Математика во благо: новый простой метод ранней диагностики диабета Одной из самых важных задач в процессе лечения какого-либо заболевания является диагностика, т.е. выявление этого заболевания. И чем раньше это происходит, тем проще и эффективнее будет лечение....

habr.com/p/788494/

SPINA-DI: Fasting-Based Disposition Index For Diabetes Diagnosis - Medical News Observer A recent study in the Journal of Diabetes introduced a novel method for diabetes diagnosis: the fasting-based disposition index (SPINA-DI).

medicalnewsobserver.com/2024/01/22/s...

Figure from the paper: Two levels of perfusion in colour Doppler ultrasound. Low perfusion corresponds to level 1, high perfusion to level 2.

Table from the paper: SPINA-GT is significantly higher in level 2 perfusion than in level 1 perfusion.

Table from the paper: SPINA-GT correlates to colour Doppler ultrasound grading.

#SPINA-GT correlates to the grading of colour #Doppler #ultrasound investigations in #hyperthyroidism and #thyrotoxicosis.

pubmed.ncbi.nlm.nih.gov/35942151/
www.livivo.de/doc/M35942151
doi.org/10.1155/2022...

Table of the paper: Unadjusted and adjusted correlation models for the association between allostatic load and calculated biomarkers of thyroid homeostasis. The allostatic load correlates with Jostel's TSH index (TSHI), TTSI, TFQI and SPINA-GD.

Table of the paper: In adjusted models, SPINA-GD is higher in quartiles 2 to 4 of allostatic load than in the baseline quartile 1.

In an adjusted model, #SPINA-GD correlates significantly with type 2 allostatic load. It parallels the association to central markers of thyroid homeostasis, underscoring the TSH-T3 feedforward control.

#thyroid #allostasis

pubmed.ncbi.nlm.nih.gov/41941533/
doi.org/10.1080/1025...

Screenshot of SimulAdren 2.0 (Rubycon) on macOS 13.7 (Ventura).

Screenshot of SimulAdren 2.0 (Rubycon) on Windows 11

Screenshot of SimulAdren 2.0 (Rubycon) on Fedora Linux 38

#SimulAdren underwent a major upgrade. Version 2.0 introduces significant new features, e.g., support for different models, initial conditions, first-order delay kinetics (ASIA elements), and model continuation.

simuladren.sourceforge.io
doi.org/10.5281/zeno...
doi.org/10.5281/zeno...

Two bar plots from the paper: Yearly numbers of publications in PubMed from 1965 to 2025 on mathematical modelling in endocrinology and diabetes with (left) and without (right) machine learning. Search terms were “(“mathematical modelling” OR “computer simulation” OR “machine learning”) AND (endocrinology OR endocrine OR hormone OR hormonal OR diabetes)” for the left plot and “(“mathematical modelling” OR “computer simulation”) AND (endocrinology OR endocrine OR hormone OR hormonal OR diabetes)” for the right plot. The left chart shows a dramatic increase, peaking sharply in the year 2025 at nearly 3000 publications. The right chart shows moderate growth with peaks around four hundred around the year 2025.

Mathematical modelling, computer #simulation, and machine learning upgrade #endocrinology. Applying principles of #biocybernetics and #biophysics, they enjoy growing interest and deliver novel methods for research, diagnosis, and therapy.

pubmed.ncbi.nlm.nih.gov/41852474/
doi.org/10.3389/fend...

New calculation offers simple and reliable early prediction of diabetes Diabetes often remains undetected until it has already damaged organs or nerves. This is partly due to the fact that diagnosis at an early stage is time-consuming and difficult.

Diagnosis of #diabetes mellitus and #prediabetes: A simple calculation may be better than a complex test.

🧪 🩺 #MedSky @medsky.social #Endosky #Endocrinology

medicalxpress.com/news/2024-01...

#SPINA_Thyr predicts the prognosis of #Takotsubo syndrome. Among all predictors, #SPINA-GD showed the most significant difference.

