Association between serum leptin concentrations and homeostasis model assessment-insulin resistance of 2.5 and higher in normal weight Japanese women

Scientific Reports · 10 authors, 10 centres

AI SUMMARY

FIDELITY 100%

POPULATION251 normal-weight (BMI 18.5–24.9 kg/m²) young Japanese women (mean age 20.6 years, mean BMI 20.6 kg/m²)

INTERVENTIONNone (cross-sectional observational study)

COMPARISONWomen with HOMA-IR < 1.6 (insulin sensitive) vs. HOMA-IR 1.6–2.4 (borderline) vs. HOMA-IR ≥ 2.5 (insulin resistant)

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AGENT 01 · STRUCTURED SUMMARY

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TL;DR

In normal-weight young Japanese women, insulin resistance (HOMA-IR ≥ 2.5) is associated with higher serum leptin and fat-mass-adjusted leptin levels, independent of body fat mass. These women also show elevated free fatty acids, triglycerides, and remnant-like particle cholesterol, indicating early metabolic disturbances despite normal BMI. Serum leptin emerged as an independent determinant of insulin resistance in this population, suggesting that leptin may be a marker for identifying at-risk normal-weight individuals.

Full summary

3,251 CHARS

**Background:** Type 2 diabetes is prevalent in normal-weight and underweight individuals in Asian populations, yet the characteristics of normal-weight insulin resistance are not well understood. This study aimed to characterize the normal-weight insulin-resistant phenotype in young Japanese women, focusing on adipocytokines and metabolic profiles.

**Methods:** The authors reanalyzed cross-sectional data from 251 normal-weight (BMI 18.5–24.9 kg/m²) female university students (mean age 20.6 years, mean BMI 20.6 kg/m²) from a previous study. Participants underwent fasting blood sampling, anthropometric measurements, and whole-body dual-energy X-ray absorptiometry (DXA) for body composition. A 75 g oral glucose tolerance test (OGTT) was performed in 99 women. HOMA-IR was calculated, with <1.6 defined as insulin sensitive (IS), 1.6–2.4 as borderline, and ≥2.5 as insulin resistant (IR). Serum leptin, adiponectin, lipids, and other metabolic markers were measured. Dietary intake was assessed via a validated questionnaire. Statistical analyses included ANOVA with Bonferroni correction, Pearson correlations, and stepwise multivariate logistic regression.

**Key Results:** Among 251 women, 194 (77.3%) were IS, 41 (16.3%) borderline, and 16 (6.4%) IR. Despite no significant differences in BMI, waist circumference, percent body fat, trunk-to-leg fat ratio, or fat mass index (FMI) across groups, serum leptin was significantly higher in borderline (10.1 ± 4.3 ng/mL) and IR (11.4 ± 5.0 ng/mL) compared to IS (8.1 ± 3.2 ng/mL) (p < 0.05). Fat-mass-adjusted leptin was also higher in borderline (0.65 ± 0.18 ng/mL/kg) and IR (0.73 ± 0.24 ng/mL/kg) vs. IS (0.56 ± 0.17 ng/mL/kg) (p < 0.05). The leptin-to-adiponectin ratio (LAR) was higher in borderline (1.12 ± 0.89) and tended to be higher in IR (1.19 ± 0.79) vs. IS (0.82 ± 0.53) (p = 0.07 for IR). Resting pulse rate was significantly higher in borderline (71 ± 11 bpm) and IR (70 ± 11 bpm) compared to IS (63 ± 8 bpm) (p < 0.05). Prevalence of macrosomia (birthweight >4000 g) was higher in IR (22.2%) vs. IS (2.8%) (p = 0.016). Fasting glucose, insulin, HOMA-β, free fatty acids (FFA), triglycerides, and remnant-like particle (RLP) cholesterol increased stepwise from IS to IR. FFA was 38% higher in IR (0.73 ± 0.34 mEq/L) vs. IS (0.53 ± 0.21 mEq/L) (p < 0.05). In multivariate logistic regression including triglycerides, RLP cholesterol, FFA, leptin, and pulse rate, serum leptin emerged as the sole independent determinant of IR (odds ratio: 1.68, 95% CI: 1.08–2.63, p = 0.02).

