METABOLIC SYNDROME

Synonyms

Insulin resistance syndrome(Metabolic) Syndrome XDysmetabolic syndromeMultiple metabolic syndrome

Metabolic Syndrome

46-year-old man (for new job) denies:

any complaints recent history of illness or injury except: "few aches&epigastric pain on and

off." PMH:

Negative last P/E: 10 years ago for a job-related

injury to his kneeD.HX:

negative

Case presentation:

F/H:mother and brother having heart disease, hypertension, and

obesity.

Social /H: High-fat, high-cholesterol diet

Moderate tobacco use

 P/E: moderately obese(central), white man V/S :

Temp: 37.1°C HR:88 beats /minute RR:16 breaths /minute Average BP :144/90 mm Hg in both arms Wt: 107.7 kg Ht: 173 cm BMI: 36 kg/m2.

cont..

W/C: 112 cmThe rest of P/E: unremarkable

Diagnostic Assessment Results: ECG:NLFasting lipid profile:

Total C = 282 mg/dLLDL-C = 152 mg/dLHDL-C = 36 mg/dLTG= 248 mg/dL

FBS: 116 mg/dLCBC:NLU/A:NL

Cont...

Metabolic syndrome combination of medical disorders , increase

the risk of developing CVD & diabetes.

Prevalence: one in five people(U.S) increases with age

History:19501970

PATHOGENESIS:

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG, LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Causes

Acquired causesOverweight and obesityPhysical inactivityHigh carbohydrate diets (>60% of energy

intake) Endocrine disorders such as:polycystic

ovarian syndromeAging

Genetic causes

Metabolic Syndrome

Defining Level Risk Factor

>102 cm (>40 in)

>88 cm (>35 in)

Abdominal obesity†

MenWomen

150 mg/dL or on Rx TGTG

<40 mg/dL<50 mg/dL or Rx ↓ HDL

HDL-C Men

Women

130/85 mm Hg or on Rx Blood pressure

100 mg/dL or on Rx Fasting glucose

*Dx: 3 of these R.F †Abd.obes: more highly correlated with metabolic risk factors than BMI. ‡Some men develop metabolic risk factors when circumference is only marginally increased.

Overweight and obesity

Sedentary lifestyle

Aging

Diabetes mellitus

Coronary heart disease

Lipodystrophy

Risk factors continues

Prolonged stree

BS Insulin resistance osteoporosis

HPA-axial dys

Cortisol secretion

Risk factors cont...

Lifestyle risk factors:

Abdominal obesity

Physical inactivity

Atherogenic diet

Year 1: reduce body weight 7-10 percent Continue weight loss to goal BMI <25 kg/m2

At least 30 min ( preferably ≥60 min) continuous exercise 5X/wk, preferably daily

Reduced intake saturate fat, trans fat, chol

Metabolic risk factor:Dyslipidemia

Elevated BP

Elevated glucose

Prothrombotic state

High risk: <100 mg/dL optional <70 mg/dL Moderate risk: <130 mg/dL Lower risk: <160 mg/dL

Reduce to at least <140/90 (<130/80 if DM)

For IFG, weight reduction &exercise For type 2 DM, target A1C <7%

Low dose aspirin for high risk patients

THERAPEUTIC GOALS FOR MANAGE OF METABOLIC SYN...

Diabetes mellitus

Overview of Diabetes in the United States

Now,145000pts are affected,estimated to be 400000,in 2030

more than 1.5 million: DM in Iran the prevalence of DM in Yazd: 7.3%

Overall, 20% of the Iranian aged 30yr/old& over at risk of DM

Prevalence of `DM in 30 yr old & over in various locations of IRAN

Diabetes mellitusDiabetes mellitus, which is characterized by high concentrations of blood glucose resulting from defects in insulin secretion and/or insulin action

type 2 diabetesmost common : 90% to 95%

type 1 diabetes:5% to 10%.

Other forms( 1% to 2% ):specific genetic syndromes surgeryDrugsMalnutritioninfections

ethnic groups Latin Americans African Americans

strong F.HX

PCOS, or GDM

IGT,IFG:(25-40% in5later)

dyslipidemia

Hypertension

central obesity

Who are at risk?Diabetes mellitus…

Prevalence of R.F for DM2 in Iran

Dx & Classification of D.MDiagnosis Glucose test Diagnostic level Comments

Diabetes Random>200mg/dL Plus classic symptoms*

Diabetes Fasting>126mg/dL

8-hour fast; need confirmation

Diabetes B.S (75g)>200mg/dL at 2h Need confirmation

Diabetes HbA1c≥6.5% New

Prediabetes IFG Fasting100-126mg/dL Decreased insulin secretion

Prediabetes IGT B.S (75g)140-199mg/dL at 2h� Increased insulin resistance

Prediabetes HbA1c5.7-6.4%� New

IN pts with DM:

