Metabolic Syndrome

What is Metabolic Syndrome?

Coined in 1990s as "Syndrome X", now commonly known as metabolic syndrome. Insulin resistance is the hallmark feature of metabolic syndrome.  This is a condition that probably causes most chronic disease (diabetes, hypertension, cardiovascular disease, nonalcoholic fatty liver disease, PCOS, cancer, dementia). It is 75% of all healthcare dollars.  

See also section on how to interpret labs in the setting of abnormal metabolism. 

There are three types

1. Subcutaneous fat hypothesis (an  issue)

-eating too much food and overwhelm ability of the subcutaneous tissue to hold fat and the rest spills into visceral fat 

2. Visceral fat "stress" hypothesis (important)  

- stressed people have higher sympathetic nervous system activation which affects neuro PYY cofactor of norepinephrine along with some cortisol effects.  (depression,  shift workers, etc)  

3. Liver fat hypothesis (most important) 

-what you eat will is very important. see below

Are you overweight and healthy or are you overweight and unhealthy? 

Metabolic Syndrome is not obesity. Obese defined as BMI more than 30.  Incorrect dogma is that all obese persons are unhealthy and thin patients are healthy. 40% of normal weight patients AND 80% of obese patients are SICK. Sickness defined as having LIVER (intrabdominal) FAT DEPOSITS. High insulin causes tighter arteries, increase tissue growth (cancers), lowers glucose

Remember that insulin is the 'hibernation fat storage hormone' so high levels could given these symptoms: fatigue, moodiness, hunger, weight gain

Define Metabolic Syndrome mechanistically?

Dietary sugar and alcohol are the primary drivers of fatty liver. 

NORMAL-  (fig 1) Food is eaten, Insulin is released into the liver and stops the liver production of glucose into the blood AND converts sugar into triglycerides and sends into blood stream

ABNORMAL - (fig 2) Food is eaten, insulin released into the liver but there is inability to block glucose production from the liver AND yet still converts sugar into triglycerides into the blood stream.  Changes in blood: High Triglycerides, Low HDL, High blood sugar, Hypertension all due to excess insulin. 

Why does the abnormal metabolism occur? Probably due to ingestion of dietary fructose sugar and processed foods. 

Glucose and fructose are both monosaccharides. Glucose is so important that even if you do not consumes it you will make it  (from amino acids or from fatty acids via gluconeogenesis in the liver). Fructose is a storage form of energy in plants and humans have a limited capacity to metabolize it. Biochemically glucose is a 6 member ring and fructose is a 5 member ring. The linear forms of glucose and fructose cause bananas (and humans) to brown (age) via the amidori effect. Glucose causes this rate at a low reaction but fructose at a 7x higher rate and throws off reactive hydrogen peroxide and creates inflammatory response. Fructose does not stimulate ghrelin hormone unlike glucose which then does not tell your brain you have eaten. Also fructose is a stimulant of the brain dopamine pleasure center of the brain similar to cocaine. There are no biomarkers of fructose metabolism. But uric acid and ALT represent this issue.  

If your liver is glycogen depleted (tons of exercise) then ingesting fructose may be useful to replete glycogen rapidly but there is no clinical benefit. Sports drinks are unnecessary. 

What is Fatty Liver disease?

Fat accumulation in the liver causes selective insulin resistance which leads to very high insulin levels throughout your body which causes many bad effects. There is no difference between between the appearance of fatty liver due to alcohol consumption or due to fructose / processed food. 

There is a equilibrium of production of liver fat and clearance of the fat from the liver

Production:

1. Dietary fat intake (75%)

2. De Novo lipogenesis (25%)- creating fat from dietary sugar see fig 1. 

Clearance:

1. Fatty acid oxidation

2. Export of VLDL  (high triglycerides - see below) triglycerides (VLDL is same term as triglycerides) exported from the liver transfer fat to distant tissues and then leave a residual molecules such as large buoyant LDL and small dense LDL (see below).  This VLDL to all tissues and creates other fatty organs

How is  fatty liver diagnosed?

AST more than 25 is an indicator. 25 is lower than the "normal" range so see Dr. Jogi section on lab interpretation.  Also other causes of toxin-induced liver damage should be excluded. And a liver biopsy is required for final diagnosis. There are two sub-categories: NAFL (Non alcoholic fatty liver disease) and NASH (Non alcoholic steatohepatitis). NAFL is presence of excess fat and NASH is when inflammation is present. The reason "alcohol" is mentioned is historical because alcolohol was historically the most common cause of the fatty deposits but the most common cause is processed foods and excess carbohydrate intake.