Topic: Obesity, pseudo-Cushing, bariatric surgery and hypoglycemia
Aim
The overall aim is to elucidate potential relations between cortisol, cortisol metabolism and obesity before and after bariatric surgery. We will perform quantification of circulating cortisol concentration, characterization of cortisol metabolites and assessment of HPA axis. A detailed mapping of these pathways in obesity might contribute to the understanding of why some people with overweight and obesity, develop obesity related comorbidity, while others remain apparently metabolic healthy. In addition, we aim to explore the consequences of weight loss induced by bariatric surgery, on peripheral and central cortisol metabolism.
We hypothesize that altered cortisol secretion and metabolism is associated with obesity related comorbidities and change along with weight loss after bariatric surgery, and that the changes contribute to the risk of postbariatric hypoglycemia.
This hypothesis is explored through the following three studies:
Study 1: Cortisol metabolism across the weight spectrum and association with obesity related comorbidities.
Study 2: Changes in cortisol metabolism observed after bariatric surgery and associations with obesity related comorbidities and/or improvements of comorbidities.
Study 3: Postbariatric hypoglycemia – association with cortisol metabolism
Study 1
Investigator: Charlotte Røn Stolberg
The primary aim of the study is to investigate cortisol metabolism in individuals with a BMI > 30 kg/m2 compared to a normal-weight control group.
The secondary aim is to examine whether cortisol metabolism differs in patients with severe obesity who suffer from obesity-related comorbidities, compared to patients with severe obesity without comorbidities. The study includes blood and urine samples from 500 individuals from the Southern Denmark Obesity Initiative (SDOI). SDOI is a population-based cohort consisting of individuals between 18-60 years old with a BMI over 30 kg/m2 referred to Sydvestjysk Hospital for assessment and treatment of obesity-related disorders. The individuals are already included and examined, and the samples are stored in a biobank. SDOI also includes a normal-weight control group (BMI 18.5 – 25 kg/m2).
Study 2
Investigator: TBA
The primary aim is to investigate cortisol metabolism after weight loss achieved through bariatric surgery. The secondary aim is to investigate if the changes in cortisol metabolism observed after bariatric surgery are different among individuals with and without obesity-related comorbidities. In order to detect the expected change, it is necessary to include 100 individuals. The study will include individuals referred from SDOI for bariatric surgery, as they have undergone a comprehensive baseline examination. Approximately 40 patients are referred annually from SDOI for bariatric surgery, and assuming that 50% of patients desire a follow-up examination 1 year after bariatric surgery, the study will last for approximately 6 years.
Study 3
Investigator: Charlotte Røn Stolberg
Post bariatric hypoglycemia (PBH) is a potentially serious complication to bariatric surgery. The prevalence varies between 0.4 - 75 % of people who underwent bariatric surgery, depending on the diagnostic tool used. The mechanisms leading to PBH is poorly understood. Impaired counterregulatory cortisol response to hypoglycemia might contribute.
The objective is to evaluate cortisol metabolism in persons with hypoglycemia compared to people without hypoglycemia. To determine if people with low cortisol response during an ACTH test are more likely to experience PBH
One hundred people who have undergone bariatric surgery from the outpatient clinics will be included. Inclusion criteria: Bariatric surgery 12 – 48 month’s prior to inclusion. Exclusion criteria: diabetes, treatment with glucocorticoids or with medication influencing glucose metabolism, hormone replacement therapy or pregnancy.
We will perform a mixed meal tolerance test (with measurements of cortisol CBG, glucose, insulin and C-peptide during the test), ACTH test and a period of 7-day continuous glucose monitoring. Fasting blood samples include glucose, C-peptide, insulin, cortisol and corticosteroid binding globulin. Additionally, a 24-hour urine sampling will be performed Hypoglycemia is defined as blood glucose ≤ 3.0 mmol/L
This project will provide new knowledge on the pathophysiological role of cortisol in the development of PBH and may foster development of new treatment options