English)

    Gang Wu; Dong-Liang Liu; Xiang-Jun Li; Xiao-Yun Fan

    2016-01-01

    Objective:To investigate the influence of oral antidiabetic drug and combined with basal insulin treatment on diabetic control and micro-inflammatory state in type 2 diabetes mellitus patients.Methods:From May 2014 to June 2015, 128 cases of Type 2 diabetes mellitus were recruited and divided randomly into two groups as observation group and control group. The observation group was given metformin (Glucophage, 0.25 tid) plus basal insulin (glargine) treatment, while the control group was given metformin (Glucophage, initial dose of 0.25 tid; the largest total dose of 2 g) plus other non-euglycemic OADs necessarily for 6 months to adjust dose and control blood glucose at target. The diabetic control indexes, islet function and micro-inflammatory factors were detected and analyzed.Results:After 6 months of medication, the observation group showed significantly lower level of FPG, and HbA1cthan the control group. While AUCc-p, HOMA-β and HOMA-IR of the observation group showed significant difference compared to that of the control group after treatment. Also the micro-inflammatory indexes including hs-CRP, IGF-1, IL-6 and TNF-α of the observation group after treatment were significantly lower than the control group .Conclusions:Type 2 diabetes given metformin plus glargine not only could control and steady blood glucose, but also significant decrease the micro-inflammation state.

  4. Beyond the era of NPH insulin--long-acting insulin analogs: chemistry, comparative pharmacology, and clinical application.

    Science.gov (United States)

    Owens, D R; Bolli, G B

    2008-10-01

    The new rDNA and DNA-derived "basal" insulin analogs, glargine and detemir, represent significant advancement in the treatment of diabetes compared with conventional NPH insulin. This review describes blood glucose homeostasis by insulin in people without diabetes and outlines the physiological application of exogenous insulin in patients with type 1 and type 2 diabetes. The requirements for optimal basal insulin treatment are discussed and the methods used in the evaluation of basal insulins are presented. An essential criterion in the development of an "ideal" basal insulin preparation is that the molecular modifications made to the human insulin molecule do not compromise safety. It is also necessary to obtain a clear understanding of the pharmacokinetic and pharmacodynamic characteristics of the two currently available basal insulin analogs. When comparing glargine and detemir, the different molar concentration ratios of the two insulin formulations should be considered along with the nonspecificity of assay systems used to determine insulin concentrations. However, euglycemic clamp studies in crossover study design provide a good basis for comparing the pharmacodynamic responses. When the latter is analyzed by results of intervention clinical trials, it is concluded that both glargine and detemir are superior to NPH in type 1 and type 2 diabetes. However, there is sufficient evidence to demonstrate that these two long-acting insulin analogs are different in both their pharmacokinetic and pharmacodynamic profiles. These differences should be taken into consideration when the individual analogs are introduced to provide basal insulin supplementation to optimize blood glucose control in patients with type 1 and type 2 diabetes as well. PubMed-Medline was searched for articles relating to pharmacokinetics and pharmacodynamics of glargine and detemir. Articles retrieved were reviewed and selected for inclusion if (1) the euglycemic clamp method was used with a

  5. Diabetes reduces basal retinal insulin receptor signaling: reversal with systemic and local insulin.

    Science.gov (United States)

    Reiter, Chad E N; Wu, Xiaohua; Sandirasegarane, Lakshman; Nakamura, Makoto; Gilbert, Kirk A; Singh, Ravi S J; Fort, Patrice E; Antonetti, David A; Gardner, Thomas W

    2006-04-01

    Diabetic retinopathy is characterized by early onset of neuronal cell death. We previously showed that insulin mediates a prosurvival pathway in retinal neurons and that normal retina expresses a highly active basal insulin receptor/Akt signaling pathway that is stable throughout feeding and fasting. Using the streptozotocin-induced diabetic rat model, we tested the hypothesis that diabetes diminishes basal retinal insulin receptor signaling concomitantly with increased diabetes-induced retinal apoptosis. The expression, phosphorylation status, and/or kinase activity of the insulin receptor and downstream signaling proteins were investigated in retinas of age-matched control, diabetic, and insulin-treated diabetic rats. Four weeks of diabetes reduced basal insulin receptor kinase, insulin receptor substrate (IRS)-1/2-associated phosphatidylinositol 3-kinase, and Akt kinase activity without altering insulin receptor or IRS-1/2 expression or tyrosine phosphorylation. After 12 weeks of diabetes, constitutive insulin receptor autophosphorylation and IRS-2 expression were reduced, without changes in p42/p44 mitogen-activated protein kinase or IRS-1. Sustained systemic insulin treatment of diabetic rats prevented loss of insulin receptor and Akt kinase activity, and acute intravitreal insulin administration restored insulin receptor kinase activity. Insulin treatment restored insulin receptor-beta autophosphorylation in rat retinas maintained ex vivo, demonstrating functional receptors and suggesting loss of ligand as a cause for reduced retinal insulin receptor/Akt pathway activity. These results demonstrate that diabetes progressively impairs the constitutive retinal insulin receptor signaling pathway through Akt and suggests that loss of this survival pathway may contribute to the initial stages of diabetic retinopathy.

  6. Lantus, the first peakless basal insulin analogue: 10 years of clinical experience in children and adolescents

    OpenAIRE

    Tamara Leonodovna Kuraeva

    2014-01-01

    This review analyses existing literature, including authors' own data, describing the results of clinical trials which assess safety and efficacy of insulin Glargine (Lantus®) in children and adolescents, as well as peculiar features of T1D management in this age group, including the challenge of reducing the rate of hypoglycemia while maintaining adequate glycemic control. The article also discusses various issues in T1D management in children and adolescents, including the role of glycemic ...

  7. Degludec, a new ultra-long-acting basal insulin for the treatment of diabetes mellitus type 1 and 2: advances in clinical research.

    Science.gov (United States)

    Muñoz Torres, Manuel

    2014-03-01

    Degludec is the most recent molecule of the ultra-long-acting basal insulin analogues approved for human use. It forms soluble multihexamers which after subcutaneous injection are converted into monomers, and are thus slowly and continuously absorbed into the bloodstream. This absorption mechanism confers degludec an ultra-long and stable action profile, with no concentration peaks. This paper discusses the most recent studies in patients with type 1 and 2 diabetes mellitus, which showed degludec to be non inferior in decreasing HbA1c, ensuring optimum glycemic control similar to that achieved with insulin glargine or detemir. Degludec also had an improved safety profile, as it was associated to a significantly lower rate of nocturnal hypoglycemia in both types of diabetes and to a potentially lower overall hypoglycemia rate in type 2 DM. Degludec also opens the possibility to use more flexible regimens.

  8. Patient-led versus physician-led titration of insulin glargine in patients with uncontrolled type 2 diabetes: a randomized multinational ATLAS study.

    Science.gov (United States)

    Garg, Satish K; Admane, Karim; Freemantle, Nick; Odawara, Masato; Pan, Chang-Yu; Misra, Anoop; Jarek-Martynowa, Iwona R; Abbas-Raza, Syed; Mirasol, Roberto C; Perfetti, Riccardo

    2015-02-01

    Self-adjustment of insulin dose is commonly practiced in Western patients with type 2 diabetes but is usually not performed in Asian patients. This multinational, 24-week, randomized study compared patient-led with physician-led titration of once-daily insulin glargine in Asian patients with uncontrolled type 2 diabetes who were on 2 oral glucose-lowering agents. Patient-led (n = 275) or physician-led (n = 277) subjects followed the same dose-titration algorithm guided by self-monitored fasting blood glucose (FBG; target, 110 mg/dL [6.1 mmol/L]). The primary endpoint was change in mean glycated hemoglobin (HbA1c) at week 24 in the patient-led versus physician-led titration groups. Patient-led titration resulted in a significantly higher drop in HbA1c value at 24 weeks when compared with physician-led titration (-1.40% vs. -1.25%; mean difference, -0.15; 95% confidence interval, -0.29 to 0.00; P = .043). Mean decrease in FBG was greatest in the patient-led group (-2.85 mmol/L vs. -2.48 mmol/L; P = .001). The improvements in HbA1c and FBG were consistent across countries, with similar improvements in treatment satisfaction in both groups. Mean daily insulin dose was higher in the patient-led group (28.9 units vs. 22.2 units; P<.001). Target HbA1c of <7.0% without severe hypoglycemia was achieved in 40.0% and 32.9% in the patient-led and physician-led groups, respectively (P = .086). Severe hypoglycemia was not different in the 2 groups (0.7%), with an increase in nocturnal and symptomatic hypoglycemia in the patient-led arm. Patient-led insulin glargine titration achieved near-target blood glucose levels in Asian patients with uncontrolled type 2 diabetes who were on 2 oral glucose-lowering drugs, demonstrating that Asian patients can self-uptitrate insulin dose effectively when guided.

  9. Lixisenatide as add-on therapy to basal insulin

    Directory of Open Access Journals (Sweden)

    Brown DX

    2013-12-01

    Full Text Available Dominique Xavier Brown, Emma Louise Butler, Marc Evans Diabetes Department, University Hospital Llandough, Cardiff, UK Abstract: Many patients with type 2 diabetes mellitus do not achieve target glycosylated hemoglobin A1c levels despite optimally titrated basal insulin and satisfactory fasting plasma glucose levels. Current evidence suggests that HbA1c levels are dictated by both basal glucose and postprandial glucose levels. This has led to a consensus that postprandial glucose excursions contribute to poor glycemic control in these patients. Lixisenatide is a once-daily, prandial glucagon-like peptide 1 (GLP-1 receptor agonist with a four-fold affinity for the GLP-1 receptor compared with native GLP-1. Importantly, lixisenatide causes a significant delay in gastric emptying time, an important determinant of the once-daily dosing regimen. An exendin-4 mimetic with six lysine residues removed at the C-terminal, lixisenatide has pronounced postprandial glucose-lowering effects, making it a novel incretin agent for use in combination with optimally titrated basal insulin. Lixisenatide exerts profound effects on postprandial glucose through established mechanisms of glucose-dependent insulin secretion and glucagon suppression in combination with delayed gastric emptying. This review discusses the likely place that lixisenatide will occupy in clinical practice, given its profound effects on postprandial glucose and potential to reduce glycemic variability. Keywords: lixisenatide, add-on therapy, insulin, GLP-1 receptor agonist, postprandial glucose, pharmacodynamics

  10. Statistical optimization of insulin-loaded Pluronic F-127 gels for buccal delivery of basal insulin.

    Science.gov (United States)

    Das, Nilanjana; Madan, Parshotam; Lin, Senshang

    2012-01-01

    The principle of statistical optimization was employed to fabricate insulin-loaded Pluronic F-127 (PF-127) gel formulations having the potential for buccal delivery of basal insulin. A two-level resolution III fractional factorial design was applied to simultaneously evaluate five independent formulation variables: PF-127 concentration, insulin concentration, sodium sulfate concentration, hydroxypropylmethyl cellulose (HPMC) concentration, and presence of sodium glycocholate. The amount of insulin released and permeated from gels as well as gelation time and mucoadhesion force of gels were measured and used as dependent response variables for formulation optimization. Optimization of a gel formulation was achieved by applying constrained optimization via regression analysis. In vitro permeation flux of insulin from the optimized formulation through procine buccal mucosa was 93.17 (±0.058, n = 3) μg/cm(2). Plasma insulin levels following buccal administration of the optimized formulation at 10, 25 and 50 IU/kg to healthy rats were found to be dose dependent and basal insulin levels were maintained at least for 8 h. Furthermore, continuous hypoglycemia for at least 8 h was observed with 89%, 51% and 25% of blood glucose reduction, respectively, for these three doses. The results of this investigation conclude the feasibility of development of optimized buccal insulin-loaded Pluronic F-127 gels for basal insulin delivery.

  11. Validation of Algorithms for Basal Insulin Rate Reductions in Type 1 Diabetic Patients Practising Physical Activity

    Science.gov (United States)

    2013-04-19

    Type 1 Diabetes With a Subcutaneous Insulin Pump; Adjustment of the Recommended Basal Insulin Flow Rate in the Event of Physical Activity; Adjustment of the Recommended Prandial Insulin in the Event of Physical Activity

  12. Insulin degludec/insulin aspart is the first co-formulation of basal and prandial insulin analogues

    Directory of Open Access Journals (Sweden)

    Ivan Ivanovich Dedov

    2014-12-01

    Full Text Available Achievement of glycemic control is the major therapeutic aim to prevent or delay the onset and progression of diabetes related complications. Insulin therapy represents a cornerstone in the treatment of diabetes and has been used widely for achieving glycemic goals. The aim for insulin therapy is to mimic the physiological profile of insulin secretion seen in nondiabetic patients. Development of the insulin analogs has offered new opportunities in the diabetes management to achieve greater safety and tolerability of diabetes treatment. Insulin degludec/insulin aspart(IDegAsp (Ryzodeg®, Novo Nordisk, Denmark is the first soluble co-formulation of 70% ultra-long acting insulin degludec and 30% rapid-acting prandial insulin aspart, providing both basal insulin coverage and a prandial insulin bolus in a single injection. This review discusses data regarding the efficacy, safety, tolerability and clinical benefits of IDegAsp. According to the clinical development program IDegAspprovides an achievement of similar glycemic control with superiority in lowering FPG with using less number of injections and lower daily insulin dose, and also associated with numerically lower rates of confirmed and nocturnal confirmed hypoglycaemia in comparison with premixed or basal insulin analogues, as well as a basal component for basal–bolus therapy with supplementary mealtime insulin aspart.Trial results suggest that IDegAspQD or BID maybe an appropriate and reasonable option for initiating insulin therapy in type 1 and type 2 diabetic patients inadequately controlled on maximal doses of oral antidiabetic drugs,and also a simple alternative to basal–bolus treatment in patients who require intensification of insulin therapy, especially when adherence to more complex regimens is challenging.

  13. In Vivo and In Vitro Characterization of Basal Insulin Peglispro: A Novel Insulin Analog.

    Science.gov (United States)

    Owens, Rebecca A; Hansen, Ryan J; Kahl, Steven D; Zhang, Chen; Ruan, Xiaoping; Koester, Anja; Li, Shun; Qian, Hui-Rong; Farmen, Mark W; Michael, M Dodson; Moyers, Julie S; Cutler, Gordon B; Vick, Andrew; Beals, John M

    2016-06-01

    The aim of this research was to characterize the in vivo and in vitro properties of basal insulin peglispro (BIL), a new basal insulin, wherein insulin lispro was derivatized through the covalent and site-specific attachment of a 20-kDa polyethylene-glycol (PEG; specifically, methoxy-terminated) moiety to lysine B28. Addition of the PEG moiety increased the hydrodynamic size of the insulin lispro molecule. Studies show there is a prolonged duration of action and a reduction in clearance. Given the different physical properties of BIL, it was also important to assess the metabolic and mitogenic activity of the molecule. Streptozotocin (STZ)-treated diabetic rats were used to study the pharmacokinetic and pharmacodynamic characteristics of BIL. Binding affinity and functional characterization of BIL were compared with those of several therapeutic insulins, insulin AspB10, and insulin-like growth factor 1 (IGF-1). BIL exhibited a markedly longer time to maximum concentration after subcutaneous injection, a greater area under the concentration-time curve, and a longer duration of action in the STZ-treated diabetic rat than insulin lispro. BIL exhibited reduced binding affinity and functional potency as compared with insulin lispro and demonstrated greater selectivity for the human insulin receptor (hIR) as compared with the human insulin-like growth factor 1 receptor. Furthermore, BIL showed a more rapid rate of dephosphorylation following maximal hIR stimulation, and reduced mitogenic potential in an IGF-1 receptor-dominant cellular model. PEGylation of insulin lispro with a 20-kDa PEG moiety at lysine B28 alters the absorption, clearance, distribution, and activity profile receptor, but does not alter its selectivity and full agonist receptor properties. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  14. Cost Effectiveness of Insulin Degludec Plus Liraglutide (IDegLira) in a Fixed Combination for Uncontrolled Type 2 Diabetes Mellitus in Sweden.

    Science.gov (United States)

    Ericsson, Åsa; Lundqvist, Adam

    2017-04-01

    Patients with uncontrolled type 2 diabetes mellitus (T2DM) are a priority group for intensified therapy without weight gain and with low risk of hypoglycaemia. This study evaluates the cost effectiveness of insulin degludec plus liraglutide (IDegLira, Xultophy(®)) compared with six potential intensification treatment options for patients with T2DM that is uncontrolled with basal insulin. The Swedish Institute for Health Economics (IHE) Cohort Model of Type 2 Diabetes was used with Swedish input data, a 40-year time frame and a societal perspective. The comparators for treatment intensification included insulin glargine, neutral protamine Hagedorn (NPH) insulin, insulin aspart plus either glargine or NPH, and liraglutide plus either glargine or NPH. Clinical data for all comparators (except NPH insulin) were based on an indirect treatment comparison of several studies. Prices were obtained from the 2014 Swedish Dental and Pharmaceutical Benefits Agency (Tandvårds- och läkemedelsförmånsverket [TLV]) database, and utility values were obtained from published studies. Sensitivity analyses were undertaken. Overall incremental cost-effectiveness ratios (ICER) were Swedish krona (SEK) 70,000 or lower per quality-adjusted life-year (QALY). IDegLira compared with intensified basal insulin showed an ICER of SEK 28,000 per QALY versus insulin glargine, SEK70,000 per QALY versus NPH insulin and SEK 60,000 per QALY versus NPH insulin plus liraglutide. IDegLira was dominant over insulin glargine plus liraglutide and insulin aspart plus insulin glargine or NPH insulin. Results were driven by the difference in glycated haemoglobin (HbA1c) reduction between treatments, as confirmed by sensitivity analyses. IDegLira is estimated to be a cost-effective treatment in Sweden compared with commonly used intensification treatments for patients with T2DM uncontrolled with basal insulin.

  15. 新诊断T2MD格列吡嗪联合甘精胰岛素强化治疗的研究%Newly Diagnosed Type 2 Diabetes Glipizide and Insulin Aspart Joint Insulin Glargine Intensive Therapy Research

    Institute of Scientific and Technical Information of China (English)

    赵积海; 董效珍; 高静

    2015-01-01

    目的:观察新诊断2型糖尿病患者采用格列吡嗪和门冬胰岛素分别联合甘精胰岛素强化治疗的有效性、安全性及性价比。方法整群选取2013年2月—2014年12月在该院住院治疗的82例T2DM患者随机分为格列吡嗪联合甘精胰岛素(A组)和门冬胰岛素联合甘精胰岛素(B组),治疗两周后复查患者FBG、2 hBG、FC-P、2 hC-P、血糖达标时间、低血糖发生率及药品费用。结果2周后,两组FBG、2 hBG、较治疗前明显下降,FC-P、2 hC-P较治疗前明显升高(P0.05);两组治疗费用A组明显低于B组,差异有统计学意义(P0.05); two groups of treatment cost was lower in group A than in group B, the difference was statistically significant (P<0.01). Conclusion For patients with newly diagnosed T2DM, Glip-izide combined with Glargine insulin intensive treatment, can control blood glucose well, improve the islet beta cell function in patients with T2DM, and the effect of Insulin aspart Insulin glargine quite, but the former costs less, more convenient.

  16. Lower risk of hypoglycaemia and greater odds for weight loss with initiation of insulin detemir compared with insulin glargine in Turkish patients with type 2 diabetes mellitus: local results of a multinational observational study.

    Science.gov (United States)

    Damci, Taner; Emral, Rifat; Svendsen, Anne Louise; Balkir, Tanzer; Vora, Jiten

    2014-07-21

    The purpose of this analysis is to evaluate the safety and effectiveness of insulin initiation with once-daily insulin detemir (IDet) or insulin glargine (IGlar) in real-life clinical practice in Turkish patients with type 2 diabetes mellitus (T2DM). This was a 24-week multinational observational study of insulin initiation in patients with T2DM. The Turkish cohort (n = 2886) included 2395 patients treated with IDet and 491 with IGlar. The change in glycosylated haemoglobin (HbA1c) from the pre-insulin levels was -2.21% [95% confidence interval (CI) -2.32, -2.09] in the IDet group and -1.88% [95% CI -2.17, -1.59] in the IGlar group at the final visit. The incidence rate of minor hypoglycaemia increased in both groups from the pre-insulin to the final visit (+0.66 and +2.23 events per patient year in the IDet and IGlar groups, respectively). Weight change in the IDet group was -0.23 kg [95% CI -0.49, 0.02 kg], and +1.55 kg [95% CI 1.11, 2.00 kg] in the IGlar group. Regression analysis with adjustment for previously identified confounders (age, gender, duration of diabetes, body mass index, previous history of hypoglycaemia, microvascular disease, number and change in oral anti-diabetic drug therapy, HbA1c at baseline and insulin dose) identified an independent effect of insulin type (IDet versus IGlar) with a risk of at least one episode of hypoglycaemia (odds ratio (OR): 0.33 [95% CI 0.21, 0.52], p insulin analogues, IDet and IGlar, were associated with clinically significant glycaemic improvements. A lower risk of minor hypoglycaemia and greater odds of weight loss ≥1 kg was observed with IDet compared with IGlar. NCT00825643 and NCT00740519.

  17. Review of basal-plus insulin regimen options for simpler insulin intensification in people with Type 2 diabetes mellitus.

    Science.gov (United States)

    Raccah, D; Huet, D; Dib, A; Joseph, F; Landers, B; Escalada, J; Schmitt, H

    2017-09-01

    To identify simple insulin regimens for people with Type 2 diabetes mellitus that can be accepted and implemented earlier in primary and specialist care, taking into consideration each individual's needs and capabilities. Using randomized clinical trials identified by a search of the PubMed database, as well as systematic reviews, meta-analyses and proof-of-concept studies, this review addresses topics of interest related to the progressive intensification of a basal insulin regimen to a basal-plus regimen (one basal insulin injection plus stepwise addition of one to three preprandial short-acting insulin injections/day) vs a basal-bolus regimen (basal insulin plus three short-acting insulin injections per day) in people with Type 2 diabetes. The review explores approaches that can be used to define the meal for first prandial injection with basal-plus regimens, differences among insulin titration algorithms, and the importance of self-motivation and autonomy in achieving optimum glycaemic control. A basal-plus regimen can provide glycaemic control equivalent to that obtained with a full basal-bolus regimen, with fewer injections of prandial insulin. The first critical step is to optimize basal insulin dosing to reach a fasting glucose concentration of ~6.7 mmol/l; this allows ~40% of patients with baseline HbA1c >75 mmol/mol (9%) to be controlled with only one basal insulin injection per day. Compared with a basal-bolus regimen, a basal-plus insulin regimen is as effective but more practical, and has the best chance of acceptance and success in the real world. © 2017 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.

  18. Insulin glargine combined with glimepiride in treatment of elderly patients with diabetes clinical effectiveness evaluation%甘精胰岛素联合格列美脲治疗老年糖尿病临床效果初评

    Institute of Scientific and Technical Information of China (English)

    周英; 吴强

    2015-01-01

    目的:对甘精胰岛素联合格列美脲治疗老年糖尿病临床效果进行评估.方法 :选取我院2013年至2014年收治的90例老年糖尿病患者作为本次研究的对象 ,随机分成观察和对照组各45 例.对照组采用鱼精蛋白锌胰岛素(N P H )联合格列美脲治疗法 ;观察组采用甘精胰岛素联合格列美脲治疗法.结果 :两组患者治疗后各项指标均有所改善.结论 :甘精胰岛素联合格列美脲治疗老年糖尿病有显著效果.%Objective:the clinical effect of diabetes on insulin glargine combined with glimepiride treatment is evaluated .Methods :90 cases of elderly patients with diabetes in our hospital from 2013 to 2014 were as the research object ,randomly divided into observation and control group with 45 cases in each group .Patients in control group were treated with protamine zinc insulin (NPH) combined with glimepiride therapy ;the observation group treated with insulin glargine combined with glimepiride therapy .Results :the two groups of patients after treatment ,the indexes were improved .Conclu-sion:insulin glargine combined with glimepiridein treatment of elderly patients with diabetes have a significant effect .

  19. A Comparison of the Effects of the GLP-1 Analogue Liraglutide and Insulin Glargine on Endothelial Function and Metabolic Parameters: A Randomized, Controlled Trial Sapporo Athero-Incretin Study 2 (SAIS2.

    Directory of Open Access Journals (Sweden)

    Hiroshi Nomoto

    Full Text Available GLP-1 improves hyperglycemia, and it has been reported to have favorable effects on atherosclerosis. However, it has not been fully elucidated whether GLP-1 is able to improve endothelial function in patients with type 2 diabetes. Therefore, we investigated the efficacy of the GLP-1 analogue, liraglutide on endothelial function and glycemic metabolism compared with insulin glargine therapy.In this multicenter, prospective randomized parallel-group comparison study, 31 diabetic outpatients (aged 60.3 ± 10.3 years with HbA1c levels of 8.6 ± 0.8% with current metformin and/or sulfonylurea treatment were enrolled and randomly assigned to receive liraglutide or glargine therapy once daily for 14 weeks. Flow mediated dilation (FMD, a comprehensive panel of hemodynamic parameters (Task Force Monitor, and serum metabolic markers were assessed before and after the treatment period.A greater reduction (worsening in %FMD was observed in the glargine group, although this change was not statistically different from the liraglutide group (liraglutide; 5.7 to 5.4%, glargine 6.7 to 5.7%. The augmentation index, C-peptide index, derivatives of reactive oxygen metabolites and BMI were significantly improved in the liraglutide group. Central systolic blood pressure and NT-proBNP also tended to be improved in the liraglutide-treated group, while improvements in HbA1c levels were similar between groups. Cardiac index, blood pressure and most other metabolic parameters were not different.Regardless of glycemic improvement, early liraglutide therapy did not affect endothelial function but may provide favorable effects on beta-cell function and cardioprotection in type 2 diabetics without advanced atherosclerosis.UMIN Clinical Trials Registry System as trial ID UMIN000005331.

  20. Basal insulin therapy strategy is superior to premixed insulin therapy in the perioperative period blood glucose management

    Institute of Scientific and Technical Information of China (English)

    HUANG Qing-xian; LOU Fu-chen; WANG Ping; LIU Qian; WANG Kun; ZHANG Li; ZHU Lei

    2013-01-01

    Background The probability and risk of operations increase in patients with type 2 diabetes mellitus.For diabetic patients,blood glucose control is a key factor to improving the prognosis of surgery.During perioperative period,insulin therapy is usually advised to be used for surgical patients with type 2 diabetes.However,the insulin regimen which one is better remains controversial.In this study,we estimated the efficacy,safety and advantage of different insulin therapy strategy during perioperative period.Methods A total of 1086 cases of surgical patients with type 2 diabetes mellitus enrolled in the present study.According to the glucose level at admission,all patients were divided into relatively high glucose group (group A,fasting blood glucose (FBG) <13.9 mmol/L) and higher glucose group (group B,FBG >13.9 mmol/L).Patients in group A randomly accepted premixed insulin twice a day,or basal insulin plus oral medications,and were divided into group A1 and A2 respectively.Patients in group B randomly received premixed insulin twice daily,basal insulin plus oral hypoglycemic agents,or basal insulin plus preprandial insulin,and were divided into group B1,B2 and B3 respectively.The data of the preoperative preparation time,the daily doses of insulin used in different periods,postoperative incision healed installments,hypoglycemic events,the total hospitalization time,postoperative complications were all collected and statistically analyzed.Results Compared the main outcome measures in groups treated by premixed insulin therapy,both in preoperative preparation and postoperative period,the daily insulin dosage and the frequency of hypoglycemic events were decreased in groups treated by basal insulin therapy (P <0.05).The preoperative preparation time and the total hospitalization time in groups with basal insulin therapy were shorter than that in groups with premixed insulin therapy (P <0.05).The incision healing rate of stage Ⅰ,Ⅱ and Ⅲ among different

  1. Insulin Analogs: Impact on Treatment Success, Satisfaction, Quality of Life, and Adherence

    OpenAIRE

    Hartman, Israel

    2008-01-01

    A growing body of medical research has demonstrated that intensive control of serum glucose levels can minimize the development of diabetes-related complications. Success with insulin management ultimately depends on how closely a given regimen can mimic normal physiologic insulin release patterns. The new insulin analogs, including the rapid-acting analogs (aspart, lispro, glulisine), the long-acting basal analogs (glargine, detemir), and the premixed insulin analog formulations (75% neutral...

  2. Insulin aspart insulin glargine combined effect of type 2 diabetes advantage%门冬胰岛素联合甘精胰岛素治疗2型糖尿病的疗效优势

    Institute of Scientific and Technical Information of China (English)

    李超炎; 陈爱民

    2015-01-01

    目的:探讨门冬胰岛素联合甘精胰岛素治疗2型糖尿病的疗效优势。方法选取2012年1月~2014年6月住院的68例2型糖尿病患者,随机分为门冬胰岛素联合甘精胰岛素组(实验组)和胰岛素泵组(对照组),均为34例,两组均接受正规的糖尿病饮食、运动指导及其他教育,生活作息时间及治疗规律。实验组的所有患者均予以门冬胰岛素(早、中、晚餐前,即刻皮下注射,诺和锐)+甘精胰岛素(晚睡前,皮下注射,来得时)治疗;对照组的所有患者均予以胰岛素泵持续皮下注射门冬胰岛素,两组患者均观察每日空腹血糖、3餐餐后2h血糖、晚10时血糖、空腹C肽、空腹淀粉酶、空腹脂肪酶、日血糖波动情况、日胰岛素用量、低血糖例数、体质指数、治疗达标时间及治疗费用。结果各组治疗前后的血糖控制情况、空腹C肽、空腹淀粉酶、空腹脂肪酶这些指标差异均有统计学意义(P<0.05),体质指数差异无统计学意义(P>0.05);两组的日胰岛素用量、日血糖波动情况差异无统计学意义(P>0.05);实验组较对照组的治疗费用低,低血糖例数多(P<0.05),但达标所需时间长(P<0.05)。结论门冬胰岛素联合甘精胰岛素治疗的低血糖发生率高、达标时间长,但费用低,适用于基层医院及经济困难的患者,值得推广。%Objective To explore joint glargine insulin aspart treatment of type 2 diabetes treatment benefit. Methods Select from January 2012 to June 2014 68 hospitalized patients with type 2 diabetes in hospitalized patients were randomly divided into joint glargine insulin aspart group(experimental group)and insulin pump (control group) were 34 cases,two group were to receive formal diabetic diet,exercise instruction and other educational,lifestyle and treatment time rule.All patients in the experimental group were to be insulin

  3. Lantus, the first peakless basal insulin analogue: 10 years of clinical experience in children and adolescents

    Directory of Open Access Journals (Sweden)

    Tamara Leonodovna Kuraeva

    2014-05-01

    Full Text Available This review analyses existing literature, including authors' own data, describing the results of clinical trials which assess safety and efficacy of insulin Glargine (Lantus® in children and adolescents, as well as peculiar features of T1D management in this age group, including the challenge of reducing the rate of hypoglycemia while maintaining adequate glycemic control. The article also discusses various issues in T1D management in children and adolescents, including the role of glycemic control in development of vascular complications, hypoglycemia and the variability of glycemia. The data confirm the high efficacy of Lantus insulin in respect to metabolic control, including the decrease in the incidence of hypoglycemia and in variability of glycemic profile, the safety of its clinical use in treatment of children, including young children, and adolescents, as well as its ability to improve the quality of life for patients and their parents.

  4. Acarbose insulin glargine combined on treatment of elderly diabetic%甘精胰岛素联合阿卡波糖治疗老年糖尿病的疗效观察

    Institute of Scientific and Technical Information of China (English)

    王明岗

    2010-01-01

    目的 探讨甘精胰岛素联合阿卡波糖治疗老年糖尿病的临床疗效.方法 2008年1月至2010年1月门诊或住院诊治的老年2型糖尿病患者246例,随机分为治疗组126例,对照组120例,治疗组采用甘精胰岛素联合阿卡波糖治疗,对照组采用精蛋白锌重组人胰岛素混合注射液治疗;观察两组临床效果及B细胞功能变化.结果 两组血糖达标时间比较,P<0.05有显著差异性;两组胰岛素日用量、低血糖发生率比较,P<0.01有显著差异性;治疗前、后C肽+胰岛素释放试验检测比较P<0.05有显著差异性.结论 甘精胰岛素联合阿卡波糖能达到良好控制血糖,又能减少胰岛素用量,降低低血糖发生率,有效的改善β细胞功能.而且用药依从性良好的治疗老年2型糖尿病方案.%Objective To investigate insulin glargine combined acarbose treatment of senile diabetes therapy. Methods 246 cases type 2 diabetes were treated in out - patient or in hospital from January 2008 to January 2010 who were randomly divided into treatment group( 126 ) and control group (120). Treatment group patients treated with insulin glargine combined acarbose treatment, and control group were treated by Protamine zinc mixed recombinant human insulin injection treatment;To observe clinical effects and β -cell function. Results Comparison of two groups of blood glucose time, P < 0. 05; Two groups of insulin daily dose, the incidence of hypoglycemia,P < 0. 01 ;Treatment before and after the C peptide + insulin release test comparison, P < 0. 05; Conclusion Insulin glargine combined acarbose can achieve good control of blood glucose and reducing insulin dosage, reducing the incidence of low blood sugar, which an improvement of β cell function. It is a good drug compliance and treatment program in elderly type 2 diabetes.

  5. Efficacy Observation of Insulin Glargine Combined with Nateglinide in Treatment of Senile Type 2 Diabetes Mellitus%甘精胰岛素联合那格列奈治疗老年2型糖尿病32例

    Institute of Scientific and Technical Information of China (English)

    宁尚侠; 李桃荣

    2011-01-01

    目的 观察甘精胰岛素联合那格列奈治疗老年2型糖尿病的效果.方法 将64例老年2型糖尿病患者随机均分为甘精胰岛素组(以下简称"甘精组")和预混胰岛素组(以下简称"预混组").甘精组于三餐前10 min口服那格列奈90~180 mg,晚10:00皮下注射甘精胰岛素;预混组于早晚餐前30min注射预混胰岛素.应用强生稳步血糖仪,每日监测两组患者三餐餐后2h血糖以及晚10:00、凌晨3:00、晨8:00指尖血糖,根据血糖值每2~3 d增减胰岛素剂量2~4 U.空腹血糖低于7.0 mmoL/L和餐后2 h血糖低于10.0 mmol/L为血糖达标,观察血糖达标时间、胰岛素用量、低血糖发生次数和发生病例数.以及16周后患者的空腹血糖、餐后2 h血糖、糖化血红蛋白、体重指数,结果 两组患者的血糖控制均达标,血糖达标时间差异无统计学意义;16周后空腹血糖、餐后2 h血糖、糖化血红蛋白比较,组间差异无统计学意义,治疗前后组内差异有统计学意义(P<0.01);甘精组体重指数无明显变化,预混组较治疗前明显增加(P<0.05);甘精组胰岛素日用量和低血糖发生病例数均显著低于预混组(P<0.01).结论 两种治疗方案对控制血糖都有效,但甘精胰岛素联合那格列奈能减少胰岛素的注射次数和日用量.降低低血糖风险,不增加体重指数,患者依从性好.%Objective To observe the effect of insulin glargine combined with nateglinide in the treatment of senile type 2 diabetes mellitus.Methods Sixty-four patients with type 2 diabetes were divided into 2 groups randomly;glargine group (32 cases) and pre-mixed insulin group (32 cases). The glargine group was given oral nateglinide 90- 180 mg at 10 min before breakfast, lunch and supper respectively and hypodermical injection of glargine once at 22 o'clock every night, while the pre -mixed insulin group was hypodermically injected with the pre-mixed insulin at 30 min before breakfast and supper

  6. Rationale supporting basal insulin-incretin combined therapies in type 2 diabetes

    OpenAIRE

    Scheen, André; Paquot, Nicolas

    2013-01-01

    Type 2 diabetes is characterized by an insulin secretory defect that cannot compensate for insulin resistance. Such relative defect is present in the fasting state (insufficient basal insulin levels) and contributes to overnight hyperglycaemia; it is even more pronounced in the postprandial state when it is then the main responsible factor for hyperglycaemia following meals. An original approach to correct these two disturbances is to propose a therapy combining the injection of a basal insul...

  7. Insulin degludec is a new ultra-long-acting insulin analogue

    Directory of Open Access Journals (Sweden)

    Ivan Ivanovich Dedov

    2014-06-01

    Full Text Available Achieving optimal glycemic control is an important aspect of preventing and slowing the progression of diabetes-associated complications, and reducing the cost of their treatment. Long-acting insulin analogues, glargine and detemir, provide better metabolic control with reduced risk of hypoglycaemia as compared to NPH insulin. However, fear of hypoglycaemia and weight gain, as well as the complexity of regimen, are still the most important barriers to well-timed initiation and intensification of insulin therapy. Insulin degludec (Tresiba® is a new ultra-long-acting insulin analogue. After subcutaneous injection degludec forms repository of soluble multi-hexamers, which are gradually absorbed to the bloodstream, providing a flat, stable antihyperglycemic effect lasting more than 42 h, and low intra-individual variability as opposed to currently used basal insulin analogues, insulin glargine and insulin detemir. In the seven randomized, open label, controlled phase 3 trials lasting 26 or 52 weeks, using treat-to-target (no more non-inferiority design, insulin degludec provided glycemic control similar to that of insulin glargine with lower risk of nocturnal hypoglycaemia and good safety profile in patients with type 1 or 2 diabetes. Furthermore, trials examining a flexible dosing regimen of insulin degludec in patients with type 1 or 2 diabetes have shown that it is possible to vary the injection time without compromising glycemic control or safety of the therapy.

  8. Combining a GLP-1 receptor agonist and basal insulin: study evidence and practical considerations.

    Science.gov (United States)

    Carris, Nicholas W; Taylor, James R; Gums, John G

    2014-12-01

    Most patients with diabetes mellitus require multiple medications to achieve glycemic goals. Considering this and the increasing incidence of type 2 diabetes worldwide, the need for effective combination therapy is pressing. Basal insulin and glucagon-like peptide 1 (GLP-1) receptor agonists are frequently used to treat type 2 diabetes. Though both classes of medication are exclusively injectable, which may cause initial hesitation from providers, evidence for their combined use is substantial. This review summarizes the theoretical benefit, supporting evidence, and implementation of a combined basal insulin-GLP-1 receptor agonist regimen. Basal insulin added to a GLP-1 receptor agonist reduces hemoglobin A1c (HbA1c) without weight gain or significantly increased hypoglycemia. A GLP-1 receptor agonist added to basal insulin reduces HbA1c and body weight. Compared with the addition of meal-time insulin to basal insulin, a GLP-1 receptor agonist produces similar or greater reduction in HbA1c, weight loss instead of weight gain, and less hypoglycemia. Gastrointestinal adverse events are common with GLP-1 receptor agonists, especially during initiation and titration. However, combination with basal insulin is not expected to augment expected adverse events that come with using a GLP-1 receptor agonist. Basal insulin can be added to a GLP-1 receptor agonist with a slow titration to target goal fasting plasma glucose. In patients starting a GLP-1 receptor agonist, the dose of basal insulin should be decreased by 20 % in patients with an HbA1c ≤8 %. The evidence from 15 randomized prospective studies supports the combined use of a GLP-1 receptor agonist with basal insulin in a broad range of patients with uncontrolled type 2 diabetes.

  9. Safety and efficacy of a glucagon-like peptide-1 receptor agonist added to basal insulin therapy versus basal insulin with or without a rapid-acting insulin in patients with type 2 diabetes: results of a meta-analysis.

    Science.gov (United States)

    Wysham, Carol H; Lin, Jay; Kuritzky, Louis

    2017-05-01

    To consolidate the evidence from randomized controlled trials evaluating the use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) as add-on to basal insulin therapy in type 2 diabetes (T2D) patients. We searched the EMBASE® and NCBI PubMed (Medline) databases and relevant congress abstracts for randomized controlled trials evaluating the efficacy and safety of GLP-1 RAs as add-on to basal insulin compared with basal insulin with or without rapid-acting insulin (RAI) through 23 May 2016. The pooled data were analyzed using a random-effects meta-analysis model. A subanalysis was performed for trials investigating basal insulin plus GLP-1 RAs versus basal insulin plus RAI. Of the 2617 retrieved records, 19 randomized controlled trials enrolling 7,053 patients with T2D were included. Compared with basal insulin ± RAI, reduction in glycated hemoglobin (HbA1c) from baseline (difference in means: -0.48% [95% confidence interval (CI), -0.67 to -0.30]; p insulin plus GLP-1 RA. The subanalysis similarly showed significant results for change in HbA1c from baseline and for weight loss, as well as a significantly lower risk of symptomatic hypoglycemia in patients treated with basal insulin plus GLP-1 RA versus basal insulin plus RAI (odds ratio, 0.52 [95% CI, 0.42 to 0.64]; p insulin provided improved glycemic control, led to weight reduction and similar hypoglycemia rates versus an intensified insulin strategy; however, symptomatic hypoglycemia rates were significantly lower when compared with a basal insulin plus RAI.

  10. Drug-use patterns of initially prescribed insulin detemir and insulin glargine in the Netherlands; A comparative analysis using pharmacy data from IADB.nl

    NARCIS (Netherlands)

    Visser, S.T.; Vegter, S.; Boersma, C.; De Grooth, R.; Postma, M.J.

    2010-01-01

    OBJECTIVES: Newer long-acting insulin analogs have shown to result in several treatment improvements if compared with NPH insulins. Promising results from clinical trials require confirmation from observational settings reflecting potential “real-life” benefits. Therefore, the current study aimed to

  11. Drug-use patterns of initially prescribed insulin detemir and insulin glargine in the Netherlands; A comparative analysis using pharmacy data from IADB.nl

    NARCIS (Netherlands)

    Visser, S.T.; Vegter, S.; Boersma, C.; De Grooth, R.; Postma, M.J.

    2010-01-01

    OBJECTIVES: Newer long-acting insulin analogs have shown to result in several treatment improvements if compared with NPH insulins. Promising results from clinical trials require confirmation from observational settings reflecting potential “real-life” benefits. Therefore, the current study aimed to

  12. Combining basal insulin analogs with glucagon-like peptide-1 mimetics.

    Science.gov (United States)

    Perfetti, Riccardo

    2011-09-01

    Basal insulin analogs are recognized as an effective method of achieving and maintaining glycemic control for patients with type 2 diabetes. However, the progressive nature of the disease means that some individuals may require additional ways to maintain their glycemic goals. Intensification in these circumstances has traditionally been achieved by the addition of short-acting insulin to cover postprandial glucose excursions that are not targeted by basal insulin. However, intensive insulin regimens are associated with a higher risk of hypoglycemia and weight gain, which can contribute to a greater burden on patients. The combination of basal insulin with a glucagon-like peptide-1 (GLP-1) mimetic is a potentially attractive solution to this problem for some patients with type 2 diabetes. GLP-1 mimetics target postprandial glucose and should complement the activity of basal insulins; they are also associated with a relatively low risk of associated hypoglycemia and moderate, but significant, weight loss. Although the combination has not been approved by regulatory authorities, preliminary evidence from mostly small-scale studies suggests that basal insulins in combination with GLP-1 mimetics do provide improvements in A1c and postprandial glucose with concomitant weight loss and no marked increase in the risk of hypoglycemia. These results are promising, but further studies are required, including comparisons with basal-bolus therapy, before the complex value of this association can be fully appreciated.

  13. Observe the use of insulin glargine in diabetic stroke rehabilitation%甘精胰岛素在糖尿病脑卒中康复的应用观察

    Institute of Scientific and Technical Information of China (English)

    李锐莉; 李莲花; 兰倩

    2014-01-01

    目的:观察甘精胰岛素联合口服降糖药物在2型糖尿病脑卒中康复治疗中的疗效。方法将2型糖尿病脑卒中患者80例随机分为试验组和对照组,每组40例,2组均行常规康复治疗。试验组给予入院后胰岛素的强化治疗,7 d~10 d后甘精胰岛素联合一种降糖药物降血糖,对照组给予常规口服药物降血糖。观察2组患者治疗后4周、8周神经功能评分,比较患者康复治疗疗效。结果试验组康复效果优于对照组,尤以治疗后8周效果显著。结论甘精胰岛素在糖尿病脑卒中康复治疗中具有良好作用,值得推广。%Objective Clinical observation of insulin glargine combined with oral hypoglycemic drugsin type2 diabetes, stroke rehabilitation. Methods 80 cases of type 2 diabeticpatients with stroke,randomly divided into experimental group,control group.40 patients in each group,two groups were given conventional rehabilitation therapy. The experimental group received intensive therapy of insulinafter admission ,7-10 days after insulin glargine combined with a hypoglycemic drug reducing blood sugar.The control group was given conventional oral hypoglycemicdrugs. The two groups were observed respectively after treatment 4 weeks,8 weeks,the use of neural function score,compared with the effect of rehabilitation therapy. Results The effect of experimental group is better than the control group. Conclusion insulin glargine have a good effect on stroke rehabilitation in the treatment of diabetes.

  14. Additional lunchtime basal insulin during insulin lispro intensive therapy in a randomized, multicenter, crossover study in adults - A real-life design

    NARCIS (Netherlands)

    Stades, AME; Hoekstra, JBL; van den Tweel, [No Value; Erkelens, DW; Holleman, F

    2002-01-01

    OBJECTIVE - This study vas performed to evaluate whether an additional dose of NPH insulin at lunchtime might overcome the deleterious effects of waning basal insulinemia on pre-dinner and evening glucose values during insulin lispro intensive therapy with once daily basal insulin at night, RESEARCH

  15. Insulin pump basal adjustment for exercise in type 1 diabetes: a randomised crossover study.

    Science.gov (United States)

    McAuley, Sybil A; Horsburgh, Jodie C; Ward, Glenn M; La Gerche, André; Gooley, Judith L; Jenkins, Alicia J; MacIsaac, Richard J; O'Neal, David N

    2016-08-01

    The aim of this study was to investigate the effects of exercise, vs rest, on circulating insulin and glucose, following pre-exercise insulin pump basal rate reduction. This was an open-label, two-stage randomised crossover study of 14 adults (seven women, seven men) with type 1 diabetes established on insulin pump therapy. In each stage, participants fasted and insulin delivery was halved following a single insulin basal rate overnight. Exercise (30 min moderate-intensity stationary bicycle exercise, starting 60 min post-basal reduction) and rest stages were undertaken in random order at a university hospital. Randomisation was computer-generated, and allocation concealed via sequentially numbered sealed opaque envelopes. Venous blood was collected at 15 min intervals from 60 min pre- until 210 min post-basal rate reduction. Changes in plasma free insulin (the primary outcome), and changes in plasma glucose, with exercise were compared with changes when resting. Outcomes were assessed blinded to group assignment. Following basal rate reduction when rested, mean (± SE) free insulin decreased by 4.9 ± 2.9%, 16.2 ± 2.6% and 18.6 ± 3.2% at 1, 2 and 3 h, respectively (p insulin increased by 6 ± 2 pmol/l after 15 min and 5 ± 2 pmol/l after 30 min (p insulin rate 1 h prior to exercise did not significantly reduce circulating free insulin by exercise commencement. Exercise itself transiently increased insulin levels. In participants with low-normal glucose pre-exercise, hypoglycaemia was not prevented by insulin basal rate reduction alone. Greater insulin basal rate reduction and supplemental carbohydrate may be required to prevent exercise-induced hypoglycaemia. ANZCTR.org.au ACTRN12613000581763 FUNDING: Australian Diabetes Society, Hugh DT Williamson Foundation, Lynne Quayle Charitable Trust Fund.

  16. Adding prandial GLP-1 receptor agonists to basal insulin: a promising option for type 2 diabetes therapy.

    Science.gov (United States)

    Goldenberg, Ronald M; Berard, Lori

    2017-08-24

    Diabetes mellitus is a serious and increasingly prevalent condition in Canada and around the world. Treatment strategies have become increasingly complex, with a widening array of pharmacological agents available for glycemic management in type 2 diabetes mellitus (T2DM). New therapies that act in concert with available basal insulins may represent alternatives to basal insulin intensification with prandial or premixed insulin. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have recently shown promise as useful additions to basal insulin, with significant reductions in glycated hemoglobin and potentially beneficial effects on body weight. This review will focus on pivotal clinical trials to assess the potential benefits of adding prandial GLP-1 RAs to basal insulin in patients with T2DM. Clinical studies combining prandial GLP-1 RAs and basal insulin (published between 2011 and July 2017) were identified and reviewed in PubMed, the Cochrane Central Register of Clinical Trials (Issue 6, June 2017) and clinicaltrials.gov. Most of the studies presented in this review show that the addition of a prandial GLP-1 RA to basal insulin results in equal or slightly superior efficacy compared to the addition of prandial insulin, together with weight loss and less hypoglycemia. The results of the studies suggest that a prandial GLP-1 RA as an add-on to basal insulin may be a safe and effective treatment intensification option (vs basal-plus or basal-bolus insulin).

  17. Therapeutic effect of glargine insulin combined with acarbose in elderly diabetic patients%甘精胰岛素联合阿卡波糖在老年糖尿病患者中的应用

    Institute of Scientific and Technical Information of China (English)

    罗小勇

    2013-01-01

    Objective To investigate the clinical efficacy and safety of glargine insulin combined with protamine zinc recombinant lispro insulin in elderly diabetic patients.Methods 96 cases of elderly diabetic were divided into the observation group (52 cases) and control group (44 cases),the control group was given protamine zinc recombinant insulin lispro treatment,and therapeutic effect was observed.Results After treatment FEG,2PBG and HbAlc were significantly lower than those before treatment (P<0.05); after treatment,glycemic index showed no significant difference between the two groups (P>0.05); the observation group' s hypoglycemia was 3.64%,significantly lower than 15.91% of the control group (P<0.05).Conclusion The combined therapy of the glargine insulin and acarbose treatment for senile diabetes is secure,effective,and patients are easier to accept.%目的 探讨甘精胰岛素联合阿卡波糖治疗老年糖尿病的临床疗效及安全性.方法 将96例老年糖尿病患者分为观察组52例和对照组44例,观察组给予甘精胰岛素联合阿卡波糖治疗,对照组给予精蛋白锌重组赖脯胰岛素治疗,观察两组患者治疗效果.结果 两组患者治疗后FEG、2PBG及HbAlc均明显低于治疗前(P<0.05);两组患者治疗后各血糖指标比较差异无统计学意义(P>0.05).观察组低血糖发生率为3.64%,明显低于对照组的15.91% (P<0.05).结论 甘精胰岛素联合阿卡波糖治疗老年糖尿病安全、有效,更易被患者接受.

  18. 30 cases of metformin combined with insulin glargine in the treatment of type 2 diabetes mellitus curative effect analysis%30例二甲双胍联合甘精胰岛素治疗2型糖尿病疗效分析

    Institute of Scientific and Technical Information of China (English)

    杨丽明

    2012-01-01

    Objective To observe the effect of metformin combined with insulin glargine in the treatment of type 2 diabetes mellitus. Methods 30 cases of type 2 diabetes mellitus patients with metformin combined with insulin glargine in the treatment curative effect analysis. Results the fasting plasma glucose and glycosylated hemoglobin decreased significantly, no hypoglycemia, weight index declined. Conclusion metformin combined with insulin glargine in the treatment of type 2 diabetes mellitus patients with medicine, from the good, safe, effective, feasible.%目的观察二甲双胍联合甘精胰岛素治疗2型糖尿病的疗效。方法对30例2型糖尿病患者经二甲双胍联合甘精胰岛素治疗疗效进行临床分析。结果空腹血糖及糖化血红蛋白明显下降,无低血糖发生,体重指数有所下降。结论二甲双胍联合甘精胰岛素治疗2型糖尿病,患者医从性好,安全、有效,具有可行性。

  19. Exercise Increases Insulin Content and Basal Secretion in Pancreatic Islets in Type 1 Diabetic Mice

    Directory of Open Access Journals (Sweden)

    Han-Hung Huang

    2011-01-01

    Full Text Available Exercise appears to improve glycemic control for people with type 1 diabetes (T1D. However, the mechanism responsible for this improvement is unknown. We hypothesized that exercise has a direct effect on the insulin-producing islets. Eight-week-old mice were divided into four groups: sedentary diabetic, exercised diabetic, sedentary control, and exercised control. The exercised groups participated in voluntary wheel running for 6 weeks. When compared to the control groups, the islet density, islet diameter, and β-cell proportion per islet were significantly lower in both sedentary and exercised diabetic groups and these alterations were not improved with exercise. The total insulin content and insulin secretion were significantly lower in sedentary diabetics compared to controls. Exercise significantly improved insulin content and insulin secretion in islets in basal conditions. Thus, some improvements in exercise-induced glycemic control in T1D mice may be due to enhancement of insulin content and secretion in islets.

  20. Basal and insulin-stimulated skeletal muscle sugar transport in endotoxic and bacteremic rats

    Energy Technology Data Exchange (ETDEWEB)

    Westfall, M.V.; Sayeed, M.M.

    1988-04-01

    Membrane glucose transport with and without insulin was studied in soleus muscle from 5-h endotoxic rats (40 mg/kg Salmonella enteritidis lipopolysaccharide), and in soleus and epitrochlearis muscles from 12-h bacteremic (Escherichia coli, 4 X 10(10) CFU/kg) rats. Glucose transport was measured in muscles by evaluating the fractional efflux of /sup 14/C-labeled 3-O-methylglucose (/sup 14/C-3-MG) after loading muscles with /sup 14/C-3-MG. Basal 3-MG transport was elevated in soleus muscles from endotoxic as well as in soleus and epitrochlearis muscles from bacteremic rats compared with time-matched controls. Low insulin concentrations stimulated /sup 14/C-3-MG transport more in bacteremic and endotoxic rat muscles than in controls. However, sugar transport in the presence of high insulin dose was attenuated in soleus and epitrochlearis muscles from bacteremic rats and soleus muscles from endotoxic rats compared with controls. Analysis of the dose-response relationship with ALLFIT revealed that the maximal transport response to insulin was significantly decreased in both models of septic shock. Sensitivity to insulin (EC50) was increased in endotoxic rat muscles, and a somewhat similar tendency was observed in bacteremic rat soleus muscles. Neural and humoral influences and/or changes in cellular metabolic energy may contribute to the increase in basal transport. Shifts in insulin-mediated transport may be due to alterations in insulin-receptor-effector coupling and/or the number of available glucose transporters.

  1. OPTIMAL REGIMENS OF THE BASAL-BOLUS INSULIN THERAPY IN ADOLESCENTS WITH TYPE 1 DIABETES MELLITUS

    Directory of Open Access Journals (Sweden)

    G. A. Galkina

    2015-01-01

    Full Text Available This study was aimed to determine peculiarities in regimens of the pump insulin therapy and to reveal the optimal basal-to-bolus insulin ratio that are necessary for achieving optimal glycemic control in adoles-cents with type 1 diabetes mellitus (T1DM.  82 adolescents at the age of 14–18 with T1DM, using continuous subcutaneous insulin infusion (CSII from 5 months to 7.5 years were monitored with continuous glucose monitoring (CGM system «Guar-dian Real Time» or CGM system, built in MiniMed Paradigm Revel System 722 (Medtronic Minimed, USA. Assessing the quality of glycaemic control was based on the level of glycated haemoglobin (HbA1c. The results of CGM were reviewed and average for 3 days performances: total daily dose of insulin, dose of basal and bolus insulin, basal-to-bolus insulin ratio, carbohydrate content of the meal, expressed in BE, carbohydrate ratio, insulin sensitivity factor were determined. The patients were subdivided into 2 groups: group 1 – adolescents with the optimal/suboptimal glycemic control (n = 55, 2 – adolescents with long-standing poorly controlled T1DM (n = 27. Average total daily dose of basal insulin (U in a day, U per kg in a day in adolescents group 1 was significantly higher, com-pared with patients in group 2 (р = 0.043; р = 0.038 respectively. Patients in group 2 received more car-bohydrates with a meal intake and had higher doses of average total daily bolus insulin. The average ba-sal-to-bolus ratio from group 1 patients was 51/49%, compared with group 2 patients – 45/55% (р = 0.026.  An important condition for achieving optimal glycemic control is a high level of compliance and skills of adolescents. Optimal well-balanced basal-to-bolus insulin ratio in adolescents with T1DM on CSII, which can provide improvements in blood glucose management and reducing the risk of complications of the disease, is 51/49%. 

  2. Use of the DISST model to estimate the HOMA and Matsuda indexes using only a basal insulin assay.

    Science.gov (United States)

    Davidson, Shaun M; Docherty, Paul D; Chase, J Geoffrey

    2014-07-01

    It is hypothesized that early detection of reduced insulin sensitivity (SI) could prompt intervention that may reduce the considerable financial strain type 2 diabetes mellitus (T2DM) places on global health care. Reduction of the cost of already inexpensive SI metrics such as the Matsuda and HOMA indexes would enable more widespread, economically feasible use of these metrics for screening. The goal of this research was to determine a means of reducing the number of insulin samples and therefore the cost required to provide an accurate Matsuda Index value. The Dynamic Insulin Sensitivity and Secretion Test (DISST) model was used with the glucose and basal insulin measurements from an Oral Glucose Tolerance Test (OGTT) to predict patient insulin responses. The insulin response to the OGTT was determined via population based regression analysis that incorporated the 60-minute glucose and basal insulin values. The proposed method derived accurate and precise Matsuda Indices as compared to the fully sampled Matsuda (R = .95) using only the basal assay insulin-level data and 4 glucose measurements. Using a model employing the basal insulin also allows for determination of the 1-day HOMA value. The DISST model was successfully modified to allow for the accurate prediction an individual's insulin response to the OGTT. In turn, this enabled highly accurate and precise estimation of a Matsuda Index using only the glucose and basal insulin assays. As insulin assays account for the majority of the cost of the Matsuda Index, this model offers a significant reduction in assay cost.

  3. IDegLira Versus Alternative Intensification Strategies in Patients with Type 2 Diabetes Inadequately Controlled on Basal Insulin Therapy

    DEFF Research Database (Denmark)

    Freemantle, Nick; Mamdani, Muhammad; Vilsbøll, Tina;

    2015-01-01

    glycated hemoglobin (HbA1c) and other outcomes. METHODS: A pooled analysis of five completed Novo Nordisk randomized clinical trials in patients with type 2 diabetes inadequately controlled on basal insulin was used to compare indirectly IDegLira (N = 199) with: addition of liraglutide to basal insulin (N...

  4. Controlled clinical research of poor glycemic control in type 2 diabetes treating with exenatide and insulin glargine%艾塞那肽与甘精胰岛素治疗血糖控制不佳的2型糖尿病的临床对照研究

    Institute of Scientific and Technical Information of China (English)

    杜予俊

    2014-01-01

    Objective To investigate the clinical curative effect,medication compliance and safety of poor gly-cemic control in type 2 diabetes treating with exenatide and insulin glargine. Methods Poor glycemic control patients in our hospital were chose and randomly divided into exenatide group and insulin glargine group,on the basis of the o-riginal oral hypoglycemic drugs treating,respectively gave exenatide and insulin glargine injection to control blood sug-ar,observed and recorded the blood sugar,glycosylated hemoglobin (HbA1c),body weight changes of the two groups before and after treatment, and contrastively analysed the medication adherence and the adverse reactions during the treatment. Results After 26 weeks treatment,the clinical symptoms and blood sugar of the two groups significantly improved than before treatment,the significant efficiency of insulin glargine group was slightly higher than exenatide group,but there was no significant difference (P>0. 05). FBG,2hPG,HbA1c levels of both groups significantly im-proved than before treatment (P0. 05). The weight of exenatide group decreased,the weight of insulin glargine in-creased,but compared with before treatment,the differences had no significance (P>0. 05). The hypoglycemia inci-dence of exenatide group significantly lowered than insulin glargine group (P0. 05 ) . The medication compliance of exenatide group was significantly better than that of insulin glargine group,the difference was significant (P0.05)。两组患者 FBG、2hPG、HbA1c水平均较治疗前有明显改善(P0.05)。艾塞那肽组患者体重呈进行性降低,甘精胰岛素组患者体重呈进行性增加,但与治疗前比较差异均无统计学意义(P>0.05)。艾塞那肽组患者低血糖发生率低于甘精胰岛素组,恶心、腹泻发生率均高于甘精胰岛素组,但差异均无统计学意义(P>0.05)。艾塞那肽组患者用药依从性明显优于甘精胰岛素组,差异有统计学意义(P<0.05)

  5. Rationale for, Initiation and Titration of the Basal Insulin/GLP-1RA Fixed-Ratio Combination Products, IDegLira and IGlarLixi, for the Management of Type 2 Diabetes.

    Science.gov (United States)

    Valentine, Virginia; Goldman, Jennifer; Shubrook, Jay H

    2017-08-01

    Type 2 diabetes (T2D) is a progressive disease affecting glucose regulation and a major cause of morbidity and mortality globally. Many patients are not escalated up the treatment ladder appropriately despite failing to achieve glycemic control, with barriers such as fear of hypoglycemia, weight gain, and treatment burden recognized as factors. Exogenous basal insulin is titrated to address control of fasting plasma glucose and may preserve residual β-cell function, thus promoting a greater endogenous prandial insulin response. Native glucagon-like peptide-1 (GLP-1) is a peptide hormone secreted by the gut in response to nutrient ingestion; it increases insulin secretion, inhibits glucagon secretion, and prolongs gastric emptying, thereby lowering overall food intake. As its glucose-lowering action is glucose dependent, a GLP-1 receptor agonist (GLP-1RA) achieves these benefits with a lower risk of hypoglycemia compared with other diabetes therapies. Two products, an insulin degludec/liraglutide combination (IDegLira) and an insulin glargine/lixisenatide combination (IGlarLixi), were approved for use in adults with T2D by the US Food and Drug Administration in 2016. The efficacy and safety of these two basal insulin/GLP-1RA combination products were studied in the DUAL program (NCTs 01336023, 01392573, 01676116, 01618162, 01952145, and 02298192) and the LixiLan program (NCTs 02058160 and 02058147). Compared with basal insulin, insulin/GLP-1RA fixed-ratio combinations are superior at reducing HbA1c with weight neutrality or weight loss rather than weight gain, as well as reduced hypoglycemia rates, and reduced insulin-dose requirement with IDegLira. A combination of different medications may often be required to achieve glycemic control, and fixed-ratio combination products allow such therapies to be given in simple regimens. Clinical trial data for these products highlight the great potential of these agents, not merely their efficacy and safety but also their

  6. Development of AIDA v4.3b Diabetes Simulator: Technical Upgrade to Support Incorporation of Lispro, Aspart, and Glargine Insulin Analogues

    Directory of Open Access Journals (Sweden)

    Eldon D. Lehmann

    2011-01-01

    Full Text Available Introduction. AIDA is an interactive educational diabetes simulator available on the Internet without charge since 1996 (accessible at: http://www.2aida.org/. Since the program’s original release, users have developed new requirements, with new operating systems coming into use and more complex insulin management regimens being adopted. The current work has aimed to design a comprehensive diabetes simulation system from both a clinical and information technology perspective. Methods. A collaborative development is taking place with a new generic model of subcutaneous insulin absorption, permitting the simulation of rapidly-acting and very long-acting insulin analogues, as well as insulin injections larger than 40 units. This novel, physiological insulin absorption model has been incorporated into AIDA v4. Technical work has also been undertaken to install and operate the AIDA software within a DOSBox emulator, to ensure compatibility with Windows XP, Vista and 7 operating systems as well as Apple Macintosh computers running Parallels PC emulation software. Results. Plasma insulin simulations are demonstrated following subcutaneous injections of a rapidly-acting insulin analogue, a short-acting insulin preparation, intermediate-acting insulin, and a very long-acting insulin analogue for injected insulin doses up to 60 units of insulin. Discussion. The current work extends the useful life of the existing AIDA v4 program.

