Liver PPARs Quantum-Biophysical-Semeiotic Evaluation of Pre-Metabolic and Metabolic Syndrome, at Rest and under Stress Tests.

The metabolic syndrome, admittedly a multi-component riskfactor for CVD, may be more or lessstrongly linked with insulin resistance. In my opinion, neither the ATP IIInor the WHO definitions consider the many other similarly relatedCVD risk factors, such as age, physical activity, or historyof CVD events, not to speak of until now overlooked CVD Quantum-Biophysical-Semeiotic Inherited Real Risk, I’ve discovered, which proved to be, in my long clinical experience, conditio sine qua non of such macro- and micro-vessels disorders  (1-5).

Really, the Framingham risk equation, largely accepted by authors who ignore Quantum-Biophysical Semeiotics, does not unfortunately includeimportant CVD risk factors (e.g., previous CVD events, familyhistory), and has been shown to be much less useful than otherrisk equations in predicting future CVD events in people withdiabetes.

Other newly identified CVD risk factorshave been shown to be strongly associated with insulin resistanceand CVD, but, taking no knowledge on above-mentioned CVD congenital real risk, it is unclear if they should be added to the syndromeand given equal or greater weight than the current components [1-5].

Because the criteria for the syndrome will capture individualswith frank disease (e.g., diabetes, hypertension, dyslipidaemia, microalbuminuria,clinical CVD), as well as people with far milder forms of the sameconditions, it is likely that there is a risk gradient for CVDevents among patients with both Pre-Metabolic and Metabolic Syndrome.

First of all, without CVD quantum-biophysical-semeiotic inherited real risk, CVD is not possible, despite presence and seriousness of all components of Metabolic Syndrome. Thus, the definitionwill capture a spectrum of severities, and it is likelythat a person who satisfies the diagnostic criteria with riskfactor levels just over the cut point will have a much lowerCVD risk than another individual with the same combination buthigher risk factor levels (4).

Such as problem solution is far more practical and exhaustive with the aid of Quantum-biophysical Semeiotics, as well as less expensive than that ofthe Framingham and UKPDS (U.K. Prospective Diabetes Study) risk models, in which the spectrum of severities is weighted,  so that it is clear who may be at greater or lesser risk. In addition, all authors, who have been studying Metabolic Syndrome, do not know Pre-Metabolic Syndrome, that comes first for decades in individuals involved by some quantum-biophysical-semeiotic constitutions and related congenital real risks, as I illustrated in earlier articles [1-5].

Interestingly, all around the world, physicians can now-a-days utilize easily an original clinical tool, among a lot of others, reliable and efficient in recognising and monitoring  individuals with diabetic and/or dyslipidemic and/or arteriosclerotic and/or hypertensive and/or gouthy, a.s.o., quantum-biophysical-semeiotic constitutions, slowly evolving firstly to Pre-Metabolic and then to Metabolic Syndrome (2).

As a matter of fact, physicians can bedside evaluate PPARs activity in the liver, adipose tissue, and skeletal muscles  by means of Quantum-biophysical Semeiotics (www.semeioticabiofisica.it,  Practical Applications), as suggested briefly in following.

Whereas it’s sufficiently  known the role of PPARs (especially γ) in regulating adipocyte differentiation and insulin-responsive glucose up-take, at my best knowledge, no author knows the possibility to utilize liver PPARS (α) activity bedside evaluation of glucose-lipid metabolism, in assessing Pre-Metabolic Syndrome, and monitoring its slow evolution to Metabolic Syndrome.

Interestingly, such assessment can be performed at the bedside in individuals at rest, and soon thereafter, under stress tests, i.e., stimulating PPARs with endogenous Melatonin, Thyroid hormones, and adipokine, obtained respectively, e.g., by closing both eyes, stimulating thyroid trigger-points, i.e., pinching the skin upon thyroid gland (= trigger points of thyroid), and finally by pinching adipose tissue of lateral abdominal regions  (= adipokine secretion). For further information about aspecific gastric reflex evaluation, See www.semeioticabiofisica.it, Practical Applications, Technical Page N° 1, URL:

http://www.semeioticabiofisica.it/semeioticabiofisica/Documenti/Eng/pagina1stomaco_eng.doc

From diagnostic view-point, important is the rate of increasing PPARs activity in the second evaluation, i.e., under stress conditions, paralleling the efficiency of these nuclear receptors. As regards liver PPARs (α) bedside assessment, we can gather this way a large number of precious information on present glucose-lipid metabolism, surely more precise than all other laboratory data [1-10].

