{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T15:44:55Z","timestamp":1792597495856,"version":"4.5.0"},"reference-count":43,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,8,5]],"date-time":"2020-08-05T00:00:00Z","timestamp":1596585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015617","name":"Industrial Health Foundation","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100015617","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Calcium and phosphate may play an important role in cardio-metabolic abnormalities, including type 2 diabetes; however, epidemiological evidence of the association of calcium and phosphate status with glucose metabolism among Asians is limited. In the current study, we performed a cross-sectional analysis of the association of serum calcium, phosphate, and calcium\u2013phosphate product concentrations with glucose metabolism markers among Japanese individuals. Overall, 1701 workers (aged 18\u201378 years) who participated in a health survey were enrolled in this study. Multivariable linear regression models were used to estimate means of homeostatic model assessment of insulin resistance (HOMA-IR), homeostatic model assessment of \u03b2-cell function (HOMA-\u03b2), and glycated hemoglobin (HbA1c). Serum calcium concentration was positively associated with HOMA-IR and HbA1c (p for trend &lt; 0.01). Multivariable-adjusted means (95% confidence interval (CI)) of HOMA-IR for the lowest and highest quartiles of serum calcium were 0.78 (0.75\u20130.82) and 1.01 (0.96\u20131.07), respectively. The corresponding values for HbA1c were 5.24 (5.22\u20135.27) and 5.29 (5.26\u20135.32), respectively. Serum phosphate and calcium\u2013phosphate product concentrations were inversely associated with HOMA-IR (p for trend &lt; 0.01). Multivariable-adjusted means (95% CI) of HOMA-IR for the lowest and highest quartiles of serum phosphate were 1.04 (0.99\u20131.09) and 0.72 (0.69\u20130.76), respectively. The corresponding values for calcium\u2013phosphate product were 1.04 (0.99\u20131.09) and 0.73 (0.69\u20130.77), respectively. The current findings suggest that higher serum calcium and lower serum phosphate concentrations are associated with IR among apparently healthy adults.<\/jats:p>","DOI":"10.3390\/nu12082344","type":"journal-article","created":{"date-parts":[[2020,8,5]],"date-time":"2020-08-05T15:13:18Z","timestamp":1596640398000},"page":"2344","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Association of Serum Calcium and Phosphate Concentrations with Glucose Metabolism Markers: The Furukawa Nutrition and Health Study"],"prefix":"10.3390","volume":"12","author":[{"given":"Shamima","family":"Akter","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Prevention, Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo 162-8655, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masafumi","family":"Eguchi","sequence":"additional","affiliation":[{"name":"Department of Health Administration, Furukawa Electric Corporation, Tokyo 100-8322, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Kochi","sequence":"additional","affiliation":[{"name":"Department of Health Administration, Furukawa Electric Corporation, Tokyo 100-8322, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isamu","family":"Kabe","sequence":"additional","affiliation":[{"name":"Department of Health Administration, Furukawa Electric Corporation, Tokyo 100-8322, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Nanri","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Prevention, Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo 162-8655, Japan"},{"name":"Department of Food and Health Sciences, Fukuoka Women\u2019s University, Fukuoka 813-8529, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuya","family":"Mizoue","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Prevention, Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo 162-8655, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1016\/S0140-6736(17)32152-9","article-title":"Global, regional, and national age-sex specific mortality for 264 causes of death, 1980\u20132016: A systematic analysis for the Global Burden of Disease Study 2016","volume":"390","author":"Naghavi","year":"2017","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1016\/S0140-6736(18)32335-3","article-title":"Global, regional, and national disability-adjusted life-years (DALYs) for 359 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990\u20132017: A systematic analysis for the Global Burden of Disease Study 2017","volume":"392","author":"Kyu","year":"2018","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"107843","DOI":"10.1016\/j.diabres.2019.107843","article-title":"Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition","volume":"157","author":"Saeedi","year":"2019","journal-title":"Diabetes Res. Clin. Pr."},{"key":"ref_4","unstructured":"International Diabetes Federation (2020, August 05). IDF Diabetes Atlas, Available online: https:\/\/diabetesatlas.org\/en\/#."