  7. Treatment intensification using long-acting insulin -predictors of future basal insulin supported oral therapy in the DIVE registry.

    Science.gov (United States)

    Danne, Thomas; Bluhmki, Tobias; Seufert, Jochen; Kaltheuner, Matthias; Rathmann, Wolfgang; Beyersmann, Jan; Bramlage, Peter

    2015-10-07

    In patients with type-2 diabetes receiving oral antidiabetic drugs (OADs), the addition of insulin is frequently required to achieve sufficient control over blood glucose levels. It is, however, difficult to predict if, when and in which patients insulin therapy will be needed. We aimed to identify patient related variables associated with the addition of basal insulin to oral therapy resulting in a basal supported oral therapy (BOT). DIVE (DIabetes Versorgungs-Evaluation) is a prospective, observational, multi-centre diabetes registry established in Germany in 2011. For the present explorative analysis, 31,008 patients with type-2 diabetes prescribed at least one OAD were included. Patients who had previously received insulin and those over 90 years old were excluded. The event of interest was defined as the initiation of BOT during the observational period. Cause-specific Cox proportional hazards models based on a competing risk framework were applied for risk quantification. Multivariable adjusted hazard ratios demonstrated that longer diabetes duration, higher BMI, poorer glycaemic control, documentation of any micro- or macrovascular comorbidity, the presence of concomitant non-antidiabetic pharmacotherapies, and greater numbers of prescribed OADs increased the likelihood of BOT initiation. On the other hand BOT initiation was less likely in patients with older age and female gender. Analysing the likelihood of OAD termination without initiation of BOT provided supportive evidence for the variables predictive of BOT initiation. Analysis of the DIVE registry has resulted in the identification of a number of factors that may be predictive for the initiation of BOT for type-2 diabetes patients initially prescribed one or more OADs. Poor glycaemic control, the presence of vascular comorbidities and concomitant medications, and a greater number of OADs were all detected to increase the risk of a switch to BOT. Female gender and younger age showed protective

  8. An update on the treatment of type 1 and type 2 diabetes mellitus: focus on insulin detemir, a long-acting human insulin analog

    Directory of Open Access Journals (Sweden)

    Katarina Raslova

    2010-05-01

    Full Text Available Katarina RaslovaMetabolic Center Ltd and Slovak Medical University, Bratislava, Slovak RepublicAbstract: Basal insulin analogs are used to minimize unpredictable processes of NPH insulin. Modification of the human insulin molecule results in a slower distribution to peripheral target tissues, a longer duration of action with stable concentrations and thus a lower rate of hypoglycemia. Insulin detemir is a basal insulin analog that provides effective therapeutic options for patients with type 1 and type 2 diabetes. For glycemic control, no significant differences were found in HbA1c levels compared with NPH and insulin glargine. It is comparable with insulin glargine in significantly reducing rates of all types of hypoglycemia. Clinical studies have demonstrated that detemir is responsible for significantly lower within-subject variability and no or less weight gain than NPH insulin and glargine. Recent pharmacodynamic studies have shown that detemir can be used once daily in many patients with diabetes. Together with patient-friendly injection devices and dose adjustments, it provides a treatment option with the potential to lower the key barriers of adherence to insulin therapy in type 2 diabetes. Recent guidelines for treatment of type 2 diabetes suggest starting intensive therapy of hyperglycemia at an early stage of diabetes and recommend therapeutic options that provide the possibility of reaching HbA1c goals individually, with a low risk of hypoglycemia or other adverse effects of treatment. The properties of insulin detemir match these requirements.Keywords: insulin analog, insulin detemir, diabetes mellitus, hypoglycemia, within-subject variability

  9. Insulin use and persistence in patients with type 2 diabetes adding mealtime insulin to a basal regimen: a retrospective database analysis

    Directory of Open Access Journals (Sweden)

    Torres Amelito M

    2011-01-01

    Full Text Available Abstract Background The objective of this study was to characterize insulin use and examine factors associated with persistence to mealtime insulin among patients with type 2 diabetes (T2D on stable basal insulin therapy initiating mealtime insulin therapy. Methods Insulin use among patients with T2D initiating mealtime insulin was investigated using Thomson Reuters MarketScan® research databases from July 2001 through September 2006. The first mealtime insulin claim preceded by 6 months with 2 claims for basal insulin was used as the index event. A total of 21 months of continuous health plan enrollment was required. Patients were required to have a second mealtime insulin claim during the 12-month follow-up period. Persistence measure 1 defined non-persistence as the presence of a 90-day gap in mealtime insulin claims, effective the date of the last claim prior to the gap. Persistence measure 2 required 1 claim per quarter to be persistent. Risk factors for non-persistence were assessed using logistic regression. Results Patients initiating mealtime insulin (n = 4752; 51% male, mean age = 60.3 years primarily used vial/syringe (87% and insulin analogs (60%. Patients filled a median of 2, 3, and 4 mealtime insulin claims at 3, 6, and 12 months, respectively, with a median time of 76 days between refills. According to measure 1, persistence to mealtime insulin was 40.7%, 30.2%, and 19.1% at 3, 6, and 12 months, respectively. Results for measure 2 were considerably higher: 74.3%, 55.3%, and 42.2% of patients were persistent at 3, 6, and 12 months, respectively. Initiating mealtime insulin with human insulin was a risk factor for non-persistence by both measures (OR Conclusions Mealtime insulin use and persistence were both considerably lower than expected, and were significantly lower for human insulin compared to analogs.

  10. Effect of insulin glargine on heart and kidney damage in burned rats with delayed fluid resuscitation%甘精胰岛素对延迟复苏烧伤大鼠心脏肾脏损伤的影响

    Institute of Scientific and Technical Information of China (English)

    喻翔; 孔豫苏; 李伟人; 鲁加祥; 李嘉琥

    2015-01-01

    Objective To investigate the protective effect of insulin glargine against heart and kidney damage in burned rats with delayed fluid resuscitation.Methods Twenty-four male Sprague-Dawley ( SD) rats were randomly divided into three groups with 8 rats in each group:sham burn group, burn control group and burn plus insulin group.The sham burn group was immersed into 37 ℃ warm water for 15 seconds to simulate the burn process.The burn control group and burn plus insulin group were immersed into (95 ±0.5)℃ hot water for 15 seconds to make a rat model of 30% total burn surface area ( TBSA) ,Ⅲ degree burn injury rats received an intraperitoneal injection of physiological saline (40 mL/kg) at 6 h after burn.Insulin glargine [1.0 U/(kg· d)] was administered subcutaneously at 2 h postburn in burn plus insulingroup, and subcutaneous injection of the same volume physiological saline in the burn control group.Rats were sacrificed 24 h after burn, abdominal aorta blood was gathered and blood glucose, lactate dehydrogenase ( LDH ), α-hydroxybutyrate dehydrogenase (α-HBDH) , creatine kinase ( CK) , blood urea nitrogen( BUN) , creatinine ( Cr) were analysised.Oxidation and antioxidation parameters in heart and kidney obtained from rats, such as malondialdehyde (MDA), xanthine oxidase (XO), myeloperoxidase (MPO), superoxide dismutase 1 (SOD1), catalase (CAT), glutathion peroxidase (GPx) and the total antioxidant capacity (T-AOC), these parameters were detected by spectrophotometry.Creatine kinase MB ( CK-MB) was determined by immunosuppression.Results (1) Compared with the sham burn group, LDH, α-HBDH, CK, CK-MB, BUN, Cr were significantly higher in the burn control group (P<0.05).In the burn plus insulin group, LDH,α-HBDH, CK, CK-MB, BUN, Cr were significantly lower in comparison with the burn control group (P<0.05).(2) Compared with the sham burn group, the burn control group MDA, XO, MPO in the heart and kidney tissues were significantly higher (P<0.05); SOD1, CAT

  11. Patient safety and minimizing risk with insulin administration - role of insulin degludec.

    Science.gov (United States)

    Aye, Myint M; Atkin, Stephen L

    2014-01-01

    Diabetes is a lifelong condition requiring ongoing medical care and patient self-management. Exogenous insulin therapy is essential in type 1 diabetes and becomes a necessity in patients with longstanding type 2 diabetes who fail to achieve optimal control with lifestyle modification, oral agents, and glucagon-like peptide 1-based therapy. One of the risks that hinders insulin use is hypoglycemia. Optimal insulin therapy should therefore minimize the risk of hypoglycemia while improving glycemic control. Insulin degludec (IDeg) is a novel basal insulin that, following subcutaneous injection, assembles into a depot of soluble multihexamer chains. These subsequently release IDeg monomers that are absorbed at a slow and steady rate into the circulation, with the terminal half-life of IDeg being ~25 hours. Thus, it requires only once-daily dosing unlike other basal insulin preparations that often require twice-daily dosing. Despite its long half-life, once-daily IDeg does not cause accumulation of insulin in the circulation after reaching steady state. IDeg once a day will produce a steady-state profile with a lower peak:trough ratio than other basal insulins. In clinical trials, this profile translates into a lower frequency of nocturnal hypoglycemia compared with insulin glargine, as well as an ability to allow some flexibility in dose timing without compromising efficacy and safety. Indeed, a study that tested the extremes of dosing intervals of 8 and 40 hours showed no detriment in either glycemic control or hypoglycemic frequency versus insulin glargine given at the same time each day. While extreme flexibility in dose timing is not recommended, these findings are reassuring. This may be particularly beneficial to elderly patients, patients with learning difficulties, or others who have to rely on health-care professionals for their daily insulin injections. Further studies are required to confirm whether this might benefit adherence to treatment, reduce long

  12. Lower dose basal insulin infusion has positive effect on glycaemic control for children with type I diabetes on continuous subcutaneous insulin infusion therapy

    NARCIS (Netherlands)

    Schulten, Ron J; Piet, Jessica; Bruijning-Verhagen, Patricia; de Waal, Wouter J

    2017-01-01

    Objective: The aim of our study was to explore a possible relationship between proportion of basal insulin dose (%BD/T) and glycaemic control in children with type I diabetes on continuous subcutaneous insulin infusion (CSII) therapy. Methods: All patients under the age of 18 with type I diabetes

  13. Efficacy of insulin glargine combined with repaglinide in treatment of type 2 diabetes mellitus in elders%甘精胰岛素联合瑞格列奈治疗老年2型糖尿病的疗效观察

    Institute of Scientific and Technical Information of China (English)

    宁尚侠

    2011-01-01

    目的 观察老年2型糖尿病(T2DM)病人甘精胰岛素联合瑞格列奈降糖治疗的效果.方法 60例T2DM患者随机分为甘精组和预混组,甘精组三餐前15 min口服瑞格列奈0.5~1.0 mg,晚10∶00皮下注射甘精胰岛素.预混组于早晚饭前30 min注射预混胰岛素,应用罗康全血糖仪,住院期间监测空腹、三餐后2 h、夜10∶00、夜3∶00指尖血糖,根据血糖调整胰岛素剂量.空腹血糖(FPG)0.05),组内与治疗前相比差异有统计学意义(P0.05),甘精组BMI较治疗前无明显增加(P>0.05),预混组BMI较治疗前明显增加(P0.05 ). The duration for reaching the aim was similar in 2 groups ( P >0.05 );and the body mass index ( BMI) was markedly increased in mixed insulin group compared with pre - trial ( P 0.05). The incidence of hypoglycemia in glargine group was significantly lower than that of mixed insulin group ( P <0.01 ). The daily dosage of insulin in glargine group was significantly lower than that of mixed insulin group ( P <0.01 ). Conclusion Both of mixed insulin and insulin glargine combined with repaglinide have visible effects on controlling blood level of glucose, but the latter has better efficacy, better adherence and lower risk of hypoglycemia, it will not increase the body mass index, and it can decrease the frequency of injection and daily dosage of insulin.

  14. Relationship of body mass index with efficacy of exenatide twice daily added to insulin glargine in patients with type 2 diabetes

    NARCIS (Netherlands)

    Wolffenbuttel, B. H. R.; Van Gaal, L.; Duran-Garcia, S.; Han, J.

    2016-01-01

    This post hoc analysis assessed the evidence behind common reimbursement practices by evaluating the relationship of body mass index (BMI) ranges (35 kg/m(2)) with treatment effects of exenatide twice daily among patients with type 2 diabetes. Patients received exenatide twice daily added to insulin

  15. Double-blind, randomized, multicentre, and active comparator controlled investigation of the effect of Pioglitazone, Metformin, and the combination of both on cardiovascular risk in patients with type 2 diabetes receiving stable basal insulin therapy: the PIOCOMB study

    Directory of Open Access Journals (Sweden)

    Kleine Iris

    2011-07-01

    Full Text Available Abstract Background We analyzed specific effects of an add-on therapy with pioglitazone compared to metformin and their combination in patients with basal insulin treatment on biomarkers of CV risk. Methods In this double-blind, randomized, multicentre, active comparator controlled trial, 121 patients with type 2 diabetes were enrolled. Inclusions: treatment with basal insulin, HbA1C 6.5% - 8.5%, age 30 - 75 years. After glargine therapy over 2 weeks for titration towards FBG ≤ 7.8 mmol/L, patients received either (A bid 850 mg metformin (n = 42, (B bid 15 mg pioglitazone (n = 40, or (C 30 mg pioglitazone plus 1.7 g metformin (n = 39 over 6 months. Matrix Metal Proteinase 9 (MMP-9 was primary objective, together with biomarkers of CV risk. Results Pioglitazone (B reduced MMP-9 versus baseline by 54.1 + 187.1 ng/mL, with metformin (A it was increased by 49.6 + 336.2 ng/mL (p = 0.0345; B vs. A, and with the combination of both (C it was decreased by 67.8 + 231.4 ng/mL (A vs. C: p = 0.0416; B vs. C: p = 0.8695. After logarithmic transformation due to high variances the exploratory results showed significance for A vs. B (p = 0.0043 and for A vs. C (p = 0.0289. Insulin dosage was reduced by 7.3 units in group B (p 1C was only significantly decreased in the combination group. No significant effects were observed for NFkB and PGFα. peripheral edema were seen in 11.9% vs. 40.0% vs. 20.5%, and weight change was -0.7 kg vs. +4.3 kg vs. +2.7 kg (A vs. B vs. C. Conclusions Addition of pioglitazone but not of metformin reduces MMP-9, hs-CRP and increased insulin sensitivity and adiponectin in this study. The combination of both had no additional effect on inflammation. Pioglitazone is suggested to be a rational add-on therapy to basal insulin in patients with high CV risk.

  16. Effect of insulin glargine in combination with nateginide on type 2 diabetes%甘精胰岛素联合那格列奈在门诊2型糖尿病中的应用

    Institute of Scientific and Technical Information of China (English)

    胡利东; 栾晓军; 陈劲松

    2011-01-01

    Objective To observe the clinical efficacy of Lantus (insulin glargine)combinaed with nateginide on type 2 diabetes cases. Methods Sixty-eight type 2 diabetes cases meeting the diagnostic criteria of type 2 diabetes were injected with Lantus bedtime and administrated nateginide orally before 3 meals and observed for 12 weeks.. The levels of fasting blood sugar(FBG),glycated hemoglobin(HBALC )and Postprandial Blood Glucose(PBG)were measured before and after treatment,2 hours after treatment. Results 1,2,4,8,12 weeks after treatment,the FBG,PBG,HbAlc were significantly lower than that before treatment (P<0.05)with a low incidence of hypoglycemia. Conclusion The effect of combination of Lantus and nateginide can better simulate the physiological insulin secretion and reduce blood sugar. And the adverse reactions were mild and the patient compliance was good.%目的 观察来得时(甘精胰岛素)与那格列奈联合应用治疗门诊2型糖尿病的临床疗效.方法 选择符合诊断标准的2型糖尿病患者68例,给予睡前注射来得时并三餐前口服那格列奈,观察12周,分别检测治疗前、后空腹血糖(FBG)、餐后2h血糖(PBG)、糖化血红蛋白(HbA1c).结果 治疗后1、2、4、8、12周的FBG、PBG、HbA1c均较治疗前显著降低(P<0.05),低血糖的发生率低.结论 来得时联合应用那格列奈可更好的模拟生理性胰岛素分泌,有效降低血糖,不良反应少,病人依从性好.

  17. Asymmetric changes in circulating insulin levels after an increase compared with a reduction in insulin pump basal rate in people with Type 1 diabetes.

    Science.gov (United States)

    McAuley, S A; Ward, G M; Horsburgh, J C; Gooley, J L; Jenkins, A J; MacIsaac, R J; O'Neal, D N

    2017-08-01

    To investigate circulating insulin profiles after a clinically relevant insulin pump basal rate increase vs a reduction, and the associated glucose responses. A cohort of 12 adults with Type 1 diabetes undertook this two-stage university hospital study using Accu-Chek pumps (Roche Diagnostics, Mannheim, Germany) and insulin aspart. An insulin basal rate change of 0.2 unit/h (increase in first stage, reduction in second stage) was implemented at ~09:30 h, after a single overnight basal rate (without bolus insulin), while fasting participants rested. Frequent venous samples for the assessment of plasma free insulin, glucose and cortisol were collected from 60 min before until 300 min after rate change. The primary outcome was time to steady-state insulin. The 0.2-unit/h rate change represented a mean ± sd alteration of 23 ± 6%. After the rate increase, the median (interquartile range) times to 80% and 90% steady-state insulin were 170 (45) min and 197 (87) min, respectively. By contrast, after rate reduction, 80% steady-state insulin was not achieved. After the rate increase, mean ± se insulin levels increased by 4.3 ± 3.1%, 12.0 ± 2.9% and 25.6 ± 2.6% at 60, 120 and 300 min, respectively (with no significant difference until 180 min). After the rate reduction, insulin decreased by 8.3 ± 3.0% at 300 min (with no significant difference until 300 min). After rate reduction, glucose levels paradoxically declined by 17.4 ± 3.7% after 300 min; cortisol levels also fell during observation (P = 0.0003). The time to circulating insulin change after a 0.2-unit/h basal rate change was substantial, and was greater after a reduction than after an increase. Counter-regulatory hormone circadian variation may affect glycaemia when implementing minor changes at low basal rates. Both direction of basal rate change, and time of day, warrant consideration when anticipating the clinical effects of basal rate changes. © 2017 Diabetes UK.

  18. Variability of Basal Rate Profiles in Insulin Pump Therapy and Association with Complications in Type 1 Diabetes Mellitus.

    Directory of Open Access Journals (Sweden)

    Markus Laimer

    Full Text Available Traditionally, basal rate profiles in continuous subcutaneous insulin infusion therapy are individually adapted to cover expected insulin requirements. However, whether this approach is indeed superior to a more constant BR profile has not been assessed so far. This study analysed the associations between variability of BR profiles and acute and chronic complications in adult type 1 diabetes mellitus.BR profiles of 3118 female and 2427 male patients from the "Diabetes-Patienten-Verlaufsdokumentation" registry from Germany and Austria were analysed. Acute and chronic complications were recorded 6 months prior and after the most recently documented basal rate. The "variability index" was calculated as variation of basal rate intervals in percent and describes the excursions of the basal rate intervals from the median basal rate.The variability Index correlated positively with severe hypoglycemia (r = .06; p<0.001, hypoglycemic coma (r = .05; p = 0.002, and microalbuminuria (r = 0.05; p = 0.006. In addition, a higher variability index was associated with higher frequency of diabetic ketoacidosis (r = .04; p = 0.029 in male adult patients. Logistic regression analysis adjusted for age, gender, duration of disease and total basal insulin confirmed significant correlations of the variability index with severe hypoglycemia (β = 0.013; p<0.001 and diabetic ketoacidosis (β = 0.012; p = 0.017.Basal rate profiles with higher variability are associated with an increased frequency of acute complications in adults with type 1 diabetes.

  19. Severe hypoglycemia rates and associated costs among type 2 diabetics starting basal insulin therapy in the United States.

    Science.gov (United States)

    Ganz, Michael L; Wintfeld, Neil S; Li, Qian; Lee, Yuan-Chi; Gatt, Elyse; Huang, Joanna C

    2014-10-01

    To derive current real-world data on the rates and costs of severe hypoglycemia (SH) for people with type 2 diabetes mellitus (T2D) who have initiated basal insulin therapy and to examine differences in SH rates and costs stratified by history of prior SH events. We used a nation-wide electronic health records database that included encounter and laboratory data, as well as clinical notes, to estimate the rates and costs of SH events among adults with T2D who initiated basal insulin between 2008 and 2011. Unadjusted and regression-adjusted rates and quarterly costs were calculated for all patients as well as stratified by history of a SH event before starting basal insulin and history of a SH event during the basal insulin titration period. We identified 7235 incident cases of basal insulin use among patients with T2D who did not use insulin during the previous 12 months. Regression-adjusted incidence and total event rates were 10.36 and 11.21 per 100 patient-years, respectively. A history of SH events during the pre-index baseline and post-index titration periods were statistically significantly associated with both the incidence and total event rates (p costs were statistically significantly (p associated with costs. These results suggest that the real-world burden of SH is high among people with T2D who start using basal insulin and that history of previous SH events, both before starting insulin and during the insulin titration period, influences future SH. These results can also provide insights into interventions that can prevent or delay SH. These results should, however, be interpreted in light of the key limitations of our study: not all SH events may have been captured or coded in the database, data on filled prescriptions were not available, and the post-titration follow-up period could have been divided into time units other than quarters (3 month blocks) resulting in potentially different conclusions. Further real-world studies on the frequency and

  20. Insulin initiation in patients with type 2 diabetes mellitus: treatment guidelines, clinical evidence and patterns of use of basal vs premixed insulin analogues.

    Science.gov (United States)

    Vaag, Allan; Lund, Søren S; Lund, Sørens

    2012-02-01

    This review addresses the apparent disconnect between international guideline recommendations, real-life clinical practice and the results of clinical trials, with regard to the initiation of insulin using basal (long-acting) or premixed insulin analogues in patients with type 2 diabetes (T2D). English language guidelines vary considerably with respect to recommended glycaemic targets, the selection of human vs analogue insulin, and choice of insulin regimen. Randomised trials directly comparing insulin initiation between basal and premixed analogues are scarce, and hard endpoint outcome data are inadequate. The evidence presented suggests that a major component of the HbA1c not being attained in every day clinical practice may be a result of factors that are not adequately addressed in forced titration trials of highly motivated patients, including failure to comply with complex treatment and monitoring regimens. Enforced intensification of unrealistic complex treatment regimens and glycaemic targets may theoretically worsen the psychological well-being in some patients. More simple and sustainable treatment regimens and guidelines are urgently needed. As for the use of insulin in T2D, there is limited evidence to convincingly support that initiation of insulin using basal insulin analogues is superior to initiation using premixed insulin analogues. While awaiting improved clinical efficacy and cost-effectiveness data, practical guidance from national and international diabetes organisations should consider more carefully the importance of: i) being clear and consistent; and ii) the early implementation of sustainable and cost-effective insulin treatment regimens with an emphasis on optimising treatment ease of use and patient compliance.

  1. Observation of clinical effect by insulin glargine in the treatment of senile type 2 diabetes mellitus ;patients%甘精胰岛素治疗老年2型糖尿病患者的临床效果观察

    Institute of Scientific and Technical Information of China (English)

    王匀; 黄伟鹏; 梁煜; 郑雯文; 黄海玲; 严志辉

    2015-01-01

    目的:观察老年2型糖尿病患者采用甘精胰岛素治疗的临床效果。方法120例患有2型糖尿病的老年患者,将其随机分为对照组和观察组,每组60例,对照组采用精蛋白锌重组赖脯胰岛素治疗,观察组采用甘精胰岛素治疗。对比两组疗效。结果观察组患者治疗后的低血糖的发生率(13.33%)明显低于对照组(41.67%),观察组患者治疗后餐后2 h的血糖和空腹血糖、血糖达标时间、糖化血红蛋白(HbA1c)水平均好于对照组患者,两组比较差异具有统计学意义(P<0.05)。结论甘精胰岛素治疗老年患者2型糖尿病可缩短患者的血糖达标时间,治疗方案经济、安全、有效,临床价值较高。%Objective To observe the clinical effect of insulin glargine in the treatment of senile type 2 diabetes mellitus patients. Methods A total of 120 senile patients with type 2 diabetes mellitus were randomly divided into control group and observation group, with 60 cases in each group. The control group received insulin protamine zinc restructuring lispro for treatment, and the observation group received insulin glargine for treatment. Curative effects of the two groups were compared. Results The observation group had much lower incidence of hypoglycemia (13.33%) than the control group (41.67%) after treatment. The observation group also had better levels of 2 h postprandial blood glucose, fasting blood-glucose, blood glucose standard time, and glycosylated hemoglobin (HbA1c) than the control group. The differences between the two groups had statistical significance (P<0.05). Conclusion Insulin glargine can shorten blood glucose standard time in treating senile type 2 diabetes mellitus patients, and this method contains high clinical value as economical, safe and effective.

  2. The association between nonadherence and glycated hemoglobin among type 2 diabetes patients using basal insulin analogs

    Directory of Open Access Journals (Sweden)

    DiBonaventura M

    2014-06-01

    Full Text Available Marco DiBonaventura,1 Neil Wintfeld,2 Joanna Huang,2 Amir Goren1 1Health Outcomes Practice, Kantar Health, New York, NY, 2Health Economics and Outcomes Research, Novo Nordisk, Princeton, NJ, USA Background: The main objective of this study was to investigate the relationship between adherence and both clinical (ie, glycated hemoglobin [HbA1c] and nonclinical (ie, health status, work impairment, and health care-resource use health outcomes among type 2 diabetes (T2D patients using basal insulin. Materials and methods: The 2012 US National Health and Wellness Survey dataset was used for this study (n=71,141. A total of 1,198 respondents who reported a diagnosis of T2D, were currently using basal insulin, and reported both their HbA1c and level of nonadherence were included in the analyses. Classical test theory and item response theory (IRT analyses were used to provide evidence for the Morisky Medication Adherence Scale (MMAS in this population. Adherence was then used as a predictor of HbA1c and nonclinical outcomes using regression modeling, controlling for demographics and health history. Results: A total of 61.44% of respondents were male, and the mean age was 60.65 (standard deviation 10.74 years. Internal consistency of the eight-item MMAS (MMAS-8 was adequate (Cronbach's α=0.68, and one factor was retained (eigenvalue =1.80. IRT analyses suggested that the MMAS-8 was most precise for those with high levels of nonadherence. A significant relationship between variables emerged, whereby each point increase in the level of nonadherence was associated with a 0.21 increase in HbA1c (B=0.212, P<0.05. A modest quadratic trend was also observed (B=0.026, P<0.05, indicating that the benefit to HbA1c may taper off at high adherence. Each point of nonadherence was associated with a 4.6%, 20.4%, and 20.9% increase in the number of physician visits, emergency room visits, and hospitalizations, respectively. Discussion: This study provides evidence that

  3. Research on the efficacy and safety of insulin glargine in different administration time for treatment of type 1 diabetes%甘精胰岛素不同给药时间治疗1型糖尿病的疗效及安全性研究

    Institute of Scientific and Technical Information of China (English)

    李颖

    2014-01-01

    目的:探讨不同时间皮下注射甘精胰岛素治疗1型糖尿病的疗效及安全性。方法选取50例1型糖尿病患者,应用门冬胰岛素联合甘精胰岛素进行治疗,在甘精胰岛素不改变用量前提下,给药时间由22:00调整到18:00前后,比较时间调整前后3 d患者空腹血糖( FBG)、早中晚餐后2 h血糖(2hPG)和午餐前血糖的变化情况、门冬胰岛素的用量及午餐前患者低血糖事件发生情况。结果甘精胰岛素调整用药时间后,患者午餐前血糖调整至理想水平,FBG(7.28±2.13)mmol/L比(8.33±2.20)mmol/L、午餐后2hPG下降显著(8.61±2.59)mmol/L 比(9.70±1.75)mmol/L(U=2.425、3.034,均 P<0.05),早餐后2hPG (8.27±2.02)mmol/L比(8.56±2.33)mmol/L和晚餐后2hPG(9.54±1.55)mmol/L比(9.61±1.75)mmol/L变化均不明显(均P>0.05);门冬胰岛素早餐前用量减少,午餐前和晚餐前用量增加;午餐前低血糖事件显著减少(χ2=4.105、5.005,均P<0.05)。结论甘精胰岛素联合门冬胰岛素治疗1型糖尿病患者,在不改变甘精胰岛素用量情况下,给药时间由22:00调整为18:00,可平稳降低空腹血糖,减少午餐前低血糖的发生。%Objective To explore the clinical efficacy and safety of insulin glargine in different administra-tion time for treatment of type 1 diabetes .Methods 50 patients with type 1 diabetes were given insulin aspart and in-sulin glargine treatment scheme , under the premise of not change insulin glargine dosage , delivery time of insulin glargine varied from 22:00 to 18:00,and fasting blood glucose(FBG),2 hours postprandial blood glucose(2hPG), blood glucose and occurrence of hypoglycemia before lunch , amount of insulin aspart were noted and compared between before and after the adjustment .Results After adjustment of insulin glargine′s medication time , patients

  4. The quest for physiologic insulin replacement.

    Science.gov (United States)

    Owens, David R

    2004-11-01

    Historically, the objective of insulin replacement has been to simulate the 2 major components of insulin secretion in individuals without diabetes mellitus: the low-level basal secretion during the night and periods of fasting, and the prandial secretion in response to food intake. The variable pharmacokinetic and pharmacodynamic characteristics of conventional insulin preparations have made mimicking these physiologic profiles virtually impossible. Balancing the effects of diet, exercise, and the numerous factors contributing to intra- and inter-individual variations in insulin absorption and action, such as type, site of injection, and dosage of insulin, while avoiding the very serious side effect of hypoglycemia in seeking normoglycemia, presents a further challenge. Recently, these limitations have been addressed by recombinant DNA-mediated development of insulin analogues, such as rapid-acting insulin lispro, aspart and glulisine, and the long-acting insulin preparations, insulin glargine and detemir. The molecular structures of these analogues have produced time-action profiles that better approach prandial and basal insulin secretion, thus allowing for easier, safer, and more flexible treatment regimens.

  5. 甘精胰岛素联合阿卡波糖治疗老年糖尿病30例及护理分析%Clinical Effect of Insulin Glargine Combined with Acarbose in Treating Senile Diabetes and Nursing Analysis in 30 Cases

    Institute of Scientific and Technical Information of China (English)

    胡明伟; 毛柳

    2015-01-01

    目的:观察甘精胰岛素联合阿卡波糖治疗老年糖尿病的临床疗效。方法选取老年2型糖尿病患者60例,随机均分为治疗组和对照组。治疗前护理人员对所有患者的基本情况进行评估,在整个过程中对其进行健康教育、饮食护理、运动护理、预防低血糖等。治疗组采用甘精胰岛素联合阿卡波糖治疗,甘精胰岛素皮下注射、1次/日,阿卡波糖片口服、3次/日;对照组采用门冬胰岛素30皮下注射,早晚餐前各1次。16周后评价两组疗效。结果治疗组餐后2 h血糖明显高于对照组( P 0.05);治疗组低密度脂蛋白胆固醇低于治疗前水平( P0.05)。结论甘精胰岛素联合阿卡波糖治疗老年糖尿病,能较好控制患者血糖,且低血糖发生率低,依从性好,值得临床推广。%Objective To observe the clinical effect of insulin glargine combined with acarbose in treating senile diabetes and to analyze its nursing. Methods 60 elderly patients with type 2 diabetes mellitus ( T2DM ) were selected and divided into the treatment group and the control group randomly and equally. The nursing staff conducted the evaluation on the basic situation of all patients before treatment and performed the health education, dietary nursing, exercise nursing, hypoglycemia prevention, etc. The treatment group was treated by in-sulin glargine combined with acarbose, insulin glargine by subcutaneous injection once daily, oral acarbose tablets 3 times daily;the con-trol group adopted the Insulin Aspart 30 Injection by subcutaneous injection, once before breakfast and again before dinner. The fasting and postprandial blood glucose level, glycated hemoglobin and incidence of hypoglycemia after 16 weeks were observed and compared between the two groups. The blood pressure and blood lipids in the treatment group were compared between before and after treat-ment. Results The postprandial 2 h blood glucose level in the

  6. Reduced insulin-receptor mediated modulation of striatal dopamine release by basal insulin as a possible contributing factor to hyperdopaminergia in schizophrenia.

    Science.gov (United States)

    Caravaggio, Fernando; Hahn, Margaret; Nakajima, Shinichiro; Gerretsen, Philip; Remington, Gary; Graff-Guerrero, Ariel

    2015-10-01

    Schizophrenia is a severe and chronic neuropsychiatric disorder which affects 1% of the world population. Using the brain imaging technique positron emission tomography (PET) it has been demonstrated that persons with schizophrenia have greater dopamine transmission in the striatum compared to healthy controls. However, little progress has been made as to elucidating other biological mechanisms which may account for this hyperdopaminergic state in this disease. Studies in animals have demonstrated that insulin receptors are expressed on midbrain dopamine neurons, and that insulin from the periphery acts on these receptors to modify dopamine transmission in the striatum. This is pertinent given that several lines of evidence suggest that insulin receptor functioning may be abnormal in the brains of persons with schizophrenia. Post-mortem studies have shown that persons with schizophrenia have less than half the number of cortical insulin receptors compared to healthy persons. Moreover, these post-mortem findings are unlikely due to the effects of antipsychotic treatment; studies in cell lines and animals suggest antipsychotics enhance insulin receptor functioning. Further, hyperinsulinemia - even prior to antipsychotic use - seems to be related to less psychotic symptoms in patients with schizophrenia. Collectively, these data suggest that midbrain insulin receptor functioning may be abnormal in persons with schizophrenia, resulting in reduced insulin-mediated regulation of dopamine transmission in the striatum. Such a deficit may account for the hyperdopaminergic state observed in these patients and would help guide the development of novel treatment strategies. We hypothesize that, (i) insulin receptor expression and/or function is reduced in midbrain dopamine neurons in persons with schizophrenia, (ii) basal insulin should reduce dopaminergic transmission in the striatum via these receptors, and (iii) this modulation of dopaminergic transmission by basal insulin

  7. Controlled clinical study of the effect of exenatide and insulin glargine for poor glycemic control in type 2 diabetes%艾塞那肽与甘精胰岛素治疗血糖控制不佳2型糖尿病的临床对照研究

    Institute of Scientific and Technical Information of China (English)

    简强; 李德东; 李鹏飞

    2016-01-01

    Objective To investigate the effect of exenatide and insulin glargine for poorly glycemic controlled in type 2 diabetes.Method 92 poor glycemic control patients with type 2 diabetes in the navy general hospital were chosen and divided into exenatide group and insulin glargine group, that each group has 46 cases. The clinical efficiency of the two groups were observed and compared, the changes of the body mass index, glycemic control, and the incidence of associated complications.ResultThe difference of the clinical curative effect between two groups was not statistically significant(P>0.05). Compared two groups’ respective change of their body mass index between before and after treatment, there was no significant difference (P>0.05); the body mass index of exenatide group was lower than the insulin glargine after treatment (P0.05). ConclusionRelative to insulin glargine, exenatide can more effectively reduce body mass index, lower glycated hemoglobin, lower incidence of hypoglycemia, which is worth promoting in clinical practice.%目的:探讨艾塞那肽与甘精胰岛素治疗血糖控制不佳2型糖尿病的临床对照效果。方法选取海军总医院收治的血糖控制不佳2型糖尿病患者92例,按照随机数字表法分为艾塞那肽组和甘精胰岛素组各46例,比较两组患者的各项指标。结果两组患者的临床疗效比较,差异无显著性(P>0.05)。两组患者治疗前的体重指数差异均无显著性(P>0.05)。但治疗后艾塞那肽组体重指数较甘精胰岛素组明显降低(P<0.05)。两组患者治疗后的血糖控制情况均较治疗前有明显好转(P<0.05);甘精胰岛素组的空腹血糖控制水平明显优于艾塞那肽组(P<0.05);艾塞那肽组的餐后2小时血糖、糖化血红蛋白控制水平明显优于甘精胰岛素组(P<0.05);两组患者不良反应发生率比较,差异无显著性(P>0.05)。结论相对甘精胰岛素而言,

  8. Potential value of the Asian Treat to Target Lantus Study (ATLAS) for type 2 diabetes management in China: safety and efficacy of two treatment algorithms using insulin glargine%患者主导与医生主导甘精胰岛素剂量调整:ATLAS中国结果

    Institute of Scientific and Technical Information of China (English)

    潘长玉; 田慧; 李启富; 杨文英; 彭永德; 冯波; 洪天配; 邝建; 杜建玲

    2015-01-01

    Objective The Asian Treat to Target Lantus Study (ATLAS) is designed to compare the effectiveness of a patient-versus physician-led initiation of insulin glargine-based basal management in the specific setting of Asia.This report presents the ATLAS study in China.Methods A total of 161 Chinese patients were randomized to either the patient-led (n =80) titration group or the physician-led (n =81) titration group.In the physician-led group,the patients were asked to be reviewed by a physician every two weeks at outpatient department.In the patient-led group,the patients were empowered to adjust their insulin doses every three days,under strict investigator's supervision,according to the middle value of the last 3 continuous values of FBG.ResultsAfter24 weeks treatment,HbA1C level in each group decreased significantly as compared with baseline and the decreases ranges were similar in the two groups (-1.38% vs-1.21%,P=0.581).A little more patients in the physician-led group (45.7%) achieved blood glucose control (HbA1C < 7%) than those in the patient-led group (43.8%).Severe hypoglycemia was rare in both groups.Body weight did not significantly increase in both groups by 24 weeks.The patients' satisfaction and quality of life were all improved.Conclusion Glargine is safe and effective in improving glycemic control in T2DM patients.A simple patient-led titration algorithm conferred a similar level better glycemic control as compared with physician-led titration,being with no increase in incidence of severe hypoglycemia.Meanwhile,patients' satisfaction and quality of life were improved.%目的 亚洲来得时治疗达标研究(Asian Treat to Target Lantus Study,ATLAS)纳入161例中国2型糖尿病患者,旨在明确患者主导与医生主导甘精胰岛素剂量调整在血糖控制、安全性、生活质量等方面的差异.方法 患者随机分为患者主导和医生主导剂量调整组,医生调整组:患者每2周1次

  9. 利拉鲁肽和甘精胰岛素治疗2型糖尿病的最小成本分析Δ%Cost-minimization Analysis of Liraglutide and Insulin Glargine in the Treatment of Type 2 Diabetes Mellitus

    Institute of Scientific and Technical Information of China (English)

    蒙光义; 王冬晓; 庞家莲; 彭评志; 莫金权; 严浩林; 梁慧; 张萍

    2016-01-01

    OBJECTIVE:To evaluate the clinical efficacy of liraglutide and insulin glargine in the treatment of type 2 diabetes mellitus (T2DM) and conduct pharmacoeconomic analysis, and to provide economical and reasonable T2DM treatment plan. METHODS:80 T2DM patients were randomized into liraglutide group and insulin glargine group,with 40 cases in each group. Both groups were given Metformin hydrochloride sustained-release tablet orally 0.5-2.0 g/d,and diabetes mellitus diet and sport training guide after oral antidiabetic drug withdrawal of previous treatment plan. Liraglutide group was given Liraglutide injection hypodermically,0.6-1.2 mg,qd;insulin glargine group was given insulin glargine hypodermically at 22 o’clock,initial dose of 0.2 IU/(kg·d),adjusted according to the levels of PG,FBG,nocturnal blood glucose level till FBG≤7 mmo1/L and 2 h PG ≤10 mmol/L in both group. Treatment course of 2 groups lasted for 12 weeks. The changes of FBG,2 h PG,HbA1c and BMI were ob-served in 2 groups before and after treatment. 2 therapy plans were evaluated and compared by cost-minimization analysis. RE-SULTS:After treatment,the levels of FBG,2 h PG and HbA1c decreased significantly in 2 groups,compared to before treatment, with statistical significance (P0.05). After treat-ment,BMI of liraglutide group decreased significantly compared with before treatment and insulin glargine group,with statistical significance (P0.05). Cost-minimization analysis showed that the cost of insulin glargine group in reducing FBG,2 h PG and HbA1c were less than liraglutide group,but were more than liraglutide group in reducing BMI. Sensitivity analysis demonstrated the stability and reliability of cost-minimization analysis. CONCLUSIONS:Lira-glutide and insulin glargine have the same clinical efficacy,but insulin glargine need lower cost in blood glucose control,and liraglutide is better therapy plan for body weight control.%目的:评价利拉鲁肽和甘精胰岛素治疗2型糖尿病(T2

  10. Carcinogenicity of insulin analogues

    NARCIS (Netherlands)

    Braak, Sebastiaan Johannes ter

    2015-01-01

    There is epidemiological evidence that the use of some insulin analogues by diabetic patients is correlated with an increased cancer risk. In vitro exposure experiments revealed that insulin glargine (LANTUS) was the only commercial insulin analogue with an increased mitogenic potential. In the huma

  11. Insulin Glargine (rDNA origin) Injection

    Science.gov (United States)

    ... and high blood sugar can develop serious or life-threatening complications, including heart disease, stroke, kidney problems, ... following: albuterol (Accuneb, Proair, Proventil, others); angiotensin-converting enzyme inhibitors (ACE inhibitors) such as benazepril (Lotensin, in ...

  12. Basal insulin treatment intensification in patients with type 2 diabetes mellitus: A comprehensive systematic review of current options.

    Science.gov (United States)

    Raccah, D

    2017-04-01

    As type 2 diabetes mellitus progresses, most patients require treatment with basal insulin in combination with another agent to achieve recommended glycaemic targets. The purpose of this systematic review was to examine the evidence supporting the use of the available add-on treatments [rapid-acting insulin (RAI), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), dipeptidyl peptidase (DPP)-4 inhibitors and sodium-glucose cotransporter-2 (SGLT-2) inhibitors] to basal insulin. MEDLINE, EMBASE and EBSCOhost were searched for English-language articles, and all those captured were original articles (case studies and narrative reviews were omitted). Data on study design, population demographics, interventions and outcomes were tabulated. The extracted outcome data included changes in glycated haemoglobin (HbA1c), fasting plasma glucose (FPG) and postprandial plasma glucose (PPG), as well as body weight and safety data. A total of 88 publications were deemed relevant. All treatments reduced HbA1c and FPG. The most pronounced reductions in PPG, an unmet need in patients not controlled by basal insulin, were seen following administration of RAIs and short-acting GLP-1 RAs, although data for this outcome are generally lacking. Body weight benefits were observed with GLP-1 RAs and SGLT-2 inhibitors. However, as only articles in English were included, the result was a possible publication bias, while the diversity of study designs and drug combinations limited comparisons between studies. The evidence supports effectiveness of the available add-on treatments to basal insulin. However, other factors, such as potential body-weight increases, convenience/compliance and adverse events, particularly hypoglycaemia, should be considered on a patient-by-patient basis to optimalize treatment outcomes. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  13. 甘精胰岛素联合口服降糖药物对血糖控制不佳的2型糖尿病患者的疗效观察%Efficacy of insulin glargine combined with oral hypoglycemic agent in type 2 diabetic patients with poor glycemic control

    Institute of Scientific and Technical Information of China (English)

    徐迎侠; 刘洪英

    2011-01-01

    Objective To investigate the efficacy and safety of insulin glargine(lantus(R))combined with metformin and pioglitazone in type 2 diabetic patients whose blood glucose levels Were inadequately controlled by oral antidiabetic drugs(OAD).Methods 78 type 2 diabetic patients with poor glycemic control of OAD were randomly divided into group A and B.Patients in group A and B received insulin glargine and NPH insulin respectively in addition to OAD of metformin and pioglitazone.Fasting blood glucose(FBG),2-bour postprandial blood glucose(2 hVG),glycosylated hemoglobin(Hb)A1c and the increase of weight,as well as hypoglycemia rate were abserved after therapy.Results Levels of FBG,2 hPG and HbA1c were lower in group A than those in group B(P0.05).Conclusion The treatment of insulin glargine with metformin and piglitazone in type 2 diabetic patients with poor glycemic control is more efficient.As the basic insulin treatment,glarglne Was more efficient than NPH insulin.%目的 评价甘精胰岛素(来得时(R))与盐酸吡格列酮和二甲双胍联合应用治疗口服降糖药物控制不佳的2型糖尿病患者的有效性和安全性.方法 采用随机法将78例口服降糖药物控制不佳的2型糖尿病患者分为A、B两组.A组为甘精胰岛素(来得时(R))组,B组为精蛋白锌胰岛素(诺和灵N)组,两组均口服吡格列酮和二甲双胍,观察治疗后空腹血糖(FBG)、餐后2 h血糖(2 hPG)、糖化血红蛋白(Hb)A1c水平,以及体重增加值和低血糖发生率.结果 A组FBG、2 hPG及HbA1c水平均低于B组(P均0.05).结论 口服降糖药物疗效差的2型糖尿病患者应用甘精胰岛素联合吡咯列酮和二甲双胍治疗,有更显著的降糖效果;作为基础胰岛素治疗,甘精胰岛素优于精蛋白锌胰岛素.

  14. Hypoglycemia After Initiation of Basal Insulin in Patients with Type 2 Diabetes in the United States: Implications for Treatment Discontinuation and Healthcare Costs and Utilization.

    Science.gov (United States)

    Dalal, Mehul R; Kazemi, Mahmood; Ye, Fen; Xie, Lin

    2017-08-04

    Hypoglycemia and fear of hypoglycemia may contribute to basal insulin discontinuation, poor glycemic control, and increased healthcare burden in patients with type 2 diabetes (T2D). This study aimed to determine the impact of hypoglycemia soon after basal insulin initiation on treatment discontinuation and economic outcomes in patients with T2D. Hypoglycemic events within 6 months of basal insulin initiation were identified using retrospective cohort data from patients with T2D, at least 18 years of age, initiated on basal insulin therapy in the Clinformatics™ Data Mart for Multiplan claims database from January 1, 2008, through August 31, 2012. Data were adjusted for baseline characteristics. Discontinuation was established for patients with 12-month follow-up data, while discontinuation risk was assessed in the extended analysis (6- to 24-month follow-up) by Cox regression analysis. Healthcare use and costs were determined. Of 55,608 patients, 4.5% experienced hypoglycemia within 6 months of basal insulin initiation. Patients with hypoglycemia were more likely to discontinue basal insulin within 12 months of initiation (79.0% vs. 74.2%; P cause ($30,719 vs. $19,079; P < 0.001) healthcare costs. US patients with T2D who experienced hypoglycemia within 6 months of basal insulin initiation were more likely to discontinue treatment, accompanied by a greater healthcare burden. Sanofi US, Inc.

  15. Patient safety and minimizing risk with insulin administration – role of insulin degludec

    Directory of Open Access Journals (Sweden)

    Aye MM

    2014-04-01

    Full Text Available Myint M Aye,1 Stephen L Atkin21Hull Royal Infirmary, Michael White Diabetes Centre, Hull, UK; 2Weill Cornell Medical College Qatar, Qatar Foundation, Doha, QatarAbstract: Diabetes is a lifelong condition requiring ongoing medical care and patient self-management. Exogenous insulin therapy is essential in type 1 diabetes and becomes a necessity in patients with longstanding type 2 diabetes who fail to achieve optimal control with lifestyle modification, oral agents, and glucagon-like peptide 1-based therapy. One of the risks that hinders insulin use is hypoglycemia. Optimal insulin therapy should therefore minimize the risk of hypoglycemia while improving glycemic control. Insulin degludec (IDeg is a novel basal insulin that, following subcutaneous injection, assembles into a depot of soluble multihexamer chains. These subsequently release IDeg monomers that are absorbed at a slow and steady rate into the circulation, with the terminal half-life of IDeg being ~25 hours. Thus, it requires only once-daily dosing unlike other basal insulin preparations that often require twice-daily dosing. Despite its long half-life, once-daily IDeg does not cause accumulation of insulin in the circulation after reaching steady state. IDeg once a day will produce a steady-state profile with a lower peak:trough ratio than other basal insulins. In clinical trials, this profile translates into a lower frequency of nocturnal hypoglycemia compared with insulin glargine, as well as an ability to allow some flexibility in dose timing without compromising efficacy and safety. Indeed, a study that tested the extremes of dosing intervals of 8 and 40 hours showed no detriment in either glycemic control or hypoglycemic frequency versus insulin glargine given at the same time each day. While extreme flexibility in dose timing is not recommended, these findings are reassuring. This may be particularly beneficial to elderly patients, patients with learning difficulties, or others

  16. Lower dose basal insulin infusion has positive effect on glycaemic control for children with type I diabetes on continuous subcutaneous insulin infusion therapy.

    Science.gov (United States)

    Schulten, Ron J; Piet, Jessica; Bruijning, Patricia Cjl; de Waal, Wouter J

    2017-02-01

    The aim of our study was to explore a possible relationship between proportion of basal insulin dose (%BD/T) and glycaemic control in children with type I diabetes on continuous subcutaneous insulin infusion (CSII) therapy. All patients under the age of 18 with type I diabetes mellitus, treated in a general hospital in Utrecht, The Netherlands, who were on CSII therapy between 2000 and 2011 were selected for inclusion. All data as recorded during outpatient visits were retrospectively collected from patients' charts. Analyses were performed using R Statistical Software. Data of 847 outpatient visits of 78 patients [31 males (39.7%) and 47 females (60.3%)] were analyzed. Mean age at diagnosis was 7.1 ± 3.7 yr, mean age at start of pump therapy 10.1 ± 3.8 yr. Mean HbA1c before pump start was 8.3 ± 1.0%, median BMI standard deviation score for age and gender was 0.64 (-1.89-3.79). Median follow-up time per patient was 29 months with an average of 10 visits (range: 3-25). Multivariate analysis revealed that a change of 10% in %BD/T resulted in a decrease or increase of HbA1c of 0.22% [95% confidence interval (CI): 0.15-0.29). No significant effect was observed from SDS BMI, sex, or duration of diabetes. Low dose basal insulin infusion as a percentage of total insulin dose has a positive effect on metabolic outcome as expressed in HbA1c-levels. A change of 10% in %BD/T results in a decrease or increase of HbA1c of 0.22%. This supports the tendency to aim at the lowest basal insulin requirements in pump setting strategy. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. 甘精胰岛素联合那格列奈治疗老年2型糖尿病疗效观察%Therapeutic effect and safety of nateglinide combined with insulin glargine in treatment of aged patients with type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    郭秋慧

    2009-01-01

    OBJECTIVE To evaluate the comparison of efficacy and safety between nateglinide combined with insulin glargine and mixed protamine zinc recombinant human insulin in treatment of aged patients with type 2 diabetes. METHOOS Fourty aged patients with type 2 diabetes under unsatisfied blood glucose control were randomly divided into 2 groups. 20 patients in the trial group were treated by nateglinide with insulin glargine injection. The other 20 patients in the control group were treated by mixed protamine zinc recombinant human insulin injection. Fasting blood glucose(FBG), 2 h postprandial blood glucose (2hPG), glycosylated hemoglobin( HbA1C)and hypoglycemia before and after the treatment were observed in two groups. RE-SULTS The levels of FBG,2hPG and HbAIc in trial and control groups after treatment showing significant difference in com-parison with those before treatment. But no significant difference between the two groups(P>0. 05). Hypoglycemia in trial group appeared more frequently than in control group. (P<0. 01 ). CONCLUSION Insulin glargine with Nateglinide can con-trol the blood glucose effectively in aged patients with type 2 diabetes possessing low incidence of hypoglycemia and high safety accompanied by simple and easy way in application.%目的:比较使用甘精胰岛素联合那格列奈与使用预混胰岛素治疗老年2型糖尿病的疗效差异.方法:将40例血糖控制差的老年2型糖尿病患者随机分为甘精胰岛素组和预混胰岛素组.甘精胰岛素组采用甘精胰岛素联合那格列奈治疗,预混胰岛素组采用预混胰岛素2次皮下注射.观察治疗前后2组空腹血糖(FBG)、餐后血糖(2hPG)、糖化血红蛋白(HbA1C),低血糖发生率.结果:2组在空腹血糖、餐后血糖、糖化血红蛋白差异无统计学意义,但甘精胰岛素组在低血糖发生率方面显著低于预混胰岛素组(P<0.01).结论:甘精胰岛素联合那格列奈治疗老年2型糖尿病安全、有效,方法简单易行.

  18. Therapeutic Options for the Management of Postprandial Glucose in Patients With Type 2 Diabetes on Basal Insulin

    OpenAIRE

    Hinnen, Debbie A.

    2015-01-01

    In Brief For patients with type 2 diabetes who require add-on therapy to metformin plus basal insulin, GLP-1 receptor agonists may be a favorable option because they effectively manage postprandial glucose, reduce body weight, and have an overall favorable safety profile compared to other agents. Given the wide range of treatment combinations available for type 2 diabetes management, health professionals must partner with patients to determine the best choices based on patients’ individual li...

  19. [Quality of life and hypoglycemia burden in patients with type 2 diabetes mellitus on basal-bolus insulin therapy].

    Science.gov (United States)

    Ionova, T I; Odin, V I; Nikitina, T P; Kurbatova, K A

    2014-01-01

    This paper presents the results of the observational program "Parameters of life quality, symptoms of hypoglycemia and treatment satisfaction in patients with type 2 diabetes mellitus on basal-bolus insulin therapy" (2012-2014). The analysis included 1000 patients. It showed that their quality of life was below that of the general population due to compromised physical, role physical, and role emotional functioning (p diabetes mellitus on basal-bolus insulin therapy. They are characterized by impaired physical, psychological, and social functioning compared with the patients without hypoglycemic episodes (p quality of life was much worse (ES = 0.22-0.51). The profile of hypoglycemic episodes differed in different forms of hypoglycemia. The spectrum of symptoms and problems related to hypoglycemia was broader in patients with severe and/or nocturnal hypoglycemia. Patients free from hypoglycemia were less afraid of it than those used to have hypoglycemic episodes (p quality of life and hypoglycemia-related symptoms in patients with type 2 diabetes mellitus on basal-bolus insulin therapy allows for comprehensive estimation of the effectiveness of therapy on an individual basis.

  20. Effect of basal insulin combined with acarbose on blood glucose level and complications in patients with newly diagnosed elderly diabetes

    Institute of Scientific and Technical Information of China (English)

    Yu-Qing Guo; Chen-Ru Zhang; Ai-Ge Yang; Fan Liu; Shan-Shan Dong; Yan Kang

    2016-01-01

    Objective:To analyze the effect of basal insulin combined with acarbose on blood glucose level and complications in patients with newly diagnosed elderly diabetes.Methods:A total of 135 cases of patients with newly diagnosed elderly diabetes who were treated in our hospital from July 2012 to January 2015 were enrolled as research subjects and divided into observation group 66 cases and control group 69 cases according to different treatment methods. Control group received acarbose therapy alone, observation group received basal insulin combined with acarbose therapy, and then differences in blood glucose level, oxidative stress indicators, nerve conduction velocity, vascular injury and inflammatory factor levels of two groups were compared.Results:FPG, 2hPG and HbA1C levels of observation group after treatment were lower than those of control group; AGE-P, MDA and NADPH levels were lower than those of control group, and SOD level was higher than that of control group; median MNCV, ulnar MNCV, tibial MNCV, median SNCV and sural SNCV levels were higher than those of control group; sVCAM-1, hs-CRP and IL-6 levels were lower than those of control group. Conclusion:Basal insulin combined with acarbose therapy for patients with newly diagnosed elderly diabetes can effectively optimize the levels of blood glucose and complication-related factors, and it has active clinical significance.

  1. Changes in basal rates and bolus calculator settings in insulin pumps during pregnancy in women with type 1 diabetes

    DEFF Research Database (Denmark)

    Mathiesen, Jonathan M; Secher, Anna L; Ringholm, Lene

    2014-01-01

    and HbA1c were recorded. Results were compared with 96 women with type 1 diabetes on multiple daily injection therapy. RESULTS: Throughout pregnancy, the carbohydrate-to-insulin ratio decreased at all three main meals. The most pronounced decrease was observed at breakfast, where the carbohydrate......-to-insulin ratio was reduced, from median 12 (range 4-20) in early pregnancy to 3 (2-10) g carbohydrate per unit insulin in late pregnancy. Basal insulin delivery increased by ∼50%, i.e. from 0.8 (0.5-2.2) to 1.2 (0.6-2.5) IU/h at 5 a.m. and from 1.0 (0.6-1.5) to 1.3 (0.2-2.3) IU/h at 5 p.m. during pregnancy. HbA1......c levels during pregnancy, the occurrence of severe hypoglycemia and pregnancy outcomes were similar in the two groups. CONCLUSIONS: In women with type 1 diabetes on insulin pump therapy with a bolus calculator, the carbohydrate-to-insulin ratio declined 4-fold from early to late pregnancy, whereas...

  2. 甘精胰岛素联合二甲双胍治疗血糖控制不佳2型糖尿病的临床价值%Clinical Value of Insulin Glargine Combined with Metformin in the Treat-ment of Type 2 Diabetes with Poorly Controlled Glucose

    Institute of Scientific and Technical Information of China (English)

    李嵘

    2015-01-01

    目的:探讨分析甘精胰岛素联合二甲双胍治疗血糖控制不佳2型糖尿病的临床疗效。方法选取该院2012年12月—2013年12月收治的101例口服降糖药血糖控制不佳的2型糖尿病患者为研究对象,将其依数字表法随机分成两组,观察组55例患者给予甘精胰岛素联合二甲双胍治疗,对照组46例患者给予精蛋白锌胰岛素联合二甲双胍治疗,观察两组临床疗效。结果两组患者空腹血糖(FBG)、餐后2 h血糖(2hPG)及糖化血红蛋白(HbAlc)水平均较治疗前有所改善,观察组改善情况显著优于对照组,差异有统计学意义(P0.05)。结论甘精胰岛素联合二甲双胍治疗血糖控制不佳的2型糖尿病,临床疗效较显著。%Objective To investigate and analyze the clinical efficacy of insulin glargine combined with metformin in the treatment of type 2 diabetes with poorly controlled glucose. Methods One hundred and one type 2 diabetes patients with poorly controlled glucose by oral antidiabetic drug admitted in our hospital from December 2012 to December 2013 were selected as the subjects and randomly divided into two groups in accordance with the digital table method. 55 cases in the observation group were treated by insulin glargine combined with metformin, and 46 cases in the control group were treated by protamine zinc insulin combined with metformin. And the clinical efficacy of the two groups was observed. Results The levels of FBG, 2hPG and HbAlc of the two groups were improved after treatment compared with those before treatment, but the improvement of the observation group was bet-ter than that of the control group, the differences were statistically significant (P0.05). Conclusion The clinical effect of insulin glargine combined with metformin in the treatment of type 2 diabetes with poorly controlled glucose is more significant.

  3. 预混胰岛素治疗的2型糖尿病患者转为甘精胰岛素联合口服药的疗效分析%Analysis of the effect of premixed insulin converted to glargine combined with oral medicine for the treatment of patients with type 2 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    陈云华

    2015-01-01

    目的:探讨预混胰岛素治疗的2型糖尿病患者转为甘精胰岛素联合口服药的临床疗效。方法:将2型糖尿病患者144例随机平分为两组,观察组停用预混胰岛采用甘精胰岛素联合口服降糖药进行治疗,对照组采用预混胰岛素联合口服降糖药进行治疗。观察并比较两组患者FBG(空腹血糖)、HbA1c(糖化血红蛋白)、2 hPG(餐后2 h血糖)及治疗期间患者BMI(体重指数)、低血糖发生次数。结果:两组治疗后FBG、HbA1c、2 hPG等各项指标均下降,下降幅度观察组明显优于对照组;观察组治疗过程中患者BMI无明显变化,而对照组BMI明显上升,且对照组低血糖发生次数明显多于观察组,P<0.05,差异有统计学意义。结论:预混胰岛素治疗效果欠佳的2型糖尿病患者采用甘精胰岛素联合口服降糖药进行治疗,可有效改善患者的FBG、HbA1c水平,降低低血糖风险,且患者体重不会增加。%Objective:To investigate the clinical effect of premixed insulin converted to glargine combined with oral medicine for the treatment of patients with type 2 diabetes mellitus.Methods:144 patients with type 2 diabetes mellitus were randomly divided into the two groups on average.Patients in the observation group deactivated the premixed insulin therapy,and they were treated by the combination of glargine and oral hypoglycemic agents.Patients in the control group were treated by the combination of premixed insulin and oral hypoglycemic agents.We observed and compared the FBG(fasting blood glucose),HbA1c(glycosylated hemoglobin),2 hPG(2 h postprandial blood sugar)and BMI(body mass index),the number of occurrences of hypoglycemia during treatment.Results:The indicators of FBG,HbA1c,2 hPG were all decreased of the two groups after treatment,and the decline of the observation group was significantly better than the control group.Patients in the observation group had no significant change in BMI

  4. Efficacy and safety of insulin glargine in combination with sitagliptin on elderly patients with type 2 diabetes%甘精胰岛素与西格列汀联用治疗老年2型糖尿病临床观察

    Institute of Scientific and Technical Information of China (English)

    于湛; 田力

    2013-01-01

    Objective To investigate the efficacy and safety of insulin glargine in combination with sitagliptin on elderly patients with type 2 diabetes. Methods 78 patients ( > 60 year-old ) were randomly divided into two groups:insulin glargine/sitagliptin combination group( n =40,group G )and biosynthesis premixed 30/70 insulin group ( n =38,group N ). The dose was adjusted according to blood glucose,the fasting glucose,2 h postprandial blood glucose ,glycosylated hemoglobin( HbA1C ),the incidence of hypoglycemia and body mass index( BMI )after 12 weeks of treatment of the two groups were compared. Results 2 h postprandial blood glucose and the incidence of hypoglycemi-a in group G were less than those in group N( P 0. 05 ). Conclusion The treatment of insulin glargine in combination with sitagliptin is safe, effective and convenient for elderly patients with type 2 diabetes. This treatment program with a small incidence of hypoglycemia is very suitable for old patients with type 2 diabetes complicated with poor cognitive activities inconvenient, poor eyesight or a variety of chronic diseases.%目的 探讨甘精胰岛素联用西格列汀治疗高龄2型糖尿病的疗效及安全性.方法 将78例60岁以上的2型糖尿病患者随机分成甘精胰岛素联用西格列汀组(G组)40例和生物合成预混30/70人胰岛素组(N组)38例,根据血糖情况调整用药剂量,治疗12周后比较两组的空腹血糖、餐后2 h血糖、糖化血红蛋白(HbA1c)、低血糖发生率及体重指数(BMI).结果 G组在空腹2 h血糖和低血糖发生率方面均低于N组,两组比较差异有统计学意义(P<0.05);在餐后血糖、HbA1c和BMI方面两组比较差异无统计学意义(P>0.05).结论 甘精胰岛素与西格列汀联用对老年2型糖尿病患者是一种安全、有效且方便的治疗方案,低血糖发生率低,尤其是对认知力较差、活动不方便、视力差或合并多种慢性病的高龄2型糖尿病患者尤为适用.