🧪 🩺 #MedSky @medsky.social #Endocrinology

Figure: Definition of clusters. Thyroid response and pituitary response curves denote the median of thyroid’s secretory capacity (SPINA-GT) and empirical thyrotropic pituitary response.

Figure: Association of clusters with total fatality (left) and time-course of survival (right).

Table: Characteristics of the three clusters. The figures in the first two lines refer to medoids of TSH and FT4 concentration as identified by the clustering algorithm.

#Takotsubo syndrome (TTS) is a poorly understood life-threatening #cardiomyopathy. With machine learning, we found 3 signatures of #thyroid #homeostasis heralding the prognosis of patients affected by TTS.

pubmed.ncbi.nlm.nih.gov/38502972/
doi.org/10.1016/j.eb...
www.livivo.de/doc/M38502972

<em>Journal of Internal Medicine</em> | Wiley Online Library Background Several reports have described Takotsubo syndrome (TTS) secondary to thyrotoxicosis. A complex interaction of central and peripheral catecholamines with thyroid homeostasis has been sugge...

Calculating #SPINA-GT has helped to distinguish two different ways leading to #thyroid-related #Takotsubo #cardiomyopathy.

www.livivo.de/doc/M33179374
pubmed.ncbi.nlm.nih.gov/33179374/
doi.org/10.1111/joim...

Figure: Bivariate null isokline plot of first measured FT4 and TSH serum concentrations per subject in relation to percentiles of subsystem responses of thyroid homeostasis. Shown are three different point clouds, representing three clusters: Normal controls (green dots in the center), critically-ill patients with acute coronary syndroms (black dots in the lower zone of TSH concentration) and patientes with Takotsubo syndrome (red dots in two cloucs with low and high TSH concentration).

Distribution (mean ± SEM) of measured and derived parameters in TTS during the first seven days of treatment. The shaded rectangles mark the reference ranges for the respective parameters. *P < 0.05, **P < 0.01, ***P < 0.001, *****P < 1e–5 compared to reference range with binomial test; P values are adjusted with the Benjamini–Hochberg method. SPINA-GT is elevated, and SPINA-GD is reduced during the first three days of Takotsubo syndrome. TTSI is elevated on day 3, representing a high set point of thyroid homeostasis as a consequence of type 2 allostatic load.

Abnormal thyroid function in Takotsubo syndrome is marked by two distinct phenotypes: an endocrine type representing primary hyperthyroidism and a stress type with an elevated set point of thyroid homeostasis. The results suggest a stress-dependent adaptive endocrine response or type 2 thyroid allostasis.

#Takotsubo syndrome is a dangerous stress-related #heart disease. Since #T3 upregulates β-receptors, we assumed a link to #thyroid homeostasis. With machine learning, we identified interesting allostatic patterns.

www.livivo.de/doc/M33179374
pubmed.ncbi.nlm.nih.gov/33179374/
doi.org/10.1111/joim...

Previsione precoce semplice e affidabile del diabete. Il diabete spesso rimane inosservato finché non ha già danneggiato organi o nervi. Ciò è in parte dovuto al fatto che la diagnosi in fase precoce è difficile e dispendiosa in termini di tempo. Un t…

Previsione precoce semplice e affidabile del diabete

blogpinali.wordpress.com/2024/01/23/p...

Information processing structure of the feedback model. [G](t): glucose concentration; S(t): insulin secretion rate; [I](t): insulin concentration; M(t): proximal insulin signalling; N(t) distal insulin signalling; P(t): constitutive glucose production rate; Q(t): regulated glucose production rate; W(t): intestinal glucose absorption rate; R(t): glucose arrival rate. G1 and G3 represent gains of ASIA elements. Units of measurement are displayed in the small, rounded boxes with red margins.

