Leptin Attenuates Cardiac Hypertrophy in Patients With Generalized Lipodystrophy.

Abstract

CONTEXT:

Lipodystrophy syndromes are rare disorders of deficient adipose tissue, low leptin, and severe metabolic disease, affecting all adipose depots (generalized lipodystrophy, GLD) or only some (partial lipodystrophy, PLD). Left ventricular (LV) hypertrophy is common (especially in GLD); mechanisms may include hyperglycemia, dyslipidemia, or hyperinsulinemia.

OBJECTIVE:

Determine effects of recombinant leptin (metreleptin) on cardiac structure and function in lipodystrophy.

METHODS:

Open-label treatment study of 38 subjects (18 GLD, 20 PLD) at the National Institutes of Health before and after 1 (N = 27), and 3 to 5 years (N = 23) of metreleptin. Outcomes were echocardiograms, blood pressure (BP), triglycerides, A1c, and homeostasis model assessment of insulin resistance.

RESULTS:

In GLD, metreleptin lowered triglycerides (median [interquartile range] 740 [403-1239], 138 [88-196], 211 [136-558] mg/dL at baseline, 1 year, 3-5 years, P < .0001), A1c (9.5 ± 3.0, 6.5 ± 1.6, 6.5 ± 1.9%, P < .001), and HOMA-IR (34.1 [15.2-43.5], 8.7 [2.4-16.0], 8.9 [2.1-16.4], P < .001). Only HOMA-IR improved in PLD (P < .01). Systolic BP decreased in GLD but not PLD. Metreleptin improved cardiac parameters in patients with GLD, including reduced posterior wall thickness (9.8 ± 1.7, 9.1 ± 1.3, 8.3 ± 1.7 mm, P < .01), and LV mass (140.7 ± 45.9, 128.7 ± 37.9, 110.9 ± 29.1 g, P < .01), and increased septal e' velocity (8.6 ± 1.7, 10.0 ± 2.1, 10.7 ± 2.4 cm/s, P < .01). Changes remained significant after adjustment for BP. In GLD, multivariate models suggested that reduced posterior wall thickness and LV mass index correlated with reduced triglycerides and increased septal e' velocity correlated with reduced A1c. No changes in echocardiographic parameters were seen in PLD.

CONCLUSION:

Metreleptin attenuated cardiac hypertrophy and improved septal e' velocity in GLD, which may be mediated by reduced lipotoxicity and glucose toxicity. The applicability of these findings to leptin-sufficient populations remains to be determined.

• Authors: My-Le Nguyen, Vandana Sachdev, Thomas R Burklow, Wen Li, Megan Startzell, Sungyoung Auh, Rebecca J Brown
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 106 Issue 11 Pg. e4327-e4339 (10 21 2021) ISSN: 1945-7197 [Electronic] United States
• PMID: 34223895 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)
• Copyright: Published by Oxford University Press on behalf of the Endocrine Society 2021.

Chemical References

• Glycated Hemoglobin A
• Leptin
• Triglycerides
• metreleptin

Topics

• Adolescent
• Adult
• Blood Pressure
• Cardiomegaly (etiology, prevention & control)
• Echocardiography
• Female
• Glycated Hemoglobin (analysis)
• Humans
• Hypertrophy, Left Ventricular (pathology, physiopathology, prevention & control)
• Insulin Resistance
• Leptin (analogs & derivatives, therapeutic use)
• Lipodystrophy (complications, drug therapy, pathology)
• Lipodystrophy, Congenital Generalized (complications, diet therapy)
• Male
• Middle Aged
• National Institutes of Health (U.S.)
• Prospective Studies
• Triglycerides (blood)
• United States
• Ventricular Septum (pathology, physiopathology)
• Young Adult