To Örebro University

Introduction: One environmental factor that in the last decade repeatedly has been linked to increased risk of developing multiple sclerosis (MS) is overweight, including obesity, early in life. The incidence of both MS and overweight are increasing, making elucidation of this connection important. The adipokine leptin is strongly correlated to both body mass index and total fat mass and the peptide hormone insulin is associated with obesity and type 2 diabetes, making leptin and insulin suitable biomarkers to investigate the connection between overweight and MS.

Objectives: To determine if leptin or insulin are risk factors for developing relapsing MS.

Aims: To further the understanding of how overweight influence MS risk.

Methods: In this case-control study, we compared concentrations of leptin and insulin in 649 individuals that later developed relapsing-remitting MS with 649 matched controls. Cases were matched for biobank, sex, date of sampling and age with decreasing priority. Only prospectively collected samples from individuals below the age of 40 were included in the study. Conditional logistic regression was performed on log10 transformed and z-scored values for the entire group, separately for men and women and divided into age groups.

Results: A 1-unit leptin z-score increase was associated with increased risk of MS in individuals below 20 years of age (odds ratio [OR] 1.4, 95% confidence interval [CI] 1.1–1.9) and for all men (OR 1.4, 95% CI 1.0–2.0). In contrast, for women aged 30-39 years there was a lower risk of MS with increased leptin levels (OR 0.74, 95% CI 0.54–1.0) when adjusting for insulin levels. No statistically significant association was found between insulin levels and MS risk.

Conclusions: We show that the pro-inflammatory adipokine leptin is a risk factor for MS among young individuals. The age dependent relationship between leptin and MS risk in women - for whom leptin levels are several-fold higher than in men - suggests a possible role for leptin as being the link between MS risk and being overweight early in life.