MON-728 Proposal of Leptin Secretion Index (LSI) and Its Diagnostic Application for Lipodystrophy

Abstract Disclosure: K. Nakao: None. I. Yamauchi: None. T. Kusakabe: None. T. Tanaka: None. T. Kikuchi: None. Background and Aim: Leptin is an adipocyte-derived hormone, adipokine, discovered in 1994. In Japan, leptin replacement therapy has been used not only for generalized lipodystrophy (GL) but also partial lipodystrophy (PL) since 2013, and serum leptin measurement with ELISA was approved for diagnosis of GL in 2019. Thus, leptin is a representative adipokine for diagnosing and treating lipodystrophy syndromes. In the present study, we propose a novel leptin-related clinical parameter, leptin secretion index (LSI). Materials and Methods: We have established the Japanese adult serum leptin concentration standard (JALS) using significant correlations between BMI and serum leptin concentrations in Japanese adult men (n=549, r=0.73) and women (n=549, r=0.75) and are usable to speculate the corresponding serum leptin concentration from BMI in Japanese adults. LSI (%) is the measured serum leptin concentration divided by the JALS value of the same BMI. Lipodystrophy syndromes in the study consist of 14 GL (12 congenital and two acquired) and 10 PL (7 Köbberling type FPLD1, 2 Dunnigan type FPLD2, and one patient after hematopoietic stem cell transplantation). All patients had increased insulin resistance, hypertriglyceridemia, and steatohepatitis. The clinical diagnosis was performed doubly and independently by KN (senior author) and the respective home doctor according to the practice guideline for lipodystrophy syndromes of the Japan Endocrine Society (Endocrine J, 68:1027-1042, 2021). Serum leptin concentrations were measured with the highly sensitive leptin ELISA (Cosmic, Tokyo, Japan). Results: Serum leptin concentrations in GL were all under the lower limit of JALS values between 18.5 and 25 of normal BMI. BMIs in 7 out of 14 GL were underweight, more petite than 18.5, whereas BMIs of the remaining 7 GL were normal (18.5-25). These results are consistent with “absolute leptin deficiency” in GL. Eight of 10 PL patients showed values within the normal serum leptin concentrations of JALS. Five PLs with underweight and normal BMI ranged from 18.3 to 22.9. Meanwhile, the remaining 5 PL Japanese showed a BMI from 25.1 to 29.2, classified as grade 1 obesity (BMI: 25-30) by the Japan Society for the Study of Obesity, indicating the possible underdiagnosis of PL judging from BMI and serum leptin concentrations. LSI of the almost normal-BMI PL group(n=5) ranged from 5.8 % to 69.2 % (mean:37 %), and LSI of the grade 1 obese PL group(n=5) was from 25.5 % to 86.6 % (mean: 64 %), indicating that LSI of all PL are less than 100 %, that is, “relative leptin deficiency.”As for the Summary of BMI, it should be remembered that half of GL have normal BMI and that half of PL show grade 1 obesity in Japan. Conclusion: These results demonstrate that the measurement of serum leptin concentrations and the novel clinical parameter, LSI, are helpful for diagnosis and pathophysiological understanding of lipodystrophy syndromes. Presentation: Monday, July 14, 2025