The Enigma of Low Levels of High Density Lipoprotein in Lipodystrophy

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 723-745-Lipids: Fatty Liver Disease & Lipodystrophies
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-733
Jalaja Joseph*1, Robert D Shamburek2, Elaine Cochran3, Phillip Gorden1 and Rebecca J Brown*4
1National Institutes of Health, Bethesda, MD, 2NIH, Bethesda, MD, 3NIDDK, National Institutes of Health, Bethesda, MD, 4National Institutes of Health, Rockville, MD
Background:  In insulin resistant states there appears to be an inverse relationship between triglycerides (TG) and high density lipoproteins (HDL). Interventions, such as weight loss, that improve insulin resistance lead to a decrease in TG and increase in HDL. Patients with lipodystrophy (LD) have extreme insulin resistance with high TG and low HDL. Leptin replacement in LD leads to improved insulin sensitivity and a marked decrease in TG (~60%). We sought to determine the effect of leptin on HDL.

Methods:  We examined the effects of leptin on HDL and TG in patients enrolled in an ongoing, open-label, prospective trial of recombinant leptin treatment in LD.  Due to variable duration of follow-up, lipids prior to the initiation of leptin were compared to lipids at the time of lowest TG to assess the maximal effect of leptin. To contrast lipids in LD to the common, obesity-associated metabolic syndrome, we extracted data from four major clinical trials in which a weight loss intervention was performed.  Due to the highly skewed distribution of TG in LD patients, change in TG and HDL before and after intervention was expressed as % change for this analysis.

Results:  68 LD patients had TG and HDL levels available before and after leptin treatment, of which 58 were women. The mean duration of leptin treatment at the time of lowest TG was 18 months.  Patient age ranged from 2 to 68 years. 12 patients had acquired generalized LD, 31 had congenital generalized LD, 5 had acquired partial LD and 20 had familial partial LD.  At baseline, the mean HDL in women was 29.7 mg/dL and in men was 36.4. In large clinical trials in the obesity-associated metabolic syndrome, every 1% decrease in triglycerides from a weight-loss intervention was associated with a 0.5% increase in HDL (P=0.0006, linear regression). However, in patients with LD, a 1% decrease in triglyceride was associated with only a 0.1% increase in HDL, and this relationship was not statistically significant (P=0.12).

Conclusion:  The relationship between TG and HDL change in response to interventions that change insulin resistance is different in LD patients compared to patients with metabolic syndrome, with a 5-fold difference in HDL change for the same TG change. The most obvious physiologic difference between these two groups is the paucity of fat in LD, versus excess fat in patients with the metabolic syndrome. We therefore hypothesize that adipocytes may be involved in HDL regulation in an unknown manner.

Disclosure: PG: Employee, Amylin Pharmaceuticals. Nothing to Disclose: JJ, RDS, EC, RJB

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