A single blood sample may improve early diagnosis of diabetes, thanks to mathematical modelling

What is it about?

An international group of researchers from Germany, India, Singapore and the UK has developed a novel fasting-based disposition index (SPINA-DI) that is defined as the product of insulin receptor gain (SPINA-GR) multiplied by beta-cell function (SPINA-GBeta). SPINA-DI is reduced due to insulin resistance with insufficient dynamical compensation of beta-cell mass or due to primary beta-cell failure. SPINA-DI was validated in three cohorts. It has significant advantages in validity, reliability and diagnostic power compared to established criteria.

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Photo by Nguyễn Hiệp on Unsplash

Photo by Nguyễn Hiệp on Unsplash

Why is it important?

Early diagnosis of diabetes mellitus continues to be a challenge. Established test protocols are either elaborate and expensive or of limited quality. The key determinants of glucose homeostasis, i.e. pancreatic beta-cell function and insulin sensitivity, have low diagnostic 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. However, it still has severe limitations, since its determination requires a frequently sampled oral glucose tolerance test, a complex and time-consuming procedure. The new fasting-based disposition index (SPINA-DI) combines the advantages of an integrated measure of the homeostatic system and the economic benefits of a single determination of two fasting hormone and metabolite concentrations. Using computer simulations, it could be shown that the new parameter could confirm a theory of dynamical compensation of insulin resistance by enhanced beta cell output in the metabolic syndrome. This assumption could be corroborated in a subsequent evaluation performed in three cohorts from the United States, Germany and India. In all three populations, SPINA-DI correlated with predictors of metabolic function including the response to oral glucose tolerance testing (OGTT), the composite index according to Matsuda and DeFronzo, glycated haemoglobin fraction, waist circumference and concentrations of free fatty acids and adipocytokines. 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.

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