Download Metabolic Syndrome Symposium

Metabolic Syndrome
Symposium
Dar Al-Kalima Health and Wellness
Center
Bethlehem, Palestine
Oct. 2005
Metabolic Syndrome:
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What is it?
Is it important?
How common is it?
What should be done about it?
Metabolic Syndrome Concept Not New:
• 1923 - Kylin first to describe the clustering
of hypertension, hyperglycemia,
hyperuricemia
• 1936 - Himsworth first reported Insulin
insensitivity in diabetics
• 1965 - Yalow and Berson developed insulin
assay and correlated insulin levels &
glucose lowering effects in resistant and
non-resistant individuals
History (cont.)
• 1988 - Reaven in his Banting lecture at the
ADA meeting coined the term Syndrome X
and brought into focus the clustering of
features of Metabolic Syndrome
• Reaven now prefers the name, InsulinResistance Syndrome - feels insulin
resistance is the common denominator for
Metabolic Syndrome
• Literature now extensive
Other Names Used:
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Syndrome X
Cardiometabolic Syndrome
Cardiovascular Dysmetabolic Syndrome
Insulin-Resistance Syndrome
Metabolic Syndrome
Beer Belly Syndrome
Reaven’s Syndrome
etc.
Clustering of Components:
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Hypertension
Hypertriglyceridemia
Low HDL-cholesterol
Obesity (central)
Impaired Glucose Handling
Microalbuninuria (WHO)
Is it a Syndrome?
• The Metabolic Syndrome: Time for a
Critical Appraisal.
– Joint Statement from the American Diabetes
Association and the European Association for
the Study of Diabetes
– Kahn, R, et al. Diabetes Care 2005;28:22892304
Is it a Syndrome?
• “…too much clinically important
information is missing to warrant its
designations as a syndrome.”
• “Until much needed research is completed,
clinicians should evaluate and treat all CVD
risk factors without regard to whether a
patient meets the criteria for diagnosis of
the ‘metabolic syndrome’.”
Criteria for diagnosis:
• World Health Organization
• International Diabetes Federation (IDF) European Association for the Study of
Diabetes (EASD)
• National Cholesterol Education Project,
Adult Treatment Panel (NCEP-ATP III)
• Others
Hypertension:
• IDF:
– BP >130/85 or on Rx for previously Dxed
hypertension
• WHO:
– BP >140/90
• NCEP ATP III:
– BP >130/80
Obesity:
• IDF:
– Central obesity - waist circumference >94 cm
for Europid men, >80 Europid women with
ethnicity specific values for other groups
• WHO:
– Waist-hip ratio >0.9 - men or >0.85 - women
• ATP III:
– Waist circumference >40 in. - men, 35 in. women
Glucose Abnormalities:
• IDF:
– FPG >100 mg/dL (5.6 mmol.L) or previously
diagnosed type 2 diabetes
• WHO:
– Presence of diabetes, IGT, IFG, insulin
resistance
• ATP III:
– FBS >110 mg%, <126 mg% (ADA: FBS >100)
Dyslipidemia:
• IDF:
– Triglycerides - >150mg/dL (1.7 mmol/L)
– HDL - <40 mg/dL (men), <50 mg/dL (women)
• WHO:
– Triglycerides - >150 mg/dL (1.7 mmol/L)
– HDL - <35 mg/dL (men), >39 mg/dL) women
• ATP III:
– Same as IDF
Necessary Criteria to Make
Diagnosis:
• IDF:
– Require central obesity plus two of the other
abnormalities
• WHO:
– Also requires microalbuminuria - Albumen/
creatinine ratio >30 mg/gm creatinine
• ATP III:
– Require three or more of the five criteria
Linked Metabolic Abnormalities:
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Impaired glucose handling/insulin resistance
Atherogenic dyslipidemia
Endothelial dysfunction
Prothrombotic state
Hemodynamic changes
Proinflammatory state
Excess ovarian testosterone production
Sleep-disordered breathing
Resulting Clinical Conditions:
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Type 2 diabetes
Essential hypertension
Polycystic ovary syndrome (PCOS)
Nonalcoholic fatty liver disease
Sleep apnea
Cardiovascular Disease (MI, PVD, Stroke)
Cancer (Breast, Prostate, Colorectal, Liver)
Prevalence of Metabolic
Abnormalities:
• Global - approx. 314 million people with
impaired glucose metabolism (500 million
by 2025)
• Palestine: (Hanan F. Abdul-Rahim, MSC)
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HTN - 25.4%(R) vs 21.5% (U)
Diabetes - 9.8%(R) vs 12%(U)
IGT -8.6%(R) vs 5.9%(U)
(17% of both groups had either DM or IGT!!)
Hypertriglyceridemia - 22.6%(R) vs 34.8%(U)
Prevalence - Palestine: (cont.)
