Metabolic syndrome E88.9

In the 70s of the 20th century, Dresden physicians coined the term "metabolic syndrome". In 1988, Gerald Reaven postulated the terms "syndrome X" and "insulin resistance" (Fritsche 2015).

The term "insulin resistance syndrome" was coined in 1992 by Haffner et al. to emphasize that insulin resistance precedes other symptoms of metabolic syndrome (Roberts 2013).

The syndrome was first defined by the WHO in 1998 (Kasper 2015).

Gale, on the other hand, called metabolic syndrome a myth in 2005 (Fritsche 2015).

Bariatric surgery: Sleeve gastrectomy was first performed by Hess and Marceau in the late 1980s to reduce duodenoileal ulcers. Since then, the procedure has been used in extremely obese patients (Keck 2017).

Insulin resistance syndrome is a spectrum of disorders that increase the risk of developing type 2 diabetes mellitus and cardiovascular disease. The main features are:

• central obesity (the most important feature)
• hypertriglyceridemia
• low HDL levels
• hyperglycemia
• arterial hypertension (Kasper 2015).

Often, metabolic syndrome is also described as a premorbid risk condition that requires urgent preventive measures (Fritsche 2015).

The definition of metabolic syndrome (MS or MetS [Kassi 2011]) is based on different criteria. The most common classifications are:

• 1. WHO (1999):
  • A metabolic syndrome is present if A and ≥ 2 criteria of B - F apply:
    • A: IFG (impaired fasting glucose), IGT (impaired glucose tolerance ) or diabetes or in NGT (normal glucose tolerance) with insulin resistance.
    • B: BMI > 30 kg / m² and / or waist-hip ratio > 0.9 in men or > 0.85 in women.
    • C: blood pressure ≥ 140 / 90 mmHg
    • D: triglycerides ≥ 1.7 mmol / l (150 mg / dl) and / or
    • E: HDL- cholesterol < 0.9 mmol / l (< 35 mg / dl) in men, < 1 mmol / l (< 39 mg / dl) in women
    • F: microalbuminuria ≥ 20 µg / min (Fritsche 2015).

• 2. NCEP: ATP III = National Cholesterol Education Program (2005 revision).
  • A metabolic syndrome is present if ≥ 3 criteria of A - E apply:
    • A: fasting blood glucose > 6.1 mmol / l (110 mg / dl)
    • B: waist circumference in men > 102 cm and in women > 88 cm
    • C: Blood pressure ≥ 130 / 85 mmHg or arterial hypertension requiring therapy.
    • D: triglycerides ≥ 1.7 mmol / l (150 mg / dl)
    • E: HDL- cholesterol < 1.03 mmol / l (< 40 mg / dl) in men and 1.29 mmol / l (< 50 mg / dl) in women (Huang 2009)

• 3. IDF = International Diabetes Federation (2005)
  • A metabolic syndrome is present if B and ≥ 2 criteria of A, C, D, E apply:
    • A: fasting blood glucose > 6.1 mmol / l (110 mg / dl).
    • B: Waist circumference specific according to ethnicity (see "Diagnostics").
    • C: Blood pressure ≥ 130 / 85 mmHg or arterial hypertension requiring therapy.
    • D: Triglycerides ≥ 1.7 mmol / l (150 mg / dl)
    • E: HDL- cholesterol < 1.0 mmol / l (< 40 mg / dl) in men and 1.3 mmol / l (< 50 mg / dl) in women (Fritsche 2015).

• 4. harmonizing definition:

According to this definition, three of the following characteristics are found in the metabolic syndrome:

• Waist circumference increased (see "Diagnostics").
• Fasting triglyceride level > 150 mg / dl
• HDL- cholesterol < 40 mg / dl in men and < 50 mg / dl in women
• Blood pressure: > 130 mmHg systolic or > 85 mmHg diastolic
• Fasting plasma glucose level ≥ 100 mg / dl (Kasper 2015).

Due to the vagueness of the definition, the frequency of the metabolic syndrome is difficult to ascertain (Fritsche 2015).

Worldwide estimates assume that around 100 million people are affected (Roberts 2013).