  5. [Practical aspects of intensified insulin therapy using the basal bolus principle].

    Science.gov (United States)

    Berger, W; Spinas, G A

    1990-01-01

    In type 1 (insulin-dependent) diabetic patients, a good metabolic control can often be achieved only by means of an intensified insulin-giving regimen. This requires multiple insulin injections, whereby 60 to 70% of the total daily insulin amount are administered as preprandial boli of short or intermediate acting insulin. The remaining 30 to 40% of the daily insulin dosage are usually given as bedtime injection. With this form of therapy, sufficient metabolic control can be achieved in the majority of patients; however, due to the kinetics of subcutaneously injected insulin, there are some limitations to this therapeutic regimen. Physiological overnight insulin requirements, i.e. relatively small insulin requirement during the first part and increased insulin requirement during the second part of the night, are difficult to meet with currently available insulin preparations. It is, therefore, nearly impossible to achieve euglycemic fasting blood glucose levels without taking the risk of nocturnal hypoglycemia. Moreover, intensified insulin therapy requires regular selfmonitoring of blood glucose, and the patients have to stick to a quantitative diet and to a relatively fixed time schedule for meal ingestion. Several practical aspects as to the time and site of injection, postponing or "skipping" meals, etc., are discussed.

  6. Adding once-daily lixisenatide for type 2 diabetes inadequately controlled by established basal insulin: a 24-week, randomized, placebo-controlled comparison (GetGoal-L)

    National Research Council Canada - National Science Library

    Riddle, Matthew C; Aronson, Ronnie; Home, Philip; Marre, Michel; Niemoeller, Elisabeth; Miossec, Patrick; Ping, Lin; Ye, Jenny; Rosenstock, Julio

    2013-01-01

    ...). We conducted a double-blind, parallel-group, placebo-controlled trial. Patients (n = 495) with established basal insulin therapy but inadequate glycemic control were randomized to add lixisenatide 20...

  7. Basal lipolysis, not the degree of insulin resistance, differentiates large from small isolated adipocytes in high-fat fed mice.

    Science.gov (United States)

    Wueest, S; Rapold, R A; Rytka, J M; Schoenle, E J; Konrad, D

    2009-03-01

    Adipocytes in obesity are characterised by increased cell size and insulin resistance compared with adipocytes isolated from lean patients. However, it is not clear at present whether hypertrophy actually does drive adipocyte insulin resistance. Thus, the aim of the present study was to metabolically characterise small and large adipocytes isolated from epididymal fat pads of mice fed a high-fat diet (HFD). C57BL/6J mice were fed normal chow or HFD for 8 weeks. Adipocytes from epididymal fat pads were isolated by collagenase digestion and, in HFD-fed mice, separated into two fractions according to their size by filtration through a nylon mesh. Viability was assessed by lactate dehydrogenase and 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium assays. Basal and insulin-stimulated D-[U-(14)C]glucose incorporation and lipolysis were measured. Protein levels and mRNA expression were determined by western blot and real-time RT-PCR, respectively. Insulin-stimulated D-[U-(14)C]glucose incorporation into adipocytes isolated from HFD-fed mice was reduced by 50% compared with adipocytes from chow-fed mice. However, it was similar between small (average diameter 60.9 +/- 3.1 microm) and large (average diameter 83.0 +/- 6.6 microm) adipocytes. Similarly, insulin-stimulated phosphorylation of protein kinase B and AS160 were reduced to the same extent in small and large adipocytes isolated from HFD-mice. In addition, insulin failed to inhibit lipolysis in both adipocyte fractions, whereas it decreased lipolysis by 30% in adipocytes of chow-fed mice. In contrast, large and small adipocytes differed in basal lipolysis rate, which was twofold higher in the larger cells. The latter finding was associated with higher mRNA expression levels of Atgl (also known as Pnpla2) and Hsl (also known as Lipe) in larger adipocytes. Viability was not different between small and large adipocytes. Rate of basal lipolysis but not insulin responsiveness is different between small and large

  8. Review of biphasic insulin aspart in the treatment of type 1 and 2 diabetes

    Directory of Open Access Journals (Sweden)

    Nazia Raja-Khan

    2008-01-01

    Full Text Available Nazia Raja-Khan, Sarah S Warehime, Robert A GabbayDivision of Endocrinology, Diabetes, and Metabolism, Penn State Institute for Diabetes and Obesity, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USABackground: Insulin is an effective treatment for achieving glycemic control and preventing complications in patients with diabetes. In order to make insulin therapy more acceptable to patients, newer formulations of insulin have been developed, such as biphasic insulins. Biphasic insulins conveniently provide both prandial and basal insulin in a single injection. One of the most well-studied biphasic insulins is biphasic insulin aspart 70/30.Objective: Our goal was to review the current literature on the safety and efficacy of biphasic insulin aspart in type 1 and type 2 diabetes.Methods: A MEDLINE search was conducted using the terms “biphasic insulin aspart” to identify clinical studies and reviews.Results: Biphasic insulin aspart more effectively reduces post-prandial glucose compared to other biphasic insulins and basal insulins. Compared to biphasic insulin aspart, fasting glucose levels are lower with NPH, similar with glargine, and similar or lower with biphasic human insulin. Treat-to-target trials have shown that a goal HbA1c below 6.5 or 7% can be achieved with biphasic insulin aspart. The risk of hypoglycemia is similar to or less than that seen with other biphasic insulins or NPH insulin.Conclusion: Biphasic insulin aspart 70/30 is a safe and effective treatment option for patients with diabetes.Keywords: biphasic insulin aspart, insulin, diabetes

  9. 甘精胰岛素与格列美脲联合应用治疗口服降糖药控制不佳2型糖尿病的有效性和安全性%Efficacy and safety of insulin glargine combined with glimepiride in type 2 diabetic patients with poor glycemic control

    Institute of Scientific and Technical Information of China (English)

    吕朝晖; 潘长玉; 陈家伦; 傅祖植; 高妍; 陆菊明; 宁光; 程桦; 高燕明

    2009-01-01

    Objective To investigate the efficacy and safety of insulin glarsine(Lantus~(R))combined with glimepiride(Amaryl~(R))in type 2 diabetic patients whose blood glucose levels were inadequately controlled by oral antidiabetic drugs(OAD).Methods In this open-labeled,randomized,parallel,muhicenter,and non-inferiority study,122 patients were given either once.daily insulin glarsine(n=62)or NPH insulin(n=60)at bedtime,plus glimepiride for 24 weeks.Results Baseline characteristics were similar between the two groups.HbA_(1C) levels were decreased in the insulin glargine and NPH groups over the study period in the per-protocol population (1.38% vs 1.41%).Fasting blood glucose(12.30 to 6.05 mmoL/L and 11.90 to 6.19 mmol/L,respectively)and the mean daily blood glucose(6.28 vs 5.72 mmol/L)decreased similarly in beth groups during the study.Moreover.the number of hypoglycemic episodes was significantly lower in patients with insulin glarsine than those with NPH insulin(46.8% vs 71.1%,P<0.05),being particularly severe(3.2% vs 15.0%,P<0.05)and expressing nocturnal hypoglycemia(37.1% vs 61.7%,P<0.01).Daily insulin dose was increased from 9.7 to 32.5 IU in the insulin glarine group and from 9.8 to 29.5 IU in the NPH insulin group.Conclusion These results confirm earlier reports that insulin glargine provides similar glyeemic control with less hypoglycemia compared with NPH insulin. Insulin glargine yields better results in lowering the incidence of severe and nocturnal hypoglycemia.%目的 评价甘精胰岛素(来得时~(R))与格列美脲(亚莫利~(R))联合应用治疗口服降糖药控制不佳的2型糖尿病的有效性和安全性.方法 采用随机、开放、低精蛋白锌胰岛素注射液(诺和灵N)平行对照和多中心临床研究方法.122例口服降糖药控制不佳的2型糖尿病患者随机分为睡前注射一次甘精胰岛素(n=62)或低精蛋白胰岛素(n=60),清晨口服3mg格列美脲两组,进行为期24周的观察.结果 (1)基线时除甘精胰

  10. Perceptions of diabetes control among physicians and people with type 2 diabetes uncontrolled on basal insulin in Sweden, Switzerland, and the United Kingdom

    DEFF Research Database (Denmark)

    Brod, Meryl; Pfeiffer, Kathryn M; Barnett, Anthony H

    2016-01-01

    of physicians. The purpose of the study was to investigate perceptions of control and views on insulin intensification among physicians and PWUD. Research design and methods Web surveys of 1012 PWUD on basal insulin and 300 physicians were conducted in Sweden, Switzerland, and the United Kingdom. Results...

  11. 基础加餐时胰岛素治疗儿童1型糖尿病的疗效%Primary Observation of Basal-Bolus Insulin Therapy in Children with Type 1 Diabetes Mellitus

    Institute of Scientific and Technical Information of China (English)

    刘栋; 李堂

    2011-01-01

    Objective To observe the clinical effect by using a basal - bolus insulin therapy in children with type 1 diabetes mellitus ( T1 DM ). Methods Fifteen children with T1 DM used conventional regimen ( premixed insulin 30/70,2/3 dose 30 minutes before breakfast,1/3 dose 30 minutes before dinner) for 16 months;then they were treated with basal -bolus insulin therapy (injection of insulin aspart 0 - 15 minutes before meals and a bedtime injection of insulin glargine) for at least 12 months. Glycolated hemoglobin(HbAlc) values ,daily insulin dose, incidence of severe and non - severe hypoglycemia events before and after the institution of basal - bolus therapy, were collected. Results Basal - bolus therapy was associated with lower level of HbAlc at 3,6,9 and 12 months for 15 subjects of T1 DM compared with conventional therapy ( t = 7.15 ,4.88,3.46,5.28, Pa < 0.01 ). No statistical difference was observed between 3,6,9 and 12 months ( t = 2.08,1.64,1.73,1.85, 1. 96,1.66, Pa > O. 05 ). There was no clinically important change in the daily dose of insulin ( t = 1.56, P > O. 05 ). During con ventional therapy, severe hyperglycemia occurred in 7 cases, while using basal -bolus therapy, severe hyperglycemia didn't happen. Incidence of severe and non - severe hypoglycemia events obviously reduced ( t = 13.31, P < 0.001 ). Conclusions Institution of basal - bolus therapy is associated with improved glycemic control and decreased rates of hypoglycemia while dose of insulin did not increase. It can also improve patients' satisfaction and quality of life.%目的 观察应用基础加餐时胰岛素治疗儿童1型糖尿病(T1DM)的临床效果.方法 15例T1DM患儿采用传统治疗方案治疗平均16个月:双时相低精蛋白锌胰岛素30/70,2/3量早餐前30 min皮下注射,1/3量晚餐前30 min皮下注射;之后采用基础加餐时治疗方案治疗至少12个月:3餐前0~15 min门冬胰岛素皮下注射,睡前甘精胰岛素皮下注射.观察基础加餐

  12. **-Postprandial pancreatic [(11)C]methionine uptake after pancreaticoduodenectomy mirrors basal beta cell function and insulin release.

    Science.gov (United States)

    Steiner, Emanuel; Kazianka, Lukas; Breuer, Robert; Hacker, Marcus; Wadsak, Wolfgang; Mitterhauser, Markus; Stimpfl, Thomas; Reiter, Birgit; Karanikas, Georgios; Miholic, Johannes

    2017-03-01

    [S-methyl-(11)C]-L-methionine ([(11)C]MET) uptake in the pancreas might be a central indicator of beta cell function. Since gastric emptying was recently shown to influence glycemic control in subjects after pancreaticoduodenectomy (PD, the surgical treatment of neoplasms of the pancreas head), we looked for imaginable relationships between gastric emptying, pre- and postprandial insulin concentrations, and [(11)C]MET uptake. Nineteen tumor-free survivors after PD (age mean ± SD: 61 ± 8.7 yrs.; 10 male, 9 female) and 10 healthy controls (age: 27 ± 8.7 yrs.; 7 male, 3 female) were given a mixed test meal. One gram of paracetamol was ingested with the meal to evaluate the speed of gastric emptying. Insulin, glucose, and paracetamol plasma concentrations were measured before and over 180 minutes after ingestion. Beta cell function was calculated from fasting glucose and insulin plasma concentrations. Simultaneously, 800 MBq of [(11)C]MET were administered and the activity (maximum tissue standardized uptake values [SUVmax]) over the pancreas was measured at 15, 30, and 60 minutes after injection. Total integrated SUVmax (area under the curve [AUC]) and incremental SUVmax were calculated. The uptake of [(11)C]MET in the pancreas was significantly higher (p insulin AUC60 (R(2) = 0.66,p insulin AUC60 and beta cell function, calculated from the fasting insulin to glucose ratio, as independent predictors of (11)C-methionine uptake, i.e. total integrated SUVmax, in patients after PD (R(2) = 0.78, p < 0.0001). Postprandial [(11)C]MET uptake may represent basal and postprandial beta cell function. The findings suggest a possible usefulness of this imaging procedure for further studying beta cell function.

  13. 甘精胰岛素联合瑞格列奈在新诊断2型糖尿病中的应用研究%Research on Repaglinide in Insulin Glargine Combined with Newly Diagnosed Type 2 Diabetes

    Institute of Scientific and Technical Information of China (English)

    陈林江

    2012-01-01

    目的 探讨甘精胰岛素联合瑞格列奈治疗新诊断的2型糖尿病的临床疗效,以及对胰岛β细胞功能的影响.方法 选取80例新诊断的2型糖尿病患者,随机分为观察组和对照组各40例,观察组给予瑞格列奈片及甘精胰岛素,对照组给予格列吡嗪片及甘精胰岛素,观察两组患者空腹血糖(FPG)、餐后2h血糖(2hPG)、糖化血红蛋白(HbA1C),以及应用胰岛素第1时相分泌和稳态模型评价胰岛β细胞功能.结果 观察组患者总有效率95.00%,明显高于对照组的80.00%,二者差异具有统计学意义(P<0.05);治疗6个月后,两组患者FPG、2hPG及HbA1C水平均下降,但观察组下降更明显(P<0.05),并且观察组患者FINS、空腹C肽、AIR 和HOMA-βF优于对照组(P<0.05).观察组患者低血糖发生率为7.50%,低于对照组的30.00%,差异具有统计学意义(P<0.05).结论 甘精胰岛素联合瑞格列奈能有效控制新诊断2型糖尿病患者的血糖,保持和恢复胰岛β细胞功能,低血糖发生率低,安全可靠,值得临床推广应用.%Objective: To investigate the effect of insulin glargine combined with repaglinide in the treatment of newly diagnosed type 2 diabetes, as well as on the function of islet β cell effect. Method: 80 patients with newly diagnosed type 2 diabetic patients, were randomly divided into the observation group and the control group, 40 cases in each group, the groups were observed given repaglinide tablet and insulin glargine, the control group was given glipizide and insulin glargine, two groups were observed in patients with impaired fasting glucose ( FPG ), 2h postprandial plasma glucose ( 2hPG ), glycosylated hemoglobin ( HbA1 C ), as well as the application of first phase insulin secretion and homeostasis model assessment of islet B cell function. Result: In the observation group, the total effective rate was 95% , It was significantly higher than that in control group 80% , the difference was statistically

  14. Clinical Observation of Insulin Glargine Treatment of Elderly Type 2 Diabetic Oral Drugs in Poorly Controlled%甘精胰岛素治疗老年2型糖尿病口服药物控制不佳的临床观察

    Institute of Scientific and Technical Information of China (English)

    冉秀荣; 王晓东

    2012-01-01

      Objective To investigate insulin glargine ( Lantus ) in treating elderly patients with type 2 diabetes mellitus oral drug effect is poor curative effect. Blood glucose, glycosylated hemoglobin were observed before and after treatment, serum lipid, body weight changes, incidence of hypoglycemia in the changes of indexes. Methods 38 cases of elderly patients with type 2 diabetes, in the use of oral drug suboptimal glycemic control (FBG>10.0mmol/L) based on the use of Lantus therapy, follow-up of three months. Results after treatment of patients with blood glucose after meals, bedtime blood glucose, glycosylated hemoglobin were significantly decreased (P10.0mmol/L)的基础上加用来得时治疗,随访3个月.结果治疗后患者三餐前后血糖,睡前血糖、糖化血红蛋白均较治疗前明显下降(P<0.01),体质量变化不大,低血糖发生率低.结论老年2型糖尿病口服药物不达标时,应用来得时,可以有效控制血糖,平稳达标,低血糖发生率低.

  15. Introduction of biosimilar insulins in Europe.

    Science.gov (United States)

    Davies, M; Dahl, D; Heise, T; Kiljanski, J; Mathieu, C

    2017-10-01

    Regulatory approval of the first biosimilar insulin in Europe, LY2963016 insulin glargine (Abasaglar(®) ), in 2014 expanded the treatment options available to people with diabetes. As biosimilar insulin products come to market, it is important to recognize that insulin products are biologicals manufactured through complex biotechnology processes, and thus biosimilar insulins cannot be considered identical to their reference products. Strict regulatory guidelines adopted by authorities in Europe, the USA and some other countries help to ensure that efficacy and safety profiles of biosimilar insulins are not meaningfully different from those of the reference products, preventing entry of biological compounds not meeting quality standards and potentially affecting people's glycaemic outcomes. This review explains the concept of biosimilar medicines and outlines regulatory requirements for registration of biosimilar insulins in Europe, which is illustrated by the successful development of LY2963016 insulin glargine and MK-1293 insulin glargine (Lusduna(®) ). Preclinical and clinical comparative studies of the biosimilar insulin glargine programmes include in vitro bioassays for insulin and insulin-like growth factor 1 receptor binding, assessment of in vitro biological activity, evaluation of pharmacokinetic/pharmacodynamic profiles in phase I studies and assessment of long-term safety and efficacy in phase III studies. The emergence of biosimilar insulins may help broaden access to modern insulins, increase individualized treatment options and reduce costs of insulin therapy. © 2017 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.

  16. 甘精胰岛素联合口服药物治疗2型糖尿病的疗效及安全性分析%Analysis of Efficacy and Safety of the Treatment of Insulin Glargine Combined with Oral Hypoglycemic Drugs for Type 2 Diabetic Patients

    Institute of Scientific and Technical Information of China (English)

    李敬华; 刘丽楠; 王素莉; 关树梅; 候雯莉

    2011-01-01

    Objective Evaluation of the efficacy end safety of the treatment insulin glargine combined with OADs for type 2 diabetic patients with poor glycemic control using premixed insulin therapy. Methods 50 cases of type 2 diabetic patients were randomly divided into treatment group (convert premixed insulin into insulin glargine plus OADs) (n= 30) and control group (continue to use the premixed insulin plus OADs) (n= 20), all groups were adjusted the dosage of insulin and OADs based on the levels of blood glucose. After 12 weeks the index of FBG、2hPG、HbA1c、BMI and the incidence of hypoglycemia during the test were compared in two groups. Results Compared with those before treatment, HbA1c、FBG、2hPG of the two groups have declined (P all < 0.01); the treatment group has no significant change in BMI (P >0.05). Compared with the control group, FBG、lunch 2hPG and HbA1c of the treatment group is lower (P all<0.01); BMI of treatment group is lower (P< 0.01); the incidence of hypoglycemia during the test of the treatment group is lower(P< 0.01). Conclusion The treatment of insulin glargine combined OADs for poor glycemic control in type 2 diabetic patients using premixed insulin,can significantly improve the levels of FBG and HbA1c, do not increase body weight, be simple, and can greatly reduce the risk of hypoglycemia.%目的 评价甘精胰岛素联合口服降糖药物(oral hypoglycemic drugs,OADs)治疗方案对使用预混胰岛素血糖控制欠佳的2型糖尿病患者的疗效及安全性.方法 预混胰岛素30/70单独或联合使用OADs血糖控制不良的2型糖尿病患者50例,随机分为治疗组(停用预混胰岛素,改为皮下注射甘精胰岛素联合OADs) (n= 30)和对照组(继续使用预混胰岛素早晚餐前皮下注射联合OADs)(n=20),各组均依据血糖监测水平调整胰岛素及OADs用量.12周后对比两组患者空腹血糖(fasting blood glucose,FBG)、三餐后2h血糖(2-hour postprandial blood glucose,2hPG

  17. Pharmacokinetics of the Long‐Acting Basal Insulin LY2605541 in Subjects With Varying Degrees of Renal Function

    Science.gov (United States)

    Linnebjerg, Helle; Choi, Siak Leng; Lam, Eric Chen Quin; Mace, Kenneth F.; Hodgson, Teri S.; Sinha, Vikram P.

    2016-01-01

    Abstract The pharmacokinetics of LY2605541 (basal insulin peglispro), a novel long‐acting basal insulin analogue, was evaluated in 5 groups of subjects with varying degrees of renal function based on creatinine clearance: normal renal function (>80 mL/min), mild renal impairment (51–80 mL/min), moderate renal impairment (30–50 mL/min), severe renal impairment (renal disease (ESRD) requiring hemodialysis. Serial blood samples for pharmacokinetic analyses were collected up to 12 days following a single 0.33 U/kg subcutaneous dose of LY2605541. The apparent clearance (CL/F) and half‐life across groups were not affected by renal function. Cmax values were lower in subjects with increasing severity of renal impairment; however, the small decrease in Cmax did not affect the overall exposure. Regression analysis showed that LY2605541 clearance is independent of renal function (slope = 0.000863; P = .885). The mean fraction of LY2605541 eliminated by a single hemodialysis session was 13% in subjects with ESRD. LY2605541 was generally well tolerated in healthy subjects and those with renal impairment following a single 0.33 U/kg subcutaneous dose. Given these data, no dose adjustment of LY2605541 based on pharmacokinetics is recommended in renal impairment or in patients undergoing hemodialysis. PMID:27163501

  18. High intensity aerobic exercise training improves chronic intermittent hypoxia-induced insulin resistance without basal autophagy modulation

    Science.gov (United States)

    Pauly, Marion; Assense, Allan; Rondon, Aurélie; Thomas, Amandine; Dubouchaud, Hervé; Freyssenet, Damien; Benoit, Henri; Castells, Josiane; Flore, Patrice

    2017-01-01

    Chronic intermittent hypoxia (IH) associated with obstructive sleep apnea (OSA) is a major risk factor for cardiovascular and metabolic diseases (insulin resistance: IR). Autophagy is involved in the pathophysiology of IR and high intensity training (HIT) has recently emerged as a potential therapy. We aimed to confirm IH-induced IR in a tissue-dependent way and to explore the preventive effect of HIT on IR-induced by IH. Thirty Swiss 129 male mice were randomly assigned to Normoxia (N), Intermittent Hypoxia (IH: 21–5% FiO2, 30 s cycle, 8 h/day) or IH associated with high intensity training (IH HIT). After 8 days of HIT (2*24 min, 50 to 90% of Maximal Aerobic Speed or MAS on a treadmill) mice underwent 14 days IH or N. We found that IH induced IR, characterized by a greater glycemia, an impaired insulin sensitivity and lower AKT phosphorylation in adipose tissue and liver. Nevertheless, MAS and AKT phosphorylation were greater in muscle after IH. IH associated with HIT induced better systemic insulin sensitivity and AKT phosphorylation in liver. Autophagy markers were not altered in both conditions. These findings suggest that HIT could represent a preventive strategy to limit IH-induced IR without change of basal autophagy. PMID:28255159

  19. Basal insulin analogues in diabetic pregnancy: a literature review and baseline results of a randomised, controlled trial in type 1 diabetes

    DEFF Research Database (Denmark)

    Mathiesen, Elisabeth R; Damm, Peter; Jovanovic, Lois;

    2011-01-01

    and HbA1c = 8.0% at randomization. At confirmation of pregnancy all subjects must have HbA1c = 8.0%. Exclusion criteria include impaired hepatic function, cardiac problems, and uncontrolled hypertension. Subjects are randomized to either insulin detemir or neutral protamine hagedorn insulin, both...... of the current literature concerning basal insulin analogue use in diabetic pregnancy, and to present the design and preliminary, non-validated baseline characteristics of a currently ongoing randomized, controlled, open-label, multicentre, multinational trial comparing insulin detemir with neutral protamine...... hagedorn insulin, both with insulin aspart, in women with type 1 diabetes planning a pregnancy (n = 306) or are already pregnant (n = 164). Inclusion criteria include type 1 diabetes > 12 months' duration; screening HbA1c = 9.0% (women recruited prepregnancy), or pregnant with gestational age 8-12 weeks...

  20. Surfactant protein d deficiency in mice is associated with hyperphagia, altered fat deposition, insulin resistance, and increased basal endotoxemia.

    Directory of Open Access Journals (Sweden)

    Jacob V Stidsen

    Full Text Available Pulmonary surfactant protein D (SP-D is a host defence lectin of the innate immune system that enhances clearance of pathogens and modulates inflammatory responses. Recently it has been found that systemic SP-D is associated with metabolic disturbances and that SP-D deficient mice are mildly obese. However, the mechanism behind SP-D's role in energy metabolism is not known.Here we report that SP-D deficient mice had significantly higher ad libitum energy intake compared to wild-type mice and unchanged energy expenditure. This resulted in accumulation but also redistribution of fat tissue. Blood pressure was unchanged. The change in energy intake was unrelated to the basal levels of hypothalamic Pro-opiomelanocortin (POMC and Agouti-related peptide (AgRP gene expression. Neither short time systemic, nor intracereberoventricular SP-D treatment altered the hypothalamic signalling or body weight accumulation.In ad libitum fed animals, serum leptin, insulin, and glucose were significantly increased in mice deficient in SP-D, and indicative of insulin resistance. However, restricted diets eliminated all metabolic differences except the distribution of body fat. SP-D deficiency was further associated with elevated levels of systemic bacterial lipopolysaccharide.In conclusion, our findings suggest that lack of SP-D mediates modulation of food intake not directly involving hypothalamic regulatory pathways. The resulting accumulation of adipose tissue was associated with insulin resistance. The data suggest SP-D as a regulator of energy intake and body composition and an inhibitor of metabolic endotoxemia. SP-D may play a causal role at the crossroads of inflammation, obesity, and insulin resistance.

  1. Design of ultra-stable insulin analogues for the developing world

    Directory of Open Access Journals (Sweden)

    Michael A Weiss

    2013-01-01

    Full Text Available The engineering of insulin analogues illustrates the application of structure-based protein design to clinical medicine. Such design has traditionally been based on structures of wild-type insulin hexamers in an effort to optimize the pharmacokinetic (PK and pharmacodynamic properties of the hormone. Rapid-acting insulin analogues (in chronological order of their clinical introduction, Humalog ® [Eli Lilly & Co.], Novolog ® [Novo-Nordisk], and Apidra ® [Sanofi-Aventis] exploit the targeted destabilization of subunit interfaces to facilitate capillary absorption. Conversely, long-acting insulin analogues exploit the stability of the insulin hexamer and its higher-order self-assembly within the subcutaneous depot to enhance basal glycemic control. Current products either operate through isoelectric precipitation (insulin glargine, the active component of Lantus ® ; Sanofi-Aventis or employ an albumin-binding acyl tether (insulin detemir, the active component of Levemir ® ; Novo-Nordisk. Such molecular engineering has often encountered a trade-off between PK goals and product stability. Given the global dimensions of the diabetes pandemic and complexity of an associated cold chain of insulin distribution, we envisage that concurrent engineering of ultra-stable protein analogue formulations would benefit the developing world, especially for patients exposed to high temperatures with inconsistent access to refrigeration. We review the principal mechanisms of insulin degradation above room temperature and novel molecular approaches toward the design of ultra-stable rapid-acting and basal formulations.

  2. **-Postprandial pancreatic [{sup 11}C]methionine uptake after pancreaticoduodenectomy mirrors basal beta cell function and insulin release

    Energy Technology Data Exchange (ETDEWEB)

    Steiner, Emanuel; Kazianka, Lukas; Breuer, Robert; Miholic, Johannes [Medical University of Vienna, Department of Surgery, Vienna (Austria); Hacker, Marcus; Wadsak, Wolfgang; Mitterhauser, Markus [Medical University of Vienna, Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, Vienna (Austria); Stimpfl, Thomas; Reiter, Birgit [Medical University of Vienna, Clinical Institute of Laboratory Medicine, Forensic Toxicology, Vienna (Austria); Karanikas, Georgios [Medical University of Vienna, Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, Divisional Head PET-PET/CT (Nuclear Medicine), Vienna (Austria)

    2017-03-15

    [S-methyl-{sup 11}C]-L-methionine ([{sup 11}C]MET) uptake in the pancreas might be a central indicator of beta cell function. Since gastric emptying was recently shown to influence glycemic control in subjects after pancreaticoduodenectomy (PD, the surgical treatment of neoplasms of the pancreas head), we looked for imaginable relationships between gastric emptying, pre- and postprandial insulin concentrations, and [{sup 11}C]MET uptake. Nineteen tumor-free survivors after PD (age mean ± SD: 61 ± 8.7 yrs.; 10 male, 9 female) and 10 healthy controls (age: 27 ± 8.7 yrs.; 7 male, 3 female) were given a mixed test meal. One gram of paracetamol was ingested with the meal to evaluate the speed of gastric emptying. Insulin, glucose, and paracetamol plasma concentrations were measured before and over 180 minutes after ingestion. Beta cell function was calculated from fasting glucose and insulin plasma concentrations. Simultaneously, 800 MBq of [{sup 11}C]MET were administered and the activity (maximum tissue standardized uptake values [SUVmax]) over the pancreas was measured at 15, 30, and 60 minutes after injection. Total integrated SUVmax (area under the curve [AUC]) and incremental SUVmax were calculated. The uptake of [{sup 11}C]MET in the pancreas was significantly higher (p < 0.0001) in controls compared to the PD group. Gastric emptying was significantly slower in controls compared to pancreatectomy subjects (p < 0.0001). Paracetamol AUC{sub 30} correlated with the SUVmax increment between 15 and 30 minutes (R{sup 2} = 0.27, p = 0.0263), suggesting a relationship between gastric emptying and the uptake of [{sup 11}C]MET. Total integrated SUVmax correlated with insulin AUC{sub 60} (R{sup 2} = 0.66,p < 0.0001) in patients after PD. Multivariate regression analysis revealed insulin AUC{sub 60} and beta cell function, calculated from the fasting insulin to glucose ratio, as independent predictors of {sup 11}C-methionine uptake, i.e. total integrated SUVmax, in

  3. 甘精胰岛素联合阿卡波糖对2型糖尿病患者血糖达标率及胰岛β细胞功能的影响%The effect of insulin glargine combined with carbose on blood glucose attaining standardand pancreatic β cell function of type 2 diabetic patients

    Institute of Scientific and Technical Information of China (English)

    包灵敏; 刘存安

    2013-01-01

    Objective To explore the effect of insulin glargine combined with carbose onblood glucose attaining standard and pancreatic β cell function of type 2 diabetic patients.Methods 70 type 2 diabetic patients were divided into observation group and control group.All the patients got fundamental treatment as diet control and physical exercise.Patients of observing group got extra treatment as using insulin glargine combined with carbose,while patients of control group got extra treatment as using premixed insulin 30R(isophane protamine biosynthetic human insulin),all the treatment lasted for 8 weeks.Results 8 weeks after treatment,the rate of reaching standard of FBG and 2h postprandial plasma glucose and glycosylated hemoglobin (95.0%,85.0% and 77.5%) of observing group were significantly higher than those of control group (77.5%,62.5% and 55.0%) (x2 =5.16,5.23 and 4.53,all P <0.05).The levels of FCP and PCP increased significantly in both groups than that of before treatment (t =2.43,2.32,2.28,2.19,all P < 0.05),and the change of observation group was more obviously than that of control group (t =2.17,2.13,all P < 0.05).The occurrence rate of hypoglycemia of observation group was significantly lower than that of control group(x2 =4.11,P <0.05).Conclusion Treating diabetic patient by insulin glargine combined with acarbose has high safety,and helps to reach the standard of FBG and glycosylated hemoglobin,reduce the incurrence rate of hypoglycemia,protect and improve the function of pancreatic 3 cell,and postpone the beginning and progress of complication.%目的 探讨甘精胰岛素联合阿卡波糖对2型糖尿病患者血糖达标率及胰岛β细胞功能的影响.方法 选择2型糖尿病患者70例,按就诊病历号顺序随机分为观察组与对照组.两组患者均予以饮食控制和体育锻炼等基础治疗.观察组在此基础上予以甘精胰岛素联合阿卡波糖治疗,对照组在此基础上予以精蛋白生物合成人

  4. Sliding-scale versus basal-bolus insulin in the management of severe or acute hyperglycemia in type 2 diabetes patients: a retrospective study.

    Directory of Open Access Journals (Sweden)

    Hasniza Zaman Huri

    Full Text Available Sliding-scale and basal-bolus insulin regimens are two options available for the treatment of severe or acute hyperglycemia in type 2 diabetes mellitus patients. Although its use is not recommended, sliding-scale insulin therapy is still being used widely. The aims of the study were to compare the glycemic control achieved by using sliding-scale or basal-bolus regimens for the management of severe or acute hyperglycemia in patients with type 2 diabetes and to analyze factors associated with the types of insulin therapy used in the management of severe or acute hyperglycemia. This retrospective study was conducted using the medical records of patients with acute or severe hyperglycemia admitted to a hospital in Malaysia from January 2008 to December 2012. A total of 202 patients and 247 admissions were included. Patients treated with the basal-bolus insulin regimen attained lower fasting blood glucose (10.8 ± 2.3 versus 11.6 ± 3.5 mmol/L; p = 0.028 and mean glucose levels throughout severe/acute hyperglycemia (12.3 ± 1.9 versus 12.8 ± 2.2; p = 0.021 compared with sliding-scale insulin regimens. Diabetic ketoacidosis (p = 0.043, cardiovascular diseases (p = 0.005, acute exacerbation of bronchial asthma (p = 0.010, and the use of corticosteroids (p = 0.037 and loop diuretics (p = 0.016 were significantly associated with the type of insulin regimen used. In conclusion, type 2 diabetes patients with severe and acute hyperglycemia achieved better glycemic control with the basal-bolus regimen than with sliding-scale insulin, and factors associated with the insulin regimen used could be identified.

  5. Effects of biphasic, basal-bolus or basal insulin analogue treatments on carotid intima-media thickness in patients with type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Lundby-Christensen, Louise; Vaag, Allan; Tarnow, Lise;

    2016-01-01

    in combination with insulin detemir once daily (n=138) versus insulin detemir alone once daily (n=137), aiming at HbA1c≤7.0% (≤53 mmol/mol). OUTCOMES: Primary outcome was change in mean carotid IMT (a marker of subclinical cardiovascular disease). HbA1c, insulin dose, weight, and hypoglycaemic and serious...

  6. Safety of Nighttime 2-Hour Suspension of Basal Insulin in Pump-Treated Type 1 Diabetes Even in the Absence of Low Glucose

    Science.gov (United States)

    Sherr, Jennifer L.; Palau Collazo, Miladys; Cengiz, Eda; Michaud, Camille; Carria, Lori; Steffen, Amy T.; Weyman, Kate; Zgorski, Melinda; Tichy, Eileen; Tamborlane, William V.; Weinzimer, Stuart A.

    2014-01-01

    OBJECTIVE An integrated sensor-augmented pump system has been introduced that interrupts basal insulin infusion for 2 h if patients fail to respond to low-glucose alarms. It has been suggested that such interruptions of basal insulin due to falsely low glucose levels detected by sensor could lead to diabetic ketoacidosis. We hypothesized that random suspension of basal insulin for 2 h in the overnight period would not lead to clinically important increases in blood β-hydroxybutyrate levels despite widely varying glucose values prior to the suspension. RESEARCH DESIGN AND METHODS Subjects measured blood glucose and blood β-hydroxybutyrate levels using a meter each night at 9:00 p.m., then fasted until the next morning. On control nights, the usual basal rates were continued; on experimental nights, the basal insulin infusion was reprogrammed for a 2-h zero basal rate at random times after 11:30 p.m. RESULTS In 17 type 1 diabetic subjects (mean age 24 ± 9 years, diabetes duration 14 ± 11 years, A1C level 7.3 ± 0.5% [56 mmol/mol]), blood glucose and blood β-hydroxybutyrate levels were similar at 9:00 p.m. on suspend nights (144 ± 63 mg/dL and 0.09 ± 0.07 mmol/L) and nonsuspend nights (151 ± 65 mg/dL and 0.08 ± 0.06 mmol/L) (P = 0.39 and P = 0.47, respectively). Fasting morning blood glucose levels increased after suspend nights compared with nonsuspend nights (191 ± 68 vs. 141 ± 75 mg/dL, P insulin for 2 h are safe and do not lead to clinically significant ketonemia even if the blood glucose level is elevated at the time of the suspension. PMID:24170766

  7. Basal insulin analogues in diabetic pregnancy: a literature review and baseline results of a randomised, controlled trial in type 1 diabetes

    DEFF Research Database (Denmark)

    Mathiesen, Elisabeth R; Damm, Peter; Jovanovic, Lois

    2011-01-01

    As basal insulin analogues are being used off-label, there is a need to evaluate their safety (maternal hypoglycaemia and fetal and perinatal outcomes) and efficacy [haemoglobin A1c(HbA1c), fasting plasma glucose, and maternal weight gain]. The aim of this review is to provide an overview...

  8. 2型糖尿病从预混胰岛素转换为甘精胰岛素联合口服降糖药物治疗的观察性研究%Study of treatment switching from premixed insulin to glargine combined with oral antidiabetic drugs of patients with type 2 diabetic

    Institute of Scientific and Technical Information of China (English)

    杨艳; 李蓬秋; 包明晶; 刘丽梅; 张学军; 鲜杨; 吴冀川; 张磊; 朱显军

    2014-01-01

    目的 观察2型糖尿病患者从预混胰岛素转换为甘精胰岛素联合口服降糖药物(OADs)治疗的效果、安全性和患者的满意度.方法 采用自身前后对照研究,选择2型糖尿病患者,接受预混胰岛素治疗至少3个月,联合/或未联合OADs治疗,且糖化血红蛋白(HbA1c)≤10.0%的2型糖尿病患者43例,基于患者和医师的考虑,将预混胰岛素转换为甘精胰岛素联合OADs治疗,由医师根据血糖调整胰岛素和OADs的剂量,随访16周,目标空腹血糖≤5.6 mmol/L.结果 共36例患者完成全部随访观察,治疗16周后空腹血糖、餐后2h血糖、HbA1c均与治疗前相当(P均>0.05),而胰岛素用量明显减少[(23.8±6.0)、(9.6±4.0) U/d,t=13.59,P<0.01],体质量指数较治疗前明显下降[(24.4±2.9)、(23.8±2.8)kg/m2,t=3.25,P<0.05];随访期间36例入组患者中15例患者共发生低血糖30次,低血糖发生率41.7%(15/36),均无需他人帮助,少量进食后缓解,无重度低血糖发生,无患者因低血糖反应而退出本研究;36例患者转换前治疗总体满意率为36.1% (13/36),转换后为72.2%(26/36),转换后总体满意度明显高于转换前(x2=6.26,P<O.05).结论 HbA1c≤7.0%时将预混胰岛素转换为甘精胰岛素联合OADs治疗能有效控制血糖,且胰岛素用量及注射次数减少,患者体质量减轻,治疗满意度高.%Objective To evaluation the efficacy,safety and treatment satisfaction of glargine plus oral medications(OADs) switching from premixed insulin on patients with type 2 diabetic.Methods Forty-three patients with type 2 diabetes were enrolled into our study.All patients were treated with twice-daily premixed insulin therapy for at least 3 months with or without OADs and their glycosylated haemoglobin(HbA1c) were less than 10.0%.The aim of OADs treatment was FBG ≤ 5.6 mmol/L Results Thirty-six cases were performed a 16 weeks follow-up and no one lost.After 4 months OADs treatment,the levels of fasting

  9. Initiating insulin therapy in children and adolescents with type 1 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Subhash Kumar Wangnoo

    2015-01-01

    Full Text Available The primary clinical goals to be achieved with insulin initiation are elimination of ketosis and hyperglycemia with prevention of chronic complications. Insulin therapy is the mainstay in management of type 1 diabetes, which should be aimed at achieving good glycemic control, with achievement of hemoglobin A1c (HbA1c <7.5%, pre-meal self-monitored blood glucose (SMBG of 90-130 mg/dL, bed time SMBG of 100-140 mg/dL, mean blood glucose level of 120-160 mg/dL and no ketonuria. Two classes of insulin are available for use in T1DM viz. bolus/prandial insulins (rapid-acting insulins and short-acting insulins and basal insulins (intermediate-acting insulin and long-acting insulin. Insulin glargine and glulisine can be used in children above 6 years, lispro in children above 3 years and detemir and aspart in children above 2 years. The caution for hypoglycemia should be exercised while prescribing them. Degludec is currently not approved for pediatric use. The initial insulin regimen should comprise of ≥2 daily bolus and ≥1 basal insulin injections. Insulin intensification would be required if the initial regimen fails, which can be achieved by increasing frequency of long and rapid acting insulin analogues. The American Diabetes Association guidelines recommend HbA1c targets of <8.0% for children <6 years of age, ≤7.5% for children 6 to 12 years of age, and ≤7.0% for adolescents, 12-18 years of age. However, the evidence is now in favor of a single target HbA1c of ≤7.5% for all children and adolescents <19 years of age.

  10. [Clinical experiences with basal analogue insulin in routine care. Retrospective follow up analysis of a database from daily routine care].

    Science.gov (United States)

    Sudár, Zsolt; Muth, Lajos; Nyirati, Csaba; Szí, Vince; Tornóczky, János; Ulrich, Gabriella

    2013-09-15

    Bevezetés: 2-es típusú cukorbetegségben egyre gyakrabban kerül alkalmazásra a bázis-bolus inzulinkezelési rendszer, az anyagcserekontroll javítása és a szövődmények kockázatának csökkentése érdekében. Napjaink kérdése, hogy az inzulinanalógok alkalmazása milyen gyakorlati változásokat hoz a humán inzulinkezelési rendszerekhez képest. Célkitűzés: A szerzők retrospektív adatelemzéssel vizsgálták a teljes humán bázis-bolus kezelésről teljes inzulinanalóg-kezelésre váltás hatásait az anyagcserehelyzetre, a testsúlyra, az inzulindózisokra és a bázis-bolus inzulin arányra. Módszer: Olyan 2-es típusú cukorbetegeket (n = 137) vontak be a vizsgálatba, akik napi egyszeri bázisinzulint használtak a főétkezésekhez adott gyors hatású inzulinok mellett, és a humán inzulinokról analóg inzulinokra cserélték a gyógyszerüket. A betegeket detemirt (n = 103) és glargint (n = 34) használó csoportokba sorolták. Eredmények: Tizenhét hónapos inzulinanalóg-terápia során a HbA1c 0,34%-kal csökkent (detemir: –0,44%; glargin: –0,17%). A testsúly 1,11 kg-mal növekedett (detemir: +1,0 kg; glargin: +1,43 kg). A bázisinzulin aránya minden esetben emelkedett (teljes populáció: 6,04%, detemir: 5,26%, glargin: 8,37%). Az átlagos inzulindózis a vizsgálat végén 80,76 egység volt, és nem volt szignifikáns különbség sem a bázis-, sem a teljes inzulindózisokat illetően a detemir- (27,89 E, illetve 79,78 E) és a glargin- (32,85 E, 83,74 E) csoportok között. Következtetések: Az adatok alátámasztják, hogy a humánról analóg inzulinra történő váltáskor, bázis-bolus kezelési rendszerben a bázisinzulin dózisának emelésével, a bázis/bolus arány növelésével javítható az anyagcserekontroll. A detemir- és glarginalapú terápia hasonló anyagcserekontroll-javulás mellett azonos inzulindózisokkal járt, és valamelyest több testsúlynövekedéssel a glargincsoportban. Orv. Hetil

  11. 糖尿病及长效胰岛素类似物是否增加病人罹患肿瘤的风险?——1例糖尿病合并胰腺癌患者的循证治疗%Does Diabetes and Long-acting Insulin Glargine Increase the Risk of Malignancies: An Evidence-based Treatment for a Diabetic Patient Accompanied with Pancreatic Cancer

    Institute of Scientific and Technical Information of China (English)

    孙倩倩; 王双; 郑玉霞; 廖再波

    2011-01-01

    Objective Through studying a diabetic patient accompanied with pancreatic cancer by means of evidence-based clinical practice, to find out the relationship between diabetes mellitus and cancer and whether the longacting insulin glargine increases the risk of cancer or not, which is regarded as a disputable hot issue at present.Methods Such databases as The Cochrane Library (Issue 3, 2010), OVID-EBM Reviews (1991 to Sept.2010), MEDLINE (1950 to Sept.2010) and CNKI (2000 to Sept.2010) were retrieved to collect high quality clinical evidence, and the best therapy was formulated in accordance with the willingness of patients themselves.Results Eight randomized controlled trials (RCTs), four meta-analyses and one RCT meta-analysis were included.The evidence indicated that: a) Diabetes mellitus was kind of related to the occurrence of malignancies; b) There was no evidence at present showing the relationship between long-acting insulin glargine and cancer; c) Strictly controlling of blood sugar did not increase the risk of tumorigenesis, but hyperglycemia causing cancer was proofless; and d) Whether the diabetic patient with cancer should stop taking long-acting insulin glargine or not should require suggestions from specialists rather than patients themselves.Conclusion No evidence at present shows that tumorigenesis is related to diabetes mellitus, long-acting insulin glargine and strict controlling of blood sugar.It is necessary to require more evidence to decide whether the therapy should be adjusted or not for the diabetic patient with cancer who is in the process of glargine therapy.%目的 糖尿病与肿瘤的关系以及长效胰岛素类似物是否致癌是目前颇有争议的热点问题,结合1例糖尿病合并胰腺癌患者的病情,用循证临床实践的方法,对糖尿病与肿瘤的关系及长效胰岛素类似物是否致癌进行讨论.方法 计算机检索Cochrane图书馆(2010年第3期)、OVID-EBM Reviews (1991~2010.9),MEDLINE(1950~2010

  12. Use of an implantable pump for controlled subcutaneous insulin delivery in healthy cats.

    Science.gov (United States)

    Zini, E; Padrutt, I; Macha, K; Riederer, A; Pesaresi, M; Lutz, T A; Reusch, C E

    2017-01-01

    The aim of this study was to examine the safety and reliability of a research-grade implantable pump for controlled delivery of insulin glargine in cats. For this purpose, a small telemetrically controlled drug delivery pump with a refillable reservoir was implanted into the subcutaneous tissues of the dorsal neck in 10 clinically healthy cats. The reservoir was filled with insulin glargine, and the pump was programmed to deliver four boluses of 0.25 IU/kg, 2-3 weeks apart. As a control, insulin glargine (0.25 IU/kg) was injected SC. Blood glucose and plasma insulin glargine concentrations were measured before each bolus and SC injection and for 8 h afterward. Cats were monitored for signs of discomfort. Pumps were easily implanted and well tolerated by all cats. The experiment was completed in five of 10 cats. In four, the pump failed because of technical reasons; another cat developed severe hypoglycaemia attributable to insulin leakage. Overall, plasma insulin glargine increased after six of eight (75%) initial boluses and after one of 16 (6%) successive boluses. Glucose decreased after seven of eight (88%) initial boluses and after four of 16 (25%) successive boluses. Only the first bolus significantly increased plasma insulin glargine (P = 0.008) and decreased glucose (P = 0.008). Of 20 SC injections, 10 (50%) increased plasma insulin glargine (P pump did not cause discomfort in cats, but life-threatening hypoglycaemia occurred in one. Frequent device problems suggest that the pump needs improvements. Because successive boluses did not increase plasma insulin glargine, this type of insulin may not be appropriate with the pump.

  13. Differences in bioactivity between human insulin and insulin analogues approved for therapeutic use- compilation of reports from the past 20 years

    OpenAIRE

    Werner Haim; Chantelau Ernst A

    2011-01-01

    Abstract In order to provide comprehensive information on the differences in bioactivity between human insulin and insulin analogues, published in vitro comparisons of human insulin and the rapid acting analogues insulin lispro (Humalog®), insulin aspart ( NovoRapid®), insulin glulisine (Apidra®), and the slow acting analogues insulin glargine (Lantus®), and insulin detemir (Levemir®) were gathered from the past 20 years (except for receptor binding studies). A total of 50 reports were retrie...

  14. Moderate alcohol consumption is associated with improved insulin sensitivity, reduced basal insulin secretion rate and lower fasting glucagon concentration in healthy women

    DEFF Research Database (Denmark)

    Bonnet, F; Disse, E; Laville, M

    2012-01-01

    Moderate alcohol consumption is associated with a reduced risk of type 2 diabetes with a stronger effect in women. As the underlying mechanisms remain poorly characterised, we investigated its relationship with insulin resistance, insulin secretion, clearance of insulin and glucagon concentration....

  15. The GLP-1 Analogue Exenatide Improves Hepatic and Muscle Insulin Sensitivity in Diabetic Rats: Tracer Studies in the Basal State and during Hyperinsulinemic-Euglycemic Clamp

    Directory of Open Access Journals (Sweden)

    Hui Wu

    2014-01-01

    Full Text Available Objective. Glucagon-like peptide-1 (GLP-1 analogues (e.g., exenatide increase insulin secretion in diabetes but less is known about their effects on glucose production or insulin-stimulated glucose uptake in peripheral tissues. Methods. Four groups of Sprague-Dawley rats were studied: nondiabetic (control, C; nondiabetic + exenatide (C + E; diabetic (D; diabetic + exenatide (D + E with diabetes induced by streptozotocin and high fat diet. Infusion of 3-3H-glucose and U-13C-glycerol was used to measure basal rates of appearance (Ra of glucose and glycerol and gluconeogenesis from glycerol (GNG. During hyperinsulinemic-euglycemic clamp, glucose uptake into gastrocnemius muscles was measured with 2-deoxy-D-14C-glucose. Results. In the diabetic rats, exenatide reduced the basal Ra of glucose (P<0.01 and glycerol (P<0.01 and GNG (P<0.001. During the clamp, Ra of glucose was also reduced, whereas the rate of disappearance of glucose increased and there was increased glucose uptake into muscle (P<0.01 during the clamp. In the nondiabetic rats, exenatide had no effect. Conclusion. In addition to its known effects on insulin secretion, administration of the GLP-1 analogue, exenatide, is associated with increased inhibition of gluconeogenesis and improved glucose uptake into muscle in diabetic rats, implying improved hepatic and peripheral insulin sensitivity.

  16. Efficacy of basal-bolus insulin regimens in the inpatient management of non-critically ill patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Christensen, Merete B; Gotfredsen, Anders; Nørgaard, Kirsten

    2017-01-01

    BACKGROUND: Hyperglycemia during hospitalization is associated with increased rates of complications and longer hospital stays. Various insulin regimens are used in the inpatient diabetes management of non-critically ill patients. We aimed to assess the efficacy and safety of basal-bolus insulin...... therapy (BBI) by summarizing evidence from studies of BBI versus sliding scale insulin therapy (SSI) in the management of hospitalized non-critically ill type 2 diabetes patients. METHODS: We searched MEDLINE, EMBASE, Scopus and the Cochrane Library for studies comparing BBI therapy with SSI therapy...... in hospitalized non-critically ill patients with type 2 diabetes. Primary outcome was mean daily blood glucose (BG) during admission. Secondary outcomes were incidence of hypoglycemia and length of hospital stay. Results of included randomized controlled trials (RCT) were pooled and meta-analyzed to provide...

  17. Perceptions of diabetes control among people with type 2 diabetes treated with basal insulin in Sweden, Switzerland, and the United Kingdom

    DEFF Research Database (Denmark)

    Brod, Meryl; Pfeiffer, Kathryn M; Barnett, Anthony H

    2016-01-01

    /extremely important for deciding whether they are well controlled, including diet (80.7%), HbA1c value (78.9%), times per day insulin taken (78.8%), insulin units taken per day (77.6%), and energy levels (74.5%). Fifty-one percent of uncontrolled respondents considered the past week or more recently when thinking...... people with uncontrolled T2D (HbA1c >8.0% or 64 mmol/mol) on basal insulin in Sweden, Switzerland, and the UK and 295 people with well controlled T2D (HbA1c ... were significantly more likely to consider the last 24 hours/current time when thinking about control (50% vs. 21%, p 

  18. Combined insulin treatment and intense exercise training improved basal cardiac function and Ca(2+)-cycling proteins expression in type 1 diabetic rats.

    Science.gov (United States)

    Le Douairon Lahaye, Solène; Gratas-Delamarche, Arlette; Malardé, Ludivine; Zguira, Sami; Vincent, Sophie; Lemoine Morel, Sophie; Carré, François; Rannou Bekono, Françoise

    2012-02-01

    This study investigated the effects of 8 weeks of intense exercise training combined with insulin treatment on the Ca(2+)-cycling protein complex expression and their functional consequences on cardiac function in type 1 diabetic rat hearts. Diabetic Wistar rats were randomly assigned into the following groups: received no treatment, insulin-treated diabetic, trained diabetic, and trained insulin-treated diabetic. A control group was also included. Insulin treatment and (or) treadmill intense exercise training were conducted over 8 weeks. Basal cardiac function was evaluated by Langendorff technique. Cardiac expression of the main Ca(2+)-cycling proteins (RyR2, FKBP 12.6, SERCA2, PLB, NCX1) was assessed by Western blot. Diabetes altered basal cardiac function (±dP/dt) and decrease the expression of the main Ca(2+)-cycling proteins expression: RyR2, SERCA2, and NCX1 (p < 0.05). Whereas combined treatment was not able to normalize -dP/dt, it succeeded to normalize +dP/dt of diabetic rats (p < 0.05). Moreover, both insulin and intense exercise training, applied solely, increased the expression of the Ca(2+)-cycling proteins: RyR2, SERCA2, PLB. and NCX1 (p < 0.05). But this effect was higher when the 2 treatments were combined. These data are the first to show that combined insulin treatment and intense exercise training during diabetes synergistically act on the expression of the main Ca(2+)-cycling proteins, providing insights into mechanisms by which the dual treatment during diabetes improves cardiac function.

  19. Insulin, insulin analogues and diabetic retinopathy.

    Science.gov (United States)

    Chantelau, Ernst; Kimmerle, Renate; Meyer-Schwickerath, Rolf

    2008-02-01

    Insulin is absolutely vital for living beings. It is not only involved in metabolism, but also in the regulation of growth factors, e.g. IGF-1. In this review we address the role insulin has in the natural evolution of diabetic retinopathy. On the one hand, chronic deficiency of insulin and IGF-1 at the retina is thought to cause capillary degeneration, with subsequent ischaemia. On the other hand, acute abundance of (exogenously administered) insulin and IGF-1 enhances ischaemia-induced VEGF expression. A critical ratio of tissue VEGF-susceptibility: VEGF-availability triggers vascular proliferation (i.e. of micro-aneurysms and/or abnormal vessels). The patent-protected insulin analogues Lispro, Glulisine, Aspart, Glargine and Detemir are artificial insulin derivatives with altered biological responses compared to natural insulin (e.g. divergent insulin and /or IGF-1 receptor-binding characteristics, signalling patterns, and mitogenicity). Their safety profiles concerning diabetic retinopathy remain to be established by randomised controlled trials. Anecdotal reports and circumstantial evidence suggest that Lispro and Glargine might worsen diabetic retinopathy.

  20. The basal kinetic parameters of glycogen synthase in human myotube cultures are not affected by chronic high insulin exposure

    DEFF Research Database (Denmark)

    Gaster, M; Schrøder, H D; Handberg, A

    2001-01-01

    There is no consensus regarding the results from in vivo and in vitro studies on the impact of chronic high insulin and/or high glucose exposure on acute insulin stimulation of glycogen synthase (GS) kinetic parameters in human skeletal muscle. The aim of this study was to evaluate the kinetic...... parameters of glycogen synthase activity in human myotube cultures at conditions of chronic high insulin combined or not with high glucose exposure, before and after a subsequent acute insulin stimulation. Acute insulin stimulation significantly increased the fractional activity (FV(0.1)) of GS, increased...

  1. Metabolic hormones regulate basal and growth hormone-dependent igf2 mRNA level in primary cultured coho salmon hepatocytes: effects of insulin, glucagon, dexamethasone, and triiodothyronine.

    Science.gov (United States)

    Pierce, A L; Dickey, J T; Felli, L; Swanson, P; Dickhoff, W W

    2010-03-01

    Igf1 and Igf2 stimulate growth and development of vertebrates. Circulating Igfs are produced by the liver. In mammals, Igf1 mediates the postnatal growth-promoting effects of growth hormone (Gh), whereas Igf2 stimulates fetal and placental growth. Hepatic Igf2 production is not regulated by Gh in mammals. Little is known about the regulation of hepatic Igf2 production in nonmammalian vertebrates. We examined the regulation of igf2 mRNA level by metabolic hormones in primary cultured coho salmon hepatocytes. Gh, insulin, the glucocorticoid agonist dexamethasone (Dex), and glucagon increased igf2 mRNA levels, whereas triiodothyronine (T(3)) decreased igf2 mRNA levels. Gh stimulated igf2 mRNA at physiological concentrations (0.25x10(-9) M and above). Insulin strongly enhanced Gh stimulation of igf2 at low physiological concentrations (10(-11) M and above), and increased basal igf2 (10(-8) M and above). Dex stimulated basal igf2 at concentrations comparable to those of stressed circulating cortisol (10(-8) M and above). Glucagon stimulated basal and Gh-stimulated igf2 at supraphysiological concentrations (10(-7) M and above), whereas T(3) suppressed basal and Gh-stimulated igf2 at the single concentration tested (10(-7) M). These results show that igf2 mRNA level is highly regulated in salmon hepatocytes, suggesting that liver-derived Igf2 plays a significant role in salmon growth physiology. The synergistic regulation of igf2 by insulin and Gh in salmon hepatocytes is similar to the regulation of hepatic Igf1 production in mammals.

  2. Glycemic control and long-acting insulin analog utilization in patients with type 2 diabetes

    NARCIS (Netherlands)

    E.M. Heintjes (Edith); T.L. Thomsen (Trine Lyager); F.J.A. Penning-Van Beest (Fernie); T.E. Christensen (Torsten); R.M.C. Herings (Ron)

    2010-01-01

    textabstractIntroduction: The objective was to compare glycemic control, insulin utilization, and body weight in patients with type 2 diabetes (T2D) initiated on insulin detemir (IDet) or insulin glargine (IGlar) in a real-life setting in the Netherlands. Methods: Insulin-naïve patients with T2D, st

  3. Isomeric C12-alkamides from the roots of Echinacea purpurea improve basal and insulin-dependent glucose uptake in 3T3-L1 adipocytes.

    Science.gov (United States)

    Kotowska, Dorota; El-Houri, Rime B; Borkowski, Kamil; Petersen, Rasmus K; Fretté, Xavier C; Wolber, Gerhard; Grevsen, Kai; Christensen, Kathrine B; Christensen, Lars P; Kristiansen, Karsten

    2014-12-01

    Echinacea purpurea has been used in traditional medicine as a remedy for the treatment and prevention of upper respiratory tract infections and the common cold. Recent investigations have indicated that E. purpurea also has an effect on insulin resistance. A dichloromethane extract of E. purpurea roots was found to enhance glucose uptake in adipocytes and to activate peroxisome proliferator-activated receptor γ. The purpose of the present study was to identify the bioactive compounds responsible for the potential antidiabetic effect of the dichloromethane extract using a bioassay-guided fractionation approach. Basal and insulin-dependent glucose uptake in 3T3-L1 adipocytes were used to assess the bioactivity of extract, fractions and isolated metabolites. A peroxisome proliferator-activated receptor γ transactivation assay was used to determine the peroxisome proliferator-activated receptor γ activating properties of the extract, active fractions and isolated metabolites. Two novel isomeric dodeca-2E,4E,8Z,10E/Z-tetraenoic acid 2-methylbutylamides together with two known C12-alkamides and α-linolenic acid were isolated from the active fractions. The isomeric C12-alkamides were found to activate peroxisome proliferator-activated receptor γ, to increase basal and insulin-dependent glucose uptake in adipocytes in a dose-dependent manner, and to exhibit characteristics of a peroxisome proliferator-activated receptor γ partial agonist. Georg Thieme Verlag KG Stuttgart · New York.

  4. Chronic insulin therapy reduces adipose tissue macrophage content in LDL-receptor-deficient mice.

    Science.gov (United States)

    Yoon, J; Subramanian, S; Ding, Y; Wang, S; Goodspeed, L; Sullivan, B; Kim, J; O'Brien, K D; Chait, A

    2011-05-01

    Insulin has anti-inflammatory effects in short-term experiments. However, the effects of chronic insulin administration on inflammation are unknown. We hypothesised that chronic insulin administration would beneficially alter adipose tissue inflammation and several circulating inflammatory markers. We administered two forms of long-acting insulin, insulin glargine (A21Gly,B31Arg,B32Arg human insulin) and insulin detemir (B29Lys[ε-tetradecanoyl],desB30 human insulin), to LDL-receptor-deficient mice. After 8 weeks on a diet that causes obesity, hyperglycaemia, adipose tissue macrophage accumulation and atherosclerosis, the mice received subcutaneous glargine, detemir or NaCl (control) for 12 weeks. Serum amyloid A (SAA) and serum amyloid P (SAP), metabolic variables, adipose tissue macrophages and aortic atherosclerosis were evaluated. Weight gain was equivalent in all groups. The glycated haemoglobin level fell equivalently in both insulin-treated groups. Plasma cholesterol and triacylglycerol levels, and hepatic triacylglycerol level significantly improved in the glargine compared with the detemir or control groups. Levels of mRNA expression for monocyte chemotactic protein-1 and F4/80, a macrophage marker, in adipose tissue were decreased only in the glargine group (p adipose tissue macrophage content decreased in both insulin groups (p insulin-treated group, but IL-6 levels fell in the glargine-treated mice. While chronic insulin administration did not decrease SAA and SAP, administration of glargine but not detemir insulin improved dyslipidaemia, IL-6 levels and atherosclerosis, and both insulins reduced macrophage accumulation in visceral adipose tissue. Thus, chronic insulin therapy has beneficial tissue effects independent of circulating inflammatory markers in this murine model of diet-induced obesity and diabetes.