• Low HDL - 28.3%(R) vs 61.2% (U)
• Overall Obesity - 28.2%(R) vs 41.5%(U)
• Central Obesity - 65.7%(R) vs 39.0% (U)
• Clustering of components with and without
diabetes were similar in both populations.
• Individuals with DM or IGT - 73.4% also
had two additional components of Met. Syn.
Prevalence in U.S.:
• Varies with ethnicity:
– Native Americans with diabetes - 55.2%
– Metabolic syndrome more prevalent in
Mexican/Americans and African Americans
than non-Hispanic caucasians (ATP III)
– Prevalence increasing in juveniles as well as
adults due to overnutrition and sedentary lifestyles, smoking
• Prevalence increases with aging
Insulin Resistance:
• Etiology is polygenic and environmental
(overnutrition, sedentary life-style)
• Sensitivity to insulin varies widely in the
general population
• Insulin-mediated glucose uptake by cells is
compromised
• As beta cells fail and insulin is insufficient,
hyperglycemia occurs
Insulin Resistance:
• Hyperinsulinemic individuals are at risk for
developing diabetes, hyperlipidemia, HTN,
& ultimately cardiovascular disease
• Patients with Metabolic Syndrome are 3.5
times as likely to die from CVD as normal
people
Multiple Risk Factor
Management
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Obesity
Glucose Intolerance
Insulin Resistance
Lipid Disorders
Hypertension
Goals: Minimize Risk of Type 2 Diabetes
and Cardiovascular Disease
Diabetes Control - How
Important?
• For every 1% rise in Hgb A1c there is an
18% rise in risk of cardiovascular events &
a 28% increase in peripheral arterial disease
• Evidence is accumulating to show that tight
blood sugar control in both Type 1 and Type
2 diabetes reduces risk of CVD
• Goals: FSBS - premeal 90-130, postmeal
<180. Hgb A1c <7%
BP Control - How Important?
• MRFIT and Framingham Heart Studies:
– Conclusively proved the increased risk of CVD
with long-term sustained hypertension
– Demonstrated a 10 year risk of cardiovascular
disease in treated patients vs non-treated
patients to be 0.40.
– 40% reduction in stroke with control of HTN
• Precedes literature on Metabolic Syndrome
• Goal: <130/80
Lipid Control - How Important?
• Multiple major studies show 24 - 37%
reductions in cardiovascular disease risk
with use of statins and fibrates in the control
of hyperlipidemia.
• Goals: LDL <70 mg% (<2.6 mmol/l)
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Triglycerides <150 mg% (<1.7
mmol/l)
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HDL >40 mg% (>1.1 mmol/l)
Medications:
• Hypertension:
– ACE inhibitors, ARBs
– Others - thiazides, calcium channel blockers,
beta blockers, alpha blockers
• Hyperlipidemia:
– Statins, Fibrates, Niacin
• Platelet inhibitors:
– ASA, clopidogrel
Insulin Resistance/Diabetes:
• Insulin Sensitizers:
– Biguanides - metformin
– PPAR α, γ & δ agonists - Glitazones, Glitazars
– Can be used in combination
• Insulin Secretagogues:
– Sulfonylureas - glipizide, glyburide,
glimeparide, glibenclamide
– Meglitinides - repaglanide, netiglamide
Insulin
• Insulin Analogues:
– Lys-pro/Aspart/glulysine used with meals
– Glargine as basal insulin
• Continuous Subcutaneous Insulin Infusion
(CSII)
• NPH/Regular, NPH/logs - Mixed or in fixed
combinations (70/30, 75/25, 50/50)
• Insulin combined with oral agents
New Pharmacologic Agents:
• Incretin Mimetics:
– GLP-1 agonist - exenatide
• Dual PPAR Dual Agonists:
– Glitazars
• CB1 Endocannabinoid Receptor (Appetite)
Antagonist:
– Rimonabant
Antihypertensive Medications:
• Angiotensin-converting Enzyme Inhibitors
(ACEI)
• Angiotensin II Receptor (ARB) Blockers
• Combination with Thiazides, Calcium
Channel Blockers, Cardioselective Beta
Blockers
• Target BP: <130/80
Life-Style Modification: Is it
Important?
• Exercise
– Improves CV fitness, weight control, sensitivity
to insulin, reduces incidence of diabetes
• Weight loss
– Improves lipids, insulin sensitivity, BP levels,
reduces incidence of diabetes
• Goals: Brisk walking - 30 min./day
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10% reduction in body wt.
Smoking Cessation/Avoidance:
• A risk factor for development in children
and adults
• Both passive and active exposure harmful
• A major risk factor for:
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insulin resistance and metabolic syndrome
macrovascular disease (PVD, MI, Stroke)
microvascular complications of diabetes
pulmonary disease, etc.
Screening/Public Health
Approach
• Public Education
• Screening for at risk individuals:
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Blood Sugar/Hgb A1c
Lipids
Blood pressure
Tobacco use
Body habitus
Family history