Biophysical-Semeiotic Bed-Side Evaluating PPARs Activity in Metabolic Syndrome.
Sergio Stagnaro, Biophysical Semeiotics Laboratory Research
19 September 2005
Sirs,
in my 48-year-long clinical experience, the primary prevention of all components of metabolic syndrome, as IIR, IGT and type 2 diabetes, dyslipidaemia, is principally based on recognizing on very large scale Pre-Metabolic syndrome, classic and “variant” (See web site www.semeioticabiofisica.it/microangiologia.it, Pre-Metabolic Syndrome, URL http://www.semeioticabiofisica.it/microangiologia/Documenti/Eng/Pre-metabolic%20syndrome%), and its early evolution to metabolic syndrome, since the well-known diabetes and dyslipidaemia complications begin years or decades before disorder onset.
Dyslipidaemia is a major risk factor for atherosclerotic coronary heart disease, which in turn is the commonest cause of mortality in type 2 diabetes, caused by dyslipidaemia-dependent insulin-resistance. Management is typically multifactorial and includes dietary recommendations, routine physical exercise, aggressive control of other lifestyle risk factors, and for many patients drug intervention. Future drug treatments will improve other facets of diabetic dyslipidaemia, atherogenesis and vascular risk.
One of the most active areas of metabolic research into potential treatments surrounds the role of nuclear receptors as a treatment target for both glucose and lipid metabolism. For example, agonists of the peroxisome proliferator-activated receptor (PPAR) offer unique potential in several respects. PPAR agonists (such as fibrates) have been shown to lower triglyceride and increase HDL-c, with a variable effect upon LDL-c blood levels. PPARγ agonists (such as the thiazolidinediones) have variable effects on the lipid profile, in addition to improving insulin sensitivity and blood glucose levels in patients with type 2 diabetes. Pre-clinical studies suggest that both PPARα and PPARγ agonists have direct anti-atherogenic effects (1).
Therefore, single agents that promote both PPARα and PPARγ agonism could theoretically offer significant benefits in improving dyslipidaemia and reducing hyperglycaemia, and thus reduce these cardiovascular risk factors associated with type 2 diabetes and metabolic syndrome.
In addition, PPAR physiological functioning indicates clearly a normal glyco-lipidaemic metabolism (2).
Among a lot of biophysical-semeiotic methods, different in technical difficulty, but similarly reliable and useful in assessing peroxisome proliferator-activated receptors (PPARs) (3), I suggest two methods, based on melatonin and thyroide hormone secretion, which allows doctor to bed-side evaluate the activity of such nuclear receptors in individuals with Pre-Metabolic Syndrome (3-6). In a few words, PPARs are members of the nuclear receptor family that regulates the expression of genes that control fatty acid synthesis, storage, catabolism, as well as glucose homeostasis and insulin sensitivity, e.g., in the liver. PPARs bind as heterodimers with another member of the nuclear receptor family, the retinoid X receptor (RXR- ROR), stimulated also by melatonin (3-6), to peroxisome proliferator response elements (PPREs) in the P450 4A1 and 4A6 genes. In addition, recent data suggest that PPAR alpha and gamma activation decreases atherosclerosis progression not only by correcting metabolic disorders, but also through direct effects on the vascular wall (ibidem). PPARs modulate the recruitment of leukocytes to endothelial cells, control the inflammatory response and lipid homeostasis of monocytes/macrophages and regulate inflammatory cytokine production by smooth muscle cells. In conclusion, Biophysical-Semeiotic Evaluating PPARs activity, described for the first time from clinical view-point, represents a paramount event in Preventive Medicine.
1) Camejo G, Rosengren B, Hallberg C, Wallin B. PPAR agonists vascular effects contributing to their apparent anti-atherogenic action. Presented at the 2nd International Symposium on PPARs: from basic science to clinical applications. March, 2003.
2) Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346:393-403.
3) Stagnaro Sergio. Bed-Side Biophysical-Semeiotic Evaluation of PPARs Activity.
4) Stagnaro Sergio, Stagnaro-Neri Marina. Introduzione alla Semeiotica Biofisica. Il Terreno oncologico”. Travel Factory SRL., Roma, 2004. http://www.travelfactory.it/semeiotica_biofisica.htm
5) Stagnaro S., Stagnaro-Neri M., La Melatonina nella Terapia del Terreno Oncologico e del “Reale Rischio” Oncologico. Ediz. Travel Factory, Roma, 2004.
6) Stagnaro S., Stagnaro-Neri M., Le Costituzioni Semeiotico-Biofisiche.Strumento clinico fondamentale per la prevenzione primaria e la definizione della Single Patient Based Medicine. Ediz. Travel Factory, Roma, 2004. http://www.travelfactory.it/semeiotica_biofisica.htm
Cardiovascular Diabetology
Biophysical-Semeiotic Bed-Side Evaluating PPARs Activity in Metabolic Syndrome.
