Metabolic Syndrome: Causes

Pathogenesis (disease development)

The central feature of metabolic syndrome is insulin resistance (decreased response of cells of the human body to the hormone insulin; this primarily affects skeletal muscle, liver, and adipose tissue) or hyperinsulinemia (excessive concentration of insulin in the blood). Genetic factors are probably mainly responsible for insulin resistance. In terms of pathophysiological changes, insulin resistance is central to both glucose and lipid metabolism (carbohydrate and fat metabolism) disorders. Insulin resistance can also explain, at least theoretically, the development of hypertension (high blood pressure) via regulatory circuits of the sympathetic nervous system. Experimentally, insulin has been shown to increase sympathetic activity, thereby stimulating renal (kidney-related) sodium reabsorption (reuptake of sodium) and thus having a direct proliferative effect on the smooth muscle cells of the vessel wall and possibly contributing to the development of hypertension.The major pacemaker for the clinical manifestation of the metabolic syndrome is obesity, and thus the individual components often become clinically manifest during periods of weight gain. A high-fat, hypercaloric diet can also induce or exacerbate insulin resistance and worsen all parameters of glucose and lipid metabolism. A lowering of HDL and an altered composition of LDL cholesterol into small and dense – thus particularly atherogenic (atherosclerosis-promoting) – particles result from the increased triglyceride and fatty acid turnover that occurs with a hypercaloric and high-fat diet.High free fatty acid concentrations inhibit hepatic insulin uptake and inactivation, thus leading to peripheral hyperinsulinemia. The high supply of these fatty acids simultaneously causes increased endogenous (“internally generated”) synthesis of triglyceride-rich lipoproteins and – indirectly – increased gluconeogenesis (new sugar formation) in the liver. This process is additionally promoted via an oversupply of adipose tissue-derived glycerol and lactate. Insulin-dependent glucose utilization in the muscles is impaired by high free fatty acid levels through various mechanisms that are associated with a deterioration in glucose tolerance. Furthermore, chronic inflammation (subclinical inflammation) plays an essential role in the pathophysiology.The combination of hypertension (high blood pressure), diabetes mellitus type 2 or glucose tolerance disorder (impaired sugar utilization), dyslipidemia (lipid metabolism disorder), and obesity (overweight) leads to a very high risk of atherosclerosis (risk of arterial calcification), because these factors/diseases especially promote plaque formation (deposits) in the vessels.

Etiology (Causes)

Biographic Causes

  • Genetic burden from parents, grandparents.
  • Age – prevalence (disease incidence) increases with age; today, metabolic syndrome occurs earlier and earlier, especially due to obesity in children and adolescents

Behavioral causes

  • Nutrition
    • Chronic overeating
      • High caloric intake ↑↑ [due toobesity, hypertension (high blood pressure), type 2 diabetes mellitus, hypercholesterolemia (LDL elevation)]
      • High proportion of saturated fatty acids (↑) [due toobesity, hypertension, diabetes mellitus type 2, hypercholesterolemia (LDL elevation)]
      • High proportion of monounsaturated fatty acids (↑) [due toobesity]
      • High proportion of polyunsaturated fatty acids ? [due toobesity ?]
      • High sugar consumption, esp. mono- and disaccharides (simple and multiple sugars) [due toobesity, hypertension, diabetes mellitus type 2].
      • High consumption of table salt ? [due toobesity?, hypertension]
      • High alcohol intake (↑) [due toobesity?]
    • Too low a proportion of monounsaturated fatty acids [diabetes mellitus type 2, hypercholesterolemia (LDL elevation)].
    • Too low a proportion of polyunsaturated fatty acids [diabetes mellitus type 2, hypercholesterolemia (LDL elevation)]
    • Low proportion of complex carbohydrates [due toobesity, diabetes mellitus type 2]
    • Low fiber diet [due toobesity, hypertension, diabetes mellitus type 2, hypercholesterolemia (LDL elevation)]
    • High intake of sodium and table salt [due tohypertension]
    • Micronutrient deficiency (vital substances) – see Prevention with micronutrients.
  • Pleasure food consumption
    • Alcohol (woman: > 20 g/day; man: > 30 g/day).
    • Tobacco (smoking)
  • Physical activity
    • Physical inactivity or lack of exercise
  • Psycho-social situation
    • Psychological conflicts
    • Stress
  • Overweight (BMI ≥ 25; obesity).
  • Android body fat distribution, that is, abdominal/visceral, truncal, central body fat (apple type) – there is a high waist circumference or waist-to-hip ratio (THQ; waist-to-hip ratio (WHR)). When measuring waist circumference according to the International Diabetes Federation guideline (IDF, 2005), the following standard values apply:
    • Men < 94 cm
    • Women < 80 cm

    The German Obesity Society published somewhat more moderate figures for waist circumference in 2006: < 102 cm for men and < 88 cm for women.

Disease-related causes

  • Cholestasis (bile stasis) – mainly caused by gallstones.
  • Dyslipidemia (fat metabolism disorder)
  • Glucose tolerance disorders to diabetes mellitus (diabetes).
  • Hypothyroidism (hypothyroidism)
  • Liver disease
  • Kidney diseases

Laboratory diagnoses – laboratory parameters that are considered independent risk factors.

  • Age-related hyperleptinemia – hormone that can inhibit hunger sensations; can develop into leptin resistance.
  • Fasting insulin ↑
  • Fasting glucose (fasting blood glucose) ↑
  • SHBG (sex hormone-binding globulin) ↓ – decreased in women with clinical or biochemical androgen excess, respectively, who, in association with oligoamenorrhea or anovulation, respectively, with or without polycystic ovaries, have a “hyperandrogenic syndrome” as defined by the Androgen Excess Society, i.e., polycystic ovary syndrome (PCOS).

Medications (Subsequent medications increase appetite or decrease energy expenditure – increased body weight is the result).