Circular Maps of the correlation networks of novel biomarkers for insulin-glucose homeostasis with anthropometric and experimental data in the NHANES cohort (A) and the clamp study (B). Shown are significant correlations (p < 0.05) only, and line thickness indicates the strength of negative (blue) or positive (red) correlation. A green segment in the inner ring indicates a reduction of the corresponding biomarker in subjects with diabetes.

Plot of SPINA-GBeta against SPINA-GR, suggesting a compensatory rise of beta cell function in the case of declining insulin sensitivity in subjects with normal glucose homeostasis (green dots). This ability of beta cell compensation is partly lost in subjects with prediabetes (orange dots) or diabetes (red dots).

Mathematical modelling of #insulin-#glucose #homeostasis delivers new and improved methods for metabolic endotyping. #prediabetes #diabetes #metabolic_syndrome #betacell pubmed.ncbi.nlm.nih.gov/36271244/ doi.org/10.1038/s415...

Molecular Mechanisms in gestational diabetes mellitus (GDM). Pregnancy-induced insulin resistance is driven by placental hormones (human placental lactogen (hPL), placental growth hormone, estrogen, progesterone, cortisol) and inflammatory cytokines (tumour necrosis factor α (TNF α), interleukin 6 (IL-6), interleukin 1β (IL-1β)). Inadequate β-cell adaptation due to mitochondrial dysfunction, and impaired incretin signaling leads to hyperglycemia. Dysregulated adipokines (decreased adiponectin, increased leptin, resistin, visfatin), oxidative stress, and epigenetic modifications (deoxyribonucleic acid (DNA) methylation, non-coding ribonucleic acids (RNAs)) further exacerbate disease and contribute to adverse maternal and fetal outcomes.

Gestational #diabetes mellitus (GDM) is linked to significant adverse outcomes for both mothers and their offspring. Since #SPINA-GBeta outperforms #HOMA-Beta, its use is advised as a preferred calculated #biomarker for the evolution and pathophysiology of #GDM.

pubmed.ncbi.nlm.nih.gov/40943638/

Screenshot of the web site of the Research Topic "Mechanistic, Machine Learning and Hybrid Models of the 'Other' Endocrine Regulatory Systems in Health and Disease: Volume II" in Frontiers in Systems Endocrinology

Are you researching #endocrine #feedback control systems?

Our Research Topic "Mechanistic, Machine Learning and Hybrid Models of the 'Other' Endocrine Regulatory Systems in Health and Disease: Volume II" is still open for submission.

www.frontiersin.org/research-top...

#endocrinology #cybernetics

Table showing increased risk of dementia, atrial fibrillation and fatality in patients with treated hypothyroidism in a follow-up of 20 years

Forest plot showing increased risk of dementia in patients with treated hypothyroidism

Table with the results of multivariable regression analysis, showing significantly increased risk for dementia and fatality in monotherapy with L-T4 compared to combination therapy of L-T4 and L-T3 or DTE

Table showing increased risk for dementia, atrial fibrillation and fatality in patients receiving monotherapy with L-T4 compared to combination therapy consisting of L-T4 and L-T3 or DTE.

Patients with #hypothyroidism, even when treated with levothyroxine (L-T4), face increased risk of #dementia and #fatality. Fortunately, the risk can be lowered again by a combination therapy with L-T4 and L-T3, as shown by a recent study.

pubmed.ncbi.nlm.nih.gov/40579157/
doi.org/10.1210/clin...

#SPINA_Thyr helps in decision-making to implement this algorithm.

Sketch of pituitary-thyroid feedback control (HPT axis) maintaining thyroid homeostasis. This figure provides an overview of biomarkers for TR-alpha (Heart rate, ECG QT interval, JT interval, Tp-e interval and ostase concentration, painted in cyan) and TR-beta (concentrations of ceruloplasmin, copper, SHBG, CK, lipids, painted in orange) signalling and of functional biomarkers (SPINA-GT, SPINA-GD, Jostel’s TSH index, TTSI, TFQI, rounded boxes).

