Metabolic Syndrome

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Metabolic Syndrome

• Laura Welch, Pharm.D.
• Associate Professor, Department of Pharmacy
  Practice
• University of Charleston School of Pharmacy

laurawelch_at_ucwv.edu
www.pharmacy.ucwv.edu
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The Economist, December 2003
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Metabolic Syndrome

• Metabolic syndrome is characterized by insulin
  resistance, visceral distribution of body fat,
  dyslipidemia, hypertension, and a prothrombotic
  state. In particular, it's characterized by the
  lipid triad of elevated triglycerides, low
  high-density lipoprotein (HDL), and small, dense
  low-density lipoprotein (LDL) particles. And the
  management focuses on therapeutic lifestyle
  changes, and also LDL reduction and overall
  optimization of the lipid profile.

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Metabolic Syndrome

• Synonyms
• Insulin resistance syndrome
• (Metabolic) Syndrome X
• Dysmetabolic syndrome
• Multiple metabolic syndrome

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Metabolic Syndrome Operational Definition

• Supposed to be useful for healthcare providers
• Many definitions
• WHO (1998/1999)
• NCEP (2001)
• AACE (2002)
• IDF (2005)
• AHA/NHLBI (2005)

Slide Source Lipids Online Slide
Library www.lipidsonline.org
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Metabolic syndrome The NCEP ATP III definition
2001, updated 2005
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Metabolic syndromeKey underlying defects

• It is suggested that insulin resistance and
  central obesity are the key underlying defects in
  the aetiology of type 2 diabetes.
• A universal definition of metabolic syndrome is
  urgently needed to identify individuals at high
  risk of developing diabetes and cardiovascular
  disease.

Dyslipidaemia
Impaired glucose regulation
Hypertension
Obesity
Insulin resistance
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Metabolic syndrome Prevalence in the US as
defined by NCEP ATP III
(N8814)
Ford. JAMA 2002
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The Metabolic Syndrome

• Constellation of major risk factors, life-habit
  risk factors, and emerging risk factors
• Over-represented among populations with CHD
• Clue is distinctive body type with increased
  abdominal circumference (although some leaner
  men and women with abdominal obesity without
  increased waist)

Slide SourceLipids Online Slide Library
www.lipidsonline.org
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Metabolic Syndrome

• Abdominal obesity
• Hyperinsulinemia
• High fasting plasma glucose
• Impaired glucose tolerance
• Hypertriglyceridemia
• Low HDL-cholesterol
• Hypertension

Slide Source Obesityonline.org
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Insulin resistance
Insulin resistance A state in which a given
level of insulin produces a less than expected
biological effect.
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Insulin resistance

• Insulin resistance is an underlying feature of
  both the metabolic syndrome and type 2 diabetes.
• It is associated with abnormalities in both
  glucose and lipid metabolism.
• These abnormalities are associated with an
  increased risk of cardiovascular disease and are
  often present before the onset of type 2 diabetes.

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Screening for undiagnosed diabetes

• Half or more of type 2 diabetes is undiagnosed.
• Opportunistic screening during a healthcare visit
  for other reasons can identify undiagnosed
  diabetes, particularly in individuals at high
  risk.
• Up to half of those afflicted already have signs
  of complications at diagnosis.
• Strong scientific evidence relating good
  metabolic control to the prevention or delay of
  these complications is now available.

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Characteristics of the Metabolic Syndrome
NCEP-ATP III
Abdominal obesity Glucose intolerance/ Insulin
resistance Hypertension Atherogenic
dyslipidemia Proinflammatory/ Prothrombotic state
Diabetes
CVD
Slide Source Obesityonline.org
National Cholesterol Educational Program (NCEP),
Adult Treatment Panel (ATP) III 2001.
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Metabolic Syndrome Increases Risk for CHD and
Type 2 Diabetes
HighLDL-C
MetabolicSyndrome
Type 2Diabetes
Coronary Heart Disease
Slide Source Lipids Online Slide
Library www.lipidsonline.org
Expert Panel on Detection, Evaluation, and
Treatment of High Blood Cholesterol in Adults.
JAMA 20012852486-2497.
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Metabolic Syndrome Impact on Mortality

Without metabolic syndrome With metabolic syndrome

Mortality Rate ()
P lt 0.001.
Isomaa B et al. Diabetes Care. 200124683-689.
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The clinical consequences of diabetes and
cardiovascular disease

• People with type 2 diabetes have the same risk of
  heart attack as people without diabetes who have
  already had a heart attack.
• Women with diabetes are subject to sudden death
  300 more often and men with diabetes 50 more
  often than their counterparts without diabetes of
  the same age.
• Strokes occur twice as often in people with
  diabetes and hypertension as in those with
  hypertension alone.
• A person with diabetes has a two to three-fold
  greater risk of heart failure compared to a
  person without diabetes.

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Metabolic Syndrome Impact on Cardiovascular
Health

Without metabolic syndrome With metabolic syndrome
Prevalence ()
P lt 0.001.