 

A) In health, lying down in supine position, relaxed and with open eyes to inhibit  melatonin secretion, “mean-intense” hand pressure applied on liver skin projection area brings about hepatic-aspecific gastric reflex, after a latency time of 8 sec. exactly. Moreover, reflex duration lasts less than 4 sec. (= paramount parameter value, paralleling the efficiency of hepatic Microcirculatory Functional Reserve, and thus informing on microcirculatory structure and function) (1-5). Such as result excludes local microcirculatory remodelling, and thus the presence of newborn-pathological Endoarteriolar Blocking Devices.

Under above-referred stress tests, or immediately after their stopping, latency time raises to the highest value, i.e., from basal value 8 sec. to 16 sec., doubling former value.

 

B) On the contrary, in individuals involved by both diabetic and dyslipidaemic constitutions, showing related Inherited Real Risk, basal hepatic-aspecific gastric reflex latency time, caused my “mean-intense” stimulation of liver trigger-points, results still 8 sec. (NN = 8 sec.), but reflex duration is 4 sec., indicating initial, pathologically modified, microcirculatory bed, i.e.,  microcirculatory remodelling, characterized by newborn-pathological,  type I, subtype b), aspecific, Endoarteriolar Blocking Devices, as demonstrates a more difficult, refined evaluation, based on the uretheral reflexes (1-5). Such data are really important from diagnostic viewpoint.  After stress tests, latency time raises to about 15 sec. (NN = 16 sec.),  augmenting of about 90% of basal value.

 

C) In individuals with Pre-Metabolic Syndrome, basal hepatic- aspecific gastric reflex latency time persists still 8 sec. (NN = 8 sec.), whereas reflex duration rises to 5 sec. (in health, less than 4 sec.), showing that metabolic disorder is evolving slowly. As above referred, reflex duration give precise, as well as rapid information about PPARs efficiency, allowing also the therapeutic monitoring.

Interestingly, soon thereafter stress tests, latency time raises to >13 <15 sec., i.e., about 70% of initial value, indicating  the worsening  of glucose-lipids metabolism impairment.

 

D) In patients with Metabolic Syndrome, the latency time of basal hepatic-aspecific gastric reflex decreases to about 7 sec. (NN = 8 sec.); reflex duration is clearly prolonged: > 5 sec. ≤ 6 sec.  In addition, either during dynamic tests or immediately after stress test stopping, latency time raises ≥ 12 < 13 (augmenting about 50% of basal value)

 

Finally, in overt diabetes and/or dyslipidaemia, basal hepatic-aspecific gastric reflex latency time may be pathologically lowered, less than 8 sec.  (NN = 8 sec.), especially in overt disorder,  but reflex duration is always prolonged as far as to its highest levels: ≥ 6 sec. Moreover, in health, under above-mentioned stress tests or soon thereafter, latency time rises in a significant manner to 16 sec. (double value than that at rest).

On thy contrary, in patients involved by glucose and lipid metabolism impairment, latency time either do not  change at all, or ameliorates, but no significantly, in relation to the severity of underlying disorder.

At this point, I remember the numerous quantum-biophysical-semeiotic signs and manoeuvres, which allow doctors to bedside evaluate, in reliable way, blood glucose level, insulin secretion, insulin receptor sensitivity  in every peripheral target tissue (10-19).

Finally, we must take into accounts the paramount diagnostic value of liver preconditioning: after exact 5 sec. since the end of first assessing hepatic PPARs, doctor performs a second evaluation.

In health, negative for both diabetic and dyslipidaemic constitutions, after preconditioning the reflex duration raises significantly from 8 sec. to 16 sec. , doubling basal value, as it happen under above-illustrated stress tests.

