SPINA-GR

SPINA-GR is a calculated biomarker for insulin sensitivity.^[1][a] It represents insulin receptor gain.

SPINA-GR
Reference range	1.41–9.00 mol/s
Calculator	https://doi.org/10.5281/zenodo.7479856
Purpose	Medical diagnosis, research
Test of	Insulin sensitivity

The method of calculation is based on a time-discrete nonlinear feedback model of insulin-glucose homeostasis that is rooted in the MiMe-NoCoDI modeling platform for endocrine systems.^[2]

How to determine GR

The index is derived from a mathematical model of insulin-glucose homeostasis.^[3] For diagnostic purposes, it is calculated from fasting insulin and glucose concentrations with:

${\displaystyle {\widehat {G}}_{R}={\frac {{G}_{1}P(\infty )({D}_{R}+\left[I\right](\infty ))}{{G}_{E}\left[I\right](\infty )[G](\infty )}}-{\frac {{D}_{R}}{{G}_{E}[I](\infty )}}-{\frac {1}{{G}_{E}}}}$.^[1]

[I](∞): Fasting Insulin plasma concentration (μU/mL)
[G](∞): Fasting blood glucose concentration (mg/dL)
G₁: Parameter for pharmacokinetics (154.93 s/L)
D_R: EC₅₀ of insulin at its receptor (1,6 nmol/L)
G_E: Effector gain (50 s/mol)
P(∞): Constitutive endogenous glucose production (150 μmol/s)

Clinical significance

Validity

Compared to healthy volunteers, SPINA-GR is significantly reduced in persons with prediabetes and diabetes mellitus, and it correlates with the M value in glucose clamp studies, triceps skinfold, subscapular skinfold and (better than HOMA-IR and QUICKI) with the two-hour value in oral glucose tolerance testing (OGTT), glucose rise in OGTT, waist-to-hip ratio, body fat content (measured via DXA) and the HbA1c fraction.^[1]

Clinical utility

Both in the FAST study, an observational case-control sequencing study including 300 persons from Germany, and in a large sample from the NHANES study, SPINA-GR differed more clearly between subjects with and without diabetes than the corresponding HOMA-IR, HOMA-IS and QUICKI indices.^[4]

Scientific implications and other uses

Together with the secretory capacity of pancreatic beta cells (SPINA-GBeta), SPINA-GR provides the foundation for the definition of a fasting based disposition index of insulin-glucose homeostasis (SPINA-DI).^[4]

In combination with SPINA-GBeta and whole-exome sequencing, calculating SPINA-GR helped to identify a new form of monogenetic diabetes (MODY) that is characterised by primary insulin resistance and results from a missense variant of the type 2 ryanodine receptor (RyR2) gene (p.N2291D).^[5]

Pathophysiological implications

In lean subjects it is significantly higher than in a population with obese persons.^[1] In several populations, SPINA-GR correlated with the area under the glucose curve and 2-hour concentrations of glucose, insulin and proinsulin in oral glucose tolerance testing, concentrations of free fatty acids, ghrelin and adiponectin, and the HbA1c fraction.^[4]

In hidradenitis suppurativa, an inflammatory skin disease, SPINA-GR is reduced. If this state is uncompensated by increased beta-cell function the static disposition index (SPINA-DI) is reduced, resulting in the onset of diabetes mellitus.^[6]

Predictive aspects

In a longitudinal evaluation of the NHANES study, a large sample of the general US population, over 10 years, reduced SPINA-DI, calculated as the product of SPINA-GBeta times SPINA-GR, significantly predicted all-cause mortality.^[7]

See also

• SPINA-GBeta
• SPINA-GD
• SPINA-GT
• Homeostatic model assessment
• QUICKI

Notes

1. SPINA is an acronym for "structure parameter inference approach".