A Novel Method to Evaluate Insulin Sensitivity by Combining Continuous Glucose Monitoring and Urinary C‐Peptide Excretion

ABSTRACT Aim Assessing insulin sensitivity is a central component of clinical research in metabolism. Although considered the gold standard, the euglycemic‐hyperinsulinemic clamp evaluates insulin sensitivity under non‐physiological conditions and is highly burdensome and costly, thereby prompting the development of alternative methods. The 24‐h urinary C‐peptide excretion rate adjusted for energy intake is a surrogate marker of insulin sensitivity in non‐diabetic adults. We hypothesized that the combination of 24‐h continuous glucose monitoring (CGM) and 24‐h urinary C‐peptide excretion (24 h‐glycemia/C‐peptide ratio) would be a better predictor of insulin sensitivity than the C‐peptide excretion rate adjusted for energy intake or other widely accepted indexes. Methods Thirteen non‐diabetic individuals (7 women, 6 men; 52.2 ± 13.8 years; BMI: 26.1 ± 3.7 kg/m 2 ) participated in this cross‐sectional study. They completed a 24‐h stay in a whole‐room indirect calorimeter wearing a CGM sensor (Dexcom G6 Pro) while all produced urine was collected. Insulin sensitivity was assessed by a 2‐step hyperinsulinemic‐euglycemic clamp [180 min at 10 mU/min/m 2 (low‐dose) and 120 min at 80 mU/min/m 2 (high‐dose)]. Results The 24 h‐glycemia/C‐peptide ratio was positively associated with the clamp's low‐dose glucose infusion rate (GIR: R 2 = 0.401, p = 0.020) and tended to be associated with the high‐dose GIR ( R 2 = 0.266, p = 0.086). The associations between GIR and previously accepted markers of insulin sensitivity resulted in R 2 ranging from 0.248 to 0.456 for the clamp low dose and R 2 ranging from 0.108 to 0.174 for the clamp high dose. Conclusions These results suggest that the 24 h‐glycemia/C‐peptide ratio is a promising simple, inexpensive, non‐invasive, and physiological marker of insulin sensitivity that deserves further investigation.