CVD:primary cause of death(55%)

IHD:40% of death

Risk of mortality 2-4 times higher than others

CVD &DM:

With Type 2 Diabetes With or Without Previous MI

Degree of glycemic control:Preprandial 70-130� mg/dL; <110 ideallyPostprandial (1 to 2h) <180 minimal; <140 ideally•HbA1c <7% minimally; 6% or less if possible in selected patients early in disease course

•

• Management of CV risk factors:BP<130/80LDL <100mg/dL; optional <70mg/dL Non-HDL <130mg/dL; optional <100mg/dLHDL >40mg/dL (men); >50mg/dL (women)Triglycerides <150mg/dL

Treatment goals:D.M…

• Non-pharmacologic therapy

•Diet

•Exercise

•Intensive lifestyle modification

• Medical therapy

Treatment continue..

Intervention advantages disadvantages dose

500mg TIDMAX:850mg TID

Broad benefits

Weight neutral

Insufficient for most at first

GI side effects, contraindicated with CRD

Step 1:

Lifestyle :Wt loss& inc. Act

metformin

2.5-10mg Bid-Qid(tab5mg)2.5-10mgBid-Qid(tab5mg)

No dose limit rapideffec,improve lipid profile

Rapidly effective

1-4inj.dailymonitore Bs

Wtgain,hypoglycemia (especially withglibenclamid

Step 2 :Insulin

Sulfonylurea Glibenclamide

glipizide

Improved lipid profile

Weight loss

Edema, HF, wt gain, bone fx, expensive

2 inj daily, GI side effects, long-term safety not docum..

Step3:less validatedTZDs

GLP-1 agonist

intervention frequency noteHx&P/E:

Blood pressure Every visit Goal <130/80

Dilated eye examination

Annually onset of DM2& 3 - 5 yr after onset of DM1,retinopathy,Exam more than annually

Foot examination Annually Every visit if PVDxor neuropathy

Laboratory studies :

Fasting lipid profile Annually every 2 years if profile is low risk

HbA1C Every 3 to 6 months Goal <7%

Microalbuminuria Annually 3 to 5 yrs after onset of DM1, Pr exc and serum Cr, should monitore if persistent alburea

Serum creatinine Initially, as indicated

Vaccinations :

Pneumococcus One time Pts > 65 need a second dose if received ≥5 years previously

Influenza Annually

ABDOMINAL OBESITY

CLASSIFICATION

TERM BMI kg/m2

Obesity class

WC & risk of dx

Men ≤102 cm >102

cm

Women ≤88 cm >88 cm

Underweight <18.5 - - -

normal 18.5-24.9 - - -

overweight 25-29.9 - Increased High

obesity 30-34.9 I High Very high

35-39.9 II Very high

Extreme obesity >40 III Extremely high

Etiologic classification of obesityIatrogenic causes

Drugs cause weight gain Hypothalamic surgery

Dietary obesity Infant feeding practices Frequency of eating High fat diets Overeating

Neuroendocrine obesities Seasonal affective disorder Cushing's syndrome Polycystic ovary syndrome Hypogonadis&def of G.H

Genetic (dysmorphic) obesities X-linked traits Chromosomal abnormalities

Elevated Cholesterol, Triglycerides…

Major modifiable R.F for CHD

Dyslipidemia

Screening/Detection:

Complete lipoprotein profile : Fasting total chol, LDL, HDL, TG

Secondary option: Non-fasting total cholesterol and HDL If TC 200 mg/dL or HDL <40 mg/dL:

Proceed to lipoprotein profile

New Features of ATP III (continued)

STEP1: determine

LDL Cholesterol (mg/dL)

<100 Optimal

100–129 Near optimal/above optimal

130–159 Borderline high

160–189 High

190 Very high

NCEP/ ATP III Lipid Classification

Total Cholesterol (mg/dL):

<200 Desirable

200–239 Borderline high

240 High

HDL –c (mg/dL):<40 low

>60 High

ATP III Lipid Classification (continued)

step1

Step 2: CHD equivalents risk factors:

(10-year risk for hard CHD >20%)

Diabetes

Framingham projections of 10-year

CHD risk(age,HTN,T-chol&HDL)

metabolic syndrome

Symptomatic carotid artery dx

Peripheral artery dx

Abdominal aortic aneurysm

New Features of ATP III

Cigarette smoking

HTN : BP 140/90 mmHg or on Rx

Low HDL chol (<40 mg/dL)

F.H of premature CHD: CHD in male first degree relative <55 years CHD in female first degree relative <65 years

Age: (men 45 years; women 55 years)

Step 3 :Major CHD factors other than LDL

† HDL cholesterol 60 mg/dL counts as a “negative” risk factor; its presence removes one risk factor from the total count.

