Lipoatrophic diabetes in Familial Partial Lipodystrophy type 2: from insulin resistance to diabetes.

Guillaume Treiber; Alice Guilleux; Kevin Huynh; Oriane Bonfanti; Ania Flaus-Furmaniuk; David Couret; Natalie Mellet; Céline Bernard; Nathalie Le-Moullec; Berenice Doray; Isabelle Jéru; Jean-Christophe Maiza; Bhoopendrasing Domun; Muriel Cogne; Olivier Meilhac; Corinne Vigouroux; Peter J Meikle; Estelle Nobécourt
Abstract
Subjects with Familial Partial Lipodystrophy type 2 (FPLD2) are at high risk to develop diabetes. To better understand the natural history and variability of this disease, we studied glucose tolerance, insulin response to an oral glucose load, and metabolic markers in the largest cohort to date of subjects with FPLD2 due to the same LMNA variant.A total of 102 patients aged > 18 years, with FPLD2 due to the LMNA 'Reunionese' variant p.(Thr655Asnfs*49) and 22 unaffected adult relatives with normal glucose tolerance (NGT) were enrolled. Oral Glucose Tolerance Tests (OGTT) with calculation of derived insulin sensitivity and secretion markers, and measurements of HbA1c, C-reactive protein, leptin, adiponectin and lipid profile were performed.In patients with FPLD2: 65% had either diabetes (41%) or prediabetes (24%) despite their young age (median: 39.5 years IQR 29.0-50.8) and close-to-normal BMI (median: 25.5 kg/m IQR 23.1-29.4). Post-load OGTT values revealed insulin resistance and increased insulin secretion in patients with FPLD2 and NGT, whereas patients with diabetes were characterized by decreased insulin secretion. Impaired glucose tolerance with normal fasting glucose was present in 86% of patients with prediabetes. Adiponectin levels were decreased in all subjects with FPLD2 and correlated with insulin sensitivity markers.2OGTT reveals early alterations of glucose and insulin metabolism in patients with FPLD2, and should be systematically performed before excluding a diagnosis of prediabetes or diabetes to adapt medical care. Decreased adiponectin is an early marker of the disease. Adiponectin replacement therapy warrants further study in FPLD2.
Journal DIABETES & METABOLISM
ISSN 1878-1780
Published 15 Nov 2022
Volume
Issue
Pages 101409
DOI 10.1016/j.diabet.2022.101409
Type Journal Article
Sponsorship