SPINA-GBeta
SPINA-GBeta is a calculated biomarker for pancreatic [beta cell function]. It represents the maximum amount of insulin that beta cells can produce per time-unit.
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 GBeta
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
Dβ: EC50 for glucose at beta cells
G3: Parameter for pharmacokinetics
Clinical significance
Validity
SPINA-GBeta significantly correlates with the M value in glucose clamp studies and with the two-hour value in oral [glucose tolerance test]ing, glucose rise in OGTT, subscapular skinfold, truncal fat content and the HbA1c fraction.It has the additional advantage that it circumvents the HOMA-blind zone, which renders the calculation of HOMA-Beta impossible if the fasting glucose concentration is 3.5 mmol/L or below. Unlike HOMA-Beta, SPINA-Beta can be sensibly calculated in the whole range of measurements.
Reliability
In repeated measurements, SPINA-GBeta had higher retest reliability than HOMA-Beta, a measurement for beta cell function from the homeostasis model assessment.Clinical utility
In the FAST study, an observational case-control sequencing study including 300 persons from Germany, SPINA-GBeta differed more clearly between subjects with and without diabetes than the corresponding HOMA-Beta index.Scientific implications and other uses
Together with the reconstructed insulin receptor gain, SPINA-GBeta provides the foundation for the definition of a fasting based disposition index of insulin-glucose homeostasis.In combination with SPINA-GR and whole-exome sequencing, calculating SPINA-GBeta 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 several populations, SPINA-GBeta 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-GBeta is increased to compensate for reduced insulin sensitivity. This dynamical compensation is insufficient, however, in a subset of affected patients, resulting in a reduced static disposition index and the onset of diabetes mellitus.
Since SPINA-GBeta has higher predictive power than HOMA-Beta, its use has been suggested as a calculated early biomarker for the evolution and pathophysiology of gestational diabetes.