New Features of ATP III (continued)

Risk Category LDL-C Goal LDL-C Level for Initiate TLC

LDL-C Level for Drug Therapy

CHD or CHD risk equivalents (10-year risk >20%)

<100 mg/dL ≥100 mg/dL ≥130 mg/dL (100-129 mg/dL, drug optional

2+ (10-year risk ≤20%)

<130 mg/dL ≥130 mg/dL ≥160mg/dl

0 OR +1(<10%)

<160 mg/dL ≥160 mg/dL ≥190 mg/dL (160-189 �mg/dL, drug optional)

Step 4 : initiate therapeutic lifestyle change(TLC)& drug Tx

Treatment:

Therapeutic Lifestyle Changes (TLC)

Drug therapies

New Features of ATP III (continued)

TLC Diet

Reduced intake:Saturated fats <7% of total caloriesDietary cholesterol <200 mg / day

LDL-lowering therapeutic: Plant sterols (2 g /day)Viscous (soluble) fiber (10–25 g / day)

Weight reduction

Increased physical activity

Lifestyle …

Limit intake of food rich in cholesterol and saturated fats

Treatment: DIET

fish more than meat or poultryLimit intake of egg yolks to 3-4 times a week more of dried beans, peas and legumesmore cereals and grains

Treatment: DIET

30-60 min of aerobic exercise 3-4 times a week

Increase physical activity at home and at work

Treatment: EXERCISE

• Reinforce

saturated

• Increase fiber

intake

• Refere

• Tx MetabolicSyndrome

• Intensify wt &ph.act

• refere

6 wks 6 wks 4-6 mo

•

saturated fat &chol

moderate ph.act• refere

Visit I

Lifestyle

Visit 2

LDL response?

not: Treatment

Visit 3

LDL response?

not :add drug Tx

Therapeutic Lifestyle Changes (TLC):

MonitorTLC

Visit N

Drug class Dosing Major side effects

Statins (HMG CoA ):

AtorvastatinLovastatinSimvastatin

LDL 18–55%

10-80 mgd/(tab10-20-40-80)20-80mg/d(tab 20mg)5-80 mg/d(tab 10-20mg)

Headachenausea; sleep disturb; elevate LFT Myositis rhabdomyolysis

Fibric acid

Gemfibrosilclofibrate

TG 20–50%

600 mg BID(cap300) 1000mg BID

May raise LDL-C (with high TG)

Potentiates warfarin action

Nicotinic acid

Raise HDL 15–35%

(Tab 100-500mg)

After 6 weeks: Check: lipids, glu , LFT, uric acid.

Bile acid

cholestyramine

Reduce LDL-C 15–30%

4-24 g/d(powder)

May increase TG

Ezetimibe 10 mg/day

Neomycin 1 g BID(tab500mg) Ototoxic, nephrotoxic

Probucol 500 mg BID Loose stools; QT prolong; edema.

For patients with TG 200 mg/dL

LDL cholesterol: primary target

Non-HDL cholesterol: secondary

New Features of ATP III (continued)

Non HDL-C = total cholesterol – HDL cholesterol

Drug Therapy in Primary Prevention

LDL response?

Not: intensify therapy

LDL response?

intensify drug therapy

or refer to a lipid specialist

Monitor response & adherence to therapy

statin

bile acid

nicotinic acid

• higher dose of statin

or

• add a bileacid or

• nicotinic acid

6 wks 6 wks Q 4-6 moInitiate:

HYPERTENSION

Types:

Primary/ Essential Hypertension no medications/ Lifestyle Modification

Secondary Hypertension(with medications)a. Kidney Diseaseb. Thyroid Diseasec. Adrenal Disease

Office or White Coat Hypertension - may affect as 50% of hypertensive patients.

HYPERTENSION:

Risk factors:

Controllable

Obesity

Eating too much salt

Alcohol

Lack of exercise

Stress

Uncontrollable

Race

Heredity

Age

Signs and Symptoms:

Headache

Neck Pains

Blurring of Vision

Dizziness/ Sweating

Palpitation

Chest pain

Difficulty of Breathing

HYPERTENSION…

Usually asymptomatic

Not refer to being tense, nervous or hyperactive

only way to detect is to checked it

A single high BP no maen for HTN But

it is a sign to watch carefully

HYPERTENSION…

Diagnostic Work-Up:

CBC

U/A

CXR

Lipid Profile

Other Blood Chemistry (SGPT/SGOT/BUN/Cr/Uric Acid)

ECG

2D- Echo

Hypertension…

Management of HTN by BP ClassificationInitial Drug Therapy

BP Classification Lifestyle Without Indication With Indication

Normal<120/80 mmHg

Encouraged

Pre- Hypertension120-139/80-89 mmHg

Yes No drug indicated Drug(s) for indications

Stage I Hypertension140-159/90-99 mmHg

Yes Thiazide ACE-I, ARB, BB, CCB, or combination

Drug(s) for indications

Stage 2 Hypertension> 160/100mmHg

Yes 2- drug usually :thiazide-type diuretic & Ace-I, ARB, BB, or CCB)

