TY - JOUR
T1 - Phenotypic Differences among Familial Partial Lipodystrophy Due to LMNA or PPARG Variants
AU - Vasandani, Chandna
AU - Li, Xilong
AU - Sekizkardes, Hilal
AU - Brown, Rebecca J.
AU - Garg, Abhimanyu
N1 - Publisher Copyright:
© 2022 The Author(s). Published by Oxford University Press on behalf of the Endocrine Society.
PY - 2022/12/1
Y1 - 2022/12/1
N2 - Context: Despite several reports of familial partial lipodystrophy (FPLD) type 2 (FPLD2) due to heterozygous LMNA variants and FPLD3 due to PPARG variants, the phenotypic differences among them remain unclear. Objective: To compare the body fat distribution, metabolic parameters, and prevalence of metabolic complications between FPLD3 and FPLD2. Methods: A retrospective, cross-sectional comparison of patients from 2 tertiary referral centers - UT Southwestern Medical Center and the National Institute of Diabetes and Digestive and Kidney Diseases. A total of 196 females and 59 males with FPLD2 (age 2-86 years) and 28 females and 4 males with FPLD3 (age 9-72 years) were included. The main outcome measures were skinfold thickness, regional body fat by dual-energy X-ray absorptiometry (DXA), metabolic variables, and prevalence of diabetes mellitus and hypertriglyceridemia. Results: Compared with subjects with FPLD2, subjects with FPLD3 had significantly increased prevalence of hypertriglyceridemia (66% vs 84%) and diabetes (44% vs 72%); and had higher median fasting serum triglycerides (208 vs 255mg/dL), and mean hemoglobin A1c (6.4% vs 7.5%). Compared with subjects with FPLD2, subjects with FPLD3 also had significantly higher mean upper limb fat (21% vs 27%) and lower limb fat (16% vs 21%) on DXA and increased median skinfold thickness at the anterior thigh (5.8 vs 11.3mm), calf (4 vs 6mm), triceps (5.5 vs 7.5mm), and biceps (4.3 vs 6.8mm). Conclusion: Compared with subjects with FPLD2, subjects with FPLD3 have milder lipodystrophy but develop more severe metabolic complications, suggesting that the remaining adipose tissue in subjects with FPLD3 may be dysfunctional or those with mild metabolic disease are underrecognized.
AB - Context: Despite several reports of familial partial lipodystrophy (FPLD) type 2 (FPLD2) due to heterozygous LMNA variants and FPLD3 due to PPARG variants, the phenotypic differences among them remain unclear. Objective: To compare the body fat distribution, metabolic parameters, and prevalence of metabolic complications between FPLD3 and FPLD2. Methods: A retrospective, cross-sectional comparison of patients from 2 tertiary referral centers - UT Southwestern Medical Center and the National Institute of Diabetes and Digestive and Kidney Diseases. A total of 196 females and 59 males with FPLD2 (age 2-86 years) and 28 females and 4 males with FPLD3 (age 9-72 years) were included. The main outcome measures were skinfold thickness, regional body fat by dual-energy X-ray absorptiometry (DXA), metabolic variables, and prevalence of diabetes mellitus and hypertriglyceridemia. Results: Compared with subjects with FPLD2, subjects with FPLD3 had significantly increased prevalence of hypertriglyceridemia (66% vs 84%) and diabetes (44% vs 72%); and had higher median fasting serum triglycerides (208 vs 255mg/dL), and mean hemoglobin A1c (6.4% vs 7.5%). Compared with subjects with FPLD2, subjects with FPLD3 also had significantly higher mean upper limb fat (21% vs 27%) and lower limb fat (16% vs 21%) on DXA and increased median skinfold thickness at the anterior thigh (5.8 vs 11.3mm), calf (4 vs 6mm), triceps (5.5 vs 7.5mm), and biceps (4.3 vs 6.8mm). Conclusion: Compared with subjects with FPLD2, subjects with FPLD3 have milder lipodystrophy but develop more severe metabolic complications, suggesting that the remaining adipose tissue in subjects with FPLD3 may be dysfunctional or those with mild metabolic disease are underrecognized.
KW - diabetes mellitus
KW - dual-energy X-ray absorptiometry
KW - familial partial lipodystrophy
KW - LMNA
KW - PPARG
KW - triglycerides
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U2 - 10.1210/jendso/bvac155
DO - 10.1210/jendso/bvac155
M3 - Article
C2 - 36397776
AN - SCOPUS:85144442707
SN - 2472-1972
VL - 6
JO - Journal of the Endocrine Society
JF - Journal of the Endocrine Society
IS - 12
M1 - bvac155
ER -