title: Kidney function, β-cell function and glucose tolerance in older men.
abstract: BACKGROUND
  Kidney dysfunction induces insulin resistance, but it is unknown if β cell function is affected.
  
  
  OBJECTIVE
  To investigate insulin release (β cell function) and glucose tolerance following a standardized oral glucose tolerance test (OGTT) across kidney function strata.
  
  
  METHODS
  Community-based cohort study from the Uppsala Longitudinal Study of Adult Men (ULSAM). PARTICIPANTS AND MAIN OUTCOME MEASURE: Included were 1015 nondiabetic Swedish men aged 70-71 years. All participants underwent OGTT and euglycaemic hyperinsulinaemic clamp (HEGC) tests, allowing determination of insulin sensitivity, β cell function, and glucose tolerance. Kidney function was estimated by cystatin C-algorithms. Mixed models were used to identify determinants of insulin secretion after the hyperglycemic load.
  
  
  RESULTS
  As many as 466 (46%) of participants presented moderate-advanced kidney disease. Insulin sensitivity (by HEGC) decreased across decreasing kidney function quartiles. After the OGTT challenge, however, β cell function indices (area under the curve for insulin release, the estimated first phase insulin release, and the insulinogenic index) were incrementally higher. Neither the oral disposition index nor the 2-h postload glucose tolerance differed across the kidney function strata. Mixed models showed that dynamic insulin release during the OGTT was inversely associated with kidney function, despite the correction for each individual's insulin sensitivity or its risk factors.
  
  
  CONCLUSIONS
  In older men, β cell function after a hyperglycemic load appropriately compensated the loss in insulin sensitivity that accompanies kidney dysfunction. As a result, the net balance between insulin sensitivity and β cell function was preserved.
authors.affiliation: Divisions of Renal Medicine and Baxter Novum, Departments of Clinical Science, Intervention and Technology (T.J., H.X., B.L., T.E.L., J.J.C.), Public Health Sciences (T.J.), and Center for Molecular Medicine (J.J.C.), Karolinska Institutet, Stockholm, Sweden; Department of Public Health and Caring Sciences, Section of Geriatrics (J.A.), Clinical Nutrition and Metabolism (U.R., P.S., T.C.), Uppsala University, Uppsala, Sweden; School of Health and Social Studies (J.A.), Dalarna University, Falun, Sweden; and Department of Medicine (T.A.I.), Division of Nephrology, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Ting
authors.initials: T
authors.lastname: Jia
authors.forename: Ulf
authors.initials: U
authors.lastname: Risérus
authors.forename: Hong
authors.initials: H
authors.lastname: Xu
authors.forename: Bengt
authors.initials: B
authors.lastname: Lindholm
authors.forename: Johan
authors.initials: J
authors.lastname: Ärnlöv
authors.forename: Per
authors.initials: P
authors.lastname: Sjögren
authors.forename: Tommy
authors.initials: T
authors.lastname: Cederholm
authors.forename: Tobias E
authors.initials: TE
authors.lastname: Larsson
authors.forename: Talat Alp
authors.initials: TA
authors.lastname: Ikizler
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Carrero
mesh_terms: D000368:Aged; D001786:Blood Glucose; D015309:Glucose Clamp Technique; D018149:Glucose Intolerance / Q000503:physiopathology*; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000502:physiology*; D007668:Kidney / Q000502:physiology*; D008137:Longitudinal Studies; D008297:Male
chemical_list: D001786:Blood Glucose