In this series, we will be addressing many of the signs and symptoms of Insulin Resistance. If you have a specific question or comment on this topic, please email me at: DrPaulBerez@syndromexassoc.org. 

 

INSULIN RESISTANCE and  LIPIDS

 

Insulin resistance causes hyperlipidemia by 3 mechanisms. The initial mechanism is caused by elevated insulin levels with elevated glucose levels (such as in impaired glucose tolerance). These elevated levels turn on the SREBP family of lipid synthesis regulators, which increase productions of cholesterol, triglycerides, HDL and LDL ⁽¹⁾ – this pattern is seen in early insulin resistance disease. 

The second mechanism is that insulin resistance increases activity of cholesterol ester transfer protein (CETP), which transfers triglycerides from VLSL particles to LDL and HDL particles, and hepatic lipase and lipoprotein lipase (HL, LL) which cause HDL and LDL to “shrink down” ⁽²⁾, which causes HDL to decrease, since small HDL particles are eliminated by the kidneys. 

Finally, as insulin resistance becomes more severe, insulin's action of fat cells, especially viceral fat cells, is impaired – insulin holds fat in fat cells ⁽³⁾.  When this impairment occurs, it leads to high levels of free fatty acids especially in the visceral portal giving the “full blown” phenotype of very high cholesterol, very high triglycerides, low HDL, variable LDL (calculated) and very high Apo B, which represents LDL particles.

 

References:

⁽¹⁾      Stinson, J. 35 al DIABETIC MED 10: 412-419, 1993

⁽²⁾      Riemans, S. SCAN J CLIN LAB INVEST 61: 1-10, 2001

⁽³⁾     Kwiterovich, P. AM J CARDIOL 90 (sUPPL): 30I-47I, 2002