1. Fundamentals

Like the HOMA and QUICKI indices, the structure parameters are calculated from fasting concentrations of insulin and glucose^[1]. The equations are derived from a platform for nonlinear modelling of endocrine feedback loops (MiMe-NoCoDI approach)^[2].

The calculations require simultaneous measurements of insulin and glucose concentrations in the blood after eight hours of fasting.

The calculated biomarkers correlate with the M value in euglycaemic clamp investigations, the two-hour result of the oral glucose tolerance test (OGTT), the glucose rise in OGTT, the proportion of glycated haemoglobin, and the abdominal fat mass. In three independent cohorts, it was demonstrated that the parameters have higher reliability and diagnostic accuracy than alternative methods for assessing glucose homeostasis^[1][3].

Calculating SPINA-GBeta and SPINA-GR has helped to identify a new type of MODY diabetes characterised by insulin resistance and caused by a mutation in the gene encoding the ryanodine receptor type 2^[4].

In hidradenitis suppurativa (acne inversa), an inflammatory skin disease, SPINA-GR is reduced and often uncompensated by SPINA-GBeta, so that a subset of affected patients has low SPINA-DI with subsequent type 2 diabetes^[5].

2. Calculation

The parameters are calculated as follows^[1][3]:

with:

I₀: fasting insulin concentration (mol/L)

G₀: fasting glucose concentration (mol/L)

D_Beta: EC50 of glucose at pancreatic beta cells (7 mmol/L)

G₁: parameter for pharmacokinetics (154,93 s/L)

G₃: parameter for pharmacokinetics (58,8 s/L)

D_R: association constant of the insulin receptor (1,6 nmol/L)

G_E: effector gain (50 s/mol)

P₀: constitutive endogenous glucose production (150 µmol/s)

3. Interpretation

Reference ranges have been defined based on the NHANES 2009/2010 cohort and are 0.64–3.73 pmol/s for SPINA-GBeta, 1.41–9.00 mol/s for SPINA-GR and 4.01–7.65 for SPINA-DI. Of note, SPINA-GBeta is elevated if SPINA-GR is low in order to compensate for low insulin sensitivity. In this situation, the static disposition index (SPINA-DI) remains constant. In prediabetes and type 2 diabetes, this capacity of dynamical compensation is impaired^[6].