Isomaa B et al. Diabetes Care. 200124683-689.
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New Features of ATP III

• CHD Risk Equivalents
• 1. Type 2 Diabetes Mellitus
• 2. Non-Cardiac Forms of Atherosclerosis
• 3. Framingham Projection of 10 yr.
• If Risk gt20 (identifies individuals with
  multiple risk factors in need of more aggressive
  lipid lowering)

CHD Coronary Heart Disease
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Targets for common cardiovascular risk factors
in people with diabetes
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Potential Problems with the Metabolic Syndrome
Term

• Loss of data using dichotomous variables
• Do the cutpoints developed in the United States
  apply to countries with different lifestyles?
• Low BMI in Asia and low HDL-C in countries with
  high-carbohydrate diets
• Components of the metabolic syndrome differ in
  their ability to predict diabetes and CVD
• Does the metabolic syndrome predict CVD
  independently of its components?
• Does the metabolic syndrome have a single
  etiology (is a single etiology necessary for
  syndrome?)

Slide Source Lipids Online Slide
Library www.lipidsonline.org
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Potential Advantages of the Metabolic Syndrome
Terminology

• Metabolic syndrome is an operational definition
  for "cardiometabolic" risk
• "Nobody" measures global risk or uses
  multivariate predicting equations (metabolic
  syndrome is easier)
• Encourages providers to look for other risk
  factors
• Encourages behavioral therapy rather than just
  treating risk factors individually
• Metabolic syndrome better predictor of diabetes
  than CVD

Slide Source Lipids Online Slide
Library www.lipidsonline.org
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Obesity and Metabolic SyndromeA Cluster of
Coronary Heart Disease Risk Factors
Obesity
DietPhysical InactivityStress
RaisedBlood Pressure
GeneticSusceptibility
AutonomicDysfunction
ProthromboticState
ProinflammatoryState
InsulinResistance
AtherogenicDyslipidemia
?High-Density Lipoprotein Cholesterol
?Triglycerides
?Small Low-Density Lipoprotein Particles
Slide Source Obesityonline.org
Adapted from Grundy SM. J Clin Endocrinol Metab.
2005892595-2600.
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Medical Consequences of Obesity
Pulmonary disease abnormal function obstructive
sleep apnea hypoventilation syndrome
Idiopathic intracranial hypertension
Stroke
Cataracts
Nonalcoholic fatty liver disease steatosis steatoh
epatitis cirrhosis
Coronary heart disease Diabetes
Dyslipidemia Hypertension
Gall bladder disease
Cancer breast, uterus, cervix colon, esophagus,
pancreas kidney, prostate
Gynecologic abnormalities abnormal
menses infertility polycystic ovarian syndrome
Osteoarthritis
Phlebitis venous stasis
Skin
Slide Source Obesityonline.org
Gout
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Obesity Trends Among U.S. AdultsBRFSS, 1990,
1995, 2005
(BMI ?30, or about 30 lbs overweight for 54
person)
1995
1990
WV 10-14
2005
WV 15-19
WV gt30
No Data lt10 1014
1519 2024 2529
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Source BRFSS, CDC
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Obesity in West Virginia

• 64 of West Virginians do not maintain a healthy
  weight and one in four West Virginians is obese.
  (There is a strong correlation (67) between an
  unhealthy weight and diabetes, high blood
  pressure, hypertension, heart disease, asthma
  and/or cancer). (Source Bureau for Public
  Health, Obesity in West Virginia)

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Obesity West Virginia

• BRFSS
• Behavioral Risk Factor Surveillance System
• 1990-94 State average 16.9
• 1995-99 State average 21.3
• gt 25 Wyoming, Logan, McDowell

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BMI
Slide Source Obesityonline.org
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Obesity

• BMI gt 30 kg/m2
• Definitions
• Obesity having a very high amount of body fat in
  relation to lean body mass, or Body Mass Index
  (BMI) of 30 or higher.
• Body Mass Index (BMI) a measure of an adults
  weight in relation to his or her height,
  specifically the adults weight in kilograms
  divided by the square of his or her height in
  meters.

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Measuring obesity WHO classification of adult
categories of BMI
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Measuring obesity up to hereThe limitations of
the Body Mass Index

• BMI DOES NOT
• show the difference between excess fat and
  muscle.
• identify whether the fat is laid down in
  particular sites. For example, abdominal fat has
  more serious health consequences than fat located
  elsewhere.
• The relation between fatness and BMI differs with
  age, race and gender.

.
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Obesity

• Additional risks
• Large waist circumference (mengt40 in women gt35
  in)
• 5 kg or more weight gain since age 18-20 y
• Poor aerobic fitness
• Specific races and ethnic groups
• Clinical Guidelines on the Identification,
  Evaluation, and Treatment of Overweight and
  Obesity in AdultsThe Evidence Report. Obes Res
  19986(suppl 2).

Slide Source Obesityonline.org
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Obesity

• Source of the data
• The data shown in these maps were collected
  through CDCs Behavioral Risk Factor Surveillance
  System (BRFSS). Each year, state health
  departments use standard procedures to collect
  data through a series of monthly telephone
  interviews with U.S. adults.
• Prevalence estimates generated for the maps may
  vary slightly from those generated for the states
  by BRFSS (http//aps.nccd.cdc.gov/brfss) as
  slightly different analytic methods are used.

