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 (e.g. in one second). 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:
G ^ β = [ I ] ( ∞ ) ( D β + [ G ] ( ∞ ) ) G 3 [ G ] ( ∞ ) {\displaystyle {\widehat {G}}_{\beta }={\frac {[I](\infty )({D}_{\beta }+\left[G\right](\infty ))}{{G}_{3}[G](\infty )}}} . [I](∞): Fasting Insulin plasma concentration (mol/L) [G](∞): Fasting blood glucose concentration (mol/L) Dβ: EC50 for glucose at beta cells (7 mmol/L) G3: Parameter for pharmacokinetics (58,8 s/L)
Clinical significance
Validity SPINA-GBeta significantly correlates with the M value in glucose clamp studies and (better than HOMA-Beta) with the two-hour value in oral glucose tolerance testing (OGTT), 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 (63 mg/dL) 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-GR), SPINA-GBeta provides the foundation for the definition of a fasting based disposition index of insulin-glucose homeostasis (SPINA-DI). In combination with SPINA-GR and whole-exome sequencing, calculating SPINA-GBeta 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 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. SPINA-GBeta declines with increasing adherence to mediterranean diet, which has been explained with a reduction in the chronic stimulus for dynamical compensation, i.e. insulin hypersecretion. 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 (SPINA-DI) 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.
Predictive aspects In a longitudinal evaluation of the NHANES study, a large sample of the general US population, over 10 years, reduced SPINA-GBeta significantly predicted all-cause mortality.
See also SPINA-GR SPINA-GD SPINA-GT Homeostatic model assessment QUICKI
Notes
References
External links Software for calculating SPINA-GBeta and other parameters for endotyping glucose homeostasis. (Permanent DOI), (General information and US mirror) Functions for R and S for calculating SPINA-GBeta, SPINA-GR and SPINA-DI. (Permanent DOI)
