Noninvasive assessment of insulin resistance in the liver using the fasting (13)C-glucose breath test

Abstract

Evaluating hepatic insulin resistance (IR) is the key to making a sensitive an accurate diagnosis of glucose intolerance. However, there is currently no suitable method to perform this procedure. This study was conducted to investigate whether the fasting (13)C-glucose breath test (FGBT) is useful as a convenient and highly sensitive clinical test for evaluating hepatic IR. Healthy nonobese subjects and a disease group consisting of patients with mild glucose intolerance were administered 100 mg (13)C-glucose after an overnight fast. A series of breath samples was collected until 360 minutes after ingestion, and the (13)CO2-to-(12)CO2 ratio was measured using an infrared spectrometer and was plotted as a kinetic curve of (13)C excretion. The area under the curve until 360 minutes (AUC360) of the (13)C excretion kinetic curve of the FGBT reflects the efficiency of energy production in the liver. First, we assessed the correlations between the AUC360 (or the (13)C excretion rate at 120 minutes) and the HOMA-IR and HbA1c levels as standard measurements of IR and diabetes mellitus (DM). There were relatively strong correlation coefficients (r = -0.49 to -0.81, r(2) = 0.24-0.66, P < 0.01; n = 35 males, n = 33 females). Second, we compared the AUC360 of healthy subjects and that of the patients with mild glucose intolerance. The AUC360 of the healthy subjects was consistently higher than that of the patients with mild glucose intolerance. The presence of IR or DM in males and females was diagnosed using cutoff values. The FGBT is a novel glucose metabolism test that can be used conveniently and safely to evaluate the balance of glucose metabolism in the liver. This test has excellent sensitivity for diagnosing alterations in hepatic glucose metabolism, particularly hepatic IR.

Keywords: (13)C excretion rate at 120 minutes; ADA; AUC(360); AUROC; American Diabetes Association; BSA; C(120); DM; FGBT; FPG; GLUT-2; GLUT-4; HOMA-IR; HbA1c; IR; ROC; area under the curve until 360 minutes; area under the receiver operating characteristic; body surface area; diabetes mellitus; fasting (13)C-glucose breath test; fasting plasma glucose; glucose transporter 2; glucose transporter 4; hemoglobin A1c; homeostasis model assessment of insulin resistance; insulin resistance; receiver-operating characteristic.