  5. 两种甘精胰岛素治疗糖尿病的疗效及安全性比较:多中心、随机、开放、对照试验%Efficacy and safety of glargine insulin injection Uslen versus Lantus in diabetic patients: a multicenter, randomized, open-labeled controlled trial

    Institute of Scientific and Technical Information of China (English)

    刘云慧; 侯丽琼; 赵铁耘; 田浩明; 吕肖锋; 杨金奎; 李玲; 朱旅云; 张力辉

    2014-01-01

    Objective To evaluate the efficacy and safety of glargine insulin injection (Uslen) in treatment of diabetic patients.Methods A multicenter,randomized,open-labeled and positive control clinical trial included the patients with type 1 or type 2 diabetes mellitus having poor glucose control after using oral antidiabetic drug or short-acting insulin.All patients were treated with Uslen or Lantus for 16 weeks in two groups by a ratio of 1 ∶ 1.The decreased value and qualification rates of glycated hemoglobin A1 c (HbA1 c) and fasting blood glucose (FBG),the incidence of hypoglycemic and the adverse events were compared pretreatment at the end of 16 weeks' treatment.Results All of 664 cases were randomized into two groups and received therapy (1 ∶ 1).But 623 cases were in complete conformity to design plan,313 cases received Uslen therapy and 310 cases received Lantus therapy.There were no different in age,sex,nation,height and weight between two groups.At the end of 16 weeks' treatment,according to the perprotocol analysis (PPS),the decreased values of HbA1c separately (9.2 ± 1.5)% vs (7.7 ± 1.2)% and (9.3±1.5) vs (7.7±1.1)%,FBGseparately (10.2±2.1 vs7.2±2.0) mmol/Land (10.3±2.3 vs 7.4 ± 2.3) mmol/L were all proved significantly in both Uslen group and Lantus group (all P < 0.001).But the changes of HbA1c(1.5% vs 1.6%,F=0.766,P=0.382) and FBG(3.0 vs 2.9 mmol/L,F=0.280,P =0.597) from baseline to endpoint were similar between the treatment groups (P > 0.05).There were no significant difference in the two groups on the qualification rates of HbA1c(26.2% (82/313)vs 21.3% (66/310),P =0.155) and FBG(29.1% (91/313) vs 28.4% (88/310),P >0.05).There were no significant difference separately 22.7% (75/330) and 22.0% (74/333) on hypoglycemia incidences,and the other adverse events incidences were similar separately 0.3% (1/330 vs 1/333,P > 0.05) in two groups.Conclusion Compared with Lantus,the glargine insulin injection of Uslen has

  6. Switching from NPH insulin to once-daily insulin detemir in basal-bolus-treated patients with diabetes mellitus: data from the European cohort of the PREDICTIVE study.

    LENUS (Irish Health Repository)

    Sreenan, S

    2008-12-01

    The PREDICTIVE study is a multinational observational study designed to follow up patients with diabetes who started insulin detemir (IDet) in routine care. Recruitment started in June 2004 and is ongoing in some countries.

  7. Could recombinant insulin compounds contribute to adenocarcinoma progression by stimulating local angiogenesis?

    NARCIS (Netherlands)

    Rensing, K.L.; Houttuijn Bloemendaal, F.M.; Weijers, E.M.; Richel, D.J.; Büller, H.R.; Koolwijk, P.; van der Loos, C.M.; Twickler, T.B.; von der Thüsen, J.H.

    2010-01-01

    Negative effects on the progression of adenocarcinomas by hyperinsulinaemia and the insulin analogue glargine (A21Gly,B31Arg,B32Arg human insulin) have recently been suggested. Most actions of this insulin analogue have hitherto been explained by direct stimulation of growth potential of neoplastic

  8. Could recombinant insulin compounds contribute to adenocarcinoma progression by stimulating local angiogenesis?

    NARCIS (Netherlands)

    Rensing, K.L.; Houttuijn Bloemendaal, F.M.; Weijers, E.M.; Richel, D.J.; Büller, H.R.; Koolwijk, P.; van der Loos, C.M.; Twickler, T.B.; von der Thüsen, J.H.

    2010-01-01

    Negative effects on the progression of adenocarcinomas by hyperinsulinaemia and the insulin analogue glargine (A21Gly,B31Arg,B32Arg human insulin) have recently been suggested. Most actions of this insulin analogue have hitherto been explained by direct stimulation of growth potential of neoplastic

  9. Acute administration of unacylated ghrelin has no effect on Basal or stimulated insulin secretion in healthy humans.

    Science.gov (United States)

    Tong, Jenny; Davis, Harold W; Summer, Suzanne; Benoit, Stephen C; Haque, Ahrar; Bidlingmaier, Martin; Tschöp, Matthias H; D'Alessio, David

    2014-07-01

    Unacylated ghrelin (UAG) is the predominant ghrelin isoform in the circulation. Despite its inability to activate the classical ghrelin receptor, preclinical studies suggest that UAG may promote β-cell function. We hypothesized that UAG would oppose the effects of acylated ghrelin (AG) on insulin secretion and glucose tolerance. AG (1 µg/kg/h), UAG (4 µg/kg/h), combined AG+UAG, or saline were infused to 17 healthy subjects (9 men and 8 women) on four occasions in randomized order. Ghrelin was infused for 30 min to achieve steady-state levels and continued through a 3-h intravenous glucose tolerance test. The acute insulin response to glucose (AIRg), insulin sensitivity index (SI), disposition index (DI), and intravenous glucose tolerance (kg) were compared for each subject during the four infusions. AG infusion raised fasting glucose levels but had no effect on fasting plasma insulin. Compared with the saline control, AG and AG+UAG both decreased AIRg, but UAG alone had no effect. SI did not differ among the treatments. AG, but not UAG, reduced DI and kg and increased plasma growth hormone. UAG did not alter growth hormone, cortisol, glucagon, or free fatty acid levels. UAG selectively decreased glucose and fructose consumption compared with the other treatments. In contrast to previous reports, acute administration of UAG does not have independent effects on glucose tolerance or β-cell function and neither augments nor antagonizes the effects of AG.

  10. Treatment intensification in patients with inadequate glycemic control on basal insulin: rationale and clinical evidence for the use of short‐acting and other glucagon‐like peptide‐1 receptor agonists

    Science.gov (United States)

    Bonadonna, Riccardo C.; Gentile, Sandro; Vettor, Roberto; Pozzilli, Paolo

    2016-01-01

    Summary A substantial proportion of patients with type 2 diabetes mellitus do not reach glycemic targets, despite treatment with oral anti‐diabetic drugs and basal insulin therapy. Several options exist for treatment intensification beyond basal insulin, and the treatment paradigm is complex. In this review, the options for treatment intensification will be explored, focusing on drug classes that act via the incretin system and paying particular attention to the short‐acting glucagon‐like peptide‐1 receptor agonists exenatide and lixisenatide. Current treatment guidelines will be summarized and discussed. © 2016 The Authors. Diabetes/Metabolism Research and Reviews Published by John Wiley & Sons Ltd. PMID:26787264

  11. The fluctuation of blood glucose, insulin and glucagon concentrations before and after insulin therapy in type 1 diabetes

    Science.gov (United States)

    Arif, Idam; Nasir, Zulfa

    2015-09-01

    A dynamical-systems model of plasma glucose, insulin and glucagon concentrations has been developed to investigate the effects of insulin therapy on blood glucose, insulin and glucagon regulations in type 1 diabetic patients. Simulation results show that the normal regulation of blood glucose concentration depends on insulin and glucagon concentrations. On type 1 diabetic case, the role of insulin on regulating blood glucose is not optimal because of the destruction of β cells in pancreas. These β cells destructions cause hyperglycemic episode affecting the whole body metabolism. To get over this, type 1 diabetic patients need insulin therapy to control the blood glucose level. This research has been done by using rapid acting insulin (lispro), long-acting insulin (glargine) and the combination between them to know the effects of insulin therapy on blood glucose, insulin and glucagon concentrations. Simulation results show that these different types of insulin have different effects on blood glucose concentration. Insulin therapy using lispro shows better blood glucose control after consumption of meals. Glargin gives better blood glucose control between meals and during sleep. Combination between lispro and glargine shows better glycemic control for whole day blood glucose level.

  12. Insulin analogues display atypical differentiative activities in skin keratinocytes.

    Science.gov (United States)

    Solomon Zemler, Ravid; Weingarten, Galina; Sarfstein, Rive; Laron, Zvi; Werner, Haim; Wertheimer, Efrat

    2015-02-01

    We have previously shown that both insulin and IGF1 lead to increased proliferation of keratinocytes. However, whereas insulin supports keratinocytes differentiation, IGF1 inhibits this process. The aim of the present study was to examine the proliferative and differentiative effects of insulin analogues (glargine, detemir, lispro and aspart) in primary keratinocytes in comparison with insulin and IGF1. Primary keratinocytes cultures were produced from newborn BALB/c mice skin. Proliferation rates were assessed by [(3)H]-thymidine incorporation and XTT assays and differentiation was evaluated by Western blots analysis. Insulin receptor and IGF1 receptor phosphorylation was assessed by immunoprecipitation assays. Treatment with glargine or detemir resulted in an insulin-like effect on the differentiation process whereas lispro and aspart treatment led to an IGF1-like effect. In addition, treatment of keratinocytes with aspart led to a rapid phosphorylation of the IGF1 receptor. Our study provides evidence that insulin analogues elicit atypical actions in the skin.

  13. Research Progress of Insulin Detemir%地特胰岛素的研究进展

    Institute of Scientific and Technical Information of China (English)

    罗惠辛

    2012-01-01

    地特胰岛素是基础胰岛素类似物,有其独特的分子结构,可与血浆白蛋白可逆性结合,具有长且相对平缓的时间作用曲线,可以显著减少受试者个体内变异性,作用持续时间与甘精胰岛素没有任何差异.众多的临床试验及观察显示地特胰岛素可明显降低糖化血红蛋白、空腹血糖(FPG)、FPG变异性,与甘精胰岛素和中性鱼精蛋白锌胰岛素无明显差异.但在减少低血糖发生和体质量控制方面显示出其优越性.地特胰岛素与胰岛素样生长因子1受体亲和力低,很多研究证实其和人胰岛素相比促生长效应没有变化,但是胰岛素类似物长期应用的安全性尚有争议.%Insulin detemir is one of basal human insulin analogues. It has unique molecule structure, with an acylated fatty acid chain that enables reversible binding to albumin. It has longer and relative flat time action curve,can decrease individual variability significantly,and its duration of action is similar with insulin glargine. Many clinical studies have showed insulin detemir reduced glycosylated hemoglobin, fasting plasma glucose ( FPG )and FPG variability obviously compared with insulin glargine and neutral protamin hagedorn. It showed its advantage in hypoglycaemia event rate and weight gain. Insulin detemir has low affinity with insulin-like growth factor-1 receptor,and is proved,by many studies,no increased or decreased growth promoting effect compared to human insulin, though the safety of long-term insulin analogues treatment is still controversial.

  14. Surfactant protein d deficiency in mice is associated with hyperphagia, altered fat deposition, insulin resistance, and increased Basal endotoxemia

    DEFF Research Database (Denmark)

    Stidsen, Jacob V; Khorooshi, Reza; Rahbek, Martin K U

    2012-01-01

    Pulmonary surfactant protein D (SP-D) is a host defence lectin of the innate immune system that enhances clearance of pathogens and modulates inflammatory responses. Recently it has been found that systemic SP-D is associated with metabolic disturbances and that SP-D deficient mice are mildly obese...... with elevated levels of systemic bacterial lipopolysaccharide.In conclusion, our findings suggest that lack of SP-D mediates modulation of food intake not directly involving hypothalamic regulatory pathways. The resulting accumulation of adipose tissue was associated with insulin resistance. The data suggest SP...

  15. Can Fasting Glucose Levels or Post-Breakfast Glucose Fluctuations Predict the Occurrence of Nocturnal Asymptomatic Hypoglycemia in Type 1 Diabetic Patients Receiving Basal-Bolus Insulin Therapy with Long-Acting Insulin?

    Science.gov (United States)

    Mitsuishi, Sumie; Nishimura, Rimei; Ando, Kiyotaka; Tsujino, Daisuke; Utsunomiya, Kazunori

    2015-01-01

    To investigate whether the occurrence of nocturnal asymptomatic hypoglycemia may be predicted based on fasting glucose levels and post-breakfast glucose fluctuations. The study subjects comprised type 1 diabetic patients who underwent CGM assessments and received basal-bolus insulin therapy with long-acting insulin. The subjects were evaluated for I) fasting glucose levels and II) the range of post-breakfast glucose elevation (from fasting glucose levels to postprandial 1- and 2-hour glucose levels). The patients were divided into those with asymptomatic hypoglycemia during nighttime and those without for comparison. Optimal cut-off values were also determined for relevant parameters that could predict nighttime hypoglycemia by using ROC analysis. 64 patients (mean HbA1c 8.7 ± 1.8%) were available for analysis. Nocturnal asymptomatic hypoglycemia occurred in 23 patients (35.9%). Fasting glucose levels (I) were significantly lower in those with hypoglycemia than those without (118 ± 35 mg/dL vs. 179 ± 65 mg/dL; P fasting glucose level 54 mg/dL (0.65/0.61/0.71, P = 0.006), 2-h postprandial elevation > 78 mg/dL (0.65/0.73/0.71, P = 0.005). Nocturnal asymptomatic hypoglycemia was associated with increases in post-breakfast glucose levels in type 1 diabetes. Study findings also suggest that fasting glucose levels and the range of post-breakfast glucose elevation could help predict the occurrence of nocturnal asymptomatic hypoglycemia.

  16. Insulin analogues: have they changed insulin treatment and improved glycaemic control?

    DEFF Research Database (Denmark)

    Madsbad, Sten

    2002-01-01

    in a long half-life with a residual activity of about 50% 24 h after injection. Insulin glargine is a peakless insulin and studies in both type 1 and type 2 diabetic patients indicate that glargine improves fasting blood glucose control and reduces the incidence of nocturnal hypoglycaemia. Surprisingly...... have not been able to show any improvement in overall glycaemic control with the fast-acting analogues. A reduced post-prandial increase in blood glucose has been found in all studies, whereas between 3 and 5 h after the meal and during the night an increased blood glucose level is the normal course....... This is probably the main explanation for the absence of improvement in overall glycaemic control when compared with regular human insulin. A tendency to a reduction in hypoglycaemic events during treatment with fast-acting analogues has been observed in most studies. Recent studies have indicated that NPH insulin...

  17. Insulin treatment and breast cancer risk; A systematic review of in vitro, animal and epidemiological evidence

    NARCIS (Netherlands)

    Bronsveld, Heleen K.|info:eu-repo/dai/nl/371740819; Ter Braak, Bas; Karlstad, Øystein; Vestergaard, Peter; Starup-Linde, Jakob; Bazelier, Marloes T.|info:eu-repo/dai/nl/341589802; de Bruin, Marieke|info:eu-repo/dai/nl/270270906; De Boer, Anthonius|info:eu-repo/dai/nl/075097346; Siezen, Christine L.E.; Van De Water, Bob; Van Der Laan, Jan Willem; Schmidt, Marjanka K.

    2015-01-01

    Background: In 2009, the concern has been raised that insulin analogues, especially insulin glargine, might increase risk of (breast) cancer. Many in vitro and epidemiological and some animal studies have been performed, but there is still no clarity on this issue. Objectives: The aim of this study

  18. Impact of race/ethnicity on efficacy and safety of two starter insulin regimens in patients with type 2 diabetes : A posthoc analysis of the DURABLE trial

    NARCIS (Netherlands)

    Davidson, Jaime A.; Wolffenbuttel, Bruce H.; Arakaki, Richard F.; Caballero, A. Enrique; Jiang, Honghua H.; Hardin, Dana S.

    2013-01-01

    OBJECTIVE: To explore the impact of race/ethnicity on efficacy and safety of twice-daily insulin lispro mix 75/25 (LM75/25; 75% lispro protamine suspension, 25% insulin lispro) and once daily insulin glargine (GL). DESIGN, SETTING, PATIENTS: More than 2,000 Patients with type 2 diabetes enrolled in

  19. Drug: D03250 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D03250 Drug Insulin glargine (genetical recombination) (JAN); Insulin glargine (USA...llaneous 2492 Pancreatic hormones D03250 Insulin glargine (genetical recombinatio...ogues for injection, long-acting A10AE04 Insulin glargine D03250 Insulin glargine (genetical recombination) ...cose Regulators Insulins Insulin glargine D03250 Insulin glargine (genetical recombination) (JAN); Insulin g...7] Insulin glargine [ATC:A10AE04] D03250 Insulin glargine (genetical recombination) (JAN); Insulin glargine

  20. Continuation versus discontinuation of insulin secretagogues when initiating insulin in type 2 diabetes

    NARCIS (Netherlands)

    S.G. Swinnen; M.P. Dain; D. Mauricio; J.H. Devries; J.B. Hoekstra; F. Holleman

    2010-01-01

    We compared the combined use of basal insulin, metformin and insulin secretagogues with a combination of basal insulin and metformin in patients with type 2 diabetes starting basal insulin analogue therapy. This analysis was part of a 24-week trial, in which 964 insulin-naive patients with type 2 di

  1. Real-world medication persistence and outcomes associated with basal insulin and glucagon-like peptide 1 receptor agonist free-dose combination therapy in patients with type 2 diabetes in the US

    Science.gov (United States)

    Lin, Jay; Lingohr-Smith, Melissa; Fan, Tao

    2017-01-01

    Background Free-dose combination treatment with basal insulin and short-acting glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduces hyperglycemia via complementary targeting of fasting and postprandial blood glucose levels, however, in the real world, due to injection burden and clinical inertia, the full efficacy may not be able to translate into clinical and economic benefits. Objective The aim of the study was to evaluate treatment persistence and associated outcomes in patients with type 2 diabetes (T2D) treated with a GLP-1 RA in free-dose combination with basal insulin. Methods Claims data were extracted on US adults with T2D with ≥1 prescription claim for both a GLP-1 RA and a basal insulin from July 1, 2008 to June 30, 2013, and continuous health plan coverage for 6 months prior to (baseline) and 12 months after the index date (follow-up period). Outcomes analyzed for patients stratified by treatment persistence included glycemic control, hypoglycemia, and health care costs and resource utilization. Multivariate analyses were used to examine factors associated with persistence or hypoglycemia. Results The analysis included 7,320 patients, of whom 16.9% were persistent with free-dose combination treatment. The median time to treatment discontinuation was 133 days. Compared with nonpersistent patients, persistent patients had greater glycated hemoglobin A1c (A1C) reductions (−0.80% vs −0.42%; P=0.032), were more likely to achieve A1C GLP-1 RA and basal insulin treatment is low, improved treatment persistence is associated with greater A1C reductions and lower total medical charges. PMID:28053550

  2. Lipoproteína (a está associada com níveis basais de insulina em pacientes com Diabetes Mellitus tipo 2 Lipoproteína (a está asociada a niveles basales de insulina en pacientes con Diabetes Mellitus tipo 2 Lipoprotein (a is associated with basal insulin levels in patients with type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Syed Shahid Habib

    2009-07-01

    Full Text Available FUNDAMENTO: Ainda não foi claramente estabelecido se a resistência/deficiência insulínica leva diretamente à aterogênese ou através de sua associação com outros fatores de risco como os níveis de lipoproteína (a[Lp(a]. OBJETIVO: O objetivo do estudo foi estabelecer a relação entre os níveis basais de insulina, lípides e lipoproteína (a em pacientes com diabetes mellitus (DM tipo 2. MÉTODOS: Amostras de sangue foram colhidas em jejum e os níveis de insulina, lipoproteína (a, colesterol total (CT, triglicérides (TG, lipoproteína de baixa densidade (LDL-C, lipoproteína de alta densidade (LDL-C, glicose e hemoglobina glicada (HbA1c foram medidos em 60 pacientes com DM tipo 2 e 28 indivíduos saudáveis. Nós dividimos os pacientes em dois grupos baseados nos níveis basais de insulina: > 10 µIU/ml e 10 µIU/ml comparados com aqueles que apresentavam insulina basal FUNDAMENTO: Todavía no se aclaró totalmente si la resistencia/deficiencia insulínica lleva directamente a la aterogénesis o a través de su asociación con otros factores de riesgo como los niveles de lipoproteína (a [Lp(a]. OBJETIVO: : El objetivo del estudio fue establecer la relación entre los niveles basales de insulina, lípidos y lipoproteína (a en pacientes con diabetes mellitus (DM tipo 2. MÉTODOS: Se extrajeron muestras de sangre en ayuno y se determinaron los niveles de insulina, lipoproteína (a, colesterol total (CT, triglicéridos (TG, lipoproteína de baja densidad (LDL-C, lipoproteína de alta densidad (LDL-C, glucosa y hemoglobina glicosilada (HbA1c en 60 pacientes con DM tipo 2 y 28 individuos sanos. Dividimos a los pacientes en dos grupos basados en los niveles basales de insulina: > 10 µIU/ml y 10 µIU/ml comparados con aquellos que presentaban insulina basal BACKGROUND: It has not been clearly established whether insulin resistance/deficiency leads directly to atherogenesis or through its association with other risk factors such as

  3. Which oral antidiabetic drug to combine with metformin to minimize the risk of hypoglycemia when initiating basal insulin?: A randomized controlled trial of a DPP4 inhibitor versus insulin secretagogues.

    Science.gov (United States)

    Gautier, J F; Monguillon, P; Verier-Mine, O; Valensi, P; Fiquet, B; Dejager, S; Charbonnel, B

    2016-06-01

    We conducted a pilot study to evaluate two therapeutic strategies at the time of insulin initiation in type 2 diabetic patients insufficiently controlled with metformin+insulin-secretagogues (IS, sulfonylureas or glinides). Patients were randomized to remain under the same dual therapy or to receive metformin+DPP4 inhibitors while starting insulin. Similar glycemic control was achieved in both groups. However less hypoglycemia was observed with DPP4 inhibitors despite higher doses of insulin.

  4. Twenty-four-hour simultaneous subcutaneous basal-bolus administration of insulin and amylin in adolescents with type 1 diabetes decreases postprandial hyperglycemia

    Science.gov (United States)

    The purpose of this study was to examine the effect of continuous subcutaneous (sc) replacement of amylin and insulin for a 24-h period on glucose homeostasis in adolescents with type 1 diabetes. Thirteen adolescents with type 1 diabetes on insulin pump therapy participated in a randomized, controll...

  5. Lack of relationship between 11 beta-hydroxysteroid dehydrogenase setpoint and insulin sensitivity in the basal state and after 24h of insulin infusion in healthy subjects and type 2 diabetic patients

    NARCIS (Netherlands)

    Kerstens, MN; Riemens, SC; Sluiter, WJ; Pratt, JJ; Wolthers, BG; Dullaart, RPF

    OBJECTIVES To test whether insulin resistance in type 2 diabetes mellitus is associated with an altered overall setpoint of the 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) mediated cortisol to cortisone interconversion towards cortisol, and to evaluate whether changes in insulin sensitivity

  6. Real-world medication persistence and outcomes associated with basal insulin and glucagon-like peptide 1 receptor agonist free-dose combination therapy in patients with type 2 diabetes in the US

    Directory of Open Access Journals (Sweden)

    Lin J

    2016-12-01

    Full Text Available Jay Lin,1 Melissa Lingohr-Smith,1 Tao Fan2 1Health Economics and Outcomes Research, Novosys Health, Green Brook, NJ, USA; 2North America Medical Affairs, Sanofi US, Inc., Bridgewater, NJ, USA Background: Free-dose combination treatment with basal insulin and short-acting glucagon-like peptide-1 receptor agonists (GLP-1 RAs reduces hyperglycemia via complementary targeting of fasting and postprandial blood glucose levels, however, in the real world, due to injection burden and clinical inertia, the full efficacy may not be able to translate into clinical and economic benefits. Objective: The aim of the study was to evaluate treatment persistence and associated outcomes in patients with type 2 diabetes (T2D treated with a GLP-1 RA in free-dose combination with basal insulin. Methods: Claims data were extracted on US adults with T2D with ≥1 prescription claim for both a GLP-1 RA and a basal insulin from July 1, 2008 to June 30, 2013, and continuous health plan coverage for 6 months prior to (baseline and 12 months after the index date (follow-up period. Outcomes analyzed for patients stratified by treatment persistence included glycemic control, hypoglycemia, and health care costs and resource utilization. Multivariate analyses were used to examine factors associated with persistence or hypoglycemia. Results: The analysis included 7,320 patients, of whom 16.9% were persistent with free-dose combination treatment. The median time to treatment discontinuation was 133 days. Compared with ­nonpersistent patients, persistent patients had greater glycated hemoglobin A1c (A1C reductions (–0.80% vs –0.42%; P=0.032, were more likely to achieve A1C <7.0% (39% vs 22%; P<0.001, and were less likely to experience hypoglycemia (9.5% vs 6.8%; P=0.002. Persistent patients also had significantly fewer hospitalizations and shorter hospital stays. While prescription costs were significantly higher (all-cause: $14,691 vs $10,791; P<0.001; diabetes-related: $8

  7. Insulin analogues in pregnancy and specific congenital anomalies

    DEFF Research Database (Denmark)

    de Jong, Josta; Garne, Ester; Wender-Ozegowska, Ewa

    2016-01-01

    in the congenital anomaly rate among foetuses exposed to insulin analogues (lispro, aspart, glargine or detemir) compared with those exposed to human insulin or Neutral Protamine Hagedorn insulin. The total prevalence of congenital anomalies was not increased for foetuses exposed to insulin analogues. The small...... included 1286 foetuses of mothers using short-acting insulin analogues with 1089 references of mothers using human insulin and 768 foetuses of mothers using long-acting insulin analogues with 685 references of mothers using long-acting human insulin (Neutral Protamine Hagedorn). The congenital anomaly rate...... samples in the included studies provided insufficient statistical power to identify a moderate increased risk of specific congenital anomalies. Copyright © 2015 John Wiley & Sons, Ltd....

  8. 甘精胰岛素治疗1型糖尿病16例临床体会%Glargine for treatment of type 1 diabetes

    Institute of Scientific and Technical Information of China (English)

    柴杰

    2009-01-01

    Objective To observe the effect of glargine for treatment of type 1 diabetes. Methods Sixteen type 1 diabetes patients were randomized in two groups. In the Glargine group, 10 patients were given injection Nov-olin R before every meal and injection Glargine at bedtime daily. Meanwhile 6 patients in the NPH group were given injection Novolin R before every meal and injection NPH at bedtime daily. The dosage of insulin was adjusted by blood glucose level, seeking a target of FBG ≤6.5 mmol/L and 2 h PBG≤10.0 mmoL/L. The blood glucose level and incidence of hypoglycemia were observed. Results Mean blood glucose level was similiar in the 2 groups(P > 0.10), but the incidence of hypoglycemia in the Glargine group was significantly lower than that in the NPH group (P < 0.05). Conclusion Glargine initiates the physiological secretion of insulin and controls the blood glucose lev-el more effectively.%目的 比较每日注射一次甘精胰岛素与中性低精蛋白锌人胰岛素(NPH)分别联合3餐前注射短效人胰岛紊(Novolin R)治疗1型糖尿病的疗效.方法 16例1型糖尿病患者(包括儿童l型糖尿病3例,成人迟发自身免疫糖尿病13例)根据用药情况分为2组,甘精胰岛素组10例,每日3餐前注射Novolin R,8例患者每天22:00注射甘精胰岛素,2例患者每天7:00注射甘精胰岛素;对照组6例每日3餐前注射Nov-olin R,22:00注射NPH.根据血糖水平调整胰岛素用量,观察血糖变化和低血糖发生的情况.结果 2组患者治疗后血糖均较治疗前明显下降(P<0.01),2组血糖控制达标所用时间差异有统计学意义(P<0.05).甘精胰岛素组酮体消退时间短于对照组(P<0.05),日用胰岛素剂量低于对照组(P<0.05),血糖平稳下降,血糖波动小,低血糖发生率低于对照组(P<0.05).结论 长效重组甘精胰岛素能模拟人体生理性基础胰岛素分泌,利于1型糖尿病患者的血糖控制,安全性较好.

  9. Enhanced hepatic insulin signaling in the livers of high altitude native rats under basal conditions and in the livers of low altitude native rats under insulin stimulation: a mechanistic study.

    Science.gov (United States)

    Al Dera, Hussain; Eleawa, Samy M; Al-Hashem, Fahaid H; Mahzari, Moeber M; Hoja, Ibrahim; Al Khateeb, Mahmoud

    2017-07-01

    This study was designed to investigate the role of the liver in lowering fasting blood glucose levels (FBG) in rats native to high (HA) and low altitude (LA) areas. As compared with LA natives, besides the improved insulin and glucose tolerance, HA native rats had lower FBG, at least mediated by inhibition of hepatic gluconeogenesis and activation of glycogen synthesis. An effect that is mediated by the enhancement of hepatic insulin signaling mediated by the decreased phosphorylation of TSC induced inhibition of mTOR function. Such effect was independent of activation of AMPK nor stabilization of HIF1α, but most probably due to oxidative stress induced REDD1 expression. However, under insulin stimulation, and in spite of the less activated mTOR function in HA native rats, LA native rats had higher glycogen content and reduced levels of gluconeogenic enzymes with a more enhanced insulin signaling, mainly due to higher levels of p-IRS1 (tyr612).

  10. High-intensity interval training without weight loss improves exercise but not basal or insulin-induced metabolism in overweight/obese African American women.

    Science.gov (United States)

    Arad, Avigdor D; DiMenna, Fred J; Thomas, Naketa; Tamis-Holland, Jacqueline; Weil, Richard; Geliebter, Allan; Albu, Jeanine B

    2015-08-15

    The purpose of this randomized controlled clinical trial was to determine the effect of a 14-week high-intensity interval training (HIIT) intervention with weight stability on metabolic flexibility, insulin sensitivity, and cardiorespiratory fitness in sedentary, premenopausal, nondiabetic, overweight/obese African American women. Twenty-eight subjects were allocated to one of two groups: HIIT, which performed three sessions per week of four high-intensity cycling intervals, or a control group (CON), which maintained their normal level of physical activity. Diet was controlled for all subjects to ensure weight stability. Pre- and postintervention (pre/post), subjects completed an incremental cycling test to limit of tolerance and, following a 10-day high-fat controlled feeding period, a euglycemic-hyperinsulinemic clamp to determine insulin sensitivity and substrate oxidation. Nine members of HIIT (age, 29 ± 4 yr; body mass, 90.1 ± 13.8 kg) and eleven members of CON (age, 30 ± 7 yr; body mass, 85.5 ± 10.7 kg) completed the study. HIIT experienced an increased limit of tolerance (post, 1,124 ± 202 s; pre, 987 ± 146 s; P exchange threshold (post, 1.29 ± 0.34 liters/min; pre, 0.97 ± 0.23 liters/min; P rate compared with CON (P flexibility were not different in HIIT compared with CON. High-intensity interval training with weight stability increased exercise fat oxidation and tolerance in subjects at risk for diabetic progression, but did not improve insulin sensitivity or fat oxidation in the postabsorptive or insulin-stimulated state.

  11. Differences in bioactivity between human insulin and insulin analogues approved for therapeutic use- compilation of reports from the past 20 years.

    Science.gov (United States)

    Werner, Haim; Chantelau, Ernst A

    2011-01-01

    In order to provide comprehensive information on the differences in bioactivity between human insulin and insulin analogues, published in vitro comparisons of human insulin and the rapid acting analogues insulin lispro (Humalog®), insulin aspart ( NovoRapid®), insulin glulisine (Apidra®), and the slow acting analogues insulin glargine (Lantus®), and insulin detemir (Levemir®) were gathered from the past 20 years (except for receptor binding studies). A total of 50 reports were retrieved, with great heterogeneity among study methodology. However, various differences in bioactivity compared to human insulin were obvious (e.g. differences in effects on metabolism, mitogenesis, apoptosis, intracellular signalling, thrombocyte function, protein degradation). Whether or not these differences have clinical bearings (and among which patient populations) remains to be determined.

  12. Differences in bioactivity between human insulin and insulin analogues approved for therapeutic use- compilation of reports from the past 20 years

    Directory of Open Access Journals (Sweden)

    Werner Haim

    2011-06-01

    Full Text Available Abstract In order to provide comprehensive information on the differences in bioactivity between human insulin and insulin analogues, published in vitro comparisons of human insulin and the rapid acting analogues insulin lispro (Humalog®, insulin aspart ( NovoRapid®, insulin glulisine (Apidra®, and the slow acting analogues insulin glargine (Lantus®, and insulin detemir (Levemir® were gathered from the past 20 years (except for receptor binding studies. A total of 50 reports were retrieved, with great heterogeneity among study methodology. However, various differences in bioactivity compared to human insulin were obvious (e.g. differences in effects on metabolism, mitogenesis, apoptosis, intracellular signalling, thrombocyte function, protein degradation. Whether or not these differences have clinical bearings (and among which patient populations remains to be determined.

  13. Pregnancy and the long-acting insulin analogue: a case study.

    Science.gov (United States)

    Caronna, Silvana; Cioni, Federico; Dall'Aglio, Elisabetta; Arsenio, Leone

    2006-04-01

    R.S. is a 22 years old Caucasian woman suffering from obesity, hypertension and Type I Diabetes Mellitus since the age of 6 years. Type I DM treatment includes 3 insulin injections at meal time and one glargine injection at bedtime. The insulin therapy regimen was prolonged during pregnancy and continued after childbirth. Optimal glycemic compensations were monitored throughout the pregnancy using HbA1c variations and other standard controls included in the OBG routine protocols, all within normal values. The pregnancy ended at the 38th week of gestation with a caesarean birth, during which a 3,54 Kg healthy boy with an APGAR of 9 was born. Both the mother and the newborn resulted in perfect health conditions confirming that the possibility of using glargine insulin profiles during pregnancy in selected cases with close monitoring may exist.

  14. Hyperinsulinemic hypoglycemia associated with insulin antibodies caused by exogenous insulin analog

    Directory of Open Access Journals (Sweden)

    Chih-Ting Su

    2016-11-01

    Full Text Available Insulin antibodies (IA associated with exogenous insulin administration seldom caused hypoglycemia and had different characteristics from insulin autoantibodies (IAA found in insulin autoimmune syndrome (IAS, which was first described by Dr Hirata in 1970. The characteristic of IAS is the presence of insulin-binding autoantibodies and related fasting or late postprandial hypoglycemia. Here, we report a patient with type 1 diabetes mellitus under insulin glargine and insulin aspart treatment who developed recurrent spontaneous post-absorptive hyperinsulinemic hypoglycemia with the cause probably being insulin antibodies induced by exogenous injected insulin. Examinations of serial sera disclosed a high titre of insulin antibodies (33%, normal <5%, high insulin concentration (111.9 IU/mL and undetectable C-peptide when hypoglycemia occurred. An oral glucose tolerance test revealed persistent high serum levels of total insulin and undetectable C-peptide. Image studies of the pancreas were unremarkable, which excluded the diagnosis of insulinoma. The patient does not take any of the medications containing sulfhydryl compounds, which had been reported to cause IAS. After administering oral prednisolone for 3 weeks, hypoglycemic episodes markedly improved, and he was discharged smoothly.

  15. Insulin Like Growth Factor 2 Expression in the Rat Brain Both in Basal Condition and following Learning Predominantly Derives from the Maternal Allele.

    Directory of Open Access Journals (Sweden)

    Xiaojing Ye

    Full Text Available Insulin like growth factor 2 (Igf2 is known as a maternally imprinted gene involved in growth and development. Recently, Igf2 was found to also be regulated and required in the adult rat hippocampus for long-term memory formation, raising the question of its allelic regulation in adult brain regions following experience and in cognitive processes. We show that, in adult rats, Igf2 is abundantly expressed in brain regions involved in cognitive functions, like hippocampus and prefrontal cortex, compared to the peripheral tissues. In contrast to its maternal imprinting in peripheral tissues, Igf2 is mainly expressed from the maternal allele in these brain regions. The training-dependent increase in Igf2 expression derives proportionally from both parental alleles, and, hence, is mostly maternal. Thus, Igf2 parental expression in the adult rat brain does not follow the imprinting rules found in peripheral tissues, suggesting differential expression regulation and functions of imprinted genes in the brain.

  16. A New Choice for Combination Therapy with Insulin:Adding SGLT-2 Inhibitors to Basal Insulin%胰岛素联合治疗的新选择--基础胰岛素+SGLT-2抑制剂

    Institute of Scientific and Technical Information of China (English)

    郭琳; 李强

    2016-01-01

    Mechanism complementary, simple and effective treatment is important for decreasing the blood glucose level of type 2 diabetes patient. Aglycone SGLT2 inhibitors with competitive combined glucose transporters, effectively restrain the activity of renal proximal convoluted tubules SGLT-2, reduce renal tubular epithelial cells reabsorption of glucose, increase the excretion of urine glucose, thereby reducing the blood sugar level. Because the mechanism is not dependent on insulin secretion and insulin action of unique mechanism of action of SGLT2 inhibitor is especially suitable for as a choice for insulin combined treatment drugs. This paper reviews the basic evidence for insulin combined SGLT-2 inhibitor treatment in the following respects:starting time, patients and safety, to point out the combination therapy in the treatment of type 2 diabetes will have good application prospects.%机制互补且简单有效的治疗方案更利于2型糖尿病患者的血糖管理。S G LT-2抑制剂的糖苷配基通过与葡萄糖竞争性结合转运蛋白,有效抑制肾脏近曲小管S G LT-2的活性,减少肾小管上皮细胞对葡萄糖的重吸收,使尿葡萄糖排泄增加,从而降低血糖水平。由于其不依赖于胰岛素分泌和胰岛素作用的独特的作用机制,SGLT-2抑制剂特别适合作为胰岛素联合治疗的选择药物。本文综述了基础胰岛素联合SGLT-2抑制剂治疗的循证证据、起始时机、适应人群和安全性,指出这种联合治疗在2型糖尿病的治疗中将拥有良好的应用前景。

  17. [Treatment by external insulin pump].

    Science.gov (United States)

    Clavel, Sylvaine

    2010-12-01

    Since the recent recommendations by the French speaking association for research on diabetes and metabolic illnesses (Alfediam), treatment by insulin pump has found itself in competition with basal-bolus, a procedure using similar injections of insulin which has become a benchmark treatment. The latest Alfediam guidelines focus on defining ways of treating diabetics with an external insulin pump.

  18. Update on insulin treatment for dogs and cats: insulin dosing pens and more

    Directory of Open Access Journals (Sweden)

    Thompson A

    2015-04-01

    Full Text Available Ann Thompson,1 Patty Lathan,2 Linda Fleeman3 1School of Veterinary Science, The University of Queensland, Gatton, QLD, Australia; 2College of Veterinary Medicine Mississippi State University, Starkville, MS, USA; 3Animal Diabetes Australia, Melbourne, VIC, Australia Abstract: Insulin therapy is still the primary therapy for all diabetic dogs and cats. Several insulin options are available for each species, including veterinary registered products and human insulin preparations. The insulin chosen depends on the individual patient's requirements. Intermediate-acting insulin is usually the first choice for dogs, and longer-acting insulin is the first choice for cats. Once the insulin type is chosen, the best method of insulin administration should be considered. Traditionally, insulin vials and syringes have been used, but insulin pen devices have recently entered the veterinary market. Pens have different handling requirements when compared with standard insulin vials including: storage out of the refrigerator for some insulin preparations once pen cartridges are in use; priming of the pen to ensure a full dose of insulin is administered; and holding the pen device in place for several seconds during the injection. Many different types of pen devices are available, with features such as half-unit dosing, large dials for visually impaired people, and memory that can display the last time and dose of insulin administered. Insulin pens come in both reusable and disposable options. Pens have several benefits over syringes, including improved dose accuracy, especially for low insulin doses. Keywords: diabetes, mellitus, canine, feline, NPH, glargine, porcine lente

  19. Clinical use of the co-formulation of insulin degludec and insulin aspart

    DEFF Research Database (Denmark)

    Kumar, A; Awata, T; Bain, S C;

    2016-01-01

    AIMS: To provide a review of the available data and practical use of insulin degludec with insulin aspart (IDegAsp). Premixed insulins provide basal and prandial glucose control; however, they have an intermediate-acting prandial insulin component and do not provide as effective basal coverage...... as true long-acting insulins, owing to the physicochemical incompatibility of their individual components, coupled with the inflexibility of adjustment. The molecular structure of the co-formulation of IDegAsp, a novel insulin preparation, allows these two molecules to coexist without affecting...... (HbA1c ) to current modern insulins, but with lower risk of nocturnal hypoglycaemia. In prior insulin users, glycaemic control was achieved with lower or equal insulin doses vs. other basal+meal-time or premix insulin regimens. In insulin-naïve patients with T2DM, IDegAsp can be started once or twice...

  20. Higher concentration insulins: an overview of clinical considerations.

    Science.gov (United States)

    Reid, Timothy S; Schafer, Fryn; Brusko, Cynthia

    2017-06-01

    Three higher concentration insulin products (insulin lispro 200 units/mL, insulin degludec 200 units/mL, and insulin glargine 300 units/mL) received US Food and Drug Administration (FDA) approval in 2015. Although human regular insulin 500 units/mL (U-500) was approved in 1997, a pen and dedicated U-500 syringe became available in 2016. These products offer more treatment options for the increasing numbers of patients requiring insulin to achieve and maintain glycemic targets. Higher concentration insulins have some unique safety and efficacy considerations. Important considerations when transitioning patients from the 100 unit/mL concentration (U-100) to the higher concentration include bioequivalence, pen dose increments, and pen appearance. Bioequivalent insulins have similar pharmacokinetic properties and no dose adjustments are expected when transitioning from the U-100 to the higher concentration. In contrast, higher concentration insulins with different pharmacokinetic and pharmacodynamic properties compared with the U-100 formulation may require dose adjustments. In order to provide safe and effective therapy to patients with higher daily insulin dose requirements, it is important for healthcare professionals to become very familiar with the characteristics of and differences between each of the higher concentration insulins. This paper highlights differences between the U-100 and higher concentration insulins and focuses on practical aspects of use.

  1. Insulin analogues in pregnancy and specific congenital anomalies: a literature review.

    Science.gov (United States)

    de Jong, Josta; Garne, Ester; Wender-Ozegowska, Ewa; Morgan, Margery; de Jong-van den Berg, Lolkje T W; Wang, Hao

    2016-05-01

    Insulin analogues are commonly used in pregnant women with diabetes. It is not known if the use of insulin analogues in pregnancy is associated with any higher risk of congenital anomalies in the offspring compared with use of human insulin. We performed a literature search for studies of pregnant women with pregestational diabetes using insulin analogues in the first trimester and information on congenital anomalies. The studies were analysed to compare the congenital anomaly rate among foetuses of mothers using insulin analogues with foetuses of mothers using human insulin. Of 29 studies, we included 1286 foetuses of mothers using short-acting insulin analogues with 1089 references of mothers using human insulin and 768 foetuses of mothers using long-acting insulin analogues with 685 references of mothers using long-acting human insulin (Neutral Protamine Hagedorn). The congenital anomaly rate was 4.84% and 4.29% among the foetuses of mothers using lispro and aspart. For glargine and detemir, the congenital anomaly rate was 2.86% and 3.47%, respectively. No studies on the use of insulin glulisine and degludec in pregnancy were found. There was no statistically significant difference in the congenital anomaly rate among foetuses exposed to insulin analogues (lispro, aspart, glargine or detemir) compared with those exposed to human insulin or Neutral Protamine Hagedorn insulin. The total prevalence of congenital anomalies was not increased for foetuses exposed to insulin analogues. The small samples in the included studies provided insufficient statistical power to identify a moderate increased risk of specific congenital anomalies.

  2. [INITIATING AND INTENSIFYING INSULIN THERAPY IN GENERAL PRACTICE: INSUSTAR, AN OBSERVATIONAL BELGIAN PROSPECTIVE STUDY IN TYPE 2 DIABETES].

    Science.gov (United States)

    Scheen, A J; Mathieu, C; Nobels, F

    2015-09-01

    Initiating or intensifying insulin therapy is often considered as a challenge in general practice. The observational prospective Belgian study InsuStar was performed in 2011-2013 among 150 representative general practitioners, who were invited to initiate or intensify insulin therapy when necessary in 523 patients with type 2 diabetes (mean age: 65.5 years; mean HbAk: 8.8%). The initiation of insulin therapy (glargine in > 50%) was justified by insufficient glycaemic control (96%) and its intensification (replacement of insulin NPH or premixed insulins by insulin glargine, eventually with the addition of a short-acting insulin analogue) aimed at improving glucose control (58%), avoiding hypoglycaemia (17%) or both (17%). After a follow up of 6:1 months, HbAlc level decreased from 8.79% to 7.52% (-1.27%; 95% confidence interval: -1.43, -1.11; pphysi- cian confidence level regarding insulin therapy. These results should encourage general practitioners to initiate insulin therapy at an earlier stage and to intensify it when necessary in patients with insufficiently controlled type 2 diabetes.

  3. Insulin analogues versus human insulin in type 1 diabetes: direct and indirect meta-analyses of efficacy and safety

    Directory of Open Access Journals (Sweden)

    Andréia Cristina Conegero Sanches

    2013-09-01

    Full Text Available All patients with Diabetes Mellitus (DM receive insulin therapy. In this study, we evaluated the efficacy, safety and tolerability of human insulin and insulin analogues. We performed a systematic review of the literature and a meta-analysis according to the Cochrane Collaboration methodology. In the absence of clinical studies comparing insulins, we performed a mixed treatment comparison to establish the differences between the active treatments. We included studies published from 1995 to 2010. HbA1c results, episodes of hypoglycemia and nocturnal hypoglycemia data were extracted and analyzed. Thirty-five randomized clinical trials were selected after examining the abstract and a full text review. These studies included 4,206 patients who received long-acting insulin analogues and 5,733 patients who received short-acting insulin analogues. Pooled data regarding efficacy indicated no significant differences in HbA1c values between glargine or detemir (once daily and NPH insulin. However, a twice-daily dose of detemir produced differences in HbA1c values that favored detemir (-0.14% [95% CI: -0.21 to -0.08]; p<0.0001; I²=0%. Direct and indirect comparisons are consistent and show that there were no significant differences between human insulin and insulin analogues in efficacy or safety. Our results indicate that long- and short-acting insulin analogues offer few clinical advantages over conventional human insulin.

  4. Flexibility in insulin prescription

    Directory of Open Access Journals (Sweden)

    Sanjay Kalra

    2016-01-01

    Full Text Available This communication explores the concept of flexibility, a propos insulin preparations and insulin regimes used in the management of type 2 diabetes. The flexibility of an insulin regime or preparation is defined as their ability to be injected at variable times, with variable injection-meal time gaps, in a dose frequency and quantum determined by shared decision making, with a minimal requirement of glucose monitoring and health professional consultation, with no compromise on safety, efficiency and tolerability. The relative flexibility of various basal, prandial and dual action insulins, as well as intensive regimes, is compared. The biopsychosocial model of health is used to assess the utility of different insulins while encouraging a philosophy of flexible insulin usage.

  5. Insulin pump therapy in pregnancy.

    Science.gov (United States)

    Kesavadev, Jothydev

    2016-09-01

    Control of blood glucose during pregnancy is difficult because of wide variations, ongoing hormonal changes and mood swings. The need for multiple injections, pain at the injection site, regular monitoring and skillful handling of the syringes/pen further makes insulin therapy inconvenient. Insulin pump is gaining popularity in pregnancy because it mimics the insulin delivery of a healthy human pancreas. Multiple guidelines have also recommended the use of insulin pump in pregnancy to maintain the glycaemic control. The pump can release small doses of insulin continuously (basal), or a bolus dose close to mealtime to control the spike in blood glucose after a meal and the newer devices can shut down insulin delivery before the occurrence of hypoglycaemia. Pump insulin of choice is rapid acting analogue insulin. This review underscores the role of insulin pump in pregnancy, their usage, advantages and disadvantages in the light of existing literature and clinic experience.

  6. Production and manufacturing of biosimilar insulins: implications for patients, physicians, and health care systems

    Directory of Open Access Journals (Sweden)

    Kuhlmann MK

    2014-11-01

    Full Text Available Martin K Kuhlmann,1 Andrea Schmidt2 1Department of Internal Medicine–Nephrology, Klinikum im Friedrichshain, Berlin, Germany; 2Sanofi, Frankfurt, Germany Abstract: More than 380 million people worldwide have diabetes, a disease that accounts for almost US$550 billion in global health care spending. The majority of patients with diabetes will require insulin replacement as part of their therapeutic regimen. In some countries, the approaching patent expiry dates for the long-acting insulin analog insulin glargine mean there is increasing interest in the potential of biosimilar insulins. However, the production and manufacturing of biosimilar insulins is a proprietary, complex, multistep process in which each stage can potentially introduce variability, possibly leading to adverse clinical and safety outcomes. Thus, marketing authorization in countries in which stringent regulatory requirements are in place requires manufacturers to demonstrate similarity in pharmacokinetic/pharmacodynamic properties, clinical efficacy, and adverse event and immunogenicity profiles, as well as provide proof of the quality of the production process between the biosimilar and the reference insulin product. A risk management plan and pharmacovigilance program may also be needed for the approval process. Regulatory guidelines for the introduction of biosimilar insulins differ between countries but are most developed for the European Union. As of the date of submission of this manuscript (April 30, 2014, no insulin or insulin analogs have received marketing authorization based on the European Union standards established for biosimilars; however, European Medicines Agency approval of a biosimilar glargine insulin is awaited for the end of 2014. In recent years several copies of the long-acting insulin glargine have been brought onto the market in countries such as India, the People’s Republic of China, Pakistan, Mexico, and Kenya without following a biosimilar

  7. 地特胰岛素加三餐前速效胰岛素与胰岛素泵短期强化治疗对2型糖尿病的疗效比较%Comparison of the efficacy between basal insulin detemir with pre-meal insulin aspart and continuous subcutaneous insulin infusion (CSII) in type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    邢莉; 申虎威

    2012-01-01

    Objective To compare the efficacy and safety between insulin aspart combined with insulin detemir and insulin pump in the intensified therapy of patients with type 2 diabetes mellitus (T2DM). Methods 68 patients with T2DM were randomly divided into two groups. The patients in group A were given insulin aspart combined with insulin detemir, and the patients in group B received insulin pump therapy with insulin aspart. Time to target glucose, insulin dosage and hypoglycaemia incidence before and after 3 months therapy were measured and compared in both groups. Results After 3 month's therapy,the HbA1c(%) levels significantly decreased in both groups[group A: (10. 1 + 0. 2) vs (7. 2+ 0. L);group B:(10. 2+ 0. 3) vs (7. 1+ 0. 2),P0. 05), but hospitalization cost was obviously lower in group A than group B[(19. 71+2. 03) vs (39. 83+6. 23) ¥/d,P<0. 05]. Conclusion Insulin detemir combined with pre-meals insulin aspart could imitate the physiological insulin secretion and control the hyperglycemia effectively with reduced hypoglycemia risk and less cost of hospitalization.%目的 对比基础—餐时胰岛素与胰岛素泵在T2DM治疗中的有效性和安全性. 方法 将68例T2DM患者随机分为两组,A组采用三餐前门冬胰岛素联合睡前地特胰岛素治疗,B组采用胰岛素泵(使用门冬胰岛素)降糖治疗.治疗3个月后对比两组血糖控制情况、血糖达标所需要的时间、胰岛素用量、低血糖发生率等情况. 结果 两组治疗后HbA1c、HPG、2hFG均较治疗前显著下降(P<0.01),而FC-P、2hC-P均较治疗前明显升高(P<0.01).上述指标两组之间无统计学差异(P>0.05).两组血糖达标时间、日治疗剂量及低血糖发生率均无统计学差异(P>0.05),但A组的日治疗费用明显低于B组(P<0.05).结论 地特胰岛素联合三餐前门冬胰岛素强化治疗能有效模拟人生理胰岛素分泌,有效控制高血糖,且效价比优于胰岛素泵强化治疗.

  8. Insulin and Glucagon

    DEFF Research Database (Denmark)

    Holst, Jens Juul; Holland, William; Gromada, Jesper

    2017-01-01

    In August 2016, several leaders in glucagon biology gathered for the European Association for the Study of Diabetes Hagedorn Workshop in Oxford, England. A key point of discussion focused on the need for basal insulin to allow for the therapeutic benefit of glucagon blockade in the treatment...

  9. Insulin Secretagogues

    Science.gov (United States)

    ... Your Body in Balance › Insulin Secretagogues Fact Sheet Insulin Secretagogues March, 2012 Download PDFs English Espanol Editors ... medicines can help you stay healthy. What are insulin secretagogues? Insulin secretagogues (pronounced seh-KREET-ah-gogs) ...

  10. Insulin and Insulin Resistance

    OpenAIRE

    Wilcox, Gisela

    2005-01-01

    As obesity and diabetes reach epidemic proportions in the developed world, the role of insulin resistance and its consequences are gaining prominence. Understanding the role of insulin in wide-ranging physiological processes and the influences on its synthesis and secretion, alongside its actions from the molecular to the whole body level, has significant implications for much chronic disease seen in Westernised populations today. This review provides an overview of insulin, its history, stru...

  11. THE ASSESSMENT OF THE FUNCTIONAL-CAPACITY OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS BY MEASUREMENT OF BASAL PLASMA AND URINARY CORTISOL IN COMPARISON WITH INSULIN-INDUCED HYPOGLYCEMIA AND METYRAPONE TESTS

    NARCIS (Netherlands)

    DELANGE, WE; SLUITER, WJ

    1993-01-01

    In 58 patients with a pituitary adenoma or hypothalamic-pituitary disease an insulin-induced hypoglycaemia test and a metyrapone test were performed. The results of these tests were compared with morning plasma cortisol levels and daily urinary cortisol excretion as indicators of insufficiency of th

  12. Continuous Subcutaneous Insulin Infusion (CSII) Pumps for Type 1 and Type 2 Adult Diabetic Populations: An Evidence-Based Analysis.

    Science.gov (United States)

    2009-01-01

    treatment of many individuals with diabetes. Type 1, or juvenile-onset diabetes, is a life-long disorder that commonly manifests in children and adolescents, but onset can occur at any age. It represents about 10% of the total diabetes population and involves immune-mediated destruction of insulin producing cells in the pancreas. The loss of these cells results in a decrease in insulin production, which in turn necessitates exogenous insulin therapy. Type 2, or 'maturity-onset' diabetes represents about 90% of the total diabetes population and is marked by a resistance to insulin or insufficient insulin secretion. The risk of developing type 2 diabetes increases with age, obesity, and lack of physical activity. The condition tends to develop gradually and may remain undiagnosed for many years. Approximately 30% of patients with type 2 diabetes eventually require insulin therapy. CSII PUMPS: In conventional therapy programs for diabetes, insulin is injected once or twice a day in some combination of short- and long-acting insulin preparations. Some patients require intensive therapy regimes known as multiple daily injection (MDI) programs, in which insulin is injected three or more times a day. It's a time consuming process and usually requires an injection of slow acting basal insulin in the morning or evening and frequent doses of short-acting insulin prior to eating. The most common form of slower acting insulin used is neutral protamine gagedorn (NPH), which reaches peak activity 3 to 5 hours after injection. There are some concerns surrounding the use of NPH at night-time as, if injected immediately before bed, nocturnal hypoglycemia may occur. To combat nocturnal hypoglycemia and other issues related to absorption, alternative insulins have been developed, such as the slow-acting insulin glargine. Glargine has no peak action time and instead acts consistently over a twenty-four hour period, helping reduce the frequency of hypoglycemic episodes. Alternatively, intensive

  13. Incorporating a Generic Model of Subcutaneous Insulin Absorption into the AIDA v4 Diabetes Simulator 3. Early Plasma Insulin Determinations

    Science.gov (United States)

    Lehmann, Eldon D.; Tarín, Cristina; Bondia, Jorge; Teufel, Edgar; Deutsch, Tibor

    2009-01-01

    Introduction AIDA is an interactive educational diabetes simulator that has been available without charge via the Internet for over 12 years. Recent articles have described the incorporation of a novel generic model of insulin absorption into AIDA as a way of enhancing its capabilities. The basic model components to be integrated have been overviewed, with the aim being to provide simulations of regimens utilizing insulin analogues, as well as insulin doses greater than 40 IU (the current upper limit within the latest release of AIDA [v4.3a]). Some preliminary calculated insulin absorption results have also recently been described. Methods This article presents the first simulated plasma insulin profiles from the integration of the generic subcutaneous insulin absorption model, and the currently implemented model in AIDA for insulin disposition. Insulin absorption has been described by the physiologically based model of Tarín and colleagues. A single compartment modeling approach has been used to specify how absorbed insulin is distributed in, and eliminated from, the human body. To enable a numerical solution of the absorption model, a spherical subcutaneous depot for the injected insulin dose has been assumed and spatially discretized into shell compartments with homogeneous concentrations, having as its center the injection site. The number of these compartments will depend on the dose and type of insulin. Insulin inflow arises as the sum of contributions to the different shells. For this report the first bench testing of plasma insulin determinations has been done. Results Simulated plasma insulin profiles are provided for currently available insulin preparations, including a rapidly acting insulin analogue (e.g., lispro/Humalog or aspart/Novolog), a short-acting (regular) insulin preparation (e.g., Actrapid), intermediate-acting insulins (both Semilente and neutral protamine Hagedorn types), and a very long-acting insulin analogue (e.g., glargine/Lantus), as

  14. Insulin and insulin mutants stimulate glucose uptake in rat adipocytes

    Institute of Scientific and Technical Information of China (English)

    姚矢音; 张新堂; 许英镐; 张信娜; 朱尚权

    1999-01-01

    A simple method to determine the in vitro biological activity of insulin by measuring glucose uptake in the rat adipocytes is presented here. In the presence of insulin, the glucose uptake is 5-6 times more than the basal control. And the uptake of D-[3-3H]-glucose is linear as the logarithm of insulin concentration from 0.2 μg/L to 1.0 μg/L. Glucose and 3-O-methyl-glucose inhibit D-[3-3H]-glucose uptake into adipocytes. By this method, the in vitro biological activity of [B2-Lys]-insulin and [B3-Lys]-insulin was measured to be 61.6% and 154% respectively, relative to that of insulin.

  15. Basal Reinforced Piled Embankments

    NARCIS (Netherlands)

    Van Eekelen, S.J.M.

    2015-01-01

    A basal reinforced piled embankment consists of a reinforced embankment on a pile foundation. The reinforcement consists of one or more horizontal layers of geosynthetic reinforcement (GR) installed at the base of the embankment. The design of the GR is the subject of this thesis. A basal

  16. Basal Reinforced Piled Embankments

    NARCIS (Netherlands)

    Van Eekelen, S.J.M.

    2015-01-01

    A basal reinforced piled embankment consists of a reinforced embankment on a pile foundation. The reinforcement consists of one or more horizontal layers of geosynthetic reinforcement (GR) installed at the base of the embankment. The design of the GR is the subject of this thesis. A basal reinforce

  17. Basal Reinforced Piled Embankments

    NARCIS (Netherlands)

    Van Eekelen, S.J.M.

    2015-01-01

    A basal reinforced piled embankment consists of a reinforced embankment on a pile foundation. The reinforcement consists of one or more horizontal layers of geosynthetic reinforcement (GR) installed at the base of the embankment. The design of the GR is the subject of this thesis. A basal reinforce

  18. Insulin Test

    Science.gov (United States)

    ... especially as a result of taking non-human (animal or synthetic) insulin, these can interfere with insulin testing. In this case, a C-peptide may be performed as an alternative way to evaluate insulin production. Note also that ...

  19. Insulin Secretagogues

    Science.gov (United States)

    ... Nondiabetic Hypoglycemia Featured Resource Find an Endocrinologist Search Insulin Secretagogues March 2012 Download PDFs English Espanol Editors ... Julio Rosenstock, MD Additional Resources FDA What are insulin secretagogues? Insulin secretagogues (pronounced seh-KREET-ah-gogs) ...

  20. Insulin therapy in type 2 diabetes.

    Science.gov (United States)

    Mudaliar, S; Edelman, S V

    2001-12-01

    concentration is normalized. If combination therapy is not successful, a split-mixed regimen of intermediate- and rapid-acting insulin equally divided between the prebreakfast and pre-dinner periods is advised for oese patients, and more intensive regimens are advised for thin patients. Insulin therapy is invariably associated with weight gain and hypoglycemia. The use of metformin or glitazones in combination with insulin has been demonstrated to have insulin-sparing properties. Also, metformin use may ameliorate weight gain. The use of continuous subcutaneous insulin infusion pumps can be particularly beneficial in treating patients with type 2 diabetes mellitus who do not respond satisfactorily to more conventional treatment strategies. Intraperitoneal insulin delivery systems hold considerable promise in type 2 diabetes because of their more physiologic delivery of insulin and their ability to inhibit hepatic glucose production selectively, with less peripheral insulinemia than with subcutaneous insulin injections. Newer insulin analogues such as the rapidly acting Lispro insulin and the peakless, long-acting glargine insulin are increasingly being used because of their unique physiologic pharmacokinetics. New developments such as inhaled and buccal insulin preparations will also make it easier for many patients to initiate and maintain a proper insulin regimen. Finally, a new generation of gut peptides such as amylin and GLP-1 will add a new dimension to glycemic control through modification of nutrient delivery and other mechanisms; however, the ultimate goal in the management of type 2 diabetes is the primary prevention of the disease. The Diabetes Prevention Program (DPP) sponsored by the National Institutes of Health has currently randomly assigned more than 3000 persons with impaired glucose tolerance and at high risk of developing diabetes into three treatment arms: metformin arm, an intensive lifestyle-modification arm, and a placebo arm. The study will conclude in

  1. Effects of metformin on body weight in patients with type 2 diabetes mellitus,receiving insulin analogue treatment

    Directory of Open Access Journals (Sweden)

    T I Romantsova

    2013-03-01

    Full Text Available Aims. To study the dynamics of body weight, waist circumference, blood lipid and insulin demand in patients with type 2 diabetes mellitus (T2DM during first year of combined treatment with metformin and insulin analogues, compared with insulin analogue monotherapy.Materials and Methods. We examined 78 patients with T2DM on newly initiated insulin therapy, including 54 females and 24 males. Median age was 56 [51.0; 64.0] years, median disease duration – 9 [6.8;14.0] years. Participants were subdivided in two groups. First group was comprised of 48 subjects (33 females and 15 males, who received monotherapy with insulin analogues (glargine, de- temir, biphasic Aspart 30 and Humalog Mix 25 or rapid-acting lispro and aspart. Second group included 30 patients (18 females and12 males, who were treated with combined therapy (insulin analogues plus metformin. We measured HbA1c, plasma lipid composition, BMI, waist circumference and insulin demand initially and after one year of follow-up.Results. We showed that combined therapy vs. insulin monotherapy allows better glycemic compensation while reducing insulin demand and lowering risks for weight gain.Conclusions. Combined insulin analogue plus metformin treatment delivers better metabolic control in patients with T2DM and is as- sociated with lower risks for body weight gain and increase in insulin demand against monotherapy with insulin analogues.

