DEFINITION INTRODUCTION

The term metabolic syndrome is used to describe a complex of metabolic disorders. The main underlying cause of these abnormalities is insulin resistance. 

The presence of the complex of these metabolic disorders increases the risk of early onset of cardiovascular disease.

The metabolic syndrome in relation to insulin resistance was first described by Reaven (1988) when, evaluating earlier observations, he described the coexistence of insulin resistance with hyperinsulinemia, impaired glucose tolerance, hypertriglyceridemia, reduced HDL-cholesterol and hypertension, which he called the syndrome X. The main characteristic of the syndrome was considered to be hyperinsulinemia, which is the main metabolic disorder of insulin resistance. In the following years, other parameters were added to the complex of manifestations of syndrome X (table 1) and various other names were given such as polymetabolic syndrome, insulin resistance syndrome, metabolic cardiovascular syndrome, insulin resistance-dyslipidemia syndrome. 

• Original description (Reaven)

Insulin resistance
Hyperinsulinemia
Impaired glucose tolerance
Hypertension
Hypertriglyceridemia
Reduced HDL-cholesterol

• Syndrome extensions

Central obesity
Increased small dense fractions of LDL-cholesterol
Hyperuricemia
Decreased PAI-1
Increased postprandial lipemia decreased SHBG hyperfibrinogenemia microalbuminuria leptin resistance hyperleptinemia

EXTENSIONS OF CENTRAL OBESITY SYNDROME RELATIONSHIP OF INSULIN RESISTANCE AND CARDIOVASCULAR DISEASE

Metabolic syndrome is not rare, epidemiological studies have shown that over 25% of the population gradually develops insulin resistance showing the manifestations of metabolic syndrome. The term insulin resistance indicates a condition in which normal concentrations of the hormone show a reduction in the expected biological response. Because the main action of insulin is to maintain glucose homeostasis, Reaven considered that the main disorder of resistance is located in the insulin-mediated uptake of glucose in peripheral tissues and mainly in skeletal muscles and adipose tissue. Today, insulin resistance is referred to as a general metabolic disorder that predisposes patients to non-T2DM and other cardiovascular risk factors such as hypertension and dyslipidemia, a condition estimated to affect more than 200 million people worldwide.

FACTORS AFFECTING THE METABOLIC SYNDROME

Age : Its increase has an adverse effect on the glycemic clamp. For each decade of life, fasting blood sugar increases by 0.9 mg% and postprandial glycemia by 7.2 – 12.6 mg%. This deterioration is mainly attributed to the decrease in insulin sensitivity

Obesity : generally accepted to increase insulin resistance. An increase above 35 – 40% of the ideal weight results in a decrease in tissue sensitivity to insulin by 30 – 40%. In obesity, and especially in central obesity, it is believed that the increase in free fatty acids (FFA) flowing into the portal vein causes the appearance of insulin resistance in the liver cells resulting in an increase in neoglycogenesis leading to worsening resistance and hyperinsulinemia. In Caucasians there is a negative linear correlation between body fat and insulin sensitivity, while in Pima Indians a similar relationship exists when body fat increases above 26%. This association is further influenced by the distribution of adipose tissue with its central distribution showing a stronger correlation with insulin resistance.

Physical activity : Increased physical activity increases the availability of glucose in the tissues through insulin and the sensitivity of the liver to insulin. This result has been found to occur after 4 – 6 weeks of intensive exercise.

PATHOLOGICAL CONDITIONS ASSOCIATED WITH THE METABOLIC SYNDROME – DIAGNOSTIC CRITERIA

Metabolic syndrome includes pathological conditions that are considered risk factors for cardiovascular disease. Although associations between these risk factors have been shown in many studies, since about 15 years the existence of a distinct syndrome underlying insulin resistance has not been fully accepted. The main point of dispute is the finding that although insulin resistance is attributed to genetic damage, in a small proportion of patients possible genes have been identified. Diagnostic criteria of the Metabolic Syndrome have been proposed in 1999 by the WHO and in 2001 by the NCEP (National Cholesterol Education Program).

According to the WHO criteria, the diagnosis is made when there is:

Disturbance in glucose homeostasis IFG, IGT, T2DM and/or insulin resistance
and 2 or more of the following factors:

1: IFG= Impaired Fasting Glucose (Impaired Fasting Glucose) i.e., fasting blood glucose 100-125mg/dl

2: IGT= Impaired Glucose Tolerance i.e. blood glucose in the glucose tolerance test 2 hours after oral administration of 75 g. glucose 140-199mg/dl.

3. Arterial pressure > 140/90 mmHg

4. Tg > 150 mg/dL or HDL-cholesterol < 35 mg/dL(Men), < 39 mg/dL (Women)  

5. W/H > 0.9 (M), > 0.85 (W) or BMI⁴ > 30 Kg/m2

6. Urine albumin: 20 – 200 μg/min

According to the NCEP criteria, the diagnosis is made when three or more of the following factors are present

• Dyslipidemia: Tg >150 mg/dL
• HDL-cholesterol: < 40 mg/dL (Μ), < 50 mg/ dL(W).
• Central obesity: waist circumference: > 102 cm (M), > 88 cm (W)
• Blood pressure: > 135/85 mmHg
• Fasting glucose: > 110 mg/dL

Based on the above, in order to reveal Metabolic Syndrome, a test should be done to reveal dyslipidemia, obesity, hypertension, microalbuminuria, diabetes mellitus or impaired glucose tolerance and hyperinsulinemia. Dyslipidemia associated with metabolic syndrome is defined by fasting triglyceride levels > 200 mg% and low HDL-cholesterol levels < 35 mg%. Obesity is considered when BMI is >27.3 Kg/m² for women and >27.8 Kg/m² for men that corresponds approximately to 120% of ideal body weight. Central obesity is considered when the waist/hip ratio is > 1.0 for men and > 0.9 for women. In some epidemiological studies, central obesity is assessed only by waist circumference (> 1.0 m in men and > 0.9 m in women). Hypertension is diagnosed by two resting blood pressure readings that exceed 140/90 mm Hg. Type 2 Diabetes Mellitus is defined when the fasting venous blood sugar value is > 126 mg% or > 200 mg% 2 hours after a glucose load and impaired glucose tolerance when the sugar value two hours after a glucose load is >140 mg% and < 200 mg%.

• W/H : Waist / Hip ratio
• BMI (Body Mass Index)

    Microalbuminuria: Test is positive when albumin excretion is > 30 IU/24h or > 20μg/min in 8h or 4h urine or albumin/creatinine ratio > 30mg/g in random urine specimen OR biological variation of microalbuminuria from day to day is high (~40%) and therefore any diagnosis cannot be based on a single value. In order to establish the diagnosis of microalbuminuria, it is necessary to find two positives in three measurements that will be made over a period of 3-6 months.

     Hyperinsulinemia considered when the fasting insulin value exceeds 114 pmol/L (20 IU/ml).

Measurement of insulin must be evaluated with great care because the various methods we use often present a cross-reaction with proinsulin and other precursor molecules of insulin resulting in an overestimation of the true levels of insulin.

GRADUATE COURSES IN ENDOCRINOLOGY AND DIABETES- DEPARTMENT OF ENDOCRINOLOGY DIABETES AND METABOLISM OF EVANGELISMOS GENERAL HOSPITAL OF ATHENS- 2004