{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T06:19:59Z","timestamp":1781245199298,"version":"3.54.1"},"reference-count":21,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01 AR 071381"],"award-info":[{"award-number":["R01 AR 071381"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01 AR 072602"],"award-info":[{"award-number":["R01 AR 072602"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Endocrino Diabet &amp;amp; Metabol"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background and Aims<\/jats:title><jats:p>Skeletal muscle is the primary site for insulin\u2010mediated glucose uptake and is critical in maintaining whole\u2010body glucose homeostasis. Muscle cells from malignant hyperthermia\u2010susceptible (MHS) individuals exhibit elevated resting cytosolic calcium concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyto<\/jats:sub>), and MHS subjects have a higher incidence of hyperglycaemia. This study investigates the association between elevated resting [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyto<\/jats:sub> and fasting blood sugar (FBS) levels while accounting for subject demographics and clinical variables.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We measured resting [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyto<\/jats:sub> in myotubes derived from muscle biopsies of control and MHS subjects. We analysed the impact of [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyto<\/jats:sub> on FBS levels based on age, sex, and MH status through correlation and comparative analyses. Data were stratified by FBS, [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyto<\/jats:sub>, and age, and heat map and 3D mesh plot analyses were performed to assess the risk of prediabetes in subjects with varying [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyto<\/jats:sub> and age.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Between 2013 and 2024, muscle biopsies from 152 subjects (90 MHS, 62 controls) were used to establish primary myotube culture. MHS myotubes exhibited significantly higher resting [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyto<\/jats:sub> than controls and [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyto<\/jats:sub> positively correlated with fasting blood sugar (FBS) in MHS subjects (<jats:italic>r<\/jats:italic>\u2009=\u20090.227; <jats:italic>p<\/jats:italic>\u2009=\u20090.031) and across the entire cohort (<jats:italic>r<\/jats:italic>\u2009=\u20090.176; <jats:italic>p<\/jats:italic>\u2009=\u20090.034). This correlation was high in prediabetic individuals (<jats:italic>r<\/jats:italic>\u2009=\u20090.43; <jats:italic>p<\/jats:italic>\u2009=\u20090.005) but absent in those with normal FBS. Subjects over 40\u2009years with [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyto<\/jats:sub> &gt;\u2009150\u2009nM showed a higher risk of prediabetes. While aging is a significant risk factor for type 2 diabetes, increased age did not impact FBS levels in individuals with [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyto<\/jats:sub> below 150\u2009nM. However, in those with [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyto<\/jats:sub> exceeding 150\u2009nM, increasing age significantly influenced FBS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Elevated resting [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>cyto<\/jats:sub> in skeletal muscle amplifies the risk of hyperglycemia and may contribute to the onset of type 2 diabetes.<\/jats:p><\/jats:sec>","DOI":"10.1002\/edm2.70052","type":"journal-article","created":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T04:39:01Z","timestamp":1746592741000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Age\u2010Dependent Effects of Muscle Resting Calcium on Fasting Blood Glucose: Implications for Prediabetes Risk"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7290-9326","authenticated-orcid":false,"given":"Eshwar R.","family":"Tammineni","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics Rush University Medical Center  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lourdes","family":"Figueroa","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics Rush University Medical Center  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Fill","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics Rush University Medical Center  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila","family":"Riazi","sequence":"additional","affiliation":[{"name":"Malignant Hyperthermia Unit, Department of Anesthesiology and Pain Medicine University Health Network, University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Manno","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics Rush University Medical Center  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,6]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc09\u2010S302"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2022.872624"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.7555\/JBR.33.20180089"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bja.2018.08.009"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542\u2010199205000\u201000008"},{"key":"e_1_2_8_7_1","first-page":"85","article-title":"[Ca2+]i in Muscles of Malignant Hyperthermia Susceptible Pigs Determined In\u00a0Vivo With Ca2+ Selective Microelectrodes","volume":"9","author":"Lopez J. 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