Metabolic syndrome 2

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Metabolic syndrome 2

  1. 1. Metabolic Syndrome 2 Dr. Yousef Elshrek
  2. 2. • Recent evidence has shown that adults with metabolic syndrome have significantly higher systolic blood pressure (SBP) than normal during childhood. • However, it has not been welldocumented the extent to which systolic blood pressure predicts metabolic syndrome in male adolescents. • Early treatment of metabolic syndrome components decreases morbidity and mortality.
  3. 3. • The obesity epidemic has spread in children around the world and may lead to an increased incidence of metabolic syndrome. • Furthermore, some evidence suggests that this metabolic derangement persists into adulthood. • Therefore, identification of children at risk of developing metabolic syndrome later in life can be critical in the overall effort to reduce mortality.
  4. 4. • Blood pressure measurements tend to be omitted in routine assessments of children. • When it is measured, the variation of normal BP with age can lead to missing the diagnosis of hypertension. • Normal ranges are : 1. 2. 3. Prehypertensive = 90th centile to 120 mmHg Stage 1 hypertension = 95 th centile upwards Stage 2 hypertension = 99 th centile + 5 mmHg
  5. 5. Any reading equal to or above the readings in the simplified table indicates potentially abnormal blood pressures in one of three ranges: prehypertension; stage 1 hypertension; or stage 2 hypertension and identifies blood pressures that requires additional evaluation
  6. 6. • Childhood obesity, can be identified by high triglyceride (TG) levels, hyperinsulinemia, high C-reactive protein* (CRP) level, and a family history of hypertension or diabetes as determinants of adult metabolic syndrome. _________________________________________ • *Possible mechanisms by which CRP could provide protection from SLE. Clearance pathway: CRP binds to nuclear remnants, such as apoptotic cells, snRNPs or altered chromatin, and then binds to FcγR on macrophages. • It activates complement, resulting in the binding of C1q and C3 split products to CRs. • This leads to improved opsonization of potential autoantigens and the secretion of anti-inflammatory cytokines, such as IL-10 and TGFß.
  7. 7. Regulatory pathway: CRP binds to activating FcγR on macrophages, inducing the production of inflammatory cytokines and anti-inflammatory cytokines, such as IL-10 and TGF-ß. These macrophages develop a suppressive phenotype, producing more IL10 and TGF-ß, which downregulate Th1 cells and inflammatory macrophages found in SLE and may lead to Treg cells that provide long-term suppression in SLE. CR: Complement receptor; CRP: C-reactive protein; FcγR: Fcγ receptor; snRNP: Small nuclear ribonucleoprotein particle; SLE: Systemic lupus erythematosus.
  8. 8. • Regulatory pathway: CRP binds to activating FcγR on macrophages, inducing the production of inflammatory cytokines and antiinflammatory cytokines, such as IL-10 and TGFß. • These macrophages develop a suppressive phenotype, producing more IL-10 and TGF-ß, which downregulate Th1 cells and inflammatory macrophages found in SLE and may lead to Treg cells that provide long-term suppression in SLE. CR: Complement receptor; CRP: C-reactive protein; FcγR: Fcγ receptor; snRNP: Small nuclear ribonucleoprotein particle; SLE: Systemic lupus erythematosus
  9. 9. • During childhood, the adults with metabolic syndrome had significantly higher systolic blood pressure (SBP) than that of normal adults at that age. • Researchers from Japan showed that elevated SBP in obese children is associated with hyperinsulinemia and visceral fat accumulation regardless of family history of hypertension.
  10. 10. • The cause of hypertension in Metabolic Syndrome is multifactorial and likely includes all the elements of the syndrome, including obesity, insulin resistance, and dyslipidemia. • Obesity may be the most important factor, however, the other elements of the syndrome also play a role in creating and mediating the changes that ultimately result in hypertension
  11. 11. • However, the potential of SBP in male adolescents to predict the incidence of metabolic syndrome later in life remains unknown. • Therefore SBP in male adolescents is an independent predictor for metabolic syndrome in male adolescents and could be included in routine metabolic risk assessment.
  12. 12. • Taller children have slightly higher average BPs. Centile values shown are for 50th height centile: average BPs vary by ± 3-5mmHg for 5th 95th height centiles (so range typically varies 6-10mmHg for height at any age).
  13. 13. Proposals of Definition of Metabolic Syndromein Children and Adolescents • The first proposal of definition was published in 2003. • It was elaborated by assessing adolescents from 12 to 19 years old using modified criteria, based on the criteria of NCEP/ATP-III, including abdominal circumference over percentile 90, blood pressure over the limits established by the National Blood Pressure Education Program, lipids over the limits established by the National Cholesterol • Education Program for children, and glycemia over the • values for adults. • The general prevalence found in this population of 1219 years old patients was 4.2%, and when only obese patients over the percentile 95 were considered, the prevalence was 28.7% .
  14. 14. • The second proposal of definition is very similar to the previous one, but the cut offs were inferior regarding abdominal circumference and lipid profile. • Thus, prevalence is higher (when considering patients with BMI percentile adjusted over the percentile 85.
  15. 15. • The third proposal chose BMI to serve as a base, justifying that it would be less dependent on ethnical variations – It should be aware that abdominal circumference may vary according to the race. • The prevalence in moderately obese patients (considering those who had Z of 2 and 2.5) and in severe obese patients (with Z over 2.5 of pattern deviations (Table 1).
  16. 16. • The most appropriate definition that include SBD that is the proposed by the IDF. • It divided children into age groups. • There was not a well defined proposal for children under • 6 years of age, due to the lack of data. • Differently from the criteria presented above, in this proposal, for a matter of convenience, the cut-offs were fixed for pressure, lipids and glycaemia, and abdominal circumference points were assessed by percentile.