Brown (2016) highlights that the prevalence of metabolic syndrome and insulin resistance is increasing, particularly in younger populations and developing countries. In particular, Indian-Asian men show a higher prevalence of metabolic syndrome - compared to the European population.

Kasper (2015) speaks of the highest prevalence in Native Americans worldwide, with nearly 60% of women aged 45-49 and 45% of men of the same age. In African-American men, for example, metabolic syndrome is less common, while it is more common in Mexican-American women (Kasper 2015).

The cause of metabolic syndrome is strongly dependent on lifestyle and environmental factors, but genetic aspects also play a role. Significant progress has recently been made here in identifying genetic loci (Brown 2016).

Predisposing factors for metabolic syndrome are:

• Physical inactivity:

Individuals who spend > 4 h a day sitting in front of the TV / computer etc. double the risk of developing metabolic syndrome compared to individuals who spend < 1 h doing so.

• Aging:

Of those > 50 years of age, nearly 50% of the population in the US is affected, and more women than men from age > 60 years.

(Kasper 2015)

• Insulin resistance
• oxidative stress
• Chronic low grade inflammation (Roberts 2013).
• Diabetes mellitus:

It is estimated that approximately 75% of type 2 diabetics and patients with impaired glucose tolerance have metabolic syndrome.

• Cardiovascular diseases:

Approximately 50% of patients with metabolic syndrome suffer from CHD, with a particularly high prevalence in women (Kasper 2015).

• Lipodystrophy:

This can be a congenital lipodystrophy, but also an acquired lipodystrophy. The acquired form is often found in HIV patients receiving antiretroviral therapy (Kasper 2015).

There is no generally accepted pathophysiology of the metabolic syndrome, although many articles exist about it (Fritsche 2015).

The most widely accepted hypothesis is that of insulin resistance. This is considered the primary pathophysiological mechanism for MetS.

Insulin resistance is caused by a defect in insulin action that has not yet been fully elucidated. With the onset of insulin resistance, postprandial hyperinsulinemia occurs, followed by fasting hyperinsulinemia and finally hyperglycemia (Kasper 2015).

Patients with arterial hypertension and associated increase in waist circumference should be searched for other biochemical abnormalities associated with metabolic syndrome. (Kasper 2015)

Diagnostic tests for the metabolic syndrome include:

• Determination of body weight
• Calculation of BMI
• Measurement of waist circumference (see below for details)
• Blood pressure measurement
• Laboratory determinations fasting:
  • HDL cholesterol
  • Triglycerides
  • Plasma glucose

Other examination (see below) are complementary but not mandatory (Fritsche 2015).

Physical examination:

Physical examination may reveal lipoatrophies or acanthosis nigricans (Kasper 2015).

Measurement of waist circumference:

However, it should be taken into account that the distribution of adipose tissue varies between visceral depot and subcutaneous fat for the same waist circumference and different norm variations exist for different geographical regions. Thus, depending on the population, there is a lower or higher risk for the same waist circumference (Kasper 2015).

-- Europe, Sub-Saharan Africa, East and Middle East:

Waist circumference males ≥ 94 cm, females ≥ 80 cm.

-- China, South Asian region, South and Central America:

Waist circumference males ≥ 90 cm, females ≥ 80 cm.

- Japan:

Waist circumference men ≥ 85 cm, women ≥ 90 cm (Kasper 2015).

• Sleep Study

Patients with V. a. a sleep apnea should be examined more closely in the sleep laboratory (Kasper 2015).

Sonography

This examination is to be carried out especially from the point of view of steatosis hepatis (Fritsche 2015).

• oral glucose tolerance test (OGTT) with determination of insulin and glucose
• Urinalysis:
  • Microalbuminuria
• Laboratory determinations fasting:
  • HDL cholesterol
  • Triglycerides
  • plasma glucose (Fritsche 2015)
• ApoB
• C- reactive protein (CRP)
• Fibrinogen
• Uric acid
• Liver function values
• In v. a. polycystic ovary syndrome:
  • follicle stimulating hormone (FSH)
  • luteinizing hormone (LH)
  • Testosterone

(Kasper 2015)

• Cardiovascular diseases
  • Apoplexy
  • Myocardial infarction
• non-alcoholic fatty liver disease (occurs in 25-60% of patients with metabolic syndrome)
• type 2 DM (develops in 62 % of men and 47 % of women)
• obstructive sleep apnea (found in 35% of patients [Herold 2021])
• Hyperuricemia
• Polycystic ovary syndrome:

This is associated with insulin resistance and metabolic syndrome in 50-80% of cases - the prevalence of the latter is between 40-50%.

