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  • 1
    Online Resource
    Online Resource
    Proinsulin levels in patients with pancreatic diabetes are associated with functional changes in insulin secretion rather than pancreatic β-cell area
    Oxford University Press (OUP) ; 2010
    In:  European Journal of Endocrinology Vol. 163, No. 4 ( 2010-10), p. 551-558
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 163, No. 4 ( 2010-10), p. 551-558
    Abstract: Hyperproinsulinaemia has been reported in patients with type 2 diabetes. It is unclear whether this is due to an intrinsic defect in β-cell function or secondary to the increased demand on the β-cells. We investigated whether hyperproinsulinaemia is also present in patients with secondary diabetes, and whether proinsulin levels are associated with impaired β-cell area or function. Patients and methods Thirty-three patients with and without diabetes secondary to pancreatic diseases were studied prior to pancreatic surgery. Intact and total proinsulin levels were compared with the pancreatic β-cell area and measures of insulin secretion and action. Results Fasting concentrations of total and intact proinsulin were similar in patients with normal, impaired (including two cases of impaired fasting glucose) and diabetic glucose tolerance ( P =0.58 and P =0.98 respectively). There were no differences in the total proinsulin/insulin or intact proinsulin/insulin ratio between the groups ( P =0.23 and P =0.71 respectively). There was a weak inverse association between the total proinsulin/insulin ratio and pancreatic β-cell area ( r 2 =0.14, P =0.032), whereas the intact proinsulin/insulin ratio and the intact and total proinsulin levels were unrelated to β-cell area. However, a strong inverse relationship between homeostasis model assessment index of β-cell function and both the total and the intact proinsulin/insulin ratio was found ( r 2 =0.55 and r 2 =0.48 respectively). The association of insulin resistance (IR) with intact proinsulin was much weaker than the correlation with fasting insulin. Conclusions Hyperproinsulinaemia is associated with defects in insulin secretion rather than a reduction in β-cell area. The weak association between intact proinsulin and IR argues against the usefulness of this parameter in clinical practice.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1530/EJE-10-0330
    RVK:
    WA 15000
    Language: Unknown
    Publisher: Oxford University Press (OUP)
    Publication Date: 2010
    detail.hit.zdb_id: 1485160-X
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  • 2
    Online Resource
    Online Resource
    Cardiovascular Safety and Benefits of Semaglutide in Patients With Type 2 Diabetes: Findings From SUSTAIN 6 and PIONEER 6
    Frontiers Media SA ; 2021
    In:  Frontiers in Endocrinology Vol. 12 ( 2021-3-29)
    Details
    In: Frontiers in Endocrinology, Frontiers Media SA, Vol. 12 ( 2021-3-29)
    Abstract: To exclude an excess risk of cardiovascular (CV) events, CV outcomes trials (CVOTs) have assessed the effects of new glucose-lowering therapies, including glucagon-like peptide-1 receptor agonists (GLP-1RAs), in patients with type 2 diabetes and established CV disease or CV risk factors. The CV safety of semaglutide vs. placebo, when added to standard care, was evaluated in the SUSTAIN 6 trial for the formulation administered once-weekly subcutaneously and in PIONEER 6 for the new once-daily oral formulation. In SUSTAIN 6 and PIONEER 6, both powered to demonstrate noninferiority (upper 95% confidence interval [CI] of the hazard ratio [HR] & lt;1.8), there were fewer first major adverse CV events with semaglutide vs. placebo, with HRs of 0.74 (95% CI 0.58–0.95) and 0.79 (0.57–1.11), respectively. In SUSTAIN 6, the results were significant for noninferiority and superiority, although the latter was not prespecified. Surprisingly, CV and all-cause mortality were significantly reduced by oral semaglutide in PIONEER 6. The ongoing SOUL CVOT will further inform about CV outcomes with oral semaglutide vs. placebo (NCT03914326). Findings from SUSTAIN 6 and PIONEER 6 fall within the spectrum reported with other GLP-1RA CVOTs: noninferiority vs. placebo for major CV events was seen with lixisenatide and exenatide extended-release, while superiority was demonstrated with liraglutide, albiglutide, and dulaglutide. Beneficial outcomes have been recognized in international guidelines, which recommend subcutaneous liraglutide, semaglutide, and dulaglutide to reduce the risk of CV events in high-risk patients. Both indirect mechanisms via risk factor modification and direct effects via GLP-1 receptors in the CV system have been proposed to be responsible for CV event reductions. The exact mechanism(s) remains to be characterized, but appears to be mainly linked to anti-atherosclerotic effects. Further research is needed to elucidate the relevant mechanisms for CV benefits of GLP-1RAs.