On the contrary, in case B) duration lowers from 16 sec. to 15 sec. or less, rather than increasing: the intensity of pathological reflex duration lowering parallels the seriousness of underlying metabolism impairment.

At this point,  I must emphasize that the absence of dyslipidaemic constitution among individuals is indeed very rear in my experience, occurring about 1 every 100 individuals, due perhaps to thrift genes.

In conclusion, aiming to realise an efficacious primary prevention of Pre-Metabolic and Metabolic Syndrome and its slow evolution towards various disorders on very large scale, in individuals rationally enrolled, doctors have to bedside recognize, possibly since birth, all subjects positive for dylsipidaemic and/or diabetic constitutions, conditio sine qua non of  dyslipidaemias and diabetes, when both conditions are associated.

Subsequently,  physicians have to ascertain the presence of related inherited real risks of dyslipidaemia and diabetes [1-5,20-25].

From the above remarks, the numerous suggested predictors of future cardiovascular events, as moderate elevations in CPR present in apparently healthy individuals [26-28], seem less significant than admitted now.

 

References

 

1. Stagnaro Sergio.  Pre-Metabolic Syndrome and Metabolic Syndrome: Biophysical-Semeiotic Viewpoint. www.athero.org, 29 April, 2009. http://www.athero.org/commentaries/comm904.asp

2. Stagnaro Sergio. CAD Inherited Real Risk, Based on Newborn-Pathological, Type I, Subtype B, Aspecific, Coronary Endoarteriolar Blocking Devices. Diagnostic Role of Myocardial Oxigenation and Biophysical-Semeiotic Preconditioning. www.athero.org, 29 April, 2009  http://www.athero.org/commentaries/comm907.asp

3. Stagnaro S.  Metabolic Syndrome, even initial: diagnostic  Role of clinical, quantitative, biophysical-semeiotic PPAR Evaluation  by endogenous Thyroid Hormon and Melatonin.

http://www.semeioticabiofisica.it/semeioticabiofisica/Documenti/Eng/Metabolic%20Syndrome%20PPARS%20engl.doc

4.  Stagnaro Sergio. Epidemiological evidence for the non-random clustering of the components of the metabolic syndrome: multicentre study of the Mediterranean Group for the Study of Diabetes. Eur J Clin Nutr. 2007 Feb 7;   [MEDLINE]

5.  Stagnaro S.     Bed-Side Biophysical-Semeiotic Evaluation of PPARs Activity.

http://www.semeioticabiofisica.it/semeioticabiofisica/Documenti/Eng/PPARs%20BS%20Evaluation%20eng.doc

6.   Stagnaro S.      Biophysical-Semeiotic bed-side Evaluation of Adiponectin in classic and variant Pre-Metabolic and Metabolic Syndrome. http://www.semeioticabiofisica.it/semeioticabiofisica/Documenti/Eng/Adiponectin%20lavoro%20engl.doc

7. Stagnaro Sergio Biophysical-Semeiotic Bed-Side Evaluating PPARs Activity in Metabolic Syndrome.   Cardiovascular Diabetology. (19 September 2005)   http://www.cardiab.com/content/4/1/14/comments#211488

8. Stagnaro Sergio. Bedside biophysical-semeiotic PPARs evaluation in glucose-lipid metabosism monitoring. Annals of Family Medicine, 2007; 5: 14-20. http://www.annfammed.org/cgi/eletters/   

9. Stagnaro  Sergio.  Pivotal PPARs Activity Bed-side Evaluation in Pre-Metabolic Syndrome and Metabolic Syndrome Primary Prevention. Cardiovascular Diabetology. 2005, 4:13     doi:10.1186/1475-2840-4-13 2005

10. Stagnaro Sergio.  Pivotal Role of Liver PPARs Activity Bed-side Evaluation in Monitoring glucidic and lipidic Metabolism. Lipids in Healt and Disease. 02 June 2007, http://www.lipidworld.com/content/6/1/12/comments#284542 2007

11.   Stagnaro Sergio.  Biophysical-Semeiotic Diagnosis of Diabetes Mellitus since its initial stages.

http://www.semeioticabiofisica.it/semeioticabiofisica/Documenti/Eng/Diagnosi%20Semeiotico-Biofisica%20del%20Diabete%20Mellito_eng.doc

