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

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.

Thirteen non-diabetic individuals (7 women, 6 men; 52.2 ± 13.8 years; BMI: 26.1 ± 3.7 kg/m²) 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/m² (low-dose) and 120 min at 80 mU/min/m² (high-dose)].

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.

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.