Linked Metabolic Abnormalities:

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Linked Metabolic Abnormalities

• Impaired glucose handling/ insulin resistance
• Atherogenic dyslipidemia
• Endothelial dysfunction
• Prothrombotic state
• Hemodynamic changes
• Proinflammatory state
• Excess ovarian testosterone production
• Sleep-disordered breathing

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Resulting Clinical Conditions

• 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)

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Multiple Risk Factor Management

• Obesity
• Glucose Intolerance
• Insulin Resistance
• Lipid Disorders
• Hypertension
• Goals Minimize Risk of Type 2 Diabetes and
  Cardiovascular Disease

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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/dL,
• (ADA FBS 100 mg/dL 5.6 mmol/L )

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Hypertension

• IDF
• BP 130/85 or on Rx for previously diagnosed
  hypertension
• WHO
• BP 140/90
• NCEP ATP III
• BP 130/80

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Dyslipidemia

• IDF
• Triglycerides - 150mg/dL (1.7 mmol /L)
• HDL -
• WHO
• Triglycerides - 150 mg/dL (1.7 mmol/L)
• HDL - 39 mg/dL) women
• ATP III
• Same as IDF

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Adipocytokines and Insulin Resistance
Adipokines and Metabolic Syndrome
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INSULIN MODULATION OF ENDOTHELIAL ACTIVITIES
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Insulin Resistance

• Hyperinsulinemic individuals are at risk for
  developing Diabetes, Dyslipidemia, Hypertension
  ultimately Cardiovascular disease
• Patients with Metabolic Syndrome are 3.5 times as
  likely to die from Cardiovascular disease
  compared to normal people

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Screening/Public Health Approach

• Public Education
• Screening for at risk individuals
• Blood Sugar/ HbA1c
• Lipids
• Blood pressure
• Tobacco use
• Body habitus
• Family history

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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
• 10 reduction in body wt.

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Smoking Cessation / Avoidance

• A risk factor for development in children and
  adults
• Both passive and active exposure harmful
• A major risk factor for
• insulin resistance and metabolic syndrome
• macrovascular disease (PVD, MI, Stroke)
• microvascular complications of diabetes
• pulmonary disease, etc.

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Diabetes Control - How Important?

• For every 1 rise in Hb 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
• FBS - premeal
• postmeal
• HbA1c

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Overcome Insulin Resistance/ Diabetes

• Insulin Sensitizers
• Biguanides - metformin
• PPAR a, ? d agonists Glitazones, Gltazars
• Rosiglitazon,
  Pioglitazon
• Can be used in combination
• Insulin Secretagogues
• Sulfonylurea - glipizide, glyburide,
  glimeparide, glibenclamide
• Meglitinides - repaglanide, netiglamide

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Insulin

• Insulin Analogues
• Lyspro /Aspart /glulysine used with meals
• Glargine Livemer 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

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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 BP.

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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
• (high risk mmol/L)
• TG
• HDL 40 mg (1.1 mmol /l)

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Medications

• Hypertension
• ACE inhibitors, ARBs
• Others - thiazides, calcium channel blockers,
  beta blockers, alpha blockers
• Central acting Alfa agonist Moxolidin
• Dylipidemia
• Statins, Fibrates, Niacin
• Platelet inhibitors
• ASA, clopidogrel

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Antihypertensive Medications

• Angiotensin -converting Enzyme Inhibitors (ACEI)
• Angiotensin II Receptor (ARB) Blockers
• Combination with Thiazides, Calcium Channel
  Blockers, Cardioselective Beta Blockers
• Target BP

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A Critical Look at the Metabolic Syndrome

• Is it a Syndrome?
• too much clinically important information is
  missing to warrant its designations as a
  syndrome.
• Unclear pathogenesis, Insulin resistance may not
  underlie all factors, is not a consistent
  finding in some definitions.
• CVD risks associated with metabolic syndrome has
  not shown to be greater than the sum of its
  individual components.
• ADA EASD

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A Critical Look at the Metabolic 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.
• The advice remains to treat individual risk
  factors when present to prescribe therapeutic
  lifestyle changes weight management for obese
  patients with multiple risk factors.

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Individual metabolic abnormalities among Qatari
population according to gender (Musallam et al
08)

• Men (n 405) Women (n412)
• Variable n() n() p-Value
• ATP III
• Abdominal obesity 227(56.0) 308(74.8)
• Hypertension 143(35.3) 156(37.9) 0.448
• Diabetes 77(19.0) 107(26.0) 0.017
• Hypertriglyceridemia 113(27.9) 83(20.1) 0.009
• Low HDL 95(23.5) 121(29.4) 0.055

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Individual metabolic abnormalities among Qatari
population according to gender
No of components of ATP III

• Men (n 405) Women (n412)
• Variable n() n() p-Value
• None 88(21.7) 74(18.0)
• One 103(25.4) 100(24.3) 0.033
• Two 125(30.9) 111(26.9)
• Three or more 89(22.0) 127(30.8)

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Multivariate logistic regression analysis of
factors associated with Metabolic Syndrome
according to (ATP III criteria)

• Odds ratio 95 CI p-Value
• Age 1.07 1.051.09
• Female gender 1.86 1.302.67 0.001
• Body Mass Index 1.05 1.021.07
• Fam his of DM 1.66 1.122.44 0.011
• Smoking 3.27 1.636.55 0.001

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Prevalence of MeS in different Countries
Crude rates Mussallam et
al. Int J Food Safety and PH 2008
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Prevalence of MeS in different Countries
Crude rates Mussallam et
al. Int J Food Safety and PH 2008
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Thank You