Abstract Aims Impaired insulin sensitivity is an under‐recognised risk in Type 1 diabetes but is challenging to measure with ‘gold‐standard’ euglycaemic clamps. Adding stable‐isotope glucose distinguishes hepatic and muscle insulin action (assessed by endogenous glucose production EGP and glucose infusion rate GIR, respectively). We therefore searched for a blood‐biomarker alternative. Methods Two‐step clamps were conducted in 40 adults with Type 1 diabetes, participating in the INTIMET trial (INsulin resistance in Type 1 diabetes managed with METformin, ACTRN12619001440112). Participants were characterised with 33 baseline biomarkers. Results Exhaustive search analyses derived a formula predicting an ‘unfavourable GIR’ (dichotomous variable: below median of 60.4 μmol/kg fat‐free mass FFM/min) using: total daily insulin dose (TDI), fasting triglycerides (TGs), insulin‐like growth factor 1 and aspartate aminotransferase levels (area under the receiver operating characteristic curve (AUROC) 0.97, p < 0.0001, R 2 Nagelkerke = 0.83, 92.5% accuracy). An ‘unfavourable EGP level’ (above median of 6.2 μmol/kg FFM/min) during low‐dose clamp was predicted by TDI, TGs, alkaline phosphatase and uric acid levels (AUROC 0.86, p = 0.001, R 2 (Nagelkerke) = 0.50, 80% accuracy). A free online tool ( https://bit.ly/EGP-GIR-calculator ) converts these variables into dichotomised EGP and GIR estimates. Conclusions We demonstrate that clinical and research biomarkers can be used to estimate tissue specific insulin sensitivity in adults with Type 1 diabetes.
Januszewski et al. (2026) studied this question.