SPINA-GR
Insulin receptor gain, biomarker From Wikipedia, the free encyclopedia
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
Summarize
Perspective
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:
.[1]
)}{{G}_{E}\left[I\right](\infty )[G](\infty )}}-{\frac {{D}_{R}}{{G}_{E}[I](\infty )}}-{\frac {1}{{G}_{E}}}}](http://wikimedia.org/api/rest_v1/media/math/render/svg/fb6f6b0ebd5243ed47663596f0541e2875c81540)
[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)
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
Notes
References
External links
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