Cardiometabolic syndrome

Question 1

Define metabolic syndrome

Answer 1

• Compilation of risk factors that predispose individuals to developing type 2 diabetes and cardiovascular disease

Diagnosis occurs when any three of the following 5 risk factors are present:
- waist circumference: population specific definitions
- TGs: >= 1.7 mmol/L
- HDL: Men<1 mmol/L, women < 1.3 mmol/L
- Blood pressure: >= 130/85
- fasting glucose >= 5.5 mmol/L

• Drug treatment for elevated triglycerides, low HDL cholesterol, elevated blood pressure, or elevated glucose are alternate indicators

Question 2

Describe the prevalence of metabolic syndrome

Answer 2

• Varies depending on criteria used to define the MetS and the age, gender, ethnicity, and environment of the population being studied
• The National Health and Nutrition Examination Survey (NHANES) reported the overall prevalence of MetS in adults ≥20 years in the US from 2003-2012 was 33%
• 67% Australian adults are overweight or obese (AIHW 2017-18)

Question 3

Describe the pathophysiology of cardiometabolic syndrome

Answer 3

Target organ damage occurs through multiple mechanisms in metabolic syndrome. The individual diseases leading to metabolic syndrome produce adverse clinical consequences. For example, hypertension in metabolic syndrome causes left ventricular hypertrophy, progressive peripheral arterial disease, and renal dysfunction. [14] However, the cumulative risk for metabolic syndrome appears to cause microvascular dysfunction, which further amplifies insulin resistance and promotes hypertension. [15]

Metabolic syndrome promotes coronary heart disease through several mechanisms. It increases the thrombogenicity of circulating blood, in part by raising plasminogen activator type 1 and adipokine levels, and it causes endothelial dysfunction. [16] Metabolic syndrome may also increase cardiovascular risks by increasing arterial stiffness. [17] Additional mechanisms include oxidative stress, [18] which has been associated with numerous components of metabolic syndrome.

Etiology is unclear but includes the following:
- Insulin resistance
- Pancreatic beta-cell dysfunction
- Cellular dysfunction by protein kinases and phoshatases
- Suppression of insulin receptor substrate-1 and 2 (IRS1/IRS2) gene expression and function
- Obesity and lipid toxicity
- Oxidative stress and glucose toxicity
- Chronic inflammation
- Dysrupted circadian rhythm
- Genetics and epigenetics
- Gut microbial imbalance
- Dietary effects

Question 4

Discuss the association between metabolic syndrome and cardiovascular disease

Answer 4

Several risk factors for cardiovascular disease in patients with MetS and T2DM:
- pancreas: hyperinsulinaemia
- Genetic predisposition e.g. hyperglycaemia
- Hyperglycaemia: glycated protein and advanced glycation end-produts
- thrombosis
- liver: PAI-1, fibrinogen, CRP, TNF-a
- obesity: FFAs, decreased HDL, increased TGs, lipaemia
- skeletal muscle: increased ffas, hyperglycaemia - contributing to insulin resistance
- hypertension and LDL

Question 5

Discuss measures of obesity

Answer 5

• Thresholds based on Caucasian populations
  
  • BMI Classification
    
    • Underweight: BMI (kg/m2) <18.5
    • Normal range: ≥18.5 and <24.9
    • Overweight: ≥25 and <29.9
    • Obese
      
      • Obese class I: ≥30 and <34.9
      • Obese class II: ≥35 and <39.9
      • Obese class III: ≥40
  • Waist Circumference
    
    • Measured midway between the lower rib margin and iliac crest
    • Gender
      
      • Males
        
        • Increased disease risk: ≥ 94 cm
        • High disease risk: ≥ 102 cm
      • Females
        
        • Increased disease risk: ≥ 80 cm
        • High disease risk: ≥ 88 cm

Adjustments are needed for ethnic groups, patient groups (athletes,aged)

Question 6

What are some factors contributing to increasing diabetes prevalence?

Answer 6

• Evolution?
• Ageing and Energy Expenditure
• Activity is declining