Drug(s) for indications

Modification Recommendation Ave SBP Reduc.Range

Weight Reduction BMI= 18.5-24.9 5-20 mmHg/10 kg

Eating plan fruits, vegetables, low fat dairy 8-14 mm Hg

Dietary sodium reduction Reduce dietary sodium intake to (2.4 g Na or 6 g NaCl)

2-8 mm Hg

Aerobic physical activity Regular aerobic physical activity (eg: brisk walking) atleast 30

minutes/day

4-9 mm Hg

Moderation of alcohol consumption

Men: limit to ≤ 2 drinks/d* Women : Limit to ≤ 1 drink per /d

2-4 mm Hg

*1 drink = 15 mL ethanol

Lifestyle Modification Recommendations

: بزنید چرت خواهید می ساعت یک

: بروید نیک پیک به بخواهید روز یک

: بروید تعطیالت به بخواهید هفته یک

: کنید ازدواج بخواهید ماه !!یک

: ببرید ارث به ثروت بخواهید سال یک

خواهید عمریک می :

داشته دوست را میدهید انجام که کاری بگیرید یادباشید

برای خوشبختیاگر را :

A leading cause of SICKNESS and DEATH

Coronary Heart Disease

- also known as Ischemic Heart Disease, Myocardial Infarction

- Blockage of blood flow due to focal narrowing of coronary arteries as a result of Atheromatous plaqu.

- Injury to the heart muscle- caused by a loss of blood supply- resulting to “heart attack”

CORONARY ARTERY DISEASE

Non-modifiable

SEX

AGE

• FAMILY HISTORY

DIABETES

SMOKING

OBESITY

DYSLIPIDEMIA

• HYPERTENSION

Risk factors:

modifiable

Diagnosis:

1) Hx&P/E (Typical signs and symptoms)2) 3) Lab: CBC, Electrolytes, BT, PTT,PT

4) Cardiac Enzymes: CPK-MB, Troponin

5) ECG

6) CXR (PA & lateral)

7) Nuclear Scan

8) 2-D Echo/3 D-Echo with Doppler

9) Coronary Catheterization/Angiogram

Coronary Heart Disease

Need for Hospitalization1) 02 administration2) Need for Surgical Procedures

Percutaneous Transluminal Coronary Angioplasty (PTCA)

Coronary Artery Bypass Graft (CABG)1 vessel, 2 vessels, 3 vessels

Cardiac Rehabilitation Medications Lifestyle changes Emotional issues

TREATMENT

:Social /H:High-fat, high-cholesterol diet

Moderate tobacco use P/E: BP :144/90

Wt: 107.7 kg

BMI: 36 kg/m2.

W/C: 112 cm(centrally)Diagnostic Assessment Results:

Total C = 282 mg/dLLDL-C = 152 mg/dLHDL-C = 36 mg/dLTG= 248 mg/dL

FBS: 116 mg/dL

SUMMARY...

F.H:mother and brother having heart disease,HTN, and obesity

.

Follow-up :

Due to his age and F.hx& examination( include obesity, stage I hypertension, and metabolic syndrome.)

SHOULD consider DM2 and atherosclerotic CVD

the primary purpose is to establish treatment goals for associated risk factors such as:

HTN,HLP&hyperinsulinemia all of which result in increased CVA&CVD and

mortality

Case present...

Teaching Plan:

A F/U visit for TLC:

Weight reductioneating plan, including fruits, vegetables, low-fat

dairy, whole grains, fish, and nuts; and minimal amounts of fats, red meat, sweets...

Reduction in dietary sodium intake

Increased physical activity

Stop smoking

Case presentation:

Pharmacologic Considerations:

low-dose ACE I: to control HTN stageI

atorvastatin (Lipitor): to reduce his LDL-C & TG levels

Fibrates : effective in lowering TG

(Combination therapy with a fibrate and a statin useful for patients with atherogenic lipid profiles)

Metformin(optional)

Case present...

ده قرار ارامش و صلح برای ای ...مراوسیله : بکارم عشق بذر است تنفر جا هر بگذار

ببخشایم هست ازردگی جا هر , امید هست یاس جا هر ایمان هست شک جا هر

کنم نثار شادی غم جای و روشنائی است تاریکی جا هرکنم دردی هم همدردی طلب از بیش ده توفیقم الهی

کنم درک را دیگران بفهمند مرا انکه از پیشستانیم می که است کردن عطا در زیرا

شویم می بخشیده که است بخشیدن در وع ... بیم یا می ابدی حیات که است مردن در و

:خدایا

Thanks for your attention