Presentation on theme: "بسم الله الرحمن الرحيم. Metabolic syndrome, where have we been and where are we going? By Amr Abdelmonem,MD. Assistant professor of anesthesia,surgical."— Presentation transcript:
Metabolic syndrome, where have we been and where are we going? By Amr Abdelmonem,MD. Assistant professor of anesthesia,surgical intensive care and clinical nutrition in faculty of medicine, Cairo university Member of North American Association For The Study Of Obesity Member of the American society of regional anesthesia and pain medicine
The perfect survivor must be able to eat and store as many calories as possible when food is readily available as a buffer against periods of scarcity. He must also reduce energy expenditure when food is scarce and efficiently and accurately restore lost adipose stores when food is again available.
Question 1: What Are the Signals from the Periphery and How Are They Sensed and Integrated Within Systems that Regulate Energy Homeostasis? Levin, BE. (2004) The drive to regain is mainly in the brain Am J Physiol Regul Integr Comp Physiol. 287,R1297-R1300 Woods, SC, Seeley, RJ. (2002) Understanding the physiology of obesity: review of recent developments in obesity research Int J Obes Relat Metab Disord. 26(Suppl 4),S8-S10 Horvath, TL, Diano, S. (2004) The floating blueprint of hypothalamic feeding circuits Nat Rev Neurosci. 5,662-667
Question 3: Why Do Some Individuals Eat Beyond Their Metabolic Needs? Levin, BE, Keesey, RE. (1998) Defense of differing body weight set-points in diet- induced obese and resistant rats Am J Physiol. 274,R412-R419 Clegg, DJ, Benoit, SC, Reed, JA, Woods, SC, Levin, BE. (2005) Reduced anorexic effects of insulin in obesity-prone rats and rats fed a moderate fat diet Am J Physiol Regul Integr Comp Physiol. 288,R981-R986 Levin, BE, Dunn-Meynell, AA. (2002) Reduced central leptin sensitivity in rats with diet-induced obesity Am J Physiol Regul Integr Physiol. 283,R941-R948 Levin, BE, Dunn-Meynell, AA, Banks, WA. (2004) Obesity-prone rats have normal blood-brain barrier transport but defective central leptin signaling prior to obesity onset Am J Physiol Regul Integr Physiol. 286,R143-R150
Rationale Barry E. Levin. (2006) Central Regulation of Energy Homeostasis Intelligent Design: How to Build the Perfect Survivor Obes Res. 14:192S-196S
Inborn elevation in the threshold of the metabolic neurones located in the brain for detecting or responding to the inhibitory signals from the GIT,pancreas or adipose tissue These are present before they become obese Diet-induced obese is genetically programmed so that they can increase the adipose stores far above the metabolic needs when energy dense foods are abundant
What happens when we eat? When we eat,our bodies break down the food into its basic components ( protein- carbohydrates- fat), and absorbs them into blood stream rise in blood sugar pancreas will release insulin moves sugar into cells either burned for energy or stored away as fat in fat cells or glycogen in liver and muscles
In genetically programmed susceptible patients Hyperinsulinemia and hyperliptinemia
Lets walk through the fat metabolism pathway and follow the flow of fat molecules: Fat travels in the form of triglycerides at cells ezymatic breakdowen fatty acids enter the cells mitochondria breakdowen fat in order to enter mitochondria,fats need carnitine insulin inhibits Fat- carnitine shuttle system fats move back into blood Insulin stimulates lipoprotein lipase that transports fatty acid into fat cells Insulin inhibits hormone sensitive lipase that releases the fat from fat cells into the blood
The Early Event is Increased intracellular triglycerides Shulman, GI. (2000) Cellular mechanisms of insulin resistance J Clin Invest. 106,171-176 Boden, G, Shulman, GI. (2002) Free fatty acids in obesity and type 2 diabetes: defining their role in the development of insulin resistance and beta-cell dysfunction Eur J Clin Invest. 32(Suppl 3),14-23 Increased adipose tissue
Is the adipose tissue an endocrine organ ? The answer is
Defect in adenosine monophosphate –activated protein kinase Ruderman, N, Prentki, M. (2004) AMP kinase and malonyl-CoA: targets for therapy of the metabolic syndrome. Nat Rev Drug Discov. 3,340-351 No phosphorylation of the insulin receptors No intracellular signaling No translocation of glucose Insulin resistance
