METABOLIC SYNDROME: Lifestyle Strikes Again

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METABOLIC SYNDROME Lifestyle Strikes Again
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What is the Metabolic Syndrome?

• A concurrence of disturbed glucose and insulin
  metabolism, overweight and abdominal fat
  distribution, mild dyslipidemia, and
  hypertension associated with subsequent
  development of T2D and CVD. (Reavan et al.1988
  Stanford University)
• Term for a cluster of metabolic conditions, that,
  when occurring together, may indicate a
  predisposition to diabetes and heart disease.
  (Lakka et al. 2002)

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METABOLIC SYNDROME (MS)

• Nomenclature
• Metabolic Syndrome X
• Insulin Resistance Syndrome
• Dysmetabolic Syndrome
• Deadly Quartet
• Multiple Metabolic Syndrome
• Controversy exists re the true mediator of the
  syndrome (what is the main culprit?)

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METABOLIC SYNDROME (MS)Overview of Presentation

• Diagnosis of the MS
• The forgotten factors contributing to the MS
• Proposed causes for the development of the MS
• Exercise and diet in the prevention and control
  of the MS

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Metabolic Syndrome (MS)

• Prevalence
• According to the Mayo Clinic (2005), nearly 50
  million US adults have been diagnosed with the
  metabolic syndrome (one in four US adults)
• Diagnosis
• 3 leading organizations have developed criteria
  for the diagnosis of the MS

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World Health Organization (1999)

• Criteria Diabetes, IFG, IGT, or insulin
  resistance gt 2 of the following risk factors
• Central obesity as measured by waisthip ratio
• Men gt 0.90mg/dL women gt 0.85 mg/dL
• Fasting blood TG gt 150mg/dL
• Blood HDL cholesterol
• Men lt 35mg/dL women lt 39 mg/dL
• BP gt 160/90
• Microalbuminuria
• Kidney disorder resulting in abnormally high
  amounts of protein the urine
• urinary albumin excretion rate gt 20 ug/min
• Relationship with abnormal glycemic control CVD

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National Cholesterol Education Program ATP III
(2001)

• Criteria gt 3 of the following risk factors
• Central obesity as measured by waist
  circumference
• Men gt 102 cm women gt 88 cm
• Fasting blood TG gt 150mg/dL
• Blood HDL cholesterol
• Men lt 40mg/dL women lt 50 mg/dL
• BP gt 130/85
• Fasting glucose gt 110 mg/dL / high insulin levels

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International Diabetes Federation (2005)

• Criteria Central Obesity (men gt94cm women
  gt80cm) any 2 of the following risk factors
• Increased TG concentrations (gt150 mg/dL)
• Reduced HDL cholesterol levels
• Men lt 40mg/dL women lt 50 mg/dL
• BP gt 130/85
• Increased fasting glucose (gt100mg/dl)
• Previously diagnosed T2D

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Additional metabolic research criteria
contributing to MS

• Lack of physical activity / poor fitness
• Smoking
• Western diet high in saturated fat simple
  carbohydrates
• Atherogenic dyslipidemia (i.e., increased LDL and
  cholesterol)
• Prothrombic state
• High Plasminogen Activator Inhibitor (PAI-1)
  assoc with clot formation

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Additional metabolic research criteria
contributing to MS

• Proinflammatory state markers of inflammation
• Elevated C-reactive protein (CRP)
• Elevated Cytokines
• Interleukin-1, 6, 10 (IL-1,IL-6, IL-10) and tumor
  necrosis factor a (TNFa)
• Anti-inflammatory
• Decreased serum Adiponectin
• Endothelial dysfunction
• Linked to pathogenesis of atherosclerosis
• Predicts future cardiovascular events
• Low carbohydrate diet (Brock et al.)

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Proposed schemes for the development of the MS

• Central Obesity (AVF) - Traditional viewpoint
  (Kaplan 1989)
• Insulin resistance and hypertension hypothesis
  (DeFronzo 1991)
• Combination of physical inactivity and high-fat,
  refined sugar diet (Barnard and Wen 1994)
• MUST HAVE GENETIC SUSCEPTIBILITY

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Simplified Web of Causation Applied to CVD and T2D
Deep abdominal adipose tissue Releases FFA into
portal circulation secretes TG-rich
VLDLs Inhibits insulin clearance Hardening of
the arteries
Diet
Stress
Smoking
Physical inactivity
HTN
Dyslipidemia
Heredity
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Genetic Factors
Exercise Diet
Abdominal Obesity
Elevated TGs
T2D
Peripheral Insulin Resistance
Hyperinsulinemia
Altered Blood vessel structure
Increased Na H20 retention
Increased SNS activity
Hypertension
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PHYSICAL INACTIVITY and HIGH-FAT, REFINED SUGAR
DIET
Hyperinsulinemia
Insulin Resistance
T2D Hypertension Hypertriglyceridemia Obesity Smal
l, dense VLDL LDL Reduced HDL Enhanced clotting
Genetic susceptibility
Atherosclerosis
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Linkage between metabolic factors

• What is the hypothesized link between AVF, HTN,
  IGT, and dyslipidemias?
• Visceral fat accumulation is due to
• High levels of steroid hormones (cortisol,
  androgens and progesterone)
• excess FFA output by catecholamines, leading to
  the shut down of glucose metabolism
• AVF and CAD is most likely linked by
  hyperinsulinemia
• Ultimately affects lipid metabolism, increased
  SNS, increased Na retention, increased vascular
  hypertrophy

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How exercise and diet might prevent or control
the MS

• Diets high in fat and/or sucrose leads to insulin
  resistance within a few weeks (Storlien et al.
  1993)
• Intervention studies diet no weight loss
  (Haffner et al. 1998)
• Intervention studies exercise little to no
  weight loss (Tremblay et al. 1999, Bjorntorp et
  al. 2000)
• High complex carb, high fiber diet regular
  exercise attenuates or reverses the MS (Pritikin
  et al. 1998)
• Reductions in BP related to how much insulin
  levels dropped, not by how much fat the subjects
  lost (Krotkiewski et al. 1997)

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How exercise and diet might prevent or control
the MS

• Muscular strength independently and inversely
  associated with MS incidence (Jurca et. al. 2005)
• Studies completed on the Aborigines and Pima
  Indians
• High incidence of insulin resistance some
  aspects of the MS since these societies have
  adopted a Western diet and lifestyle
• Chronic, high levels of stress
• Release of hormones, especially glucocorticoids,
  that antagonize the actions of insulin ? insulin
  resistance
• Effect of exercise intensity of the MS
• Lemarche et al. low intensity exercise results
  in improvements in the MS, and is more easily
  adhered to
• Paffenbarger et al. only vigorous activity
  seemed to impart some sort of protective effect
  (contradictory to previous studies)

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What is the bottom line?

• Lifestyle is the major underlying factor in the
  MS
• Not an obesity epidemic, but rather an
  Epidemic of physical inactivity and poor
  nutrition
• Strategies that address all the factors
• Regular aerobic exercise
• Healthy diet
• Secondary weight loss
• Last resort drug therapy

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