Higher Leptin Levels, Body Fat Linked to MDS in Study

A study accepted for publication in the British Journal of Nutrition explores links among measures of leptin, adiponectin, and adiposity in patients with myelodysplastic syndrome (MDS). The authors, all from the Federal University of Ceará, in Fortaleza, Brazil, found significant links among the measures, which they said showed the need for “comprehensive and systematic evaluation of patients with MDS, in order to identify and control negative factors not related to the disease at an early stage.”

Obesity has previously been linked to poor rates of survival in MDS, and about a third of patients with MDS progress to acute myeloid leukemia (AML). An analysis of more than 2700 patients found that obesity increased the risk of developing AML by 53%, when compared with normal weight individuals.

In this new study, authors wanted to focus on clinical indicators that could signal increased risk. This cross-sectional study of 102 patients with MDS and 102 age- and sex-matched controls looked at clinical characteristics, comorbidities, height and weight, data such as waist circumference and skinfold thickness, laboratory values, and genetic analysis, including specific polymorphisms of the LEP and ADIPOQ genes.

The hormone leptin has a key role in regulating appetite and energy consumption, and also has a role in inflammation; higher levels of this hormone are associated with obesity. By contrast, adiponectin is anti-inflammatory and regulates glucose levels, and its presence inversely correlates with elevated body mass index and visceral fat. The authors cited multiple studies that show the association between higher leptin, lower adiponectin, and cancer progression.

However, they wrote, “Previous few studies among MDS individuals found increased leptin and decreased adiponectin concentration when compared to healthy controls.”

The authors discussed a polymorphism of LEP associated not only with cancer, but also with chronic diseases including obesity and diabetes, and noted that this offered investigators a reason to look into the relationship between LEP and MDS, as “cardiovascular events are the most frequent cause of death unrelated to the disease” in these patients.

Patient characteristics were as follows:

• 22.5% younger than 65 years and 77.5% 65 years or older; the mean (SD) age of all MDS patients was 72.0 (11.6) years (range, 38-96).
• Most patients were women 64.7% (n = 66).
• According to World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia, 71.6% of patients were classified as lower risk and 28.4% as higher risk.
• According to the revised International Prognostic Scoring System (IPSS-R) of 2012, 6.9% had very low risk, 28.4% of patients had low-risk disease (different from the WHO classification), while 18.6% had intermediate risk, 7.8% had high risk, and 8.8% had very high risk.
• 36.3% of patients (n = 37) reported transfusion dependency, with iron overload observed in 13.7% (n = 14). Most patients with MDS reported anemia (89.2%; n = 91). Neutropenia and thrombocytopenia were seen in 52.0% (n = 53) and 58.8% (n = 60), respectively.
• 23.5% of the patients had 5% or more blasts in the bone marrow.

Results of the analysis were as follows:

• Among patients with MDS, mean (SD) serum leptin was 298.3 (153.07) ng/mL; among the patients in the control group, it was 184.68 (83.61) ng/mL (P = .03).
• Higher mean serum leptin was seen among patients with high waist circumference (P < .001) and fat mass index (P = .017).
• Among patients with MDS, there was a significant positive correlation between serum leptin levels and certain values related to obesity: BMI (r = 0.264; P = .025), waist circumference (r = 0.235; P = .047), body fat percentage (r = 0.373; P < .001), and fat mass index (r = 0.371; P < .001).
• Other values showed no significant correlation between leptin levels and the variables. These included age (r = 0.112; P = .322), hemoglobin (r = 0.042; P = .727), neutrophils (r = –0.199; P = .094), platelets (r = –0.165; P = .166), percentage of blasts (r = 0.70; P = .557), and ferritin (r = –0.017; P = .924).
• Serum adiponectin was significantly lower among MDS patients than in the control group (P = .033). The mean (SD) serum adiponectin among MDS group was 7.10 (4.87) μg/mL, compared with 9.00 (5.38) μg/mL for control group individuals.
• Investigators found no difference in serum leptin between MDS WHO subtypes and controls (P > .05).
• Female MDS patients had significantly higher serum leptin concentration than male patients (P = .036).

In looking at the genetic analysis, investigators found a significant association a mutant genotype of a LEP polymorphism and male gender and blast excess of greater than 5%. In addition, an association was seen between a mutant genotype of a key ADIPOQ polymorphism and iron overload. The authors noted as limitations the fact that only a few polymorphisms were evaluated and the fact that theirs was a cross-sectional study.

“These results demonstrate the importance of a comprehensive and systematic evaluation in MDS patients, in order to identify and early control negative non-disease related factors,” the investigators wrote.

“Nutritional status, circulating adipokines, and leptin and adiponectin polymorphisms may play a potential role in disease pathogenesis. The association between these factors, not only with anthropometric parameters, but also with some characteristics of the MDS, deserves further in-depth studies.”

Reference

Nogueria-Aguiar AP, da Silva-Mendonca P, Pereira Lima RC, et al. The role of adiposity, adipokines, and polymorphisms of leptin and adiponectin in myelodysplastic syndromes. Br J Nutr. Published online October 19, 2023. doi:10.1017/S0007114523002283