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Managing obesity

• Obesity is the main modifiable risk factor for
  type 2 diabetes.
• Small amounts of weight loss (510) can prevent
  or delay the development of type 2 diabetes in
  individuals with a high risk of the disease.
• Even a 5 weight reduction in those who are
  overweight or obese improves the risk of
  complications such as heart disease.

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Clinical Management of Metabolic Syndrome

• Goals
• Prevention of Type 2 Diabetes
• Prevention of Cardiovascular events
• Methods
• Therapeutic Lifestyle Changes
• Pharmacologic Therapy

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Approaches to Treating Metabolic Syndrome

• Medication to achieve lipid and cholesterol value
  goals
• Medication to achieve blood pressure goals
• Medication to achieve blood glucose goals
• Medication to minimize prothrombotic state

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Clinical Management of Metabolic Syndrome

• Management of underlying causes
• Weight control enhances LDL lowering and
  reduces all risk factors
• Physical activity reduces VLDL and LDL and
  increases HDL
• Treat lipid and nonlipid risk factors
• Hypertension
• Aspirin in CHD patients
• Elevated triglycerides
• Low HDL

Expert Panel on Detection, Evaluation, and
Treatment of High Blood Cholesterol in Adults.
JAMA 20012852486-2497.
Slide Source Lipids Online Slide
Library www.lipidsonline.org
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Approaches to Treating Metabolic Syndrome

• Therapeutic Lifestyle Changes
• Dietary restriction of calories, simple
  carbohydrates, saturated fats
• Regular aerobic exercise
• Weight control
• To reduce underlying causes
• Overweight and obesity
• Physical inactivity
• To treat associated lipid and non-lipid risk
  factors
• Hypertension
• Prothrombotic state (Aspirin)
• Atherogenic dyslipidemia (lipid triad)

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Treatment Goals for Metabolic Syndrome

• Correct atherogenic dyslipidemia
• While a primary target of therapy, LDL-C
  reduction alone does not result in full benefit
• Correct hypertension
• Administer aspirin for the prothrombotic state
• Correct insulin resistance
• Weight reduction
• Increased physical activity
• Drugs that decrease insulin resistance have not
  been proven to reduce CAD risk
• Control type 2 DM, if present

National Cholesterol Education Program Adult
Treatment Panel III. Circulation.
20021063143-3421.
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Summary of Metabolic Syndrome

• The metabolic syndrome predicts the development
  of both diabetes and CHD
• Insulin resistance and obesity characterize most
  individuals with the metabolic syndrome, although
  insulin resistance and obesity are not required
  features of the NCEP metabolic syndrome
• Initial therapy for the metabolic syndrome should
  consist of caloric restriction and increased
  physical activity
• Conventional cardiovascular risk factors such as
  lipids and blood pressure should be treated in
  individuals with the metabolic syndrome, although
  no national recommendations have so far suggested
  intensification of risk factor management
• No consensus exists on whether insulin
  sensitizers should be used in nondiabetic
  individuals with the metabolic syndrome

Slide Source Lipids Online Slide
Library www.lipidsonline.org
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Intensity of Therapy Should be Proportionate to
Level of Risk

• What is the impact of the metabolic syndrome on
  health outcomes?
• Cardiovascular disease
• Type 2 diabetes

Slide Source Lipids Online Slide
Library www.lipidsonline.org
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National Focus

• American Diabetes Association
• Cardiometabolic Risk Initiative
• www.diabetes.org, then Health Professionals
  Scientists, then Resources for Professionals

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Pharmacist Impact

• Medication Compliance
• Patient Education and Understanding
• Chronic Disease Management programs for high-risk
  metabolic syndrome patients
• Hyperlipidemia management
• Obesity clinic
• Blood Pressure management
• Diabetes management program

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Wheres the Evidence?

• AHA 47th Annual Conference on Cardiovascular
  Disease Epidemiology and Prevention, 2007
• 112 high risk adults were screened and monitored
  for 4 months.
• No medication intervention, only education and
  awareness.
• 30 originally met the criteria for metabolic
  syndrome
• At 4 months, only 18 continued to meet the
  criteria
• Improvement seen in total cholesterol, blood
  pressure.

TS Warmack, DS West. UAMS COP, 2006
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Wheres the Evidence?

• Nationally, pharmacist manage chronic disease
  clinics independently or University or Hospital
  affiliated
• Collaborative Practice agreements are critical.
• Pharmacists receive payment for these services
• Self pay
• Commercial insurance
• CMS

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Pharmacists need to

• Learn about the trends and the science of
  treating metabolic syndrome
• Understand the treatment guidelines for diabetes,
  lipids, hypertension and obesity.
• Advocate for pharmacy Collaborative Practice
  within your local district and with your local
  legislators
• Identify opportunities to help payers alleviate
  or redistribute health care costs.
• Network with other pharmacists to outline key
  elements of successful pharmacy practice models.
• Network with other pharmacists to market and
  implement pharmacist metabolic syndrome
  management services

For additional information, www.aphafoundation.or
g
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