    Type of Medium: Online Resource
    ISSN: 1664-2392
    URL: Article
    DOI: 10.3389/fendo.2021.645566
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2592084-4
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  • 3
    Online Resource
    Online Resource
    Is glucagon-like peptide 1 an incretin hormone?
    Springer Science and Business Media LLC ; 1999
    In:  Diabetologia Vol. 42, No. 3 ( 1999-2-19), p. 373-379
    Details
    In: Diabetologia, Springer Science and Business Media LLC, Vol. 42, No. 3 ( 1999-2-19), p. 373-379
    Type of Medium: Online Resource
    ISSN: 0012-186X , 1432-0428
    URL: Article
    DOI: 10.1007/s001250051165
    RVK:
    XA 40615
    Language: Unknown
    Publisher: Springer Science and Business Media LLC
    Publication Date: 1999
    detail.hit.zdb_id: 1458993-X
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  • 4
    Online Resource
    Online Resource
    MANAGEMENT OF ENDOCRINE DISEASE: Are all GLP-1 agonists equal in the treatment of type 2 diabetes?
    Oxford University Press (OUP) ; 2019
    In:  European Journal of Endocrinology Vol. 181, No. 6 ( 2019-12), p. R211-R234
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 181, No. 6 ( 2019-12), p. R211-R234
    Abstract: GLP-1, a peptide hormone secreted from the gut, stimulating insulin and suppressing glucagon secretion was identified as a parent compound for novel treatments of diabetes, but was degraded (dipeptidyl peptidase-4) and eliminated (mainly by kidneys) too fast (half-life 1–2 min) to be useful as a therapeutic agent. GLP-1 receptor agonist has been used to treat patients with type 2 diabetes since 2007, when exenatide (twice daily) was approved in 2007. Compounds with longer duration of action (once daily, once weekly) and with increasingly better efficacy with respect to glycaemic control and body weight reduction have been developed, and in a recent ADA/EASD consensus statement, were recommended as the first injectable diabetes therapy after failure of oral glucose-lowering medications. Most GLP-1 receptor agonists (lixisenatide q.d., liraglutide q.d., exenatide q.w., dulaglutide q.w., albiglutide q.w., semaglutide q.w., all for s.c. injection, and the first oral preparation, oral semaglutide) have been examined in cardiovascular outcomes studies. Beyond proving their safety in vulnerable patients, most of whom had pre-existing heart disease, liraglutide, semaglutide, albiglutide, and dulaglutide reduced the time to first major adverse cardiovascular events (non-fatal myocardial infarction and stroke, cardiovascular death). Liraglutide, in addition, reduced cardiovascular and all-cause mortality. It is the purpose of the present review to describe clinically important differences, regarding pharmacokinetic behaviour, glucose-lowering potency, effectiveness of reducing body weight and controlling other cardiovascular risk factors, and of the influence of GLP-1 receptor agonist treatment on cardiovascular outcomes in patients either presenting with or without pre-existing cardiovascular disease (atherosclerotic, ischemic or congestive heart failure).
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1530/EJE-19-0566
    RVK:
    WA 15000
    Language: Unknown
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 1485160-X
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  • 5
    Online Resource
    Online Resource
    Exploiting the antidiabetic properties of incretins to treat type 2 diabetes mellitus: glucagon-like peptide 1 receptor agonists or insulin for patients with inadequate glycemic control?
