SPINA-GR
SPINA-GR is a calculated biomarker for insulin sensitivity. It represents insulin receptor gain.
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.
How to determine GR
The index is derived from a mathematical model of insulin-glucose homeostasis that incorporates fundamental physiological motifs. For diagnostic purposes, it is calculated from fasting insulin and glucose concentrations with:: Fasting Insulin plasma concentration
: Fasting blood glucose concentration
G1: Parameter for pharmacokinetics
DR: EC50 of insulin at its receptor
GE: Effector gain
P: Constitutive endogenous glucose production
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 technique|glucose clamp studies], triceps skinfold, subscapular skinfold and with the two-hour value in oral [glucose tolerance test]ing, glucose rise in OGTT, waist-to-hip ratio, body fat content 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-GR provides the foundation for the definition of a fasting based disposition index of insulin-glucose homeostasis.In combination with SPINA-GBeta and whole-exome sequencing, calculating SPINA-GR helped to identify a new form of monogenetic diabetes that is characterised by primary insulin resistance and results from a missense variant of the type 2 ryanodine receptor gene.
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.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 is reduced, resulting in the onset of diabetes mellitus.