METABOLIC SYNDROME

METABOLIC SYNDROME

            The term syndrome x coined by Gerald Reaver in 1988. It suggests physical inactivity and obesity.

Metabolic syndrome (3/5)

1.      Elevated waist circumference based on population and country specific definition.

2.      Elevated triglyceradies (³ 150mg/dl)

3.      Reduced HDL cholesterol (<40mg/dl for males and <50mg/dl for females)

4.      Elevated blood pressure (SBP/DBP ³ 130/85)

5.      Elevated fasting glucose (³ 100mg/dl)

            Subjects of metabolic syndrome have 2 fold increased risk of diabetes and atherosclerosis.  It is important to evaluate all diabetics for cardiovascular disease risk.

CVD risk factors in Diabetes

1. Abnormal glycemia (dysglycemia)
2. Visceral obesity and waist circumference
3. Atherogenic dyslipedemia
4. Hypertension
5. Proinflammatory and prothtrombotic state
6. Smoking and CV risk
7. Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis
8. Age, gender and family history
9. Sedentary life styles and physical inactivity
10. Microalbuminuria

Abnormal glycemia

            All forms of diabetes above a standard normal range are associated with increased risk of microvascular complications i.e. nephropathy, retinopathy, neuropathy, also CHD (MI) cardiac failure, PAD and Stroke.

            The reduction mean glucose level i.e. HbA1c have protect against microvascular complications of diabetes also MI in diabetes (UKPDS). Effect of sustained hyperglycemia lead to endothelial dysfunction and atherosclerosis through

1. Glucotoxicity
2. Lipid oxidation
3. AGE production
4. Decreased nitric oxide production
5. Increased entothelium and basement membrane thickening

Visceral Obesity and Waist Circumference

            It correlates more strongly with insulin resistance. Abnormal obesity is associated with increased levels of plasma fattyacids that results in increased accumulation of TG in muscle and liver. The net effect are

1. Increased IR in muscle
2. Altered hepatic fat accumulation and altered metabolism
3. Dyslipidemia
4. Increased proinflammatory adipokines which again give rise to IR
5. Decreased in adiponectin levels leading to endothelial dysfunction and vasculitis, ultimately increased risk of atherosclerosis vascular disease

            Waist circumference is a good indicator of visceral fat. Therefore it is an essential component of metabolic syndrome as defined by IDF.  Waist > 90cm in male, >80 cm in female, hypertension >130/80, dyslipidemia (TG>150mg/dl, HDL <35mg/dl, LDL >100mg/dl) hyperglycemia. Thus measurement of waist circumference is an integral part of CV risk assessment in II DM, more important than BMI.

Atherogenic Dyslipedimia

            Important marker in future CVD events in DM increase no. of small dense LDL particles, low levels of HDL cholesterol, high levels of TG. HDLC is atheroprotective and low HDLC is independent risk factor for CHD risk even when LDL is normal or low.

Hypertension

            Hypertension and diabetes frequently co-exist. Hypertension exaggerates ASCVD in diabetes and increase risk of microvascular complications. 15% increase in CAD per 10mmHg rise in SBP. In obese patients, BP is sensitive to sodium intake and this sensitivity related to fasting insulin level.

The following contribute to development of hypertension

1. The antinatriuretic effect of insulin
2. Ability to activate sympathetic nervous system
3. Drive abnormal vascular function

            Both hyperglycemia and insulin activate RAAS by enhancing expression of angiotensionogen, angiotension II and ATI receptor which contributes to increase in BP in patient with IR/DM.

Proinflammatory and Prothrombotic State

            Chronic subclinical inflammation characteristics by elevated cytokines (TNF - a IL-6) and acute phase reactants (CRP and fibrinogen) is part of metabolic syndrome. Immunity and inflammatory play a role in development of IR and II DM. prothrombotic state characteristics by increased level of PAI-1 and fibrinogen which results in impaired fibrinolysis as in IR and II DM. Therefore diabetes is a prothrombotic state resulting in increased blood viscocity, decrease blood flow in microcirculation and several defects of coagulation and fibrinolysis.

Smoking and CV Risk

            It is a strong CVD risk factor highly reversible. Effect of chronic smoking are;

1. Accelerated atherogenesis
2. Increased platelet aggregation
3. Other clotting abnormalities result in vascular occlusion

NAFDD and NASH

            In these conditions  increased prevalence of obesity, metabolic syndrome, IR and type II diabetes end up in cirrhosis of liver.

Age, Gender and Family History

            Irreversible risk factor. Indian phenotype is prone for type II diabetes, hypertension, CHD. Important predictors of diabetes;

1. Low birth weight (<2.5kgs)
2. Weight at one years (<8kg)

Risk factor for CHD are;

1. CHD and hypertension in adult life
2. Increasing age
3. Male gender
4. Family history of premature CHD

Sedentary Life Style and Physical Inactivity

Microalbuminuria

Note:

Present day target

1. Life style BMI <23 kg/m²

                                Waist circumference <94 cm in male and <80cm in female

2. Glycemic control HbA1c <7% (ADA)

<6.5% (AACE)

3. BP control <130/80
4. Lipid control LDL <100mg/dl <70 in high risk

                                    HDL >40mg/dl in male

                                                >46mg/dl in female

                                    TG <174 mg/dl

                                    TG <150mg/dl

REFERENCE:

            Medicine update, API