Urinary C-Peptide Excretion: A Novel Alternate Measure of Insulin Sensitivity in Physiological Conditions.

Insulin sensitivity (IS) is measured by the euglycemic–hyperinsulinemic clamp under a nonphysiological condition. Daily C-peptide urinary excretion may be a physiological index of IS, because C-peptide is co-secreted with insulin as a function of nutrient intake and IS. The amount of ²H₂O released from glycolytic glucose metabolism after [6,6-²H₂]-glucose ingestion was recently proposed as a physiological measure of IS. We compared these IS surrogates to the gold standard (euglycemic–hyperinsulinemic clamp). Thirty (15 male/15 female) sedentary, nondiabetic participants (27.2 ± 4.0 (s.d.) kg/m², 35 ± 12 years) were admitted for 3 days to our in-patient unit. After a 10-h fast, they received 60 g of glucose and 15 g of [6,6-²H₂]-glucose. Before glucose ingestion and hourly thereafter for 4 h, plasma glucose and insulin concentrations, and plasma deuterium enrichment were determined. Plasma ²H₂O production divided by insulin response was used as the glycolytic index. On day 2, subjects spent 23 h in a metabolic chamber (eucaloric diet, 50% carbohydrate, 30% fat). Urinary C-peptide excretion was divided by energy intake yielding the C-peptide to energy intake ratio (CPEP/EI). After leaving the chamber (day 3, 10-h fast), IS was measured by a 2-h clamp (120 mU/m²/min). Average IS (clamp) was 7.3 ± 2.6 mg glucose/kg estimated metabolic body size/min (range: 3.6–13.2). These values were inversely correlated with CPEP/EI (r = −0.62; P < 0.01) and positively with the glycolytic rate (r = 0.60; P < 0.01). In nondiabetic subjects, two novel estimates of IS—daily urinary C-peptide urinary excretion and glycolytic rate during an oral glucose tolerance test —were related to IS by a clamp. [ABSTRACT FROM AUTHOR]