Increased Hepatic gluconeogesis DeFronzo, RA, Bonadonna, RC, Ferrannini, E. (1992) Pathogenesis of NIDDM: a balanced overview Diabetes Care 15,318-368 Reduced glucose uptake by muscles Boden, G, Chen, X, Ruiz, J, White, JV, Rossetti, L. (1994) Mechanisms of fatty acid-induced inhibition of glucose uptake J Clin Invest. 93,2438-2446 Arner, P. (2002) Insulin resistance in type 2 diabetes: role of fatty acids Diabetes Metab Res Rev. 18(Suppl 2),S5-S9 [Santomauro, AT, Boden, G, Silva, ME, et al (1999) Overnight lowering of free fatty acids with Acipimox improves insulin resistance and glucose tolerance in obese diabetic and nondiabetic subjects Diabetes 48,1836-1841 Peterson FK,Shulman IG. new insights into the pathogenesis of insulin resistance in humans using magnetic resonance spectroscopy.Obes Res 2006;14s:34s Hyperinsulinemia and insulin resistance
Role of free fatty acid Beta cells Insulin Reduction of FFA Persistent drive IR 11 β-hydroxysteroid dehydrogenase 1 Cortisol Cytokines 1.Inhibition of insulin receptors 2.Suppression of secretion of adiponectin
It is now clear that an individual could be insulin-resistant from one of two main reasons 1. Could acquire the resistance by becoming obese
2. Or insulin resistant lean individuals The concept of insulin resistance as underlying a cluster of risk factors or end points of disease originated with Dr. Gerald Reaven in 1988. Insulin resistance syndrome, or syndrome X, as he called it, was originally described in lean individuals Reaven, GM. (1988) Banting lecture 1988: role of insulin resistance in human disease Diabetes 37,1595-1607
The insulin resistant obese are candidates for development of The metabolic syndrome
The World Health Organization defined a version of the metabolic factors in 1998. In 2001, the National Cholesterol Education Program Adult Treatment Panel III guidelines defined a cluster of metabolic factors that increase the risk for atherosclerotic cardiovascular disease (ASCVD). They called this cluster the "metabolic syndrome" and defined afflicted individuals by the presence of three of the following five characteristics
ATP III Guidelines WHO Guidelines Abdominal Obesity Waist Circumference Waist/Hip Ratio Men > 40 inches (102 CM) >0.90 Women > 35 inches (88 CM) >0.85 Triglycerides 150 mg/dL 150 mg/dL HDL-Cholesterol Men < 40 mg/dL <35 mg/dL Women < 50 mg/dL <39 mg/dL Blood Pressure 130/ 85 mm Hg >140/>90 mm Hg Fasting Glucose 110 mg/dL 110 mg/dL
IDF NCEP International Diabetes Federation National Cholesterol Education Program Central Obesity Waist Circumference Men 90 CM Women 80 CM Triglycerides 150 mg/dL HDL-Cholesterol Men < 40 mg/dL Women < 50 mg/dL Blood Pressure 130/ 85 mm Hg Fasting Glucose 100mg/dL
Obesity Research (2007) 15, 1096–1100; Probable Blind Spot in the International Diabetes Federation Definition of Metabolic Syndrome Hsin-Jen Chen and Wen-Harn Pan The prevalence of IDF-MS was lower than NCEP-MS, and IDF-MS failed to identify individuals with smaller waists but similar cardiovascular risk profiles to those defined by NCEP
On the other hand, several studies have reported a higher prevalence of IDF-MS than the original NCEP-MS in European-, Mexican-, and African- American people Adams, R. J., Appleton, S., Wilson, D. H., et al (2005) Population comparison of two clinical approaches to the metabolic syndrome: implications of the new International Diabetes Federation consensus definition. Diabetes Care 28: 2777–2779. Athyros, V. G., Ganotakis, E. S., Elisaf, M., Mikhailidis, DP. (2005) The prevalence of the metabolic syndrome using the National Cholesterol Educational Program and International Diabetes Federation definitions. Curr Med Res Opin. 21: 1157– 1159. Ford, ES. (2005) Prevalence of the metabolic syndrome defined by the International Diabetes Federation among adults in the U.S. Diabetes Care 28: 2745–2749.
Meals are the biological units of eating behavior in humans,and the gut – brain axis is a critical neural network in the control of energy intake and meal size Survival of species is dependant on the development of systems that drive the individual to seek and ingest food and to conserve energy stores during times of low food availability This is an excellent survival strategy when food is only intermittently available but would promote the development of obesity in such individuals in our modern human society Understanding the neurobiological and pathophysiological natures of the MS will enable physicians and scientists to approach the phenotypic problems ( hypertension, diabetes, dyslipidemia,obesity ) in a more rational and mechanism – based manner.