{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T14:52:46Z","timestamp":1793976766470,"version":"4.8.0"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:p>\n                    Kidney disease leads to clinically relevant disturbances in glucose and insulin homeostasis, but the pathophysiology in moderate-severe CKD remains incompletely defined. In a cross-sectional study of 59 participants with nondiabetic CKD (mean eGFR =37.6 ml\/min per 1.73 m\n                    <jats:sup>2<\/jats:sup>\n                    ) and 39 healthy control subjects, we quantified insulin sensitivity, clearance, and secretion and glucose tolerance using hyperinsulinemic-euglycemic clamp and intravenous and oral glucose tolerance tests. Participants with CKD had lower insulin sensitivity than participants without CKD (mean[SD] 3.9[2.0] versus 5.0 [2.0] mg\/min per \u00b5U\/ml;\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    &lt;0.01). Insulin clearance correlated with insulin sensitivity (\n                    <jats:italic toggle=\"yes\">r<\/jats:italic>\n                    =0.72;\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    &lt;0.001) and was also lower in participants with CKD than controls (876 [226] versus 998 [212] ml\/min;\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    &lt;0.01). Adjustment for physical activity, diet, fat mass, and fatfree mass in addition to demographics and smoking partially attenuated associations of CKD with insulin sensitivity (adjusted difference, \u22120.7; 95% confidence interval, \u22121.4 to 0.0 mg\/min per \u00b5U\/ml) and insulin clearance (adjusted difference, \u221285; 95% confidence interval, \u2212160 to \u221210 ml\/min). Among participants with CKD, eGFR did not significantly correlate with insulin sensitivity or clearance. Insulin secretion and glucose tolerance did not differ significantly between groups, but 65% of participants with CKD had impaired glucose tolerance. In conclusion, moderate-severe CKD associated with reductions in insulin sensitivity and clearance that are explained, in part, by differences in lifestyle and body composition. We did not observe a CKD-specific deficit in insulin secretion, but the combination of insulin resistance and inadequate augmentation of insulin secretion led to a high prevalence of impaired glucose tolerance.\n                  <\/jats:p>","DOI":"10.1681\/asn.2015070756","type":"journal-article","created":{"date-parts":[[2016,1,28]],"date-time":"2016-01-28T23:14:13Z","timestamp":1454022853000},"page":"2861-2871","source":"Crossref","is-referenced-by-count":104,"title":["Impaired Glucose and Insulin Homeostasis in Moderate-Severe CKD"],"prefix":"10.1681","volume":"27","author":[{"given":"Ian H.","family":"de Boer","sequence":"first","affiliation":[{"name":"Division of Nephrology and Kidney Research Institute and"},{"name":"Veterans Affairs Puget Sound Health Care System, Seattle, Washington; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leila","family":"Zelnick","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Kidney Research Institute and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Afkarian","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Kidney Research Institute and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernest","family":"Ayers","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Kidney Research Institute and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Curtin","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Kidney Research Institute and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Himmelfarb","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Kidney Research Institute and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. Alp","family":"Ikizler","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Vanderbilt Center for Kidney Disease, Vanderbilt University Medical Center, Nashville, Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven E.","family":"Kahn","sequence":"additional","affiliation":[{"name":"Division of Metabolism, Endocrinology, and Nutrition, University of Washington, Seattle, Washington;"},{"name":"Veterans Affairs Puget Sound Health Care System, Seattle, Washington; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan","family":"Kestenbaum","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Kidney Research Institute and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Utzschneider","sequence":"additional","affiliation":[{"name":"Division of Metabolism, Endocrinology, and Nutrition, University of Washington, Seattle, Washington;"},{"name":"Veterans Affairs Puget Sound Health Care System, Seattle, Washington; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2016,1,28]]},"reference":[{"key":"B1-20231016","doi-asserted-by":"crossref","first-page":"275","DOI":"10.7326\/0003-4819-65-2-275","volume":"65","author":"Hutchings","year":"1966","journal-title":"Ann Intern Med"},{"key":"B2-20231016","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1172\/JCI109144","article-title":"Glucose intolerance in uremia. 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