  2. Early insulin treatment to prevent cardiovascular disease in prediabetes and overt diabetes.

    Science.gov (United States)

    Roman, G; Hancu, N

    2009-02-01

    Type 2 diabetes mellitus (DM) is a major risk factor for cardiovascular disease (CVD), and CVD represents the leading cause of death in people with type 2 DM. The cardiovascular risk is increased long before diabetes is diagnosed, in the prediabetes stage, when impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) develop. These stages are characterized by dysglycemia, defined as any elevated fasting or postprandial glycemia, extending from the normal range into diabetic range, associated with an increased risk of CVD. Due to metabolic memory demonstrated for type 2 DM as well, early interventions addressed to achieve and maintain glycemic control are required for long-term benefits in terms of both microvascular and macrovascular complications. The recommendation of early insulin therapy in type 2 DM is sustained by its pleiotropic effects, which may be cardioprotective and potentially anti-atherosclerotic. Insulin therapy in prediabetes and earlier in type 2 DM, could be a strategy in preventing cardiovascular disease and type 2 DM progression. To test this hypothesis, a large trial has been designed. Outcome Reduction with an Initial Glargine Intervention trial (ORIGIN) is an international, multicenter, randomized controlled, 2 x 2 factorial trial, investigating the possibility to prevent cardiovascular morbidity and mortality in people with type 2 DM, IGT, and/or IFG, and high cardiovascular risk by treating the normoglycemia with either insulin glargine or omega-3 fatty acid, compared to the standard intervention.

  3. Insulin Requirements in Relation to Insulin Pump Indications in Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Gabriela GHIMPEŢEANU

    2015-09-01

    Full Text Available The purpose of the current research was to assess changes in daily insulin requirements in type 1 diabetic patients transitioning from multiple daily injections (MDI of insulin to continuous subcutaneous insulin infusion (CSII using an external insulin pump, according to clinical indications for changing therapy. The charts of 70 patients with type 1 diabetes (T1D initiating insulin pump therapy were retrospectively reviewed before CSII and after optimization of glycaemic profile with CSII during hospital admission. Daily insulin doses, basal/bolus distributions, dose changes during treatment transition and glycaemic outcomes with MDI and optimized CSII according to insulin pump indications were evaluated. Daily insulin doses were not significantly different among indication groups, with both MDI and CSII; likewise, the overall daily distribution of basal/rapid insulin ratio was similar, around 40/60. With optimized CSII, significant differences were found only in basal/bolus distribution in patients initiating CSII for recurrent hypoglycemia, who had a significantly lower basal (6.4% lower and a complementary higher bolus requirement, compared to patients initiating CSII for HbA1c ≥ 8.5%. At transition, basal insulin needs declined similarly in the high HbA1c and impractical/inflexible MDI groups by approximately 20%, and up to 30% in the recurrent hypoglycaemia group; bolus doses decreased by 20% when the indication was high HbA1c and by approximately 15% for the other indications. Glycaemic control was significantly improved only in patients initiating CSII for high HbA1c (≥8.5%. Insulin pump indication should be considered when starting T1D patients on CSII. These findings may support clinicians in decision making regarding insulin dose changes when initiating insulin pump therapy.

  4. Adipocyte lipolysis and insulin resistance.

    Science.gov (United States)

    Morigny, Pauline; Houssier, Marianne; Mouisel, Etienne; Langin, Dominique

    2016-06-01

    Obesity-induced insulin resistance is a major risk factor for the development of type 2 diabetes. Basal fat cell lipolysis (i.e., fat cell triacylglycerol breakdown into fatty acids and glycerol in the absence of stimulatory factors) is elevated during obesity and is closely associated with insulin resistance. Inhibition of adipocyte lipolysis may therefore be a promising therapeutic strategy for treating insulin resistance and preventing obesity-associated type 2 diabetes. In this review, we explore the relationship between adipose lipolysis and insulin sensitivity. After providing an overview of the components of fat cell lipolytic machinery, we describe the hypotheses that may support the causality between lipolysis and insulin resistance. Excessive circulating fatty acids may ectopically accumulate in insulin-sensitive tissues and impair insulin action. Increased basal lipolysis may also modify the secretory profile of adipose tissue, influencing whole body insulin sensitivity. Finally, excessive fatty acid release may also worsen adipose tissue inflammation, a well-known parameter contributing to insulin resistance. Partial genetic or pharmacologic inhibition of fat cell lipases in mice as well as short term clinical trials using antilipolytic drugs in humans support the benefit of fat cell lipolysis inhibition on systemic insulin sensitivity and glucose metabolism, which occurs without an increase of fat mass. Modulation of fatty acid fluxes and, putatively, of fat cell secretory pattern may explain the amelioration of insulin sensitivity whereas changes in adipose tissue immune response do not seem involved. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  5. Treatment with insulin analog X10 and IGF-1 increases growth of colon cancer allografts.

    Directory of Open Access Journals (Sweden)

    Henning Hvid

    Full Text Available Obesity and type 2 diabetes are associated with an increased risk for development of certain forms of cancer, including colon cancer. The publication of highly controversial epidemiological studies in 2009 raised the possibility that use of the insulin analog glargine increases this risk further. However, it is not clear how mitogenic effects of insulin and insulin analogs measured in vitro correlate with tumor growth-promoting effects in vivo. The aim of this study was to examine possible growth-promoting effects of native human insulin, insulin X10 and IGF-1, which are considered positive controls in vitro, in a short-term animal model of an obesity- and diabetes-relevant cancer. We characterized insulin and IGF-1 receptor expression and the response to treatment with insulin, X10 and IGF-1 in the murine colon cancer cell line (MC38 cells in vitro and in vivo. Furthermore, we examined pharmacokinetics and pharmacodynamics and monitored growth of MC38 cell allografts in mice with diet-induced obesity treated with human insulin, X10 and IGF-1. Treatment with X10 and IGF-1 significantly increased growth of MC38 cell allografts in mice with diet-induced obesity and we can therefore conclude that supra-pharmacological doses of the insulin analog X10, which is super-mitogenic in vitro and increased the incidence of mammary tumors in female rats in a 12-month toxicity study, also increase growth of tumor allografts in a short-term animal model.

  6. Jointly amplified basal and pulsatile growth hormone (GH) secretion and increased process irregularity in women with anorexia nervosa: indirect evidence for disruption of feedback regulation within the GH-insulin-like growth factor I axis

    DEFF Research Database (Denmark)

    Støving, R K; Veldhuis, J D; Flyvbjerg, A;

    1999-01-01

    pulsatility in AN using the techniques of deconvolution analysis and approximate entropy, which quantify secretory activity and serial irregularity of underlying hormone release not reflected in peak occurrence or amplitudes. To this end, 24-h GH profiles were obtained by continuous blood sampling aliquoted...... and the basal as well as pulsatile GH secretion rates. Moreover, AN patients exhibited significantly greater GH approximate entropy scores than the controls, denoting marked irregularity of the GH release process. In contrast to previous reports in healthy fasting subjects, cortisol levels in AN patients were....... Accordingly, GH secretion in AN probably reflects altered neuroendocrine feedback regulation, e.g. associated with increased hypothalamic GHRH discharge superimposed on reduced hypothalamic somatostatinergic tone....

  7. Adherence to insulin treatment in insulin-naïve type 2 diabetic patients initiated on different insulin regimens

    Directory of Open Access Journals (Sweden)

    Gogas Yavuz D

    2015-08-01

    Full Text Available Dilek Gogas Yavuz, Sevim Ozcan, Oguzhan DeyneliDepartment of Endocrinology and Metabolism, Marmara University School of Medicine, Istanbul, TurkeyObjective: We aimed to evaluate adherence to insulin treatment in terms of treatment persistence and daily adherence to insulin injections among insulin-naïve type 2 diabetic patients initiating insulin therapy with basal (long acting, basal-bolus, and premixed insulin regimens in a tertiary endocrinology outpatient clinic.Methods: A total of 433 (mean age of 55.5±13.0 years; 52.4% females insulin-naïve type 2 diabetic patients initiated on insulin therapy were included in this questionnaire-based phone interview survey at the sixth month of therapy. Via the telephone interview questions, patients were required to provide information about persistence to insulin treatment, self-reported blood glucose values, and side effects; data on demographics and diabetes characteristics were obtained from medical records.Results: Self-reported treatment withdrawal occurred in 20.1% patients, while 20.3% patients were nonadherent to daily insulin. Negative beliefs about insulin therapy (24.1% and forgetting injections (40.9% were the most common reasons for treatment withdrawal and dose skipping, respectively. Younger age (49.5±15.0 vs 56.4±12.0 years (P=0.001 and shorter duration of diabetes (4.8±4.3 vs 8.8±6.3 years (P=0.0008 and treatment duration (5.2±2.4 vs 10.7±2.4 months (P=0.0001 were noted, respectively, in discontinuers vs continuers. Basal bolus was the most commonly prescribed insulin regimen (51.0%, while associated with higher likelihood of skipping a dose than regular use (61.3% vs. 46.0%, P=0.04.Conclusions: Persistence to insulin therapy was poorer than anticipated but appeared to be higher in patients with the basal bolus regimen. Negative perceptions about insulin therapy seemed to be the main cause for poor adherence in our cohort.Keywords: type 2 diabetes, insulin treatment adherence

  8. Excess exposure to insulin is the primary cause of insulin resistance and its associated atherosclerosis.

    Science.gov (United States)

    Cao, Wenhong; Ning, Jie; Yang, Xuefeng; Liu, Zhenqi

    2011-11-01

    The main goal of this review is to provide more specific and effective targets for prevention and treatment of insulin resistance and associated atherosclerosis. Modern technologies and medicine have vastly improved human health and prolonged the average life span of humans primarily by eliminating various premature deaths and infectious diseases. The modern technologies have also provided us abundant food and convenient transportation tools such as cars. As a result, more people are becoming overfed and sedentary. People are generally ingesting more calories than their bodies' need, leading to the so-called "positive energy imbalance", which is inseparable from the development of insulin resistance and its associated atherosclerosis. A direct consequence of insulin resistance is hyperinsulinemia. The current general view is that insulin is not functional properly in the presence of insulin resistance. Thus, the role of insulin itself in the development of insulin resistance and associated atherosclerosis has not been recognized. We have recently observed that the basal level of insulin signaling is increased in the presence of insulin resistance and hyperinsulinemia. In this review, we will explain how the increased basal insulin signaling contributes to the development of insulin resistance and associated atherosclerosis. We will first explain how insulin causes insulin resistance through two arbitrary stages (before and after the presence of obvious insulin resistance), and, then, explain how the excess exposure to insulin and the relative insulin insufficiency contributes to the atherosclerotic diseases. We propose that blockade of the excess insulin signaling is a viable approach to prevent and/or reverse insulin resistance and its associated atherosclerosis.

  9. Quantitation of Insulin Analogues in Serum Using Immunoaffinity Extraction, Liquid Chromatography, and Tandem Mass Spectrometry.

    Science.gov (United States)

    Van Der Gugten, J Grace; Wong, Sophia; Holmes, Daniel T

    2016-01-01

    Insulin analysis is used in combination with glucose, C-peptide, beta-hydroxybutyrate, and proinsulin determination for the investigation of adult hypoglycemia. The most common cause is the administration of too much insulin or insulin secretagogue to a diabetic patient or inadequate caloric intake after administration of either. Occasionally there is a question as to whether hypoglycemia has been caused by an exogenous insulin-whether by accident, intent, or even malicious intent. While traditionally this was confirmed by a low or undetectable C-peptide in a hypoglycemic specimen, this finding is not entirely specific and would also be expected in the context of impaired counter-regulatory response, fatty acid oxidation defects, and liver failure-though beta-hydroxybutyrate levels can lend diagnostic clarity. For this reason, insulin is often requested. However, popular automated chemiluminescent immunoassays for insulin have distinctly heterogeneous performance in detecting analogue synthetic insulins with cross-reactivities ranging from near 0 % to greater than 100 %. The ability to detect synthetic insulins is vendor-specific and varies between insulin products. Liquid Chromatography and Tandem Mass Spectrometry (LC-MS/MS) offers a means to circumvent these analytical issues and both quantify synthetic insulins and identify the specific type. We present an immunoaffinity extraction and LC-MS/MS method capable of independent identification and quantitation of native sequence insulins (endogenous, Insulin Regular, Insulin NPH), and analogues Glargine, Lispro, Detemir, and Aspart with an analytical sensitivity for endogenous insulin of between 1 and 2 μU/mL in patient serum samples.

  10. The role of insulin detemir in overweight type 2 diabetes management

    Directory of Open Access Journals (Sweden)

    Yared N Demssie

    2009-06-01

    Full Text Available Yared N Demssie1, Naveed Younis2, Handrean Soran31Department of Diabetes and Endocrinology, Salford Royal Foundation NHS Trust, Salford, UK; 2Department of Medicine, University Hospital South Manchester Foundation NHS Trust, Wythenshawe, Manchester, UK; 3University Department of Medicine, Central Manchester and Manchester Children’s NHS Foundation Trust, Manchester, UKAbstract: The recent evidence-based shift towards an algorithm of early initiation and aggressive titration of insulin therapy in the management of type 2 diabetes requires the use of an effective insulin formulation that is both safe and acceptable to patients and physicians alike. The advent of the long-acting insulin analogues, insulin detemir and glargine, in the last decade has revolutionized insulin therapy in type 2 diabetes. Their unique pharmacokinetic and pharmacodynamic properties have offered tangible advantage over the conventional intermediate and long-acting insulin preparations in terms of improving glucose control as well as reducing risk of hypoglycemia and weight gain. This review focuses on the pharmacodynamic properties of the long-acting insulin analogue detemir, the outcome of studies on its relative efficacy and safety as well as its proposed place in the management of type 2 diabetes.Keywords: insulin detemir, type 2 diabetes, overweight

  11. [Anaphylactic shock due to recombinant human insulin: follow-up of a desensitization protocol by basophil activation test].

    Science.gov (United States)

    Luyasu, S; Hougardy, N; Hasdenteufel, F; Jacquenet, S; Weber, E; Moneret-Vautrin, A; Kanny, G

    2011-01-01

    Despite the occurrence of a severe allergic reaction including an anaphylactic shock, a drug may remain essential and impossible to replace. This may be the case of insulin in a diabetic patient. We describe the case of an anaphylactic shock to human insulin in whom a desensitization protocol was successfully achieved. A 50-year-old type 2 diabetic man presented one year after initiation of the insulin therapy an anaphylactic shock following the subcutaneous administration of a human insulin containing protamine (Insulatard®). A desensitization protocol to human insulin was performed and allowed to use two human insulin analogues containing no protamine (asparte and glargine), with a two-year event-free follow-up. Positive skin tests with insulin and protamine, and the presence of insulin specific IgE were evidenced of an IgE-mediated mechanism. Desensitization was monitored by skin tests, Maunsell's test, measurement of specific IgE and IgG4, and the basophil activation test. The decrease of basophil sensitivity to insulin is an early marker for tolerance induction. The effectiveness of the desensitization to human insulin underlines the importance to define the modalities of such desensitization protocol and of the monitoring of the tolerance induction. Copyright © 2010 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  12. Pragmatic use of insulin degludec/insulin aspart co-formulation: A multinational consensus statement

    Science.gov (United States)

    Kalra, Sanjay; Latif, Zafar A.; Comlekci, Abdurrahman; Galvez, Guillermo Gonzalez; Malik, Rached; Pathan, Md Faruque; Kumar, Ajay

    2016-01-01

    Insulin degludec/insulin aspart (IDegAsp) is a modern coformulation of ultra-long-acting basal insulin degludec, with rapid-acting insulin aspart. IDegAsp provides effective, safe, well-tolerated glycemic control, with a low risk of hypoglycemia while allowing flexibility in meal patterns and timing of administration. This consensus statement describes a pragmatic framework to identify patients who may benefit from IDegAsp therapy. It highlights the utility of IDegAsp in type 2 diabetic patients who are insulin-naive, suboptimally controlled on basal or premixed insulin, or dissatisfied with basal–bolus regimens. It also describes potential IDegAsp usage in type 1 diabetic patients. PMID:27366723

  13. Insulin Injection

    Science.gov (United States)

    ... or buttocks. Do not inject insulin into muscles, scars, or moles. Use a different site for each ... you are using insulin.Alcohol may cause a decrease in blood sugar. Ask your doctor about the ...

  14. Insulin analogues: have they changed insulin treatment and improved glycaemic control?

    DEFF Research Database (Denmark)

    Madsbad, Sten

    2002-01-01

    To improve insulin therapy, new insulin analogues have been developed. Two fast-acting analogues with a more rapid onset of effect and a shorter duration of action combined with a low day-to-day variation in absorption rate are now available. Despite this favourable time-action profile most studi......, the new fast-acting analogues have not achieved the expected commercial success, which emphasises the need for new strategies for basal insulin supplementation, exercise, diet and blood glucose monitoring....

  15. Early enhancements of hepatic and later of peripheral insulin sensitivity combined with increased postprandial insulin secretion contribute to improved glycemic control after Roux-en-Y gastric bypass

    DEFF Research Database (Denmark)

    Bojsen-Møller, Kirstine N; Dirksen, Carsten; Jørgensen, Nils Bruun;

    2014-01-01

    to an intravenous glucose-glucagon challenge as well as an oral glucose load. Already within 1 week, RYGB reduced basal glucose production, improved basal hepatic insulin sensitivity and increased insulin clearance highlighting the liver as an important organ responsible for the early effects on glucose metabolism...

  16. A novel adaptive basal therapy based on the value and rate of change of blood glucose.

    Science.gov (United States)

    Wang, Youqing; Percival, Matthew W; Dassau, Eyal; Zisser, Howard C; Jovanovic, Lois; Doyle, Francis J

    2009-09-01

    Modern insulin pump therapy for type 1 diabetes mellitus offers the freedom to program several basal profiles that may accommodate diurnal ariability in insulin sensitivity and activity level. However, these basal profiles do not change even if a pending hypoglycemic or hyperglycemic event is foreseen. New insulin pumps could receive a direct feed of glucose values from a continuous glucose monitoring (CGM) system and could enable dynamic basal adaptation to improve glycemic control. The proposed method is a two-step procedure. After the design of an initial basal profile, an adaptation of the basal rate is suggested as a gain multiplier based on the current CGM glucose value and its rate of change (ROC). Taking the glucose value and its ROC as axes, a two-dimensional plane is divided into a nine-zone mosaic, where each zone is given a predefined basal multiplier; for example, a basal multiplier of zero indicates a recommendation to shut off the pump. The proposed therapy was evaluated on 20 in silico subjects (ten adults and ten adolescents) in the Food and Drug Administration-approved UVa/Padova simulator. Compared with conventional basal therapy, the proposed basal adjustment improved the percentage of glucose levels that stayed in the range of 60-180 mg/dl for all 20 subjects. In addition, the adaptive basal therapy reduced the average blood glucose index values. The proposed therapy provides the flexibility to account for insulin sensitivity variations that may result from stress and/or physical activities. Because of its simplicity, the proposed method could be embedded in a chip in a future artificial pancreatic beta cell or used in a "smart" insulin pump. 2009 Diabetes Technology Society.

  17. Insulin allergy.

    Science.gov (United States)

    Ghazavi, Mohammad K; Johnston, Graham A

    2011-01-01

    Insulin reactions occur rarely but are of tremendous clinical importance. The first was reported in 1922 as a callus reaction at the injection site of insufficiently purified bovine insulin. Porcine insulin was subsequently found to be less allergenic than bovine insulin. Increasingly pure insulins have decreased the risk of adverse reactions, and the production of recombinant insulin with the same amino sequence as human insulin saw a large decrease in adverse reactions. Currently, the prevalence of allergic reactions to insulin products appears to be approximately 2%, and less than one-third of these events have been considered related to the insulin itself. Other reactions occur due to the preservatives added to insulin, including zinc, protamine, and meta-cresol. Allergic reactions can be type I or immunoglobulin E-mediated, type III or Arthus, and type IV or delayed-type hypersensitivity reactions. Type I reactions are the most common and can, rarely, cause anaphylaxis. In contrast, type IV reactions can occur after a delay of several days. Investigations include skin prick testing, patch testing, intradermal testing, and occasionally, skin biopsy.

  18. Biosimilar insulins.

    Science.gov (United States)

    Heinemann, Lutz

    2012-08-01

    Until now most insulin used in developed countries is manufactured and distributed by a small number of multinational companies. Other pharmaceutical companies - many of these are located in countries such as India or China - are also able to manufacture insulin with modern biotechnological methods. Additionally, the patents for many insulin formulations have expired or are going to expire soon. This enables such companies to produce insulins and to apply for market approval of these as biosimilar insulins (BIs) in highly regulated markets such as the EU or the US. To understand the complexity of BIs' approval and usage, scientific and regulatory aspects have to be discussed. Differences in the manufacturing process (none of the insulin-manufacturing procedures are identical) result in the fact that all insulin that might become BIs differ from the originator insulin to some extent. The question is, have such differences in the structure of the insulin molecule and or the purity and so on clinically relevant consequences for the biological effects induced or not. The guidelines already in place in the EU for market approval require that the manufacturer demonstrates that his insulin has a safety and efficacy profile that is similar to that of the 'original' insulin formulation. Recently guidelines for biosimilars were issued in the US; however, these do not cover insulin. Although a challenging approval process for insulins to become BI might be regarded as a hurdle to keep companies out of certain markets, it is fair to say that the potential safety and efficacy issues surrounding BI are substantial and relevant, and do warrant a careful and evidence-driven approval process. Nevertheless, it is very likely that in the next years, BIs will come to the market also in highly regulated markets.

  19. Neuropsychiatry of the basal ganglia

    OpenAIRE

    Ring, H.; Serra-Mestres, J

    2002-01-01

    This review aims to relate recent findings describing the role and neural connectivity of the basal ganglia to the clinical neuropsychiatry of basal ganglia movement disorders and to the role of basal ganglia disturbances in "psychiatric"' states. Articles relating to the relevant topics were initially collected through MEDLINE and papers relating to the clinical conditions discussed were also reviewed. The anatomy and connections of the basal ganglia indicate that these structures are import...

  20. Short- and Longterm Glycemic Control of Streptozotocin-Induced Diabetic Rats Using Different Insulin Preparations.

    Directory of Open Access Journals (Sweden)

    Gerd Luippold

    Full Text Available The chemical induction of diabetes with STZ has gained popularity because of the relative ease of rendering normal animals diabetic. Insulin substitution is required in STZ-rats in long-term studies to avoid ketoacidosis and consequently loss of animals. Aim of the present studies was to test different insulin preparations and different ways of administration in their ability to reduce blood glucose in STZ-induced diabetic rats. Single dosing of the long-acting insulin analogue glargine was able to dose-dependently reduce blood glucose over 4 h towards normoglycemia in STZ-treated rats. However, this effect was not sustained until 8 h post injection. A more sustained glucose-lowering effect was achieved using insulin-releasing implants. In STZ-rats, 1 insulin implant moderately lowered blood glucose levels 10 days after implantation, while 2 implants induced normoglycemia over the whole day. According to the glucose-lowering effect 1 as well as 2 insulin implants significantly reduced HbA1c measured after 26 days of implantation. In line with the improved glucose homeostasis due to the implants, urinary glucose excretion was also blunted in STZ-treated rats with 2 implants. Since diabetic nephropathy is one of the complications of longterm diabetes, renal function was characterized in the STZ-rat model. Increases in creatinine clearance and urinary albumin excretion resemble early signs of diabetic nephropathy. These functional abnormalities of the kidney could clearly be corrected with insulin-releasing implants 27 days after implantation. The data show that diabetic STZ-rats respond to exogenous insulin with regard to glucose levels as well as kidney parameters and a suitable dose of insulin implants for glucose control was established. This animal model together with the insulin dosing regimen is suitable to address diabetes-induced early diabetic nephropathy and also to study combination therapies with insulin for the treatment of type 1

  1. Basal or bolus dose, which is the key factor in CSII?

    Institute of Scientific and Technical Information of China (English)

    YANG Nai-long; XUE Bing; LIN Peng

    2006-01-01

    Objective: To observe the value of HbA1c level evaluating the total daily basal insulin dose by continuous subcutaneous insulin infusion (CSII) in 268 patients with type 2 diabetes mellitus. Methods: 5-point capillary blood glucose was monitored in pre- and post-CSII and the insulin dose which could stabilize blood glucose was defmed as the total daily dose of insulin,including basal and bolus total dose. Correlation between HbA1c level and total daily dose of insulin in patients with type 2 diabetes mellitus was analyzed. Correlation between HbA1c level and 5-point capillary blood glucose was also analyzed. Results:Obvious correlation was observed between HbA1c level and the basal total daily dose of insulin if HbA1c was more than 9.3%(r=0.635, P<0.05). The average of 5-point capillary blood glucose was best correlated with HbA1c and fasting blood glucose next best. Conclusion: HbA1c level can forecast basal total daily dose of insulin in CSII.

  2. Structure and pharmaceutical formulation development of a new long-acting recombinant human insulin analog studied by NMR and MS.

    Science.gov (United States)

    Bednarek, Elżbieta; Sitkowski, Jerzy; Bocian, Wojciech; Borowicz, Piotr; Płucienniczak, Grażyna; Stadnik, Dorota; Surmacz-Chwedoruk, Weronika; Jaworska, Beata; Kozerski, Lech

    2017-02-20

    A monomer structure of a novel human insulin analog A22(S)-B3(K)-B31(R) (SK3R) has been characterized by NMR in water/acetonitrile solution and compared with the structure of human insulin (HIS) established in the same medium. The composition of the oligomer ensemble for neat insulins in water was qualitatively assessed by monitoring, derived from NMR experiment, translational diffusion coefficient Dix10(-10)m(2)s(-1), whose value is a population averaged of individual coefficients for species in oligomeric ensemble. Nanospray ESI/MS experiment was used to establish the masses of oligomers in pharmaceutical formulation of the SK3R insulin. The pharmacodynamic data were established and compared to insulin glargine characterized by the same profile of action in diabetics. The oligomerization process of insulin during development of pharmaceutical formulation with routinely used excipients has been studied using translation diffusion coefficient Dix10(-10)m(2)s(-1) established in water solution. These properties were compared with those of human insulin (HIS) which is a standard reference for novel recombinant insulins. Copyright © 2016. Published by Elsevier B.V.

  3. Clinical experience with insulin detemir, biphasic insulin aspart and insulin aspart in people with type 2 diabetes: Results from the Kerala cohort of the A 1 chieve study

    Directory of Open Access Journals (Sweden)

    Sreejith N Kumar

    2013-01-01

    Full Text Available Background: The A 1 chieve, a multicentric (28 countries, 24-week, non-interventional study evaluated the safety and effectiveness of insulin detemir, biphasic insulin aspart and insulin aspart in people with T2DM (n = 66,726 in routine clinical care across four continents. Materials and Methods: Data was collected at baseline, at 12 weeks and at 24 weeks. This short communication presents the results for patients enrolled from Kerala, India. Results: A total of 1732 patients were enrolled in the study. Four different insulin analogue regimens were used in the study. Patients had started on or were switched to biphasic insulin aspart (n = 1203, insulin detemir (n = 212, insulin aspart (n = 312, basal insulin plus insulin aspart (n = 1 and other insulin combinations (n = 1. At baseline glycaemic control was poor for both insulin naïve (mean HbA 1 c: 10.0% and insulin user (mean HbA 1 c: 8.3% groups. After 24 weeks of treatment, both the groups showed improvement in HbA 1 c (insulin naïve: −2.4%, insulin users: −0.5%. SADRs including major hypoglycaemic events or episodes did not occur in any of the study patients. Conclusion: Starting or switching to insulin analogues was associated with improvement in glycaemic control with a low rate of hypoglycaemia.

  4. Clinical experience with insulin detemir, biphasic insulin aspart and insulin aspart in people with type 2 diabetes: Results from the Karnataka cohort of the A 1 chieve study

    Directory of Open Access Journals (Sweden)

    Neeta Deshpande

    2013-01-01

    Full Text Available Background: The A 1 chieve, a multicentric (28 countries, 24-week, non-interventional study evaluated the safety and effectiveness of insulin detemir, biphasic insulin aspart and insulin aspart in people with T2DM (n = 66,726 in routine clinical care across four continents. Materials and Methods: Data was collected at baseline, at 12 weeks and at 24 weeks. This short communication presents the results for patients enrolled from Karnataka, India. Results: A total of 2243 patients were enrolled in the study. Four different insulin analogue regimens were used in the study. Patients had started on or were switched to biphasic insulin aspart (n = 1855, insulin detemir (n = 211, insulin aspart (n = 111, basal insulin plus insulin aspart (n = 16 and other insulin combinations (n = 40. At baseline glycaemic control was poor for both insulin naïve (mean HbA 1 c: 9.2% and insulin user (mean HbA 1 c: 9.0% groups. After 24 weeks of treatment, both the groups showed improvement in HbA 1 c (insulin naïve: −1.4%, insulin users: −1.7%. SADRs including major hypoglycaemic events or episodes did not occur in any of the study patients. Conclusion: Starting or switching to insulin analogues was associated with improvement in glycaemic control with a low rate of hypoglycaemia.

  5. Clinical experience with insulin detemir, biphasic insulin aspart and insulin aspart in people with type 2 diabetes: Results from the Hyderabad cohort of the A1chieve study

    Science.gov (United States)

    Santosh, R.; Mehrotra, Ravi; Sastry, N. G.

    2013-01-01

    Background: The A1chieve, a multicentric (28 countries), 24-week, non-interventional study evaluated the safety and effectiveness of insulin detemir, biphasic insulin aspart and insulin aspart in people with T2DM (n = 66,726) in routine clinical care across four continents. Materials and Methods: Data was collected at baseline, at 12 weeks and at 24 weeks. This short communication presents the results for patients enrolled from Hyderabad, India. Results: A total of 1249 patients were enrolled in the study. Four different insulin analogue regimens were used in the study. Patients had started on or were switched to biphasic insulin aspart (n = 893), insulin detemir (n = 158), insulin aspart (n = 124), basal insulin plus insulin aspart (n = 19) and other insulin combinations (n = 54). At baseline glycaemic control was poor for both insulin naïve (mean HbA1c: 9.0%) and insulin user (mean HbA1c: 9.5%) groups. After 24 weeks of treatment, both the groups showed improvement in HbA1c (insulin naïve: −0.9%, insulin users: −1.1%). SADRs including major hypoglycaemic events or episodes did not occur in any of the study patients. Conclusion: Starting or switching to insulin analogues was associated with improvement in glycaemic control with a low rate of hypoglycaemia. PMID:24404501

  6. Unintended Insulin Pump Delivery in Hyperbaric Conditions.

    Science.gov (United States)

    Bertuzzi, Federico; Pintaudi, Basilio; Bonomo, Matteo; Garuti, Fabio

    2017-04-01

    Unintended pump insulin delivery was reported to occur as a consequence of decreased atmospheric pressure, probably mediated by air bubble formation and the expansion of existing bubbles. This observation has been used to explain some hypoglycemic episodes occurring in patients on insulin pump treatment in between 1 and 1 h 45 min after the flight takeoff. New models of insulin pumps have been introduced in the market, most of them are waterproof certified. It is not clear if in these new pumps the influence of atmospheric pressure changes on the insulin delivery is still present. Moreover, there are no evidences related to the insulin pump operations in hyperbaric conditions, like as during diving activities. Our aim is therefore to verify the eventual variation of insulin pump delivery determined by atmospheric pressure changes in hyperbaric conditions. Three new models of insulin pumps were tested in hyperbaric conditions at a flow rate of 2 U/h. Atmospheric pressure variation affected pump insulin release. An increase in the atmospheric pressure from 1 to 1.3 atmosphere (ATA) induced a decrease of pump basal insulin release (about -0.2 U/10 min); conversely, when the atmospheric pressure returned from 1.3 to 1 ATA, an unintended insulin delivery was observed (about +0.3 U/10 min). This phenomenon appeared to be independent of the insulin pump rate and dependent on the presence of air bubbles within the insulin tube setting and cartridge. Unintended insulin delivery driven by atmospheric pressure changes in hyperbaric conditions occurred in the new insulin pumps available. Patients should pay attention to possible variation of insulin rate during the flight or during diving activities.

  7. Insulin Lispro Injection

    Science.gov (United States)

    ... is a short-acting, man-made version of human insulin. Insulin lispro works by replacing the insulin ... received the right type of insulin from the pharmacy.Insulin lispro comes in vials, cartridges that contain ...

  8. Insulin therapy for diabetes mellitus: treatment regimens and associated costs.

    Science.gov (United States)

    Charbonnel, B; Penfornis, A; Varroud-Vial, M; Kusnik-Joinville, O; Detournay, B

    2012-04-01

    To describe insulin therapy in patients with diabetes, to determine treatment costs and to compare costs among treatment regimens. This observational study was performed by 734 French pharmacists. Adult patients filling an insulin prescription were invited to participate. Participants provided information on their diabetes history and management. Levels of intensification of insulin therapy were determined by the number of injections in type 1 diabetes mellitus (T1DM) patients, and by the different schemes used in type 2 (T2DM) patients, such as basal/intermediate-acting insulin only, and regimens using both basal and rapid-acting insulin. Costs were evaluated according to official medication costs, nurse visits and glucose monitoring kits. A total of 361 patients with T1DM and 1902 with T2DM were enrolled in the survey. Patients with T1DM more frequently took 1-2 injections per day (46.3% of patients) and used single-dose basal insulin together with ≥1 dose of rapid insulin (43.8%). Patients with T2DM used multiple treatment regimens, with 58 different combinations documented. Most took basal/intermediate insulin only (42.5%) or combinations of basal/intermediate and rapid insulins (52.7%). Mean cost of insulin therapy was €27.4/week for T1DM and €45.4/week for T2DM. In T1DM, insulin was the biggest cost component and increased with the number of injections/day. In T2DM, nurse visits were the most important cost contributors irrespective of treatment regimen. Overall, the cost of insulin therapy increased with the complexity of the insulin schemes. Considerable heterogeneity is found in insulin treatment regimens used in everyday diabetes care. Payers should consider the full costs associated with the use of insulin rather than the cost of insulin alone. Treatment algorithms to harmonize insulin therapy should help to improve care, while encouraging patients to self-inject insulin should help to reduce costs. Copyright © 2011 Elsevier Masson SAS. All rights

  9. Microvascular Recruitment in Insulin Resistance

    DEFF Research Database (Denmark)

    Sjøberg, Kim Anker

    the resonating sound from the microbubbles in the systemic circulation were recorded for determination of microvascular recruitment in designated muscle segments. Results showed that microvascular recruitment increased with insulin stimulation by ~30% in rats and ~40% in humans (study I). Furthermore......, it was observed that muscle contractions increased muscle perfusion rapidly by 3-4 fold and by 1-2 fold compared to basal and insulin, respectively, in both rat and human skeletal muscle (study I). The real-time contrast-enhanced ultrasound method was applied to investigate the vaso-active effect of the incretin...... hormone glucagon-like-peptide-1 (GLP-1) in the microcirculation. Glucagon-like-peptide-1 analogs are drugs used for treatments of insulin resistance and type 2 diabetes but the vascular effects of GLP-1 in vivo are elusive. Here it was shown that GLP-1 rapidly increased the microvascular recruitment...

  10. Vismodegib in basal cell carcinoma.

    Science.gov (United States)

    Amaria, R N; Bowles, D W; Lewis, K D; Jimeno, A

    2012-07-01

    Vismodegib is a novel, small-molecule inhibitor of smoothened, a key component of the hedgehog signaling pathway. Increased hedgehog pathway signaling is critical in the development of hereditary and spontaneous basal cell carcinomas of the skin, and has been implicated in the development of a number of other tumors. In preclinical models, vismodegib demonstrated potent antitumor activity in hedgehog-dependent tumors, particularly basal cell carcinomas. Clinically, phase I and II studies showed dramatic anticancer activity in patients with advanced basal cell carcinomas. In January 2012, vismodegib was approved by the FDA for the treatment of unresectable or metastatic basal cell carcinomas of the skin.

  11. In vitro modulation of pancreatic insulin secretion, extrapancreatic insulin action and peptide glycation by Curcuma longa aqueous extracts

    Directory of Open Access Journals (Sweden)

    Violet Kasabri

    2014-09-01

    Conclusion: This study has revealed that water soluble bioactive principles in C.longa AEs stimulate basal- and potentiate glucose evoked- insulin secretion, enhance insulin action and inhibit insulin glycation but not starch digestion. Future work assessing the use of C.longa AEs as dietary adjunct or as a source of active antidiabetic agents may provide new opportunities for the combinatorial treatment/prevention of diabetes. [J Exp Integr Med 2014; 4(3.000: 187-193

  12. Effects of insulin detemir and NPH insulin on body weight and appetite-regulating brain regions in human type 1 diabetes: a randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Larissa W van Golen

    Full Text Available Studies in rodents have demonstrated that insulin in the central nervous system induces satiety. In humans, these effects are less well established. Insulin detemir is a basal insulin analog that causes less weight gain than other basal insulin formulations, including the current standard intermediate-long acting Neutral Protamine Hagedorn (NPH insulin. Due to its structural modifications, which render the molecule more lipophilic, it was proposed that insulin detemir enters the brain more readily than other insulins. The aim of this study was to investigate whether insulin detemir treatment differentially modifies brain activation in response to food stimuli as compared to NPH insulin. In addition, cerebral spinal fluid (CSF insulin levels were measured after both treatments. Brain responses to viewing food and non-food pictures were measured using functional Magnetic Resonance Imaging in 32 type 1 diabetic patients, after each of two 12-week treatment periods with insulin detemir and NPH insulin, respectively, both combined with prandial insulin aspart. CSF insulin levels were determined in a subgroup. Insulin detemir decreased body weight by 0.8 kg and NPH insulin increased weight by 0.5 kg (p = 0.02 for difference, while both treatments resulted in similar glycemic control. After treatment with insulin detemir, as compared to NPH insulin, brain activation was significantly lower in bilateral insula in response to visual food stimuli, compared to NPH (p = 0.02 for right and p = 0.05 for left insula. Also, CSF insulin levels were higher compared to those with NPH insulin treatment (p = 0.003. Our findings support the hypothesis that in type 1 diabetic patients, the weight sparing effect of insulin detemir may be mediated by its enhanced action on the central nervous system, resulting in blunted activation in bilateral insula, an appetite-regulating brain region, in response to food stimuli.ClinicalTrials.gov NCT00626080.

  13. Insulin resistance in porphyria cutanea tarda.

    Science.gov (United States)

    Calcinaro, F; Basta, G; Lisi, P; Cruciani, C; Pietropaolo, M; Santeusanio, F; Falorni, A; Calafiore, R

    1989-06-01

    It has been reported that patients with porphyria cutanea tarda (PCT) develop carbohydrate (CHO) intolerance and manifest diabetes melitus (DM) more frequently than the normal population. In order to verify whether this is due to insulin resistance we studied 5 patients with PCT and 5 normal subjects matched for age, sex and weight. In all the patients an evaluation consisted of the glycemic curve and insulin response to an iv glucose tolerance test (IVGTT: 0.33 g/kg) as well as of an evaluation of the circulating monocyte insulin receptors. Blood samples were drawn in the basal state to measure plasma levels of NEFA, glycerol, and intermediate metabolites. The patients with PCT showed normal glucose tolerance which was obtained, however, at the expense of the elevated insulin levels: therefore a condition of insulin resistance was demonstrated in these subjects. An involvement of the lipid metabolism, observed by the raised levels of plasma NEFA and glycerol, was also evident. The insulin binding to circulating monocytes was reduced but not enough to justify the degree of insulin resistance observed. Therefore, it could be hypothesized, in agreement with similar studies, that a postreceptor defect is responsible for the insulin-resistance observed in patients with PCT and that the reduction of insulin receptors is determined by the down regulation in response to elevated insulinemic levels. An alteration of the porphyrin metabolism might be responsible for this disorder.

  14. Anti-insulin antibody test

    Science.gov (United States)

    Insulin antibodies - serum; Insulin Ab test; Insulin resistance - insulin antibodies; Diabetes - insulin antibodies ... You appear to have an allergic response to insulin Insulin no longer seems to control your diabetes

  15. Tolerability, safety and adherence to treatment with insulin detemir injection in the treatment of type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Athena Philis-Tsimikas

    2008-11-01

    Full Text Available Athena Philis-TsimikasScripps Whittier Diabetes Institute, La Jolla, CA, USAAbstract: The progressive nature of type 2 diabetes poses challenges in the clinic: treatment must be continually reviewed and adjusted in response to the patient’s changing pathophysiology. Ultimately, insulin replacement therapy will be necessary as the physiological insulin response is compromised. The modern basal insulin analog insulin detemir has been the subject of several clinical trials and observational studies in type 2 diabetes. Compared with NPH insulin, insulin detemir offers an improved balance between achieving current glycemic targets with acceptable tolerability. Insulin detemir also has a unique weight-sparing effect which is associated with body mass index, and this may be a particular advantage to obese patients with type 2 diabetes. This review summarizes data from key clinical studies of insulin detemir, and also provides insights from observational studies.Keywords: type 2 diabetes mellitus, insulin detemir, modern analog, basal insulin

  16. Successful Management of Insulin Allergy and Autoimmune Polyendocrine Syndrome Type 4 with Desensitization Therapy and Glucocorticoid Treatment: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Joselyn Rojas

    2014-01-01

    Full Text Available Introduction. Insulin allergy is a rare complication of insulin therapy, especially in type 1 diabetes mellitus (T1DM. Key manifestations are hypersensitivity-related symptoms and poor metabolic control. T1DM, as well as insulin allergy, may develop in the context of autoimmune polyendocrine syndrome (APS, further complicating management. Case Report. A 17-year-old male patient, diagnosed with T1DM, was treated with various insulin therapy schemes over several months, which resulted in recurrent anaphylactoid reactions and poor glycemic control, after which he was referred to our Endocrinology and Immunology Department. A prick test was carried out for all commercially available insulin presentations and another insulin scheme was designed but proved unsuccessful. A desensitization protocol was started with Glargine alongside administration of Prednisone, which successfully induced tolerance. Observation of skin lesions typical of vitiligo prompted laboratory workup for other autoimmune disorders, which returned positive for autoimmune gastritis/pernicious anemia. These findings are compatible with APS type 4. Discussion. To our knowledge, this is the first documented case of insulin allergy in type 4 APS, as well as this particular combination in APS. Etiopathogenic components shared by insulin allergy and APS beg for further research in immunogenetics to further comprehend pathophysiologic aspects of these diseases.

  17. Hippocampal memory processes are modulated by insulin and high-fat-induced insulin resistance.

    Science.gov (United States)

    McNay, Ewan C; Ong, Cecilia T; McCrimmon, Rory J; Cresswell, James; Bogan, Jonathan S; Sherwin, Robert S

    2010-05-01

    Insulin regulates glucose uptake and storage in peripheral tissues, and has been shown to act within the hypothalamus to acutely regulate food intake and metabolism. The machinery for transduction of insulin signaling is also present in other brain areas, particularly in the hippocampus, but a physiological role for brain insulin outside the hypothalamus has not been established. Recent studies suggest that insulin may be able to modulate cognitive functions including memory. Here we report that local delivery of insulin to the rat hippocampus enhances spatial memory, in a PI-3-kinase dependent manner, and that intrahippocampal insulin also increases local glycolytic metabolism. Selective blockade of endogenous intrahippocampal insulin signaling impairs memory performance. Further, a rodent model of type 2 diabetes mellitus produced by a high-fat diet impairs basal cognitive function and attenuates both cognitive and metabolic responses to hippocampal insulin administration. Our data demonstrate that insulin is required for optimal hippocampal memory processing. Insulin resistance within the telencephalon may underlie the cognitive deficits commonly reported to accompany type 2 diabetes.

  18. Amino acid-sensing mTOR signaling is involved in modulation of lipolysis by chronic insulin treatment in adipocytes

    OpenAIRE

    Zhang, Chongben; Yoon, Mee-Sup; Chen, Jie

    2009-01-01

    Chronically high insulin levels and increased circulating free fatty acids released from adipose tissue through lipolysis are two features associated with insulin resistance. The relationship between chronic insulin exposure and adipocyte lipolysis has been unclear. In the present study we found that chronic insulin exposure in 3T3-L1 adipocytes, as well as in mouse primary adipocytes, increased basal lipolysis rates. This effect of insulin on lipolysis was only observed when the mammalian ta...

  19. Clinical experience with insulin detemir, biphasic insulin aspart and insulin aspart in people with type 2 diabetes: Results from the Rajasthan cohort of the A 1 chieve study

    Directory of Open Access Journals (Sweden)

    Akhil Joshi

    2013-01-01

    Full Text Available Background: The A 1 chieve, a multicentric (28 countries, 24-week, non-interventional study evaluated the safety and effectiveness of insulin detemir, biphasic insulin aspart and insulin aspart in people with T2DM (n = 66,726 in routine clinical care across four continents. Materials and Methods: Data was collected at baseline, at 12 weeks and at 24 weeks. This short communication presents the results for patients enrolled from Rajasthan, India. Results: A total of 477 patients were enrolled in the study. Four different insulin analogue regimens were used in the study. Patients had started on or were switched to biphasic insulin aspart (n = 340, insulin detemir (n = 90, insulin aspart (n = 37, basal insulin plus insulin aspart (n = 7 and other insulin combinations (n = 2. At baseline glycaemic control was poor for both insulin naïve (mean HbA 1 c: 8.3% and insulin user (mean HbA 1 c: 8.4% groups. After 24 weeks of treatment, both the groups showed improvement in HbA 1 c (insulin naïve: −0.9%, insulin users: −1.2%. Major hypoglycaemic events decreased from 0.5 events/patient-year to 0.0 events/patient-year in insulin naïve group while no change from baseline (1.3 events/patients-year was observed for insulin users. SADRs were not reported in any of the study patients. Conclusion: Starting or switching to insulin analogues was associated with improvement in glycaemic control with a low rate of hypoglycaemia.

  20. Diabetes and Insulin

    Science.gov (United States)

    ... in the abdomen just behind the stomach, produces insulin. Insulin is a hormone that takes glucose from the ... occurs when the pancreas does not produce enough insulin or when the body doesn’t use insulin ...

  1. Insulin initiation in patients with type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Vaag, Allan; Lund, Søren

    2012-01-01

    This review addresses the apparent disconnect between international guideline recommendations, real-life clinical practice and the results of clinical trials, with regard to the initiation of insulin using basal (long-acting) or premixed insulin analogues in patients with type 2 diabetes (T2D......). English language guidelines vary considerably with respect to recommended glycaemic targets, the selection of human vs analogue insulin, and choice of insulin regimen. Randomised trials directly comparing insulin initiation between basal and premixed analogues are scarce, and hard endpoint outcome data...... are inadequate. The evidence presented suggests that a major component of the HbA1c not being attained in every day clinical practice may be a result of factors that are not adequately addressed in forced titration trials of highly motivated patients, including failure to comply with complex treatment...

  2. Insulin Resistance

    DEFF Research Database (Denmark)

    Jensen, Benjamin Anderschou Holbech

    Insulin resistance (IR) is escalating with alarming pace and is no longer restricted to westernized countries. As a forerunner for some of the most serious threats to human health including metabolic syndrome, cardiovascular diseases, and type 2-diabetes, the need for new treatment modalities...... interventions. We further show that improving the inflammatory toning, using fish oil as fat source, protects mice against diet induced obesity and -inflammation while preserving insulin sensitivity, even in the absence of free fatty acid receptor 4. Conversely, HFD-induced intestinal dysbiosis is associated...

  3. Choosing the Right Basal Reader.

    Science.gov (United States)

    Robbins, Ruth H.

    1980-01-01

    Looks at factors in the textbook publishing industry, especially costs and censorship, which affect the quality of available reading series. Notes the problem of readability and content bias. Finally, presents a checklist of basal reader evaluation criteria. (SJL)

  4. Clinical comparative study of three kinds of insulin application schemes in the treatment of patients with type 2 diabetes for poor glycemic control by oral hypoglycemic drugs%三种胰岛素应用方案治疗口服降糖药物血糖控制不佳2型糖尿病临床对比研究

    Institute of Scientific and Technical Information of China (English)

    刘咏梅

    2016-01-01

    Objective:To investigate the clinical effects and safety differences of three kinds of insulin application schemes in the treatment of pa-tients with type 2 diabetes for poor glycemic control by oral hypoglycemic drugs including neutral protamine zinc insulin ,insulin glargine and insulin detemir .Methods :150 patients with type 2 diabetes for poor glycemic control by oral hypoglycemic drugs were chosen in our hospital in the period from March 2012 to June 2015 and randomly divided into 3 groups including A group (50 patients) with neutral protamine zinc insulin ,B group (50 pa-tients) with insulin glargine and C group (50patients) with insulin detemir ;and the blood glucose index level before and after treatment ,insulin dosage and the incidence of hypoglycemia of 3 groups were compared .Results:The blood glucose index level after treatment of 3 groups was significantly lower than before treatment(P0 .05) .The insulin dosage of A group was significantly fewer than B group and C group(P0 .05);A 组患者胰岛素用量显著多于B组、C组 ,差异有统计学意义(P<0 .05);A 组患者低血糖发生率显著高于B组、C组 ,差异有统计学意义(P<0 .05).结论:三种胰岛素应用方案治疗口服降糖药物血糖控制不佳2 型糖尿病临床疗效接近 ,但甘精胰岛素和地特胰岛素应用可有效减少胰岛素用量 ,降低低血糖发生风险.

  5. Clinical experience with insulin detemir, biphasic insulin aspart and insulin aspart in people with type 2 diabetes: Results from the Eastern Saudi Arabia cohort of the A 1 chieve study

    Directory of Open Access Journals (Sweden)

    Faisal Hashim

    2013-01-01

    Full Text Available Background: The A 1 chieve, a multicentric (28 countries, 24-week, non-interventional study evaluated the safety and effectiveness of insulin detemir, biphasic insulin aspart and insulin aspart in people with T2DM (n = 66,726 in routine clinical care across four continents. Materials and Methods: Data was collected at baseline, at 12 weeks and at 24 weeks. This short communication presents the results for patients enrolled from Eastern Saudi Arabia. Results: A total of 1040 patients were enrolled in the study. Four different insulin analogue regimens were used in the study. Study patients had started on or were switched to biphasic insulin aspart (n = 489, insulin detemir (n = 360, insulin aspart (n = 37, basal insulin plus insulin aspart (n = 96 and other insulin combinations (n = 57. At baseline glycaemic control was poor for both insulin naïve (mean HbA 1 c: 10.0% and insulin user (mean HbA 1 c: 9.2% groups. After 24 weeks of treatment, both the groups showed improvement in HbA 1 c (insulin naïve: −2.7%, insulin users: −1.7%. No major hypoglycaemic episodes were observed at 24 weeks. SADR was reported in 0.6% of insulin users. Conclusion: Starting or switching to insulin analogues was associated with improvement in glycaemic control with a low rate of hypoglycaemia.

  6. Novel Simple Insulin Delivery Device Reduces Barriers to Insulin Therapy in Type 2 Diabetes: Results From a Pilot Study

    OpenAIRE

    Hermanns, Norbert; Lilly, Leslie C.; Mader, Julia K.; Aberer, Felix; Ribitsch, Anja; Kojzar, Harald; Warner, Jay; Pieber, Thomas R.

    2015-01-01

    Background: The PaQ® insulin delivery system is a simple-to-use patch-on device that provides preset basal rates and bolus insulin on demand. In addition to feasibility of use, safety, and efficacy (reported elsewhere), this study analyzed the impact of PaQ on patient-reported outcomes, including barriers to insulin treatment, diabetes-related distress, and attitudes toward insulin therapy in patients with type 2 diabetes on a stable multiple daily injection (MDI) regimen. Methods: This singl...

  7. Anaesthesia generates neuronal insulin resistance by inducing hypothermia

    Directory of Open Access Journals (Sweden)

    Sutherland Calum

    2008-10-01

    Full Text Available Abstract Background Anaesthesia is commonly employed prior to surgical investigations and to permit icv injections in rodents. Indeed it is standard practise in many studies examining the subsequent actions of hormones and growth factors on the brain. Recent evidence that the basal activity of specific intracellular signalling proteins can be affected by anaesthesia prompted us to examine the effect of anaesthesia not only on the basal activity but also the insulin sensitivity of the major insulin signalling pathways. Results We find that urethane- and ketamine-induced anaesthesia results in rapid activation of the phosphatidylinositol (PI 3-kinase-protein kinase B (PKB signalling pathway in the brain, increases tau phosphorylation while at the same time reducing basal activity of the Ras-ERK pathway. Subsequent injection of insulin does not alter the activity of either the PI 3-kinase or ERK signalling pathways, indicating a degree of neuronal molecular insulin resistance. However, if body temperature is maintained during anaesthesia then there is no alteration in the basal activity of these signalling molecules. Subsequent response of both pathways to insulin injection is restored. Conclusion The data is consistent with a hypothermia related alteration in neuronal signalling following anaesthesia, and emphasises the importance of maintaining the body temperature of rodents when monitoring insulin (or growth factor/neurotrophic agent action in the brain of anesthetised rodents.

  8. Insulin sensitivity in post-obese women

    DEFF Research Database (Denmark)

    Toubro, S; Western, P; Bülow, J

    1994-01-01

    1. Both increased and decreased sensitivity to insulin has been proposed to precede the development of obesity. Therefore, insulin sensitivity was measured during a 2 h hyperinsulinaemia (100 m-units min-1 m-2) euglycaemic (4.5 mmol/l) glucose clamp combined with indirect calorimetry in nine weight......-1 kg-1, not significant). Basal plasma concentrations of free fatty acids were similar, but at the end of the clamp free fatty acids were lower in the post-obese women than in the control women (139 +/- 19 and 276 +/- 48 mumol/l, P = 0.02). 3. We conclude that the insulin sensitivity of glucose...... metabolism is unaltered in the post-obese state. The study, however, points to an increased antilipolytic insulin action in post-obese subjects, which may favour fat storage and lower lipid oxidation rate postprandially.(ABSTRACT TRUNCATED AT 250 WORDS)...

  9. Chronic leucine supplementation increases body weight and insulin sensitivity in rats on high-fat diet likely by promoting insulin signaling in insulin-target tissues.

    Science.gov (United States)

    Li, Xiang; Wang, Xiaolei; Liu, Rui; Ma, Yan; Guo, Huailan; Hao, Liping; Yao, Ping; Liu, Liegang; Sun, Xiufa; He, Ka; Cao, Wenhong; Yang, Xuefeng

    2013-06-01

    This study investigated the effect of chronic leucine supplementation on insulin sensitivity and the associated mechanisms in rats on high-fat diet (HFD). Male Sprague-Dawley rats were fed either normal chow diet or HFD supplemented with 0, 1.5, 3.0, and 4.5% leucine for 24 weeks. We found that chronic leucine supplementation increased insulin sensitivity together with increased body weight in rats on HFD, but had no effect on insulin sensitivity in rats on normal chow diet. The increased insulin sensitivity by leucine supplementation was not associated with altered ectopic fat accumulation in liver and muscle, plasma levels of lipids and cytokines, but is associated with reduced oxidative stress and improved insulin signaling. Chronic leucine supplementation did not enhance insulin receptor substract-1 (IRS-1) phosphorylation on serine 302, but elevated basal IRS-1 phosphorylation on tyrosine 632 and improved insulin-stimulated protein kinase B (Akt) and mammalian target of rapamycin (mTOR) phosphorylation in liver, skeletal muscle, and adipose tissue of rats on HFD rats, indicating leucine supplementation prevented HFD-induced insulin resistance in insulin-target tissues. Chronic leucine supplementation can increase insulin sensitivity and body weight likely by reducing oxidative stress and improving insulin signaling pathway in rats on HFD. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Efficacy and safety of insulin treatment in type 2 diabetes using a new index called glucose safety control index

    Institute of Scientific and Technical Information of China (English)

    CAI Xiao-ling; LUO Ying-ying; HAN Xue-yao; JI Li-nong

    2013-01-01

    Objective To recommend an index named glucose safety control index (GSCI) to evaluate the efficacy and safety for insulin regimens.Data sources We searched databases for primary studies published in English.The main search concepts were type 2 diabetes,insulin treatment,premixed insulin,premixed insulin analogs,basal inuslin,basal inuslin analogs,bolus insulin,bolus insulin analogs,safety and efficacy.Study selection Studies were eligible for inclusion if they met all of the following criteria:(1) type 2 diabetic patients aged >18 years were included; (2) random control studies with at least 12 weeks of follow-up; (3) different insulin regimens were evaluated.Results When long-acting basal insulin therapy compared with neutral protamine Hagedorn (NPH) insulin therapy,the proportion of GSCI%A1c ratio more than 1 was 100%,the proportion of GSCIΔA1c ratio more than 1 was 94.44%.When premixed insulin therapy compared with oral hypoglycemic agents plus basal insulin therapy,the proportion of GSCI%A1c ratio more than 1 was 45.5%,the proportion of GSCIΔA1c ratio more than 1 was 38.9%.When premixed insulin therapy compared with oral hypoglycemic agents,the proportion of GSCI%A1c ratio less than 1 was 100%,the proportion of GSCI△A1c ratio more than 1 was 50%.When premixed insulin therapy compared with basal-bolus insulin therapy,the proportion of GSCI%A1c ratio more than 1 was 37.5%,the proportion of GSCIΔA1c ratio more than 1 was 50%.Conclusion According to the GSCI ratio,long-acting basal insulin therapy tended to be superior to NPH therapy,oral hypoglycemic agents plus basal insulin therapy tended to be superior to premixed insulin therapy,noninsulin antidiabetic agents and premixed insulin therapy was comparable,and basal-bolus insulin therapy tended to be superior to premixed insulin therapy in type 2 diabetes.

  11. Early differential defects of insulin secretion and action in 19-year-old caucasian men who had low birth weight

    DEFF Research Database (Denmark)

    Jensen, Christine B; Storgaard, Heidi; Dela, Flemming

    2002-01-01

    were significantly lower in the LBW group. Insulin-stimulated glycolytic flux was significantly reduced, and suppression of endogenous glucose production was enhanced in the LBW group. Nevertheless, basal and insulin-stimulated rates of whole-body peripheral glucose disposal, glucose oxidation, lipid...... oxidation, exogenous glucose storage, and nonoxidative glucose metabolism were similar in the two groups. Insulin secretion was reduced by 30% in the LBW group, when expressed relative to insulin sensitivity (disposition index = insulin secretion x insulin action). We propose that reduced insulin-stimulated...

  12. Early differential defects of insulin secretion and action in 19-year-old caucasian men who had low birth weight

    DEFF Research Database (Denmark)

    Jensen, Christine B; Storgaard, Heidi; Dela, Flemming;

    2002-01-01

    were significantly lower in the LBW group. Insulin-stimulated glycolytic flux was significantly reduced, and suppression of endogenous glucose production was enhanced in the LBW group. Nevertheless, basal and insulin-stimulated rates of whole-body peripheral glucose disposal, glucose oxidation, lipid...... oxidation, exogenous glucose storage, and nonoxidative glucose metabolism were similar in the two groups. Insulin secretion was reduced by 30% in the LBW group, when expressed relative to insulin sensitivity (disposition index = insulin secretion x insulin action). We propose that reduced insulin-stimulated...

  13. Hypoglycaemia

    Institute of Scientific and Technical Information of China (English)

    Piya Sen Gupta; Andrea N Green; Tahseen A Chowdhury

    2011-01-01

    @@ A 58 year old white man who has had type 2 diabetes for 10 years is concerned about increasingly frequent hypoglycaemic episodes, usually in the late afternoon.He has been taking a stable, once daily dose of basal insulin glargine 14 units for two years, as well as twice daily gliclazide 160 mg and metformin 1000 mg.

  14. An Adaptive Nonlinear Basal-Bolus Calculator for Patients With Type 1 Diabetes.

    Science.gov (United States)

    Boiroux, Dimitri; Aradóttir, Tinna Björk; Nørgaard, Kirsten; Poulsen, Niels Kjølstad; Madsen, Henrik; Jørgensen, John Bagterp

    2017-01-01

    Bolus calculators help patients with type 1 diabetes to mitigate the effect of meals on their blood glucose by administering a large amount of insulin at mealtime. Intraindividual changes in patients physiology and nonlinearity in insulin-glucose dynamics pose a challenge to the accuracy of such calculators. We propose a method based on a continuous-discrete unscented Kalman filter to continuously track the postprandial glucose dynamics and the insulin sensitivity. We augment the Medtronic Virtual Patient (MVP) model to simulate noise-corrupted data from a continuous glucose monitor (CGM). The basal rate is determined by calculating the steady state of the model and is adjusted once a day before breakfast. The bolus size is determined by optimizing the postprandial glucose values based on an estimate of the insulin sensitivity and states, as well as the announced meal size. Following meal announcements, the meal compartment and the meal time constant are estimated, otherwise insulin sensitivity is estimated. We compare the performance of a conventional linear bolus calculator with the proposed bolus calculator. The proposed basal-bolus calculator significantly improves the time spent in glucose target ( P < .01) compared to the conventional bolus calculator. An adaptive nonlinear basal-bolus calculator can efficiently compensate for physiological changes. Further clinical studies will be needed to validate the results.

  15. Nevoid basal cell carcinoma syndrome

    Directory of Open Access Journals (Sweden)

    Kannan Karthiga

    2006-01-01

    Full Text Available Binkley and Johnson first reported this syndrome in 1951. But it was in 1960, Gorlin-Goltz established the association of basal cell epithelioma, jaw cyst and bifid ribs, a combination which is now frequently known as Gorlin-Goltz syndrome as well as Nevoid Basal Cell Carcinoma Syndrome (NBCCS. NBCCS is inherited as an autosomal dominant trait with high penetrance and variable expressivity. NBCCS is characterized by variety of cutaneous, dental, osseous, opthalmic, neurologic and sexual abnormalities. One such case of Gorlin-Goltz syndrome is reported here with good illustrations.

  16. Basal Organelles of Bacterial Flagella

    Science.gov (United States)

    Cohen-Bazire, Germaine; London, Jack

    1967-01-01

    Liberated by enzymatic lysis of the cells, the flagella of Rhodospirillum rubrum, R. molischianum, and R. fulvum all have a similar structure. The hook at the base of the flagellum is connected by a short, narrow collar to a paired disc in the basal organelle. This paired disc is in turn connected to a second paired disc. The disposition of flagella to which fragments of the cell membrane still adhere suggests that the narrow collar at the base of the hook traverses both the wall and the membrane, and that the upper pair of discs in the basal organelle lies just beneath the surface of the membrane. Images PMID:6039362

  17. Insulin adherence behaviours and barriers in the multinational Global Attitudes of Patients and Physicians in Insulin Therapy study.

