Characterisation of non-obese diabetic patients with marked insulin resistance identifies a novel familial partial lipodystrophy-associated PPARγ mutation (Y151C)

Aims/hypothesis Familial partial lipodystrophy (FPLD) is a rare metabolic disorder with clinical features that may not be readily recognised. As FPLD patients require a specific therapeutic approach, early identification is warranted. In the present study we aimed to identify cases of FPLD among non...

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Vydané v:	Diabetologia Ročník 54; číslo 7; s. 1639 - 1644
Hlavní autori:	Visser, M. E., Kropman, E., Kranendonk, M. E., Koppen, A., Hamers, N., Stroes, E. S., Kalkhoven, E., Monajemi, H.
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	Berlin/Heidelberg Springer-Verlag 01.07.2011 Springer
Predmet:	Adult Aged Biological and medical sciences Body mass Dermatology Diabetes Diabetes Mellitus, Type 2 - drug therapy Diabetes Mellitus, Type 2 - genetics Diabetes. Impaired glucose tolerance DNA Endocrine pancreas. Apud cells (diseases) Endocrinopathies Etiopathogenesis. Screening. Investigations. Target tissue resistance Evaluation Female Hormones Human Physiology Humans Insulin - administration & dosage Insulin - therapeutic use Insulin Resistance - genetics Insulin Resistance - physiology Internal Medicine Lipodystrophy, Familial Partial - diagnosis Lipodystrophy, Familial Partial - genetics Male Measurement Medical sciences Medicine Medicine & Public Health Metabolic Diseases Middle Aged Mutation Objectives Patients PPAR gamma - genetics Short Communication Skin involvement in other diseases. Miscellaneous. General aspects Y151C FPLD LMNA Insulin resistance Lipodystrophy Type 2 diabetes mellitus PPARγ BMI Endocrinopathy Type 2 diabetes Human Skin disease Metabolic diseases Target tissue resistance Adipose tissue disorders Mutation
ISSN:	0012-186X, 1432-0428, 1432-0428
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Shrnutí:	Aims/hypothesis Familial partial lipodystrophy (FPLD) is a rare metabolic disorder with clinical features that may not be readily recognised. As FPLD patients require a specific therapeutic approach, early identification is warranted. In the present study we aimed to identify cases of FPLD among non-obese patients with type 2 diabetes mellitus and marked insulin resistance. Methods We searched the databases of three diabetic outpatient clinics for patients with marked insulin resistance, arbitrarily defined as the use of ≥100 U insulin/day, and BMI ≤ 27 kg/m 2 . In all patients, metabolic variables and anthropomorphic measurements were evaluated and DNA was sequenced for mutations in the genes encoding lamin A/C (LMNA), peroxisome proliferator-activated receptor γ (PPARγ) and cell death-inducing DFFA-like effector c (CIDEC). Results Out of 5,221 diabetic individuals, 24 patients fulfilled all criteria. Twelve patients were willing to participate, of whom five showed clinical features of lipodystrophy. In three of these patients the clinical diagnosis of FPLD was confirmed by the presence of mutations in LMNA or PPARG ; one patient harboured a novel heterozygous mutation (Y151C) in PPARG . The Y151C mutant displayed impaired DNA-binding capacity and hence reduced transcriptional activity compared with wild-type PPARγ. Dominant-negative activity was absent. Conclusion/interpretation The combination of BMI ≤ 27 kg/m 2 and the use of >100 U insulin/day increases the chance of identifying lipodystrophy. Thus careful assessment of clinical features of FPLD should be considered in these patients, allowing earlier therapeutic interventions.
Bibliografia:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0012-186X 1432-0428 1432-0428
DOI:	10.1007/s00125-011-2142-4