SPINA-GR

SPINA-GR is a calculated biomarker for insulin sensitivity. It represents insulin receptor gain.

How to determine GR
The index is derived from a mathematical model of insulin-glucose homeostasis. For diagnostic purposes, it is calculated from fasting insulin and glucose concentrations with:

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

[I](∞): Fasting Insulin plasma concentration (μU/mL)

[G](∞): Fasting blood glucose concentration (mg/dL)

G1: Parameter for pharmacokinetics (154.93 s/L)

DR: EC50 of insulin at its receptor (1,6 nmol/L)

GE: Effector gain (50 s/mol)

P(∞): Constitutive endogenous glucose production (150 μmol/s)

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.

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.

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).

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).

Pathophysiological implications
In lean subjects it is significantly higher than in a population with obese persons. 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.