Lipid regulation in lipodystrophy versus the obesity-associated metabolic syndrome: the dissociation of HDL-C and triglycerides.

Abstract

CONTEXT:

There is an inverse relationship between triglycerides and high-density lipoprotein cholesterol (HDL-C) in insulin resistance, such that improvement in insulin resistance decreases triglycerides and increases HDL-C. Patients with lipodystrophy have extreme insulin resistance with high triglycerides and low HDL-C. Leptin replacement in lipodystrophy leads to a marked decrease in triglycerides (∼60%).

OBJECTIVE:

Our objective was to study the effects of metreleptin on triglycerides and HDL-C in lipodystrophy in contrast to changes in triglycerides and HDL-C in interventions for the obesity-associated metabolic syndrome.

DESIGN, SETTING, AND PATIENTS:

This open-label nonrandomized study at the National Institutes of Health included 82 patients with various forms of lipodystrophy.

INTERVENTION:

Metreleptin (0.06-0.24 mg/kg/d) was administered for 24 months in lipodystrophy.

MAIN OUTCOME MEASURES:

Serum triglycerides and HDL-C were measured.

RESULTS:

At baseline, lipodystrophy patients had low HDL-C (30 ± 1 mg/dL) and high triglycerides (961 ± 220 mg/dL) with an inverse relationship between the two (R = -0.37, P = .0006). There was no change in HDL-C with metreleptin despite major improvement in triglycerides, and individual changes in triglycerides only weakly predicted HDL-C change. On linear regression, in obesity, a decrease of 0.1 mg/dL in log(triglycerides) was associated with a 4.2 mg/dL rise in HDL-C, whereas in lipodystrophy, a decrease of 0.1 mg/dL in log(triglycerides) was associated with only a 0.6 mg/dL rise in HDL-C.

CONCLUSIONS:

The normal reciprocal relationship between triglyceride and HDL-C change seen in response to interventions for the obesity-associated metabolic syndrome is quantitatively different from that seen in lipodystrophy in response to metreleptin. Further work is needed to understand HDL-C regulation in this condition.

• Authors: Jalaja Joseph, Robert D Shamburek, Elaine K Cochran, Phillip Gorden, Rebecca J Brown
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 99 Issue 9 Pg. E1676-80 (Sep 2014) ISSN: 1945-7197 [Electronic] United States
• PMID: 24926953 (Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Intramural)

Chemical References

• Cholesterol, HDL
• Leptin
• Triglycerides
• metreleptin

Topics

• Adolescent
• Adult
• Child
• Cholesterol, HDL (blood)
• Female
• Humans
• Insulin Resistance (physiology)
• Leptin (administration & dosage, analogs & derivatives)
• Lipid Metabolism (drug effects, physiology)
• Lipodystrophy (drug therapy, metabolism, pathology)
• Male
• Metabolic Syndrome (drug therapy, metabolism, pathology)
• Middle Aged
• Obesity (drug therapy, metabolism, pathology)
• Treatment Outcome
• Triglycerides (blood)
• Young Adult