Sex differences in circulating leptin as a marker of adiposity in obese or overweight adolescents with type 1 diabetes

Authors: REDONDO, MARIA - Baylor College Of Medicine; SILLER, ALEJANDOR - Baylor College Of Medicine; GU, XIANGJUN - Baylor College Of Medicine; TOSUR, MUSTAFA - Baylor College Of Medicine; BONDY, MELISSA - Carnegie Institute - Stanford; DEVARAJ, SRIDEVI - Baylor College Of Medicine; SISLEY, STEPHANIE - Children'S Nutrition Research Center (CNRC)

Submitted to: BMJ Open Diabetes Research & Care
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/4/2020
Publication Date: 10/21/2020
Citation: Redondo, M., Siller, A., Gu, X., Tosur, M., Bondy, M., Devaraj, S., Sisley, S. 2020. Sex differences in circulating leptin as a marker of adiposity in obese or overweight adolescents with type 1 diabetes. BMJ Open Diabetes Research & Care. https://doi.org/10.1136/bmjdrc-2020-001683.
DOI: https://doi.org/10.1136/bmjdrc-2020-001683

Interpretive Summary: Although excess fat mass is a root cause of many disorders, including diabetes, high blood pressure, liver disease, and sleep apnea, measuring the percentage of body fat mass is difficult. Calculations of body mass index (BMI), which require height and weight measurements, correlate imperfectly and are not always available due to a lack of accurate height measurements. Proteins secreted by fat cells, called adipokines, circulate in the blood but whether they would be useful as a surrogate marker for fat mass are unknown. If a serum marker can be used instead of BMI, then a person's risk for other disorders could be determined which would be important for both research and telemedicine, where measurements are very difficult to obtain. In this study, we compared body fat percentage determined by the gold standard dual-energy X-ray absorptiometry (DEXA) to circulating adipokines including leptin and adiponectin in subjects with Type 1 diabetes. We found that body fat percentage was more strongly correlated with leptin than with BMI overall. However we also found sex-specific differences as body fat percentage correlated the strongest with leptin in boys but with waist circumference in girls. Thus, our research shows that circulating leptin could be used as a surrogate marker of adiposity in boys with type 1 diabetes but more research needs to be performed in girls.

Technical Abstract: We aimed to test whether the serum adipokines leptin and adiponectin are more strongly associated with body fat percentage (BF%) than body mass index (BMI) in adolescents with type 1 diabetes (T1D) and overweight/obesity. We studied all participants in the T1D Exchange Metformin Study (n=122, median age 12.9 years, range 12–19.5; 32% males; 77% non-Hispanic whites, 100% overweight or obesity; median diabetes duration 6.7 years, range 1.4–15) with a baseline serum sample where we measured leptin and adiponectin concentrations. Anthropometric, clinical, laboratory and dual- energy X- ray absorptiometry (DEXA) scan measurements were analyzed. We compared correlation coefficients between variables of interest. BF% by DEXA was significantly correlated with BMI Z- score (r=0.38, p<0.0001), BMI per cent of the 95th percentile (BMI%95) (r=0.45, p<0.0001), waist circumference (r=0.46, p<0.0001), leptin (r=0.58, p<0.00001) and leptin/adiponectin ratio (r=0.36, p<0.0001), while it was not significantly correlated with absolute body weight, adiponectin or insulin dose (total or basal). BF% was significantly more strongly correlated with leptin than with BMI Z-score in the overall group (p=0.022). However, there were sex- based differences. Among the significant correlations in the overall group, BF% was most strongly associated with leptin (r=0.75) in boys (n=39) but with waist circumference (r=0.58) in girls (n=83) (all p<0.0001). Conclusions Serum leptin could be used as a surrogate convenient marker of adiposity in overweight/obese adolescent boys with T1D, equivalent to BMI Z-score or BMI%95. In girls, waist circumference was the best performing marker overall, and was also strongly correlated with %BF in boys.