    Science.gov (United States)

    Peyrot, M; Barnett, A H; Meneghini, L F; Schumm-Draeger, P-M

    2012-05-01

    To examine patient and physician beliefs regarding insulin therapy and the degree to which patients adhere to their insulin regimens. Internet survey of 1250 physicians (600 specialists, 650 primary care physicians) who treat patients with diabetes and telephone survey of 1530 insulin-treated patients (180 with Type 1 diabetes, 1350 with Type 2 diabetes) in China, France, Japan, Germany, Spain, Turkey, the UK or the USA. One third (33.2%) of patients reported insulin omission/non-adherence at least 1 day in the last month, with an average of 3.3 days. Three quarters (72.5%) of physicians report that their typical patient does not take their insulin as prescribed, with a mean of 4.3 days per month of basal insulin omission/non-adherence and 5.7 days per month of prandial insulin omission/non-adherence. Patients and providers indicated the same five most common reasons for insulin omission/non-adherence: too busy; travelling; skipped meals; stress/emotional problems; public embarrassment. Physicians reported low patient success at initiating insulin in a timely fashion and adjusting insulin doses. Most physicians report that many insulin-treated patients do not have adequate glucose control (87.6%) and that they would treat more aggressively if not for concern about hypoglycaemia (75.5%). Although a majority of patients (and physicians) regard insulin treatment as restrictive, more patients see insulin treatment as having positive than negative impacts on their lives. Glucose control is inadequate among insulin-treated patients, in part attributable to insulin omission/non-adherence and lack of dose adjustment. There is a need for insulin regimens that are less restrictive and burdensome with lower risk of hypoglycaemia. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

  18. A primer on concentrated insulins: what an internist should know.

    Science.gov (United States)

    Barnosky, Adrienne; Shah, Lisa; Meah, Farah; Emanuele, Nicholas; Emanuele, Mary Ann; Mazhari, Alaleh

    2016-05-01

    The common insulin concentration in most preparations of insulin is 100 units per mL or U-100. Human regular U-500 insulin was the first concentrated insulin introduced and it has been available in the United States since the 1950s. Humulin R is the only human regular U-500 available on the market. Human regular U-500 is five times more concentrated than U-100 and because of its pharmacodynamic properties, works as both a basal and a bolus insulin. Human regular U500 allows for delivery of a larger insulin dose with a smaller volume leading to better absorption compared to U-100 and has traditionally been used in patients with moderate to severe insulin resistance. More recently other forms of concentrated insulin have become available and the newer concentrated insulin preparations can be used in diabetic patients with or without insulin resistance. Our intent is to provide primary care physicians with a review of the pharmacology and current literature on concentrated insulins as well as recommendations for patient selection, dose initiation, and dose adjustment.

  19. Fetal and perinatal outcomes in type 1 diabetes pregnancy : a randomized study comparing insulin aspart with human insulin in 322 subjects

    NARCIS (Netherlands)

    Hod, Moshe; Damm, Peter; Kaaja, Risto; Visser, Gerard H. A.; Dunne, Fidelma; Demidova, Irina; Hansen, Anne-Sofie Pade; Mersebach, Henriette

    2008-01-01

    OBJECTIVE: The objective of the study was a comparison of insulin aspart (IAsp) with human insulin (HI) in basal-bolus therapy with neutral protamine Hagedorn for fetal and perinatal outcomes of type 1 diabetes in pregnancy. STUDY DESIGN: This was a randomized, parallel, open-label, controlled, mult

  20. Cryotherapy in basal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Sandra A

    1999-01-01

    Full Text Available Cryotherapy has proved to be an effective tool in the management of various dermatoses. We report 6 patients with histopathologically proven basal cell carcinoma of variable sizes treated with liquid nitrogen cryotherapy by the open spray technique. Lesions tended to heal with depigmentation and scar formation. However depigmented areas often repigmented over a period of time.

  1. APPL1 potentiates insulin sensitivity by facilitating the binding of IRS1/2 to the insulin receptor.

    Science.gov (United States)

    Ryu, Jiyoon; Galan, Amanda K; Xin, Xiaoban; Dong, Feng; Abdul-Ghani, Muhammad A; Zhou, Lijun; Wang, Changhua; Li, Cuiling; Holmes, Bekke M; Sloane, Lauren B; Austad, Steven N; Guo, Shaodong; Musi, Nicolas; DeFronzo, Ralph A; Deng, Chuxia; White, Morris F; Liu, Feng; Dong, Lily Q

    2014-05-22

    Binding of insulin receptor substrate proteins 1 and 2 (IRS1/2) to the insulin receptor (IR) is essential for the regulation of insulin sensitivity and energy homeostasis. However, the mechanism of IRS1/2 recruitment to the IR remains elusive. Here, we identify adaptor protein APPL1 as a critical molecule that promotes IRS1/2-IR interaction. APPL1 forms a complex with IRS1/2 under basal conditions, and this complex is then recruited to the IR in response to insulin or adiponectin stimulation. The interaction between APPL1 and IR depends on insulin- or adiponectin-stimulated APPL1 phosphorylation, which is greatly reduced in insulin target tissues in obese mice. appl1 deletion in mice consistently leads to systemic insulin resistance and a significant reduction in insulin-stimulated IRS1/2, but not IR, tyrosine phosphorylation, indicating that APPL1 sensitizes insulin signaling by acting at a site downstream of the IR. Our study uncovers a mechanism regulating insulin signaling and crosstalk between the insulin and adiponectin pathways.

  2. APPL1 Potentiates Insulin Sensitivity by Facilitating the Binding of IRS1/2 to the Insulin Receptor

    Directory of Open Access Journals (Sweden)

    Jiyoon Ryu

    2014-05-01

    Full Text Available Binding of insulin receptor substrate proteins 1 and 2 (IRS1/2 to the insulin receptor (IR is essential for the regulation of insulin sensitivity and energy homeostasis. However, the mechanism of IRS1/2 recruitment to the IR remains elusive. Here, we identify adaptor protein APPL1 as a critical molecule that promotes IRS1/2-IR interaction. APPL1 forms a complex with IRS1/2 under basal conditions, and this complex is then recruited to the IR in response to insulin or adiponectin stimulation. The interaction between APPL1 and IR depends on insulin- or adiponectin-stimulated APPL1 phosphorylation, which is greatly reduced in insulin target tissues in obese mice. appl1 deletion in mice consistently leads to systemic insulin resistance and a significant reduction in insulin-stimulated IRS1/2, but not IR, tyrosine phosphorylation, indicating that APPL1 sensitizes insulin signaling by acting at a site downstream of the IR. Our study uncovers a mechanism regulating insulin signaling and crosstalk between the insulin and adiponectin pathways.

  3. Insulin Human Inhalation

    Science.gov (United States)

    Insulin inhalation is used in combination with a long-acting insulin to treat type 1 diabetes (condition in which the body does not produce insulin and therefore cannot control the amount of sugar ...

  4. Clinical utility of insulin and insulin analogs

    Science.gov (United States)

    Sanlioglu, Ahter D.; Altunbas, Hasan Ali; Balci, Mustafa Kemal; Griffith, Thomas S.; Sanlioglu, Salih

    2013-01-01

    Diabetes is a pandemic disease characterized by autoimmune, genetic and metabolic abnormalities. While insulin deficiency manifested as hyperglycemia is a common sequel of both Type-1 and Type-2 diabetes (T1DM and T2DM), it does not result from a single genetic defect—rather insulin deficiency results from the functional loss of pancreatic β cells due to multifactorial mechanisms. Since pancreatic β cells of patients with T1DM are destroyed by autoimmune reaction, these patients require daily insulin injections. Insulin resistance followed by β cell dysfunction and β cell loss is the characteristics of T2DM. Therefore, most patients with T2DM will require insulin treatment due to eventual loss of insulin secretion. Despite the evidence of early insulin treatment lowering macrovascular (coronary artery disease, peripheral arterial disease and stroke) and microvascular (diabetic nephropathy, neuropathy and retinopathy) complications of T2DM, controversy exists among physicians on how to initiate and intensify insulin therapy. The slow acting nature of regular human insulin makes its use ineffective in counteracting postprandial hyperglycemia. Instead, recombinant insulin analogs have been generated with a variable degree of specificity and action. Due to the metabolic variability among individuals, optimum blood glucose management is a formidable task to accomplish despite the presence of novel insulin analogs. In this article, we present a recent update on insulin analog structure and function with an overview of the evidence on the various insulin regimens clinically used to treat diabetes. PMID:23584214

  5. [Guidelines concerning insulin dosage in children and adolescents with type 1 diabetes on continuous subcutaneous insulin infusion].

    Science.gov (United States)

    Szypowska, Agnieszka; Pańkowska, Ewa; Lipka, Maria

    2006-01-01

    The treatment of diabetes mellitus with a continuous subcutaneous insulin infusion (CSII) has become very popular and is well accepted by diabetic patients. Pump therapy mimics the physiological insulin secretion and has been shown to be a safe and effective method of insulin administration alternative to the method of multiple injections. Continuous insulin infusion provides greater flexibility in the timing of meals and snacks with higher treatment satisfaction. Programmed basal rates improve nocturnal glycemic control and help to minimize a pre-breakfast increase of blood glucose level (the dawn phenomenon). Moreover, CSII can reduce exercise-induced and nocturnal hypoglycemia. Insulin pump therapy is effective in lowering glycated hemoglobin levels without higher risk of severe hypoglycaemia and ketoacidosis. To achieve a proper metabolic control with this method of treatment, the patient and his family requires appropriate education including knowledge of diet management, insulin therapy and manual competence of pump device. Here we present general guidelines for patients education concerning insulin dosage, programming of basal insulin rates and meal boluses based on carbohydrates and protein-fat exchanges.

  6. Insulin resistance induced by physical inactivity is associated with multiple transcriptional changes in skeletal muscle in young men

    DEFF Research Database (Denmark)

    Alibegovic, A C; Sonne, M P; Højbjerre, L

    2010-01-01

    Physical inactivity is a risk factor for insulin resistance. We examined the effect of 9 days of bed rest on basal and insulin-stimulated expression of genes potentially involved in insulin action by applying hypothesis-generating microarray in parallel with candidate gene real-time PCR approaches...... contribute to the development of insulin resistance induced by bed rest. Lack of complete normalization of changes after 4 wk of retraining underscores the importance of maintaining a minimum of daily physical activity....

  7. Tolerability, safety and adherence to treatment with insulin detemir injection in the treatment of type 2 diabetes

    OpenAIRE

    Athena Philis-Tsimikas

    2008-01-01

    Athena Philis-TsimikasScripps Whittier Diabetes Institute, La Jolla, CA, USAAbstract: The progressive nature of type 2 diabetes poses challenges in the clinic: treatment must be continually reviewed and adjusted in response to the patient’s changing pathophysiology. Ultimately, insulin replacement therapy will be necessary as the physiological insulin response is compromised. The modern basal insulin analog insulin detemir has been the subject of several clinical trials and observat...

  8. Insulin detemir in the treatment of type 1 and type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Jean-Christophe Philips

    2006-09-01

    Full Text Available Jean-Christophe Philips, André ScheenDivision of Diabetes, Nutrition & Metabolic Disorders, Department of Medicine, CHU Sart-Tilman, University of Liège, Liège, Belgium Abstract: Insulin detemir is a soluble long-acting human insulin analogue at neutral pH with a unique mechanism of action. Following subcutaneous injection, insulin detemir binds to albumin via fatty acid chain, thereby providing slow absorption and a prolonged metabolic effect. Insulin detemir has a less variable pharmacokinetic profile than insulin suspension isophane or insulin ultralente. The use of insulin detemir can reduce the risk of hypoglycemia (especially nocturnal hypoglycemia in type 1 and type 2 diabetic patients. However, overall glycemic control, as assessed by glycated hemoglobin, is only marginally and not significantly improved compared with usual insulin therapy. The weight gain commonly associated with insulin therapy is rather limited when insulin detemir is used. In our experience, this new insulin analogue is preferably administrated at bedtime but can be proposed twice a day (in the morning and either before the dinner or at bedtime. Detemir is a promising option for basal insulin therapy in type 1 or type 2 diabetic patients.Keywords: diabetes mellitus, insulin detemir, hypoglycemia, insulin analogue, insulin therapy

  9. Insulin dose response analysis of free fatty acid kinetics.

    Science.gov (United States)

    Jensen, Michael D; Nielsen, Søren

    2007-01-01

    Insulin regulation of free fatty acid (FFA) release is an important aspect of metabolic function; however, FFA release is exquisitely sensitive to insulin, which complicates the design and analysis of dose response experiments. We measured FFA ([(3)H]palmitate) and glucose ([(3)H]glucose) kinetics in 7 nonobese men, 7 nonobese women, 7 obese men, and 7 obese women by using a two-step insulin clamp (0.25 and 2.5 mU/kg fat-free mass per minute). Obese men and women were characterized as having a BMI of 28 or greater and body fat of 28% and 40% or greater for men and for women, respectively. Nonobese men and women had 22% and 35% or less body fat, respectively. All volunteers were Caucasian. Glucose disposal increased in a linear fashion with plasma insulin concentrations. The nonlinear suppression of plasma palmitate flux and concentrations could be linearized by logarithmically transforming both the insulin concentration and palmitate axes, except in nonobese men. We repeated the studies in 7 nonobese and 7 obese men, using 1.0 mU/kg fat-free mass per minute as the second insulin dose, which linearized the log-transformed lipolysis measures. The indices of insulin regulation of lipolysis predicted using 2 points (basal and second insulin dose) vs 3 points (basal, low, and high dose) were not different provided the proper second dose was selected. The EC(50) for insulin suppression of lipolysis correlated linearly with plasma triglycerides (r = 0.52, P < .001) and exponentially with insulin sensitivity(glucose) (r = 0.70, P < .001). We conclude that log transformation of insulin dose response data for FFA permits straightforward data analysis and simplifies the estimation of metabolically relevant parameters.

  10. Dietary fiber stabilizes blood glucose and insulin levels and reduces physical activity in sows (Sus scrofa)

    NARCIS (Netherlands)

    Leeuw, de J.A.; Jongbloed, A.W.; Verstegen, M.W.A.

    2004-01-01

    The aim of this study was to test whether a diet with a high level of fermentable dietary fiber can stabilize interprandial blood glucose and insulin levels, prevent declines below basal levels, and reduce physical activity in limited-fed breeding sows. Stable levels of glucose and insulin may preve

  11. Dietary fiber stabilizes blood glucose and insulin levels and reduces physical activity in sows (Sus scrofa)

    NARCIS (Netherlands)

    Leeuw, de J.A.; Jongbloed, A.W.; Verstegen, M.W.A.

    2004-01-01

    The aim of this study was to test whether a diet with a high level of fermentable dietary fiber can stabilize interprandial blood glucose and insulin levels, prevent declines below basal levels, and reduce physical activity in limited-fed breeding sows. Stable levels of glucose and insulin may preve

  12. IRS-1 serine phosphorylation and insulin resistance in skeletal muscle from pancreas transplant recipients

    DEFF Research Database (Denmark)

    Bouzakri, Karim; Karlsson, Håkan K R; Vestergaard, Henrik

    2006-01-01

    Insulin-dependent diabetic recipients of successful pancreas allografts achieve self-regulatory insulin secretion and discontinue exogenous insulin therapy; however, chronic hyperinsulinemia and impaired insulin sensitivity generally develop. To determine whether insulin resistance is accompanied...... by altered signal transduction, skeletal muscle biopsies were obtained from pancreas-kidney transplant recipients (n = 4), nondiabetic kidney transplant recipients (receiving the same immunosuppressive drugs; n = 5), and healthy subjects (n = 6) before and during a euglycemic-hyperinsulinemic clamp. Basal...... insulin receptor substrate (IRS)-1 Ser (312) and Ser (616) phosphorylation, IRS-1-associated phosphatidylinositol 3-kinase activity, and extracellular signal-regulated kinase (ERK)-1/2 phosphorylation were elevated in pancreas-kidney transplant recipients, coincident with fasting hyperinsulinemia. Basal...

  13. IRS-1 serine phosphorylation and insulin resistance in skeletal muscle from pancreas tranplant recipient

    DEFF Research Database (Denmark)

    Bouzakri, K; Karlsson, HRK; Vestergaard, Henrik;

    2006-01-01

    Insulin-dependent diabetic recipients of successful pancreas allografts achieve self-regulatory insulin secretion and discontinue exogenous insulin therapy; however, chronic hyperinsulinemia and impaired insulin sensitivity generally develop. To determine whether insulin resistance is accompanied...... by altered signal transduction, skeletal muscle biopsies were obtained from pancreas-kidney transplant recipients (n = 4), nondiabetic kidney transplant recipients (receiving the same immunosuppressive drugs; n = 5), and healthy subjects (n = 6) before and during a euglycemic-hyperinsulinemic clamp. Basal...... insulin receptor substrate (IRS)-1 Ser (312) and Ser (616) phosphorylation, IRS-1-associated phosphatidylinositol 3-kinase activity, and extracellular signal-regulated kinase (ERK)-1/2 phosphorylation were elevated in pancreas-kidney transplant recipients, coincident with fasting hyperinsulinemia. Basal...

  14. Therapeutics of Diabetes Mellitus: Focus on Insulin Analogues and Insulin Pumps

    Science.gov (United States)

    Valla, Vasiliki

    2010-01-01

    Aim. Inadequately controlled diabetes accounts for chronic complications and increases mortality. Its therapeutic management aims in normal HbA1C, prandial and postprandial glucose levels. This review discusses diabetes management focusing on the latest insulin analogues, alternative insulin delivery systems and the artificial pancreas. Results. Intensive insulin therapy with multiple daily injections (MDI) allows better imitation of the physiological rhythm of insulin secretion. Longer-acting, basal insulin analogues provide concomitant improvements in safety, efficacy and variability of glycaemic control, followed by low risks of hypoglycaemia. Continuous subcutaneous insulin infusion (CSII) provides long-term glycaemic control especially in type 1 diabetic patients, while reducing hypoglycaemic episodes and glycaemic variability. Continuous subcutaneous glucose monitoring (CGM) systems provide information on postprandial glucose excursions and nocturnal hypo- and/or hyperglycemias. This information enhances treatment options, provides a useful tool for self-monitoring and allows safer achievement of treatment targets. In the absence of a cure-like pancreas or islets transplants, artificial “closed-loop” systems mimicking the pancreatic activity have been also developed. Conclusions. Individualized treatment plans for insulin initiation and administration mode are critical in achieving target glycaemic levels. Progress in these fields is expected to facilitate and improve the quality of life of diabetic patients. PMID:20589066

  15. Therapeutics of Diabetes Mellitus: Focus on Insulin Analogues and Insulin Pumps

    Directory of Open Access Journals (Sweden)

    Vasiliki Valla

    2010-01-01

    Full Text Available Aim. Inadequately controlled diabetes accounts for chronic complications and increases mortality. Its therapeutic management aims in normal HbA1C, prandial and postprandial glucose levels. This review discusses diabetes management focusing on the latest insulin analogues, alternative insulin delivery systems and the artificial pancreas. Results. Intensive insulin therapy with multiple daily injections (MDI allows better imitation of the physiological rhythm of insulin secretion. Longer-acting, basal insulin analogues provide concomitant improvements in safety, efficacy and variability of glycaemic control, followed by low risks of hypoglycaemia. Continuous subcutaneous insulin infusion (CSII provides long-term glycaemic control especially in type 1 diabetic patients, while reducing hypoglycaemic episodes and glycaemic variability. Continuous subcutaneous glucose monitoring (CGM systems provide information on postprandial glucose excursions and nocturnal hypo- and/or hyperglycemias. This information enhances treatment options, provides a useful tool for self-monitoring and allows safer achievement of treatment targets. In the absence of a cure-like pancreas or islets transplants, artificial “closed-loop” systems mimicking the pancreatic activity have been also developed. Conclusions. Individualized treatment plans for insulin initiation and administration mode are critical in achieving target glycaemic levels. Progress in these fields is expected to facilitate and improve the quality of life of diabetic patients.

  16. Effects of aging on basal fat oxidation in obese humans

    DEFF Research Database (Denmark)

    Solomon, Thomas; Marchetti, Christine M; Krishnan, Raj K

    2008-01-01

    Basal fat oxidation decreases with age. In obesity, it is not known whether this age-related process occurs independently of changes in body composition and insulin sensitivity. Therefore, body composition, resting energy expenditure, basal substrate oxidation, and maximal oxygen consumption (VO(2......)max) were measured in 10 older (age, 60 +/- 4 years; mean +/- SEM) and 10 younger (age, 35 +/- 4 years) body mass index-matched, obese, normal glucose-tolerant individuals. Fasting blood samples were also collected. Older subjects had slightly elevated fat mass (32.2 +/- 7.1 vs 36.5 +/- 6.7 kg, P...... = .16); however, waist circumference was not different between groups (104.3 +/- 10.3 vs 102.1 +/- 12.6 cm, P = .65). Basal fat oxidation was 22% lower (1.42 +/- 0.14 vs 1.17 +/- 0.22 mg/kg fat-free mass per minute, P = .03) in older subjects. The VO(2)max was also decreased in older individuals (44...

  17. IRS-1 serine phosphorylation and insulin resistance in skeletal muscle from pancreas tranplant recipient

    DEFF Research Database (Denmark)

    Bouzakri, K; Karlsson, HRK; Vestergaard, Henrik

    2006-01-01

    Insulin-dependent diabetic recipients of successful pancreas allografts achieve self-regulatory insulin secretion and discontinue exogenous insulin therapy; however, chronic hyperinsulinemia and impaired insulin sensitivity generally develop. To determine whether insulin resistance is accompanied....... In conclusion, peripheral insulin resistance in pancreas-kidney transplant recipients may arise from a negative feedback regulation of the canonical insulin-signaling cascade from excessive serine phosphorylation of IRS-1, possibly as a consequence of immunosuppressive therapy and hyperinsulinemia....... insulin receptor substrate (IRS)-1 Ser (312) and Ser (616) phosphorylation, IRS-1-associated phosphatidylinositol 3-kinase activity, and extracellular signal-regulated kinase (ERK)-1/2 phosphorylation were elevated in pancreas-kidney transplant recipients, coincident with fasting hyperinsulinemia. Basal...

  18. IRS-1 serine phosphorylation and insulin resistance in skeletal muscle from pancreas tranplant recipient

    DEFF Research Database (Denmark)

    Bouzakri, K; Karlsson, HRK; Vestergaard, Henrik

    2006-01-01

    Insulin-dependent diabetic recipients of successful pancreas allografts achieve self-regulatory insulin secretion and discontinue exogenous insulin therapy; however, chronic hyperinsulinemia and impaired insulin sensitivity generally develop. To determine whether insulin resistance is accompanied....... In conclusion, peripheral insulin resistance in pancreas-kidney transplant recipients may arise from a negative feedback regulation of the canonical insulin-signaling cascade from excessive serine phosphorylation of IRS-1, possibly as a consequence of immunosuppressive therapy and hyperinsulinemia....... insulin receptor substrate (IRS)-1 Ser (312) and Ser (616) phosphorylation, IRS-1-associated phosphatidylinositol 3-kinase activity, and extracellular signal-regulated kinase (ERK)-1/2 phosphorylation were elevated in pancreas-kidney transplant recipients, coincident with fasting hyperinsulinemia. Basal...

  19. Optimum bolus wizard settings in insulin pumps in children with Type 1 diabetes

    DEFF Research Database (Denmark)

    Andersen, A J B; Ostenfeld, A; Pipper, C B

    2016-01-01

    AIM: To evaluate current insulin pump settings in an optimally regulated paediatric population using bolus wizard. METHODS: We used a retrospective study design to analyse data from 124 children on insulin pump therapy who had optimum HbA1c levels [.... Furthermore, duration of insulin pump treatment was significantly associated with insulin sensitivity factor and percentage bolus/basal was significantly associated with insulin to carbohydrate factor. Gender, diabetes duration and BMI were not associated with any of the calculation factors. CONCLUSION......: Optimum insulin pump settings at pump initiation depend on both insulin requirements and use of the pump. Settings need to be individualized because the standardized calculation factors are not constant for children. There is a need to develop specific age- and insulin dose-dependent calculation factors....

  20. The human airway epithelial basal cell transcriptome.

    Directory of Open Access Journals (Sweden)

    Neil R Hackett

    Full Text Available BACKGROUND: The human airway epithelium consists of 4 major cell types: ciliated, secretory, columnar and basal cells. During natural turnover and in response to injury, the airway basal cells function as stem/progenitor cells for the other airway cell types. The objective of this study is to better understand human airway epithelial basal cell biology by defining the gene expression signature of this cell population. METHODOLOGY/PRINCIPAL FINDINGS: Bronchial brushing was used to obtain airway epithelium from healthy nonsmokers. Microarrays were used to assess the transcriptome of basal cells purified from the airway epithelium in comparison to the transcriptome of the differentiated airway epithelium. This analysis identified the "human airway basal cell signature" as 1,161 unique genes with >5-fold higher expression level in basal cells compared to differentiated epithelium. The basal cell signature was suppressed when the basal cells differentiated into a ciliated airway epithelium in vitro. The basal cell signature displayed overlap with genes expressed in basal-like cells from other human tissues and with that of murine airway basal cells. Consistent with self-modulation as well as signaling to other airway cell types, the human airway basal cell signature was characterized by genes encoding extracellular matrix components, growth factors and growth factor receptors, including genes related to the EGF and VEGF pathways. Interestingly, while the basal cell signature overlaps that of basal-like cells of other organs, the human airway basal cell signature has features not previously associated with this cell type, including a unique pattern of genes encoding extracellular matrix components, G protein-coupled receptors, neuroactive ligands and receptors, and ion channels. CONCLUSION/SIGNIFICANCE: The human airway epithelial basal cell signature identified in the present study provides novel insights into the molecular phenotype and biology of

  1. Figure 1: Basal-Bolus Regime

    African Journals Online (AJOL)

    Siegal_D

    Breakfast. Lunch. Dinner. Bedtime. Plasma insulin concentrations over time with a twice daily insulin mix regime .... Hypoglycaemia. Frequency, severity, awareness, precipitants, driving, ... Post GDM, family members, IGT etc. EXAMINATION.

  2. A new angle for glp-1 receptor agonist: the medical economics argument. Editorial on: Huetson P, Palmer JL, Levorsen A, et al. Cost-effectiveness of the once-daily glp-1 receptor agonist lixisenatide compared to bolus insulin both in combination with basal insulin for the treatment of patients with type 2 diabetes in Norway. J Med Econ 2015: 1-13 [Epub ahead of print].

    Science.gov (United States)

    Valencia, Willy Marcos; Florez, Hermes Jose

    2015-01-01

    Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are relatively new medications for diabetes that offer a weight-loss profile that can be considered desirable for patients with both type 2 diabetes (T2D) and obesity. GLP-1 RA are effective in combination with insulin, and even slightly superior or at least equal to short-acting insulin in T2D; however, since they work in the incretin system, they may not be effective in long-standing disease. Additionally, only recently have publications reported their cardiovascular safety, and there is limited evidence for long-term effectiveness. The work presented by Huetson et al. offers a much needed perspective through a medical economic model for the long term cost-effectiveness of GLP-1 RA. The authors found benefits in quality-adjusted life years and reduced lifetime healthcare costs. While there are a few limitations, this study contributes to the understanding of these agents and their impact on the epidemics of obesity in T2D, where weight management is no longer an option, but an essential component of the diabetes plan of care.

  3. Endurance training and insulin therapy need to be associated to fully exert their respective beneficial effects on oxidant stress and glycemic regulation in diabetic rats.

    Science.gov (United States)

    Malardé, L; Gratas-Delamarche, A; Le Douairon-Lahaye, S; Zguira, M S; Vincent, S; Lemoine-Morel, S; Groussard, C

    2014-04-01

    In type 1 diabetic subjects, hyperglycemia-induced oxidant stress (OS) plays a central role in the onset and development of diabetes complications. This study aimed to assess the benefits of an endurance training program and insulin therapy, alone or in combination, on the glycemic regulation, markers for OS, and antioxidant system in diabetic rats. Forty male Wistar rats were divided into diabetic (D), insulin-treated diabetic (D-Ins), diabetic trained (D-Tr), or insulin-treated diabetic trained (D-Ins+ Tr) groups. An additional healthy group served as control group. Insulin therapy (Lantus, insulin glargine, Sanofi) and endurance training (a treadmill run of 60 min/day, 25 m/min, 5 days/week) were initiated 1 week after streptozotocin-induced diabetes (45 mg/kg) and lasted for 8 weeks. At the end of the protocol, blood glucose and fructosamine levels, markers for skeletal muscle OS (CML, isoprostanes, GSH/GSSG) and antioxidant system (SOD and GPx activity, ORAC) were assessed. In diabetic rats, the glycemic control was altered and OS marker levels were increased, while the antioxidant system activity remained unchanged. Insulin treatment improved the glycemic regulation, the pro-antioxidant status, and contributed to the reduction of OS marker levels. Endurance training decreased OS marker levels without improving the antioxidant enzyme activity. Endurance training and insulin therapy acted independently (by different ways), but their association prolonged the insulin action and allowed a better adaptation of the antioxidant system. To conclude, our results demonstrate that combination of insulin treatment and endurance training leads to greater benefits on the glycemic regulation and oxidant status.

  4. The basal ganglia and apraxia.

    Science.gov (United States)

    Pramstaller, P P; Marsden, C D

    1996-02-01

    Ever since Liepmann's original descriptions at the beginning of the century apraxia has usually been attributed to damage confined to the cerebral cortex and/or cortico-cortical connecting pathways. However, there have been suggestions that apraxia can be due to deep subcortical lesions, which raises the question as to whether damage to the basal ganglia or thalamus can cause apraxia. We therefore analysed 82 cases of such 'deep' apraxias reported in the literature. These reports consisted of a small number (n=9) of cases studied neuropathologically, and a much larger group (n=73) in which CT or MRI was used to identify the size and extent of the lesion. The reports were subdivided into (i) those with small isolated lesions which involved nuclei of the basal ganglia or thalamus only, and not extending to involve periventricular or peristriatal white matter; (ii) those with large lesions which involved two or more of the nuclei, or one or more of these deep structures plus damage to closely adjacent areas including the internal capsule, periventricular or peristriatal white matter; and (iii) lesions sparing basal ganglia and thalamus but involving adjacent white matter. The main conclusions to be drawn from this meta-analysis are that lesions confined to the basal ganglia (putamen, caudate nucleus and globus pallidus) rarely, if ever, cause apraxia. Lesions affecting the lenticular nucleus or putamen nearly always intruded into the adjacent lateral white matter to involve association fibres, in particular those of the superior longitudinal fasciculus and frontostriatal connections. Apraxia occurred with deep lesions of the basal ganglia apparently sparing white matter in only eight out of the 82 cases. Apraxia was most commonly seen when there were lesions in the lenticular nucleus or putamen (58 out of 72 cases) with additional involvement of capsular, and particularly of periventricular or peristriatal, white matter. Lesions of the globus pallidus (no cases) or

  5. Insulin initiation and intensification in patients with T2DM for the primary care physician

    Directory of Open Access Journals (Sweden)

    Unger J

    2011-06-01

    Full Text Available Jeff UngerCatalina Research Institute, Chino, CA, USAAbstract: Type 2 diabetes mellitus (T2DM is characterized by both insulin resistance and inadequate insulin secretion. All patients with the disease require treatment to achieve and maintain the target glycosylated hemoglobin (A1C level of 6.5%–7%. Pharmacological management of T2DM typically begins with the introduction of oral medications, and the majority of patients require exogenous insulin therapy at some point in time. Primary care physicians play an essential role in the management of T2DM since they often initiate insulin therapy and intensify regimens over time as needed. Although insulin therapy is prescribed on an individualized basis, treatment usually begins with basal insulin added to a background therapy of oral agents. Prandial insulin injections may be added if glycemic targets are not achieved. Treatments may be intensified over time using patient-friendly titration algorithms. The goal of insulin intensification within the primary care setting is to minimize patients' exposure to chronic hyperglycemia and weight gain, and reduce patients' risk of hypoglycemia, while achieving individualized fasting, postprandial, and A1C targets. Simplified treatment protocols and insulin delivery devices allow physicians to become efficient prescribers of insulin intensification within the primary care arena.Keywords: diabetes, basal, bolus, regimens, insulin analogs, structured glucose testing

  6. An Adaptive Nonlinear Basal-Bolus Calculator for Patients With Type 1 Diabetes

    DEFF Research Database (Denmark)

    Boiroux, Dimitri; Aradóttir, Tinna Björk; Nørgaard, Kirsten;

    2017-01-01

    to the accuracy of such calculators. Method : We propose a method based on a continuous-discrete unscented Kalman filter to continuously track the postprandial glucose dynamics and the insulin sensitivity. We augment the Medtronic Virtual Patient (MVP) model to simulate noise-corrupted data from a continuous...... glucose monitor (CGM). The basal rate is determined by calculating the steady state of the model and is adjusted once a day before breakfast. The bolus size is determined by optimizing the postprandial glucose values based on an estimate of the insulin sensitivity and states, as well as the announced meal...

  7. The importance of palmitoleic acid to adipocyte insulin resistance and whole-body insulin sensitivity in type 1 diabetes.

    Science.gov (United States)

    Bergman, Bryan C; Howard, David; Schauer, Irene E; Maahs, David M; Snell-Bergeon, Janet K; Clement, Timothy W; Eckel, Robert H; Perreault, Leigh; Rewers, Marian

    2013-01-01

    Type 1 diabetes is an insulin-resistant state, but it is less clear which tissues are affected. Our previous report implicated skeletal muscle and liver insulin resistance in people with type 1 diabetes, but this occurred independently of generalized, visceral, or ectopic fat. The aim of the study was to measure adipose tissue insulin sensitivity and plasma triglyceride composition in individuals with type 1 diabetes after overnight insulin infusion to lower fasting glucose. Fifty subjects (25 individuals with type 1 diabetes and 25 controls without) were studied. After 3 d of dietary control and overnight insulin infusion, we performed a three-stage hyperinsulinemic/euglycemic clamp infusing insulin at 4, 8, and 40 mU/m(2) · min. Infusions of [1,1,2,3,3-(2)H(2)]glycerol and [1-(13)C]palmitate were used to quantify lipid metabolism. Basal glycerol and palmitate rates of appearance were similar between groups, decreased more in control subjects during the first two stages of the clamp, and similarly suppressed during the highest insulin dose. The concentration of insulin required for 50% inhibition of lipolysis was twice as high in individuals with type 1 diabetes. Plasma triglyceride saturation was similar between groups, but palmitoleic acid in plasma triglyceride was inversely related to adipocyte insulin sensitivity. Unesterified palmitoleic acid in plasma was positively related to insulin sensitivity in controls, but not in individuals with type 1 diabetes. Adipose tissue insulin resistance is a significant feature of type 1 diabetes. Palmitoleic acid is not related to insulin sensitivity in type 1 diabetes, as it was in controls, suggesting a novel mechanism for insulin resistance in this population.

  8. Migraine attacks the Basal Ganglia

    Directory of Open Access Journals (Sweden)

    Bigal Marcelo

    2011-09-01

    Full Text Available Abstract Background With time, episodes of migraine headache afflict patients with increased frequency, longer duration and more intense pain. While episodic migraine may be defined as 1-14 attacks per month, there are no clear-cut phases defined, and those patients with low frequency may progress to high frequency episodic migraine and the latter may progress into chronic daily headache (> 15 attacks per month. The pathophysiology of this progression is completely unknown. Attempting to unravel this phenomenon, we used high field (human brain imaging to compare functional responses, functional connectivity and brain morphology in patients whose migraine episodes did not progress (LF to a matched (gender, age, age of onset and type of medication group of patients whose migraine episodes progressed (HF. Results In comparison to LF patients, responses to pain in HF patients were significantly lower in the caudate, putamen and pallidum. Paradoxically, associated with these lower responses in HF patients, gray matter volume of the right and left caudate nuclei were significantly larger than in the LF patients. Functional connectivity analysis revealed additional differences between the two groups in regard to response to pain. Conclusions Supported by current understanding of basal ganglia role in pain processing, the findings suggest a significant role of the basal ganglia in the pathophysiology of the episodic migraine.

  9. Dissociation between fat-induced in vivo insulin resistance and proximal insulin signaling in skeletal muscle in men at risk for type 2 diabetes

    DEFF Research Database (Denmark)

    Storgaard, Heidi; Jensen, Christine B; Björnholm, Marie

    2004-01-01

    The effect of short- (2 h) and long-term (24 h) low-grade Intralipid infusion on whole-body insulin action, cellular glucose metabolism, and proximal components of the insulin signal transduction cascade was studied in seven obese male glucose intolerant first degree relatives of type 2 diabetic......-associated phosphoinositide 3-kinase (PI 3-kinase) activity, insulin receptor substrate-1-associated PI 3-kinase activity, or Akt serine phosphorylation in IGT relatives or matched controls. In fact, a paradoxical increase in both basal and insulin-stimulated PI 3-kinase activity was noted in the total study population after...

  10. Intranasal insulin therapy

    DEFF Research Database (Denmark)

    Hilsted, J; Madsbad, S; Hvidberg, A;

    1995-01-01

    To evaluate metabolic control and safety parameters (hypoglycaemia frequency and nasal mucosa physiology), 31 insulin-dependent diabetic patients were treated with intranasal insulin at mealtimes for 1 month and with subcutaneous fast-acting insulin at meals for another month in an open, crossover...... randomized trial. During both treatment periods the patients were treated with intermediate-acting insulin at bedtime. Six of the patients were withdrawn from the study during intranasal insulin therapy due to metabolic dysregulation. Serum insulin concentrations increased more rapidly and decreased more...... quickly during intranasal as compared with subcutaneous insulin administration. Metabolic control deteriorated, as assessed by haemoglobin A1c concentrations, slightly but significantly after intranasal as compared with subcutaneous insulin therapy. The bioavailability of intranasally applied insulin...

  11. Alteration in insulin action

    DEFF Research Database (Denmark)

    Tanti, J F; Gual, P; Grémeaux, T

    2004-01-01

    Insulin resistance, when combined with impaired insulin secretion, contributes to the development of type 2 diabetes. Insulin resistance is characterised by a decrease in insulin effect on glucose transport in muscle and adipose tIssue. Tyrosine phosphorylation of insulin receptor substrate 1 (IRS......-1) and its binding to phosphatidylinositol 3-kinase (PI 3-kinase) are critical events in the insulin signalling cascade leading to insulin-stimulated glucose transport. Modification of IRS-1 by serine phosphorylation could be one of the mechanisms leading to a decrease in IRS-1 tyrosine...... to phosphorylate these serine residues have been identified. These exciting results suggest that serine phosphorylation of IRS-1 is a possible hallmark of insulin resistance in biologically insulin responsive cells or tIssues. Identifying the pathways by which "diabetogenic" factors activate IRS-1 kinases...

  12. Ramadan fasting in diabetes patients on insulin pump therapy augmented by continuous glucose monitoring: an observational real-life study.

    Science.gov (United States)

    Khalil, Ali Bernard; Beshyah, Salem A; Abu Awad, Samar M; Benbarka, Mahmoud M; Haddad, Marcil; Al-Hassan, Dana; Kahwatih, Marwa; Nagelkerke, Nico

    2012-09-01

    Hypoglycemia during the daytime of Ramadan fasting is the most feared complication of diabetes. Insulin pump therapy has been proposed as the ideal "theoretical" method for insulin delivery. We report a prospective observational, single-center study of insulin-treated patients using insulin pump therapy during Ramadan 2011. Twenty-one patients (10 males and 11 females) were selected; median age was 26 years. They adjusted their insulin as per their usual practices. Outcome measures obtained before and during Ramadan included body weight, glycosylated hemoglobin, blood glucose, total insulin dose differences, overriding tendency, suspension time during fasting, and number of hypoglycemic episodes. The patients fasted for a median of 29 days. The observed changes during Ramadan were overall not significant quantitatively, but some trends were noted. The total insulin administered during Ramadan was not different from that in the pre-Ramadan period, but there was a redistribution of insulin over a 24-h period in relation to the changes in the daily lifestyle and eating patterns. Basal insulin was decreased during the daytime by 5-20% from before Ramadan and increased during the nighttime. The mean change in the overall amount of basal insulin was not significant. A larger than usual amount of insulin bolus was given at the meals Iftar, Fowala, and Suhur; the change in the total amount of bolus insulin as a percentage change from total insulin was also not significant. No major hypoglycemic episodes were reported. Minor hypoglcemic episodes were equally distributed between daytime and nighttime and were managed by either basal insulin adjustment or suspension from the pump. This study confirms the advantages provided by insulin pump use in patients with diabetes were enhanced by the use of continuous glucose monitoring. We provided more evidence-based advice on how best to adjust the insulin pump during fasting.

  13. Insulin action in adipose tissue in type 1 diabetes

    Directory of Open Access Journals (Sweden)

    F Arrieta-Blanco

    2011-02-01

    Full Text Available F Arrieta-Blanco1, JI Botella-Carretero1, P Iglesias1, JA Balsa1, I Zamarrón1, C De la Puerta1, JJ Arrieta2, F Ramos3, C Vázquez1, A Rovira21Unit of Clinical Nutrition and Dietetics, Department of Endocrinology and Nutrition, Hospital Ramóny, Cajal, Madrid, Spain, Irycis, Ciberobn; 2Fundación Jimenez Díaz. Madrid, Spain; 3Hospital Sureste de ArgandaBackground: Insulin action has been reported to be normal in type 1 diabetic patients. However, some studies have reported an insulin resistance state in these patients. The aim of this study was to investigate insulin resistance in a group of type 1 diabetic patients. We studied the insulin action in adipose tissue and analyzed the effects of duration of disease, body mass index (BMI, and glycosylated hemoglobin on insulin action at the receptor and postreceptor levels in adipocytes.Methods: Nine female type 1 diabetic patients with different durations of disease and eight nondiabetic female patients of comparable age and BMI were studied. 125I-insulin binding and U-[14C]-D-glucose transport was measured in a sample of subcutaneous gluteus adipose tissue obtained by open surgical biopsy from each subject.Results: The duration of disease was negatively correlated with both 125I-insulin binding capacity (r = -0.70, P < 0.05 and basal and maximum insulin-stimulated glucose transport (r = -0.87, P < 0.01, and r = -0.88, P < 0.01, respectively. Maximum specific 125I-insulin binding to the receptors in adipocytes was higher in the group of patients with a shorter duration of disease (P < 0.01. Basal and maximum insulin-stimulated glucose transport was significantly higher in the group with less than 5 years of disease (P < 0.01. No correlation was found between BMI and insulin action.Conclusion: Female type 1 diabetic patients have normal insulin action. There is a high glucose uptake in the early phase of the disease, although a longer duration of disease appears to be a contributing factor to a

  14. Growth Hormone and Insulin Signaling in Acromegaly

    DEFF Research Database (Denmark)

    Dal, Jakob; Lundby Høyer, Katrine; Pedersen, Steen Bønløkke;

    2016-01-01

    CONTEXT: Somatostatin analogues (SA) used in acromegaly to suppress GH secretion and tumor growth also suppress insulin secretion and may impact GH signaling. OBJECTIVE: To compare GH and insulin signaling after intravenous GH exposure in acromegalic patients controlled by surgery (n=9) or SA (n=9...... MEASURES: GH and insulin signalling in muscle and fat. GH and IGF-I in serum and interstitial fluid; insulin and FFA in serum. RESULTS: The groups were comparable as regards GH and IGF-I. The SA group exhibited higher FFA and glucose levels; basal SOCS1 mRNA in fat was increased in the SA group...... and correlated positively with SA dose (r(2)= 0.54, P=0.04). GH-induced GH signalling (pSTAT5b) in muscle occurred in both groups together with increased expression of SOCS and CISH genes. GH-induced pAKTthr(308) was observed in SA patients. In both groups mRNA expression of PTEN, a suppressor of insulin...

  15. A Micro-PIV Study of the Pulsed Micro-Flows Driven by an Insulin Pump

    Science.gov (United States)

    Wang, Bing; Demuren, Ayodeji; Gyuricsko, Eric; Hu, Hui

    2009-11-01

    In recent years, there is a surge in the popularity of using insulin pump or continuous subcutaneous insulin infusion therapy, as opposed to multiple daily injections by insulin syringe or an insulin pen. Some case studies have suggested that insulin delivery failure may be caused by precipitation of insulin within the infusion set. Speculation also exists that the flow of insulin through an insulin infusion set may be reduced or inhibited by air bubbles entrained into the micro-sized tubing system since there are chances that air be introduced into the insulin reservoir during the filling process. In the present study, a microscopic Particle Image Velocimtry (micro-PIV) system was used to characterize the transient behavior of the pulsed micro-flows inside the micro-sized tubing system of an insulin infusion set with insulin pump operating in basal mode (i.e., pulsed insulin pumping). The effects of the air bubbles entrained into the micro-sized tubing system on the insulin delivery process were assessed based on the micro-PIV measurements.

  16. Insulin resistance and acne: a new risk factor for men?

    Science.gov (United States)

    Del Prete, Michela; Mauriello, Maria Chiara; Faggiano, Antongiulio; Di Somma, Carolina; Monfrecola, Giuseppe; Fabbrocini, Gabriella; Colao, Annamaria

    2012-12-01

    The purpose of this study is to investigate the relationship between acne and insulin resistance as well as other metabolic impairment in young males. Acne is a skin disease that can be influenced by endocrine abnormalities. In females, it is associated with polycystic ovary syndrome, with peripheral insulin resistance and hyperinsulinemia, whereas few data are available in males. For investigating this, 22 young males with acne have been compared to 22 controls of comparable age and gender. Acne was scored using the global acne grading system score. Clinical as well as biochemical parameters of glucose and lipid metabolism, circulating levels of androgens, and IGF-1 were evaluated. Oral glucose tolerance test was performed and homeostasis model assessment of insulin resistance was calculated. The results thus obtained are as follows, patients had higher BMI (p = 0.003), WC (p = 0.002), WHR (p = 0.02), SBP (p = 0.0001), DBP (p = 0.001), basal (p = 0.01) and 120 min. oGTT serum insulin concentrations (p = 0.002), basal glucose concentrations (p = 0.03), HOMA-IR (p = 0.016), and lower HDL-cholesterol than controls (p = 0.001). Among the subgroup of subjects with BMI acne at multivariate analysis. In conclusion, these findings highlight a metabolic imbalance in young males affected with acne. Insulin resistance seems to play the main role for the development of acne in these subjects. Insulin resistance could represent an effective target for therapy in male acne.

  17. Dissociation of the effects of epinephrine and insulin on glucose and protein metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Castellino, P.; Luzi, L.; Del Prato, S.; DeFronzo, R.A. (Univ. of Texas Health Science Center, San Antonio (USA))

    1990-01-01

    The separate and combined effects of insulin and epinephrine on leucine metabolism were examined in healthy young volunteers. Subjects participated in four experimental protocols: (1) euglycemic insulin clamp (+80 microU/ml), (2) epinephrine infusion (50 ng.kg-1.min-1) plus somatostatin with basal replacement of insulin and glucagon, (3) combined epinephrine (50 ng.kg-1.min-1) plus insulin (+80 microU/ml) infusion, and (4) epinephrine and somatostatin as in study 2 plus basal amino acid replacement. Studies were performed with a prime-continuous infusion of (1-14C)leucine and indirect calorimetry. Our results indicate that (1) hyperinsulinemia causes a generalized decrease in plasma amino acid concentrations, including leucine; (2) the reduction in plasma leucine concentration is primarily due to an inhibition of endogenous leucine flux; nonoxidative leucine disposal decreases after insulin infusion; (3) epinephrine, without change in plasma insulin concentration, reduces plasma amino acid levels; (4) combined epinephrine-insulin infusion causes a greater decrease in plasma amino levels than observed with either hormone alone; this is because of a greater inhibition of endogenous leucine flux; and (5) when basal amino acid concentrations are maintained constant with a balanced amino acid infusion, epinephrine inhibits the endogenous leucine flux. In conclusion, the present results do not provide support for the concept that epinephrine is a catabolic hormone with respect to amino acid-protein metabolism. In contrast, epinephrine markedly inhibits insulin-mediated glucose metabolism.

  18. High-mix insulins

    Directory of Open Access Journals (Sweden)

    Sanjay Kalra

    2015-01-01

    Full Text Available Premix insulins are commonly used insulin preparations, which are available in varying ratios of different molecules. These drugs contain one short- or rapid-acting, and one intermediate- or long-acting insulin. High-mix insulins are mixtures of insulins that contain 50% or more than 50% of short-acting insulin. This review describes the clinical pharmacology of high-mix insulins, including data from randomized controlled trials. It suggests various ways, in which high-mix insulin can be used, including once daily, twice daily, thrice daily, hetero-mix, and reverse regimes. The authors provide a rational framework to help diabetes care professionals, identify indications for pragmatic high-mix use.

  19. Suicide by Insulin?

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_165701.html Suicide by Insulin? Self-harm and suicidal behavior may ... higher rates of depression, the researchers explained. And suicide or suicide attempts using insulin or other diabetes ...

  20. Improving Glycemic Control and Insulin Ordering Efficiency for Hospitalized Patients With Diabetes Through Carbohydrate Counting.

    Science.gov (United States)

    Pearson, Kristina K; Reiland, Sarah A; Meara, John G O; Brown, Julie K; Fedraw, Leslie A; Mapes, David L

    2016-01-01

    Glycemic control in hospitalized patients is challenging but important for optimal outcomes. Insulin dosing through carbohydrate counting may address patient, provider, and institutional factors that complicate hospital glycemic management. On two surgical units at a tertiary care teaching hospital, we pilot tested postmeal insulin dosing based on carbohydrate counting (plus basal insulin) rather than the current process of ordering scheduled premeal insulin without knowledge of the patient's consumption. Analysis assessed hyperglycemia, hypoglycemia, insulin orders, and nurse and provider satisfaction and confidence. On general surgery, mean glucose level improved from 188 to 137 mg/dl (p satisfaction improved for providers (preintervention, 60%; postintervention, 100%), general surgery nurses (preintervention, 72%; postintervention, 100%), and cardiovascular surgery nurses (preintervention, 69%; postintervention, 84%). Confidence in insulin dose accuracy improved for providers (preintervention, 50%; postintervention, 100%), general surgery nurses (preintervention, 59%; postintervention, 100%), and cardiovascular surgery nurses (preintervention, 48%; postintervention, 84%). Carbohydrate counting is effective and efficient and improved staff satisfaction and confidence in hospital mealtime insulin dosing.

  1. Antihyperglycemic effect of glargine injection in rat model of type 1 diabetes%甘精胰岛素注射液对1型糖尿病模型大鼠的降血糖作用

    Institute of Scientific and Technical Information of China (English)

    宋紫辉; 张慧霞; 项宗尚; 范明源; 蔡永明; 张宗鹏

    2016-01-01

    目的 采用链脲佐菌素(streptozotocin,STZ)诱导的大鼠1型糖尿病(insulin-dependent diabetes mellitus,IDDM)模型,评价甘精胰岛素注射液的降血糖作用.方法 健康雄性SD大鼠,单次尾静脉注射2%(质量分数)STZ 58 mg/kg制备IDDM模型,采用随机数字表法将造模成功的动物(禁食血糖≥16.7 mmol/L)分为供试品甘精胰岛素注射液(glargine injection)低、中和高3个剂量组、参照药来得时(Lantus)中剂量组和模型对照组,每组15只;同时设正常对照组.各组动物分别皮下注射甘精胰岛素、来得时或等体积的溶媒,每天给药,连续给药9周.每周定时检测大鼠随机血糖、体质量、摄食量和饮水量;给药结束后,采用全自动生化分析仪检测血清中尿素氮(blood urea nitrogen,BUN)、肌酐(creatinine,Cr)、总胆固醇(total cholesterol,TC)和三酰甘油(triglyceride,TG);采用比色法定量检测糖化血红蛋白(glycosylated hemoglobin,GHb).结果 与模型对照组相比,甘精胰岛素注射液各剂量组大鼠:①体质量增加、摄食量减少;②给药后lh血糖开始降低,2h降至最低,8h基本恢复到给药前,且具有剂量依赖性;③GHb不同程度地降低,具有明显的剂量-效应关系;④血清中BUN和TG降低.结论 在4~8 IU/kg剂量范围内,每日皮下注射2次甘精胰岛素注射液,明显改善IDDM模型大鼠的高血糖症状,其作用效果与来得时相当;连续给药9周后,模型大鼠的血清BUN、TG和GHb显著降低,提示其具有保护肾功能、调节血脂的作用,并能减少糖尿病合并症的发生.

  2. Effectiveness evaluation of the mobile health patients management mode on treatment compliance and glycemic control for type 2 diabetes patients using basal insulin treatment for 12 weeks%移动医疗患者管理模式对2型糖尿病基础胰岛素治疗依从性及血糖控制12周的效果评估

    Institute of Scientific and Technical Information of China (English)

    郭晓蕙; 楼青青; 吕纺; 覃丹丹; 纪立农; 陈莉明; 陈丽; 姬秋和; 孙子林; 李强; 邢秋玲; 赵芳; 袁丽

    2016-01-01

    Objective To assess the effectiveness of a novel mobile health patient management system involving doctors, nurses, and patients (" TRIO" mode) on glycemic control and self-monitoring of blood glucose (SMBG) compliance among the type 2 diabetes mellitus ( T2DM) patients using basal insulin standardization treatment in China. Methods From April 2014 to April 2015, 416 hospitals in 110 cities of 30 provinces, municipalities, and autonomous regions across China were selected to participate in the program. A Online-to-Offline ( O2O) integrated mobile health patients management system with mobile terminals for the doctors, nurses, and patients was applied in the program for patient education, follow-up, and data collection. For all the newly recruited patients, the baseline information was collected and a first-day patient education program were provided by a designated nurse. In the 12-week follow-up period, data of basal insulin doses and fasting plasma glucose ( FPG) values were collected from the patients by text messages or tracking phone call by the nurse. The patients also received timely standardized patients health education and glycemic control guidance by participating in the " patient education forum" and " doctors' hotline" in order to help them achieve the glycemic control goals. Results A total of 102 524 patients using basal insulin treatment were eligible and enrolled in the program. 64 420 patients completed the 12 weeks follow-up and provided at least one FPG value at all five follow-ups. In total, 62. 6% (40 334 / 64 420) of the patients reached the FPG control target(FPG≤7. 0 mmol/ L) at the end of follow-up period. The weekly average FPG for patients with complete SMBG data decreased from 10. 58 mmol/ L to 6. 91 mmol/ L while the FPG control rates increased from 13. 4% to 69. 2% . The weekly average FPG for the patients provided incomplete SMBG data decreased from 10. 54 mmol/ L to 7. 13 mmol/ L while the FPG control rates increased from 13. 6

  3. The Basal Ganglia and Motor Control

    OpenAIRE

    Groenewegen, Henk J.

    2003-01-01

    This paper briefly reviews the functional anatomy of the basal ganglia and their relationships with the thalamocortical system. The basal ganglia, including the striatum, pallidum, subthalamic nucleus, and substantia nigra, are involved in a number of parallel, functionally segregated cortical-subcortical circuits. These circuits support a wide range of sensorimotor, cognitive and emotional-motivational brain functions. A main role of the basal ganglia is the learning and selection of the mos...

  4. Functional Neuroanatomy of the Basal Ganglia

    OpenAIRE

    Lanciego, José L.; Luquin, Natasha; Obeso, José A.

    2012-01-01

    The “basal ganglia” refers to a group of subcortical nuclei responsible primarily for motor control, as well as other roles such as motor learning, executive functions and behaviors, and emotions. Proposed more than two decades ago, the classical basal ganglia model shows how information flows through the basal ganglia back to the cortex through two pathways with opposing effects for the proper execution of movement. Although much of the model has remained, the model has been modified and amp...

  5. Glycosphingolipids and insulin resistance

    NARCIS (Netherlands)

    M. Langeveld; J.F.M.G. Aerts

    2009-01-01

    Obesity is associated with an increased risk for insulin resistance, a state characterized by impaired responsiveness of liver, muscle and adipose tissue to insulin. One class of lipids involved in the development of insulin resistance are the (glyco)sphingolipids. Ceramide, the most simple sphingol

  6. The Results of Open-Label, Multicenter, Non-Randomized Study on the Efficacy and Safety of Insulins: Insuman Basal®, Insuman Comb 25®, Insuman Rapid® in Patients with Diabetes Mellitus Type 2 Who Underwent Basic Training in Diabetes Schools (SPIRIT

    Directory of Open Access Journals (Sweden)

    A.S. Larin

    2015-06-01

    Conclusions. Treatment with Insuman® insulins of patients with DM-2, who were not compensated while taking OADs, was associated with improved glycemic control without an increase in the incidence of severe hypoglycemia. There was no statistically significant increase in the effectiveness of therapy in patients, who have successfully completed a training program at diabetes school, compared with evaluation of overall efficiency. The state of young studied population of patients with inadequate control at baseline, and those who had developed cardiovascular complications associated with DM, improved in most cases in terms of glycemic control, and, at that, episodes of severe hypoglycemia were not detected. This may be due to the positive influence of training in diabetes school.

  7. Insulin and the Lung

    DEFF Research Database (Denmark)

    Singh, Suchita; Prakash, Y S; Linneberg, Allan

    2013-01-01

    , molecular understanding is necessary. Insulin resistance is a strong, independent risk factor for asthma development, but it is unknown whether a direct effect of insulin on the lung is involved. This review summarizes current knowledge regarding the effect of insulin on cellular components of the lung...... and highlights the molecular consequences of insulin-related metabolic signaling cascades that could adversely affect lung structure and function. Examples include airway smooth muscle proliferation and contractility and regulatory signaling networks that are associated with asthma. These aspects of insulin...

  8. Plasma adiponectin concentration is associated with skeletal muscle insulin receptor tyrosine phosphorylation, and low plasma concentration precedes a decrease in whole-body insulin sensitivity in humans.

    Science.gov (United States)

    Stefan, Norbert; Vozarova, Barbora; Funahashi, Tohru; Matsuzawa, Yuji; Weyer, Christian; Lindsay, Robert S; Youngren, Jack F; Havel, Peter J; Pratley, Richard E; Bogardus, Clifton; Tataranni, P Antonio

    2002-06-01

    Adiponectin, the most abundant adipose-specific protein, has been found to be negatively associated with degree of adiposity and positively associated with insulin sensitivity in Pima Indians and other populations. Moreover, adiponectin administration to rodents has been shown to increase insulin-induced tyrosine phosphorylation of the insulin receptor (IR) and also increase whole-body insulin sensitivity. To further characterize the relationship between plasma adiponectin concentration and insulin sensitivity in humans, we examined 1) the cross-sectional association between plasma adiponectin concentration and skeletal muscle IR tyrosine phosphorylation and 2) the prospective effect of plasma adiponectin concentration at baseline on change in insulin sensitivity. Fasting plasma adiponectin concentration, body composition (hydrodensitometry or dual energy X-ray absorptiometry), insulin sensitivity (insulin-stimulated glucose disposal, hyperinsulinemic clamp), and glucose tolerance (75-g oral glucose tolerance test) were measured in 55 Pima Indians (47 men and 8 women, aged 31 +/- 8 years, body fat 29 +/- 8% [mean +/- SD]; 50 with normal glucose tolerance, 3 with impaired glucose tolerance, and 2 with diabetes). Group 1 (19 subjects) underwent skeletal muscle biopsies for the measurement of basal and insulin-stimulated tyrosine phosphorylation of the IR (stimulated by 100 nmol/l insulin). The fold increase after insulin stimulation was calculated as the ratio between maximal and basal phosphorylation. Group 2 (38 subjects) had follow-up measurements of insulin-stimulated glucose disposal. Cross-sectionally, plasma adiponectin concentration was positively associated with insulin-stimulated glucose disposal (r = 0.58, P < 0.0001) and negatively associated with percent body fat (r = -0.62, P < 0.0001) in the whole group. In group 1 plasma adiponectin was negatively associated with the basal (r = -0.65, P = 0.003) and positively associated with the fold increase in IR

  9. Metformin and insulin receptors

    Energy Technology Data Exchange (ETDEWEB)

    Vigneri, R.; Gullo, D.; Pezzino, V.

    The authors evaluated the effect of metformin (N,N-dimethylbiguanide), a biguanide known to be less toxic than phenformin, on insulin binding to its receptors, both in vitro and in vivo. Specific /sup 125/I-insulin binding to cultured IM-9 human lymphocytes and MCF-7 human breast cancer cells was determined after preincubation with metformin. Specific /sup 125/I-insulin binding to circulating monocytes was also evaluated in six controls, eight obese subjects, and six obese type II diabetic patients before and after a short-term treatment with metformin. Plasma insulin levels and blood glucose were also measured on both occasions. Metformin significantly increased insulin binding in vitro to both IM-9 lymphocytes and MCF-7 cells; the maximum increment was 47.1% and 38.0%, respectively. Metformin treatment significantly increased insulin binding in vivo to monocytes of obese subjects and diabetic patients. Scatchard analysis indicated that the increased binding was mainly due to an increase in receptor capacity. Insulin binding to monocytes of normal controls was unchanged after metformin as were insulin levels in all groups; blood glucose was significantly reduced after metformin only in diabetic patients. These data indicate that metformin increases insulin binding to its receptors in vitro and in vivo. The effect in vivo is observed in obese subjects and in obese type II diabetic patients, paralleling the clinical effectiveness of this antidiabetic agent, and is not due to receptor regulation by circulating insulin, since no variation in insulin levels was recorded.

  10. Studies of insulin resistance in congenital generalized lipodystrophy

    DEFF Research Database (Denmark)

    Søvik, O; Vestergaard, H; Trygstad, O

    1996-01-01

    suppressed lipid oxidation in the controls. It is concluded that patients with congenital generalized lipodystrophy may present severe insulin resistance with regard to hepatic glucose production as well as muscle glycogen synthesis and lipid oxidation. The results suggest a postreceptor defect in the action......, immunoreactive protein and mRNA levels. The patients had fasting hyperinsulinaemia, and the rate of total glucose disposal was severely impaired, primarily due to a decreased non-oxidative glucose metabolism. In the patient studied with muscle biopsy, the expected activation of glycogen synthase by insulin did...... not occur. In both patients there was severely increased hepatic glucose output in the basal state, suggesting a failure of insulin to suppress hepatic gluconeogenesis. During insulin infusion a substantially elevated rate of lipid oxidation remained in the patients, in contrast to the almost completely...

  11. [Insulin, peptide C and glucide tolerance in chronic alcoholic hepatopathies].

