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Due to the resemblance with Cushing's syndrome, we hypothesized a putative role of glucocorticoid in the pathogenesis of metabolic abnormalities in FPLD2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To evaluate the phenotypic heterogeneity and glucocorticoid sensitivity in FPLD2 patients exhibiting the p.R482W or p.R644C <jats:italic>LMNA<\/jats:italic> mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design, patients and measurements<\/jats:title><jats:p>Prospective study with FPLD2 patients (n\u00a0=\u00a024) and controls (n\u00a0=\u00a024), who underwent anthropometric, body composition, metabolic profile and adipokines\/cytokine plasma measurements. Plasma and salivary cortisol were measured in basal conditions and after 0.25, 0.5 and 1.0\u00a0mg of dexamethasone (DEX) given at 23:00\u00a0hours. Glucocorticoid receptor (<jats:italic>GR)<\/jats:italic> and <jats:italic>11\u03b2HSD<\/jats:italic> isoforms expression were assessed by qPCR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Familial partial lipodystrophy type 2 individuals presented increased waist and neck circumferences, decreased hip circumference, peripheral skinfold thickness and fat mass. Patients presented increased HOMA\u2010IR, triglycerides, TNF\u2010\u03b1, IL\u20101\u03b2, IL\u20106 and IL\u201010, and decreased adiponectin and leptin plasma levels. FPLD2 patients showed decreased ability to suppress the HPA axis compared with controls after 0.5\u00a0mg DEX. The phenotype was more pronounced in patients harbouring the p.R482W <jats:italic>LMNA<\/jats:italic> mutation. <jats:italic>GR\u03b2<\/jats:italic> overexpression in PBMC was observed in female patients compared with female controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Familial partial lipodystrophy type 2 patients exhibited anthropometric, clinical and biochemical phenotypic heterogeneity related to <jats:italic>LMNA<\/jats:italic> mutation sites and to gender. <jats:italic>LMNA<\/jats:italic> mutations affecting both lamin A and lamin C lead to more severe phenotype. FPLD2 patients also showed blunted HPA axis response to DEX, probably due to the association of increased levels of proinflammatory cytokines with <jats:italic>GR\u03b2<\/jats:italic> overexpression leading to a more severe phenotype in female.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.13984","type":"journal-article","created":{"date-parts":[[2019,4,6]],"date-time":"2019-04-06T21:11:24Z","timestamp":1554585084000},"page":"94-103","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Phenotypic diversity and glucocorticoid sensitivity in patients with familial partial lipodystrophy type 2"],"prefix":"10.1111","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2726-7605","authenticated-orcid":false,"given":"Ana Teresa Prata","family":"Resende","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Ribeirao Preto Medical School University of Sao Paulo Ribeirao Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3601-9470","authenticated-orcid":false,"given":"Clarissa Silva","family":"Martins","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Ribeirao Preto Medical School University of Sao Paulo Ribeirao Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Carolina","family":"Bueno","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Ribeirao Preto Medical School University of Sao Paulo Ribeirao Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayrton Cust\u00f3dio","family":"Moreira","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Ribeirao Preto Medical School University of Sao Paulo Ribeirao Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cristina","family":"Foss\u2010Freitas","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Ribeirao Preto Medical School University of Sao Paulo Ribeirao Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4932-4623","authenticated-orcid":false,"given":"Margaret","family":"de Castro","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Ribeirao Preto Medical School University of Sao Paulo Ribeirao Preto Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,4,15]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecl.2017.01.012"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ando.2012.04.010"},{"key":"e_1_2_8_4_1","first-page":"33","article-title":"Familial lipoatrophic diabetes with dominant transmission. 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