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Insulin sensitivity in familial hypercholesterolemia

A Q Galvan1, D Santoro, A Natali

  • 1Metabolism Unit, University of Pisa, Italy.

Metabolism: Clinical and Experimental
|October 1, 1993
PubMed
Summary
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High LDL cholesterol does not impair insulin sensitivity. This study found that individuals with familial hypercholesterolemia (FHC) exhibited normal insulin sensitivity, similar to control groups, indicating isolated high LDL cholesterol doesn't affect glucose metabolism.

Area of Science:

  • Endocrinology
  • Metabolic Syndrome
  • Cardiovascular Disease Risk Factors

Background:

  • Insulin resistance is linked to obesity, diabetes, and hypertension, all risk factors for cardiovascular disease.
  • Hyperinsulinemia is associated with certain lipid disorders and typically presents with high triglycerides and low HDL cholesterol.
  • The effect of isolated high LDL cholesterol on insulin sensitivity is not well understood.

Purpose of the Study:

  • To investigate whether isolated high low-density lipoprotein (LDL) cholesterol levels affect insulin sensitivity.
  • To compare insulin sensitivity in subjects with heterozygous familial hypercholesterolemia (FHC) to normocholesterolemic controls.

Main Methods:

  • Studied 13 FHC subjects and 15 normocholesterolemic controls, ensuring controls were free of other insulin resistance causes.

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  • All subjects had normal weight, glucose tolerance, blood pressure, and triglyceride/HDL levels, differing only in LDL cholesterol.
  • Utilized a 2-hour euglycemic-hyperinsulinemic clamp to assess whole-body glucose disposal and metabolic responses.

    • Main Results:

    • FHC and control groups showed comparable fasting glucose, insulin, FFA, and potassium levels.
    • Whole-body glucose disposal rates during the clamp were virtually identical between FHC (30.4 ± 2.3) and control (31.1 ± 3.0) subjects.
    • The metabolic response to hyperinsulinemia, including carbohydrate/lipid oxidation and FFA suppression, was equivalent in both groups.

    Conclusions:

    • Isolated high LDL cholesterol, as seen in heterozygous familial hypercholesterolemia, does not impair insulin sensitivity.
    • These findings suggest that high LDL cholesterol alone does not contribute to the insulin resistance often associated with other metabolic risk factors.