Positive and negative biomarkers for thyroid hormone action in tissues. Positive biomarkers for TR-alpha signalling include bone-specific alkaline phosphatase (ostase) and heart rate, negative biomarkers for TR-alpha signalling comprise QT interval, JT interval and TP-e interval in the ECG. Positive biomarkers for TR-beta signalling are 3-methylhistidine, coeruloplasmin, copper and sex-hormone binding globulin (SHBG), negative biomarkers for TR-beta signalling include lipids (total cholesterol, low-density lipoprotein [LDL], high-density lipoprotein [HDL], lipoprotein a [Lp(a)] and triglycerides) and creatine kinase (CK).

For the diagnosis and management of #hypothyroidism, measuring #TSH (thyrotropin) concentration is necessary, but it isn’t sufficient. Additional #biomarkers help to improve diagnostic power and to identify #endotypes of dysregulation.

doi.org/10.1007/978-...

🧪 🩺 #MedSky

European flag

SPINA apps are also available from European servers, provided by #CERN's #zenodo:

doi.org/10.5281/zeno...
doi.org/10.5281/zeno...

‪@cern.bsky.social‬

#SPINA_Thyr and #SPINA_Carb, two implementations of the structure parameter inference approach (SPINA), provide evidence-based improved methods for diagnosis and endotyping of endocrine diseases. Now, thoroughly tested apps for Mac and Windows are available for free download.

spina.sf.net

Screenshot of SPINA Carb 5.1.0 Cycline on macOS 15.5 Sequoia, showing two Windows (entry and results).

SPINA Carb 5.1.0 Cyclone has been released in its final version.

#SPINA-GBeta #SPINA-GR #SPINA-DI #SPINA_Carb #insulin #glucose #homeostasis #prediabetes #diabetes

sourceforge.net/projects/spi...

doi.org/10.5281/zeno...

doi.org/10.5281/zeno...

Screenshot of release candidate 3 of SPINA Carb 5.1 Cyclone on mac OS 15.5 Sequoia

Release candidate 3 for the software SPINA Carb Cyclone is available for macOS, Windows and Linux.

sourceforge.net/projects/spi...

doi.org/10.5281/zeno...

doi.org/10.5281/zeno...

#SPINA_Carb #SPINA-GBeta #SPINA-GR #SPINA-DI #HOMA

Hypothalamic–pituitary–thyroid regulation is implemented by multiple feedforward motifs and feedback loops.

Demonstration of attainment of perfect FT3 homeostasis in hypothalamic–pituitary–thyroid axis regulation in a mathematical model. The interactive loops of the hypothalamic–pituitary–thyroid axis regulation enable the actions of TRH (not shown), TSH, and FT4 to cooperate in a way to produce an equilibrium solution of perfect homeostasis for FT3. This is an example of relational stability. The strengths of all limbs have been normalised.

Multiple feedforward motifs and feedback loops maintain #thyroid #homeostasis and #allostasis. The mechanism of relational stability maintains T3 in a balanced and safe range, even in conditions of declining thyroid function.

doi.org/10.1007/978-...

🧪 🩺 #MedSky

Table: Characteristics of euthyroid subjects with benign disease or differentiated thyroid cancer. Patients with cancer have lower SPINA-GT and a higher set point (TSHI and TT4RI) than patients with benign nodules.

Table: Association between thyroid parameters (per SD change) and differentiated thyroid cancer in total subjects. SPINA-GT is negatively associated with the presence of cancer.

In patients undergoing #thyroid surgery due to nodules, #SPINA-GT is lower (and the set point of the homeostatic system higher) in cases of thyroid cancer compared to benign nodules.

doi.org/10.3389/fend...

Table from the book "Hypothyroidism – a Paradigm Shift" by Hoermann and Dietrich: Four receptor types (THRalpha1, THRbeta1, THRbeta2, THRbeta3, p43 and alphaVbeta3) convey thyroid signals in different tissues.

