# Interactive online calculator for estimation of muscle and hepatic insulin sensitivity in adults with Type 1 diabetes using clinical and research biomarkers

## TL;DR

This study creates an online calculator to estimate muscle and liver insulin sensitivity in Type 1 diabetes patients using blood biomarkers.

## Contribution

A novel online tool is introduced to estimate tissue-specific insulin sensitivity without requiring gold-standard clamp tests.

## Key findings

- A formula using clinical biomarkers accurately predicts muscle insulin sensitivity (GIR) with 92.5% accuracy.
- Another formula predicts liver insulin sensitivity (EGP) with 80% accuracy.
- The findings suggest biomarkers can replace complex clamp tests for assessing insulin resistance in Type 1 diabetes.

## Abstract

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.

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.

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.

We demonstrate that clinical and research biomarkers can be used to estimate tissue specific insulin sensitivity in adults with Type 1 diabetes.