    Oxford University Press (OUP) ; 2008
    In:  European Journal of Endocrinology Vol. 158, No. 6 ( 2008-06), p. 773-784
    Details
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 158, No. 6 ( 2008-06), p. 773-784
    Abstract: Type 2 diabetes mellitus is associated with progressive decreases in pancreatic β-cell function. Most patients thus require increasingly intensive treatment, including oral combination therapies followed by insulin. Fear of hypoglycemia is a potential barrier to treatment adherence and glycemic control, while weight gain can exacerbate hyperglycemia or insulin resistance. Administration of insulin can roughly mimic physiologic insulin secretion but does not address underlying pathophysiology. Glucagon-like peptide 1 (GLP-1) is an incretin hormone released by the gut in response to meal intake that helps to maintain glucose homeostasis through coordinated effects on islet α- and β-cells, inhibiting glucagon output, and stimulating insulin secretion in a glucose-dependent manner. Biological effects of GLP-1 include slowing gastric emptying and decreasing appetite. Incretin mimetics (GLP-1 receptor agonists with more suitable pharmacokinetic properties versus GLP-1) significantly lower hemoglobin A1c, body weight, and postprandial glucose excursions in humans and significantly improve β-cell function in vivo (animal data). These novel incretin-based therapies offer the potential to reduce body weight or prevent weight gain, although the durability of these effects and their potential long-term benefits need to be studied further. This article reviews recent clinical trials comparing therapy with the incretin mimetic exenatide to insulin in patients with oral treatment failure, identifies factors consistent with the use of each treatment, and delineates areas for future research.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    URL: Article
    DOI: 10.1530/EJE-07-0804
    RVK:
    WA 15000
    Language: Unknown
    Publisher: Oxford University Press (OUP)
    Publication Date: 2008
    detail.hit.zdb_id: 1485160-X
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  • 6
    Online Resource
    Online Resource
    External quality assessment schemes for glucose measurements in Germany: factors for successful participation, analytical performance and medical impact
    Walter de Gruyter GmbH ; 2018
    In:  Clinical Chemistry and Laboratory Medicine (CCLM) Vol. 56, No. 8 ( 2018-07-26), p. 1238-1250
    Details
    In: Clinical Chemistry and Laboratory Medicine (CCLM), Walter de Gruyter GmbH, Vol. 56, No. 8 ( 2018-07-26), p. 1238-1250
    Abstract: Determination of blood glucose concentration is one of the most important measurements in clinical chemistry worldwide. Analyzers in central laboratories (CL) and point-of-care tests (POCT) are both frequently used. In Germany, regular participation in external quality assessment (EQA) schemes is mandatory for laboratories performing glucose testing. Methods: Glucose testing data from the two German EQAs “Reference Institute for Bioanalytics” (RfB) and “INSTAND – Gesellschaft zur Förderung der Qualitätssicherung in medizinischen Laboratorien” (Instand) were analyzed from 2012 to 2016. Multivariable odds ratios (OR) for the probability to reach a “good” result were calculated. Imprecision and bias were determined and clinical risk of measurement errors estimated. Results: The device employed was the most important variable required for a “good” performance in all EQAs. Additional participation in an EQA for CL automated analyzers improved performance in POCT EQAs. The reciprocal effect was less pronounced. New participants performed worse than experienced participants especially in CL EQAs. Imprecision was generally smaller for CL, but some POCT devices reached a comparable performance. Large lot-to-lot differences occurred in over 10% of analyzed cases. We propose the “bias budget” as a new metric to express the maximum allowable bias that still carries acceptable medical risk. Bias budgets were smallest and clinical risks of errors greatest in the low range of measurement 60–115 mg/dL (3.3–6.4 mmol/L) for most devices. Conclusions: EQAs help to maintain high analytical performances. They generate important data that serve as the foundation for learning and improvement in the laboratory healthcare system.
    Type of Medium: Online Resource
    ISSN: 1437-4331 , 1434-6621
    URL: Article
    DOI: 10.1515/cclm-2017-1142
    Language: Unknown
    Publisher: Walter de Gruyter GmbH
    Publication Date: 2018
    detail.hit.zdb_id: 1492732-9
    SSG: 15,3
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