Table from the book "Hypothyroidism – a Paradigm Shift" by Hoermann and Dietrich: Eleven types of transporters with different hormone- and tissue-specificity carry thyroid hormones through cell membranes.

Figure from the book "Hypothyroidism – a Paradigm Shift" by Hoermann and Dietrich, showing an opened cell with the interaction of different thyroid hormones, transporters, deiodinases and signaling types.

Table from the book "Hypothyroidism – a Paradigm Shift" by Hoermann and Dietrich: Three types of deiodinases mediate step-up and step-down reactions interconverting thyroid hormones and leading to activation and inactivation.

Signalling via #thyroid hormones is more than T3 and T4. It involves 27 molecules based on the thyronine skeleton, 10 transmembrane transporters, 3 deiodinases, 6 receptors, and 4 types of action, unfolding a complex firework of possibilities, explaining health and disease.

doi.org/10.1007/978-...

A stack with several printed books, "Hypothyroidism – A Paradigm Shift" by Rudolf Hoermann and Johannes W. Dietrich.

Flyer for the book "Hypothyroidism – A Paradigm Shift" by Rudolf Hoermann and Johannes W. Dietrich. Use the code SPRAUT to get a discount of 20% at Springer Nature.

Our book is now available in printed form. Use the code SPRAUT to get a discount of 20% at Springer Nature.

link.springer.com/book/9789819...

Figure from the book "Hypothyroidism: A Paradigm Shift" by Hoermann and Dietrich: Combination of peripheral and central mechanisms leading to the low-T3 syndrome. The activities of peripheral (GD1) and central (GD2) deiodinases diverge to cause the low-T3 phenotype. The graph shown has been produced by computer simulation with the free app SimThyr.

Computer simulations with #SimThyr enhance our understanding of the physiology of hypothalamic-pituitary-thyroid feedback control. This applies, for example, to the evolution of #TACITUS syndrome.

#thyroid #hypothyroidism #NTIS #biocybernetics

doi.org/10.1007/978-...

Title page of the book "Hypothyroidism" by Hoermann and Dietrich. This book revolutionizes our understanding of the regulation of the hypothalamic-pituitary-thyroid axis and the homeostasis of the thyroid system, offering a groundbreaking framework for diagnosing and treating hypothyroidism. By challenging conventional approaches, it addresses the pressing need for improved treatment quality, especially for patients experiencing persistent symptoms despite standard levothyroxine therapy. Delve into a comprehensive exploration of hypothyroidism, from its definition and pathophysiology to patient presentation and endocrine regulation. The chapters illuminate critical topics such as iodine metabolism, thyroid hormone signaling, and the intricacies of the hypothalamic-pituitary-thyroid axis. With contributions from leading experts, this book presents a paradigm shift in clinical care by integrating recent advances in thyroid regulation into practical treatment strategies. Readers will uncover why many patients fail to respond adequately to current treatments and discover innovative approaches to diagnosis and therapy. Ideal for medical professionals, researchers, clinicians, and specialists interested in thyroid disease, this book is also invaluable for general practitioners and informed patients seeking deeper insights into their condition. Aspiring endocrinologists will find it particularly educational, aligning with curriculum requirements while offering a fresh perspective on thyroid health. With its focus on cutting-edge research and practical applications, this volume is indispensable for anyone dedicated to improving patient care in the field of endocrinology.

Our eBook on #hypothyroidism has been published. The new cybernetic theory presented here summarises our scientific work of more than 20 years and lays the foundation for improved diagnosis and therapy of #thyroid disorders.

The book is available in EPUB and PDF formats.

doi.org/10.1007/978-...

Screenshot of SPINA Carb 5.1.0 (Cyclone) RC2 on macOS Ventura 13.7.5.

Release candidate 2 of #SPINA_Carb is available for testing.

sourceforge.net/projects/spi...

doi.org/10.5281/zeno...

doi.org/10.5281/zeno...

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