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      The Clash of Two Epidemics: the Relationship Between Opioids and Glucose Metabolism

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          Abstract

          Purpose of Review

          We are currently in the midst of a global opioid epidemic. Opioids affect many physiological processes, but one side effect that is not often taken into consideration is the opioid-induced alteration in blood glucose levels.

          Recent Findings

          This review shows that the vast majority of studies report that opioid stimulation increases blood glucose levels. In addition, plasma levels of the endogenous opioid β-endorphin rise in response to low blood glucose. In contrast, in hyperglycaemic baseline conditions such as in patients with type 2 diabetes mellitus (T2DM), opioid stimulation lowers blood glucose levels. Furthermore, obesity itself alters sensitivity to opioids, changes opioid receptor expression and increases plasma β-endorphin levels.

          Summary

          Thus, opioid stimulation can have various side effects on glycaemia that should be taken into consideration upon prescribing opioid-based medication, and more research is needed to unravel the interaction between obesity, glycaemia and opioid use.

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          Most cited references127

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          CDC Guideline for Prescribing Opioids for Chronic Pain - United States, 2016.

          This guideline provides recommendations for primary care clinicians who are prescribing opioids for chronic pain outside of active cancer treatment, palliative care, and end-of-life care. The guideline addresses 1) when to initiate or continue opioids for chronic pain; 2) opioid selection, dosage, duration, follow-up, and discontinuation; and 3) assessing risk and addressing harms of opioid use. CDC developed the guideline using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework, and recommendations are made on the basis of a systematic review of the scientific evidence while considering benefits and harms, values and preferences, and resource allocation. CDC obtained input from experts, stakeholders, the public, peer reviewers, and a federally chartered advisory committee. It is important that patients receive appropriate pain treatment with careful consideration of the benefits and risks of treatment options. This guideline is intended to improve communication between clinicians and patients about the risks and benefits of opioid therapy for chronic pain, improve the safety and effectiveness of pain treatment, and reduce the risks associated with long-term opioid therapy, including opioid use disorder, overdose, and death. CDC has provided a checklist for prescribing opioids for chronic pain (http://stacks.cdc.gov/view/cdc/38025) as well as a website (http://www.cdc.gov/drugoverdose/prescribingresources.html) with additional tools to guide clinicians in implementing the recommendations.
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            Global patterns of opioid use and dependence: harms to populations, interventions, and future action

            This paper summarises evidence for medicinal uses of opioids; harms related to the extra-medical use and dependence upon these drugs, and for a wide range of interventions to address the harms related to extra-medical opioid use. Finally, we use mathematical modelling to estimate harms and explore the overall health benefits of opioid agonist treatment (OAT) in a range of settings that vary in levels of opioid use and associated harms (overdose, HIV, HCV, suicide, accidental injuries) and responses. Estimates in 2017 suggest 40.5 million people were dependent upon opioids (40.5 million people, 95%UI 34.3–47.9 million) and 109,500 people died from opioid overdose (10.5,800–113,600). OAT can be highly effective in reducing illicit opioid use and improving multiple health and social outcomes, including reduced overall mortality and key causes of death including overdose, suicide, and other injuries. Modelling suggested scaling-up and retaining people in OAT, including providing OAT in prison, could avert a median of 7.7%, 14.5% and 25.9% deaths over the next 20 years (compared to scenarios without OAT) in Kentucky, Kyiv and Tehran, with more impact achieved in Tehran and Kyiv due to the added benefits on HIV mortality.. Other pharmacological and non-pharmacological treatments have varying levels of evidence for effectiveness and patient acceptability. Other effective interventions are those focused on preventing harms associated with problematic opioid use. Despite strong evidence for the effectiveness of a range of interventions to improve the health and well-being of people who are dependent on opioids, coverage is low even in high income countries. Treatment quality may be less than desirable, and considerable human, social, and economic harms arise from the criminalisation of illicit opioid use and dependence. Alternative policy frameworks are recommended that adopt a human rights and public health-based approach, do not make drug use a criminal behaviour and seek to reduce drug related harm at the population level.
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              Identification of two related pentapeptides from the brain with potent opiate agonist activity.

              Enkephalin, a natural ligand for opiate receptors is composed of the pentapepides H-Tyr-Gly-Gly-Phe-Met-OH and H-Tyr-Gly-Gly-Phe-Leu-OH. The evidence is based on the determination of the amino acid sequence of natural enkephalin by the dansyl-Edman procedure and by mass spectrometry followed by synthesis and comparison of the natural and synthetic peptides.
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                Author and article information

                Contributors
                s.e.lafleur@amsterdamumc.nl
                Journal
                Curr Diab Rep
                Curr Diab Rep
                Current Diabetes Reports
                Springer US (New York )
                1534-4827
                1539-0829
                20 May 2022
                20 May 2022
                2022
                : 22
                : 7
                : 301-310
                Affiliations
                [1 ]GRID grid.7177.6, ISNI 0000000084992262, Laboratory of Endocrinology, Department of Clinical Chemistry, Amsterdam Neuroscience, Amsterdam Gastroenterology, Endocrinology and Metabolism, , Amsterdam University Medical Center, Location AMC, University of Amsterdam, ; Meibergdreef 9, Amsterdam, Netherlands
                [2 ]GRID grid.7177.6, ISNI 0000000084992262, Department of Endocrinology and Metabolism, Neuroscience Amsterdam, Amsterdam Gastroenterology, Endocrinology and Metabolism, , Amsterdam University Medical Center, Location AMC, University of Amsterdam, ; Meibergdreef 9, K2-283, 1105 AZ Amsterdam, the Netherlands
                [3 ]GRID grid.419918.c, ISNI 0000 0001 2171 8263, Metabolism and Reward Group, , Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, ; Meibergdreef 47, Amsterdam, Netherlands
                Article
                1473
                10.1007/s11892-022-01473-0
                9188528
                35593927
                b488b5f4-a6a0-4898-89d1-d05d9cfdec94
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 5 April 2022
                Categories
                Other Forms of Diabetes and Its Complications (B Wojeck and H Yaggi, Section Editors)
                Custom metadata
                © Springer Science+Business Media, LLC, part of Springer Nature 2022

                Endocrinology & Diabetes
                opioids,blood glucose,hyperglycaemia,obesity,diabetes mellitus,β-endorphin
                Endocrinology & Diabetes
                opioids, blood glucose, hyperglycaemia, obesity, diabetes mellitus, β-endorphin

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