TY - JOUR
T1 - Lipoatrophic diabetes in familial partial lipodystrophy type 2
T2 - From insulin resistance to diabetes
AU - Treiber, Guillaume
AU - Guilleux, Alice
AU - Huynh, Kevin
AU - Bonfanti, Oriane
AU - Flaus–Furmaniuk, Ania
AU - Couret, David
AU - Mellet, Natalie
AU - Bernard, Céline
AU - Le-Moullec, Nathalie
AU - Doray, Berenice
AU - Jéru, Isabelle
AU - Maiza, Jean Christophe
AU - Domun, Bhoopendrasing
AU - Cogne, Muriel
AU - Meilhac, Olivier
AU - Vigouroux, Corinne
AU - Meikle, Peter J.
AU - Nobécourt, Estelle
N1 - Funding Information:
This project was co-financed by the European Union and the Reunion Island Regional Council. This work was also supported by the Reunion Island Hospital Research Institute under an internal call for tenders.
Publisher Copyright:
© 2022 Elsevier Masson SAS
PY - 2023/3
Y1 - 2023/3
N2 - Aim: 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. Methods: 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. Results: 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/m2 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. Conclusions: OGTT 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.
AB - Aim: 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. Methods: 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. Results: 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/m2 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. Conclusions: OGTT 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.
KW - Diabetes
KW - Dunnigan
KW - Insulin resistance
KW - Laminopathy
KW - Lipodystrophy
UR - http://www.scopus.com/inward/record.url?scp=85144490538&partnerID=8YFLogxK
U2 - 10.1016/j.diabet.2022.101409
DO - 10.1016/j.diabet.2022.101409
M3 - Article
C2 - 36400409
AN - SCOPUS:85144490538
SN - 1262-3636
VL - 49
JO - Diabetes and Metabolism
JF - Diabetes and Metabolism
IS - 2
M1 - 101409
ER -