19 September 2005
Sirs,
in my 48-year-long clinical experience, the primary prevention of all components of metabolic syndrome, as IIR, IGT and type 2 diabetes, dyslipidaemia, is principally based on recognizing on very large scale Pre-Metabolic syndrome, classic and “variant” (See web site www.semeioticabiofisica.it/microangiologia.it, Pre-Metabolic Syndrome, URL http://www.semeioticabiofisica.it/microangiologia/Documenti/Eng/Pre-metabolic%20syndrome%), and its early evolution to metabolic syndrome, since the well-known diabetes and dyslipidaemia complications begin years or decades before disorder onset.
Dyslipidaemia is a major risk factor for atherosclerotic coronary heart disease, which in turn is the commonest cause of mortality in type 2 diabetes, caused by dyslipidaemia-dependent insulin-resistance. Management is typically multifactorial and includes dietary recommendations, routine physical exercise, aggressive control of other lifestyle risk factors, and for many patients drug intervention. Future drug treatments will improve other facets of diabetic dyslipidaemia, atherogenesis and vascular risk.
One of the most active areas of metabolic research into potential treatments surrounds the role of nuclear receptors as a treatment target for both glucose and lipid metabolism. For example, agonists of the peroxisome proliferator-activated receptor (PPAR) offer unique potential in several respects. PPAR agonists (such as fibrates) have been shown to lower triglyceride and increase HDL-c, with a variable effect upon LDL-c blood levels. PPARγ agonists (such as the thiazolidinediones) have variable effects on the lipid profile, in addition to improving insulin sensitivity and blood glucose levels in patients with type 2 diabetes. Pre-clinical studies suggest that both PPARα and PPARγ agonists have direct anti-atherogenic effects (1).
Therefore, single agents that promote both PPARα and PPARγ agonism could theoretically offer significant benefits in improving dyslipidaemia and reducing hyperglycaemia, and thus reduce these cardiovascular risk factors associated with type 2 diabetes and metabolic syndrome.
In addition, PPAR physiological functioning indicates clearly a normal glyco-lipidaemic metabolism (2).
Among a lot of biophysical-semeiotic methods, different in technical difficulty, but similarly reliable and useful in assessing peroxisome proliferator-activated receptors (PPARs) (3), I suggest two methods, based on melatonin and thyroide hormone secretion, which allows doctor to bed-side evaluate the activity of such nuclear receptors in individuals with Pre-Metabolic Syndrome (3-6). In a few words, PPARs are members of the nuclear receptor family that regulates the expression of genes that control fatty acid synthesis, storage, catabolism, as well as glucose homeostasis and insulin sensitivity, e.g., in the liver. PPARs bind as heterodimers with another member of the nuclear receptor family, the retinoid X receptor (RXR- ROR), stimulated also by melatonin (3-6), to peroxisome proliferator response elements (PPREs) in the P450 4A1 and 4A6 genes. In addition, recent data suggest that PPAR alpha and gamma activation decreases atherosclerosis progression not only by correcting metabolic disorders, but also through direct effects on the vascular wall (ibidem). PPARs modulate the recruitment of leukocytes to endothelial cells, control the inflammatory response and lipid homeostasis of monocytes/macrophages and regulate inflammatory cytokine production by smooth muscle cells. In conclusion, Biophysical-Semeiotic Evaluating PPARs activity, described for the first time from clinical view-point, represents a paramount event in Preventive Medicine.
1) Camejo G, Rosengren B, Hallberg C, Wallin B. PPAR agonists vascular effects contributing to their apparent anti-atherogenic action. Presented at the 2nd International Symposium on PPARs: from basic science to clinical applications. March, 2003.
2) Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346:393-403.
3) Stagnaro Sergio. Bed-Side Biophysical-Semeiotic Evaluation of PPARs Activity.
http://www.semeioticabiofisica.it/semeioticabiofisica/Documenti/Eng/PPARs%20BS%20Evaluation%
4) Stagnaro Sergio, Stagnaro-Neri Marina. Introduzione alla Semeiotica Biofisica. Il Terreno oncologico”. Travel Factory SRL., Roma, 2004. http://www.travelfactory.it/semeiotica_biofisica.htm
5) Stagnaro S., Stagnaro-Neri M., La Melatonina nella Terapia del Terreno Oncologico e del “Reale Rischio” Oncologico. Ediz. Travel Factory, Roma, 2004.
6) Stagnaro S., Stagnaro-Neri M., Le Costituzioni Semeiotico-Biofisiche.Strumento clinico fondamentale per la prevenzione primaria e la definizione della Single Patient Based Medicine. Ediz. Travel Factory, Roma, 2004. http://www.travelfactory.it/semeiotica_biofisica.htm
Competing interests
Not declared