Metabolic Syndrome

Table 1.

Risk Factor	Cutpoint
Abdominal obesity
Men	Waist circumference ≥ 40 inches
Women	Waist circumference ≥ 35 inches
Elevated triglycerides	≥ 150 mg/dL
Low HDL cholesterol:
Men	< 40 mg /dL
Women	< 50 mg/dL
Elevated blood pressure	≥ 130 / ≥ 85 mm Hg
Elevated fasting glucose	≥ 110 mg/dL

Table 1. ATP III Diagnostic Criteria for Metabolic Syndrome^[37]

Table 1.

Risk Factor	Cutpoint
Abdominal obesity
Men	Waist circumference ≥ 40 inches
Women	Waist circumference ≥ 35 inches
Elevated triglycerides	≥ 150 mg/dL
Low HDL cholesterol:
Men	< 40 mg /dL
Women	< 50 mg/dL
Elevated blood pressure	≥ 130 / ≥ 85 mm Hg
Elevated fasting glucose	≥ 110 mg/dL

Table 1. ATP III Diagnostic Criteria for Metabolic Syndrome^[37]

Table 2.

Risk Factor Component	Cutpoint for Abnormality
Overweight/obesity	BMI ≥ 25 kg/m²
Elevated triglycerides	≥ 150 mg/dL
Low HDL-C
Men	< 40 mg/dL
Women	< 50 mg/dL
Elevated blood pressure	≥ 130/85 mm Hg
2-hour postglucose challenge
Other risk factors	Family history of type 2 diabetes, hypertension, or cardiovascular disease
	Polycystic ovary syndrome
	Sedentary lifestyle
	Advancing age
	Ethnic groups having high risk for type 2 diabetes or cardiovascular disease

Table 2. AACE Diagnostic Criteria for the Insulin Resistance Syndrome*^[37]

AACE = American Association of Clinical Endocrinologists; BMI = body mass index
*Diagnosis depends on clinical judgment, which is based on risk factors.

Table 3.

Parameter	Mean (SD)
Parameter	Metabolic Syndrome (n = 194)	No Metabolic Syndrome (n = 382)
LDL-C, mg/dL
Baseline	187 (20)	186 (18)
Week 12	99 (31)	96 (25)
% change	-47 (15)	-48 (12)
HDL-C, mg/dL
Baseline	44 (9)	54 (13)
Week 12	49 (11)	58 (14)
% change	+10 (13)	+9 (12)
Triglycerides (mg/dL)
Baseline	216 (60)	155 (57)
Week 12	167 (64)	122 (50)
% change	-23 (20)	-19 (24)
Non-HDL-C (mg/dL)
Baseline	230 (23)	217 (21)
Week 12	132 (35)	120 (27)
% change	-43 (14)	-45 (12)
Non-HDL-C/HDL-C ratio
Baseline	5.4 (1.2)	4.2 (1.0)
Week 12	2.8 (1.1)	2.2 (0.8)
Δ %	-47 (15)	-48 (13)
ApoB (mg/dL)
Baseline	182 (22)	173 (20)
Week 12	115 (26)	106 (21)
% change	-37 (14)	-38 (12)
ApoA-I (mg/dL)
Baseline	141 (23)	155 (25)
Week 12	150 (25)	164 (27)
% change	+7 (13)	+6 (12)
ApoB/ApoA-1 ratio
Baseline	1.3 (0.3)	1.1 (0.2)
Week 12	0.8 (0.2)	0.7 (0.2)
% change	-40 (15)	-41 (13)

Table 3. Baseline and Week 12 Lipid Levels and Percent Change From Baseline in Patients With Hypercholesterolemia Treated With Rosuvastatin 10 mg

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Pathogenesis

Complex, mutually reinforcing interactions between obesity and insulin resistance largely account for the pathogenesis of metabolic syndrome. Central pathophysiologic features of metabolic syndrome include:

Insulin resistance, which may be linked to CHD;^[24,25]
Atherogenic dyslipidemia, chiefly manifested as a triad of low HDL-C together with increases in triglycerides and small, dense LDL (sdLDL) particles -- fasting and postprandial chylomicrons and glycated LDL particles prone to oxidation are also frequently increased;^[26]
Hypertension, which occurs frequently in persons with insulin resistance;
A proinflammatory state, with increases in acute-phase reactants (eg, C-reactive protein [CRP]); and
A prothrombotic state, with increases in plasminogen activator inhibitor (PAI-1) and fibrinogen.

Both the proinflammatory and prothrombotic states of metabolic syndrome derive largely from the secretory activity of adipose tissue, particularly intra-abdominal or visceral fat. Contrary to the former concept of fat as an inert tissue mass, adipocytes are increasingly being recognized as secretory entities. Cytokines and other inflammatory markers or signaling molecules released by adipocytes -- termed "adipokines"--include leptin, tumor necrosis factor alpha (TNF-alpha), interleukin-6, resistin, and adiponectin. Adiponectin levels are inversely related to fasting plasma insulin and glucose levels.^[27] Weight loss by obese individuals has been associated with increased adiponectin levels.

Visceral fat exhibits accelerated lipolytic activity. The attendant increased release of free fatty acids (FFA) -- also termed nonesterified fatty acids -- can adversely affect insulin action and glucose disposal in several tissues.^[28-32] These increases in circulating FFA levels may also result in the development of triglyceride reservoirs in both muscle and liver, depressing insulin action and increasing hepatic very-low-density lipoprotein (VLDL) output.^[18,33] Conversely, declines in visceral adiposity and reduced FFA levels following weight-loss diets have been associated with enhanced insulin sensitivity.^[34,35]

Disparate distributions of fat in men and women may help to explain why obesity had a more atherogenic effect in men vs women in the postmortem Pathological Determinants of Atherosclerosis in Youth (PDAY) study.^[36] The abdominal adipose distribution ("apple shape") seen more frequently in men exerts a stronger adverse cardiovascular risk than the gluteofemoral distribution ("pear shape") seen in women.^[37] Abdominal adiposity is measured via waist circumference at the umbilicus or as the waist/hip ratio (WHR): waist circumference at the umbilicus divided by the hips' circumference at their widest point.

Both the proinflammatory and prothrombotic states resulting from obesity may increase the risk of coronary events. CRP is a pivotal acute-phase reactant that is considered an index of inflammation and is associated with cardiovascular risk, particularly the risk of acute coronary syndrome. Within the nondiabetic population of the Insulin Resistance Atherosclerosis Study,^[38] the CRP level varied directly as a function of the number of metabolic abnormalities .

CRP is associated with acute coronary syndrome through its ability to destabilize and rupture atherosclerotic plaque.^[39-41] PAI-1 released in increased amounts from excess abdominal adipose tissue^[42-44] tends to increase the thrombotic consequences of plaque rupture. In a study of obese women, visceral fat and PAI-1 were significantly higher in patients with type 2 diabetes (vs those without), and visceral fat mass was independently correlated with increased PAI-1 activity (ie, decreased fibrinolysis).^[44]

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Page 3 of 7

Diagnosis

References

Table 1.

Table 1.

Table 2.

Table 3.

Metabolic Syndrome: A Growing Clinical Challenge: Pathogenesis

Pathogenesis

Table of Contents

Table 1.

Table 1.

Table 2.

Table 3.

References

Faculty and Disclosures

Metabolic Syndrome: A Growing Clinical Challenge: Pathogenesis

Pathogenesis

Table of Contents