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Beta Cell Function and Glucose Tolerance in Nondiabetic Patients with Kidney Dysfunction

Mar 20, 2015

The results of insulin release and glucose tolerance across a sample with declining kidney function…

Insulin resistance is not uncommon to see when looking at patients with declining kidney function or chronic kidney disease (CKD). Insulin resistance progressively worsens with respect to kidney function decline. Although insulin resistance and chronic kidney disease is multifactorial, the primary molecular mechanism of the two is believed to be related to a post-receptor signaling abnormality in the skeletal muscle.


The primary objective of this study was to to investigate insulin release (beta-cell function) and glucose tolerance following a standardized oral glucose tolerance test (OGTT) across kidney function strata. The setting and design is a community-based cohort study from the Uppsala Longitudinal Study of Adult Men (ULSAM). ULSAM originally invited 2322 men (age 50–51 years) born between 1920 and 1924 living in Uppsala County, Sweden to a thorough investigation of risk factors.

This study included 1,015 non-diabetic Swedish men who were between the age of 70 to 71 years old, all who were re-invited from the original study for this third examination in the series after exclusions were made. For the present study, men who were diagnosed with overt diabetes mellitus (DM; n = 178), lacked serum cystatin-C measurements (n = 27) or did not undergo OGTT (n = 1) were excluded. All participants underwent an OGTT and euglycaemic hyperinsulinemic clamp (HEGC) tests, which allowed for determination of insulin sensitivity, beta-cell function, and glucose tolerance. Kidney function was estimated by cystatin-C algorithms and mixed models were used to identify any determinants of insulin secretion after the hyperglycemic load was initiated. DM was defined as one or more of the following: fasting plasma glucose ≥126 mg/dL, 2-hour post-load glucose levels ≥200 mg/dL, and use of oral antidiabetes agents or insulin.

A total of 466 of the participants presented with moderate to advanced kidney disease. Insulin sensitivity (by HEGC) was seen to become smaller across decreasing kidney function quartiles. However, after the OGTT challenge, beta-cell function (area under the curve for insulin release, the estimated first phase insulin release, and the insulinogenic index) were progressively higher. Neither the beta-cell function via (oral disposition index) or the 2-hour post-load glucose tolerance differed across the kidney function strata. The linear mixed regression models showed that dynamic insulin release during the OGTT was inversely related to kidney function, despite the correction for each individual’s insulin sensitivity or its risk factors.

In conclusion, when looking at this group of older men, their beta-cell function after a hyperglycemic load appropriately compensated the loss in insulin sensitivity that occurs with kidney dysfunction. For that reason, observations show that the net balance between insulin sensitivity and beta-cell function was preserved.

Practice Pearls:

  • In this cohort, and more extensively reported in the authors previous analyses, a lower kidney function is associated with worse insulin sensitivity when assessed by the gold-standard HEGC.
  • While early studies indicate that glucose intolerance is present in CKD patients, this study demonstrates a compensatory increase of beta-cell function despite the progressive loss of insulin sensitivity inherent to kidney dysfunction.
  • An advantage of this study over the previous reports is that they estimated kidney function from cystatin-C measurements, which are less influenced by muscle mass than serum creatinine.

Ting Jia, Ulf Risérus, Hong Xu, et al. “Kidney Function, beta-Cell Function and Glucose Tolerance in Older Men”. J Clin Endocrinol Metab 100: 587–593, 2015.