    Science.gov (United States)

    Nardoni, A; Marchetti, E; Sabattini, E; Geatti, O; Nador, G

    1984-09-08

    Changes in blood glucose and insulin metabolism, both under basal conditions and after glucose and glucagon stimulus, were studied in 95 patients with chronic alcoholic hepatopathy. Peptide C was also determined in 19 patients. A high incidence of islet-cell insufficiency was noted. Stress is laid on the multiplicity of the pathogenetic mechanisms responsible for blood glucose and insulin changes during chronic alcoholic hepatopathy, particularly liver cell damage, hyperglucagonaemia, organic and/or functional islet-cell insufficiency, and peripheral insulin resistance. It is felt that the last two of these are of major importance, whereas liver cell damage is of secondary significance, at any rate as far as glucose and insulin turnover is concerned.

  12. Análogos de insulina: relevancia clínica y perspectivas futuras The clinical relevance of insulin analogues and future perspectives

    Directory of Open Access Journals (Sweden)

    Jhon Jairo BejaranoRoncancio

    2012-12-01

    Full Text Available Desde la década de los noventa han sido diseñados análogos de insulina para el manejo de pacientes diabéticos usando técnicas de ADN recombinante. Las modificaciones de la molécula original de insulina humana les confieren una rápida, ultrarrápida y prolongada acción. Entre las insulinas ultra rápidas están la Aspártica, la Lispro y la Glulisina y entre las de acción prolongada están la Glargina y la Detemir. También se encuentran mezcladas con insulina humana NPH en diferentes proporciones. Aunque existen diferentes tipos de algoritmos terapéuticos, la insulinización sigue siendo una terapia artesanal basada en la experiencia del especialista tratante. La introducción de los análogos de insulina hace más factible el empleo de bolos correctores o dosis extra de insulina para reducir las hipoglicemias puntuales en cualquier momento del día y facilitar el manejo de los carbohidratos en la dieta.Insulin analogues have been engineered through recombinant DNA techniques for managing diabetic patients since the 1990s; modifications to the original human insulin molecule have made them rapid, ultrarapid and prolonged acting. Aspart, lispro and glulisine are ultrafast insulins and glargine and detemir are longacting ones. Such insulins may be premixed in formulations combining neutral protamine Hagedorn (NPH with regular human insulin (70%/30%. Different types of therapeutic algorithms are available nowadays but insulinisation remains a crafted therapy based on the treating specialist's experience. The introduction of insulin analogues enables using correction boluses or extra doses of insulin to reduce hypoglycaemia at any time of the day and facilitates handling carbohydrates in a particular patient's diet.

  13. Critical appraisal of the safety and efficacy of insulin detemir in glycemic control and cardiovascular risk management in diabetics

    Directory of Open Access Journals (Sweden)

    Jean-Pierre Le Floch

    2010-06-01

    Full Text Available Jean-Pierre Le FlochDepartment of Diabetology, Medical Clinic, Villecresnes, FranceAbstract: Insulin detemir is an analog of human insulin designed to provide a long duration of basal insulin action. This is achieved by protracted absorption from the injection depot, which results in part from increased self-association of insulin detemir molecules and in part from reversible albumin binding. Subsequent albumin binding in the circulation is thought to buffer changes in the effects at target tissues that could otherwise arise from variability in absorption rate. In consequence, insulin detemir has shown a less variable pharmacodynamic profile than alternative basal insulins; this manifests as more consistent temporal glucose reduction profiles in repeat-clamp studies. In clinical trials, insulin detemir has been characterized by consistent risk reductions in hypoglycemia, as well as reduced weight gain in comparison with other basal insulins. Given some recent associations that have been made in prospective and epidemiologic studies between glucose variability and/or hypoglycemia and increased cardiovascular risk, and the long-known association between excess weight and cardiovascular risk, it is possible that the clinical profile of insulin detemir may carry prognostic value with regard to cardiovascular safety, although this is yet to be substantiated. There have also been some concerns raised recently over the use of insulin analogs and cancer risk, but available clinical data and the receptor interaction profile of insulin detemir suggest no excess in risk in comparison with human insulin therapy. Optimal approaches for the clinical use of insulin detemir have been emerging through an increasing clinical study base, and the analog is becoming established as a potentially valuable therapy option.Keywords: insulin detemir, type 2 diabetes, glucose variability, hypoglycemia, weight gain

  14. Early recognition of basal cell naevus syndrome

    NARCIS (Netherlands)

    Veenstra-Knol, HE; Scheewe, JH; van der Vlist, GJ; van Doorn, ME; Ausems, MGEM

    2005-01-01

    The basal cell naevus syndrome is an autosomal dominant syndrome characterised by major manifestations such as basal cell carcinomas, jaw cysts, palmar or plantar pits, and intracranial calcifications. Early recognition is important in order to reduce morbidity due to cutaneous and cerebral malignan

  15. Nevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome).

    Science.gov (United States)

    Bresler, Scott C; Padwa, Bonnie L; Granter, Scott R

    2016-06-01

    Nevoid basal cell carcinoma syndrome, or basal cell nevus syndrome (Gorlin syndrome), is a rare autosomal dominantly inherited disorder that is characterized by development of basal cell carcinomas from a young age. Other distinguishing clinical features are seen in a majority of patients, and include keratocystic odontogenic tumors (formerly odontogenic keratocysts) as well as dyskeratotic palmar and plantar pitting. A range of skeletal and other developmental abnormalities are also often seen. The disorder is caused by defects in hedgehog signaling which result in constitutive pathway activity and tumor cell proliferation. As sporadic basal cell carcinomas also commonly harbor hedgehog pathway aberrations, therapeutic agents targeting key signaling constituents have been developed and tested against advanced sporadically occurring tumors or syndromic disease, leading in 2013 to FDA approval of the first hedgehog pathway-targeted small molecule, vismodegib. The elucidation of the molecular pathogenesis of nevoid basal cell carcinoma syndrome has resulted in further understanding of the most common human malignancy.

  16. Current trend in drug delivery considerations for subcutaneous insulin depots to treat diabetes.

    Science.gov (United States)

    P V, Jayakrishnapillai; Nair, Shantikumar V; Kamalasanan, Kaladhar

    2017-05-01

    Diabetes mellitus (DM) is a metabolic disorder due to irregularities in glucose metabolism, as a result of insulin disregulation. Chronic DM (Type 1) is treated by daily insulin injections by subcutaneous route. Daily injections cause serious patient non-compliance and medication non-adherence. Insulin Depots (ID) are parenteral formulations designed to release the insulin over a specified period of time, to control the plasma blood glucose level for intended duration. Physiologically, pancreas produces and secretes insulin in basal and pulsatile mode into the blood. Delivery systems mimicking basal release profiles are known as open-loop systems and current marketed products are open-loop systems. Future trend in open-loop systems is to reduce the number of injections per week by enhancing duration of action, by modifying the depot properties. The next generation technologies are closed-loop systems that mimic the pulsatile mode of delivery by pancreas. In closed-loop systems insulin will be released in response to plasma glucose. This review focuses on future trend in open-loop systems; by understanding (a) the secretion of insulin from pancreas, (b) the insulin regulation normal and in DM, (c) insulin depots and (d) the recent progress in open-loop depot technology particularly with respect to nanosystems. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Effects of a combination butaphosphan and cyanocobalamin product and insulin on ketosis resolution and milk production.

    Science.gov (United States)

    Gordon, J L; Duffield, T F; Herdt, T H; Kelton, D F; Neuder, L; LeBlanc, S J

    2017-04-01

    The objective of this study was to determine the effects of butaphosphan-cyanocobalamin (B+C), glargine insulin, and propylene glycol on resolution of ketosis and average daily milk yield after treatment. Cows from 16 herds in Ontario, Canada, and 1 herd in Michigan were tested at weekly intervals between 3 and 16 DIM. Ketosis was defined as blood β-hydroxybutyrate (BHB) ≥1.2 mmol/L. All ketotic cows were given a baseline treatment of 3 d of 300 g of propylene glycol orally. Animals were then randomly assigned to treatment with 3 doses of either 25 mL of B+C or 25 mL of saline placebo and 1 dose of either 2 mL (200 IU) of glargine insulin or 2 mL of saline placebo in a 2 × 2 factorial arrangement. Outcomes of interest on all farms were ketosis cure (blood BHB <1.2 mmol/L 1 wk postenrollment), maintenance of ketosis cure (blood BHB <1.2 mmol/L 1 and 2 wk postenrollment), and blood BHB concentrations at 1 and 2 wk postenrollment. Milk weights were collected daily in 1 large freestall herd. Repeated measures ANOVA was used to evaluate blood BHB concentrations 2 wk after treatment and milk production for 30 d after treatment. Poisson regression was used to examine the effect of treatment on cure and maintenance of cure. Due to a regulatory delay causing temporary unavailability of B+C in Canada, data were analyzed in 2 sets of models: one for insulin and the corresponding placebo (n = 620) and one for the full trial (n = 380). Animals with blood glucose concentrations ≤2.2 mmol/L at the time of ketosis diagnosis were 2.1 times more likely (95% CI = 1.2 to 3.7) to be cured if treated with B+C. Animals in lactation 3 or higher that had blood glucose concentrations <2.2 mmol/L at enrollment produced 4.2 kg/d (95% CI = 1.4 to 7.1) more milk if treated with insulin versus placebo and 2.8 kg/d (95% CI = 0.9 to 4.7) more milk if treated with B+C versus placebo. Animals in lactation 3 or higher with blood glucose ≥2.2 mmol/L that were treated with insulin produced 2

  18. Clinical evidence and mechanistic basis for vildagliptin's effect in combination with insulin

    Directory of Open Access Journals (Sweden)

    Schweizer A

    2013-02-01

    Full Text Available Anja Schweizer,1 James E Foley,2 Wolfgang Kothny,2 Bo Ahrén31Novartis Pharma AG, Basel, Switzerland; 2Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 3Department of Clinical Sciences, Lund University, Lund, SwedenAbstract: Due to the progressive nature of type 2 diabetes, many patients need insulin as add-on to oral antidiabetic drugs (OADs in order to maintain adequate glycemic control. Insulin therapy primarily targets elevated fasting glycemia but is less effective to reduce postprandial hyperglycemia. In addition, the risk of hypoglycemia limits its effectiveness and there is a concern of weight gain. These drawbacks may be overcome by combining insulin with incretin-based therapies as these increase glucose sensitivity of both the α- and β-cells, resulting in improved postprandial glycemia without the hypoglycemia and weight gain associated with increasing the dose of insulin. The dipeptidyl peptidase-IV (DPP-4 inhibitor vildagliptin has also been shown to protect from hypoglycemia by enhancing glucagon counterregulation. The effectiveness of combining vildagliptin with insulin was demonstrated in three different studies in which vildagliptin decreased A1C levels when added to insulin therapy without increasing hypoglycemia. This was established with and without concomitant metformin therapy. Furthermore, the effectiveness of vildagliptin appears to be greater when insulin is used as a basal regimen as opposed to being used to reduce postprandial hyperglycemia, since improvement in insulin secretion likely plays a minor role when relatively high doses of insulin are administered before meals. This article reviews the clinical experience with the combination of vildagliptin and insulin and discusses the mechanistic basis for the beneficial effects of the combination. The data support the use of vildagliptin in combination with insulin in general and, in line with emerging clinical practice, suggest that treating patients with

  19. Estradiol Binds to Insulin and Insulin Receptor Decreasing Insulin Binding in vitro

    Directory of Open Access Journals (Sweden)

    Robert eRoot-Bernstein

    2014-07-01

    Full Text Available Rationale: Insulin resistance associated with hyperestrogenemias occurs in gestational diabetes mellitus, polycystic ovary syndrome, ovarian hyperstimulation syndrome, estrogen therapies, metabolic syndrome and obesity. The mechanism by which insulin and estrogen interact is unknown. We hypothesize that estrogen binds directly to insulin and the insulin receptor producing insulin resistance.Objectives: To determine the binding constants of steroid hormones to insulin, the insulin receptor, and insulin-like peptides derived from the insulin receptor; and to investigate the effect of estrogens on the binding of insulin to its receptor.Methods: Ultraviolet spectroscopy, capillary electrophoresis and NMR demonstrated estrogen binding to insulin and its receptor. Horse-radish peroxidase-linked insulin was used in an ELISA-like procedure to measure the effect of estradiol on binding of insulin to its receptor. Measurements: Binding constants for estrogens to insulin and the insulin receptor were determined by concentration-dependent spectral shifts. The effect of estradiol on insulin-HRP binding to its receptor was determined by shifts in the insulin binding curve. Main Results: Estradiol bound to insulin with a Kd of 12 x 10-9 M and to the insulin receptor with a Kd of 24 x 10-9 M, while other hormones had significantly less affinity. 200 nM estradiol shifted the binding curve of insulin to its receptor 0.8 log units to the right. Conclusions: Estradiol concentrations in many hyperestrogenemic syndromes are sufficient to interfere with insulin binding to its receptor producing significant insulin resistance.

  20. Biosimilar Insulins: Basic Considerations.

    Science.gov (United States)

    Heinemann, Lutz; Hompesch, Marcus

    2014-01-01

    Until now most of the insulin used in developed countries has been manufactured and distributed by a small number of multinational companies. Beyond the established insulin manufacturers, a number of new players have developed insulin manufacturing capacities based on modern biotechnological methods. Because the patents for many of the approved insulin formulations have expired or are going to expire soon, these not yet established companies are increasingly interested in seeking market approval for their insulin products as biosimilar insulins (BI) in highly regulated markets like the EU and the United States. Differences in the manufacturing process (none of the insulin manufacturing procedures are 100% identical) can lead to insulins that to some extent may differ from the originator insulin. The key questions are if subtle differences in the structure of the insulins, purity, and so on are clinically relevant and may result in different biological effects. The aim of this article is to introduce and discuss basic aspects that may be of relevance with regard to BI. © 2014 Diabetes Technology Society.

  1. Clinical Glargine Joint Compound Hyperthyroidism Tablet to Treat Diabetes With Hyperthyroidism%甘精胰岛素联合复方甲亢片治疗糖尿病伴甲亢的临床观察

    Institute of Scientific and Technical Information of China (English)

    杨永杰

    2015-01-01

    Objective Joint analysis glargine Fufangjiakang tablets to treat diabetes with hyperthyroidism clinical results. MethodsRetrospective analysis of December 2012 December -2014 hospital 89 cases of diabetic patients with hyperthyroidism data, divided into two groups according to the different treatment options, the control group of 43 regular routine treatment, research group of 46 routine glargine and Fufangjiakang tablets treatment, blood sugar and complications were observed.ResultsResearch on blood glucose levels were significantly lower than the control group, and the complication rate 6.5% 27.9% lower than the control group, the difference was statistically signiifcant (P<0.05).Conclusion Glargine and compound hyperthyroidism tablet to treat diabetes with hyperthyroidism effect is signiifcant.%目的:分析甘精胰岛素联合复方甲亢片治疗糖尿病伴甲亢的临床效果。方法回顾分析2012年12月~2014年12月本院89例糖尿病伴甲亢患者资料,按不同治疗方案分为两组,对照组43例行常规治疗,研究组46例行甘精胰岛素与复方甲亢片治疗,观察两组血糖及并发症。结果研究组血糖水平均低于对照组,且并发症发生率(6.5%)低于对照组(27.9%),差异具统计学意义(P<0.05)。结论甘精胰岛素与复方甲亢片治疗糖尿病伴甲亢的效果显著。

  2. Metastatic Basal Cell Carcinoma Accompanying Gorlin Syndrome

    Directory of Open Access Journals (Sweden)

    Yeliz Bilir

    2014-01-01

    Full Text Available Gorlin-Goltz syndrome or basal cell nevus syndrome is an autosomal dominant syndrome characterized by skeletal anomalies, numerous cysts observed in the jaw, and multiple basal cell carcinoma of the skin, which may be accompanied by falx cerebri calcification. Basal cell carcinoma is the most commonly skin tumor with slow clinical course and low metastatic potential. Its concomitance with Gorlin syndrome, resulting from a mutation in a tumor suppressor gene, may substantially change morbidity and mortality. A 66-year-old male patient with a history of recurrent basal cell carcinoma was presented with exophthalmus in the left eye and the lesions localized in the left lateral orbita and left zygomatic area. His physical examination revealed hearing loss, gapped teeth, highly arched palate, and frontal prominence. Left orbital mass, cystic masses at frontal and ethmoidal sinuses, and multiple pulmonary nodules were detected at CT scans. Basal cell carcinoma was diagnosed from biopsy of ethmoid sinus. Based on the clinical and typical radiological characteristics (falx cerebri calcification, bifid costa, and odontogenic cysts, the patient was diagnosed with metastatic skin basal cell carcinoma accompanied by Gorlin syndrome. Our case is a basal cell carcinoma with aggressive course accompanying a rarely seen syndrome.

  3. Metastatic Basal cell carcinoma accompanying gorlin syndrome.

    Science.gov (United States)

    Bilir, Yeliz; Gokce, Erkan; Ozturk, Banu; Deresoy, Faik Alev; Yuksekkaya, Ruken; Yaman, Emel

    2014-01-01

    Gorlin-Goltz syndrome or basal cell nevus syndrome is an autosomal dominant syndrome characterized by skeletal anomalies, numerous cysts observed in the jaw, and multiple basal cell carcinoma of the skin, which may be accompanied by falx cerebri calcification. Basal cell carcinoma is the most commonly skin tumor with slow clinical course and low metastatic potential. Its concomitance with Gorlin syndrome, resulting from a mutation in a tumor suppressor gene, may substantially change morbidity and mortality. A 66-year-old male patient with a history of recurrent basal cell carcinoma was presented with exophthalmus in the left eye and the lesions localized in the left lateral orbita and left zygomatic area. His physical examination revealed hearing loss, gapped teeth, highly arched palate, and frontal prominence. Left orbital mass, cystic masses at frontal and ethmoidal sinuses, and multiple pulmonary nodules were detected at CT scans. Basal cell carcinoma was diagnosed from biopsy of ethmoid sinus. Based on the clinical and typical radiological characteristics (falx cerebri calcification, bifid costa, and odontogenic cysts), the patient was diagnosed with metastatic skin basal cell carcinoma accompanied by Gorlin syndrome. Our case is a basal cell carcinoma with aggressive course accompanying a rarely seen syndrome.

  4. Glucose supply and insulin demand dynamics of antidiabetic agents.

    Science.gov (United States)

    Monte, Scott V; Schentag, Jerome J; Adelman, Martin H; Paladino, Joseph A

    2010-03-01

    For microvascular outcomes, there is compelling historical and contemporary evidence for intensive blood glucose reduction in patients with either type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM). There is also strong evidence to support macrovascular benefit with intensive blood glucose reduction in T1DM. Similar evidence remains elusive for T2DM. Because cardiovascular outcome trials utilizing conventional algorithms to attain intensive blood glucose reduction have not demonstrated superiority to less aggressive blood glucose reduction (Action to Control Cardiovascular Risk in Diabetes; Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation; and Veterans Affairs Diabetes Trial), it should be considered that the means by which the blood glucose is reduced may be as important as the actual blood glucose. By identifying quantitative differences between antidiabetic agents on carbohydrate exposure (CE), hepatic glucose uptake (HGU), hepatic gluconeogenesis (GNG), insulin resistance (IR), peripheral glucose uptake (PGU), and peripheral insulin exposure (PIE), we created a pharmacokinetic/pharmacodynamic model to characterize the effect of the agents on the glucose supply and insulin demand dynamic. Glucose supply was defined as the cumulative percentage decrease in CE, increase in HGU, decrease in GNG, and decrease in IR, while insulin demand was defined as the cumulative percentage increase in PIE and PGU. With the glucose supply and insulin demand effects of each antidiabetic agent summated, the glucose supply (numerator) was divided by the insulin demand (denominator) to create a value representative of the glucose supply and insulin demand dynamic (SD ratio). Alpha-glucosidase inhibitors (1.25), metformin (2.20), and thiazolidinediones (TZDs; 1.25-1.32) demonstrate a greater effect on glucose supply (SD ratio >1), while secretagogues (0.69-0.81), basal insulins (0.77-0.79), and bolus insulins (0

  5. Biosimilar Insulin and Costs

    Science.gov (United States)

    Heinemann, Lutz

    2015-01-01

    The costs for insulin treatment are high, and the steady increase in the number of patients with diabetes on insulin presents a true challenge to health care systems. Therefore, all measures to lower these costs are welcomed by patients, physicians, and health care providers. The market introduction of biosimilar insulins presents an option to lower treatment costs as biosimilars are usually offered at a lower price than the originator product. However, the assumption that a drastic reduction in insulin prices will take place, as was observed with many generic drugs, is most probably not realistic. As the first biosimilar insulin has now been approved in the EU, this commentary discusses a number of aspects that are relevant when it comes to the potential cost reduction we will see with the use of biosimilar insulins. PMID:26350722

  6. Insulin sensitivity and albuminuria

    DEFF Research Database (Denmark)

    Pilz, Stefan; Rutters, Femke; Nijpels, Giel

    2014-01-01

    OBJECTIVE: Accumulating evidence suggests an association between insulin sensitivity and albuminuria, which, even in the normal range, is a risk factor for cardiovascular diseases. We evaluated whether insulin sensitivity is associated with albuminuria in healthy subjects. RESEARCH DESIGN...... AND METHODS: We investigated 1,415 healthy, nondiabetic participants (mean age 43.9 ± 8.3 years; 54.3% women) from the RISC (Relationship between Insulin Sensitivity and Cardiovascular Disease) study, of whom 852 participated in a follow-up examination after 3 years. At baseline, insulin sensitivity...... was assessed by hyperinsulinemic-euglycemic clamps, expressed as the M/I value. Oral glucose tolerance test-based insulin sensitivity (OGIS), homeostasis model assessment of insulin resistance (HOMA-IR), and urinary albumin-to-creatinine ratio (UACR) were determined at baseline and follow-up. RESULTS...

  7. Classifying insulin regimens

    DEFF Research Database (Denmark)

    Neu, A; Lange, K; Barrett, T

    2015-01-01

    Modern insulin regimens for the treatment of type 1 diabetes are highly individualized. The concept of an individually tailored medicine accounts for a broad variety of different insulin regimens applied. Despite clear recommendations for insulin management in children and adolescents with type 1...... diabetes there is little distinctiveness about concepts and the nomenclature is confusing. Even among experts similar terms are used for different strategies. The aim of our review--based on the experiences of the Hvidoere Study Group (HSG)--is to propose comprehensive definitions for current insulin...... variety of insulin regimens applied in each center, respectively. Furthermore, the understanding of insulin regimens has been persistently different between the centers since more than 20 yr. Not even the terms 'conventional' and 'intensified therapy' were used consistently among all members. Besides...

  8. Diabetes, insulin and exercise

    DEFF Research Database (Denmark)

    Richter, Erik; Galbo, H

    1986-01-01

    The metabolic and hormonal adaptations to single exercise sessions and to exercise training in normal man and in patients with insulin-dependent as well as non-insulin-dependent diabetes mellitus are reviewed. In insulin-dependent (type I) diabetes good metabolic control is best obtained...... by a regular pattern of life which will lead to a fairly constant demand for insulin from day to day. Exercise is by nature a perturbation that makes treatment of diabetes difficult: Muscle contractions per se tend to decrease the plasma glucose concentration whereas the exercise-induced response of the so......-called counter-regulatory hormones tend to increase plasma glucose by increasing hepatic glucose production and adipose tissue lipolysis. If the pre-exercise plasma insulin level is high, hypoglycaemia may develop during exercise whereas hyperglycaemia and ketosis may develop if pre-exercise plasma insulin...

  9. Insulin aspart pharmacokinetics

    DEFF Research Database (Denmark)

    Rasmussen, Christian Hove; Roge, Rikke Meldgaard; Ma, Zhulin

    2014-01-01

    Background: Insulin aspart (IAsp) is used by many diabetics as a meal-time insulin to control postprandial glucose levels. As is the case with many other insulin types, the pharmacokinetics (PK), and consequently the pharmacodynamics (PD), is associated with clinical variability, both between...... to investigate and quantify the properties of the subcutaneous depot. Data from Brange et al. (1990) are used to determine the effects of insulin chemistry in subcutis on the absorption rate. Intravenous (i.v.) bolus and infusion PK data for human insulin are used to understand and quantify the systemic...... distribution and elimination (Porksen et al., 1997; Sjostrand et al., 2002). PK and PD profiles for type 1 diabetics from Chen et al. (2005) are analyzed to demonstrate the effects of IAsp antibodies in terms of bound and unbound insulin. PK profiles from Thorisdottir et al. (2009) and Ma et al. (2012b...

  10. Neglected Giant Scalp Basal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Anne Kristine Larsen, MD

    2014-03-01

    Full Text Available Summary: Rarely, basal cell carcinoma grows to a giant size, invading the underlying deep tissue and complicating the treatment and reconstruction modalities. A giant basal cell carcinoma on the scalp is in some cases treated with a combination of surgery and radiation therapy, resulting in local control, a satisfactory long-term cosmetic and functional result. We present a case with a neglected basal cell scalp carcinoma, treated with wide excision and postoperative radiotherapy, reconstructed with a free latissimus dorsi flap. The cosmetic result is acceptable and there is no sign of recurrence 1 year postoperatively.

  11. Neglected giant scalp Basal cell carcinoma

    DEFF Research Database (Denmark)

    Larsen, Anne Kristine; El-Charnoubi, Waseem-Asim Ghulam; Gehl, Julie;

    2014-01-01

    SUMMARY: Rarely, basal cell carcinoma grows to a giant size, invading the underlying deep tissue and complicating the treatment and reconstruction modalities. A giant basal cell carcinoma on the scalp is in some cases treated with a combination of surgery and radiation therapy, resulting in local...... control, a satisfactory long-term cosmetic and functional result. We present a case with a neglected basal cell scalp carcinoma, treated with wide excision and postoperative radiotherapy, reconstructed with a free latissimus dorsi flap. The cosmetic result is acceptable and there is no sign of recurrence...

  12. Thermodynamic Significance of Human Basal Metabolism

    Institute of Scientific and Technical Information of China (English)

    WangCuncheng

    1993-01-01

    The human basal state,a non-equilibrium steady state,is analysed in this paper in the light of the First and Second Laws of Thermodynamics whereby the thermodynamic significance of the basal metabolic rate and its distinction to the dissipation function and exergy loss are identified.The analysis demonstrates the correct expression of the effects of the blood flow on the heat balance in a human-body bio-heat model and the relationship between the basal metabolic rate and the blood perfusion.

  13. Biphasic Insulin Analogues in Type 2 Diabetes: Expert Panel Recommendations

    Directory of Open Access Journals (Sweden)

    Sema Akalın

    2011-09-01

    Full Text Available Recently, the prevalence of type 2 diabetes has reached pandemic levels all over the world, and the problem is still growing. Type 2 diabetes is a progressive disease, in which insulin resistance and decrease in beta cell function accompany obesity. Early disorder, which ensues in clinical progression of the disease, is the defect of early phase insulin secretion. Patients have already lost approximately half of their beta cell reserve at the time of diagnosis. Aims of type 2 diabetes treatment are to eliminate hyperglycemia caused by insufficient insulin secretion and/or insulin resistance, to slow down beta cell destruction/depletion, to improve concomitant metabolic problems and to prevent complications. In treatment algorithms, insulin is evaluated as a replacement therapy at the following stage after life style changes (medical nutrition therapy, exercise and oral anti-diabetic drugs (OADs options. Since beta cell depletion is present at initial stages of the disease, it transforms insulin therapy into an earlier approach in treatment stages. Premixed insulin forms are one of the proposed treatment options in patients with hyperglycemia that is not controlled by OADs. These types of insulins are developed to meet both basal and postprandial insulin requirements of patients. Currently, premixed human insulin forms are replaced by analogue insulin forms, which can mimic the physiological secretion in more acceptable manner. Biphasic analogue insulin is one of the readily available pre-mixed analogue insulin forms, an example of this, Biphasic Insulin aspart 30 which is the one of the premixed analoge insulin forms, contains 30% insulin aspart and 70% protaminated insulin aspart. Consensus recommending the individualized approach in insulin therapy implies that physicians should have more detailed information about the use of different insulin forms. Although a global consensus report about initiation, titration and intensification and the use

  14. Insulin pump treatment in children and adolescents with type 1 diabetes.

    Science.gov (United States)

    Hofer, S; Meraner, D; Koehle, J

    2012-08-01

    Within children and adolescents with type 1 diabetes insulin pump treatment is of increasing interest. Frequency of insulin pump therapy shows a rapid and steep increase in toddlers and young children. Insulin pumps allow a close to physiologic insulin delivery due to basal rates programmed over 24 hours with circadian rhythms taken into account. Furthermore, another advantage of technical devices as insulin pumps is the application of extremely small amounts of insulin, as needed in very young children, with the possibility of titration of infusion rates down to 0.01E/h. Dawn Phenomenon and hypoglycemic events are main indications for insulin pump treatment in children and adolescents. A significant reduction of severe hypoglycemia, especially nocturnal hypoglycemia was shown, whereas a reduction of HbA1c and an improvement of metabolic control has been reported in short term and in some but not all long term studies. Ketoacidosis rate did not increase in insulin pump therapy. Complications due to continuous subcutaneous insulin infusion, like local infections and dermatological changes are frequent but were not associated with glycemic control and did not lead to discontinuation of insulin pump treatment. Pump discontinuation rate in general is low, varying from 1% in very young children up to 6% in pubertal adolescent girls. Insulin pump treatment was shown to be safe and efficient and the simplicity of handling the devices as well as an improvement of quality of life may explain the rapid increase of pump treatment in young children and adolescents with type 1 diabetes.

  15. Analog insulin detemir for patients with type 1 and type 2 diabetes: a review

    Directory of Open Access Journals (Sweden)

    Gregory E Peterson

    2009-05-01

    Full Text Available Gregory E PetersonDepartment of Internal Medicine, Des Moines University, USAObjective: To review insulin detemir for clinical use to better manage patients with type 1 and type 2 diabetes.Methods: A MEDLINE search, in English, from June 30, 2006 to December 1, 2008, using the terms “insulin analogs,” “insulin detemir” and “long-acting insulin analog.”Results: Insulin detemir improves glycemic control, based on HbA1C reduction and fasting glucose levels, without increasing the risk of hypoglycemia and weight gain. Insulin detemir has lower glycemic variability, with less intra-subject variability in blood glucose levels in patients with type 1 and type 2 diabetes, without increasing the risk of hypoglycemia. When added to oral anti-diabetes agents (OADs in type 2 diabetes, insulin detemir demonstrates superiority to other basal insulin options.Conclusion: Insulin detemir appears to provide better glycemic control with a lower risk of hypoglycemia and less weight gain in the treatment of patients with type 1 and type 2 diabetes.Keywords: type 1 diabetes, type 2 diabetes, insulin analogs, insulin detemir

  16. History of insulin

    Directory of Open Access Journals (Sweden)

    Celeste C. Quianzon

    2012-07-01

    Full Text Available The advancement of diabetes treatment has gone from crude extracts of insulin and accidental discovery of sulfa-like drugs in antibiotics to the development of drugs based on improved understanding of the pathophysiology of diabetes mellitus. This article will review the history of the discovery and development of insulin. A companion focusing on non-insulin diabetes agents will follow in the next issue of JCHIMP.

  17. Landmarks in insulin research

    Directory of Open Access Journals (Sweden)

    Michael eLawrence

    2011-11-01

    Full Text Available Ever since the discovery of insulin and its role in the regulation of glucose uptake and utilization, there has been great interest in insulin, its structure and the way in which it interacts with its receptor and effects signal transduction. As the 90th anniversary of the discovery of insulin approaches, it is timely to provide an overview of the landmark discoveries relating to the structure and function of this remarkable molecule and its receptor.

  18. Landmarks in Insulin Research

    OpenAIRE

    Ward, Colin W.; Lawrence, Michael C.

    2011-01-01

    Ever since the discovery of insulin and its role in the regulation of glucose uptake and utilization, there has been great interest in insulin, its structure and the way in which it interacts with its receptor and effects signal transduction. As the 90th anniversary of the discovery of insulin approaches, it is timely to provide an overview of the landmark discoveries relating to the structure and function of this remarkable molecule and its receptor.

  19. Fibroblast growth factor 21 improves insulin sensitivity and synergizes with insulin in human adipose stem cell-derived (hASC adipocytes.

    Directory of Open Access Journals (Sweden)

    Darwin V Lee

    Full Text Available Fibroblast growth factor 21 (FGF21 has evolved as a major metabolic regulator, the pharmacological administration of which causes weight loss, insulin sensitivity and glucose control in rodents and humans. To understand the molecular mechanisms by which FGF21 exerts its metabolic effects, we developed a human in vitro model of adipocytes to examine crosstalk between FGF21 and insulin signaling. Human adipose stem cell-derived (hASC adipocytes were acutely treated with FGF21 alone, insulin alone, or in combination. Insulin signaling under these conditions was assessed by measuring tyrosine phosphorylation of insulin receptor (InsR, insulin receptor substrate-1 (IRS-1, and serine 473 phosphorylation of Akt, followed by a functional assay using 14C-2-deoxyglucose [14C]-2DG to measure glucose uptake in these cells. FGF21 alone caused a modest increase of glucose uptake, but treatment with FGF21 in combination with insulin had a synergistic effect on glucose uptake in these cells. The presence of FGF21 also effectively lowered the insulin concentration required to achieve the same level of glucose uptake compared to the absence of FGF21 by 10-fold. This acute effect of FGF21 on insulin signaling was not due to IR, IGF-1R, or IRS-1 activation. Moreover, we observed a substantial increase in basal S473-Akt phosphorylation by FGF21 alone, in contrast to the minimal shift in basal glucose uptake. Taken together, our data demonstrate that acute co-treatment of hASC-adipocytes with FGF21 and insulin can result in a synergistic improvement in glucose uptake. These effects were shown to occur at or downstream of Akt, or separate from the canonical insulin signaling pathway.

  20. Insulin Initiation in Insulin-Naïve Korean Type 2 Diabetic Patients Inadequately Controlled on Oral Antidiabetic Drugs in Real-World Practice: The Modality of Insulin Treatment Evaluation Study

    Directory of Open Access Journals (Sweden)

    Sang Soo Kim

    2015-12-01

    Full Text Available BackgroundThe Modality of Insulin Treatment Evaluation (MOTIV study was performed to provide real-world data concerning insulin initiation in Korean type 2 diabetes mellitus (T2DM patients with inadequate glycemic control with oral hypoglycemic agents (OHAs.MethodsThis multicenter, non-interventional, prospective, observational study enrolled T2DM patients with inadequate glycemic control (glycosylated hemoglobin [HbA1c] ≥7.0% who had been on OHAs for ≥3 months and were already decided to introduce basal insulin by their physician prior to the start of the study. All treatment decisions were at the physician's discretion to reflect real-world practice.ResultsA total of 9,196 patients were enrolled, and 8,636 patients were included in the analysis (mean duration of diabetes, 8.9 years; mean HbA1c, 9.2%. Basal insulin plus one OHA was the most frequently (51.0% used regimen. After 6 months of basal insulin treatment, HbA1c decreased to 7.4% and 44.5% of patients reached HbA1c <7%. Body weight increased from 65.2 kg to 65.5 kg, which was not significant. Meanwhile, there was significant increase in the mean daily insulin dose from 16.9 IU at baseline to 24.5 IU at month 6 (P<0.001. Overall, 17.6% of patients experienced at least one hypoglycemic event.ConclusionIn a real-world setting, the initiation of basal insulin is an effective and well-tolerated treatment option in Korean patients with T2DM who are failing to meet targets with OHA therapy.

  1. Deletion of insulin-degrading enzyme elicits antipodal, age-dependent effects on glucose and insulin tolerance.

    Directory of Open Access Journals (Sweden)

    Samer O Abdul-Hay

    Full Text Available BACKGROUND: Insulin-degrading enzyme (IDE is widely recognized as the principal protease responsible for the clearance and inactivation of insulin, but its role in glycemic control in vivo is poorly understood. We present here the first longitudinal characterization, to our knowledge, of glucose regulation in mice with pancellular deletion of the IDE gene (IDE-KO mice. METHODOLOGY: IDE-KO mice and wild-type (WT littermates were characterized at 2, 4, and 6 months of age in terms of body weight, basal glucose and insulin levels, and insulin and glucose tolerance. Consistent with a functional role for IDE in insulin clearance, fasting serum insulin levels in IDE-KO mice were found to be ∼3-fold higher than those in wild-type (WT controls at all ages examined. In agreement with previous observations, 6-mo-old IDE-KO mice exhibited a severe diabetic phenotype characterized by increased body weight and pronounced glucose and insulin intolerance. In marked contrast, 2-mo-old IDE-KO mice exhibited multiple signs of improved glycemic control, including lower fasting glucose levels, lower body mass, and modestly enhanced insulin and glucose tolerance relative to WT controls. Biochemically, the emergence of the diabetic phenotype in IDE-KO mice correlated with age-dependent reductions in insulin receptor (IR levels in muscle, adipose, and liver tissue. Primary adipocytes harvested from 6-mo-old IDE-KO mice also showed functional impairments in insulin-stimulated glucose uptake. CONCLUSIONS: Our results indicate that the diabetic phenotype in IDE-KO mice is not a primary consequence of IDE deficiency, but is instead an emergent compensatory response to chronic hyperinsulinemia resulting from complete deletion of IDE in all tissues throughout life. Significantly, our findings provide new evidence to support the idea that partial and/or transient inhibition of IDE may constitute a valid approach to the treatment of diabetes.

  2. Effects of Premix and Basic Insulin on Blood Glucose and Insular B Cell Function of Patients with Type 2 Diabe-tes Mellitus%预混胰岛素和基础胰岛素对2型糖尿病患者血糖及胰岛B细胞功能的影响

    Institute of Scientific and Technical Information of China (English)

    戴强; 李红; 钱科威; 李亚娟

    2016-01-01

    Objective To investigate the effects of different types of insulin on blood glucose,gyrated hemoglo-bin(HBA1c)and insular B cell function of patients with primary type 2 diabetes mellitus(T2DM). Methods A total of 90 patients with primary T2DM admitted during June 2013 and Augest 2014 were randomly divided into Novolin 30R group(n = 30),NovoMix 30 group(n = 30)and Glargine group(n = 30). Glargine group was injected with Glargine at the same time every day,and Novolin 30R group was injected with Premixed Insulin( Novolin 30R)at 30 min before breakfast and dinner,and NovoMix 30 group was injected with Insulin Aspart(NovoMix 30 right)right at breakfast and dinner. The body mass index(BMI),levels of HBA1c,triglyceride(TG),total cholesterol(TC)and low-density lipo-protein cholesterol(LDL-C)were tested,and levels of blood glucose and insulin were detected at 0,30,60,120 and 180 min before treatment using oral glucose tolerance test(OGTT)-insulin releasing test,and the insulin resistance index (HOMA-IR)and insular B cell function were evaluated using steady state model for all patients. The above indexes were detected and calculated again after 12 weeks of treatment,and the differences were compared among the 3 groups. Re-sults Compared with those before treatment in the same group,levels of blood glucose,HBA1c and HOMA-IR were sig-nificantly decreased,while the insulin secretion index( HOMA-B)levels were significantly increased in Novolin 30R, NovoMix 30 and Glargine groups after 12 weeks of treatment( P ﹤ 0. 05). BMI and fasting plasma glucose levels in Glargine group were significantly lower than those in the other two groups(P ﹤ 0. 05). The blood glucose level at 60 min before treatment in NovoMix 30 group was significantly lower than those in the other two groups(P ﹤ 0. 01). HOMA-B level in Novolin 30R group was significantly lower than those in the other two groups(P ﹤ 0. 05). The incidence rate of hypoglycemia insulin in Glargine group was significantly

  3. Insulin as a weapon.

    Science.gov (United States)

    Robinson, Samuel D; Safavi-Hemami, Helena

    2016-12-01

    The discovery of insulin and its use for the treatment of diabetes is undoubtedly one of the true successes of modern medicine. Injectable insulin would prove the first effective treatment for a previously incurable and usually fatal disease. Soon after however, the powerful effects of insulin overdose would be reported, and subsequently exploited for dubious medical and sometimes nefarious purposes. In this article we describe the discovery that certain venomous marine snails of the genus Conus also exploit the powerful effects of insulin overdose, employing it as a weapon for prey capture. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Insulin, cognition, and dementia

    Science.gov (United States)

    Cholerton, Brenna; Baker, Laura D.; Craft, Suzanne

    2015-01-01

    Cognitive disorders of aging represent a serious threat to the social and economic welfare of current society. It is now widely recognized that pathology related to such conditions, particularly Alzheimer’s disease, likely begins years or decades prior to the onset of clinical dementia symptoms. This revelation has led researchers to consider candidate mechanisms precipitating the cascade of neuropathological events that eventually lead to clinical Alzheimer’s disease. Insulin, a hormone with potent effects in the brain, has recently received a great deal of attention for its potential beneficial and protective role in cognitive function. Insulin resistance, which refers to the reduced sensitivity of target tissues to the favorable effects of insulin, is related to multiple chronic conditions known to impact cognition and increase dementia risk. With insulin resistance-associated conditions reaching epidemic proportions, the prevalence of Alzheimer’s disease and other cognitive disorders will continue to rise exponentially. Fortunately, these chronic insulin-related conditions are amenable to pharmacological intervention. As a result, novel therapeutic strategies that focus on increasing insulin sensitivity in the brain may be an important target for protecting or treating cognitive decline. The following review will highlight our current understanding of the role of insulin in brain, potential mechanisms underlying the link between insulin resistance and dementia, and current experimental therapeutic strategies aimed at improving cognitive function via modifying the brain’s insulin sensitivity. PMID:24070815

  5. Effect of bromocriptine-QR therapy on glycemic control in subjects with type 2 diabetes mellitus whose dysglycemia is inadequately controlled on insulin.

    Science.gov (United States)

    Chamarthi, Bindu; Cincotta, Anthony H

    2017-05-01

    The concurrent use of an insulin sensitizer in type 2 diabetes mellitus (T2DM) patients with inadequate glycemic control on basal-bolus insulin may help improve glycemic control while limiting further insulin requirement. Bromocriptine-QR (B-QR), a quick release, sympatholytic, dopamine D2 receptor agonist therapy for T2DM, is a postprandial insulin sensitizer. This study evaluated the effect of B-QR on dysglycemia in T2DM subjects with suboptimal glycemic control on basal-bolus insulin plus metformin. The effect of once-daily morning administration of B-QR on dysglycemia was evaluated in 60 T2DM subjects derived from the Cycloset Safety Trial, with HbA1c >7% on basal-bolus insulin plus metformin at baseline, randomized to B-QR (N = 44) versus placebo (N = 16) and completed 12 weeks of study drug treatment. The analyses also included a subset of subjects on high-dose insulin (total daily insulin dose (TDID) ≥70 units; N = 36: 27 B-QR; 9 placebo). Subjects were well matched at baseline. After 12 weeks of B-QR treatment, mean % HbA1c decreased by -0.73% relative to baseline (p insulin subset, B-QR therapy resulted in % HbA1c reductions of -0.95 and -1.49 relative to baseline (p insulin subset). B-QR therapy improves glycemic control in T2DM subjects whose glycemia is poorly controlled on metformin plus basal-bolus insulin, including individuals on high-dose basal-bolus insulin. This glycemic impact occurred without significant change in FPG, suggesting a postprandial glucose lowering mechanism of action. Cycloset Safety Trial registration: ClinicalTrials.gov Identifier: NCT00377676.

  6. Conventional insulin vs insulin infusion therapy in acute coronary syndrome diabetic patients

    Institute of Scientific and Technical Information of China (English)

    Caterina; Arvia; Valeria; Siciliano; Kyriazoula; Chatzianagnostou; Gillian; Laws; Alfredo; Quinones; Galvan; Chiara; Mammini; Sergio; Berti; Sabrina; Molinaro; Giorgio; Iervasi

    2014-01-01

    AIM:To evaluate the impact on glucose variability(GLUCV)of an nurse-implemented insulin infusion protocol when compared with a conventional insulin treatment during the day-to-day clinical activity.METHODS:We enrolled 44 type 2 diabetic patients(n=32 males;n=12 females)with acute coronary syndrome(ACS)and randomy assigned to standard a subcutaneous insulin treatment(n=23)or a nurse-implemented continuous intravenous insulin infusion protocol(n=21).We utilized some parameters of GLUCV representing well-known surrogate markers of prognosis,i.e.,glucose standard deviation(SD),the mean dailyδglucose(mean of daily difference between maximum and minimum glucose),and the coefficient of variation(CV)of glucose,expressed as percent glucose(SD)/glu-cose(mean).RESULTS:At the admission,first fasting blood glucose,pharmacological treatments(insulin and/or anti-diabetic drugs)prior to entering the study and basal glycated hemoglobin(HbA1c)were observed in the two groups treated with subcutaneous or intravenous insulin infusion,respectively.When compared with patients submitted to standard therapy,insulin-infused patients showed both increased first 24-h(median 6.9 mmol/L vs 5.7mmol/L P<0.045)and overall hospitalizationδglucose(median 10.9 mmol/L vs 9.3 mmol/L,P<0.028),with a tendency to a significant increase in first 24-h glycaemic CV(23.1%vs 19.6%,P<0.053).Severe hypoglycaemia was rare(14.3%),and it was observed only in 3 patients receiving insulin infusion therapy.HbA1c values measured during hospitalization and 3 mo after discharge did not differ in the two groups of treatment.CONCLUSION:Our pilot data suggest that no real benefit in terms of GLUCV is observed when routinely managing blood glucose by insulin infusion therapy in type 2 diabetic ACS hospitalized patients in respect to conventional insulin treatment

  7. Insulin-like effect of pinitol.

    Science.gov (United States)

    Bates, S H; Jones, R B; Bailey, C J

    2000-08-01

    D-pinitol (3-O-methyl-chiroinositol), an active principle of the traditional antidiabetic plant Bougainvillea spectabilis, is claimed to exert insulin-like effects. This study investigates the effect of D-pinitol on glucose homeostasis in animal models of diabetes, and on glucose transport by cultured muscle cells. Plasma glucose concentrations were measured in normal, obese-diabetic (ob/ob) and streptozotocin (STZ)-diabetic mice after oral (p.o.) and intraperitoneal (i.p.) administration of D-pinitol. Glucose transport was measured in L6 rat muscle cells by 2-deoxyglucose (2DG) uptake. In STZ-diabetic mice, 100 mg kg(-1) p.o. D-pinitol acutely decreased the hyperglycaemia (by 22% at 6 h). A similar decrease in plasma glucose (by 21%) was observed after 100 mg kg(-1) i.p. D-pinitol. Insulin concentrations and the rate of insulin-induced (1 unit kg(-1) actrapid i.p.) glucose disappearance were not altered by 100 mg kg(-1) p.o. D-pinitol. Chronic administration of D-pinitol (100 mg kg(-1) i.p. twice daily for 11 days) to STZ-diabetic mice maintained a reduction in plasma glucose concentrations from about 14 to 10 mmol l(-1). In normal non-diabetic and severely insulin resistant ob/ob mice, 100 mg kg(-1) p.o. D-pinitol did not significantly affect plasma glucose or insulin during acute studies. Incubation of L6 muscle cells with D-pinitol (10(-3) M) increased basal 2DG uptake by 41% after 10 min and by 34% after 4 h. The effect of D-pinitol was inhibited by the phosphatidylinositol 3-kinase inhibitor LY294002. D-pinitol did not increase insulin-stimulated 2DG uptake by L6 cells. The data support the view that D-pinitol can exert an insulin-like effect to improve glycaemic control in hypoinsulinaemic STZ-diabetic mice. D-pinitol may act via a post-receptor pathway of insulin action affecting glucose uptake.

  8. Apico-basal polarity complex and cancer

    Indian Academy of Sciences (India)

    Mohammed Khursheed; Murali Dharan Bashyam

    2014-03-01

    Apico-basal polarity is a cardinal molecular feature of adult eukaryotic epithelial cells and appears to be involved in several key cellular processes including polarized cell migration and maintenance of tissue architecture. Epithelial cell polarity is maintained by three well-conserved polarity complexes, namely, PAR, Crumbs and SCRIB. The location and interaction between the components of these complexes defines distinct structural domains of epithelial cells. Establishment and maintenance of apico-basal polarity is regulated through various conserved cell signalling pathways including TGF, Integrin and WNT signalling. Loss of cell polarity is a hallmark for carcinoma, and its underlying molecular mechanism is beginning to emerge from studies on model organisms and cancer cell lines. Moreover, deregulated expression of apico-basal polarity complex components has been reported in human tumours. In this review, we provide an overview of the apico-basal polarity complexes and their regulation, their role in cell migration, and finally their involvement in carcinogenesis.

  9. Automatic basal slice detection for cardiac analysis

    Science.gov (United States)

    Paknezhad, Mahsa; Marchesseau, Stephanie; Brown, Michael S.

    2016-03-01

    Identification of the basal slice in cardiac imaging is a key step to measuring the ejection fraction (EF) of the left ventricle (LV). Despite research on cardiac segmentation, basal slice identification is routinely performed manually. Manual identification, however, has been shown to have high inter-observer variability, with a variation of the EF by up to 8%. Therefore, an automatic way of identifying the basal slice is still required. Prior published methods operate by automatically tracking the mitral valve points from the long-axis view of the LV. These approaches assumed that the basal slice is the first short-axis slice below the mitral valve. However, guidelines published in 2013 by the society for cardiovascular magnetic resonance indicate that the basal slice is the uppermost short-axis slice with more than 50% myocardium surrounding the blood cavity. Consequently, these existing methods are at times identifying the incorrect short-axis slice. Correct identification of the basal slice under these guidelines is challenging due to the poor image quality and blood movement during image acquisition. This paper proposes an automatic tool that focuses on the two-chamber slice to find the basal slice. To this end, an active shape model is trained to automatically segment the two-chamber view for 51 samples using the leave-one-out strategy. The basal slice was detected using temporal binary profiles created for each short-axis slice from the segmented two-chamber slice. From the 51 successfully tested samples, 92% and 84% of detection results were accurate at the end-systolic and the end-diastolic phases of the cardiac cycle, respectively.

  10. Biomarkers for Basal-like Breast Cancer

    OpenAIRE

    Choo, Jennifer R.; Torsten O. Nielsen

    2010-01-01

    Initially recognized through microarray-based gene expression profiling, basal-like breast cancer, for which we lack effective targeted therapies, is an aggressive form of carcinoma with a predilection for younger women. With some success, immunohistochemical studies have attempted to reproduce the expression profile classification of breast cancer through identification of subtype-specific biomarkers. This review aims to present an in depth summary and analysis of the current status of basal...

  11. Connexin-36 contributes to control function of insulin-producing cells.

    Science.gov (United States)

    Le Gurun, Sabine; Martin, David; Formenton, Andrea; Maechler, Pierre; Caille, Dorothee; Waeber, Gérard; Meda, Paolo; Haefliger, Jacques-Antoine

    2003-09-26

    Connexin-36 (Cx36) is a gap junction protein expressed by the insulin-producing beta-cells. We investigated the contribution of this protein in normal beta-cell function by using a viral gene transfer approach to alter Cx36 content in the insulin-producing line of INS-1E cells and rat pancreatic islets. Transcripts for Cx43, Cx45, and Cx36 were detected by reverse transcriptase-PCR in freshly isolated pancreatic islets, whereas only a transcript for Cx36 was detected in INS-1E cells. After infection with a sense viral vector, which induced de novo Cx36 expression in the Cx-defective HeLa cells we used to control the transgene expression, Western blot, immunofluorescence, and freeze-fracture analysis showed a large increase of Cx36 within INS-1E cell membranes. In contrast, after infection with an antisense vector, Cx36 content was decreased by 80%. Glucose-induced insulin release and insulin content were decreased, whether infected INS-1E cells expressed Cx36 levels that were largely higher or lower than those observed in wild-type control cells. In both cases, basal insulin secretion was unaffected. Comparable observations on basal secretion and insulin content were made in freshly isolated rat pancreatic islets. The data indicate that large changes in Cx36 alter insulin content and, at least in INS-1E cells, also affect glucose-induced insulin release.

  12. Pregnancy and undernutrition alter glucose metabolic responses to insulin in sheep.

    Science.gov (United States)

    Petterson, J A; Dunshea, F R; Ehrhardt, R A; Bell, A W

    1993-07-01

    Nonpregnant and late-pregnant ditocous ewes were fed either to maintain zero energy balance in maternal tissues (fed) or at 50% of this level (underfed) for several weeks. Whole-body kinetics of glucose metabolism were measured under basal conditions, and the hyperinsulinemic, euglycemic clamp technique was used to define insulin-dose response profiles for several indices of whole-body glucose utilization, and for endogenous glucose production. Pregnancy increased and undernutrition decreased basal glucose entry rate (GER), glucose metabolic clearance rate (GMCR) and insulin-independent glucose utilization (IIGU). The consistent increment in IIGU of pregnant over nonpregnant ewes was comparable to previous estimates of uterine glucose uptake. Pregnancy resulted in higher plasma concentration for 50% maximal responses (ED50) to insulin of GER, GMCR, steady-state glucose infusion rate (SSGIR) to maintain euglycemia and insulin-dependent glucose utilization (IDGU). These changes were especially large in underfed pregnant ewes. Effects on the maximal response to insulin of these variables (Rmax) were relatively small (GMCR, IDGU) or nonsignificant (GER, SSGIR). Maximum insulin-induced suppression of endogenous glucose production was significantly lower due to undernutrition; neither Rmax nor ED50 for this response was affected by pregnancy. Insulin resistance in late-pregnant ewes is primarily due to decreased insulin sensitivity in (presumably) peripheral tissues, implying an alteration of receptor function or of early postreceptor signal transduction.

  13. Insulin signal transduction in skeletal muscle from glucose-intolerant relatives of type 2 diabetic patients [corrected

    DEFF Research Database (Denmark)

    Storgaard, H; Song, X M; Jensen, C B;

    2001-01-01

    To determine whether defects in the insulin signal transduction cascade are present in skeletal muscle from prediabetic individuals, we excised biopsies from eight glucose-intolerant male first-degree relatives of patients with type 2 diabetes (IGT relatives) and nine matched control subjects...... in signal transduction noted for IRS-1 and PI 3-kinase may be attributed to elevated basal phosphorylation/activity of these parameters, because absolute phosphorylation/activity under insulin-stimulated conditions was similar between IGT relatives and control subjects. Insulin increased Akt serine......, the elevated basal activity of these signaling intermediates and the lack of a strong correlation between these parameters to glucose metabolism suggests that other defects of insulin signal transduction and/or downstream components of glucose metabolism may play a greater role in the development of insulin...

  14. Palmitate stimulates glucose transport in rat adipocytes by a mechanism involving translocation of the insulin sensitive glucose transporter (GLUT4)

    Science.gov (United States)

    Hardy, R. W.; Ladenson, J. H.; Henriksen, E. J.; Holloszy, J. O.; McDonald, J. M.

    1991-01-01

    In rat adipocytes, palmitate: a) increases basal 2-deoxyglucose transport 129 +/- 27% (p less than 0.02), b) decreases the insulin sensitive glucose transporter (GLUT4) in low density microsomes and increases GLUT4 in plasma membranes and c) increases the activity of the insulin receptor tyrosine kinase. Palmitate-stimulated glucose transport is not additive with the effect of insulin and is not inhibited by the protein kinase C inhibitors staurosporine and sphingosine. In rat muscle, palmitate: a) does not affect basal glucose transport in either the soleus or epitrochlearis and b) inhibits insulin-stimulated glucose transport by 28% (p less than 0.005) in soleus but not in epitrochlearis muscle. These studies demonstrate a potentially important differential role for fatty acids in the regulation of glucose transport in different insulin target tissues.

  15. Cafeteria diet-induced insulin resistance is not associated with decreased insulin signaling or AMPK activity and is alleviated by physical training in rats

    DEFF Research Database (Denmark)

    Brandt, Nina; De Bock, Katrien; Richter, Erik

    2010-01-01

    Excess energy intake via a palatable low-fat diet (cafeteria diet) is known to induce obesity and glucose intolerance in rats. However, the molecular mechanisms behind this adaptation are not known, and it is also not known whether exercise training can reverse it. Male Wistar rats were assigned...... was counteracted by training. In the perfused hindlimb, insulin-stimulated glucose transport in red gastrocnemius muscle was completely abolished in CAF and rescued by exercise training. Apart from a tendency toward an approximately 20% reduction in both basal and insulin-stimulated Akt Ser(473) phosphorylation (P......) among the groups. In conclusion, surplus energy intake of a palatable but low-fat cafeteria diet resulted in obesity and insulin resistance that was rescued by exercise training. Interestingly, insulin resistance was not accompanied by major defects in the insulin-signaling cascade or in altered AMPK...

  16. Closer to ideal insulin action: ultra fast acting insulins.

    Science.gov (United States)

    Cengiz, E

    2013-09-01

    Mimicking physiologic insulin action has been the main goal of diabetes therapy since the discovery of insulin. The evolution of insulin therapy from animal insulin to recombinant insulin analogs has improved diabetes treatment significantly over the course of years. Nevertheless, the rapid-acting insulin analog pharmacokinetics and pharmacodynamics are still far from replicating physiologic insulin action resulting in poorly controlled after meal blood glucose levels. The slow action of insulin analogs has been a stumbling block for the development artificial pancreas systems that require a fast responding insulin to blood glucose changes. This review explains the rationale behind the undeniable need for ultra-fast acting insulins from a clinical and research perspective and summarizes ongoing and future projects to accelerate insulin action.

  17. Endocrine determinants of changes in insulin sensitivity and insulin secretion during a weight cycle in healthy men.

    Directory of Open Access Journals (Sweden)

    Judith Karschin

    Full Text Available Changes in insulin sensitivity (IS and insulin secretion occur with perturbations in energy balance and glycemic load (GL of the diet that may precede the development of insulin resistance and hyperinsulinemia. Determinants of changes in IS and insulin secretion with weight cycling in non-obese healthy subjects remain unclear.In a 6wk controlled 2-stage randomized dietary intervention 32 healthy men (26±4y, BMI: 24±2kg/m2 followed 1wk of overfeeding (OF, 3wks of caloric restriction (CR containing either 50% or 65% carbohydrate (CHO and 2wks of refeeding (RF with the same amount of CHO but either low or high glycaemic index at ±50% energy requirement. Measures of IS (basal: HOMA-index, postprandial: Matsuda-ISI, insulin secretion (early: Stumvoll-index, total: tAUC-insulin/tAUC-glucose and potential endocrine determinants (ghrelin, leptin, adiponectin, thyroid hormone levels, 24h-urinary catecholamine excretion were assessed.IS improved and insulin secretion decreased due to CR and normalized upon RF. Weight loss-induced improvements in basal and postprandial IS were associated with decreases in leptin and increases in ghrelin levels, respectively (r = 0.36 and r = 0.62, p<0.05. Weight regain-induced decrease in postprandial IS correlated with increases in adiponectin, fT3, TSH, GL of the diet and a decrease in ghrelin levels (r-values between -0.40 and 0.83, p<0.05 whereas increases in early and total insulin secretion were associated with a decrease in leptin/adiponectin-ratio (r = -0.52 and r = -0.46, p<0.05 and a decrease in fT4 (r = -0.38, p<0.05 for total insulin secretion only. After controlling for GL associations between RF-induced decrease in postprandial IS and increases in fT3 and TSH levels were no longer significant.Weight cycling induced changes in IS and insulin secretion were associated with changes in all measured hormones, except for catecholamine excretion. While leptin, adiponectin and ghrelin seem to be the major

  18. Effect of insulin and metformin on methylation and glycolipid metabolism of peroxisome proliferator-activated receptor γcoactivator-1A of rat offspring with gestational diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    Ai-Qin Song; Li-Rong Sun; Yan-Xia Zhao; Yan-Hua Gao; Lei Chen

    2016-01-01

    Objective: To discuss the effect of insulin and metformin on amethylation and glycolipid metabolism of peroxisome proliferator-activated receptor γ coactivator-1A (PPARGC1A) ofrat offspring with gestational diabetes mellitus (GDM). Methods: A total of 45 pregnant rats received the intraperitoneal injection of streptozotocin to establish the pregnant rat model of GDM. A total of 21 pregnant rats with GDM were randomly divided into three groups, with 7 rats in each group, namely the insulin group, metformin group and control group. Rats in the insulin group received the abdominal subcutaneous injection of 1 mL/kg recombinant insulin glargine at 18: 00 every day. Rats in the metformin group received the intragastric infusion of metformin hydrochloride at 18: 00 every day, with the first dose of 300 mg/kg. The doses of two groups were adjusted every 3 d to maintain the blood glucose level at 2.65-7.62 mmol/L. Rats in the control group received the intragastric infusion of 1 mL normal saline at 18:00 every day. After the natural delivery of pregnant rats, 10 offspring rats were randomly selected from each group. At birth, 4 wk and 8 wk after the birth of offspring rats, the weight of offspring rats was measured. The blood glucose level of offspring rats was measured at 4 wk and 8 wk, while the level of serum insulin, triglyceride and leptin was measured at 8 wk.Results: The weight of offspring rats at birth in the insulin group and metformin group was significantly lower than the one in the control group (P0.05). The fasting blood glucose and random blood glucose in the insulin group and metformin group at 4 wk and 8 wk were all significantly lower than ones in the control group (P0.05). The expression of PPARGC1A mRNA in the insulin group and metformin group was significantly higher and the methylation level of PPARGC1A was significantly lower than the one in the control group (P0.05). Insulin and leptin at 8 wk in the insulin group and metformin group were

  19. Do perceptions of insulin pump usability impact attitudes toward insulin pump therapy? A pilot study of individuals with type 1 and insulin-treated type 2 diabetes.

    Science.gov (United States)

    Chamberlain, James J; Gilgen, Emily

    2015-01-01

    We assessed the impact of perceived insulin pump usability on attitudes toward insulin pump therapy in diabetic individuals currently treated with multiple daily insulin injections (MDI). This comparative, single-arm study recruited 28 adults with type 1 (n = 16) and insulin-treated type 2 diabetes (n = 12) to evaluate 2 current insulin pumps: Medtronic Revel 723 (Pump 1), Asante Snap Insulin Pump (Pump 2). Participants were randomized 1:1 to 1 of 2 assessment sequences: Pump 1 followed by Pump 2; and Pump 2 followed by Pump 1. Structured observational protocols were utilized to assess participants' ability and time required to learn/perform common tasks associated with pump setup/use. Participants used a modified version of the System Usability Scale (SUS) and investigator-developed questionnaires to rate pump usability and task difficulty; pre-post questionnaires assessed changes in attitudes toward insulin pump therapy. All participants completed the study. SUS scores showed Pump 2 to be more usable than Pump 1 on all usability attributes. Participants rated Pump 2 more positively than Pump 1, overall mean SUS scores of 5.7 versus 4.1 respectively, F(1, 52) = 32.7, P Pump 2 last, 5.3 versus 4.4 for Pump 1 last, F(1, 52) = 10.8, P Pump 2 was preferred for all tasks: manual bolus (86%), bolus calculation (71%), managing basal rates (93%), interpreting alarms (96%), transferring settings (100%), changing insulin and infusion sets (93%), all P pump usability can directly impact acceptance and use of features that may benefit those who wear them. Simpler pump devices that decrease perceptions of complexity may encourage broader use of this technology. © 2014 Diabetes Technology Society.