12. Stagnaro Sergio.    Biophysical-Semeiotic Evaluation of Insular Amyloid in Bed-Side Diagnosing Diabetes Mellitus Type II, since Initial Stage.

http://www.semeioticabiofisica.it/semeioticabiofisica/Documenti/Eng/Diagnosis%20DM,%20amyloid.doc

13.  Stagnaro Sergio. From Diabetic and Dyslipidemic Biophysical-Semeiotic Constitutions

to Type 2 Diabetes Mellitus. http://www.semeioticabiofisica.it/semeioticabiofisica/Documenti/Eng/A%20IIR%20Lipids%20Sem.%20Biof%20Engl.doc

14. Stagnaro Sergio. Beyond Hyperinsulinemia-Insulin Resistance in the War against Arteriosclerosis and type 2 Diabetes Mellitus. http://www.semeioticabiofisica.it/semeioticabiofisica/Documenti/Eng/Beyond%20Hyperinsulinemia%20engl.doc

15. Stagnaro Sergio. Diabetic Constitution, Obesity, Insulin-Resistance, PPARs, and Type 2 Diabetes Mellitus.http://www.semeioticabiofisica.it/semeioticabiofisica/Documenti/Eng/A%20CD%20DM%20PPAR%20engl.doc

16.   Stagnaro Sergio. Beyond Glycemia: Biophysical-Semeiotic Evaluation of Glycemic Metabolism.   http://www.semeioticabiofisica.it/semeioticabiofisica/Documenti/Eng/AB%20Glicemia%20Valut%20SB%20engl.doc

17. Stagnaro-Neri M., Stagnaro S., Semeiotica Biofisica: la manovra di Ferrero-Marigo nella diagnosi clinica della iperinsulinemia-insulino resistenza. Acta Med. Medit. 13, 125, 1997.

18. Stagnaro-Neri M., Stagnaro S., Semeiotica Biofisica: valutazione clinica del picco precoce della secrezione insulinica di base e dopo stimolazione tiroidea, surrenalica, con glucagone endogeno e dopo attivazione del sistema renina-angiotesina circolante e tessutale – Acta Med. Medit. 13, 99 1997

19. Stagnaro-Neri M., Stagnaro S., Il Segno di Bilancini-Lucchi nella diagnosi clinica del diabete mellito. The Pract. Ed. It. 176, 30, 1993.

18. Stagnaro S., Stagnaro-Neri M., Le Costituzioni Semeiotico-Biofisiche.Strumento clinico fondamentale per la prevenzione primaria e la definizione della Single Patient Based Medicine. Travel Factory, Roma, 2004. http://www.travelfactory.it/

21. Stagnaro S., Stagnaro-Neri M., Single Patient Based Medicine.La Medicina Basata sul Singolo Paziente: Nuove Indicazioni della Melatonina. Ed.Travel Factory, Roma, 2005. http://www.travelfactory.it/libro_singlepatientbased.htm

22. Stagnaro  Sergio.  Biophysical Semeiotic Constitutions, Genomics, and Cardio-Vascular Diseases. BMC Cardiovascular Disorders http://www.biomedcentral.com/1471-2261/4/20/comments#95454 2004

23. Stagnaro Sergio. Teoria Patogenetica Unificata, 2006, Ed. Travel Factory, Roma.

24. Stagnaro Sergio.   Bedside diagnosing diabetic and dyslipidaemic constitutions and diabetes real risk. 2 October2006 http://www.cmaj.ca/cgi/eletters/175/7/733

25. Stagnaro Sergio.  Role of Coronary Endoarterial Blocking Devices in Myocardial Preconditioning – c007i. Lecture, V Virtual International Congress of Cardiology. http://www.fac.org.ar/qcvc/llave/c007i/stagnaros.php

26. Ridker PM, Buring JE, Shih J. Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women. Circulation. 1998;98:731-733.

27. Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med. 2000;342:836-43

28. Kervinen H, Palosuo T, Manninen V, Tenkanen L, Vaarala O, Mänttäri M. Joint effects of C-reactive protein and other risk factors on acute coronary events. Am Heart J. 2001;141:580-585.

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