Abstract
The purpose of this study was to investigate how renal loss of both C-peptide and glucose during oral glucose tolerance test (OGTT) relate to and affect plasma-derived oral minimal model (OMM) indices. All individuals were recruited during family screening between August 2007 and January 2011 and underwent a 3.5-h OGTT, collecting nine plasma samples and urine during OGTT. We obtained the following three subgroups: normoglycemic, at risk, and T2D. We recruited South Asian and Caucasian families, and we report separate analyses if differences occurred. Plasma glucose, insulin, and C-peptide concentrations were analyzed as AUCs during OGTT, OMM estimate of renal C-peptide secretion, and OMM beta-cell and insulin sensitivity indices were calculated to obtain disposition indices. Post-glucose load glucose and C-peptide in urine were measured and related to plasma-based indices. Urinary glucose corresponded well with plasma glucose AUC (Cau r = 0.64, P < 0.01; SA r = 0.69, P < 0.01), SI (Cau r = −0.51, P < 0.01; SA r = −0.41, P < 0.01), Φdynamic (Cau r = −0.41, P < 0.01; SA r = −0.57, P < 0.01), and Φoral (Cau r = −0.61, P < 0.01; SA r = −0.73, P < 0.01). Urinary C-peptide corresponded well to plasma C-peptide AUC (Cau r = 0.45, P < 0.01; SA r = 0.33, P < 0.05) and OMM estimate of renal C-peptide secretion (r = 0.42, P < 0.01). In general, glucose excretion plasma threshold for the presence of glucose in urine was ~10–10.5 mmol L−1 in non-T2D individuals, but not measurable in T2D individuals. Renal glucose secretion during OGTT did not influence OMM indices in general nor in T2D patients (renal clearance range 0–2.1 %, with median 0.2 % of plasma glucose AUC). C-indices of urinary glucose to detect various stages of glucose intolerance were excellent (Cau 0.83–0.98; SA 0.75–0.89). The limited role of renal glucose secretion validates the neglecting of urinary glucose secretion in kinetic models of glucose homeostasis using plasma glucose concentrations. Both C-peptide and glucose in urine collected during OGTT might be used as non-invasive measures for endogenous insulin secretion and glucose tolerance state.
Highlights
Mathematical approaches based on compartmental pharmacokinetic/pharmacodynamic (PK/PD) principles are used to describe the biphasic glucose–insulin system in oral function tests [1, 2], with the oral minimal model (OMM) as one of the most widely accepted approaches [3].Endocrine (2016) 52:253–262the contribution of renal clearance of endogenous glucose, insulin, and C-peptide during oral glucose tolerance test (OGTT) in various stages of glucose tolerance remains largely unclear
No significant differences were found in incremental plasma insulin AUC between normal glucose tolerance (NGT), impaired fasting glucose and/or impaired glucose tolerance (IFG/IGT), and Type 2 diabetes (T2D); a difference was found between South Asian NGT and Caucasian NGT (P \ 0.01)
With OMM, we observed a decrease in insulin sensitivity in both ethnicities with increasing glucose intolerance (P \ 0.001); differences were lower among the South Asian subgroups
Summary
Mathematical approaches based on compartmental pharmacokinetic/pharmacodynamic (PK/PD) principles are used to describe the biphasic glucose–insulin system in oral function tests [1, 2], with the oral minimal model (OMM) as one of the most widely accepted approaches [3].Endocrine (2016) 52:253–262the contribution of renal clearance of endogenous glucose, insulin, and C-peptide during oral glucose tolerance test (OGTT) in various stages of glucose tolerance remains largely unclear. As renal extraction of insulin is negligible [4], we focused on the relationship between plasma and urine concentrations of both C-peptide and glucose, collected during OGTT in the post-glucose load phase. This was performed in families to obtain groups with different risk for T2D, and we recruited families of South Asian and Caucasian origin to enable generalization of our findings. We questioned to which degree C-peptide and glucose excretion in urine influence OGTT-based plasma indices. We compared the OMM-derived estimates of renal C-peptide excretion with actual urinary C-peptide concentration. Renal loss of glucose is not taken into consideration in OMM, and the extent to which renal clearance might require correction of plasma-derived OMM calculations is unknown
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