Thiazolidinedione Response in Familial Lipodystrophy Patients with LMNA Mutations: A Case Series

A. Luedtke; M. Boschmann; C. Colpe; S. Engeli; F. Adams; A. L. Birkenfeld; S. Haufe; G. Rahn; F. C. Luft; H. H.-J. Schmidt; J. Jordan

doi:10.1055/s-0031-1301284

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2012; 44(04): 306-311
DOI: 10.1055/s-0031-1301284

Humans, Clinical

Thiazolidinedione Response in Familial Lipodystrophy Patients with LMNA Mutations: A Case Series

A. Luedtke^*

¹Departments of Medicine and Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, USA

,

M. Boschmann^*

²Franz-Volhard Clinical Research Center at the Experimental & Clinical Research Center, University Hospital Charité Campus Buch, Berlin, Germany

,

C. Colpe

³Institute of Clinical Pharmacology, Hannover Medical School, Hannover, Germany

,

S. Engeli

³Institute of Clinical Pharmacology, Hannover Medical School, Hannover, Germany

,

F. Adams

²Franz-Volhard Clinical Research Center at the Experimental & Clinical Research Center, University Hospital Charité Campus Buch, Berlin, Germany

,

A. L. Birkenfeld

⁴Department of Endocrinology, Diabetes and Nutrition, Charité University Medical School, Berlin, Germany, and German Institute of Human Nutrition, Potsdam-Rehbrücke, Germany

,

S. Haufe

³Institute of Clinical Pharmacology, Hannover Medical School, Hannover, Germany

,

G. Rahn

²Franz-Volhard Clinical Research Center at the Experimental & Clinical Research Center, University Hospital Charité Campus Buch, Berlin, Germany

,

F. C. Luft

²Franz-Volhard Clinical Research Center at the Experimental & Clinical Research Center, University Hospital Charité Campus Buch, Berlin, Germany

,

H. H.-J. Schmidt

⁵Clinic for Transplant Medicine, Westfälische Wilhelms-Universität Münster, Münster, Germany

,

J. Jordan

³Institute of Clinical Pharmacology, Hannover Medical School, Hannover, Germany

› Author Affiliations

Abstract

Type 2 familial partial lipodystrophy (FPLD2) patients show impaired glucose and lipid metabolism resulting from lipodystrophic ‘lipid pressure’ and an intrinsic defect in skeletal muscle metabolism. Since mutated lamin A may interfere with peroxisome proliferator activator gamma (PPARγ) expression, we hypothesized that PPARγ stimulation improves fat distribution and metabolic abnormalities in these patients. 5 nondiabetic FPLD2 patients were treated with rosiglitazone over 12 months. We assessed body composition, body fat distribution, and skinfold thickness/subcutaneous tissue thickness. We also determined venous glucose, insulin, and free fatty acid (FFA) concentrations, and respiratory quotient (RQ) before and during oral glucose tolerance testing. Adipose tissue and muscle fasting and postprandial metabolism were studied by microdialysis. Within 12 months treatment, hip circumference increased from 93.6±2.78 cm to 96.2±2.3 cm (p<0.05). Rosiglitazone reduced fasting glucose levels and liver transaminases. Baseline and postprandial FFA concentrations were significantly lower after 12 months treatment. RQ and muscle interstitial pyruvate and lactate did not respond to treatment. We conclude that PPARγ stimulation with rosiglitazone modestly improves glucose metabolism in FPLD2 patients presumably through proximal adipose tissue expansion. The intrinsic muscular metabolic defect does not respond to rosiglitazone.

Key words

laminopathies - adipose tissue - muscle - microdialysis - calorimetry

Full Text

References

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