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1016\/S0026-0495(97)90212-2","article-title":"Glucose intolerance is associated with altered calcium homeostasis: A possible link between increased serum calcium concentration and cardiovascular disease mortality","volume":"46","author":"Wareham","year":"1997","journal-title":"Metabolism"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1007\/s10654-013-9822-y","article-title":"Serum calcium and the calcium-sensing receptor polymorphism rs17251221 in relation to coronary heart disease, type 2 diabetes, cancer and mortality: The Troms\u00f8 Study","volume":"28","author":"Jorde","year":"2013","journal-title":"Eur. J. Epidemiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1007\/s00125-014-3241-9","article-title":"Calcium and phosphate concentrations and future development of type 2 diabetes: The Insulin Resistance Atherosclerosis Study","volume":"57","author":"Lorenzo","year":"2014","journal-title":"Diabetologia"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.3945\/ajcn.115.130021","article-title":"Serum calcium and incident type 2 diabetes: The Atherosclerosis Risk in Communities (ARIC) study","volume":"104","author":"Rooney","year":"2016","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.diabres.2017.08.022","article-title":"Serum calcium changes and risk of type 2 diabetes mellitus in Asian population","volume":"133","author":"Suh","year":"2017","journal-title":"Diabetes Res. Clin. Pr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"S206","DOI":"10.1111\/j.1440-1797.2006.00645.x","article-title":"Calcium \u00d7 phosphate product","volume":"11","author":"Hawley","year":"2006","journal-title":"Nephrology"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Fraser, A., Williams, D.M., and Lawlor, D.A. (2010). Associations of Serum 25-Hydroxyvitamin D, Parathyroid Hormone and Calcium with Cardiovascular Risk Factors: Analysis of 3 NHANES Cycles (2001\u20132006). PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0013882"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3336","DOI":"10.2337\/diabetes.54.11.3336","article-title":"Altered calcium homeostasis is correlated with abnormalities of fasting serum glucose, insulin resistance, and beta-cell function in the Newfoundland population","volume":"54","author":"Sun","year":"2005","journal-title":"Diabetes"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"nzy085","DOI":"10.1093\/cdn\/nzy085","article-title":"Serum Calcium Concentrations, Chronic Inflammation and Glucose Metabolism: A Cross-Sectional Analysis in the Andhra Pradesh Children and Parents Study (APCaPS)","volume":"3","author":"Shridhar","year":"2018","journal-title":"Curr. Dev. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.ahj.2008.05.016","article-title":"Calcium-phosphate levels and cardiovascular disease in community-dwelling adults: The Atherosclerosis Risk in Communities (ARIC) Study","volume":"156","author":"Foley","year":"2008","journal-title":"Am. Heart J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1159\/000480354","article-title":"Reduced Serum Phosphorus Levels Were Associated with Metabolic Syndrome in Men But Not in Women: A Cross-Sectional Study among the Japanese Population","volume":"71","author":"Shimodaira","year":"2017","journal-title":"Ann. Nutr. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1038\/sj.ejcn.1602375","article-title":"Association of serum phosphate levels with glucose tolerance, insulin sensitivity and insulin secretion in non-diabetic subjects","volume":"60","author":"Haap","year":"2006","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/S0140-6736(10)62037-5","article-title":"National, regional, and global trends in body-mass index since 1980: Systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1 million participants","volume":"377","author":"Finucane","year":"2011","journal-title":"Lancet"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"S37","DOI":"10.1016\/j.diabres.2003.11.024","article-title":"Insulin secretion capacity in the development from normal glucose tolerance to type 2 diabetes","volume":"66","author":"Fukushima","year":"2004","journal-title":"Diabetes Res. Clin. Pr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.clnesp.2018.01.011","article-title":"Association of dietary and serum magnesium with glucose metabolism markers: The Furukawa Nutrition and Health Study","volume":"24","author":"Akter","year":"2018","journal-title":"Clin. Nutr. ESPEN"},{"key":"ref_20","unstructured":"Science and Technology Agency (2005). Standard Tables of Food Composition in Japan."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1093\/clinchem\/38.6.904","article-title":"Single Stable Reagent (Arsenazo III) for Optically Robust Measurement of Calcium in Serum and Plasma","volume":"38","author":"Leary","year":"1992","journal-title":"Clin. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1093\/clinchem\/20.3.332","article-title":"Enzymatic Method for Determination of Inorganic Phosphate in Serum and Urine with a Centrifugal Analyzer","volume":"20","author":"Pesce","year":"1974","journal-title":"Clin. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4139","DOI":"10.1039\/C9AN00112C","article-title":"Insulin: A review of analytical methods","volume":"144","author":"Shen","year":"2019","journal-title":"Analyst"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1007\/BF00280883","article-title":"Homeostasis model assessment: Insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man","volume":"28","author":"Matthews","year":"1985","journal-title":"Diabetologia"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.metabol.2012.07.025","article-title":"Serum ferritin is associated with markers of insulin resistance in Japanese men but not in women","volume":"62","author":"Pham","year":"2013","journal-title":"Metabolism"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"542","DOI":"10.2169\/internalmedicine.44.542","article-title":"Association between C-reactive Protein and Insulin Resistance in a Japanese Population: The Minoh Study","volume":"44","author":"Nakanishi","year":"2005","journal-title":"Intern. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1111\/j.1365-277X.2008.00848.x","article-title":"Calcium intake and its relationship with adiposity and insulin resistance in post-pubertal adolescents","volume":"21","author":"Cintra","year":"2008","journal-title":"J. Hum. Nutr. Diet"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s41110-017-0046-x","article-title":"Role of vitamin D in insulin resistance in obese individuals","volume":"42","author":"Lima","year":"2017","journal-title":"Nutrire"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s00125-006-0532-9","article-title":"Serum calcium is independently associated with insulin sensitivity measured with euglycaemic\u2013hyperinsulinaemic clamp in a community-based cohort","volume":"50","author":"Hagstrom","year":"2006","journal-title":"Diabetologia"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"644","DOI":"10.2337\/dc06-1759","article-title":"Insulin Secretion and Insulin Sensitivity in Relation to Fasting Glucose in Healthy Subjects","volume":"30","author":"Ahren","year":"2007","journal-title":"Diabetes Care"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3352","DOI":"10.1016\/S0021-9258(18)53701-7","article-title":"GLUT-4 phosphorylation and its intrinsic activity. Mechanism of Ca(2+)-induced inhibition of insulin-stimulated glucose transport","volume":"268","author":"Begum","year":"1993","journal-title":"J. Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1093\/ajh\/5.7.459","article-title":"Cytosolic Calcium and Insulin Resistance in Elderly Patients With Essential Hypertension","volume":"5","author":"Byyny","year":"1992","journal-title":"Am. J. Hypertens"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.cmet.2015.06.010","article-title":"Calcium Homeostasis and Organelle Function in the Pathogenesis of Obesity and Diabetes","volume":"22","author":"Arruda","year":"2015","journal-title":"Cell Metab."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1172\/JCI29069","article-title":"Inflammation and insulin resistance","volume":"116","author":"Shoelson","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3378","DOI":"10.1096\/fj.201600473R","article-title":"Hypophosphatemia promotes lower rates of muscle ATP synthesis","volume":"30","author":"Pesta","year":"2016","journal-title":"FASEB J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2747","DOI":"10.1242\/jcs.204941","article-title":"Polyphosphate as a donor of high-energy phosphate for the synthesis of ADP and ATP","volume":"130","author":"Wang","year":"2017","journal-title":"J. Cell Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e13017","DOI":"10.1111\/eci.13017","article-title":"Energy metabolism of white adipose tissue and insulin resistance in humans","volume":"48","author":"Roden","year":"2018","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1152\/physrev.1981.61.4.914","article-title":"Regulation of insulin release by calcium","volume":"61","author":"Wollheim","year":"1981","journal-title":"Physiol. Rev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1677\/joe.0.1650173","article-title":"Non-Ca2+-homeostatic functions of the extracellular Ca2+-sensing receptor (CaR) in endocrine tissues","volume":"165","author":"Squires","year":"2000","journal-title":"J. Endocrinol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1677\/joe.1.06891","article-title":"Activation of the extracellular calcium-sensing receptor initiates insulin secretion from human islets of Langerhans: Involvement of protein kinases","volume":"190","author":"Gray","year":"2006","journal-title":"J. Endocrinol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1080\/13813450701531185","article-title":"Expression and function of the extracellular calcium-sensing receptor in pancreatic beta-cells","volume":"113","author":"Jones","year":"2007","journal-title":"Arch. Physiol. Biochem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.2337\/diacare.27.6.1487","article-title":"Use and Abuse of HOMA Modeling","volume":"27","author":"Wallace","year":"2004","journal-title":"Diabetes Care"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1136\/jcp.34.12.1368","article-title":"Increased absolute calcium binding to albumin in hypoalbuminaemia","volume":"34","author":"Besarab","year":"1981","journal-title":"J. Clin. Pathol."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/8\/2344\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:56:54Z","timestamp":1760176614000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/8\/2344"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,5]]},"references-count":43,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2020,8]]}},"alternative-id":["nu12082344"],"URL":"https:\/\/doi.org\/10.3390\/nu12082344","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,5]]}}}