Abstract

Abstract BACKGROUND AND AIMS Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common inherited kidney disorder. Defective glucose metabolism was identified as a key feature in ADPKD, and several ‘metabolic’ approaches are currently under evaluation in adults with ADPKD. Whether this defective glucose metabolism could be an early primary event and a potential therapeutic option in the early disease stages is still unknown. In this study, we evaluated the insulin sensitivity profile in genotyped children with ADPKD. METHOD We performed a cross-sectional study to evaluate the insulin sensitivity profile in a genotyped cohort of ADPKD children (<19 years) with preserved renal function [estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2]. Overweight/obese children were respectively defined as body mass index (BMI) 25–30 and > 30 kg/m2. The Homeostasis Model Assessment Index (HOMA-IR) was calculated: fasting insulin (μIU mL− 1) x fasting glucose (mmol L − 1)/22.5. The Quantitative Insulin Sensitivity Check Index (QUICKI) was calculated: 1/[log (fasting insulin μU/mL) + log (fasting glucose mg/dL)]. RESULTS A total of 37 ADPKD patients (22 boys) were included with a mean ($ \pm $ SD) age at diagnosis was 10.3 $ \pm $ 4.2 years. A total of 36 patients had PKD1 mutation (one GANAB mutation). Median BMI was 16.8 ± 4.3 kg/m2. Median serum fasting glucose: 86.0 ± 9.3 mg/dL, median fasting insulin: 6.1 ± 7.2 μU/mL and median serum C-peptide: 0.4 ± 0.3 nmol/L. Median HOMA-IR was 1.4 ± 1.7 and median QUICKI was 0.4 ± 0.1. A total of 16 patients presented a HOMA-IR > 1.6 and 6 normal-weight children had a HOMA-IR > 2.3. No patient displayed glucosuria. An oral glucose tolerance test was performed on five overweight patients, four of them showed insulin resistance and were treated with metformin. CONCLUSION Even with normal BMI, ADPKD children displayed a high index of insulin resistance. Further clinical studies are needed to determine whether ADPKD could be an additional risk factor for insulin resistance.

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