(Kasper 2015)

• Venous thromboembolism (VTE):

In a study that included more than 150,000 thrombosis patients, the more metabolic syndrome criteria were present, the higher the recurrence rate. In the full-blown met

Obesity

Since obesity is the driving force in MetS, the primary therapeutic approach should be weight reduction. Weight reduction usually leads to an improvement in insulin sensitivity, which in turn is associated with many positive metabolic improvements.

The daily restriction of about 500 kcal leads to a weight reduction of about ½ kg per week. Low-carbohydrate diets initially lead to more rapid weight loss (Kasper 2015).

Physical activity

Almost as important is sufficient physical activity. For this, however, it should be ensured beforehand that increased physical activity is not associated with a risk, i.e. in some high-risk patients there is a need for a cardiovascular examination beforehand (Kasper 2015).

Obesity

For weight loss, there are 2 main drug groups: appetite suppressants and absorption inhibitors (Kasper 2015).

• Appetite suppressants

The appetite suppressants include, for example, sibutramine (trade name Reductil). On average, a weight reduction of 4.5 kg per year can be achieved with it (Biesalski 2010).

• Resorption inhibitors

These drugs inhibit the absorption of dietary fats in the gastrointestinal tract. Examples include orlistat (trade name Xenical). This can reduce fat absorption by up to 30% (Biesalski 2010).

LDL cholesterol

Patients should follow a rigorous diet low in saturated fat, trans fat and cholesterol. If this does not lower LDL cholesterol, therapy with statins such as atorvastatin or rosuvastatin is indicated.

Statins lower LDL cholesterol by about 15-60%, but each doubling of the statin dose only lowers it by about another 6%.

For patients with a 10-year risk of < 7.5%, statin therapy is not evidence-based (Kasper 2015).

Triglycerides

Fasting triglyceride levels should be < 150 mg / dl. From a weight reduction of > 10%, a reduction in triglycerides is possible. If weight loss alone does not lead to the target value, treatment with a fibrate such as gemfibrozil or fenofibrate is required (Kasper 2015).

Arterial hypertension

All patients with MetS plus arterial hypertension should be recommended dietary measures such as a low-sodium diet high in vegetables and fruits, low-fat dairy products, and whole grains.

In patients with metabolic syndrome without diabetes, ACE inhibitors or angiotensin II receptor blockers are the first-line therapy, as these two groups of drugs appear to reduce the likelihood of developing type 2 DM (Kasper 2015).

Otherwise, see therapy of arterial hypertension.

• Bariatric surgery

In patients with a metabolic syndrome who have a body mass index of > 40 kg / m² or of > 35 kg / m² plus comorbidities, the indication for bariatric surgery is given.

The best-known surgical procedures are the so-called gastric bypass or the vertical sleeve gastrectomy (so-called tubular stomach [Bischoff 2018]).

(Kasper 2015)

Gastric bypass:

In gastric bypass, a gastric pouch is formed and connected to a jejunum loop.The residual stomach, duodenum, and upper portion of the jejunum remain in situ (Plauth 2021).

Sleeve gastrectomy:

A sleeve gastrectomy is a partial gastrectomy in which large portions of the large curvature are removed. The remaining sleeve stomach has a capacity of only about 150 ml (Bischoff 2018).

The probability of dying from cardiovascular disease is twice as high for patients with metabolic syndrome as for patients without metabolic syndrome. The risk of myocardial infarction or apoplexy is even three times higher.

According to the "Framingham Offspring Study", an ischemic insult occurs in patients with metabolic syndrome in up to 19 %, in diabetics without metabolic syndrome in only 7 %. In women, the risk differed particularly: 27 % versus 5 % (Kasper 2015).

Compared to vertical sleeve gastrectomy, a survival advantage was found for gastric bypass (Kasper 2015).

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