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SPINA-GR
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<h2 id="how-to-determine-gr">How to determine GR</h2> <p>The index is derived from a mathematical model of <a href="/facts/Blood_sugar_regulation/lYEBdPKr">insulin-glucose homeostasis</a>.<a class="footnote-ref" id="fnref:4" href="#fn:4"><sup>4</sup></a> For diagnostic purposes, it is calculated from fasting <a href="/facts/Insulin/oXG0myt1">insulin</a> and <a href="/facts/Glucose/oUSkoLCD">glucose</a> concentrations with: </p><p> G ^ R = G 1 P ( ∞ ) ( D R + [ I ] ( ∞ ) ) G E [ I ] ( ∞ ) [ G ] ( ∞ ) − D R G E [ I ] ( ∞ ) − 1 G E {\displaystyle {\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}}}} .<a class="footnote-ref" id="fnref:5" href="#fn:5"><sup>5</sup></a> </p><p>[<i>I</i>](∞): Fasting Insulin <a href="/facts/Blood_plasma/oHuwwugG">plasma</a> concentration (μU/mL) [<i>G</i>](∞): Fasting <a href="/facts/Blood_sugar_level/I4SkNzrm">blood glucose</a> concentration (mg/dL) <i>G</i>1: Parameter for <a href="/facts/Pharmacokinetics/x4CUUnle">pharmacokinetics</a> (154.93 s/L) <i>D</i><i>R</i>: <a href="/facts/EC50/x7oD7ITx">EC50</a> of insulin at its receptor (1,6 nmol/L) <i>G</i><i>E</i>: Effector gain (50 s/mol) <i>P</i>(∞): Constitutive endogenous glucose production (150 μmol/s) </p> <h2 id="clinical-significance">Clinical significance</h2> <h3>Validity</h3> <p>Compared to healthy volunteers, SPINA-GR is significantly reduced in persons with <a href="/facts/Prediabetes/MqWAdWQU">prediabetes</a> and <a href="/facts/Diabetes_mellitus/2xeHXbsI">diabetes mellitus</a>, and it correlates with the M value in <a href="/facts/Glucose_clamp_technique/CpbG0sV8">glucose clamp studies</a>, triceps <a href="/facts/Skinfold_calipers/w3EFb5BH">skinfold</a>, subscapular skinfold and (better than HOMA-IR and QUICKI) with the two-hour value in <a href="/facts/Oral_glucose_tolerance_test/3XQrFJuf">oral glucose tolerance testing</a> (OGTT), glucose rise in OGTT, <a href="/facts/Waist-to-hip_ratio/SBRr6kEk">waist-to-hip ratio</a>, body fat content (measured via <a href="/facts/Dual-energy_X-ray_absorptiometry/Qhr1hX8F">DXA</a>) and the <a href="/facts/Glycated_hemoglobin/jTNaU7Jv">HbA1c</a> fraction.<a class="footnote-ref" id="fnref:6" href="#fn:6"><sup>6</sup></a> </p> <h3>Clinical utility</h3> <p>Both in the FAST study, an observational case-control sequencing study including 300 persons from Germany, and in a large sample from the <a href="/facts/National_Health_and_Nutrition_Examination_Survey/r3ID2RVs">NHANES</a> study, SPINA-GR differed more clearly between subjects with and without diabetes than the corresponding HOMA-IR, HOMA-IS and QUICKI indices.<a class="footnote-ref" id="fnref:7" href="#fn:7"><sup>7</sup></a> </p> <h2 id="scientific-implications-and-other-uses">Scientific implications and other uses</h2> <p>Together with the secretory capacity of pancreatic beta cells (<a href="/facts/SPINA-GBeta/BIM2HnkF">SPINA-GBeta</a>), SPINA-GR provides the foundation for the definition of a fasting based <a href="/facts/Disposition_index/6uCGqGUr">disposition index</a> of insulin-glucose homeostasis (SPINA-DI).<a class="footnote-ref" id="fnref:8" href="#fn:8"><sup>8</sup></a> </p><p>In combination with SPINA-GBeta and whole-exome sequencing, calculating SPINA-GR helped to identify a new form of monogenetic diabetes (<a href="/facts/Maturity-onset_diabetes_of_the_young/NljPpzFY">MODY</a>) that is characterised by primary insulin resistance and results from a missense variant of the type 2 <a href="/facts/Ryanodine/dG6LL77t">ryanodine</a> receptor (<a href="/facts/Ryanodine_receptor_2/mLrPQamI">RyR2</a>) gene (p.N2291D).<a class="footnote-ref" id="fnref:9" href="#fn:9"><sup>9</sup></a> </p> <h2 id="pathophysiological-implications">Pathophysiological implications</h2> <p>In lean subjects it is significantly higher than in a population with obese persons.