**Clinical Implications:** This study identifies a normal-weight insulin-resistant phenotype in young Japanese women characterized by elevated leptin and leptin-to-fat-mass ratio, increased FFA, triglycerides, and RLP cholesterol, and higher resting pulse rate, despite minimal abdominal or hepatic fat accumulation. Serum leptin may serve as a marker for early metabolic risk in normal-weight individuals. These findings highlight the need for prospective studies to determine whether this phenotype predicts progression to type 2 diabetes or cardiovascular disease. Limitations include the cross-sectional design, small sample size, and restriction to young Japanese women, limiting generalizability.

PICO

PPOPULATION

251 normal-weight (BMI 18.5–24.9 kg/m²) young Japanese women (mean age 20.6 years, mean BMI 20.6 kg/m²)

IINTERVENTION

None (cross-sectional observational study)

OOUTCOME

Serum leptin, fat-mass-adjusted leptin, leptin-to-adiponectin ratio, free fatty acids, triglycerides, remnant-like particle cholesterol, resting pulse rate, and other metabolic parameters

STUDY TYPE

cross-sectional

SPECIALTY

endocrinology

SUMMARISED BY

AI pipeline

FIDELITY CHECK

100% · A

ORIGINAL PAPER

PMC10203141

Association between serum leptin concentrations and homeostasis model assessment-insulin resistance of 2.5 and higher in normal weight Japanese women

Scientific Reports

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ABSTRACT

Abstract Normal weight insulin resistant phenotype was characterized in 251 Japanese female university students using homeostasis model assessment-insulin resistance. Birth weight, body composition at age 20, cardiometabolic traits and dietary intake were compared cross-sectionally between insulin sensitive (< 1.6, n = 194) and insulin resistant (2.5 and higher, n = 16) women. BMI averaged < 21 kg/m 2 and waist < 72 cm and did not differ between two groups. The percentage of macrosomia and serum absolute and fat-mass corrected leptin concentrations were higher in insulin resistant women although there was no difference in birth weight, fat mass index, trunk/leg fat ratio and serum adiponectin. In addition, resting pulse rate, serum concentrations of free fatty acids, triglycerides and remnant-like particle cholesterol were higher in insulin resistant women although HDL cholesterol and blood pressure did not differ. In multivariate logistic regression analyses, serum leptin (odds ratio:1.68, 95% confidential interval:1.08–2.63, p = 0.02) was associated with normal weight insulin resistance independently of macrosomia, free fatty acids, triglycerides, remnant-like particle cholesterol and resting pulse rate. In conclusion, normal weight IR phenotype may be associated with increased plasma leptin concentrations and leptin to fat mass ratio in young Japanese women, suggesting higher leptin production by body fat unit. Subject terms: Endocrinology, Medical research, Risk factors

CITATION EXPORT

Satomi Minato-Inokawa, Yuuna Hayashida, Mari Honda et al.. Association between serum leptin concentrations and homeostasis model assessment-insulin resistance of 2.5 and higher in normal weight Japanese women. Scientific Reports. (2023). https://doi.org/10.1038/s41598-023-35490-0

AUTHORS

10 · 10 CENTRES

Satomi Minato-Inokawa, Yuuna Hayashida, Mari Honda, Ayaka Tsuboi-Kaji, Mika Takeuchi, Kaori Kitaoka, Miki Kurata, Bin Wu, Tsutomu Kazumi, Keisuke Fukuo

1Research Institute for Nutrition Sciences, Mukogawa Women’s University, 6-46, Ikebiraki-cho, Nishinomiya, Hyogo 663-8558 Japan
2Laboratory of Community Health and Nutrition, Department of Bioscience, Graduate School of Agriculture, Ehime University, Matsuyama, Ehime Japan
3Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan
4Department of Food Sciences and Nutrition, Mukogawa Women’s University, Nishinomiya, Hyogo Japan
5Open Research Center for Studying of Lifestyle-Related Diseases, Mukogawa Women’s University, Nishinomiya, Hyogo Japan
6Department of Health, Sports, and Nutrition, Faculty of Health and Welfare, Kobe Women’s University, Kobe, Hyogo Japan
7Department of Nutrition, Osaka City Juso Hospital, Osaka, Japan
8Department of Advanced Epidemiology, Noncommunicable Disease (NCD) Epidemiology Research Center, Shiga University of Medical Science, Otsu, Shiga Japan
9Department of Endocrinology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan China
10Department of Medicine, Kohan Kakogawa Hospital, Kakogawa, Hyogo Japan