  20. Interactions of short-acting, intermediate-acting and pre-mixed human insulins with free radicals--Comparative EPR examination.

    Science.gov (United States)

    Olczyk, Paweł; Komosinska-Vassev, Katarzyna; Ramos, Paweł; Mencner, Łukasz; Olczyk, Krystyna; Pilawa, Barbara

    2015-07-25

    Electron paramagnetic resonance (EPR) spectroscopy was used to examine insulins interactions with free radicals. Human recombinant DNA insulins of three groups were studied: short-acting insulin (Insuman Rapid); intermediate-acting insulins (Humulin N, Insuman Basal), and pre-mixed insulins (Humulin M3, Gensulin M50, Gensulin M40, Gensulin M30). The aim of an X-band (9.3GHz) study was comparative analysis of antioxidative properties of the three groups of human insulins. DPPH was used as a stable free radical model. Amplitudes of EPR lines of DPPH as the paramagnetic free radical reference, and DPPH interacting with the individual tested insulins were compared. For all the examined insulins kinetics of their interactions with free radicals up to 60 min were obtained. The strongest interactions with free radicals were observed for the short-acting insulin - Insuman Rapid. The lowest interactions with free radicals were characteristic for intermediate-acting insulin - Insuman Basal. The pre-mixed insulins i.e. Humulin M3 and Gensulin M50 revealed the fastest interactions with free radicals. The short acting, intermediate acting and premixed insulins have been found to be effective agents in reducing free radical formation in vitro and should be further considered as potential useful tools in attenuation of oxidative stress in diabetic patients.

  1. Determinants of intensive insulin therapeutic regimens in patients with type 1 diabetes: data from a nationwide multicenter survey in Brazil

    Science.gov (United States)

    2014-01-01

    Background To evaluate the determinants of intensive insulin regimens (ITs) in patients with type 1 diabetes (T1D). Methods This multicenter study was conducted between December 2008 and December 2010 in 28 public clinics in 20 Brazilian cities. Data were obtained from 3,591 patients (56.0% female, 57.1% Caucasian). Insulin regimens were classified as follows: group 1, conventional therapy (CT) (intermediate human insulin, one to two injections daily); group 2 (three or more insulin injections of intermediate plus regular human insulin); group 3 (three or more insulin injections of intermediate human insulin plus short-acting insulin analogues); group 4, basal-bolus (one or two insulin injections of long-acting plus short-acting insulin analogues or regular insulin); and group 5, basal-bolus with continuous subcutaneous insulin infusion (CSII). Groups 2 to 5 were considered IT groups. Results We obtained complete data from 2,961 patients. Combined intermediate plus regular human insulin was the most used therapeutic regimen. CSII was used by 37 (1.2%) patients and IT by 2,669 (90.2%) patients. More patients on IT performed self-monitoring of blood glucose and were treated at the tertiary care level compared to CT patients (p < 0.001). The majority of patients from all groups had HbA1c levels above the target. Overweight or obesity was not associated with insulin regimen. Logistic regression analysis showed that economic status, age, ethnicity, and level of care were associated with IT (p < 0.001). Conclusions Given the prevalence of intensive treatment for T1D in Brazil, more effective therapeutic strategies are needed for long term-health benefits. PMID:24920963

  2. The insulin-mediated modulation of visually evoked magnetic fields is reduced in obese subjects.

    Directory of Open Access Journals (Sweden)

    Martina Guthoff

    Full Text Available BACKGROUND: Insulin is an anorexigenic hormone that contributes to the termination of food intake in the postprandial state. An alteration in insulin action in the brain, named "cerebral insulin resistance", is responsible for overeating and the development of obesity. METHODOLOGY/PRINCIPAL FINDINGS: To analyze the direct effect of insulin on food-related neuronal activity we tested 10 lean and 10 obese subjects. We conducted a magnetencephalography study during a visual working memory task in both the basal state and after applying insulin or placebo spray intranasally to bypass the blood brain barrier. Food and non-food pictures were presented and subjects had to determine whether or not two consecutive pictures belonged to the same category. Intranasal insulin displayed no effect on blood glucose, insulin or C-peptide concentrations in the periphery; however, it led to an increase in the components of evoked fields related to identification and categorization of pictures (at around 170 ms post stimuli in the visual ventral stream in lean subjects when food pictures were presented. In contrast, insulin did not modulate food-related brain activity in obese subjects. CONCLUSIONS/SIGNIFICANCE: We demonstrated that intranasal insulin increases the cerebral processing of food pictures in lean whereas this was absent in obese subjects. This study further substantiates the presence of a "cerebral insulin resistance" in obese subjects and might be relevant in the pathogenesis of obesity.

  3. Insulin expression in livers of diabetic mice mediated by hydrodynamics-based administration

    Institute of Scientific and Technical Information of China (English)

    Chen-Xia He; Da-Ru Lu; Jing-Lun Xue; Ding Shi; Wen-Jun Wu; You-Fa Ding; Deng-Min Feng; Bin Lu; Hao-Ming Chen; Ji-Hua Yao; Qi Shen

    2004-01-01

    AIM: Transfer and expression of insulin gene in vivo are an alternative strategy to improve glycemic control in type 1 diabetes. Hydrodynamics-based procedure has been proved to be very efficient to transfer naked DNA to mouse livers. The basal hepatic insulin production mediated by this rapid tail vein injection was studied to determine its effect on the resumption of glycemic control in type 1diabetic mice.METHODS: Engineered insulin cDNA was inserted into plasmid vectors under a ClMlV promoter, and transferred into STZ induced diabetic mice by hydrodynamic procedure.Glucose levels, body weight of treated mice, insulin levels,immunohistology of the liver, and quantity of insulin mRNA in the liver were assayed to identify the improvement of hyperglycemic complication after plasmid administration.Sleeping Beauty, a transposon system, was also used to prolong the insulin expression in the liver.RESULTS: After plasmid administration, Plasma insulin was significantly increased in the diabetic mice and the livers were insulin-positive by immunostaining. At the same time the hyperglycemic complication was improved. The blood glucose levels of mice were reduced to normal. Glucose tolerance of the treated diabetic mice was improved. Body weight loss was also ameliorated. The rapid tail vein injection did not cause any fatal result.CONCLUSION: Our results suggested that insulin gene could be efficiently transferred into the livers of diabetic mice via rapid tail vein injection and it resulted in high level of insulin expression. The basal hepatic insulin production mediated by hydrodynamics-based administration improved the glycemic control in type 1 diabetes dramatically and ameliorated diabetic syndromes. Hydrodynamics-based administration offers a simple and efficient way in the study of gene therapy for type 1 diabetes.

  4. Clinical insights into the safety and utility of the insulin tolerance test (ITT) in the assessment of the hypothalamo-pituitary-adrenal axis.

    LENUS (Irish Health Repository)

    Finucane, Francis M

    2008-10-01

    The insulin tolerance test (ITT) is the gold standard for assessing GH and cortisol production in pituitary disease. However, areas of uncertainty remain regarding its safety in older people, the optimal duration of the test and its performance in insulin resistant states. Whether basal cortisol concentration can reliably predict an adequate adrenal response to hypoglycaemia remains to be determined.

  5. Localized basal meningeal enhancement in tuberculous meningitis

    Energy Technology Data Exchange (ETDEWEB)

    Theron, Salomine; Andronikou, Savvas; Grobbelaar, Marie; Steyn, Freda; Mapukata, Ayanda; Plessis, Jaco du [University of Stellenbosch, Department of Radiology, Tygerberg Hospital, P.O. BOX 19063, Tygerberg (South Africa)

    2006-11-15

    Focal basal meningeal enhancement may produce a confusing CT picture in children with suspected tuberculous meningitis (TBM). To demonstrate the incidence, distribution and appearance of localized basal meningeal enhancement in children with TBM. CT scans of patients with definite (culture proven) and probable (CSF suggestive) TBM were retrospectively evaluated by two observers. Localized basal enhancement was documented as involving: unilateral cistern of the lateral fossa (CLF), unilateral sylvian fissure, unilateral CLF and sylvian fissure in combination, unilateral CLF and sylvian fissure with ipsi- or contralateral ambient cistern and isolated quadrigeminal plate cistern. The study included 130 patients with TBM (aged 2 months to 13 years 9 months). Focal basal enhancement was seen in 11 patients (8.5%). The sylvian fissure was involved most commonly, followed by the lateral fossa cistern. The ambient cistern was involved in three patients and the quadrigeminal plate cistern in one. Focal areas of enhancement corresponded to the areas of infarction in every patient. Focal basal meningeal enhancement is common (8.5%) in paediatric TBM. This must be kept in mind when evaluating CT scans in children presenting with focal neurological findings, seizures or meningism in communities where TBM is endemic. (orig.)

  6. Somatotopic organization of the primate basal ganglia

    Directory of Open Access Journals (Sweden)

    Atsushi eNambu

    2011-04-01

    Full Text Available Somatotopic organization is a fundamental and key concept to understand how the cortico-basal ganglia loop works. It is also indispensable knowledge to perform stereotaxic surgery for movement disorders. Here I would like to describe the somatotopic organization of the basal ganglia, which consist of the striatum, subthalamic nucleus, globus pallidus and substantia nigra. Projections from motor cortical regions representing different body parts terminate in different regions of these nuclei. Basal ganglia neurons respond not only to the stimulation of the corresponding regions of the motor cortices, but also to active and passive movements of the corresponding body parts. On the basis of these anatomical and physiological findings, somatotopic organization can be identified in the motor territories of these nuclei in the basal ganglia. In addition, projections from functionally interrelated cortical areas partially converge through the cortico-basal ganglia loop, but nevertheless the somatotopy is still preserved. Disorganized somatotopy may explain, at least in part, the pathophysiology of movement disorders, such as Parkinson’s disease and dystonia.

  7. Insulin Resistance and Hypertension

    Institute of Scientific and Technical Information of China (English)

    张建华; 张春秀

    2002-01-01

    Summary: The insulin sensitivity in hypertensive patients with normal glucose tolerance (NGT),impaired glucose tolerance (IGT) and type 2 diabetes mellitus (DM) and the insulin resistance(IR) under the disorder of glucose metabolism and hypertension were studied. By glucose toler-ance test and insulin release test, insulin sensitivity index (ISI) and the ratio of area under glucosetolerance curve (AUCG) to area under insulin release curve (AUC1) were calculated and analyzed.The results showed that ISI was decreased to varying degrees in the patients with hypertension,the mildest in the group of NGT with hypertension, followed by the group of IGT without hyper-tension, the group of IGT with hypertension and DM (P=0). There was very significant differ-ence in the ratio of AUCG/AUC1 between the hypertensive patients with NGT and controls (P=0). It was concluded that a significant IR existed during the development of IGT both in hyperten-sion and nonhypertension. The increase of total insulin secretion (AUC1) was associated with non-hypertension simultaneously. IR of the hypertensive patients even existed in NGT and was wors-ened with the deterioration of glucose metabolism disorder, but the AUC1 in the HT groupchanged slightly. A relative deficiency of insulin secretion or dysfunction of β-cell of islet existed inIGT and DM of the hypertensive patients.

  8. Gender differences in non-glycemic responses to improved insulin sensitivity by pioglitazone treatment in patients with type 2 diabetes.

    Science.gov (United States)

    Arnetz, Lisa; Dorkhan, Mozhgan; Alvarsson, Michael; Brismar, Kerstin; Ekberg, Neda Rajamand

    2014-04-01

    Excess cortisol and GH induce insulin resistance, a central feature of type 2 diabetes (T2D). To study whether the insulin sensitizer pioglitazone affects basal cortisol levels and the GH-IGF-I axis in patients with T2D. Forty-eight patients with T2D (men/women = 28:20, age 61 ± 1 years, BMI 31 ± 0.6 kg/m(2)) were treated for 26 weeks with pioglitazone 30-45 mg daily in addition to their preexisting therapy. Insulin, proinsulin, HbA(1c), IGF-I, IGFBP-1, and basal cortisol were analyzed before and after treatment. Pioglitazone decreased proinsulin/insulin ratio and HbA(1c) decreased (HbA(1c) from 7.8 ± 0.2 to 6.6 ± 0.2% in men and from 7.6 ± 0.2 to 6.1 ± 0.2% in women, p pioglitazone increased IGF-I regardless of gender and in women also increased basal cortisol. Increased IGF-I may contribute to improved insulin sensitivity after treatment. There seems to be gender differences in treatment responses to pioglitazone on lipid metabolism and basal cortisol, perhaps correcting different mechanisms of insulin resistance between genders.

  9. Identification of triple-negative and basal-like canine mammary carcinomas using four basal markers.

    Science.gov (United States)

    Kim, N H; Lim, H Y; Im, K S; Kim, J H; Sur, J-H

    2013-05-01

    Molecular-based classification of canine mammary carcinomas (CMCs) has been a recent research focus. In human breast cancer, triple-negative and basal-like phenotypes are distinct molecular subgroups that are known for their poor prognosis, but these tumours are not yet well defined in the dog. The aim of this study was to determine whether CMCs include triple-negative and basal-like phenotypes by immunohistochemical assessment of expression of the oestrogen receptor (OR), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and four basal markers, cytokeratin (CK) 14, CK5/6, p63 and the epidermal growth factor receptor (EGFR). In this study of 241 CMCs, 45 triple-negative tumours (OR(-), PR(-) and HER2(-)) were identified and this phenotype was associated with an unfavourable prognosis. In these tumours, the expression of CK14, CK5/6 and EGFR was related to clinicopathological parameters, while the expression of p63 was not relevant. The majority of the triple-negative tumours were of the basal-like phenotype, given that 75.6% of them expressed more than two basal markers. However, three of the basal markers were not uniformly expressed; therefore, the proportion of the basal-like phenotype was altered on the basis of the selection of the markers. Although both triple-negative and basal-like phenotypes are distinct entities in CMC, further study is needed to differentiate one from the other.

  10. Insulin action and insulin resistance in vascular endothelium.

    Science.gov (United States)

    Muniyappa, Ranganath; Quon, Michael J

    2007-07-01

    Vasodilator actions of insulin are mediated by phosphatidylinositol 3-kinase dependent insulin signaling pathways in endothelium, which stimulate production of nitric oxide. Insulin-stimulated nitric oxide mediates capillary recruitment, vasodilation, increased blood flow, and subsequent augmentation of glucose disposal in skeletal muscle. Distinct mitogen-activated protein kinase dependent insulin signaling pathways regulate secretion of the vasoconstrictor endothelin-1 from endothelium. These vascular actions of insulin contribute to the coupling of metabolic and hemodynamic homeostasis that occurs under healthy conditions. Insulin resistance is characterized by pathway-specific impairment in phosphatidylinositol 3-kinase dependent signaling in both metabolic and vascular insulin target tissues. Here we discuss consequences of pathway-specific insulin resistance in endothelium and therapeutic interventions targeting this selective impairment. Shared causal factors such as glucotoxicity, lipotoxicity, and inflammation selectively impair phosphatidylinositol 3-kinase dependent insulin signaling pathways, creating reciprocal relationships between insulin resistance and endothelial dysfunction. Diet, exercise, cardiovascular drugs, and insulin sensitizers simultaneously modulate phosphatidylinositol 3-kinase and mitogen-activated protein kinase dependent pathways, improving metabolic and vascular actions of insulin. Pathway-specific impairment in insulin action contributes to reciprocal relationships between endothelial dysfunction and insulin resistance, fostering clustering of metabolic and cardiovascular diseases in insulin-resistant states. Therapeutic interventions that target this selective impairment often simultaneously improve both metabolic and vascular function.

  11. Radiologic study of basal cell nevus syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Park, Tae Won [Dept. of Oral Radiology, College of Dentistry, Seoul National University, Seoul (Korea, Republic of)

    1988-11-15

    Several cases of jaw cyst-basal cell nevus-bifid rib syndrome are presented. This syndrome consists principally of multiple jaw cysts, basal cell nevi, and bifid ribs but no one component is present in all patients. The purpose of this paper is to review the multiple characteristics of this syndrome and present three cases in a family and additional 4 cases. The many malformations associated with the syndrome have variable expressively. In the cases, multiple jaw cysts, pal mar and plantar pittings, bridging of sella, temporoparietal bossing, hypertelorism, cleft palate, and dystopia canthoru m have been observed.

  12. Molecular mechanism of insulin resistance

    Indian Academy of Sciences (India)

    Samir Bhattacharya; Debleena Dey; Sib Sankar Roy

    2007-03-01

    Free fatty acids are known to play a key role in promoting loss of insulin sensitivity, thereby causing insulin resistance and type 2 diabetes. However, the underlying mechanism involved is still unclear. In searching for the cause of the mechanism, it has been found that palmitate inhibits insulin receptor (IR) gene expression, leading to a reduced amount of IR protein in insulin target cells. PDK1-independent phosphorylation of PKCε causes this reduction in insulin receptor gene expression. One of the pathways through which fatty acid can induce insulin resistance in insulin target cells is suggested by these studies. We provide an overview of this important area, emphasizing the current status.

  13. Impaired tethering and fusion of GLUT4 vesicles in insulin-resistant human adipose cells.

    Science.gov (United States)

    Lizunov, Vladimir A; Lee, Jo-Ping; Skarulis, Monica C; Zimmerberg, Joshua; Cushman, Samuel W; Stenkula, Karin G

    2013-09-01

    Systemic glucose homeostasis is profoundly influenced by adipose cell function. Here we investigated GLUT4 dynamics in living adipose cells from human subjects with varying BMI and insulin sensitivity index (Si) values. Cells were transfected with hemagglutinin (HA)-GLUT4-green fluorescent protein (GFP)/mCherry (red fluorescence), and were imaged live using total internal reflection fluorescence and confocal microscopy. HA-GLUT4-GFP redistribution to the plasma membrane (PM) was quantified by surface-exposed HA epitope. In the basal state, GLUT4 storage vesicle (GSV) trafficking to and fusion with the PM were invariant with donor subject Si, as was total cell-surface GLUT4. In cells from insulin-sensitive subjects, insulin augmented GSV tethering and fusion approximately threefold, resulting in a corresponding increase in total PM GLUT4. However, with decreasing Si, these effects diminished progressively. All insulin-induced effects on GLUT4 redistribution and trafficking correlated strongly with Si and only weakly with BMI. Thus, while basal GLUT4 dynamics and total cell-surface GLUT4 are intact in human adipose cells, independent of donor Si, cells from insulin-resistant donors show markedly impaired GSV tethering and fusion responses to insulin, even after overnight culture. This altered insulin responsiveness is consistent with the hypothesis that adipose cellular dysfunction is a primary contributor to systemic metabolic dysfunction.

  14. Comparison of continuous subcutaneous insulin infusion and multiple daily insulin injections in Chinese patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Yang, Honghong; Heng, Xueyuan; Liang, Cuige; Liu, Xiaomeng; Du, Wenhua; Li, Shoujie; Wang, Yueli; Dong, Qingyu; Li, Wenxia; Pan, Zhenyu; Gong, Qian; Gao, Guanqi

    2014-08-01

    To investigate prospectively the insulin dose requirements of Chinese patients with type 2 diabetes mellitus treated with either multiple daily insulin injections (MDI) or continuous subcutaneous insulin infusion (CSII) therapy during a 2-week therapeutic intervention. Patients with type 2 diabetes mellitus were randomly assigned to MDI or CSII therapy. The effects of the two treatment methods were determined based on blood glucose parameters, total daily insulin dose and rates of hypoglycaemia. A total of 609 patients were enrolled in the study. Glycaemic goals were achieved after a mean ± SD of 6.90 ± 2.10 and 5.44 ± 2.22 days' treatment in the MDI and CSII groups, respectively. Once stabilized, the mean ± SD total daily insulin doses were 37.12 ± 10.19 IU and 32.58 ± 8.78 IU for the MDI and CSII groups, respectively. Once stabilized, the mean ± SD total basal and bolus doses were 19.46 ± 7.95 IU/day and 17.66 ± 3.53 IU/day for the MDI group, and 22.79 ± 7.55 IU/day and 9.81 ± 2.64 IU/day for the CSII group, respectively. There were significant differences in the total, basal and bolus insulin doses between the two groups. CSII therapy may be considered as an effective method to achieve good glycaemic control in Chinese patients with type 2 diabetes mellitus. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  15. Insulin Resistance and Atherosclerosis

    National Research Council Canada - National Science Library

    Nigro, Julie; Osman, Narin; Dart, Anthony M; Little, Peter J

    2006-01-01

    ... morbidity and mortality. It is only now being recognized that the major antecedent of type 2 diabetes, insulin resistance with its attendant syndrome, is the major underlying cause of the susceptibility to type 2 diabetes...

  16. AMPK and insulin action

    DEFF Research Database (Denmark)

    Frøsig, Christian; Jensen, Thomas Elbenhardt; Jeppesen, Jacob

    2013-01-01

    The 5'-AMP-activated protein kinase (AMPK) is considered "a metabolic master-switch" in skeletal muscle reducing ATP- consuming processes whilst stimulating ATP regeneration. Within recent years, AMPK has also been proposed as a potential target to attenuate insulin resistance, although the exact...... role of AMPK is not well understood. Here we hypothesized that mice lacking a2AMPK activity in muscle would be more susceptible to develop insulin resistance associated with ageing alone or in combination with high fat diet. Young (~4 month) or old (~18 month) wild type and muscle specific a2AMPK...... kinase-dead mice on chow diet as well as old mice on 17 weeks of high fat diet were studied for whole body glucose homeostasis (OGTT, ITT and HOMA-IR), insulin signaling and insulin-stimulated glucose uptake in muscle. We demonstrate that high fat diet in old mice results in impaired glucose homeostasis...

  17. Insulin and insulin signaling play a critical role in fat induction of insulin resistance in mouse

    Science.gov (United States)

    Ning, Jie; Hong, Tao; Yang, Xuefeng; Mei, Shuang; Liu, Zhenqi; Liu, Hui-Yu

    2011-01-01

    The primary player that induces insulin resistance has not been established. Here, we studied whether or not fat can cause insulin resistance in the presence of insulin deficiency. Our results showed that high-fat diet (HFD) induced insulin resistance in C57BL/6 (B6) mice. The HFD-induced insulin resistance was prevented largely by the streptozotocin (STZ)-induced moderate insulin deficiency. The STZ-induced insulin deficiency prevented the HFD-induced ectopic fat accumulation and oxidative stress in liver and gastrocnemius. The STZ-induced insulin deficiency prevented the HFD- or insulin-induced increase in hepatic expression of long-chain acyl-CoA synthetases (ACSL), which are necessary for fatty acid activation. HFD increased mitochondrial contents of long-chain acyl-CoAs, whereas it decreased mitochondrial ADP/ATP ratio, and these HFD-induced changes were prevented by the STZ-induced insulin deficiency. In cultured hepatocytes, we observed that expressions of ACSL1 and -5 were stimulated by insulin signaling. Results in cultured cells also showed that blunting insulin signaling by the PI3K inhibitor LY-294002 prevented fat accumulation, oxidative stress, and insulin resistance induced by the prolonged exposure to either insulin or oleate plus sera that normally contain insulin. Finally, knockdown of the insulin receptor prevented the oxidative stress and insulin resistance induced by the prolonged exposure to insulin or oleate plus sera. Together, our results show that insulin and insulin signaling are required for fat induction of insulin resistance in mice and cultured mouse hepatocytes. PMID:21586696

  18. Etiopathogenesis of Insulin Autoimmunity

    Directory of Open Access Journals (Sweden)

    Norio Kanatsuna

    2012-01-01

    Full Text Available Autoimmunity against pancreatic islet beta cells is strongly associated with proinsulin, insulin, or both. The insulin autoreactivity is particularly pronounced in children with young age at onset of type 1 diabetes. Possible mechanisms for (proinsulin autoimmunity may involve beta-cell destruction resulting in proinsulin peptide presentation on HLA-DR-DQ Class II molecules in pancreatic draining lymphnodes. Recent data on proinsulin peptide binding to type 1 diabetes-associated HLA-DQ2 and -DQ8 is reviewed and illustrated by molecular modeling. The importance of the cellular immune reaction involving cytotoxic CD8-positive T cells to kill beta cells through Class I MHC is discussed along with speculations of the possible role of B lymphocytes in presenting the proinsulin autoantigen over and over again through insulin-carrying insulin autoantibodies. In contrast to autoantibodies against other islet autoantigens such as GAD65, IA-2, and ZnT8 transporters, it has not been possible yet to standardize the insulin autoantibody test. As islet autoantibodies predict type 1 diabetes, it is imperative to clarify the mechanisms of insulin autoimmunity.

  19. Inhaled insulin: overview of a novel route of insulin administration

    Directory of Open Access Journals (Sweden)

    Lucy D Mastrandrea

    2010-01-01

    Full Text Available Lucy D MastrandreaDepartment of Pediatrics, School of Medicine and Biochemical Sciences, University at Buffalo, Buffalo, NY, USAAbstract: Diabetes is a chronic disease characterized by inadequate insulin secretion with resulting hyperglycemia. Diabetes complications include both microvascular and macrovascular disease, both of which are affected by optimal diabetes control. Many individuals with diabetes rely on subcutaneous insulin administration by injection or continuous infusion to control glucose levels. Novel routes of insulin administration are an area of interest in the diabetes field, given that insulin injection therapy is burdensome for many patients. This review will discuss pulmonary delivery of insulin via inhalation. The safety of inhaled insulin as well as the efficacy in comparison to subcutaneous insulin in the various populations with diabetes are covered. In addition, the experience and pitfalls that face the development and marketing of inhaled insulin are discussed.Keywords: glycemic control, hemoglobin A1c, inhalation, insulin, type 1 diabetes, type 2 diabetes

  20. Multiethnic Literature; Supplements for Basal Readers.

    Science.gov (United States)

    Florez-Tighe, Viola; And Others

    Children's literature can be used effectively to enrich the reading content of basal reading materials with stories and information by and about ethnic minorities. Developing an ethnic cultural web for a literary selection can stimulate language and enhance the thought processes of students. Using the webbing process, elementary school students…

  1. Traumatisk basal subaraknoidal blødning

    DEFF Research Database (Denmark)

    Lundgaard, Peter; Leth, Peter Mygind; Gregersen, Markil

    2003-01-01

    lokaliseres. Skadesmekanismen er omdiskuteret. Karrupturen kan opstå i forbindelse med brud af processus transversus atlantis eller subluksationer i halscolumna og kan indtræffe i både normale og abnorme kar. Traumatisk basal subaraknoidalblødning kan tilsyneladende opstå ved ret lette traumer, hvilket...

  2. Giant basal cell carcinoma Carcinoma basocelular gigante

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    Nilton Nasser

    2012-06-01

    Full Text Available The basal cell carcinoma is the most common skin cancer but the giant vegetating basal cell carcinoma reaches less than 0.5 % of all basal cell carcinoma types. The Giant BCC, defined as a lesion with more than 5 cm at its largest diameter, is a rare form of BCC and commonly occurs on the trunk. This patient, male, 42 years old presents a Giant Basal Cell Carcinoma which reaches 180 cm2 on the right shoulder and was negligent in looking for treatment. Surgical treatment was performed and no signs of dissemination or local recurrence have been detected after follow up of five years.O carcinoma basocelular é o tipo mais comum de câncer de pele, mas o carcinoma basocelular gigante vegetante não atinge 0,5% de todos os tipos de carcinomas basocelulares. O Carcinoma Basocelular Gigante, definido como lesão maior que 5 cm no maior diâmetro, é uma forma rara de carcinoma basocelular e comumente ocorre no tronco. Este paciente apresenta um Carcinoma Basocelular Gigante com 180cm² no ombro direito e foi negligente em procurar tratamento. Foi realizado tratamento cirúrgico e nenhum sinal de disseminação ou recorrência local foi detectada após 5 anos.

  3. Immunosuppressive Environment in Basal Cell Carcinoma

    DEFF Research Database (Denmark)

    Omland, Silje H; Nielsen, Patricia S; Gjerdrum, Lise M R;

    2016-01-01

    Interaction between tumour survival tactics and anti-tumour immune response is a major determinant for cancer growth. Regulatory T cells (T-regs) contribute to tumour immune escape, but their role in basal cell carcinoma (BCC) is not understood. The fraction of T-regs among T cells was analysed...

  4. Basal Cell Carcinoma in The Netherlands

    NARCIS (Netherlands)

    S.C. Flohil (Sophie)

    2012-01-01

    textabstractThere are many different cutaneous malignancies, but malignant melanoma, squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) represent approximately 98% of all skin cancers.In literature, these three skin cancers are often divided into melanoma and nonmelanoma skin cancers (NMSC

  5. Parallel basal ganglia circuits for decision making.

    Science.gov (United States)

    Hikosaka, Okihide; Ghazizadeh, Ali; Griggs, Whitney; Amita, Hidetoshi

    2017-02-02

    The basal ganglia control body movements, mainly, based on their values. Critical for this mechanism is dopamine neurons, which sends unpredicted value signals, mainly, to the striatum. This mechanism enables animals to change their behaviors flexibly, eventually choosing a valuable behavior. However, this may not be the best behavior, because the flexible choice is focused on recent, and, therefore, limited, experiences (i.e., short-term memories). Our old and recent studies suggest that the basal ganglia contain separate circuits that process value signals in a completely different manner. They are insensitive to recent changes in value, yet gradually accumulate the value of each behavior (i.e., movement or object choice). These stable circuits eventually encode values of many behaviors and then retain the value signals for a long time (i.e., long-term memories). They are innervated by a separate group of dopamine neurons that retain value signals, even when no reward is predicted. Importantly, the stable circuits can control motor behaviors (e.g., hand or eye) quickly and precisely, which allows animals to automatically acquire valuable outcomes based on historical life experiences. These behaviors would be called 'skills', which are crucial for survival. The stable circuits are localized in the posterior part of the basal ganglia, separately from the flexible circuits located in the anterior part. To summarize, the flexible and stable circuits in the basal ganglia, working together but independently, enable animals (and humans) to reach valuable goals in various contexts.

  6. Carbon dioxide laser surgery of basal meningiomas.

    Science.gov (United States)

    Bartal, A D; Heilbronn, Y D; Avram, J; Razon, N

    1982-02-01

    This preliminary report summarizes our results with laser surgery in patients with basal meningiomas (8 basilar and 1 intraventricular extending also into the third ventricle). Illustrative preoperative and postoperative CT scans are included. The advantages and limitations of this surgical technique are discussed briefly.

  7. Short-term cold acclimation improves insulin sensitivity in patients with type 2 diabetes mellitus

    NARCIS (Netherlands)

    Hanssen, M.J.W.; Hoeks, J.; Brans, B.; Boekschoten, M.V.; Kersten, A.H.

    2015-01-01

    Cold exposure may be a potential therapy for diabetes by increasing brown adipose tissue (BAT) mass and activity. Here we report that 10 d of cold acclimation (14–15 °C) increased peripheral insulin sensitivity by ~43% in eight type 2 diabetes subjects. Basal skeletal muscle GLUT4 translocation mark

  8. Prospective randomized study for optimal insulin therapy in type 2 diabetic patients with secondary failure

    Directory of Open Access Journals (Sweden)

    Tojo Katsuyoshi

    2008-05-01

    Full Text Available Abstract Background The large clinical trials proved that Basal-Bolus (BB insulin therapy was effective in the prevention of diabetic complications and their progression. However, BB therapy needs multiple insulin injections per a day. In this regard, a biphasic insulin analogue needs only twice-daily injections, and is able to correct postprandial hyperglycemia. Therefore it may achieve the blood glucose control as same as that of BB therapy and prevent the diabetic complications including macroangiopathy. Methods In PROBE (Prospective, Randomized, Open, Blinded-Endpoint design, forty-two type 2 diabetic patients (male: 73.8%, median(inter quartile range age: 64.5(56.8~71.0years with secondary failure of sulfonylurea (SU were randomly assigned to BB therapy with a thrice-daily insulin aspart and once-daily basal insulin (BB group or to conventional therapy with a twice-daily biphasic insulin analogue (30 Mix group, and were followed up for 6 months to compare changes in HbA1c, daily glycemic profile, intima-media thickness (IMT of carotid artery, adiponectin levels, amounts of insulin used, and QOL between the two groups. Results After 6 months, HbA1c was significantly reduced in both groups compared to baseline (30 Mix; 9.3(8.1~11.3 → 7.4(6.9~8.7%, p Conclusion Both BB and 30 mix group produced comparable reductions in HbA1c in type 2 diabetic patients with secondary failure. There was no significant change in IMT as an indicator of early atherosclerotic changes between the two groups. The basal-bolus insulin therapy may not be necessarily needed if the type 2 diabetic patients have become secondary failure. Trial registration Current Controlled Trials number, NCT00348231

  9. Molecular biocoding of insulin

    Directory of Open Access Journals (Sweden)

    Lutvo Kuric

    2010-07-01

    Full Text Available Lutvo KuricNovi Travnik, Kalinska, Bosnia and Herzegovina Abstract: This paper discusses cyberinformation studies of the amino acid composition of insulin, in particular the identification of scientific terminology that could describe this phenomenon, ie, the study of genetic information, as well as the relationship between the genetic language of proteins and theoretical aspects of this system and cybernetics. The results of this research show that there is a matrix code for insulin. It also shows that the coding system within the amino acid language gives detailed information, not only on the amino acid “record”, but also on its structure, configuration, and various shapes. The issue of the existence of an insulin code and coding of the individual structural elements of this protein are discussed. Answers to the following questions are sought. Does the matrix mechanism for biosynthesis of this protein function within the law of the general theory of information systems, and what is the significance of this for understanding the genetic language of insulin? What is the essence of existence and functioning of this language? Is the genetic information characterized only by biochemical principles or it is also characterized by cyberinformation principles? The potential effects of physical and chemical, as well as cybernetic and information principles, on the biochemical basis of insulin are also investigated. This paper discusses new methods for developing genetic technologies, in particular more advanced digital technology based on programming, cybernetics, and informational laws and systems, and how this new technology could be useful in medicine, bioinformatics, genetics, biochemistry, and other natural sciences.Keywords: human insulin, insulin model, biocode, genetic code, amino acids

  10. Effect of training on insulin sensitivity of glucose uptake and lipolysis in human adipose tissue

    DEFF Research Database (Denmark)

    Stallknecht, Bente; Larsen, J J; Mikines, K J;

    2000-01-01

    Training increases insulin sensitivity of both whole body and muscle in humans. To investigate whether training also increases insulin sensitivity of adipose tissue, we performed a three-step hyperinsulinemic, euglycemic clamp in eight endurance-trained (T) and eight sedentary (S) young men...... [insulin infusion rates: 10,000 (step I), 20,000 (step II), and 150,000 (step III) microU x min(-1) x m(-2)]. Glucose and glycerol concentrations were measured in arterial blood and also by microdialysis in interstitial fluid in periumbilical, subcutaneous adipose tissue and in quadriceps femoris muscle...... (glucose only). Adipose tissue blood flow was measured by (133)Xe washout. In the basal state, adipose tissue blood flow tended to be higher in T compared with S subjects, and in both groups blood flow was constant during the clamp. The change from basal in arterial-interstitial glucose concentration...

  11. Insulin regimens and glycemic control in different parts of Europe over 4years after starting insulin in people with type 2 diabetes: Data from the CREDIT non-interventional study.

    Science.gov (United States)

    Blonde, Lawrence; Marre, Michel; Vincent, Maya; Brette, Sandrine; Pilorget, Valerie; Danchin, Nicholas; Vespasiani, Giacomo; Home, Philip

    2017-08-31

    A number of insulin regimens are used in type 2 diabetes. This analysis aims to better understand the evolution of insulin therapy in different regions of Europe. Data from people starting any insulin were collected in eastern Europe (EEur: Croatia, Russia, Ukraine), northern Europe (NEur: Finland, Germany, UK) and southern Europe (SEur: France, Italy, Portugal, Spain). Retrospective data on starting insulin and prospective follow-up data were extracted from clinical records. At 4years, 1699 (76.0%) of 2236 eligible people had data. EEur participants were mostly female, younger and had shorter diabetes duration on starting insulin, yet had highest baseline HbA1c and more micro-/macrovascular disease. A majority (60%-64%) in all regions started on basal insulin alone, declining to 30%-38% at 4years, with most switching to basal+mealtime insulin regimen (24%-40%). Higher baseline (28%) and 4-year use (34%) of premix insulin was observed in NEur. Change in HbA1c (SD) ranged from -1.2 (2.1)% (-13 [23]mmol/mol) in NEur to -2.4 (2.0)% (-26 [22]mmol/mol) in EEur. Weight change ranged from +1.9 (8.3) kg in NEur to +3.2 (7.0) kg in SEur. Overall documented hypoglycemia ranged from 0.3 (1.3) to 1.3 (4.4) events/person/6-months (NEur vs. EEur, respectively) and was stable with time. Severe hypoglycemia rates remained low. When starting insulin, HbA1c and prevalence of complications were higher in EEur. Regional differences exist in choice of insulin regimens in Europe. However, people starting insulin improved and sustained their glycemic control regardless of regional differences or insulin regimens used. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  12. A prospective randomised cross-over study of the effect of insulin analogues and human insulin on the frequency of severe hypoglycaemia in patients with type 1 diabetes and recurrent hypoglycaemia (the HypoAna trial: study rationale and design

    Directory of Open Access Journals (Sweden)

    Kristensen Peter

    2012-06-01

    Full Text Available Abstract Background Severe hypoglycaemia still represents a significant problem in insulin-treated diabetes. Most patients do not experience severe hypoglycaemia often. However, 20% of patients with type 1 diabetes experience recurrent severe hypoglycaemia corresponding to at least two episodes per year. The effect of insulin analogues on glycaemic control has been documented in large trials, while their effect on the frequency of severe hypoglycaemia is less clear, especially in patients with recurrent severe hypoglycaemia. The HypoAna Trial is designed to investigate whether short-acting and long-acting insulin analogues in comparison with human insulin are superior in reducing the occurrence of severe hypoglycaemic episodes in patients with recurrent hypoglycaemia. This paper reports the study design of the HypoAna Trial. Methods/design The study is a Danish two-year investigator-initiated, prospective, randomised, open, blinded endpoint (PROBE, multicentre, cross-over trial investigating the effect of insulin analogues versus human insulin on the frequency of severe hypoglycaemia in subjects with type 1 diabetes. Patients are randomised to treatment with basal-bolus therapy with insulin detemir / insulin aspart or human NPH insulin / human regular insulin in random order. The major inclusion criterion is history of two or more episodes of severe hypoglycaemia in the preceding year. Discussion In contrast to almost all other studies in this field the HypoAna Trial includes only patients with major problems with hypoglycaemia. The HypoAna Trial will elucidate whether basal-bolus regimen with short-acting and long-acting insulin analogues in comparison with human insulin are superior in reducing occurrence of severe hypoglycaemic episodes in hypoglycaemia prone patients with type 1 diabetes. http://www.clinicaltrials.gov: NCT00346996.

  13. Optimizing insulin pump therapy: a quality improvement project.

    Science.gov (United States)

    Meade, Lisa T; Rushton, Wanda E

    2013-01-01

    The purpose of the study was to assess insulin pump use and provide ongoing education. A quality improvement project using a pump assessment questionnaire was implemented at an endocrinology office in the southeastern United States. The questionnaire was designed to evaluate all aspects of insulin pump therapy, including pump operations, infusion set failure, management of acute complications, and usage of advanced device features. Eighty-nine patients (80% with type 1 diabetes and 20% with type 2 diabetes) completed the questionnaire at the endocrinology practice. A certified diabetes educator reviewed the questions with each patient, identifying deficiencies and training opportunities. The most common areas of deficiency identified after implementation of the assessment form included the following: expired or no basal insulin prescription in the event of pump failure or removal, no mupirocin (Bactroban®, GlaxoSmithKline, Research Triangle Park, North Carolina) prescription for suspected site infections, lack of insulin syringe if pump stopped working, failure to check urine ketones, no antiemetic prescription for sick day intervention, using manual bolus instead of bolus calculator, and lack of in-date glucagon kit. Use of a pump assessment questionnaire allows for focused discussion concerning patient behaviors related to pump operations, troubleshooting, and self-management. Incorporating use of a pump assessment questionnaire into routine practice may result in improved patient education and avoidance of adverse events specific to insulin pump therapy.

  14. Atrophy of the basal ganglia as the initial diagnostic sign of germinoma in the basal ganglia

    Energy Technology Data Exchange (ETDEWEB)

    Okamoto, K.; Ishikawa, K.; Takahashi, N.; Furusawa, T.; Sakai, K. [Department of Radiology, Niigata University Faculty of Medicine (Japan); Ito, J.; Tokiguchi, S. [Department of Radiology, Niigata University Faculty of Dentistry (Japan); Morii, K. [Department of Neurosurgery, Niigata University Brain Research Institute (Japan); Yamada, M. [Department of Pathology, Niigata University Brain Research Institute (Japan)

    2002-05-01

    Germ-cell tumors of the central nervous system generally develop in the midline, but the tumors can also occur in the basal ganglia and/or thalamus. However, MR images have rarely been documented in the early stage of the tumor in these regions. We retrospectively reviewed MR images obtained on admission and approximately 3 years earlier in two patients with germinoma in the basal ganglia, and compared them with CT. In addition to hyperdensity on CT, both hyperintensity on T1-weighted images and a small hyperintense lesion on T2-weighted images were commonly seen in the basal ganglia. These findings may be early MRI signs of germinoma in this region, and the earliest and most characteristic diagnostic feature on MRI was atrophy of the basal ganglia, which was recognizable before development of hemiparesis. (orig.)

  15. Insulin aspart in diabetic pregnancy

    DEFF Research Database (Denmark)

    Mathiesen, Elisabeth R

    2008-01-01

    Pregnancy in women with diabetes is associated with an increased risk of obstetric complications and perinatal mortality. Maintenance of near-normal glycemia during pregnancy can bring the prevalence of fetal, neonatal and maternal complications closer to that of the nondiabetic population. Changes...... in insulin requirements during pregnancy necessitate short-acting insulins for postprandial control of hyperglycemia. The fast-acting insulin analogue insulin aspart has been tested in a large, randomized trial of pregnant women with Type 1 diabetes and offers benefits in control of postprandial...... and no increase in insulin antibodies was found. Thus, the use of insulin aspart in pregnancy is regarded safe....

  16. 胰岛素类似物联合口服降糖药治疗2型糖尿病%Insulin analogs combined with oral antidiabetic drugs in treating patients with type 2 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    周泽华; 肖蓉; 何煦; 瞿文娟; 杨刚毅; 李伶; 李志勇

    2013-01-01

    目的:评估3种胰岛素类似物(地特胰岛素、甘精胰岛素、双相门冬胰岛素30)联合口服降糖药用于治疗血糖控制欠佳的2型糖尿病患者的有效性及安全性.方法:73例血糖控制不达标的2型糖尿病患者被分为3组:每日睡前1次地特胰岛素组(n=23),每日睡前1次甘精胰岛素组(n=27)和每日早晚餐前各1次双相门冬胰岛素30组(n=23),各组均联合使用口服降糖药,共治疗16周.分析比较3组患者治疗前后糖化血红蛋白(hemoglobin A1c,HbA1c)、空腹血糖(fasting blood glucose,FBG)、餐后血糖(postprandial blood glucose,PBG)、体质指数(body mass index,BMI)的变化.评估3组间HbA1c、FBG、PBG下降幅度、HbA1c达标率(<7%)和低血糖事件的发生率.结果:治疗前3组HbA1c、FBG、PBG均无显著差异.经16周治疗,3组HbA1c、FBG、PBG均较治疗前显著下降(P<0.01),但组间比较无显著差异(P>0.05).各组治疗前后BMI均无显著变化(P>0.05).地特胰岛素组、甘精胰岛素组、双相门冬胰岛素30组HbA1c达标率(<7%)分别为43%、59%、52%,组间比较无显著差异(P>0.05).地特胰岛素组、甘精胰岛素组、双相门冬胰岛素30组分别发生3例(13%)、2例(7%)、5例(22%)轻度低血糖,均无严重低血糖事件发生,各组间低血糖发生率无显著差异(P>0.05).结论:在本研究人群中,有效控制FBG是HbA1c降低及达标的有效手段,3种胰岛素类似物联合口服降糖治疗2型糖尿病,可达到同样的降糖效果,并且体质量无明显增加、低血糖发生率较低.%Objective:To evaluate the efficacy and safety of insulin analogs (Insulin detemir,Insulin glargine,B iphasic insulin aspart 30) combined with oral antidiabetic drugs(OADs) in treating type 2 diabetic mellitus patients whose blood glucose is insufficiently controlled.Methods:Seventy-three type 2 diabetic mellitus patients with insufficiently controlled blood glucose were assigned to three groups

  17. Improved insulin sensitivity after exercise: focus on insulin signaling

    DEFF Research Database (Denmark)

    Frøsig, Christian; Richter, Erik

    2009-01-01

    After a single bout of exercise, the ability of insulin to stimulate glucose uptake is markedly improved locally in the previously active muscles. This makes exercise a potent stimulus counteracting insulin resistance characterizing type 2 diabetes (T2D). It is believed that at least part...... of the mechanism relates to an improved ability of insulin to stimulate translocation of glucose transporters (GLUT4) to the muscle membrane after exercise. How this is accomplished is still unclear; however, an obvious possibility is that exercise interacts with the insulin signaling pathway to GLUT4...... translocation allowing for a more potent insulin response. Parallel to unraveling of the insulin signaling cascade, this has been investigated within the past 25 years. Reviewing existing studies clearly indicates that improved insulin action can occur independent of interactions with proximal insulin signaling...

  18. The effects of soy isoflavone on insulin sensitivity and adipocytokines in insulin resistant rats administered with high-fat diet.

    Science.gov (United States)

    Zhang, Hong-Min; Chen, Shi-Wei; Zhang, Li-Shi; Feng, Xiao-Fan

    2008-12-01

    The effects of soy isoflavone (SIF) on insulin sensitivity and adipocytokines in high-fat-diet-induced insulin resistant (IR) rats were studied. Male Sprague Dawley rats (n = 80) were randomly assigned into a basal diet fed group and high-fat diet fed group. The high-fat-diet-induced IR rats were assigned into IR model control group and three SIF-treated groups with different dosages. Thirty days later, the fasting blood glucose, insulin and adipocytokines in serum and mRNA expressions of adipocytokines in perirenal white adipose tissue were measured. The Homeostasis Model Assessment of IR was calculated. The administration of 450 mg kg(-1) d(-1) SIF decreased the body weights and depositions of visceral adipose tissue as well as improved insulin resistance in high-fat-diet-induced IR rats. The mechanisms were associated with SIF regulating the expression of adipocytokines, including adiponectin, leptin, resistin and TNF-alpha. SIF supplements may have favourable effects on insulin resistance in high-fat-diet-induced IR rats.

  19. Insulin and norepinephrine regulate ghrelin secretion from a rat primary stomach cell culture.

    Science.gov (United States)

    Gagnon, Jeffrey; Anini, Younes

    2012-08-01

    Ghrelin is a peptide hormone primarily produced in the previously unidentified X/A endocrine cells of the stomach. Extensive studies have focused on the effects of ghrelin on growth hormone release and appetite regulation. However, the mechanisms regulating ghrelin secretion are less understood. In the present study, we developed a primary culture of newborn rat stomach cells to investigate the mechanisms regulating ghrelin synthesis and secretion. We demonstrated that this cell preparation secretes ghrelin in a regulated manner through the increase of cAMP, intracellular calcium, and activation of protein kinase C. Norepinephrine (NE) (0.1-10 μm) stimulated ghrelin secretion through the β1-adrenergic receptor via increased cAMP and protein kinase A activity, whereas acetylcholine had no effect. Because circulating ghrelin levels were previously shown to be inversely correlated with insulin levels, we investigated the effect of insulin on ghrelin secretion. We first demonstrated that ghrelin cells express the insulin receptor α- and β-subunits. Next, we determined that insulin (1-10 nm) inhibited both basal and NE-stimulated ghrelin secretion, caused an increase in phosphorylated serine-threonine kinase (AKT) and a reduction in intracellular cAMP, but did not alter proghrelin mRNA levels. The inhibitory effect of insulin was blocked by inhibiting phospho-inositol-3 kinase and AKT but not MAPK. Higher dose insulin (100 nm) did not suppress ghrelin secretion, which prompted the investigation of cellular insulin resistance by pretreating the cells with 100 nm insulin for 24 h. This caused a reduction in insulin receptor expression and prevented the insulin-mediated AKT activation and the suppression of ghrelin secretion with no impact on NE-stimulated ghrelin secretion. Our findings highlight the role of the sympathetic nervous system, insulin, and insulin resistance in the regulation of ghrelin secretion.

  20. Severe insulin-resistant diabetes mellitus in patients with congenital muscle fiber type disproportion myopathy.

    Science.gov (United States)

    Vestergaard, H; Klein, H H; Hansen, T; Müller, J; Skovby, F; Bjørbaek, C; Røder, M E; Pedersen, O

    1995-04-01

    Congenital muscle fiber type disproportion myopathy (CFTDM) is a chronic, nonprogressive muscle disorder characterized by universal muscle hypotrophy and growth retardation. Histomorphometric examination of muscle shows a preponderance of smaller than normal type 1 fibers and overall fiber size heterogeneity. Concomitant endocrine dysfunctions have not been described. We report the findings of altered insulin secretion and insulin action in two brothers affected with CFTDM and glucose intolerance as well as in their nonconsanguineous glucose-tolerant parents. Results are compared with those of six normoglycemic control subjects. All study participants underwent an oral glucose tolerance test to estimate insulin secretion. The oldest boy and his parents volunteered for studies of whole-body insulin sensitivity consisting of a 4-h euglycemic hyperinsulinemic clamp in combination with indirect calorimetry. Insulin receptor function and glycogen synthase (GS) activity and expression were examined in biopsies of vastus lateralis muscle. Despite a 45-90-fold increase in both fasting and postprandial serum insulin levels, both CFTDM patients had diabetes mellitus. Clamp studies revealed that the oldest boy had severe insulin resistance of both liver and peripheral tissues. The impaired insulin-stimulated glucose disposal to peripheral tissues was primarily due to reduced nonoxidative glucose metabolism. These changes were paralleled by reduced basal values of muscle GS total activity, allosterical activation of GS by glucose-6-phosphate, GS protein, and GS mRNA. The father expressed a lesser degree of insulin resistance, and studies of muscle insulin receptor function showed a severe impairment of receptor kinase activity. In conclusion, CFTDM is a novel form of severe hyperinsulinemia and insulin resistance. Whether insulin resistance is causally related to the muscle disorder awaits to be clarified.

  1. Neurochemical oscillations in the basal ganglia.

    Science.gov (United States)

    Noori, Hamid Reza; Jäger, Willi

    2010-01-01

    This work represents an attempt to elucidate the neurochemical processes in the basal ganglia by mathematical modelling. The correlation between neurochemistry and electrophysiology has been used to construct a dynamical system based on the basal ganglia's network structure. Mathematical models were constructed for different physical scales to reformulate the neurochemical and electrophysiological behaviour from synapses up to multi-compartment systems. Transformation functions have been developed to transit between the different scales. We show through numerical simulations that this network produces oscillations in the electrical potentials as well as in neurotransmitter concentrations. In agreement with pharmacological experiments, a parameter sensitivity analysis reveals temporary changes in the neurochemical and electrophysiological systems after single exposure to antipsychotic drugs. This behaviour states the structural stability of the system. The correlation between the neurochemical dynamics and drug-induced behaviour provides the perspective for novel neurobiological hypotheses.

  2. Learning Reward Uncertainty in the Basal Ganglia.

    Directory of Open Access Journals (Sweden)

    John G Mikhael

    2016-09-01

    Full Text Available Learning the reliability of different sources of rewards is critical for making optimal choices. However, despite the existence of detailed theory describing how the expected reward is learned in the basal ganglia, it is not known how reward uncertainty is estimated in these circuits. This paper presents a class of models that encode both the mean reward and the spread of the rewards, the former in the difference between the synaptic weights of D1 and D2 neurons, and the latter in their sum. In the models, the tendency to seek (or avoid options with variable reward can be controlled by increasing (or decreasing the tonic level of dopamine. The models are consistent with the physiology of and synaptic plasticity in the basal ganglia, they explain the effects of dopaminergic manipulations on choices involving risks, and they make multiple experimental predictions.

  3. Basal ganglia lesions in children and adults

    Energy Technology Data Exchange (ETDEWEB)

    Bekiesinska-Figatowska, Monika, E-mail: m.figatowska@mp.pl [Department of Diagnostic Imaging, Institute of Mother and Child, ul. Kasprzaka 17a, 01-211 Warsaw (Poland); Mierzewska, Hanna, E-mail: h.mierzewska@gmail.com [Department of Neurology of Children and Adolescents, Institute of Mother and Child, ul. Kasprzaka 17a, 01-211 Warsaw (Poland); Jurkiewicz, Elżbieta, E-mail: e-jurkiewicz@o2.pl [Department of Diagnostic Imaging, Children' s Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw (Poland)

    2013-05-15

    The term “basal ganglia” refers to caudate and lentiform nuclei, the latter composed of putamen and globus pallidus, substantia nigra and subthalamic nuclei and these deep gray matter structures belong to the extrapyramidal system. Many diseases may present as basal ganglia abnormalities. Magnetic resonance imaging (MRI) and computed tomography (CT) – to a lesser degree – allow for detection of basal ganglia injury. In many cases, MRI alone does not usually allow to establish diagnosis but together with the knowledge of age and circumstances of onset and clinical course of the disease is a powerful tool of differential diagnosis. The lesions may be unilateral: in Rassmussen encephalitis, diabetes with hemichorea/hemiballism and infarction or – more frequently – bilateral in many pathologic conditions. Restricted diffusion is attributable to infarction, acute hypoxic–ischemic injury, hypoglycemia, Leigh disease, encephalitis and CJD. Contrast enhancement may be seen in cases of infarction and encephalitis. T1-hyperintensity of the lesions is uncommon and may be observed unilaterally in case of hemichorea/hemiballism and bilaterally in acute asphyxia in term newborns, in hypoglycemia, NF1, Fahr disease and manganese intoxication. Decreased signal intensity on GRE/T2*-weighted images and/or SWI indicating iron, calcium or hemosiderin depositions is observed in panthotenate kinase-associated neurodegeneration, Parkinson variant of multiple system atrophy, Fahr disease (and other calcifications) as well as with the advancing age. There are a few papers in the literature reviewing basal ganglia lesions. The authors present a more detailed review with rich iconography from the own archive.

  4. Bilateral germinoma of the basal ganglia.

    Science.gov (United States)

    Rossi, Andrea; Garrè, Maria Luisa; Ravegnani, Marcello; Nozza, Paolo; Abbruzzese, Arturo; Giangaspero, Felice; Tortori-Donati, Paolo

    2008-01-01

    Germinoma arising in the bilateral basal ganglia is exceedingly rare, with only five cases reported to date. Owing to non-specific clinical findings and the frequent presence of ill-defined abnormalities without a definite tumor mass on neuroimaging, the diagnosis can be difficult. We describe a case in which magnetic resonance spectroscopy (MRS) findings suggested a tumor and supported the decision to perform biopsy of the lesion.

  5. Basal hydraulic conditions of Ice Stream B

    Science.gov (United States)

    Engelhardt, Hermann; Kamb, Barclay

    1993-01-01

    Fifteen boreholes have been drilled to the base of Ice Stream B in the vicinity of UpB Camp. The boreholes are spread over an area of about 500 x 1000 m. Several till cores were retrieved from the bottom of the 1000-m-deep holes. Laboratory tests using a simple shear box revealed a yield strength of basal till of 2 kPa. This agrees well with in-situ measurements using a shear vane. Since the average basal shear stress of Ice Stream B with a surface slope of 0.1 degree is about 20 kPa, the ice stream cannot be supported by till that weak. Additional support for this conclusion comes from the basal water pressure that has been measured in all boreholes as soon as the hot water drill reached bottom. In several boreholes, the water pressure has been continuously monitored; in two of them, over several years. The water pressure varies but stays within 1 bar of flotation where ice overburden pressure and water pressure are equal. The ratio of water and overburden pressure lies between 0.986 and 1.002. This is an extremely high value as compared to other fast-moving ice masses; e.g., Variegated Glacier in surge has a ratio of 0.8, and Columbia Glacier - a fast-moving tidewater glacier - has a ratio of 0.9. It implies that water flow under the glacier occurs in a thin film and not in conduits that would drain away water too rapidly. It also implies that basal sliding must be very effective. Water flow under the glacier was measured in a salt-injection experiment where a salt pulse was released at the bottom of a borehole while 60 m down-glacier, the electrical resistance was measured between two other boreholes. A flow velocity of 7 mm/s was obtained.

  6. Chemical and thermal stability of insulin

    DEFF Research Database (Denmark)

    Huus, Kasper; Havelund, Svend; Olsen, Helle B

    2006-01-01

    To study the correlation between the thermal and chemical stability of insulin formulations with various insulin hexamer ligands.......To study the correlation between the thermal and chemical stability of insulin formulations with various insulin hexamer ligands....

  7. PACAP stimulates insulin secretion but inhibits insulin sensitivity in mice

    NARCIS (Netherlands)

    Filipsson, K; Pacini, G; Scheurink, AJW; Ahren, B

    Although pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates insulin secretion, its net influence on glucose homeostasis in vivo has not been established. We therefore examined the action of PACAP-27 and PACAP-38 on insulin secretion, insulin sensitivity, and glucose disposal as

  8. Thrice-daily biphasic insulin aspart 30 may be another therapeutic option for Chinese patients with type 2 diabetes inadequately controlled with oral antidiabetic agents

    Institute of Scientific and Technical Information of China (English)

    YANG Wen-ying; JI Qiu-he; ZHU Da-long; YANG Jin-kui; CHEN Lu-lu; LIU Zhi-min; YU De-min; YAN Li

    2009-01-01

    In subjects with type 2 diabetes inadequately controlled with oral antidiabetic agents (OADs), insulin therapy is usually started to improve glycaemic control after failure of diet, exercise and OADs.1 Although there is no standard way to introduce insulin treatment, premixed formulations are a popular option. They offer an alternative to basal-bolus therapy and provide basal and prandial coverage with a single injection. Indeed, Koivisto et al2 in 1999 reported that 39% of patients with type 2 diabetes worldwide used premixed insulin as part of their therapeutic regimen. The modem premixed insulins, such as biphasic insulin aspart 30 (BIAsp 30) are most frequently prescribed twice-daily (BID) in clinical Department of Endocrinology, China-Japan Friendship Hospital, Beijing 100029, China (Yang WY)

  9. Development of optimal kids insulin dosing system formulas for young children with type 1 diabetes mellitus.

    Science.gov (United States)

    Alemzadeh, Ramin; Hoffmann, Raymond G; Dasgupta, Mahua; Parton, Elaine

    2012-05-01

    This study was designed to develop predictive formulas for precise insulin dosing in young children with type 1 diabetes (T1DM). Consecutive 1-year data from a group of 14 young patients (eight girls, six boys) 3.9 ± 0.8 years old with diabetes duration of 2.0 ± 0.8 years, transitioned from multiple daily injections (MDI) to continuous subcutaneous insulin infusion (CSII), were analyzed to identify parameters governing optimal insulin dosing. Body mass index (BMI), total daily dose (TDD), total basal dose, insulin-to-carbohydrate ratio (ICR), correction factor (CF), and mean amplitude of glycemic excursion (MAGE) by continuous glucose monitoring and hemoglobin A(1c) (HbA(1c)) level were evaluated at baseline and every 3 months. The slopes of CF versus 1/TDD, bolus versus TDD, ICR versus 1/TDD, and CF versus ICR were determined. Kids Insulin Dosing System (KIDS) slope constants at follow-up were associated with MAGE compared with baseline (PKIDS formulas estimated TDD=0.74×body weight, total basal dose=0.28×TDD, CF=2,800/TDD, and ICR=13.5×body weight/TDD. The interrelationships among ICR, CF, TBD, and TDD remained stable on CSII and were accompanied by decreased glycemic excursions. The KIDS formulas may yield consistent and easy estimates of insulin dosing factors in very young patients with T1DM.

  10. Field trial on glucose-induced insulin and metabolite responses in Estonian Holstein and Estonian Red dairy cows in two herds

    Directory of Open Access Journals (Sweden)

    Kaart Tanel

    2010-01-01

    Full Text Available Abstract Background Insulin secretion and tissue sensitivity to insulin is considered to be one of the factors controlling lipid metabolism post partum. The objective of this study was to compare glucose-induced blood insulin and metabolite responses in Estonian Holstein (EH, n = 14 and Estonian Red (ER, n = 14 cows. Methods The study was carried out using the glucose tolerance test (GTT performed at 31 ± 1.9 days post partum during negative energy balance. Blood samples were obtained at -15, -5, 5, 10, 20, 30, 40, 50 and 60 min relative to infusion of 0.15 g/kg BW glucose and analysed for glucose, insulin, triglycerides (TG, non-esterified fatty acids (NEFA, cholesterol and β-hydroxybutyrate (BHB. Applying the MIXED Procedure with the SAS System the basal concentration of cholesterol, and basal concentration and concentrations at post-infusion time points for other metabolites, area under the curve (AUC for glucose and insulin, clearance rate (CR for glucose, and maximum increase from basal concentration for glucose and insulin were compared between breeds. Results There was a breed effect on blood NEFA (P P P P P P th min nadir (P th min postinfusion (P Conclusion Our results imply that glucose-induced changes in insulin concentration and metabolite responses to insulin differ between EH and ER dairy cows.

  11. [Effects of chemical constituents of Crossostephium chinense on insulin secretion in rat islets in vitro].

    Science.gov (United States)

    Zou, Lei; Wu, Qi; Yang, Xiuwei; Fu, Dexian

    2009-06-01

    To investigate the effects of the chemical constituents of the whole herbs of Crossostephium chinense on insulin secretion in rat islets. Islets were isolated from rat pancreata, cultured in vitro, and measured by color signals of dithizone stained digestion solution for detection of pancreatic islets. The morphological observation of islets was carried out by inverted microscope. The effects of test compounds, scopoletin (1), scopolin (2), tanacetin (3), quercetagetin-3,6,7-trimethylether (4) and 5-O-methyl-myo-inositol (5) isolated from the whole herbs of C. chinense, on the insulin secreting level from islets were compared with those of glybenclamide as a positive control substances, and the difference in insulin secre