The Metabolic Syndrome By Alicia Rodriguez
The Metabolic Syndrome • Formerly called Syndrome X • Associated with abdominal obesity • Clustering of a group of risk factors for chronic diseases – CVD Glucose Intolerance – CKD – Type 2 DM Hyperinsulinemia
Insulin Resistance
High TG Low HDL-C
Hypertension
Features of the Metabolic Syndrome • • • • • • • •
Central adiposity ↑ plasma triglycerides ↓ HDL cholesterol Hyperglycemia Hypertension Smaller LDL-C particles Abnormal clotting Abnormal inflammatory markers
Criteria for Clinical Diagnosis • A syndrome is a set of symptoms rather than a disease • Developed by NCEP ATP III • Clinical diagnosis based on any 3 of the 5 symptoms associated with metabolic syndrome
Pathophysiology • Central adiposity is related to high amounts of fat in visceral compartments • Visceral fat sites are composed of large insulin resistant adipocytes • Present in adipocytes is the hormone adiponectin which: – Stimulates glucose uptake and fatty acid oxidation in muscle – Increases insulin sensitivity in liver – Reduces monocyte adhesion and formation of foam cells
• As visceral fat increases, the presence of this hormone decreases leading to: – Increased insulin resistance – Formation of plaque in the wall of blood vessels
Pathophysiology • Increased size of fat cells: – Raises levels of circulating free fatty acids – Increases levels of circulating cytokines • Increased lipolysis leads to: – Increased synthesis of LDL-C and VLDL-C in the liver – Increased levels of triglycerides and cholesterol in blood plasma
Schematic representation of how components of the metabolic syndrome relate to fat accumulation in the liver
Kotronen, A. et al. Arterioscler Thromb Vasc Biol 2008;28:27-38 Copyright Š2008 American Heart Association
NAFL and MetS predicts type 2 diabetes, advanced forms of liver, and cardiovascular disease
Kotronen, A. et al. Arterioscler Thromb Vasc Biol 2008;28:27-38 Copyright Š2008 American Heart Association
Populations at Risk • Males and post menopausal women • Some ethnic groups – – – –
Mexican Americans Caucasians African Americans South Asians
• Additional risk factors – – – – – –
Sedentary lifestyle Abdominal obesity Family history of diabetes or heart disease Personal history of diabetes or heart disease Polycystic ovarian syndrome Non-alcoholic fatty liver disease
Prevalence of the NCEP Metabolic Syndrome: NHANES III by Age 50%
Prevalence, %
40% 30%
44% 44%
Men Women 24% 23%
20%
10%
8%
6%
0% 20–70+ 20–29 30–39 40–49 50–59 60–69
Age, years Ford ES et al. JAMA 2002. Used with permission of the American Medical Association.
70
Prevalence of the NCEP Metabolic Syndrome: NHANES III by Sex and Race/Ethnicity
Prevalence, %
40%
White African American Mexican American Other
36%
28%
30%
26%
25% 21%
20%
23% 20%
16%
10%
0%
Men
Women
Ford ES et al. JAMA 2002. Used with permission of the American Medical Association.
Treatment of the Metabolic Syndrome • All obese individuals, especially those with central adiposity should be identified and treated for weight loss • Strategies include – Lifestyle changes • Weight Loss – Reduction in energy intake – Increase in physical activity
• Other dietary changes – Fish oil and omega 3 fatty acids? – Diacylglycerol (DGA) oil? – Alcohol? – DASH eating plan – Pharmacotherapy – Surgery
The Effect of Fish Oil /N3 Fatty Acids
The Effect of Fish Oil /N3 Fatty Acids
The Effect of Diacylglycerol (DGA) Oil
Treatment of the Metabolic Syndrome The ABCDE approach • Acronym stands for: – – – – –
Assessment Blood pressure Cholesterol Diabetes prevention and diet Exercise
• Multidisciplinary team includes: – – – – –
Physicians Health educators Nurses Registered dietitians Exercise physiologists
Focal Points • The metabolic syndrome increases the risk for diabetes and cardiovascular disease • Most individuals with metabolic syndrome have insulin resistance and obesity • Initial therapy for the metabolic syndrome should consist of weight loss through increased physical activity and calorie restriction • More research needs to be conducted to standardize definition and treatment plan • Recognizing and treating metabolic syndrome in an early stage could save health care dollars