title: Impaired Glucose and Insulin Homeostasis in Moderate-Severe CKD.
abstract: 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(2)) 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 µU/ml; P<0.01). Insulin clearance correlated with insulin sensitivity (r=0.72; P<0.001) and was also lower in participants with CKD than controls (876 [226] versus 998 [212] ml/min; P<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, -0.7; 95% confidence interval, -1.4 to 0.0 mg/min per µU/ml) and insulin clearance (adjusted difference, -85; 95% confidence interval, -160 to -10 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.
authors.affiliation: Division of Nephrology and Kidney Research Institute and Veterans Affairs Puget Sound Health Care System, Seattle, Washington; and deboer@u.washington.edu.
authors.forename: Ian H
authors.initials: IH
authors.lastname: de Boer
authors.affiliation: Division of Nephrology and Kidney Research Institute and.
authors.forename: Leila
authors.initials: L
authors.lastname: Zelnick
authors.affiliation: Division of Nephrology and Kidney Research Institute and.
authors.forename: Maryam
authors.initials: M
authors.lastname: Afkarian
authors.affiliation: Division of Nephrology and Kidney Research Institute and.
authors.forename: Ernest
authors.initials: E
authors.lastname: Ayers
authors.affiliation: Division of Nephrology and Kidney Research Institute and.
authors.forename: Laura
authors.initials: L
authors.lastname: Curtin
authors.affiliation: Division of Nephrology and Kidney Research Institute and.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Himmelfarb
authors.affiliation: Division of Nephrology and Vanderbilt Center for Kidney Disease, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: T Alp
authors.initials: TA
authors.lastname: Ikizler
authors.affiliation: Veterans Affairs Puget Sound Health Care System, Seattle, Washington; and Division of Metabolism, Endocrinology, and Nutrition, University of Washington, Seattle, Washington;
authors.forename: Steven E
authors.initials: SE
authors.lastname: Kahn
authors.affiliation: Division of Nephrology and Kidney Research Institute and.
authors.forename: Bryan
authors.initials: B
authors.lastname: Kestenbaum
authors.affiliation: Veterans Affairs Puget Sound Health Care System, Seattle, Washington; and Division of Metabolism, Endocrinology, and Nutrition, University of Washington, Seattle, Washington;
authors.forename: Kristina
authors.initials: K
authors.lastname: Utzschneider
mesh_terms: D003430:Cross-Sectional Studies; D005260:Female; D005947:Glucose / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D007328:Insulin; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000503:physiopathology*; D012720:Severity of Illness Index
chemical_list: D007328:Insulin; D005947:Glucose
keywords: chronic kidney disease; insulin resistance; metabolism; obesity; renal insulin resistance
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