<a class="footnote-ref" id="fnref:10" href="#fn:10"><sup>10</sup></a> 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, <a href="/facts/Ghrelin/0uWqCQsX">ghrelin</a> and <a href="/facts/Adiponectin/q9XhoKUp">adiponectin</a>, and the HbA1c fraction.<a class="footnote-ref" id="fnref:11" href="#fn:11"><sup>11</sup></a> </p><p>In <a href="/facts/Hidradenitis_suppurativa/tuxkrNnu">hidradenitis suppurativa</a>, 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.<a class="footnote-ref" id="fnref:12" href="#fn:12"><sup>12</sup></a> </p> <h2 id="predictive-aspects">Predictive aspects</h2> <p>In a longitudinal evaluation of the <a href="/facts/National_Health_and_Nutrition_Examination_Survey/r3ID2RVs">NHANES</a> 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.<a class="footnote-ref" id="fnref:13" href="#fn:13"><sup>13</sup></a> </p> <h2 id="see-also">See also</h2> <ul><li><a href="/facts/SPINA-GBeta/BIM2HnkF">SPINA-GBeta</a></li> <li><a href="/facts/SPINA-GD/rb04hlcr">SPINA-GD</a></li> <li><a href="/facts/SPINA-GT/57QBV78L">SPINA-GT</a></li> <li><a href="/facts/Homeostatic_model_assessment/fv6M2Pck">Homeostatic model assessment</a></li> <li><a href="/facts/Quantitative_insulin_sensitivity_check_index/BexcmnuN">QUICKI</a></li></ul> <h2 id="notes">Notes</h2> <h2 id="external-links">External links</h2> <ul><li><a href="https://doi.org/10.5281/zenodo.7479857">Functions for R and S for calculating SPINA-GBeta and SPINA-GR</a>. <a href="https://doi.org/10.5281/zenodo.7479856">(Permanent DOI)</a></li></ul> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>Dietrich, JW; Dasgupta, R; Anoop, S; Jebasingh, F; Kurian, ME; Inbakumari, M; Boehm, BO; Thomas, N (21 October 2022). "SPINA Carb: a simple mathematical model supporting fast in-vivo estimation of insulin sensitivity and beta cell function". Scientific Reports. 12 (1): 17659. Bibcode:2022NatSR..1217659D. doi:10.1038/s41598-022-22531-3. PMC 9587026. PMID 36271244. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9587026" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9587026</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>SPINA is an acronym for "structure parameter inference approach". <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>Santillán, Moisés (2025). "Quantitative Insights into Glucose Regulation: A Review of Mathematical Modeling Efforts". Dynamics of Physiological Control: 125–148. doi:10.1007/978-3-031-82396-1_7. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>Dietrich, Johannes W.; Böhm, Bernhard (27 August 2015). "Die MiMe-NoCoDI-Plattform: Ein Ansatz für die Modellierung biologischer Regelkreise". GMDS 2015; 60. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik: Biometrie und Epidemiologie e.V. (GMDS). doi:10.3205/15gmds058. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>Dietrich, JW; Dasgupta, R; Anoop, S; Jebasingh, F; Kurian, ME; Inbakumari, M; Boehm, BO; Thomas, N (21 October 2022). "SPINA Carb: a simple mathematical model supporting fast in-vivo estimation of insulin sensitivity and beta cell function". Scientific Reports. 12 (1): 17659. Bibcode:2022NatSR..1217659D. doi:10.1038/s41598-022-22531-3. PMC 9587026. PMID 36271244. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9587026" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9587026</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> <li id="fn:6"><p>Dietrich, JW; Dasgupta, R; Anoop, S; Jebasingh, F; Kurian, ME; Inbakumari, M; Boehm, BO; Thomas, N (21 October 2022). "SPINA Carb: a simple mathematical model supporting fast in-vivo estimation of insulin sensitivity and beta cell function". Scientific Reports. 12 (1): 17659. Bibcode:2022NatSR..1217659D. doi:10.1038/s41598-022-22531-3. PMC 9587026. PMID 36271244. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9587026" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9587026</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></p></li> <li id="fn:7"><p>Dietrich, Johannes W.; Abood, Assjana; Dasgupta, Riddhi; Anoop, Shajith; Jebasingh, Felix K.; Spurgeon, R.; Thomas, Nihal; Boehm, Bernhard O. (2 January 2024). "A novel simple disposition index ( SPINA-DI ) from fasting insulin and glucose concentration as a robust measure of carbohydrate homeostasis". Journal of Diabetes. 16 (9): e13525. doi:10.1111/1753-0407.13525. PMC 11418405. PMID 38169110. S2CID 266752689. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418405" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418405</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></p></li> <li id="fn:8"><p>Dietrich, Johannes W.; Abood, Assjana; Dasgupta, Riddhi; Anoop, Shajith; Jebasingh, Felix K.; Spurgeon, R.; Thomas, Nihal; Boehm, Bernhard O. (2 January 2024). "A novel simple disposition index ( SPINA-DI ) from fasting insulin and glucose concentration as a robust measure of carbohydrate homeostasis". Journal of Diabetes. 16 (9): e13525. doi:10.1111/1753-0407.13525. PMC 11418405. PMID 38169110. S2CID 266752689. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418405" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418405</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></p></li> <li id="fn:9"><p>Bansal, Vikas; Winkelmann, Bernhard R.; Dietrich, Johannes W.; Boehm, Bernhard O. (20 February 2024). "Whole-exome sequencing in familial type 2 diabetes identifies an atypical missense variant in the RyR2 gene". Frontiers in Endocrinology. 15. doi:10.3389/fendo.2024.1258982. PMC 10913019. PMID 38444585. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10913019" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10913019</a> <a href="#fnref:9" class="footnote-back-ref">↩</a></p></li> <li id="fn:10"><p>Dietrich, JW; Dasgupta, R; Anoop, S; Jebasingh, F; Kurian, ME; Inbakumari, M; Boehm, BO; Thomas, N (21 October 2022). "SPINA Carb: a simple mathematical model supporting fast in-vivo estimation of insulin sensitivity and beta cell function". Scientific Reports. 12 (1): 17659. Bibcode:2022NatSR..1217659D. doi:10.1038/s41598-022-22531-3. PMC 9587026. PMID 36271244. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9587026" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9587026</a> <a href="#fnref:10" class="footnote-back-ref">↩</a></p></li> <li id="fn:11"><p>Dietrich, Johannes W.; Abood, Assjana; Dasgupta, Riddhi; Anoop, Shajith; Jebasingh, Felix K.; Spurgeon, R.; Thomas, Nihal; Boehm, Bernhard O. (2 January 2024). "A novel simple disposition index ( SPINA-DI ) from fasting insulin and glucose concentration as a robust measure of carbohydrate homeostasis". Journal of Diabetes. 16 (9): e13525. doi:10.1111/1753-0407.13525. PMC 11418405. PMID 38169110. S2CID 266752689. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418405" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418405</a> <a href="#fnref:11" class="footnote-back-ref">↩</a></p></li> <li id="fn:12"><p>Abu Rached, Nessr; Dietrich, Johannes W.; Ocker, Lennart; Stockfleth, Eggert; Haven, Yannik; Myszkowski, Daniel; Bechara, Falk G. (21 March 2025). "Endotyping Insulin–Glucose Homeostasis in Hidradenitis Suppurativa: The Impact of Diabetes Mellitus and Inflammation". Journal of Clinical Medicine. 14 (7): 2145. doi:10.3390/jcm14072145. PMC 11990022. PMID 40217596. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11990022" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11990022</a> <a href="#fnref:12" class="footnote-back-ref">↩</a></p></li> <li id="fn:13"><p>Dietrich, Johannes W. (2024). "P4-Endokrinologie – Kybernetische Perspektiven eines neuen Ansatzes" (PDF). Leibniz Online (in German). 54. doi:10.53201/LEIBNIZONLINE54. <a href="https://leibnizsozietaet.de/wp-content/uploads/2024/12/03_03_Kybernetik-2024_DietrichLeibniz-Online-Fachbeitrag.pdf" target="_blank">https://leibnizsozietaet.de/wp-content/uploads/2024/12/03_03_Kybernetik-2024_DietrichLeibniz-Online-Fachbeitrag.pdf</a> <a href="#fnref:13" class="footnote-back-ref">↩</a></p></li> </ol>