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Abstract: TH-PO1067

Impaired Incretin Homeostasis in Non-Diabetic Moderate-Severe CKD

Session Information

Category: CKD (Non-Dialysis)

  • 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

  • Ahmadi, Armin, University of California Davis, Davis, California, United States
  • Norman, Jennifer E., University of California Davis, Davis, California, United States
  • Tucker, Madelynn, University of California Davis, Davis, California, United States
  • Gamboa, Jorge, Vanderbilt University, Nashville, Tennessee, United States
  • Cummings, Bethany P., University of California Davis, Davis, California, United States
  • de Boer, Ian H., University of Washington, Seattle, Washington, United States
  • Roshanravan, Baback, University of California Davis, Davis, California, United States
Background

Incretin hormones are critical regulators of insulin secretion and glucose homeostasis. Little is known about the incretin response in CKD. We hypothesized that CKD is associated with impaired incretin secretion during oral glucose tolerance testing (OGTT).

Methods

We performed a cross-sectional study of 59 people with non-diabetic CKD (eGFR<60 ml/min per 1.73 m2) and 39 healthy control participants (eGFR>60 ml/min per 1.73 m2). We measured total area under the curve (tAUC) of plasma glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) during a 2-hour OGTT. We used linear regression adjusting for demographic, body composition, and lifestyle factors.

Results

Mean age of CKD patients was 64±14 yrs with 51% females versus 61±12 yrs with 44% females among controls. The mean eGFR in CKD participants was 38 ± 13 compared to 89 ± 17 ml/min per 1.73 m2 in controls (Table 1). GLP-1 tAUC and GIP tAUC were higher in CKD than controls with a mean of 3420 ± 1948 versus 2384 ± 1546 pM*120min (P=0.03), and 79400 ± 38670 versus 53994 ± 28191 pg/ml*120min (P=0.01), respectively (Figure 1). After adjustment, CKD was associated with estimated 1032 pM*120min greater GLP-1 (95% CI 74, 1989) and 19103 pm/ml*120min greater GIP (95% CI 4116, 34090) compared to control. There were no differences in insulin secretion and glucose tolerance between CKD and controls.

Conclusion

CKD is associated with increased incretin hormone levels during OGTT but no difference in insulin secretory response. Further studies are needed to investigate pancreatic response to incretin hormones in CKD.

Table 1. Participant characteristics.
CharacteristicsControls
(n=39)
CKD
(n=59)
Age61.0 (12.4)63.6 (13.9)
Female (%)17 (44)30 (51)
Race (%)  
White33 (87)31 (69)
Black4 (10)13 (22)
Asian/Pacific Islander1 (3)5 (8)
Body weight (kg)82.6 (20.6)88.1 (19.8)
eGFR (mL/min/1.73 m2)88.8 (17.1)37.6 (12.5)

Figure 1. Changes in plasma GLP-1 and GIP in response to OGTT comparing CKD and controls.

Funding

  • NIDDK Support