Combined with mathematical modelling, based on SimulaBeta, a single blood sample may be better than a complex test

Early diagnosis of diabetes mellitus continues to be a challenge. Established test protocols are either elaborate and expensive or of limited quality, and even the concept of prediabetes is debated. The key determinants of glucose homeostasis, beta cell function and insulin sensitivity, have low utility when assessed independently. Their combination, the dynamic disposition index, a measure of the feedback loop’s circular gain, is a more meaningful parameter for the homeostatic function. Still, its determination requires a frequently sampled oral glucose tolerance test, a complex and time-consuming procedure.

An innovative approach developed by our team members in Germany, India, Singapore and the UK promises to be not only simpler but even better. It is derived from SPINA Carb, a method to assess key properties of the feedback control system based on single measurements of insulin and glucose, and on mathematical modelling. The new technique delivers a novel fasting-based disposition index (SPINA-DI), which is obtained from the reconstructed beta cell function (SPINA-GBeta) and static insulin sensitivity (SPINA-GR).

Using computer simulations with SimulaBeta, we could show that the new parameter confirms a theory of dynamical compensation of insulin resistance by enhanced beta cell output in the metabolic syndrome. In a subsequent evaluation that was performed in three cohorts from the United States, Germany and India this assumption could be corroborated.

SimulaBeta revealed a nonlinear multidimensional zone of nonlinearity that represents an optimum of insulin-glucose homeostasis. Therefore, in „healthy obesity“ the feedback loop can maintain normoglycemia despite increasing insulin resistance. This zone of optimality exactly aligns with the two-dimensional normal range of SPINA-DI.

In all three populations, SPINA-DI correlated with important predictors of metabolic function including the response to oral glucose tolerance testing, the disposition index according to Matsuda and DeFronzo, HbA1c fraction, waist circumference and concentrations of free fatty acids, ghrelin and adiponectin.

Furthermore, SPINA-DI had higher retest reliability than other calculated markers of glucose homeostasis. For the diagnosis of diabetes, SPINA-DI had better accuracy than alternative methods including the dynamic disposition index based on frequently sampled oral glucose tolerance testing.

In summary, the new fasting-based disposition index provides an inexpensive, precise and reliable measure for the performance of the feedback loop. It may complement and, in many cases, replace established methods that are more costly and laborious. SimulaBeta played a key role in the development of the new diagnostic approach.

Reference:
1. Dietrich JW, Abood A, Dasgupta R, Anoop S, Jebasingh FK, Spurgeon R, Thomas N, Boehm BO. A novel simple disposition index (SPINA-DI) from fasting insulin and glucose concentration as a robust measure of carbohydrate homeostasis. J Diabetes. 2024 Jan 2. doi: 10.1111/1753-0407.13525. Epub ahead of print. PMID: 38169110. https://pubmed.ncbi.nlm.nih.gov/38169110/