At least a quarter of adolescents who have been overweight since childhood have not been helped by doctor-prescribed diet, exercise and family counselling. They therefore have a very high risk of becoming severely overweight and developing type 2 diabetes while still young adults.

There is now hope of help for them, at least according to doctor and researcher Eva Winning Lehmann. She believes that, through her postdoctoral project and together with her mentors, she can fundamentally change the way we approach the treatment of childhood and adolescent obesity, thereby also preventing the precursors of diabetes and other obesity-related diseases.

Her mentors are Professor Signe Torekov of the University of Copenhagen and paediatrician Jens-Christian Holm of Holbæk Hospital.

Eva Winning Lehmann will combine knowledge from national and international experts in the field of obesity and diabetes research, ranging from behavioural experts to cellular biologists, from clinicians treating outpatients on a daily basis to the pharmaceutical companies working to develop leading-edge drug treatments for obesity and diabetes. ‘This close interdisciplinary and intersectoral collaboration will enable us to combine a broad range of new, advanced research modalities’, she says.

Eva Winning Lehmann says that it is not yet known why these young people do not respond to weight loss treatment and thus become severely obese, and that neither socioeconomic factors nor genetic variation provide an immediate explanation.

The hypothesis, therefore, is that brain, fat or gut-dependent mechanisms underlie untreatable obesity, and that treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RA) may alleviate dysfunctions in these organs and hence also the incidence of diabetes and other obesity-related diseases, she explains.

In her postdoc project, she will investigate these issues by recruiting 180 adolescents from a cohort of 4,000 children who have undergone treatment attempts by structured lifestyle intervention involving rigorous diet, exercise and family counselling. The young people will be divided into three groups according to their response to the structured lifestyle intervention: 75 poor responders (no reduction in BMI or fasting blood sugar), 75 unsatisfactory responders (reduced BMI and fasting blood sugar, but still severely overweight) and, finally, 20 good responders (reduced BMI and fasting blood sugar, and no longer severely overweight).

Eva Winning Lehmann will study potential brain, fat and gut-dependent organ dysfunction across the three groups, as well as their response to 1 year of treatment with GLP-1 RA or placebo. She believes that the project’s close interdisciplinary and intersectoral collaboration will enable the group to combine a broad range of new, advanced research modalities and therefore to help the young people to achieve an effective weight loss that they have been unable to achieve with the standard treatment.

FACTS
There are studies linking obesity to a number of organ dysfunctions, including those in the brain (related to appetite and eating behaviour), adipose tissue (activation of brown adipose tissue) and the gut (intestinal hormones and intestinal flora). Moreover, it has been shown in rodents that GLP-1 RA treatment appears to directly improve some of these obesity-related organ dysfunctions.

CONTACT
Eva Winning Lehmann
Novo Nordisk Foundation Center for Basic Metabolic Research,
University of Copenhagen
epwi@sund.ku.dk
+45 40 84 18 96

‘She believes that the project’s close interdisciplinary and intersectoral collaboration will enable the group firstly to combine a broad range of new, advanced research modalities, and then to give the young people effective help with the weight loss that they have been unable to achieve otherwise.’