  17. 17. • In children aged 6-10, the cut-offs of metabolic and blood pressure variables were not well defined, assessing simply adiposity (considering abdominal circumference over the 90 percentile). • The same criteria would be used for children aged 10-16; regarding glycemic metabolism, 1. Fasting glycaemia ≥100 mg/ dL, 2. Triglycerides ≥150 mg/ dL, 3. HDL cholesterol below 40 mg/ dL or using a hypolipemiant drug, and blood pressure limits ≥130 or ≥85 mmHg or using a antihypertensive drug.
  18. 18. • If the patient had altered abdominal circumference and two more factors, the metabolic syndrome diagnosis would be • established. • The difference is that, for adolescents over 16 • years of age, there is a differentiation between HDL ≤40 for men and ≤50 for women (Table 2) • Thus, discussions and doubts exist about which criterion to use. • Evidently, the IDF criterion, though more convenient, could fail to include some children in the diagnosis of Metabolic Syndrome. • On the other hand, it would be of easier acceptance as it does not use multiple tables to assess several anthropometric and metabolic criteria.
  19. 19. Blood Pressure Levels for the 50th, 90th, 95th and 99th Percentiles of Systolic and Diastolic Blood Pressure by Percentiles of Height in Boys and Girls of Age 3 to 18 years
  20. 20. The Relation between blood pressure and Metabolic syndrome • Several epidemiologic studies have shown that obesity represents an independent risk factor for the development of cardiovascular diseases, including hypertension, myocardial ischemic disease, and cardiac arrhythmias. One of the most appealing concepts in obesityrelated hypertension is that a specific etiology can be identified. There is now substantial evidence that human obesity is characterized by abnormalities in sympathetic cardiovascular control.
  21. 21. • The application of sensitive techniques to assess sympathetic nervous system (SNS) activity in humans, including catecholamine levels, norepinephrine (NE) spill over techniques, and microneurography have furthered this concept. • Catecholamine levels in obesity have been conflicting, with high, normal, and low levels reported. • However, studies examining weight loss have found that the fall in blood pressure (BP) was highly correlated with reductions in plasma NE.
  22. 22. • Examination of NE spill over in obesity has shown regional over activity in the kidneys. • High renal SNS activity could lead to sodium retention and abnormal glomerular hemodynamic that could raise BP. • Microneurography, which determines muscle sympathetic outflow, has shown consistent elevation in obesity, but no difference between normotensive and hypertensive obesity.
  23. 23. • However, the hyperinsulinemia of obesity may act in concert with the SNS to elevate BP, as the combination of the two seems to produce vascular constriction. • Leptin also has several cardiovascular actions that may contribute to BP regulation. • Epidemiologic studies also found that SNS activity predicts hypertension in obese subjects
  24. 24. • The Insulin Resistance Atherosclerosis Study, a large prospective study, set out to determine the association between insulin sensitivity and risk factors for cardiovascular disease. • There is an 11% lower risk of developing incident hypertension with every one unit greater of insulin sensitivity measured by the frequently sampled intravenous glucose tolerance test (FSIGT). • The association between in insulin resistance and hypertension relates to several different mechanisms.
  25. 25. • Insulin is a vasodilator when given IV to persons of normal weight and also increases renal sodium reabsorption . • The cellular mechanisms of vascular smooth muscle contraction may be altered in insulin resistance. • Normally, insulin has been shown to reduce intracellular calcium ions by inhibiting the voltage operated channel and by activating Ca ATPase resulting in the efflux of Ca ions from the cell, thus decreasing cytosolic Ca ions and decreasing vascular resistance. • In the environment of insulin resistance, this vasodilatory effect is lost whereas the sodium reabsorption is preserved.
  26. 26. • In addition, angiotensinogen, angiotensin converting enzyme and angiotensin type 1 receptors are present within human adipose tissue. Studies suggest that the regulation of the adipose renin-angiotensin system is correlated with the degree of obesity and that angiotensin II may modulate adipose tissue blood flow, growth and metabolism. Thus, an up regulated adipose reninangiotensin system may contribute to insulin resistance and hypertension in obese individuals (Prasad & Quyyumi, 2004, p.1509).
  27. 27. • In addition, angiotensinogen, angiotensin converting enzyme and angiotensin type 1 receptors are present within human adipose tissue. • Studies suggest that the regulation of the adipose renin-angiotensin system is correlated with the degree of obesity and that angiotensin II may modulate adipose tissue blood flow, growth and metabolism. • Thus, an up regulated adipose reninangiotensin system may contribute to insulin resistance and hypertension in obese individuals.
  28. 28. • Several studies suggest that angiotensin II may modulate the actions of insulin. • Insulin and the renin-angiotensin system share the P13 kinase and MAP kinase signaling pathways and tyrosine phosphorylation of the insulin receptor substrate 1 (IRS1) and substrate 2 (IRS2). • Insulin receptor mediated activation of IRS1 and IRS2 activates the P13 kinase pathways where the angiotensin II mediated activation inhibits the P13 kinase pathway.
  29. 29. • When activated, the renin-angiotensin system may inhibit the metabolic actions of insulin but promote the mitogenic actions of the MAP kinase pathway. • Further, both hyperglycemia and insulin activate the renin-angiotensin system by increasing the expression of angiotensinogen, angiotensin II and the angiotensin I receptor which may contribute to the development of hypertension in patients with insulin resistance.
  30. 30. • There is also evidence that insulin resistance and hyperinsulinemia lead to SNS activation, which may contribute to the pathogenesis of hypertension. • As a result of sympathetic activation, the kidneys increase sodium reabsorption, the heart increases cardiac output, and the arteries respond with vasoconstriction resulting in hypertension
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